Thermo Fisher Scientific Improves Workflow In HLA Laboratories With 10-Second Analysis Of DNA Microsamples Using Nanodrop 1000

Thermo Fisher Scientific Inc., the world leader in serving science, will exhibit a new spectrophotometer that offers unique benefits for human leukocyte antigen (HLA) typing laboratories dealing with donor tissue matching. The Thermo Scientific NanoDrop™ 1000 represents the growing trend of successful genome research tools finding their way to the clinical research setting. Specifically, the NanoDrop 1000 is utilized in the workflow as a replacement to time-consuming traditional spectrophotometers where efficiency and time-to-result are critical.


The NanoDrop 1000 is capable of carrying out full UV-Vis absorbance measurements with only 1 ul of undiluted sample, enabling HLA laboratories to significantly speed up analysis time. The NanoDrop 1000 has been integrated into tissue typing workflows through a validation process as set by the HLA typing community. The NanoDrop 1000 spectrophotometer will be showcased for the first time at the Thermo Scientific booth 2739 at AACC 2008, being held in Washington D.C., from July 29 - 31.


This innovative cuvetteless method enables HLA laboratories to quickly and effectively process DNA samples without compromising yield. HLA is the major histocompatibility complex in humans, and laboratories performing HLA typing have distinct requirements for instrumentation, including preserving sample yield and optimizing analysis time. The NanoDrop 1000 spectrophotometer has been successfully integrated into the HLA typing workflow in a number of leading laboratories. DNA is extracted and purified from donor tissue and quantified on the NanoDrop 1000 using a patented sample retention system requiring only 1 ul of sample. This quantitation method enables HLA laboratories to quickly and effectively process DNA samples without compromising yield.


In many HLA cases, donor workup results are required in less than four hours as the speed and accuracy of tissue analysis can affect the long-term graft survival of the tissue. The NanoDrop 1000 spectrophotometer allows laboratories to analyze microsamples of DNA in only 10 seconds, reducing labor time and increasing laboratory productivity. Additionally, the novel microsample quantitation technology of the NanoDrop 1000 is critical for typing samples of limited cell mass, such as mononucleated bone marrow specimens.


In addition to reducing spectrophotometric quantitation prior to DNA amplification, the NanoDrop 1000 enables HLA typing laboratories to comply with the strict standards set by the ASHI. The NanoDrop 1000 has passed the rigorous validation process for HLA laboratories across the United States, and is now recommended by many certified laboratory inspectors.


Notes


For more information about the Thermo Scientific NanoDrop 1000 spectrophotometer, please visit the Thermo Scientific booth 2739 at AACC 2008. Alternatively please email nanodropthermofisher, call +1 302-479-7707 or visit nanodrop.


Spectrophotometers are general purpose laboratory instruments. They have not been cleared or approved by the United States Food and Drug Administration, the European IVD Directive or any other agency for diagnostic, clinical or other medical use.


Thermo Scientific is part of Thermo Fisher Scientific Inc. the world leader in serving science.


About Thermo Fisher Scientific


Thermo Fisher Scientific Inc. (NYSE: TMO) is the world leader in serving science, enabling our customers to make the world healthier, cleaner and safer. With annual revenues of $10 billion, we have more than 30,000 employees and serve over 350,000 customers within pharmaceutical and biotech companies, hospitals and clinical diagnostic labs, universities, research institutions and government agencies, as well as environmental and industrial process control settings. Serving customers through two premier brands, Thermo Scientific and Fisher Scientific, we help solve analytical challenges from routine testing to complex research and discovery. Thermo Scientific offers customers a complete range of high-end analytical instruments as well as laboratory equipment, software, services, consumables and reagents to enable integrated laboratory workflow solutions. Fisher Scientific provides a complete portfolio of laboratory equipment, chemicals, supplies and services used in healthcare, scientific research, safety and education. Together, we offer the most convenient purchasing options to customers and continuously advance our technologies to accelerate the pace of scientific discovery, enhance value for customers and fuel growth for shareholders and employees alike.

Molecule Responsible For Axonal Branching Discovered By MDC Researchers

The human brain consists of about 100 billion (1011) neurons, which altogether form about 100 trillion (1014) synaptic connections with each other. A crucial mechanism for the generation of this complex wiring pattern is the formation of neuronal branches. The neurobiologists Dr. Hannes Schmidt and Professor Fritz G. Rathjen at the Max DelbrГјck Center for Molecular Medicine (MDC) Berlin-Buch, Germany, have now discovered a molecule that regulates this vital process. At the same time they have succeeded in elucidating the signaling cascade induced by this molecule (PNAS, Early Edition, 2009, doi:10.1073)*.



Through the ramification of its fiber-like axon, a single neuron can send branches and thus transmit information into several target areas at the same time. In principle, neurobiologists distinguish between two kinds of axonal branching: branching of the growth cone at the tip of an axon and the sprouting of collaterals (interstitial branching) from the axon shaft.



Both forms of axonal branching can be observed in sensory neurons, which transmit the sensation of touch, pain and temperature, among others. When the axons of these neurons reach the spinal cord, their growth cones first split (bifurcate) and consequently the axons divide into two branches growing in opposite directions. Later new branches sprout from the shaft of these daughter axons which penetrate the gray matter of the spinal cord.



Through investigations on sensory neurons, Dr. Hannes Schmidt and his colleagues were able to identify a protein which triggers the splitting of the growth cone of the sensory axons: the peptide CNP (the abbreviation stands for C-type natriuretic peptide). In transgenic mice the scientists were able to show that CNP is formed in the spinal cord precisely when sensory neurons grow into it. In the absence of CNP bifurcation can no longer occur which results in reduced neuronal connectivity in the spinal cord.



The new findings supplement earlier discoveries of the research group of Professor Rathjen according to which a cGMP-signaling cascade is responsible for the bifurcation of sensory axons. When CNP binds to its receptor Npr2 (natriuretic peptide receptor 2) on the surface of the axons, this signaling cascade is set in motion, which in turn induces the formation of the secondary messenger molecule cGMP. This messenger molecule then activates the protein kinase cGKI (cGMP-dependent protein kinase I), which can switch on and off a whole series of target proteins. The cytoskeleton of the neurons is thus altered in such a way that their growth cone splits into two daughter axons.



Next, the researchers want to identify these target proteins. Further analyses should clarify whether the cGMP signaling cascade likewise regulates the branching of other axon systems and whether this impacts the sensation of pain.



Notes:

*C-type natriuretic peptide (CNP) is a bifurcation factor for sensory neurons

Author affiliation: Hannes Schmidta, Agne Stonkutea, RenГ© JГјttnera, Doris Koeslingb, Andreas Friebeb,c, Fritz G. Rathjena

a Department of Developmental Neurobiology, Max Delbrück Center for Molecular Medicine, Robert Rössle Str. 10, D-13092 Berlin

b Institute for Pharmacology and Toxicology, Ruhr University Bochum, D-44780 Bochum

c Present address: Institute for Physiology I, University of Würzburg, Röntgenring 9, D-97070 Würzburg



Source:
Barbara Bachtler


Helmholtz Association of German Research Centres

Link Between Two Aging Pathways In Mice

Two previously identified pathways associated with aging in mice are connected, say researchers at the Stanford University School of Medicine. The finding reinforces what researchers have recently begun to suspect: that the age-related degeneration of tissues, organs and, yes, even facial skin with which we all struggle is an active, deliberate process rather than a gradual failure of tired cells. Derailing or slowing this molecular betrayal, although still far in the future, may enable us to one day tack years onto our lives - or at least delay the appearance of that next wrinkle.



"There is a genetic process that has to be on, and enforced, in order for aging to happen," said Howard Chang, MD, PhD, associate professor of dermatology at the school and a member of Stanford's Cancer Center. "It's possible that those rare individuals who live beyond 100 years have a less-efficient version of this master pathway, just as children with progeria - a genetic aging disease - may have components of this pathway that are more active."



The study, which will be published in the Jan. 9 issue of Cell, grew out of a three-year collaboration between Chang and Katrin Chua, MD, PhD, assistant professor of endocrinology, gerontology and metabolism at Stanford and member of the Stanford Cancer Center and the Veterans Affairs Palo Alto Health Care System. Chang and Chua are co-senior authors of the research.



The researchers focused their investigation on two seemingly separate pathways linked to aging. One involved a molecule known as SIRT6 - a member of the sirtuin family of proteins that modulate life span in organisms such as yeast and worms - that Chua's laboratory has been studying for several years. She and her lab members have previously shown that SIRT6 is involved in genomic stability and the protection of chromosomal ends called telomeres. Telomeres, which grow shorter with each cell division, are thought to function as a kind of internal molecular clock associated with aging. Furthermore, mice lacking SIRT6 are born normally but die within a few weeks because of a rapid, multi-organ degeneration that somewhat resembles premature aging.



"Sirtuin family members have been implicated in aging and age-related diseases," said Chua, "but very little was known about how SIRT6 worked on a molecular level until recently. Our new study reveals that SIRT6, in addition to its role in genomic stability and telomere protection, also regulates gene expression."



The other pathway involved a more well-known protein called NF-kappa B, or NF-kB, that binds to and regulates the expression of many genes, including those involved in aging. The expression of many of these genes increases with age, and blocking the activity of NF-kB in the skin cells of elderly mice causes them to look and act like younger cells.



The researchers wondered if NF-kB and SIRT6 somehow work together to help cells age appropriately. They found that, in human and mouse cells, SIRT6 binds to a subunit of NF-kB and modifies components of a nearby DNA packaging center, called histones. This modification makes it more difficult for NF-kB to trigger the expression of the downstream gene - perhaps by causing the DNA to twist in such a way to boot off the protein.
















"It seems that an important job of SIRT6 is to restrain NF-kB and limit the expression of genes associated with aging," said Chang. "We've been interested in the activity of regulatory genes such as NF-kB during aging for several years now, and we were quite happy to find this very clear biochemical connection between these two pathways."



Young mice lacking the SIRT6 protein displayed elevated levels of NF-kB-dependent genes involved in immune response, cell signaling and metabolism - all potentially involved in the uniformly fatal aging-like condition that killed them within four weeks of birth. Tamping down the expression of the gene for NF-kB's SIRT-binding subunit allowed some of the mice to escape this fate.



"Mice lacking SIRT6 seem to hit some kind of a wall at around four weeks of age," said Chua, "when their blood sugar drops to a level barely compatible with life. Reducing NF-kB activity somehow allows the mice to get over this critical period and to live much longer. These mice provide a great new tool to study the effect of SIRT6-deficiency in much older animals than was possible before."



The researchers are now working to understand how NF-kB knows when and to what extent during an organism's lifetime to initiate the degenerative process and what role SIRT6 may play.



"It's a very provocative question," said Chang. "We've tied together two previously separate pathways in aging. Now we'd like to better understand what regulates that pathway."







Chang and Chua's co-authors on the study include graduate students Tiara Kawahara and Mara Damian; research associate Eriko Michishita, PhD; postdoctoral scholars Adam Adler, PhD, and Ron McCord, PhD; research assistants Elisabeth Berber, PhD, Meihong Lin and Lisa Boxer; and Stanford undergraduate Kristine Ongaigui.



The research was supported by the National Institutes of Health, the Department of Veterans Affairs, the California Breast Cancer Research Program, the American Cancer Society and the Paul B. Beeson Aging Research Program.



Stanford University Medical Center integrates research, medical education and patient care at its three institutions - Stanford University School of Medicine, Stanford Hospital & Clinics and Lucile Packard Children's Hospital at Stanford. For more information, please visit the Web site of the medical center's Office of Communication & Public Affairs at mednews.stanford/.



Source: Krista Conger


Stanford University Medical Center

Malaria In Pregnant Women : A First Step Towards A New Vaccine

By managing to express the protein that enables red blood cells infected with the malaria agent Plasmodium falciparum to bind to the placenta and by deciphering its molecular mechanisms, a team of researchers from CNRS and the Institut Pasteur has taken an important first step in the development of a vaccine against pregnancy-associated malaria. Their work was published in the journal PNAS.


In endemic areas where malaria is rife, the main victims are children less than three years old. This is because adults acquire, in the course of their lives, an immunity that protects them against the parasite. However, pregnant women, especially during a first pregnancy, have potentially fatal reactions to P. falciparum. The parasites also prevent exchanges of gases and nutrients through the placenta, thereby leading to spontaneous abortions, premature deliveries and newborn babies with too low birth weight, which are serious conditions in countries where infantile mortality is very high in the first year.


Following a bite by an infectious mosquito, the parasite first multiplies in the liver, before entering the bloodstream where it invades the erythrocytes (or red blood cells). The parasite then rapidly modifies the surface of its host erythrocyte with one of the sixty variable proteins of the PfEMP1 (Plasmodium falciparum Erythrocyte Membrane Protein 1) family. These proteins protect the parasite from the host's immune response and enable it to adhere to the host's cells. The severity of pregnancy-associated malaria (PAM) has been associated with the ability of parasitized erythrocytes to bind to a sugar present in the placenta, chondroitin sulfate A (CSA). After several pregnancies, women acquire protective antibodies that block CSA-binding.


One of the potential vaccination strategies for PAM is to recreate this protective immunity, by blocking the binding of parasitized erythrocytes to the placenta. Previous work carried out by the team headed by BenoГ®t Gamain, CNRS researcher at the UnitГ© Bases GГ©nГ©tiques et MolГ©culaires des Interactions de la Cellule Eucaryote (Institut Pasteur), has shown that one of the proteins of the PfEMP1 family, known as var2CSA, plays an important role in PAM. It is thus the prime target for a vaccine. However, the var2CSA protein shows considerable polymorphism, is very large and has a very complex structure. These characteristics have, until now, prevented researchers from reproducing it in the laboratory and studying it to elucidate its structure and its action mechanisms. Only selected "chunks" of proteins involved in these binding areas, known as domains, have been synthesized.


Gamain and his colleagues have, for the first time, succeeded in producing the entire var2CSA protein for the purpose of studying it. This protein has shown specific, high-affinity binding to CSA, more than a thousand times greater than that of the simple domains synthesized previously. Therefore it is indeed a functional protein, with all the characteristics and functions of the var2CSA protein expressed at the surface of parasitized erythrocytes.


Structural studies conducted in collaboration with researchers at EMBL (European Molecular Biology Laboratory) in Grenoble then made it possible to observe the structure of this protein. Var2CSA has a compact rather than a lengthened shape, as was assumed previously, and has a CSA-binding pocket that is most probably created when the protein folds upon itself.


For the researchers, these results constitute a first step in the race to develop vaccinal or therapeutic approaches aimed at protecting women during their first pregnancies as well as their unborn fetuses. Their work, conducted within the European "Premalstruct" (1) consortium headed by Gamain, is now going to focus on the CSA-binding pocket, responsible for the adhesion of parasitized erythrocytes to the cells of the placenta.


Source: CNRS (DГ©lГ©gation Paris Michel-Ange)

Periodontal Study On Imagenetix Compound 1-TDC Published In Journal Of Periodontology

Imagenetix, Inc. (OTC Bulletin Board:
IAGX), announced today the first scientific publication of a study that was
conducted on its proprietary compound, 1-TDC, for the prevention of
periodontal disease. The study which was conducted at Boston University was
published in the April 26th issue of The Journal of Periodontology and is
available online at joponline/loi/jop.



Commenting on the results of the study, Mr. William P. Spencer,
President of Imagenetix said, "We are excited with the results of this
study, which demonstrates the potential of our compound to become a major
breakthrough for the prevention of periodontal disease." According to the
American Academy of Periodontology over 50% of the adults over the age of
50 have periodontitis or periodontal diseases, which creates a potential
multi-billion market for a product developed from our compound. We have
recently submitted and received PRE-IND approval from the FDA to begin
Safety Studies.



1-TDC is a proprietary blend of esterified fatty acids that inhibits
many oral bacteria. Many of these bacteria have been identified with
causing local and systemic inflammation. The purpose of the study was to
investigate the effect of 1-TDC on Porphyromonas gingivalis (P. gingivalis)
induced periodontitis. Boston University researchers have established the
P. gingivalis-induced periodontitis model in rabbits and have extensively
investigated the relationship of P.gingivalis infection to inflammation.



The study was performed under the direction of Hatice Hasturk, D.D.S.,
Ph.D.; Boston University, Department of Periodontology and Oral Biology.
The study was conducted using a rabbit model established by Boston
University researchers. Experimental periodontitis was induced in New
Zealand white rabbits with silk sutures tied around the mandibular second
pre-molars bilaterally and P.gingivalis applied topically. The test agent
(1-TDC) was applied topically at concentrations of 1 mg/ml and 10 mg/ml
three times per week for six weeks. After six weeks, 1-TDC showed a
reduction of inflammation, cellular infiltration, connective tissue
destruction and bone loss when compared to the placebo. "While both test
concentrations exhibited benefit, 1-TDC given at 10 mg/ml offered the most
significant improvement compared to placebo," stated Dr. Hasturk. "The
opportunity for 1-TDC to reduce the likelihood for an individual for
developing periodontal disease is exciting as there are limited options for
treating periodontitis."



Mr. Spencer added, "The scientists at the Boston University, Goldman
School of Dental Medicine have done an excellent job guiding us through the
discovery process. This study forms the foundation for outlining the
efficacy of 1-TDC for the prevention of periodontal disease. I am happy to
report that Dr. Robert Hesslink, Director of Research & Development along
with our clinical sciences staff continue to achieve research milestones in
this novel form of treating periodontal diseases. We expect to report
additional developments in the near future."
















About Imagenetix



Based in San Diego, California, Imagenetix, (OTC Bulletin Board: IAGX)
is an innovator of scientifically tested, natural-based, proprietary
bioceutical products developed to enhance human health on a global basis.
Imagenetix develops, formulates and private-labels propriety
over-the-counter topical creams, skincare products and nutritional
supplements to be marketed globally through multiple channels of
distribution. In addition, the company develops patentable compounds for
entering into licensing agreements with pharmaceutical partners. Imagenetix
is the creator of Inflame Away(TM)- Celadrin(R), which has been clinically
tested to relieve osteoarthritis pain and significantly improve joint
health. For more information, please visit, imagenetix.



This document contains forward-looking statements within the meaning of
Section 27A of the Securities Act of 1933, as amended, and Section 21E of
the Securities Exchange Act of 1934, as amended. Such statements are
subject to risks and uncertainties that could cause actual results to vary
materially from those projected in the forward-looking statements. The
company may experience significant fluctuations in future operating results
due to a number of economic, competitive, and other factors, including,
among other things, the size and timing of customer contracts, new or
increased competition, changes in market demand, and seasonality of
purchases of the company's products and services. These factors and others
could cause operating results to vary significantly from those in prior
periods and those projected in forward-looking statements. Additional
information with respect to these and other factors, which could materially
affect the company and its operations, are included in certain forms the
company has filed and will periodically file with the Securities Exchange
Commission.


Imagenetix, Inc.

imagenetix

Compound Created That Boosts Anti-Inflammatory Fat Levels

UC Irvine pharmacology researchers have discovered a way to boost levels of a natural body fat that helps decrease inflammation, pointing to possible new treatments for allergies, illnesses and injuries related to the immune system.



For decades, it has been known that this fat, called palmitoylethanolamide (PEA), is a potent anti-inflammatory substance that reduces both allergic symptoms and occurrences of rheumatic fever, but researchers understood little about how PEA works.



In a study appearing online in the Proceedings of the National Academy of Sciences, Daniele Piomelli, the Louise Turner Arnold Chair in Neurosciences at UCI, and colleagues found that levels of PEA are tightly regulated by immune system cells. In turn, PEA helps control the activity of these cells, which are called into action to fight infection, disease and injury in the body.



In addition, they found that PEA - also present in foods like eggs and peanuts - is deactivated by a protein called N-acylethanolamine-hydrolyzing acid amidase, which is an enzyme that breaks down molecules controlling cell inflammation.



Using a combination of molecular modeling and chemical library screening, the researchers created a novel compound that blocks the action of this protein.



When given to rodents, the compound increased the levels of PEA in their immune cells and reduced the amount of inflammation elicited by an inflammatory substance. Furthermore, when administered to the spinal cords of mice after spinal cord injury, the compound decreased inflammation associated with the trauma and improved the recovery of motor function.



"These findings are very exciting for the field of medicine because most drugs for inflammatory conditions are effective in only a portion of the population and have serious side effects," Piomelli says. "This compound shows wide-scale promise."



He adds that the PEA-boosting compound is a prime candidate for development into a range of immune-response drugs. This possibility will be explored through a research collaboration between UCI and the Italian Institute of Technology in Genoa.



Source: Tom Vasich


University of California - Irvine

Discovery In Plant Virus May Help Prevent HIV And Similar Viruses

In a study that could lead to new ways to prevent infection by human immunodeficiency virus (HIV) and similar organisms, Purdue University researchers have been able to genetically modify a plant to halt reproduction of a related virus.


Cauliflower mosaic virus attacks a group of plants that includes the largest number of agriculturally important plants in the world. The plant virus and HIV, which causes AIDS, use the same process to multiply in their victims' cells and spread disease.


"After HIV infects a person, it must recruit and latch onto particular human proteins so that the virus can replicate throughout the body," said Zhixiang Chen, a Purdue professor of botany and plant pathology. "We found that cauliflower mosaic virus relies on the same protein complex to multiply in plants."


Cauliflower mosaic virus, known as CaMV, attacks a plant group that includes cauliflower, broccoli, cabbages, turnips, canola and many types of mustard.


"We believe that the proteins in these host plants might be particularly important for these types of viruses, such as HIV, because if you block them, then the viruses simply can't replicate."


The retrovirus HIV and the pararetrovirus CaMV both use reverse transcription to recruit the host's proteins in order to reproduce and spread infection. Transcription in cells is the process in which a gene's DNA code is copied into RNA, which, in turn, carries the information to another part of the cell or to another cell. In reverse transcription, used by viruses such as HIV and CaMV, the virus' RNA is copied into DNA after it latches on to a victim's cell. This allows the virus to easily integrate into the host's genome and then reproduce in other cells.


Chen and his colleagues published a report on their study in the most recent issue of the journal The Plant Cell.


The researchers found that in the laboratory research plant Arabidopsis, cauliflower mosaic virus recruits a protein complex called CDKC. This is the same protein complex that HIV uses, known in humans as P-TEFb. Since both viruses use this same process to trigger transcription, the scientists now know that this protein complex and its related genes have passed from species to species as organisms evolved over millions of years, Chen said.


"P-TEFb appears to be an evolutionarily conserved target of complex retro- and pararetroviruses for activating transcription," he said. "This must also reflect a fundamental mechanism for transcription inherited by these viruses."


Humans and organisms used for research, such as fruit flies and the tiny wormlike organism Caenorhabditis elegans, have only one gene in the protein complex that retroviruses use to activate transcription. These organisms die if that gene is completely blocked because of its essential role during transcription. This makes it difficult to analyze the function the gene may have in the organisms' growth, development and survival. Unlike those other organisms, the plant protein complex involves two genes.















"In Arabidopsis there are two genes for the CDKC protein complexes that trigger the transcription process," Chen said. "If we knock out one of these genes, the plants become resistant to CaMV and the plant is still growing."


The discovery of these two genes suggests that the mustard plant Arabidopsis is a better organism than others for studying how the proteins regulate gene function and transcription, he said.


However, blocking of one of the plant's genes caused some alteration of leaves, flowers and trichomes (tiny hairlike structures) and delayed flowering on the mutated plants, he said. In addition, mutant plants in which both genes were blocked died in the embryonic stage just as would an organism with only one gene.


Now that Chen knows that Arabidopsis has two genes involved in the transcription process, his research team wants to learn more about genes' possible roles in plant growth and development and where those tasks are performed.


"The two genes each may have specialized functions depending on where they are activated in the plant," he said. "In some tissues the genes appear to be turned on in the same place. But, for example, in the flower, one gene is expressed in one particular place and the other gene is expressed in a different place."


The key question for researchers is how blocking the function of one protein inhibits transcription and replication of the viruses. Discovering the answer could mean major advances for prevention of retroviruses and treatment of the diseases they cause in plants and animals.


The other researchers on this study were postdoctoral research assistant Xiaofeng Cui and research scientist Baofang Fan, both of the Purdue Department of Botany and Plant Pathology, and James Scholz, a University of Missouri Division of Plant Sciences professor.


Purdue's Agricultural Research Program provided funding for this project.


purdue

Leading Drug Discovery And Biotechnology Scientists And Experts Discuss Latest Advancements

SBS 13th Annual Conference & Exhibition



Guest Speakers and Topics include



Eugene Butcher, M.D., professor of pathology, Stanford University School of Medicine, Stanford, Calif., will address how the biology of human cell systems further innovation and drug discovery. The focus of recent pharmaceutical discovery on drug targets instead of drug biology has led to a decline in innovation and in the success rate of investigational drugs. Dr. Butcher describes a broadly applicable approach to evaluating lead compounds and drugs, using panels of human disease models in which primary human cells of multiple types are cultured in complex conditions to mimic disease biology. The effects of a drug in these models provide a unique and clinically informative measure of its usefulness and effectiveness. Dr. Butcher says this process can reduce costs and increase rates at which new drugs are discovered.



Larry Gold, Ph.D., chief executive officer, SomaLogic, Inc., Boulder, Colo., will address ways in which molecular diagnostics can improve health and lower health care costs. Molecular diagnostics, an evolving scientific field, involves the investigation of genes and their protein levels. Through molecular diagnostics, scientists hope to more accurately diagnose certain health conditions and diseases by assessing a gene's protein level in patients. Dr. Gold will discuss how this field can reduce overall health care costs by enabling physicians to diagnose diseases or potential health conditions early on, rather than when the patient requires more intensive treatment.



Mel Reichman, Ph.D., Lankenau Institute for Medical Research in Wynnewood, Penn., and Christopher Lipinski, Ph.D., Melior Discovery Waterford, Conn., will debate the benefits and drawbacks recently established National Institutes of Health Roadmap for Medical Research in the 21st Century. Comprised of 10 academic institutions, the NIH Roadmap was created to discover tools and data that can provide scientists with information about the biological processes of various health conditions. In particular, the two researchers will discuss whether the Roadmap has the potential to make any impact on the drug discovery process.



Other key topics to be discussed and presented at the meeting include: the advances that automation has had on categorizing, managing and synthesizing new drug compounds; proteomic vs. genomic research techniques; and new methods for testing toxicity levels of drug compounds without the use of animal research.







Contact: Ivette Morello


Society for Biomolecular Sciences

Chemists Using Light-activated Molecules To Kill Cancer Cells

A key challenge facing doctors as they treat patients suffering from cancer or other diseases resulting from genetic mutations is that the drugs at their disposal often don't discriminate between healthy cells and dangerous ones -- think of the brute-force approach of chemotherapy, for instance. To address this challenge, Florida State University researchers are investigating techniques for using certain molecules that, when exposed to light, will kill only the harmful cells.


Igor V. Alabugin is an associate professor of chemistry and biochemistry at FSU. He specializes in a branch of chemistry known as photochemistry, in which the interactions between atoms, small molecules and light are analyzed.


"When one of the two strands of our cellular DNA is broken, intricate cell machinery is mobilized to repair the damage," he said. "Only because this process is efficient can humans function in an environment full of ultraviolet irradiation, heavy metals and other factors that constantly damage our cells."


However, a cell that sustains so much damage that both DNA strands are broken at the same time eventually will commit suicide -- a process known as apoptosis.


"In our research, we're working on ways to induce apoptosis in cancer cells -- or any cells that have harmful genetic mutations -- by damaging both of their DNA strands," Alabugin said. "We have found that a group of cancer-killing molecules known as lysine conjugates can identify a damaged spot, or 'cleavage,' in a single strand of DNA and then induce cleavage on the DNA strand opposite the damage site. This 'double cleavage' of the DNA is very difficult for the cell to repair and typically leads to apoptosis."


What's more, the lysine conjugates' cancer-killing properties are manifested only when they are exposed to certain types of light, thus allowing researchers to activate them at exactly the right place and time, when their concentration is high inside of the cancer cells, Alabugin said.


"So, for example, doctors treating a patient with an esophageal tumor might first inject the tumor with a drug containing lysine conjugates," he said. "Then they would insert a fiber-optic scope down the patient's throat to shine light on the affected area." The light exposure would activate the drug, leading to double-strand DNA damage in the cancerous cells -- and cell death -- for as much as 25 percent to 30 percent of the cells in the tumor,at a rate that rivals in efficiency any of the highly complex and rare DNA-cleaving molecules produced by nature, Alabugin said -- and, perhaps just as importantly, avoids damage to healthy cells.


For tumors located deeper within the body, he pointed to other studies showing that a pulsed laser device can be used to penetrate muscle and other tissues, thereby activating the drugs using near-infrared beams of light.


As proof of principle to the idea that lysine conjugates possess anti-cancer activity, Alabugin collaborated with cancer biologist Dr. John A. Copland of the Mayo Clinic College of Medicine in Jacksonville, Fla. In their tests, several of the molecules demonstrated little effect upon cultured cancer cells -- in this case, metastatic human kidney cancer cells -- without light, but upon phototherapy activation killed more than 90 percent of the cancer cells with a single treatment. Future work will include demonstrating anti-cancer activity in an animal model. Successful completion of the preclinical studies then could lead to clinical trials with human patients.


Alabugin recently collaborated with four other FSU researchers -- Associate Professor of Chemistry and Biochemistry Nancy L. Greenbaum and her postdoctoral fellow, Jörg C. Schlatterer, as well as Alabugin's postdoctoral fellow, Serguei V. Kovalenko, and doctoral student Boris Breiner -- on a paper describing the results of their research. That paper, "DNA Damage-Site Recognition by Lysine Conjugates," was published in the July 23 issue of the prestigious science journal Proceedings of the National Academy of Sciences. It can be accessed online by visiting pnas and performing a word search for "Alabugin."


Alabugin and his FSU colleagues also have applied for a patent on their work.


Florida State University

114 Westcott Bldg.

Tallahassee, FL 32306-1430

United States

fsu

Prestigious Janssen Award Received By Researchers Who Helped Millions With Arthritis

Two British researchers who pioneered treatments which have helped millions of people with rheumatoid arthritis and other autoimmune diseases have been awarded the prestigious 2008 Dr. Paul Janssen Award for Biomedical Research.



Emeritus Professor Sir Ravinder Maini and Professor Marc Feldmann, who have been carrying out research together at Imperial College London since the 1980s, were selected for the $100K award by an international committee including Nobel Laureates and other world-renowned scientists.



Their research has led to the development of new drugs which tackle the inflammation and tissue destruction caused by rheumatoid arthritis and other diseases including ankylosing spondylitis, psoriatic arthritis, psoriasis, Crohn's disease and ulcerative colitis.



The treatments they developed, now used by millions of people across the world, have proved effective in most patients, even those resistant to all previous treatments. They also protect the joints from further destruction.



Previous treatment options for rheumatoid arthritis left almost half of all patients with symptoms of continuing disease, deterioration of physical function and progressive joint damage.



The breakthrough came for Professors Maini and Feldmann when they discovered how autoimmune diseases such as arthritis cause the immune system to fight itself. Their work showed that the key lay in molecules responsible for cell communication, known as cytokines.



Cytokines are normally released by immune cells, to alert the immune system to initiate a protective counter-response against infections. Professors Maini and Feldmann discovered that in autoimmune diseases, cytokines are over-produced, with highly increased cytokine levels around otherwise healthy cells. This leads to the signs and symptoms of disease and in rheumatoid arthritis it explains the body's aggressive reaction in areas of arthritic inflammation around patients' joints.



In 1991, the two Professors and their colleagues found that all the different cytokines causing inflammation could be stopped by blocking one kind, Tumor Necrosis Factor (TNF) alpha. In 1992, the first series of successful trials were run with rheumatoid arthritis patients at Charing Cross Hospital, now part of Imperial College Healthcare NHS Trust. The improvements in patients' health were so dramatic that the nurses could identify merely by observation, without access to blood tests, which patients had been given a placebo and which had received TNF alpha blockers.



The Professors' work stimulated the development of three anti-TNF drugs, infliximab, etanercept and adalimumab. Furthermore, a new branch of medicine known as anti-cytokine therapy is now emerging, which builds on their work. This research is looking at other cytokine messengers, in addition to TNF, to see how targeting these messengers might treat more conditions.
















Professor Feldmann, Head of the Kennedy Institute of Rheumatology at Imperial College London, said: "Our findings were exciting because we discovered a new way of treating not just rheumatoid arthritis, but also a host of other chronic inflammatory conditions and perhaps acute ones too. It's great to see that through targeting other cytokine messenger molecules, as well as TNF, we now have the potential to tackle even more diseases and help even more patients. I believe Dr Janssen would have been intrigued as we explore the range of diseases which may be treatable by these anti-cytokines."



Professor Maini, former Head of the Kennedy Institute of Rheumatology at Imperial College London, added: "Our discovery of anti-TNF therapy for disabling chronic inflammatory conditions was the result of contributions made by many colleagues and collaborators and only possible because of advances in molecular medicine and biotechnology. The joy of the fruits of our work is that it made a difference to the lives of so many patients, an outcome that Dr. Janssen especially would have appreciated."



The Dr. Paul Janssen Award for Biomedical Research honours the founder of Janssen Pharmaceutica. The award salutes the most passionate and creative scientists in basic or clinical research, whose scientific achievements have made, or have strong potential to make, a measurable impact on human health. Professors Maini and Feldmann will be presented with their award and prize at events in New York and Beerse, Belgium in September.



Solomon Snyder, Ph.D., Distinguished Service Professor of Neuroscience, Pharmacology and Psychiatry, Johns Hopkins School of Medicine and Chairman, Janssen Award Selection Committee, said: "The work of Feldmann and Maini exemplifies the bench-to-bedside approach that Paul Janssen's contributions epitomized. It is extremely rare for researchers to identify a molecular messenger in test tube studies, demonstrate its physiologic relevance in animals and themselves carry these efforts forward to a successful clinical demonstration. Feldmann and Maini did all of this, leading to therapeutic agents of inestimable, lifesaving importance." In addition to winning the 2008 Dr. Paul Janssen Award for Biomedical Research, Professors Feldmann and Maini have been widely honored for their work. They have received various prizes including the Albert Lasker Clinical Medical Research Award in 2003 and the Crafoord Prize of the Royal Swedish Academy of Science in 2000.







Source: Laura Gallagher


Imperial College London

Multi-Laboratory Study Sizes Up Nanoparticle Sizing

As a result of a major inter-laboratory study, the standards body ASTM International has been able to update its guidelines for a commonly used technique for measuring the size of nanoparticles in solutions. The study, which was organized principally by researchers from the National Institute of Standards and Technology (NIST) and the Nanotechnology Characterization Laboratory of the National Cancer Institute, enabled updated guidelines that now include statistically evaluated data on the measurement precisions achieved by a wide variety of laboratories applying the ASTM guide.



Data from the inter-laboratory comparison gathered from 26 different laboratories will provide a valuable benchmark for labs measuring the sizes and size distribution of nanoparticles suspended in fluids - one of the key measurements in nanotechnology research, especially for biological applications, according to materials researcher Vince Hackley, who led the NIST portion of the study.



Size is an important characteristic of nanoparticles in a variety of potential uses, but particularly in biotech applications where they are being studied for possible use in cancer therapies. The size of a nanoparticle can significantly affect how cells respond to it. (See, for example "Study: Cells Selectively Absorb Short Nanotubes," NIST Tech Beat, March 30, 2007 at nist/public_affairs/techbeat/tb2007_0330.htm#nanotubes.)



One widely used method for rapidly measuring the size profile of nanoparticles in, say, a buffer solution, is photon correlation spectroscopy (PCS), sometimes called "dynamic light scattering." The technique is powerful but tricky. The basic idea is to pass a laser beam through the solution and then to measure how rapidly the scattered light is fluctuating - faster moving particles cause the light scattering to change more rapidly than slower moving particles. If you know that, plus several basic parameters such as the viscosity and temperature of the fluid, says Hackley, and you can control a number of potential sources of error, then you can calculate meaningful size values for the particles.



ASTM standard E2490 is a guide for doing just that. The goal of the ASTM-sponsored study was to evaluate just how well a typical lab could expect to measure particle size following the guide. "The study really assesses, in a sense, how well people can apply these techniques given a fairly well-defined protocol and a well-defined material," explains Hackley. Having a "well-defined material" was a key factor, and one thing that made the experiment possible was the release this past year of NIST's first nanoparticle reference standards for the biomedical research community - NIST-certified solutions of gold nanoparticles of three different diameters, a project also supported by NCL. (See "NIST Reference Materials Are 'Gold Standard' for Bio-Nanotech Research, " NIST Tech Beat, Jan. 8, 2008 at nist/public_affairs/techbeat/tb2008_0108.htm#gold.)



The inter-laboratory study required participating labs to measure particle size distribution in five samples - the three NIST reference materials and two solutions of dendrimers, a class of organic molecules that can be synthesized within a very narrow size range. The labs used not only PCS, but also electron and atomic force microscopy. The results were factored into precision and bias tables that are now a part of the ASTM standard.



For more on the study and ASTM standard E2490, see the ASTM International release "Extensive Interlaboratory Study Incorporated into Revision of ASTM Nanotechnology Standard" at nist/cgi-bin/exit_nist.cgi?url=astmnewsroom/default.aspx?pageid=1840.



Source:
Michael Baum


National Institute of Standards and Technology (NIST)

"Fossil" Genes From The Most Deadly Family Of Human Viruses

Modern marsupials may be popular animals at the zoo and in children's books, but new findings by University at Buffalo biologists reveal that they harbor a "fossil" copy of a gene that codes for filoviruses, which cause Ebola and Marburg hemorrhagic fevers and are the most lethal viruses known to humans.



Published this week in the online journal BMC Evolutionary Biology, the paper ("Filoviruses are ancient and integrated into mammalian genomes") demonstrates for the first time that mammals have harbored filoviruses for at least tens of millions of years, in contrast to the existing estimate of a few thousand.



It suggests that these species, which maintain a filovirus infection without negative health consequences, could have selectively maintained these so-called "fossil" genes as a genetic defense.



The work has important implications for the development of potential human vaccines, as well as for the modeling of disease outbreaks and the discovery of emerging diseases, including new filoviruses.



"This paper identifies the first captured 'fossil' copies of filovirus-like genes in mammalian genomes," says Derek J. Taylor, PhD, associate professor of biological sciences in the UB College of Arts and Sciences and co-author. "Our results confirm for the first time that several groups of mammals, including groups such as marsupials that never colonized Africa, have had an association with filoviruses."



The UB co-authors say that if the rarely captured genes represent antiviral defenses or genomic scars from persistent infections, then the work opens up new possibilities for identifying reservoir species for filoviruses, which harbor the virus but remain asymptomatic.



"The reservoir for filovirus has remained a huge mystery," says Jeremy A. Bruenn, PhD, UB professor of biological sciences and co-author. "We need to identify it because once a filovirus hits humans, it can be deadly."



When the UB researchers studied samples from the fur of a wallaby at the Buffalo Zoo and a brown bat caught on the UB campus, they found that the genomes of both animals as well as some other small mammals contain "fossil" copies of the gene for these deadly viruses, and thus could be candidate reservoir species for them.



"Who knew that the bats in the attic as well as modern marsupials harbored fossil gene copies of the group of viruses that is most lethal to humans," asks Taylor.



The research also demonstrates a new mechanism by which different species of mammals can acquire genes, through non-retroviral integrated RNA viruses, which the UB scientists had previously identified in eukaryotes but was unknown in mammals.



The UB scientists note that it is well-known that RNA retroviruses, like HIV-AIDS, can be integrated into mammal genomes.



"But because filoviruses infect only the cytoplasm of cells and not the nucleus and because they have no means of making DNA copies that might be integrated into the genome -- as retroviruses do -- it was never thought gene transfer could occur between non-retroviral RNA viruses and hosts," says Bruenn. "This paper shows that it does and it may prove to be a far more general phenomenon than is currently known."



The research also reveals that existing estimates that filoviruses originated in mammals a few thousand years ago were way off the mark.



"Our findings demonstrate that filoviruses are, at a minimum, between 10 million and 24 million years old, and probably much older," says Taylor. "Instead of having evolved during the rise of agriculture, they more likely evolved during the rise of mammals."



In addition to Bruenn and Taylor, Robert W. Leach, scientific programmer at the Center for Computational Research in UB's New York State Center of Excellence in Bioinformatics and Life Sciences, is a co-author on the paper.



The authors are actively involved with the Molecular Recognition in Biological Systems and Bioinformatics strategic strength identified as part of the UB2020 strategic planning process.



Source: University at Buffalo

Human Proteins Evolving Slowly Thanks To Multi-Tasking Genes

Many human proteins are not as good as they might be because the gene sequences that code for them have a double role which slows down the rate at which they evolve, according to new research published in PLoS Biology.



By tweaking these dual role regions, scientists could develop gene therapy techniques that produce proteins that are even better than those found in nature, and could one day be used to help people recover from genetic disorders.



The stretch of DNA which codes for a specific protein is often interrupted by sections of apparently useless DNA - known as introns - which need to be edited out in order to produce a new protein.



Recently it has been discovered that some of the instructions on where to splice and re-splice the DNA in this editing process are contained in the coding section, or exon, of the DNA itself.



So, as well as spelling out which amino acids are needed to produce a specific protein, the part of the exon immediately next to the intron contains information that is essential for the gene editing process.



This means that these parts of genes evolve particularly slowly, making the proteins they encode for not as good as they could be had evolutionary processes been more able to improve them over time.



"Our research suggests that a gene with many exons would evolve at under half the rate of the same one that had no introns, simply owing to the need to specify where to remove introns," said Professor Laurence Hurst from the University of Bath (UK), who worked with colleagues from the University of Lausanne (Switzerland) on the project.



"This is one of the strongest predictors of rates of protein evolution known, indicating that this dual coding role is vastly more influential than previously believed."



The finding could have major implications for medicine and the development of gene therapy techniques in which people with a defective gene are given the correct version.



"Our results suggest that we could make the replacement gene even better than the normal version," said Professor Hurst, from the Department of Biology & Biochemistry at the University of Bath.



"We would just need to remove the introns and tweak the protein at the sites that were dual coding.



"We also found that genes that have lost their introns many millions of years ago evolve especially fast near where the introns once resided.



"This indicates that this tweaking of the dual role sections of genes is also what evolution does when introns are removed."



The research was funded by the Biotechnology & Biological Sciences Research Council, the Swiss National Science Foundation and the Center for Integrative Genomics at the University of Lausanne.



The University of Bath is one of the UK's leading universities, with an international reputation for quality research and teaching. In 16 subject areas the University of Bath is rated in the top ten in the country.



Contact: Andrew McLaughlin


University of Bath

German Stem Cell Research Hindered By Qualifying Date Rule

A few days before the German Federal Parliament reaches a decision on the Stem Cell Act, the Deutsche Forschungsgemeinschaft (DFG, German Research Foundation) has reinforced its stance on amending current legislation. "The current qualifying date rule, in particular, strongly impedes German stem cell research," explained DFG Vice President Professor Jorg Hinrich Hacker, while participating in a live chat session on the DFG website. "The best thing for basic research would be if this qualifying date rule, a deadline which restricts the period in which embryonic stem cell lines are allowed to be imported, were to be abolished altogether, as the DFG recommended in a statement on stem cell research it released 18 months ago," he emphasised. Hacker recently also became President of the Robert Koch Institute (RKI) in Berlin.



From the point of view of molecular biologists, even moving the deadline would be an improvement compared to the current situation. Hacker also called for an end to the "criminalisation of German researchers." The current legislation leaves the legal situation of German researchers involved in cooperative projects with stem cell researchers abroad unclear. "This deters young researchers, in particular, from becoming involved in stem cell research." The DFG is also of the opinion, said Hacker, that stem cell lines should also be used for diagnostic, therapeutic and preventative purposes.



Other topics touched upon during the one-hour live chat session, during which Hacker responded to 27 questions, were the prospects for research on adult stem cells. This, Hacker emphasised, is not viewed by the DFG as standing in contrast to research on embryonic stem cells, but as a logical extension. The recent scientific findings on "induced pluripotent stem cells" were also addressed, a topic which Hacker described as a major breakthrough for molecular biology. He also pointed out, however, that research on human embryonic stem cell lines is indispensable in order to be able to estimate and compare the potential for adult or reprogrammed cells. "Embryonic stem cell lines are more or less the gold standard for studies of this kind."



Hacker also took a stand on the issue of ovum donation, which is permitted in some countries. This practice is rejected by the DFG and has nothing to do with the production of embryonic stem cell lines. The debate in Germany is essentially about importing cell lines that have been produced abroad and have already been used for research purposes. Culturing new stem cell lines in Germany is already prohibited by the Embryo Protection Law. The DFG has repeatedly spoken out in favour of keeping the Embryo Protection Law in its current form. In answer to another question, Hacker pointed out that any stem cell lines imported from other countries are also subject to strict assessment. They are required to have originated from embryos that were produced for use in reproductive medicine, but for any one of a number of reasons can no longer be used for that purpose. "Here again, no money is allowed to change hands and the couple from whom the cell line originates need to have given their express permission," Hacker added.



On the question of potential therapeutic uses, another topic addressed during the DFG live chat, Hacker said that "as a general rule of thumb, it takes about ten to fifteen years for a new form of therapy to be developed in biomedicine. If we assume that the first human embryonic stem cell lines were produced ten years ago, then we are now looking at new therapies becoming available in the medium to long term." He also pointed out, however, that the findings being made in research involving embryonic stem cell lines were also contributing to basic research as well as research aimed at developing new forms of therapy. "Without basic research there is no way we can develop new forms of therapy," he emphasised.







Further Information:



Click here to access additional information on stem cell research at the DFG's website..



A transcript of the DFG live chat with Professor Hacker and DFG statements on stem cell research are available, in German only, at dfg/live.



This release is available in German.



Source: Dr. Eva-Maria Streier


Deutsche Forschungsgemeinschaft

Synthetic Cells Shed Biological Insights While Delivering Battery Power

Trying to understand the complex workings of a biological cell by teasing out the function of every molecule within it is a daunting task. But by making synthetic cells that include just a few chemical processes, researchers can study cellular machinery one manageable piece at a time. A new paper* from researchers at Yale University and the National Institute of Standards and Technology (NIST) describes a highly simplified model cell that not only sheds light on the way certain real cells generate electric voltages, but also acts as a tiny battery that could offer a practical alternative to conventional solid-state energy-generating devices.



Each synthetic cell built by NIST engineer David LaVan and his colleagues has a droplet of a water-based solution containing a salt - potassium and chloride ions - enclosed within a wall made of a lipid, a molecule with one end that is attracted to water molecules while the other end repels them. When two of these "cells" come into contact, the water-repelling lipid ends that form their outsides touch, creating a stable double bilayer that separates the two cells' interiors, just as actual cell membranes do.



If the researchers only did that much, nothing interesting would happen, but they also inserted into the bilayer a modified form of a protein, alpha-hemolysin, made by the bacterium Staphylococcus aureus. These embedded proteins create pores that act as channels for ions, mimicking the pores in a biological cell. "This preferentially allows either positive or negative ions to pass through the bilayer and creates a voltage across it," LaVan says. "We can harness this voltage to generate electric current."



If the solutions in the two cells start with different salt concentrations, then poking thin metal electrodes into the droplets creates a small battery: electrons will flow through a circuit connected to the electrodes, counterbalancing the ion flow through the channels. As this happens, the ion concentrations in the droplets eventually equalize as the system discharges its electric potential.



Building synthetic versions of complex real cells - such as those that enable an electric eel to zap its prey - is far too difficult a task for now, says LaVan. So the researchers instead created this far simpler system whose performance they could understand in terms a handful of basic properties, including the size of the droplets, the concentration of the aqueous solutions, and the number of ion channels in the barrier between the two cells.



A tiny battery with two droplets, each containing just 200 nanoliters of solution, could deliver electricity for almost 10 minutes. A bigger system, with a total volume of almost 11 microliters, lasted more than four hours. In terms of the energy it can deliver for a given volume, the biological battery is only about one-twentieth as effective as a conventional lead-acid battery. But in its ability to convert chemical into electrical energy, the synthetic cell has an efficiency of about 10 per cent, which compares well with solid-state devices that generate electricity from heat, light, or mechanical stress - so that synthetic cells may one day take their place in the nanotechnology toolbox.



*J. Xu, F.J. Sigworth, and D.A. LaVan. Synthetic Protocells to Mimic and Test Cell Function. Advanced Materials, published online Oct. 1, 2009



Source:
Ben Stein


National Institute of Standards and Technology (NIST)

Chemical Biologist And Entrepreneur Carolyn Bertozzi Awarded $500,000 Lemelson-MIT Prize

Internationally renowned chemical biologist Dr. Carolyn Bertozzi, whose research is applied worldwide in the biopharmaceutical industry, has achieved extraordinary success for her pioneering inventions in the field of biotechnology. The proven potential for future advances, and her current work manipulating processes within living cells to engineer their surfaces and secreted proteins, have won Bertozzi the prestigious 2010 $500,000 Lemelson-MIT Prize. She will accept the prize and present her accomplishments to the public at the Massachusetts Institute of Technology during the Lemelson-MIT Program's fourth-annual EurekaFest, a multi-day celebration of the inventive spirit, June 16 - 19.



Bertozzi's ability to identify unmet needs and craft innovative solutions has led to scientific advances with a broad range of applications. Chemical insights gleaned by Bertozzi have progressed efforts to diagnose and treat diseases such as cancer, inflammatory disorders such as arthritis, and infectious diseases like tuberculosis. Her multi-disciplinary approach has led to significant developments in the ability to engineer living cells and the proteins they produce with defined chemical properties. As a University of California, Berkeley Professor and Director of the Molecular Foundry at the Lawrence Berkeley National Laboratory, Bertozzi and her team study the biology of glycans, also known as complex carbohydrates, and develop nanotechnologies for probing biological systems.



Paving a Path in a Burgeoning Field



Bertozzi invented the world's first bioorthogonal chemical reaction, a technology for labeling biomolecules in living cells or animals. This form of labeling is a novel approach that allows researchers to specifically target cells and their functions for gene delivery and anti-tumor diagnostics. Bertozzi utilizes these reactions in her work toward imaging glycans on tumor cells, a technology that has the potential to facilitate early cancer detection. She also invented the genetically-encoded aldehyde tag technology, affording scientists with a simple method for precision protein engineering, creating an approach for the development of novel protein drugs.



Other projects Bertozzi holds patents for include a cell nanoinjector, an instrument that introduces molecules into living cells via a "nanoneedle," as well as artificial bone materials, targets for tuberculosis therapy and cell microarray platforms.



Leading the Way as a Mentor and Entrepreneur



Many of Bertozzi's revolutionary projects and findings have been achieved through her work as T.Z. and Irmgard Chu Distinguished Professor of Chemistry and Professor of Molecular and Cell Biology at the University of California, Berkeley, Senior Faculty Scientist in the Materials Science Division at the Lawrence Berkeley National Laboratory, Professor of Molecular and Cellular Pharmacology at the University of California, San Francisco, and as a Howard Hughes Medical Institute Investigator.
















Bertozzi attributes a number of her innovations and research successes to the students and postdoctoral fellows whom she mentors - over the span of her career she has trained more than 130 coworkers including undergraduates, graduate students and postdoctoral fellows. She also created the University of California, Berkeley Chemical Biology Graduate Program.



"Carolyn Bertozzi takes scientific development to a new level; beyond her extraordinary gift as a researcher and innovator, she collaborates with her students to push into new frontiers," states Michael J. Cima, faculty director of the Lemelson-MIT Program. "As a mentor, she engages those around her to develop new, creative ideas, ensuring a future pipeline of scientists, inventors and policy makers."



Lab to Marketplace



Commercialization and Adoption



As a testament to her teaching abilities and mentoring skills, as well as her true entrepreneurial spirit, Bertozzi founded biotech start-up Redwood Bioscience in 2008 with her former graduate student, Dr. David Rabuka. The company, structured around Bertozzi's advancements with the genetically-encoded aldehyde tag technology, is developing novel protein drugs with properties that conventional molecular biology approaches cannot achieve. The company was recently awarded a prestigious National Institutes of Health (NIH) Challenge Grant, bringing $1 million into the company over two years, and has raised funds from the private sector as well.



According to Professor Miquel Salmeron, director of the Materials Science Division at the Lawrence Berkeley National Laboratory, Bertozzi "transformed the field of chemical biology, creating new industries along the way, and bringing new innovations to fields as disparate as nanoscience, tuberculosis therapy, and bone tissue engineering." He adds, "She also has an outstanding record of teaching, mentorship, and service to the community."



With more than 225 publications to her name, a prestigious election to the National Academy of Sciences, and becoming one of the youngest recipients ever of a MacArthur "Genius" Award, Bertozzi has also been hailed with recognition by the American Chemical Society and selected as a Presidential Early Career Award in Science and Engineering.



Source:

Julie Staadecker

Lemelson-MIT Program

A Rare Human Genetic Disease, Primary Ciliary Dyskinesia, Is Better Understood Because Of The Canine Genome

A dog is mankind's best friend : the old saying has once again been borne out through a medical discovery concerning the genetic origins of primary ciliary dyskinesia (PCD). In using dogs as a research model in the framework of the European LUPA project, a team from the University of LiГЁge's GIGA-Research Unit has been able to bring to light new mutations in a specific gene responsible for the development of the disease in human beings.


Primary ciliary dyskinesia (PCD) is a rare genetic disease which affects one person in 20,000. The disease is characterised by motility defects in cellular micro-cilia. The flapping of these micro-cilia allows micro-organisms contained in the air to be expelled. PCD hinders this flapping and is at the root of chronic respiratory infections.


Several mutations in some dozen or so genes are responsible for the development of this disease, but they do not explain 60% of the cases in human beings. To try and resolve these cases the researchers brought their investigations to bear on...dogs.


In effect dogs and humans suffer from numerous diseases in common which very probably have the same genetic origin (cardiac disorders, epilepsy, cancer, diabetes, etc.). A recent trend in biomedical research is to use dogs which are ill as a subject for study in order to detect the genes which could also be involved in the same disease occurring in human beings.


The researchers at the GIGA-ULg Unit and their international colleagues followed this very logic in investigating PCD.


Several Old English Sheepdog (bobtail) puppies suffering from chronic bronchitis were examined in 2007 at the ULg's Faculty of Veterinary Medicine. The frequency of this complaint in this breed suggested a genetic origin and raised suspicions of a PCD, a conviction which was strengthened by the fact that one of the dogs had a situs inversus, in other words a reversal of the heart's normal position in the thoracic cage. During the embryo stage it is one of the functions of some hair cells to create a flow which enables organs to be correctly positioned; if this flow does not take place there is a risk that an organ's normal position will be reversed.


The researchers analysed the DNA of five ill bobtails brought in for consultation at the veterinary clinic and compared it to that of 15 other healthy bobtails. The analysis of this DNA, with the help of 40,000 genetic markers, enabled the identification of a region of canine chromosome 34 linked to the disease, and more particularly a mutation within gene CDC39.


'We were thus able to identify 15 different mutations of this disease,' explains Anne-Christine Merveille, a researcher in Professor Michel Georges team at the GIGA-ULg Unit. 'These mutations explain half of the cases analysed, or close to 5% of the patients throughout the world who are suffering from this disease.'


The study illustrates well the usefulness of dogs for a rapid decrypting of complex human genetic diseases. 'The demonstration of this gene's responsibility in this pathology will enable the families affected to be better advised,' adds Doctor Anne-Sophie LequarrГ©, in charge of the LUPA project.


Sources: LiГЁge University, AlphaGalileo Foundation.

Study On Guppies Sheds Light On Long-Term Costs Of Early Rapid Growth And Weight Gain

University of California, Riverside biologists working on guppies - small freshwater fish that have been the subject of long-term studies - report that rapid growth responses to increased food availability after a period of growth restriction early in life have repercussions in adulthood.



Based on their experiments, the biologists found that female guppies that grew rapidly as juveniles produced fewer offspring than usual.



Study results appear in the August issue of Ecology Letters.



"When food levels increase after a period of low availability, many organisms - including humans - undergo what is called 'catch-up' or compensatory growth," explained Sonya Auer, the first author of the research paper and a Ph.D. graduate student in the Department of Biology. "This accelerated growth response allows them to catch up, fully or in part, to the body size they would have achieved under more favorable food conditions.



"We found that female guppies that underwent compensatory growth as juveniles produced less offspring than would be expected for their body size relative to females that underwent normal growth as juveniles," she said. "In the ecological literature, however, theory and empirical research have assumed that juvenile compensatory growth has only a positive effect on reproduction - being bigger is better."



"This study is of interest even for human biology," said David Reznick, a professor of biology and Auer's advisor, "because we want to know if there are any such long-term consequences for rapid growth and weight gain early in life."



Auer explained that low early food availability alone does not have negative effects on future reproductive success in guppies.



"The long-term costs to reproduction we observed in our experiments appear to result from the compensatory growth response," she said.



She offered possible explanations for these results: The compensatory growth phase could be interfering with the development of reproductive structures. It could also negatively affect reproduction if it increases metabolic needs and thereby decreases the amount of energy available for reproduction.



"Our research helps us to better understand how organisms - including humans - respond to changes in their environment, such as food availability, and what the consequences of those responses are," she said.



Results from the study may have important implications for human reproductive success.



"Scientists have known that low birth weight and subsequent compensatory growth in humans lead to juvenile and adult obesity," Auer said. "Adult obesity is linked to problems such as type 2 diabetes. Type 2 diabetes has been linked to problems in pregnancy. However, to my knowledge, no direct link between juvenile compensatory growth and reproduction has been demonstrated until now."



The research was supported by a University of California Dissertation Research Grant, a National Science Foundation Graduate Research Fellowship to Auer and grants from the National Science Foundation to Reznick.



Auer and Reznick were joined in the research by Jeffrey D. Arendt, a research associate, and Radhika Chandramouli, an undergraduate, who work in Reznick's lab.



Study details:
To study the long-term effects of juvenile compensatory growth on later reproduction, the researchers compared different components of reproduction between female guppies that underwent compensatory growth as juveniles (called experimental females) with females that underwent normal, routine growth (called control females). To initiate the compensatory growth response, they placed young guppies on low food for two weeks followed by a return to normal food levels. They measured the guppies' compensatory growth response and then examined effects on reproduction. They looked at effects on the rate of reproduction (how frequently they produced a litter), the size of the offspring as well as the number of offspring they produced in each litter. They looked at effects of reproduction on the first four litters, the first litter being produced at around 60 days of age and subsequent litters being produced every three weeks thereafter.



Source:

Iqbal Pittalwala

University of California - Riverside

Click Chemistry, A New Technique For Labeling Biomolecules In Vitro, Goes Live

Click chemistry, one of the most exciting and proficient new techniques for labeling biomolecules in vitro, has now been extended to studies in the context of live cells as well. This breakthrough opens the door for applications to live cell imaging of numerous biomolecules, including glycans, proteins and lipids. The new version of click chemistry was developed by researchers with the Lawrence Berkeley National Laboratory (Berkeley Lab) and the University of California (UC) at Berkeley.



"We've developed a copper-free variant of the click chemistry reaction that possesses comparable kinetics to the copper-catalyzed reaction and proceeds within minutes on live cells with no apparent toxicity," said chemist Carolyn Bertozzi, the principal investigator on this project. "This is the first example of a click chemistry reaction that, like the copper-catalyzed version, proceeds at physiologically acceptable temperatures only without the toxic presence of copper."



Bertozzi is the director of Berkeley Lab's Molecular Foundry, a faculty scientist with Berkeley Lab's Materials Sciences and Physical Biosciences Divisions, the T.Z. and Irmgard Chu Distinguished Professor of Chemistry, and a professor of Molecular and Cell Biology at UC Berkeley. She is also an investigator with the Howard Hughes Medical Institute (HHMI), and a leading authority on glycobiology.



"We are already using our copper-free click chemistry technique to probe glycan dynamics in living cells and in live zebrafish embryos, which serve as a standard model of developmental biology," she said.



Bertozzi is the lead author on a paper published in the Proceedings of the National Academy of Sciences (PNAS) entitled: "Copper-free Click Chemistry for Dynamic In Vivo Imaging." Co-authoring this PNAS paper were Jeremy Baskin, Jennifer Prescher, Scott Laughlin, Nicholas Agard, Pamela Chang, Isaac Miller, Anderson Lo and Julian Codelli.



Click chemistry is the popular term for a copper-catalyzed azide-alkyne reaction that makes it possible for certain chemical building blocks to "click" together in an irreversible linkage. Since its introduction in 2001 by the Nobel laureate chemist Karl Barry Sharpless of the Scripps Research Institute, the copper-catalyzed azide-alkyne reaction has proven extremely valuable for attaching small molecular probes to various biomolecules in a test tube or on fixed cells. However, its use for biomolecule labeling in live cells or organisms is prohibited by the requirement of a cyotoxic copper catalyst.



For the past several years, Bertozzi has been developing new techniques for studying glycans. Even though glycans are ubiquitous on the surfaces of most cells and play a critical role in intercellular communications, methods for studying them have lagged behind other biomolecules.



"Glycans mediate a variety of cell surface recognition events such as bacterial and viral binding to host cells and leukocyte adhesion during an inflammatory response," said Bertozzi. "In addition to their cell surface roles, glycans can regulate many intracellular processes, including trafficking of proteins to the lysosome and transcription and translation."
















There is great scientific interest in monitoring the dynamics of glycans as they move about within cells and on the cell surface, but the means to tag glycans with imaging probes has been lacking, thereby prohibiting such studies. Bertozzi and her coworkers had previously shown that glycans can be metabolically labeled with azides, permitting their chemical tagging with imaging probes through click chemistry, but the cytotoxicity of the click reaction would not allow dynamic imaging of live cells.



To apply click chemistry to glycans, Bertozzi and her colleagues designed a new reagent called difluorinated cyclooctyne or DIFO, that reacts with azides rapidly at physiological temperatures without the need for a toxic catalyst.



"Our critical reagent, a substituted cyclooctyne, possesses ring strain and electron-withdrawing fluorine substituents that together promote the cycloaddition with azides installed metabolically into biomolecules," said Bertozzi.



"This copper-free click reaction of azides and DIFO combines the biocompatibility of the Staudinger ligation [a highly successful labeling reaction previously developed in Bertozzi's lab] with the fast reaction kinetics of click chemistry."



Bertozzi says their copper-free click chemistry technique can be used to probe any biomolecule that can be labeled with an azide, including glycans, proteins and lipids. She and her group are now using this technique to study glycan trafficking -- how glycans and their associated scaffolds move around inside cells and on cell surfaces. They have made their DIFO reagents available to other research groups and are in discussions with potential commercial suppliers to make the reagents widely available to the bio research community.



"Direct imaging of glycan trafficking under conditions of cell stimulation or pharmacological intervention can be performed in cells, tissues, or even whole organisms," said Bertozzi. "More broadly, other metabolites, post-translational modifications, enzyme activities, and site-specific labeled proteins can be monitored in real time and in living systems with our copper-free click chemistry."







This work was supported by a grant from the National Institutes of Health. Jeremy Baskin was supported by a National Defense Science and Engineering Graduate Fellowship. Baskin and Pamela Chang were supported by National Science Foundation Predoctoral Fellowships. Jennifer Prescher was supported by a Howard Hughes Medical Institute Predoctoral Fellowship.



Berkeley Lab is a U.S. Department of Energy national laboratory located in Berkeley, California. It conducts unclassified scientific research and is managed by the University of California. Visit our Website at lbl/.



Source: Lynn Yarris


DOE/Lawrence Berkeley National Laboratory

Discovery Of Genomic Link To Rheumatoid Arthritis

A paper published this week in the open access journal PLoS Medicine provides strong evidence that one specific part of the genome is associated with rheumatoid arthritis. Rene Toes and colleagues from Leiden University Medical Center, the Karolinska Institute, and Celera studied four groups of patients and matched controls. They found a consistent association with one specific region of the genome -- a region on chromosome 9 that includes the two genes, complement component 5 (C5) of the complement system (a primitive system within the body that is involved in the defense against foreign molecules) and a gene involved in the inflammatory response, TNF receptor-associated factor 1(TRAF1) .



Rheumatoid arthritis is a very common chronic illness that affects around 1% of people in developed countries. It is caused by an abnormal immune reaction to various tissues within the body. As well as affecting joints and causing an inflammatory arthritis, it can also affect many other organs of the body. An association has been shown previously in humans with the part of the genome that contains the human leukocyte antigens (HLAs), which are involved in the immune response. In addition, previous work in mice that have a disease similar to human rheumatoid arthritis has identified a number of possible candidate genes including C5.



The researchers took 40 genetic markers, single-nucleotide polymorphisms (SNPs), from across the region that included the C5 and TRAF1 genes. They compared which of the alternate forms of the SNPs were present in 290 patients with rheumatoid arthritis and 254 unaffected participants of Dutch origin. They then repeated the study in three other groups of patients and controls of Dutch, Swedish, and US origin. They found a consistent association with rheumatoid arthritis of one region of 65 kilobases that included one end of the C5 gene as well as the TRAF1 gene and then refined the area of interest to a piece marked by one particular SNP that lay between the genes. They went on to show that the genetic region in which these genes are located may be involved in the binding of a protein that modifies the transcription of genes. Furthermore, they showed that one of the alternate versions of the marker in this region was associated with more aggressive disease.



This study adds to accumulating evidence that this region of the genome is associated with rheumatoid arthritis. The next steps will be to identify the precise genetic change involved.







Everything published by PLoS Medicine is Open Access: freely available for anyone to read, download, redistribute and otherwise use, as long as the authorship is properly attributed. In this week's press release: Strong evidence that region on chromosome 9 is associated with rheumatoid arthritis



Citation: Kurreeman FAS, Padyukov L, Marques RB, Schrodi SJ, Seddighzadeh M, et al. (2007) A candidate gene approach identifies the TRAF1/C5 region as a risk factor for rheumatoid arthritis. PLoS Med 4(9): e278. doi:10.1371/journal.pmed.0040278



Click here for access to the published paper.



Contact:

Dr. Rene Toes

Leiden University Medical Center

Dept of Rheumatology

Albinusdreef 2, 2333 ZA Netherlands



About PLoS Medicine


PLoS Medicine is an open access, freely available international medical journal. It publishes original research that enhances our understanding of human health and disease, together with commentary and analysis of important global health issues. For more information, visit plosmedicine/



About the Public Library of Science


The Public Library of Science (PLoS) is a non-profit organization of scientists and physicians committed to making the world's scientific and medical literature a freely available public resource. For more information, visit plos/



Source: Andrew Hyde


Public Library of Science

Chondroitin Sulfate Proteoglycan May Have Many Roles In Spinal Cord Injury Repair

The proteoglycan chondroitin sulfate (CSPG) plays an important role not
just in the formation of the glial scar but also in the repair of
spinal cord injury, according to an article released on August 18, 2008
in the open-access journal PLoS Medicine.



In injuries to the central nervous system such as spinal cord injury,
the glial scar is formed in a similar manner to scars in other parts of
the body. However, while protecting the damaged area in many ways, it
simultaneously releases chemicals that inhibit further regeneration.
Within the glial scar, several major types of cells appear, in
particular microglia and macrophages. The proteoglycan molecule
chondroitin sulfate plays a vital role in the inhibition of neuronal
regeneration, but according to the article, the increased synthesis of
this compound indicates it might actually play a dual rold in this
process.



Michal Schwartz, of the Weizmann Institute of Science, and colleagues
performed several experiments in mice to explore this dual role in the
acute phase of healing after a spinal cord injury. Evaluating spinal
cord damage through the proteins and cells that are present, the
researchers postulate that the proteoglycan in fact has an important
role in the healing process by controlling intervening cells in
communication pathways.



They conclude that the present goal to reduce expression of chondroitin
sulfate may not be productive, and that it may be more important to
modulate it in therapies for such injuries. They say that "timing and
the extent of degradation should be carefully selected according to the
changing requirements of the ongoing dynamic repair process."



They conclude with a call for further research in the formation and
maintenance of the glial scar: "Moreover, since CSPG is a major
constituent of the glial scar, the present findings raises the
potential need to revisit the overall perception of the glial scar and
its role in recovery. A better understanding of the regulation of the
scar tissue and the role of the naturally occurring CSPG in health and
disease will enable us to increase the benefit of endogenous repair
mechanisms and improve many of the available therapies for CNS injury."




Two faces of chondroitin sulfate proteoglycan in spinal cord
repair: A role in microglia/macrophage activation.

Rolls A, Shechter R, London A, Segev Y, Jacob-Hirsch J, et al.

PLoS Med 5(8): e171.

doi:10.1371/journal.pmed.0050171

Click
Here For Full Length Article



Written by Anna Sophia McKenney

Gene That Influences Alcohol Consumption Identified

A variant of a gene involved in communication among brain cells has a direct influence on alcohol consumption in mice, according to a new study by scientists supported by the National Institute on Alcohol Abuse and Alcoholism (NIAAA), part of the National Institutes of Health (NIH), and the U.S. Army.



Scientists do not know yet whether a similar gene variant, with a similar effect on alcohol consumption, exists in humans.



Known as Grm7, the gene encodes a receptor subtype that inhibits the release of glutamate and other neurotransmitter molecules that brain cells use to communicate with one another. Researchers identified a gene variant, or polymorphism, that reduces the abundance of Grm7 messenger RNA (mRNA) in brain tissue. mRNA is the molecular intermediate between a gene and its protein product. Mice that possess this gene variant drink more alcohol than do mice with higher brain levels of Grm7 mRNA. A report of the study appears as an online Article in Press in Genomics.



"This is a noteworthy contribution, particularly since identifying genes that predispose to alcohol-related behaviors is such an arduous task," says NIAAA Director Ting-Kai Li, M.D.



Scientists have long known that genes account for a significant proportion of the risk for alcoholism. However, the fact that there are multiple such genes that interact with each other and with multiple environmental factors to influence drinking behavior has hampered studies aimed at isolating individual genes.



"Controlling for this background noise -- the various gene-gene and gene-environment interactions -- presents considerable methodological challenges," notes first author Csaba Vadasz, Ph.D., professor of psychiatric research in the department of psychiatry at New York University School of Medicine, and Director of the NeuroBehavioral Genetic Research Program at the Nathan Kline Institute in Orangeburg, N.Y.



To overcome these difficulties, Dr. Vadasz and colleagues applied a variety of genetic and analytic techniques to animals having nearly identical genetic background, but differing in their preference for alcohol, to identify a chromosomal region, and ultimately the Grm7 gene, associated with alcohol preference.



"Our findings support emerging evidence of the critical role that the brain's glutamate pathways play in addiction," says Dr. Vadasz. "While dopamine has traditionally been cast as a central actor in the neurochemistry of substance use and abuse, recent studies indicate that glutamate systems play an important role in reinforcement and addiction."



If further studies show that a similar gene variant is relevant to alcohol problems in humans, the finding by Dr. Vadasz and colleagues may lead to new opportunities for developing drugs to treat alcohol dependence. Dr. Vadasz speculates that such drugs might be designed to control the level of the Grm7 gene product or modulate the activity of the gene product itself.







The National Institute on Alcohol Abuse and Alcoholism, part of the National Institutes of Health, is the primary U.S. agency for conducting and supporting research on the causes, consequences, prevention, and treatment of alcohol abuse, alcoholism, and alcohol problems and disseminates research findings to general, professional, and academic audiences. Additional alcohol research information and publications are available at niaaa.nih/.



The National Institutes of Health (NIH) - The Nation's Medical Research Agency - includes 27 Institutes and Centers and is a component of the U. S. Department of Health and Human Services. It is the primary Federal agency for conducting and supporting basic, clinical, and translational medical research, and it investigates the causes, treatments, and cures for both common and rare diseases. For more information about NIH and its programs, visit nih/.



Source: John Bowersox


NIH/National Institute on Alcohol Abuse and Alcoholism

"Instructor" Molecule Discovered That Makes Blood Vessel Cells Form Tube-Like Structures

How do blood vessel cells understand that they should organise themselves in tubes and not in layers? A research group from Uppsala University shows for the first time that a special type of "instructor" molecule is needed to accomplish this. These findings, published in the scientific journal Blood, might be an important step towards using stem cells to build new organs.



In order for a body to develop and function the cells in the body must be able to organise themselves in relation to each other. The way in which cells are arranged depends on the organ where they are located. Blood vessel cells need to form three-dimensional, tube-like structures that can transport blood. But how do blood vessel cells know that they should do that? An important part of the communication between cells and their environment is the use of growth factors. These are proteins that bind to receptors on the surface of the cell that receives the information. When the receptor in turn forms a complex with other proteins, on the inside of the cell, the read-out from the DNA can be altered. The information has "arrived".



VEGF (vascular endothelial growth factor) is a family of closely related growth factors that control blood vessel cells throughout life. Blood vessel development in the foetus as well as later in life, for example during wound healing, is regulated by VEGF. In the present study the research group has examined how VEGF can instruct blood vessel cells to arrange themselves into a tube. The answer is that some variants of VEGF have the ability to attract another protein, an instructor molecule, which is joined together with VEGF and its reeptor. The combination of instructor molecule, VEGF and receptor results in that a specific signal is sent inside the blood vessel cells, making them form a tube. Without the instructor molecule the cells line up next to each other, in a layer.



These results may become very useful. Today stem cells are used to create new cells, organs and even tissues, that in the future might be used to for transplantation instead of donated organs. If a patient's own stem cells are used the problem with organ rejection is avoided. But so far there has been a challenge to create three-dimensional structures from stem cells.



Our contribution can make it possible to create blood vessels from stem cells and to direct them to form a tube instead of a layer. Perhaps this knowledge can be transferred to the formation of other tube-like structures in the body, such as the lung and intestines. The perspectives for the future are very exciting, says Lena Claesson-Welsh, who has led the study.







Source: Kerstin Henriksson


Uppsala University

Fertility Decline Driven By Marriage Patterns

Researchers at the University of Sheffield have applied an evolutionary 'use it or lose it' principle when studying past marriage patterns, to show that marriage can influence the evolution of age-patterns of fertility.



Researchers Duncan Gillespie, Dr Virpi Lummaa and Dr Andrew Russell, from the University's Department of Animal and Plant Sciences, studied Finnish church records from the 18th and 19th centuries, a time during which almost everyone married and divorce was forbidden, to trace the survival and marriage histories of 1,591 women.



They found that women aged 30-35 were the most likely to be married. Those that married wealthy husbands were married at a younger age but to relatively older men, thereby gaining the family size-benefits of wealth but also an increased risk of widowhood. This high chance of widowhood, coupled with low re-marriage prospects for older widows with children, limited the percentage of women in the population with the opportunity to reproduce at older ages.



In todayВґs society however, women do not start childbearing until an older age as marriage is often delayed, and casual or short-term relationships and divorce are more common. As a result, the natural selection maintaining young-age fertility might weaken and the relative strength of natural selection on old-age fertility could increase, something that could potentially lead to improvements in old-age fertility over many generations.



Duncan Gillespie from the University of SheffieldВґs Department of Animal and Plant Sciences, said: "In todayВґs society, family-building appears to be increasingly postponed to older ages, when relatively few women in our evolutionary past would have had the opportunity to reproduce. As a result, this could lead to future evolutionary improvements in old-age female fertility.



"Childbearing within a relationship is still the norm in modern society, but at ages where fewer women have the chance to reproduce, we should expect the evolution of lower fertility."



Paper:
"Pair-bonding modifies the age-specific intensities of natural selection on human female fecundity"



Source:

Shemina Davis


University of Sheffield