A Blog Around The Clock

Genetic Dissection of Behavioural and Autonomic Effects of Δ9-Tetrahydrocannabinol in Mice and the accompanying editorial Understanding Cannabinoid Psychoactivity with Mouse Genetic Models:

The fact that cannabis is the most widely used illicit drug has motivated a great deal of research aimed at understanding how it produces its psychoactive effects. Here I use the term psychoactive to describe the mild euphoria, altered perceptions, sense of relaxation, and sociability that often, but not always, accompany recreational cannabis use. Despite the difficulties inherent in working with lipophilic cannabinoids such as Δ9-tetrahydrocannabinol (THC), which is the primary psychoactive component of cannabis, our understanding of the mechanism of action of these compounds at the cellular level has increased dramatically over the past 20 years. However, a complete understanding of how cannabis elicits its psychoactive effects would include an appreciation of its actions at the cellular and network level as well as an identification of the neural circuits perturbed. The cannabinoid field has now matured to the point where investigators can begin to relate the cellular mechanisms of THC action to the behavioral effects of cannabis.

HCV-HIV Coinfection: Simple Messages from a Complex Disease:

Hepatitis C virus (HCV) and HIV infection are both major global health problems, each with their own specific unsolved and difficult issues of prevention, pathogenesis, and therapy. For HIV, many of the clinical problems experienced are related to loss of immunological control over relatively commonly encountered pathogens. In most of these cases (e.g., cytomegalovirus [CMV], Pneumocystis jiroveci. human herpesvirus-8), normal immunological control is quite efficient, and these organisms behave as “opportunists.” HCV is slightly different, in that immunological control in normal HIV-uninfected individuals is often poor, and HCV infection alone can lead to the gradual evolution of end-stage liver disease in normal hosts. However, although a consensus is forming about the basic details of the immune responses associated with acute control of HCV monoinfection, the long-term relationships between immune responses, viral load, and most importantly, disease progression in those who are persistently infected are still poorly understood.

Genes From The Father Facilitate The Formation Of New Species:

The two closely related bird species, the collared flycatcher and the pied flycatcher, can reproduce with each other, but the females are more strongly attracted to a male of their own species. This has been shown by an international research team directed by Anna Qvarnström at Uppsala University and published in Science. They demonstrate that the gene for this sexual preference is found on the sex chromosome that is inherited from the father and that only females have a copy of. The discovery sheds new light on how new species are formed.

Primitive Plants Use Heat And Odor To Woo Pollinating Insects:

University of Utah scientists discovered a strange method of reproduction in primitive plants named cycads: The plants heat up and emit a toxic odor to drive pollen-covered insects out of male cycad cones, and then use a milder odor to draw the bugs into female cones so the plants are pollinated.

When Taking A Long Time Is Seen As A Good Thing:

Consumers often use the length of time a service takes as a measure of its quality. The longer a session lasts, the better the value. Indeed, a new study shows that this holds true even when judging something primarily by its duration can backfire — for example when a longer exercise program is actually less effective than a shorter regimen or for a lock-picking service.

Brain Images Make Cognitive Research More Believable:

People are more likely to believe findings from a neuroscience study when the report is paired with a colored image of a brain as opposed to other representational images of data such as bar graphs, according to a new Colorado State University study.

New Insights Into The Evolution Of The Human Genome:

Which came first, the chicken genome or the egg genome? Researchers have answered a similarly vexing (and far more relevant) genomic question: Which of the thousands of long stretches of repeated DNA in the human genome came first? And which are the duplicates?

Elephants’ Fear Of Angry Bees Could Help To Protect Them:

At a time when encroaching human development in former wildlife areas has compressed African elephants into ever smaller home ranges and increased levels of human-elephant conflict, a study in Current Biology, suggests that strategically placed beehives might offer a low-tech elephant deterrent and conservation measure.

Malaria Research Booming, But Scientific And Technical Gaps Apparent, Report Shows:

Malaria drug and vaccine research is booming. According to a new report launched in the UK by Australian researchers at The George Institute for International Health, 16 new malaria vaccine candidates are now in clinical trials; six new malaria drugs are about to reach the market; and by 2011 we will have up to 12 new anti-malarial drug product registered. However, this unprecedented level of malaria R&D activity is not necessarily all good news. The report’s authors found that the high number of malaria vaccine candidates was the result of scientific and technical gaps and lacking policy coordination rather than a reflection of cohesive global activity. Lack of coordination and planning mean that invested funding and efforts are not delivering as much as they should, and may be costing donors tens of millions of dollars.

How Do Cells Sense And Respond To Messages? Major Signal Transduction Discovery Made:

The chemical process known as acetylation plays a central role in cytokine receptor signal transduction – a fundamental biochemical cascade inside cells that controls the activity of antiviral and tumor-suppressing genes.

In Birds, Expecting To Mate Leads To Higher Fertilization Rates:

From an evolutionary perspective, the primary task of an organism is to pass along its genes to future generations. Such genetic transmission is usually assumed to be instinctive. However, a new study shows that species also learn to adapt to their surroundings in order to increase their “reproductive fitness”– the likelihood that they will successfully reproduce.

For Honey Bee Queens, Multiple Mating Makes Her Attractive To Workers:

The success of the “reign” of a honey bee queen appears to be determined to a large degree by the number of times she mates with drone bees.That is what research by scientists in the Department of Entomology and W.M. Keck Center for Behavioral Biology at North Carolina State University suggests. Dr. Freddie-Jeanne Richard, a post-doctoral research associate; Dr. David Tarpy, assistant professor and North Carolina Cooperative Extension apiculturist; and Dr. Christina Grozinger, assistant professor of insect genomics, found that the number of times a honey bee queen mates is a key factor in determining how attractive the queen is to the worker bees of a hive.

Chimpanzees, Unlike Humans, Apply Economic Principles To Ultimatum Game:

New research from the Max Planck Institute of Evolutionary Anthropology in Leipzig, Germany shows that unlike humans, chimpanzees conform to traditional economic models. The research used a modification of one of the most widely used and accepted economic tools, the ultimatum game.

New Telomere Discovery Could Help Explain Why Cancer Cells Never Stop Dividing:

A group working at the Swiss Institute for Experimental Cancer Research (ISREC) in collaboration with the University of Pavia has discovered that telomeres, the repeated DNA-protein complexes at the end of chromosomes that progressively shorten every time a cell divides, also contain RNA.

Key Step Bird Flu Virus Takes To Spread Readily In Humans Identified:

Since it first appeared in Hong Kong in 1997, the H5N1 avian flu virus has been slowly evolving into a pathogen better equipped to infect humans. The final form of the virus, biomedical researchers fear, will be a highly pathogenic strain of influenza that spreads easily among humans.

Why Emotionally Charged Events Are So Memorable:

Both extensive psychological research and personal experiences confirm that events that happen during heightened states of emotion such as fear, anger and joy are far more memorable than less dramatic occurrences.

Negativity Is Contagious, Study Finds:

Though we may not care to admit it, what other people think about something can affect what we think about it. This is how critics become influential and why our parents’ opinions about our life choices continue to matter, long after we’ve moved out. But what kind of opinions have the most effect” An important new study in the Journal of Consumer Research reveals that negative opinions cause the greatest attitude shifts, not just from good to bad, but also from bad to worse.

Simplest Circadian Clocks Operate Via Orderly Phosphate Transfers:

Researchers at Harvard University and the Howard Hughes Medical Institute have found that a simple circadian clock found in some bacteria operates by the rhythmic addition and subtraction of phosphate groups at two key locations on a single protein. This phosphate pattern is influenced by two other proteins, driving phosphorylation to oscillate according to a remarkably accurate 24-hour cycle.

Related: A Circadian Clock that works in a test-tube explained and Bacteria do it differently…

As always on Friday, there are new article published in the community journals – PLoS Pathogens, PLoS Computational Biology and PLoS Genetics. Here are few of my picks:
Growth of H5N1 Influenza A Viruses in the Upper Respiratory Tracts of Mice
A Single Mutation in the PB1-F2 of H5N1 (HK/97) and 1918 Influenza A Viruses Contributes to Increased Virulence
Universally Sloppy Parameter Sensitivities in Systems Biology Models
Ancient Exaptation of a CORE-SINE Retroposon into a Highly Conserved Mammalian Neuronal Enhancer of the Proopiomelanocortin Gene

Fossil Data Plugs Gaps In Current Knowledge, Study Shows:

Researchers have shown for the first time that fossils can be used as effectively as living species in understanding the complex branching in the evolutionary tree of life.

Cilia: Small Organelles, Big Decisions:

Johns Hopkins researchers say they have figured out how human and all animal cells tune in to a key signal, one that literally transmits the instructions that shape their final bodies. It turns out the cells assemble their own little radio antenna on their surfaces to help them relay the proper signal to the developmental proteins “listening” on the inside of the cell.

Avoiding Sweets May Spell A Longer Life, Study In Worms Suggests:

A new study in Cell Metabolism reveals that worms live to an older age when they are unable to process the simple sugar glucose. Glucose is a primary source of energy for the body and can be found in all major dietary carbohydrates as a component of starches and other forms of sugar, including sucrose (table sugar) and lactose.

Engineers Study Brain Folding In Higher Mammals:

Engineers at Washington University in St. Louis are finding common ground between the shaping of the brain and the heart during embryonic development.

Fungus Genome Yielding Answers To Protect Grains, People And Animals:

Why a pathogen is a pathogen may be answered as scientists study the recently mapped genetic makeup of a fungus that spawns the worst cereal grains disease known and also can produce toxins potentially fatal to people and livestock.

Large-scale Head Lice Finding Kits Effective:

Working with parents and schools to provide a bug busting approach to head lice is helping to reduce infestation levels, tackle health inequalities and reduce healthcare costs, according to a review in the Journal of Clinical Nursing.

Hydrothermal Vents: Hot Spots Of Microbial Diversity:

Thousands of new kinds of marine microbes have been discovered at two deep-sea hydrothermal vents off the Oregon coast by scientists at the MBL (Marine Biological Laboratory) and University of Washington’s Joint Institute for the Study of Atmosphere and Ocean.

Census Of Protein Architectures Offers New View Of History Of Life:

The present can tell you a lot about the past, but you need to know where to look. A new study appearing this month in Genome Research reveals that protein architectures – the three-dimensional structures of specific regions within proteins – provide an extraordinary window on the history of life.

Genes Determine Mate Choice, At Least For Fat Tailed Dwarf Lemurs:

How do we choose our mates? For quite some time now, scientists suspect that it is not for looks or fashion, neither for love or sympathy. It may be the genes that determine our preference for certain males or females. A new study provides support for this idea by looking at lemurs in Madagascar.

Beyond A ‘Speed Limit’ On Mutations, Species Risk Extinction:

Harvard University scientists have identified a virtual “speed limit” on the rate of molecular evolution in organisms, and the magic number appears to be 6 mutations per genome per generation — a level beyond which species run the strong risk of extinction as their genomes lose stability.

Genetic Differences In Clover Make One Type Toxic:

That clover necklace you make for your child could well be a ring of poison. That’s because some clovers have evolved genes that help the plant produce cyanide — to protect itself against little herbivores, such as snails, slugs and voles, that eat clover. Other clover plants that do not make cyanide are found in climates with colder temperatures. So, in picking your poison, er, clover, ecology and geography play important roles.

Spouses Often Mirror Each Other’s Health Habits:

If one spouse exercises, quits smoking, stops drinking alcohol, receives a flu shot, or undergoes a cholesterol screening, the other spouse is more likely to do the same, according to a new study in Health Services Research.

Galapagos Hawk’s Evolutionary History Illuminated:

Scientists at the University of Missouri-St. Louis used DNA sequences from feather lice to study how island populations of their host, the Galápagos Hawk might have colonized the Galápagos islands, home to the endangered and declining raptor.

Huge New Dinosaur Had A Serious Bite:

The newest dinosaur species to emerge from Grand Staircase-Escalante National Monument had some serious bite, according to researchers from the Utah Museum of Natural History at the University of Utah.

New Species Of Frog Discovered: Smallest Indian Land Vertebrate:

The India’s smallest land vertebrate, a 10-millimeter frog, has been discovered from the Western Ghats of Kerala by Delhi University Systematics Biologist, S D Biju and his colleagues.

No Faking It, Crocodile Tears Are Real:

When someone feigns sadness they “cry crocodile tears,” a phrase that comes from an old myth that the animals cry while eating. Now, a University of Florida researcher has concluded that crocodiles really do bawl while banqueting – but for physiological reasons rather than rascally reptilian remorse.

Sea Otter, Peregrine Falcon Back From The Brink Of Extinction But Other Species At Risk In Canada:

There’s good news and bad news in the report the Committee on the Status of Endangered Wildlife in Canada (COSEWIC) just dropped on the Minister of the Environment’s desk.

New Suspect Identified In West Nile Deaths Of Pelicans:

Stable flies are the latest suspect that may be involved in the West Nile virus deaths of hundreds of pelican chicks at the Medicine Lake National Wildlife Refuge in northeast Montana. West Nile virus killed 800 to 1,000 pelican chicks in 2003, averaged 400 in each of the next three summers and more than 600 this year.

Individual Differences Caused By Shuffled Chunks Of DNA In The Human Genome:

A study by Yale researchers offers a new view of what causes the greatest genetic variability among individuals — suggesting that it is due less to single point mutations than to the presence of structural changes that cause extended segments of the human genome to be missing, rearranged, or present in extra copies.

How ‘Mother Of Thousands’ Makes Baby Plants:

New research shows how the houseplant “mother of thousands” (Kalanchoe diagremontiana) makes the tiny plantlets that drop from the edges of its leaves. Having lost the ability to make viable seeds, the plant has shifted some of the processes that make seeds to the leaves, said Neelima Sinha, professor of plant biology at UC Davis.

Red Wine Ingredient — Resveratrol — Fights Diabetes In Mice:

Even relatively low doses of resveratrol–a chemical found in the skins of red grapes and in red wine–can improve the sensitivity of mice to the hormone insulin, according to a new report. As insulin resistance is often characterized as the most critical factor contributing to the development of type 2 diabetes, the findings “provide a potential new therapeutic approach for preventing or treating” both conditions, the researchers said.

In Dogs, A Shortcut To Mapping Disease Genes:

Nearly two years ago, Broad Institute researchers and their colleagues announced they had successfully decoded the genome of the domestic dog, a species coaxed into hundreds of distinct types through selective breeding by humans over the past two centuries.

Dogs That Bite Children Have Often Not Bitten Kids Before:

Dogs that bite children have often not bitten kids before, but they tend to have underlying behavioural or medical problems, indicates research in the journal Injury Prevention.

Biologists Close In On Mystery Of Sea Turtles’ ‘Lost Years’:

Biologists have found a major clue in a 50-year-old mystery about what happens to green sea turtles after they crawl out of their sandy nests and vanish into the surf, only to reappear several years later relatively close to shore.

Of Mice And Men: New Male Contraceptives Successful In Rodents And Humans:

Pills, sponges, IUDs, diaphragms — women have many options for planning their fertility, none of them quite perfect. But what if men want to help out? They have only two options — vasectomy, which is usually permanent, and condoms, which are crucial for dating but get old in long-term relationships. Will men ever have a way to reliably make sure that nobody is every calling them “Daddy” before they are ready?

There are 37 new articles on PLoS ONE today, breaking the 1000 barrier! Yes, there are now more than a thousand papers on ONE. And this week is again an embarassment of riches – so many bloggable papers! And here are some of my quick picks for this week – read them, rate them, annotate them, blog about them:
Composition and Hierarchical Organisation of a Spider Silk:

Albeit silks are fairly well understood on a molecular level, their hierarchical organisation and the full complexity of constituents in the spun fibre remain poorly defined. Here we link morphological defined structural elements in dragline silk of Nephila clavipes to their biochemical composition and physicochemical properties. Five layers of different make-ups could be distinguished. Of these only the two core layers contained the known silk proteins, but all can vitally contribute to the mechanical performance or properties of the silk fibre. Understanding the composite nature of silk and its supra-molecular organisation will open avenues in the production of high performance fibres based on artificially spun silk material.

Sexual Risk Factors for HIV Infection in Early and Advanced HIV Epidemics in Sub-Saharan Africa: Systematic Overview of 68 Epidemiological Studies:

It is commonly assumed that sexual risk factors for heterosexual HIV transmission in sub-Saharan Africa, such as multi-partner sex, paid sex and co-infections, become less important as HIV epidemics mature and prevalence increases.
We conducted a systematic review of 68 African epidemiological studies from 1986 to 2006 involving 17,000 HIV positive adults and 73,000 controls. We used random-effects methods and stratified results by gender, time, background HIV prevalence rates and other variables. The number of sex partners, history of paid sex, and infection with herpes simplex virus (HSV-2) or other sexually-transmitted infections (STIs) each showed significant associations with HIV infection. Among the general population, the odds ratio (OR) of HIV infection for women reporting 3+ sex partners versus 0-2 was 3.64 (95%CI [2.87-4.62]), with similar risks for men. About 9% of infected women reported ever having been paid for sex, versus 4% of control women (OR = 2.29, [1.45-3.62]). About 31% of infected men reported ever paying for sex versus 18% of uninfected men (OR = 1.75, [1.30-2.36]). HSV-2 infection carried the largest risk of HIV infection: OR = 4.62, [2.85-7.47] in women, and OR = 6.97, [4.68-10.38] in men. These risks changed little over time and stratification by lower and higher HIV background prevalence showed that risk ratios for most variables were larger in high prevalence settings. Among uninfected controls, the male-female differences in the number of sex partners and in paid sex were more extreme in the higher HIV prevalence settings than in the lower prevalence settings.
Multi-partner sex, paid sex, STIs and HSV-2 infection are as important to HIV transmission in advanced as in early HIV epidemics. Even in high prevalence settings, prevention among people with high rates of partner change, such as female sex workers and their male clients, is likely to reduce transmission overall.

Inflated Impact Factors? The True Impact of Evolutionary Papers in Non-Evolutionary Journals:

Amongst the numerous problems associated with the use of impact factors as a measure of quality are the systematic differences in impact factors that exist among scientific fields. While in theory this can be circumvented by limiting comparisons to journals within the same field, for a diverse and multidisciplinary field like evolutionary biology, in which the majority of papers are published in journals that publish both evolutionary and non-evolutionary papers, this is impossible. However, a journal’s overall impact factor may well be a poor predictor for the impact of its evolutionary papers. The extremely high impact factors of some multidisciplinary journals, for example, are by many believed to be driven mostly by publications from other fields. Despite plenty of speculation, however, we know as yet very little about the true impact of evolutionary papers in journals not specifically classified as evolutionary. Here I present, for a wide range of journals, an analysis of the number of evolutionary papers they publish and their average impact. I show that there are large differences in impact among evolutionary and non-evolutionary papers within journals; while the impact of evolutionary papers published in multidisciplinary journals is substantially overestimated by their overall impact factor, the impact of evolutionary papers in many of the more specialized, non-evolutionary journals is significantly underestimated. This suggests that, for evolutionary biologists, publishing in high-impact multidisciplinary journals should not receive as much weight as it does now, while evolutionary papers in more narrowly defined journals are currently undervalued. Importantly, however, their ranking remains largely unaffected. While journal impact factors may thus indeed provide a meaningful qualitative measure of impact, a fair quantitative comparison requires a more sophisticated journal classification system, together with multiple field-specific impact statistics per journal.

Ant Species Differences Determined by Epistasis between Brood and Worker Genomes:

Epistasis arising from physiological interactions between gene products often contributes to species differences, particularly those involved in reproductive isolation. In social organisms, phenotypes are influenced by the genotypes of multiple interacting individuals. In theory, social interactions can give rise to an additional type of epistasis between the genomes of social partners that can contribute to species differences. Using a full-factorial cross-fostering design with three species of closely related Temnothorax ants, I found that adult worker size was determined by an interaction between the genotypes of developing brood and care-giving workers, i.e. intergenomic epistasis. Such intergenomic social epistasis provides a strong signature of coevolution between social partners. These results demonstrate that just as physiologically interacting genes coevolve, diverge, and contribute to species differences, so do socially interacting genes. Coevolution and conflict between social partners, especially relatives such as parents and offspring, has long been recognized as having widespread evolutionary effects. This coevolutionary process may often result in coevolved socially-interacting gene complexes that contribute to species differences.

Phylogeny, Diet, and Cranial Integration in Australodelphian Marsupials:

Studies of morphological integration provide valuable information on the correlated evolution of traits and its relationship to long-term patterns of morphological evolution. Thus far, studies of morphological integration in mammals have focused on placentals and have demonstrated that similarity in integration is broadly correlated with phylogenetic distance and dietary similarity. Detailed studies have also demonstrated a significant correlation between developmental relationships among structures and adult morphological integration. However, these studies have not yet been applied to marsupial taxa, which differ greatly from placentals in reproductive strategy and cranial development and could provide the diversity necessary to assess the relationships among phylogeny, ecology, development, and cranial integration. This study presents analyses of morphological integration in 20 species of australodelphian marsupials, and shows that phylogeny is significantly correlated with similarity of morphological integration in most clades. Size-related correlations have a significant affect on results, particularly in Peramelia, which shows a striking decrease in similarity of integration among species when size is removed. Diet is not significantly correlated with similarity of integration in any marsupial clade. These results show that marsupials differ markedly from placental mammals in the relationships of cranial integration, phylogeny, and diet, which may be related to the accelerated development of the masticatory apparatus in marsupials.

Effects of Insemination Quantity on Honey Bee Queen Physiology:

Mating has profound effects on the physiology and behavior of female insects, and in honey bee (Apis mellifera) queens, these changes are permanent. Queens mate with multiple males during a brief period in their early adult lives, and shortly thereafter they initiate egg-laying. Furthermore, the pheromone profiles of mated queens differ from those of virgins, and these pheromones regulate many different aspects of worker behavior and colony organization. While it is clear that mating causes dramatic changes in queens, it is unclear if mating number has more subtle effects on queen physiology or queen-worker interactions; indeed, the effect of multiple matings on female insect physiology has not been broadly addressed. Because it is not possible to control the natural mating behavior of queens, we used instrumental insemination and compared queens inseminated with semen from either a single drone (single-drone inseminated, or SDI) or 10 drones (multi-drone inseminated, or MDI). We used observation hives to monitor attraction of workers to SDI or MDI queens in colonies, and cage studies to monitor the attraction of workers to virgin, SDI, and MDI queen mandibular gland extracts (the main source of queen pheromone). The chemical profiles of the mandibular glands of virgin, SDI, and MDI queens were characterized using GC-MS. Finally, we measured brain expression levels in SDI and MDI queens of a gene associated with phototaxis in worker honey bees (Amfor). Here, we demonstrate for the first time that insemination quantity significantly affects mandibular gland chemical profiles, queen-worker interactions, and brain gene expression. Further research will be necessary to elucidate the mechanistic bases for these effects: insemination volume, sperm and seminal protein quantity, and genetic diversity of the sperm may all be important factors contributing to this profound change in honey bee queen physiology, queen behavior, and social interactions in the colony.

The Genetic Signature of Sex-Biased Migration in Patrilocal Chimpanzees and Humans:

A large body of theoretical work suggests that analyses of variation at the maternally inherited mitochondrial (mt)DNA and the paternally inherited non-recombining portion of the Y chromosome (NRY) are a potentially powerful way to reveal the differing migratory histories of men and women across human societies. However, the few empirical studies comparing mtDNA and NRY variation and known patterns of sex-biased migration have produced conflicting results. Here we review some methodological reasons for these inconsistencies, and take them into account to provide an unbiased characterization of mtDNA and NRY variation in chimpanzees, one of the few mammalian taxa where males routinely remain in and females typically disperse from their natal groups. We show that patterns of mtDNA and NRY variation are more strongly contrasting in patrilocal chimpanzees compared with patrilocal human societies. The chimpanzee data we present here thus provide a valuable comparative benchmark of the patterns of mtDNA and NRY variation to be expected in a society with extremely female-biased dispersal.

Non-Invasive In Vivo Imaging of Calcium Signaling in Mice:

Rapid and transient elevations of Ca2+ within cellular microdomains play a critical role in the regulation of many signal transduction pathways. Described here is a genetic approach for non-invasive detection of localized Ca2+ concentration ([Ca2+]) rises in live animals using bioluminescence imaging (BLI). Transgenic mice conditionally expressing the Ca2+-sensitive bioluminescent reporter GFP-aequorin targeted to the mitochondrial matrix were studied in several experimental paradigms. Rapid [Ca2+] rises inside the mitochondrial matrix could be readily detected during single-twitch muscle contractions. Whole body patterns of [Ca2+] were monitored in freely moving mice and during epileptic seizures. Furthermore, variations in mitochondrial [Ca2+] correlated to behavioral components of the sleep/wake cycle were observed during prolonged whole body recordings of newborn mice. This non-invasive imaging technique opens new avenues for the analysis of Ca2+ signaling whenever whole body information in freely moving animals is desired, in particular during behavioral and developmental studies.

Design and Pre-Clinical Evaluation of a Universal HIV-1 Vaccine:

One of the big roadblocks in development of HIV-1/AIDS vaccines is the enormous diversity of HIV-1, which could limit the value of any HIV-1 vaccine candidate currently under test.
To address the HIV-1 variation, we designed a novel T cell immunogen, designated HIVCONSV, by assembling the 14 most conserved regions of the HIV-1 proteome into one chimaeric protein. Each segment is a consensus sequence from one of the four major HIV-1 clades A, B, C and D, which alternate to ensure equal clade coverage. The gene coding for the HIVCONSV protein was inserted into the three most studied vaccine vectors, plasmid DNA, human adenovirus serotype 5 and modified vaccine virus Ankara (MVA), and induced HIV-1-specific T cell responses in mice. We also demonstrated that these conserved regions prime CD8+ and CD4+ T cell to highly conserved epitopes in humans and that these epitopes, although usually subdominant, generate memory T cells in patients during natural HIV-1 infection.
Therefore, this vaccine approach provides an attractive and testable alternative for overcoming the HIV-1 variability, while focusing T cell responses on regions of the virus that are less likely to mutate and escape. Furthermore, this approach has merit in the simplicity of design and delivery, requiring only a single immunogen to provide extensive coverage of global HIV-1 population diversity.