Let's check all seven PLoS journals today. As always, you should rate the articles, post notes and comments and send trackbacks when you blog about the papers. You can now also easily place articles on various social services (CiteULike, Mendeley, Connotea, Stumbleupon, Facebook and Digg) with just one click. Here are my own picks for the week - you go and look for your own favourites:
Circadian and Social Cues Regulate Ion Channel Trafficking:
Excitable cells, such as neurons and muscle cells, control behavior by generating action potentials, electrical signals that propagate along the cell membrane. Action potentials are generated when the cell allows charged molecules (ions) such as sodium and potassium to move across the membrane through specialized proteins called ion channels. By changing the number of ion channels in the plasma membrane, excitable cells can rapidly remodel their functional characteristics, potentially causing changes in behavior. To gain an understanding of how environmental events cause the remodeling of excitable cell membranes and the resulting behavioral adaptations, we studied the electric communication/navigation signals of an electric fish, Sternopygus macrurus. High amplitude signals facilitate communication and electrolocation, but are energetically costly and more detectable by those predators that can detect electrical signals. We found that Sternopygus increase signal amplitude at night, when they are active, and increase signal amplitude rapidly during social encounters. Electrocytes, the cells that produce the signal, rapidly boost the signal amplitude when they allow more sodium to cross the cell membrane, thereby generating larger action potentials. To increase sodium currents during the action potential, electrocytes rapidly insert additional sodium channels into the cell membrane in response to hormones released into circulation by the pituitary. By adding new ion channels to the electrocyte membrane only during periods of activity or social encounters and removing these channels during inactive periods, these animals can save energy and reduce predation risks associated with communication.
The harpy eagle (Harpia harpyja) is the largest Neotropical bird of prey and is threatened by human persecution and habitat loss and fragmentation. Current conservation strategies include local education, captive rearing and reintroduction, and protection or creation of trans-national habitat blocks and corridors. Baseline genetic data prior to reintroduction of captive-bred stock is essential for guiding such efforts but has not been gathered previously. We assessed levels of genetic diversity, population structure and demographic history for harpy eagles using samples collected throughout a large portion of their geographic distribution in Central America (n = 32) and South America (n = 31). Based on 417 bp of mitochondrial control region sequence data, relatively high levels of haplotype and nucleotide diversity were estimated for both Central and South America, although haplotype diversity was significantly higher for South America. Historical restriction of gene flow across the Andes (i.e. between our Central and South American subgroups) is supported by coalescent analyses, the haplotype network and significant FST values, however reciprocally monophyletic lineages do not correspond to geographical locations in maximum likelihood analyses. A sudden population expansion for South America is indicated by a mismatch distribution analysis, and further supported by significant (p<0.05) negative values of Fu and Li's DF and F, and Fu's FS. This expansion, estimated at approximately 60 000 years BP (99 000-36 000 years BP 95% CI), encompasses a transition from a warm and dry time period prior to 50 000 years BP to an interval of maximum precipitation (50 000-36 000 years BP). Notably, this time period precedes the climatic and habitat changes associated with the last glacial maximum. In contrast, a multimodal distribution of haplotypes was observed for Central America suggesting either population equilibrium or a recent decline. High levels of mitochondrial genetic diversity in combination with genetic differentiation among subgroups within regions and between regions highlight the importance of local population conservation in order to preserve maximal levels of genetic diversity in this species. Evidence of historically restricted female-mediated gene flow is an important consideration for captive-breeding programs.
Spread of Avian Influenza Viruses by Common Teal (Anas crecca) in Europe:
Since the recent spread of highly pathogenic (HP) H5N1 subtypes, avian influenza virus (AIV) dispersal has become an increasing focus of research. As for any other bird-borne pathogen, dispersal of these viruses is related to local and migratory movements of their hosts. In this study, we investigated potential AIV spread by Common Teal (Anas crecca) from the Camargue area, in the South of France, across Europe. Based on bird-ring recoveries, local duck population sizes and prevalence of infection with these viruses, we built an individual-based spatially explicit model describing bird movements, both locally (between wintering areas) and at the flyway scale. We investigated the effects of viral excretion duration and inactivation rate in water by simulating AIV spread with varying values for these two parameters. The results indicate that an efficient AIV dispersal in space is possible only for excretion durations longer than 7 days. Virus inactivation rate in the environment appears as a key parameter in the model because it allows local persistence of AIV over several months, the interval between two migratory periods. Virus persistence in water thus represents an important component of contamination risk as ducks migrate along their flyway. Based on the present modelling exercise, we also argue that HP H5N1 AIV is unlikely to be efficiently spread by Common Teal dispersal only.
Novel Vaccines to Human Rabies:
Rabies, the most fatal of all infectious diseases, remains a major public health problem in developing countries, claiming the lives of an estimated 55,000 people each year. Most fatal rabies cases, with more than half of them in children, result from dog bites and occur among low-income families in Southeast Asia and Africa. Safe and efficacious vaccines are available to prevent rabies. However, they have to be given repeatedly, three times for pre-exposure vaccination and four to five times for post-exposure prophylaxis (PEP). In cases of severe exposure, a regimen of vaccine combined with a rabies immunoglobulin (RIG) preparation is required. The high incidence of fatal rabies is linked to a lack of knowledge on the appropriate treatment of bite wounds, lack of access to costly PEP, and failure to follow up with repeat immunizations. New, more immunogenic but less costly rabies virus vaccines are needed to reduce the toll of rabies on human lives. A preventative vaccine used for the immunization of children, especially those in high incidence countries, would be expected to lower fatality rates. Such a vaccine would have to be inexpensive, safe, and provide sustained protection, preferably after a single dose. Novel regimens are also needed for PEP to reduce the need for the already scarce and costly RIG and to reduce the number of vaccine doses to one or two. In this review, the pipeline of new rabies vaccines that are in pre-clinical testing is provided and an opinion on those that might be best suited as potential replacements for the currently used vaccines is offered.
Drugs Associated with More Suicidal Ideations Are also Associated with More Suicide Attempts:
In randomized controlled trials (RCTs), some drugs, including CB1 antagonists for obesity treatment, have been shown to cause increased suicidal ideation. A key question is whether drugs that increase or are associated with increased suicidal ideations are also associated with suicidal behavior, or whether drug-induced suicidal ideations are unlinked epiphenomena that do not presage the more troubling and potentially irrevocable outcome of suicidal behavior. This is difficult to determine in RCTs because of the rarity of suicidal attempts and completions. To determine whether drugs associated with more suicidal ideations are also associated with more suicide attempts in large spontaneous adverse event (AE) report databases. Generalized linear models with negative binomial distribution were fitted to Food and Drug Administration (FDA) Adverse Event (AE) Reporting System (AERS) data from 2004 to 2008. A total of 1,404,470 AEs from 832 drugs were analyzed as a function of reports of suicidal ideations; other non-suicidal adverse reactions; drug class; proportion of reports from males; and average age of subject for which AE was filed. Drug was treated as the unit of analysis, thus the statistical models effectively had 832 observations. Reported suicide attempts and completed suicides per drug. 832 drugs, ranging from abacavir to zopiclone, were evaluated. The 832 drugs, as primary suspect drugs in a given adverse event, accounted for over 99.9% of recorded AERS. Suicidal ideations had a significant positive association with suicide attempts (p<.0001) and had an approximately 131-fold stronger magnitude of association than non-suicidal AERs, after adjusting for drug class, gender, and age. In AE reports, drugs that are associated with increased suicidal ideations are also associated with increased suicidal attempts or completions. This association suggests that drug-induced suicidal ideations observed in RCTs plausibly represent harbingers that presage the more serious suicide attempts and completions and should be a cause for concern.
Ensuring Integrity in Comparative Effectiveness Research: Accentuate the Negative:
In recent weeks, PLoS Medicine has published several research papers that challenge current health care practices.
One study found that a campaign to promote solar drinking water disinfection did not substantially decrease rates of childhood diarrhea [1]. Another found more than a doubled risk of hospitalization for bradycardia in older people taking cholinesterase inhibitors used to treat cognitive impairment [2]. A systematic review failed to find any randomized trials that support the internationally recommended retreatment regimen for tuberculosis [3]. Finally, a study of one of the main international registries for clinical trials, ClinicalTrials.gov, found that requirements to register clinical trials have not resulted in high publication rates [4].
A study that questions the accepted or desired way of doing things can be at least as important as one that supports a new approach. Physicians mindful of Hippocrates' vow to "first do no harm" should take a keen interest in such studies, for while a new intervention that proves efficacious in clinical trials may pass slowly, if at all, through practical barriers to effective implementation, the demonstration that an existing practice is ineffective or potentially harmful can (or should) prompt a rapid change in research agendas, policy, and clinical care. Knowing what doesn't work is particularly useful in efforts to control medical spending, where redirecting limited resources away from ineffective interventions is of obvious benefit.
Public Access to Genome-Wide Data: Five Views on Balancing Research with Privacy and Protection:
Just over twelve months ago, PLoS Genetics published a paper [1] demonstrating that, given genome-wide genotype data from an individual, it is, in principle, possible to ascertain whether that individual is a member of a larger group defined solely by aggregate genotype frequencies, such as a forensic sample or a cohort of participants in a genome-wide association study (GWAS). As a consequence, the National Institutes of Health (NIH) and Wellcome Trust agreed to shut down public access not just to individual genotype data but even to aggregate genotype frequency data from each study published using their funding. Reactions to this decision span the full breadth of opinion, from "too little, too late--the public trust has been breached" to "a heavy-handed bureaucratic response to a practically minimal risk that will unnecessarily inhibit scientific research." Scientific concerns have also been raised over the conditions under which individual identity can truly be accurately determined from GWAS data. These concerns are addressed in two papers published in this month's issue of PLoS Genetics [2],[3]. We received several submissions on this topic and decided to assemble these viewpoints as a contribution to the debate and ask readers to contribute their thoughts through the PLoS online commentary features.
Needles in the Haystack: Identifying Individuals Present in Pooled Genomic Data:
In this report, we evaluate a recently-published method for resolving whether individuals are present in a complex genomic DNA mixture. Based on the intuition that an individual will be genetically "closer" to a sample containing him than to a sample not, the method investigated here uses a distance metric to quantify the similarity of an individual relative to two population samples. Although initial applications of this approach showed a promising false-negative rate, the accuracy of the assumed null distribution (and hence the true false-positive rate) remained uninvestigated; here, we explore this question analytically and describe tests of this method to assess the likelihood that an individual who is not in the mixture is mistakenly classified as being a member. Our results show that the method has a high false-positive rate in practice due to its sensitivity to underlying assumptions, limiting its utility for inferring the presence of an individual in a population. By revealing both the strengths and limitations of the proposed method, we elucidate situations in which this distance metric may be used in an appropriate manner in forensics and medical privacy policy.
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