New and Exciting in PLoS this week

Lots of cool new papers in PLoS Biology, PLoS Medicine and PLoS Neglected Tropical Diseases today. My picks are under the fold, but you look around and see what you are interested in:

Historical and Philosophical Perspectives on Contemporary Biology by Evelyn Fox Keller:

The work of historians and philosophers of science has long benefited from conversations with practicing scientists, but to many scientific researchers–perhaps especially to those engaged in laboratory work–the value that such dialogue might have for their own endeavor is not nearly so obvious. There are of course exceptions–evolutionary biology, for one. Over the last several decades, a tradition of active engagement between historians and philosophers on the one hand, and evolutionary biologists on the other, has become well established, and, as most participants would surely agree, this tradition has proven to be of manifest and clearly mutual benefit. The new series, Historical and Philosophical Perspectives, launched in this issue of PLoS Biology, provides the opportunity to help promote a similar engagement in other areas of biology. This opportunity is both welcome and timely: not only do I believe it is long overdue (there is, after all, no reason to regard evolutionary biology as a special case in this regard), but also, such an opportunity seems to me to be especially propitious today.

Towards an Integrated Framework for Assessing the Vulnerability of Species to Climate Change:

Global climate change threatens global biodiversity, ecosystem function, and human well-being, with thousands of publications demonstrating impacts across a wide diversity of taxonomic groups, ecosystems, economics, and social structure. A review by Hughes [1] identified many of the ways that organisms may be affected by and/or respond to climate change. Since then, there has been a dramatic increase in the number of case studies attesting to ecological impacts [2], prompting several recent reviews on the subject (e.g., [3-6]). Several global meta-analyses confirm the pervasiveness of the global climate change “fingerprint” across continents, ecosystems, processes, and species [7-9]. Some studies have predicted increasingly severe future impacts with potentially high extinction rates in natural systems around the world [10,11]. Responding to this threat will require a concerted, multi-disciplinary, multi-scale, multi-taxon research effort that improves our predictive capacity to identify and prioritise vulnerable species in order to inform governments of the seriousness of the threat and to facilitate conservation adaptation and management [12,13].

‘It’s Ok, We’re Not Cousins by Blood’: The Cousin Marriage Controversy in Historical Perspective:

In February, 2008, British environment minister Phil Woolas sparked a major row in the United Kingdom when he attributed the high rate of birth defects in the Pakistani community to the practice of marriages between first cousins. “If you have a child with your cousin, the likelihood is there’ll be a genetic problem,” he told the Sunday Times [1]. Although a Muslim activist group demanded that Woolas be fired, he was instead promoted in October to the racially sensitive post of immigration minister. Most of his constituents would surely have shared Woolas’ view that the risk to offspring from first-cousin marriage is unacceptably high–as would many Americans. Indeed, in the United States, similar assumptions about the high level of genetic risk associated with cousin marriage are reflected in the 31 state laws that either bar the practice outright or permit it only where the couple obtains genetic counseling, is beyond reproductive age, or if one partner is sterile. When and why did such laws become popular, and is the sentiment that informs them grounded in scientific fact?

Animal Defenses against Infectious Agents: Is Damage Control More Important Than Pathogen Control:

Once an infectious agent is established, hosts can do two things to minimize the agent’s impact on their health. Most obviously, they can directly attack the growing pathogen population to contain or eliminate it. But hosts can also attempt to minimize the harm caused by a given number of pathogens, for instance by ramping up tissue repair and detoxifying pathogen by-products. “Resistance” and “tolerance,” as these two types of defense are known in the plant literature, were first distinguished by botanists in the late 1800s [1] and this distinction has been a focus of considerable work by plant scientists since then [2-4]. However, those advances have had a minimal effect on the study of animal diseases. Immunologists, microbiologists, and parasitologists have typically focused on the ability to limit parasite numbers (resistance) or the overall ability to maintain health irrespective of parasite burden (resistance plus tolerance), with little attempt to formally decompose human or animal health into resistance and tolerance components. That situation is only now beginning to change. The early results already have significant experimental and conceptual implications.

Identifying Neural Drivers with Functional MRI: An Electrophysiological Validation:

Our understanding of how the brain works relies on the development of neuropsychological models, which describe how brain activity is coordinated among different regions during the execution of a given task. Knowing the directionality of information transfer between connected regions, and in particular distinguishing neural drivers, or the source of forward connections in the brain, from other brain regions, is critical to refine models of the brain. However, whether functional magnetic resonance imaging (fMRI), the most common technique for imaging brain function, allows one to identify neural drivers remains an open question. Here, we used a rat model of absence epilepsy, a form of nonconvulsive epilepsy that occurs during childhood in humans, showing spontaneous spike-and-wave discharges (nonconvulsive seizures) originating from the first somatosensory cortex, to validate several functional connectivity measures derived from fMRI. Standard techniques estimating interactions directly from fMRI data failed because blood flow dynamics varied between regions. However, we were able to identify the neural driver of spike-and-wave discharges when hemodynamic effects were explicitly removed using appropriate modelling. This study thus provides the first experimental substantiation of the theoretical possibility to improve interregional coupling estimation from hidden neural states of fMRI. As such, it has important implications for future studies on connectivity in the functional neuroimaging literature.

Tissue-Specific Genetic Control of Splicing: Implications for the Study of Complex Traits:

Although humans have a relatively small complement of genes, the proteins encoded by those genes and their biologic function are far more complex. The increased complexity is achieved in part through processes that create different messages from the same gene sequence (alternative splicing) and that regulate the expression of those messages in a tissue-specific fashion. These processes expand the functional capacity of the human genome, but also can create predisposition to disease when these processes go awry. In this study, we investigated how single nucleotide polymorphisms influence both overall gene expression and alternative splicing in two important cell types (brain and blood) highly relevant to human disease. Extensive and tissue-specific regulation of gene expression and alternative splicing were observed in the two tissue types, and some of these polymorphisms were shown to be connected to other polymorphsims that have been recently implicated in human diseases through genome-wide association studies. Most of these connections appeared to relate to alternative splicing as opposed to overall expression changes, suggesting that changes in splicing patterns may be more consequential for disease than those affecting only expression. These data emphasize the importance of comprehensive studies into genetic regulation of gene expression in all human tissue types in order to help understand how genetic variation influences risk of common diseases.

Homelessness Is Not Just a Housing Problem:

Homelessness is about more than rooflessness. A home is not just a physical space: it provides roots, identity, security, a sense of belonging and a place of emotional wellbeing.” So says the United Kingdom charity Crisis [1]. This Editorial’s title comes from another charity, Shelter [2], which breaks down the causes of homelessness into individual factors such as drug and alcohol misuse; lack of social support; family background, including family breakdown and disputes; and an institutional background, including being in prison, or increasingly and perhaps especially shamefully today, the armed services.

‘A Good Personal Scientific Relationship’: Philip Morris Scientists and the Chulabhorn Research Institute, Bangkok:

Tobacco use kills 5.4 million people a year (one person every six seconds) and accounts for one in ten adult deaths worldwide. Globally, the use of tobacco is on the rise, especially in developing countries, which have become a major target for tobacco industry marketing. The tobacco industry has worked hard to try and influence public perceptions about the risks of smoking and the risk of inhaling secondhand smoke (passive smoking). The industry has used a variety of tactics to downplay the health hazards of smoking or inhaling secondhand smoke–two examples are publishing articles casting doubts about the health hazards of tobacco and funding research that is biased toward giving pro-industry results. Another tactic is for tobacco industry consultants to try and gain entry to universities and other academic centers to see if they can influence research and teaching activities.

The Natural Progression of Gambiense Sleeping Sickness: What Is the Evidence?:

Gambiense human African trypanosomiasis (HAT, sleeping sickness) is widely assumed to be 100% pathogenic and fatal. However, reports to the contrary exist, and human trypano-tolerance has been postulated. Furthermore, there is uncertainty about the actual duration of both stage 1 and stage 2 infection, particularly with respect to how long a patient remains infectious. Understanding such basic parameters of HAT infection is essential for optimising control strategies based on case detection. We considered the potential existence and relevance of human trypano-tolerance, and explored the duration of infectiousness, through a review of published evidence on the natural progression of gambiense HAT in the absence of treatment, and biological considerations. Published reports indicate that most gambiense HAT cases are fatal if untreated. Self-resolving and asymptomatic chronic infections probably constitute a minority if they do indeed exist. Chronic carriage, however, deserves further study, as it could seed renewed epidemics after control programmes cease.

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