Early neuroimaging markers of FOXP2 intragenic deletion

FOXP2 is the major gene associated with severe, persistent, developmental speech and language disorders. While studies in the original family in which a FOXP2 mutation was found showed volume reduction and reduced activation in core language and speech networks, there have been no imaging studies of different FOXP2 mutations. We conducted a multimodal MRI study in an eight-year-old boy (A-II) with a de novo FOXP2 intragenic deletion. A-II showed marked bilateral volume reductions in the hippocampus, thalamus, globus pallidus, and caudate nucleus compared with 26 control males (effect sizes from −1 to −3). He showed no detectable functional MRI activity when repeating nonsense words. The hippocampus is implicated for the first time in FOXP2 diseases. We conclude that FOXP2 anomaly is either directly or indirectly associated with atypical development of widespread subcortical networks early in life

Black Stork Down: Military Discourses in Bird Conservation in Malta

Tensions between Maltese hunters and bird conservation NGOs have intensified over the past decade. Conservation NGOs have become frustrated with the Maltese State for conceding to the hunter lobby and negotiating derogations from the European Union’s Bird Directive. Some NGOs have recently started to organize complex field-operations where volunteers are trained to patrol the landscape, operate drones and other surveillance technologies, detect illegalities, and lead police teams to arrest poachers. We describe the sophisticated military metaphors which conservation NGOs have developed to describe, guide and legitimize their efforts to the Maltese public and their fee-paying members. We also discuss why such groups might be inclined to adopt these metaphors. Finally, we suggest that anthropological studies of discourse could help understand delicate contexts such as this where conservation NGOs, hunting associations and the State have ended in political deadlock

Skyrmion fluctuations at a first-order phase transition boundary

Magnetic skyrmions are topologically protected spin textures with promising prospects for applications in data storage. They can form a lattice state due to competing magnetic interactions and are commonly found in a small region of the temperature - magnetic field phase diagram. Recent work has demonstrated that these magnetic quasi-particles fluctuate at the μeV energy scale. Here, we use a coherent x-ray correlation method at an x-ray free-electron laser to investigate these fluctuations in a magnetic phase coexistence region near a first-order transition boundary where fluctuations are not expected to play a major role. Surprisingly, we find that the relaxation of the intermediate scattering function at this transition differs significantly compared to that deep in the skyrmion lattice phase. The observation of a compressed exponential behavior suggests solid-like dynamics, often associated with jamming. We assign this behavior to disorder and the phase coexistence observed in a narrow field-window near the transition, which can cause fluctuations that lead to glassy behavior

Oldest known pantherine skull and evolution of the tiger

The tiger is one of the most iconic extant animals, and its origin and evolution have been intensely debated. Fossils attributable to extant pantherine species-lineages are less than 2 MYA and the earliest tiger fossils are from the Calabrian, Lower Pleistocene. Molecular studies predict a much younger age for the divergence of modern tiger subspecies at <100 KYA, although their cranial morphology is readily distinguishable, indicating that early Pleistocene tigers would likely have differed markedly anatomically from extant tigers. Such inferences are hampered by the fact that well-known fossil tiger material is middle to late Pleistocene in age. Here we describe a new species of pantherine cat from Longdan, Gansu Province, China, Panthera zdanskyi sp. nov. With an estimated age of 2.55–2.16 MYA it represents the oldest complete skull of a pantherine cat hitherto found. Although smaller, it appears morphologically to be surprisingly similar to modern tigers considering its age. Morphological, morphometric, and cladistic analyses are congruent in confirming its very close affinity to the tiger, and it may be regarded as the most primitive species of the tiger lineage, demonstrating the first unequivocal presence of a modern pantherine species-lineage in the basal stage of the Pleistocene (Gelasian; traditionally considered to be Late Pliocene). This find supports a north-central Chinese origin of the tiger lineage, and demonstrates that various parts of the cranium, mandible, and dentition evolved at different rates. An increase in size and a reduction in the relative size of parts of the dentition appear to have been prominent features of tiger evolution, whereas the distinctive cranial morphology of modern tigers was established very early in their evolutionary history. The evolutionary trend of increasing size in the tiger lineage is likely coupled to the evolution of its primary prey species

Chronic pain self-management for older adults: a randomized controlled trial [ISRCTN11899548]

BACKGROUND: Chronic pain is a common and frequently disabling problem in older adults. Clinical guidelines emphasize the need to use multimodal therapies to manage persistent pain in this population. Pain self-management training is a multimodal therapy that has been found to be effective in young to middle-aged adult samples. This training includes education about pain as well as instruction and practice in several management techniques, including relaxation, physical exercise, modification of negative thoughts, and goal setting. Few studies have examined the effectiveness of this therapy in older adult samples. METHODS/DESIGN: This is a randomized, controlled trial to assess the effectiveness of a pain self-management training group intervention, as compared with an education-only control condition. Participants are recruited from retirement communities in the Pacific Northwest of the United States and must be 65 years or older and experience persistent, noncancer pain that limits their activities. The primary outcome is physical disability, as measured by the Roland-Morris Disability Questionnaire. Secondary outcomes are depression (Geriatric Depression Scale), pain intensity (Brief Pain Inventory), and pain-related interference with activities (Brief Pain Inventory). Randomization occurs by facility to minimize cross-contamination between groups. The target sample size is 273 enrolled, which assuming a 20% attrition rate at 12 months, will provide us with 84% power to detect a moderate effect size of .50 for the primary outcome. DISCUSSION: Few studies have investigated the effects of multimodal pain self-management training among older adults. This randomized controlled trial is designed to assess the efficacy of a pain self-management program that incorporates physical and psychosocial pain coping skills among adults in the mid-old to old-old range

Convergence and divergence in the evolution of cat skulls: temporal and spatial patterns of morphological diversity

Background: Studies of biological shape evolution are greatly enhanced when framed in a phylogenetic perspective. Inclusion of fossils amplifies the scope of macroevolutionary research, offers a deep-time perspective on tempo and mode of radiations, and elucidates life-trait changes. We explore the evolution of skull shape in felids (cats) through morphometric analyses of linear variables, phylogenetic comparative methods, and a new cladistic study of saber-toothed cats. Methodology/Principal Findings: A new phylogenetic analysis supports the monophyly of saber-toothed cats (Machairodontinae) exclusive of Felinae and some basal felids, but does not support the monophyly of various sabertoothed tribes and genera. We quantified skull shape variation in 34 extant and 18 extinct species using size-adjusted linear variables. These distinguish taxonomic group membership with high accuracy. Patterns of morphospace occupation are consistent with previous analyses, for example, in showing a size gradient along the primary axis of shape variation and a separation between large and small-medium cats. By combining the new phylogeny with a molecular tree of extant Felinae, we built a chronophylomorphospace (a phylogeny superimposed onto a two-dimensional morphospace through time). The evolutionary history of cats was characterized by two major episodes of morphological divergence, one marking the separation between saber-toothed and modern cats, the other marking the split between large and small-medium cats. Conclusions/Significance: Ancestors of large cats in the ‘Panthera’ lineage tend to occupy, at a much later stage, morphospace regions previously occupied by saber-toothed cats. The latter radiated out into new morphospace regions peripheral to those of extant large cats. The separation between large and small-medium cats was marked by considerable morphologically divergent trajectories early in feline evolution. A chronophylomorphospace has wider applications in reconstructing temporal transitions across two-dimensional trait spaces, can be used in ecophenotypical and functional diversity studies, and may reveal novel patterns of morphospace occupation

Patterns of analgesic use, pain and self-efficacy: a cross-sectional study of patients attending a hospital rheumatology clinic

Background: Many people attending rheumatology clinics use analgesics and non-steroidal anti-inflammatories for persistent musculoskeletal pain. Guidelines for pain management recommend regular and pre-emptive use of analgesics to reduce the impact of pain. Clinical experience indicates that analgesics are often not used in this way. Studies exploring use of analgesics in arthritis have historically measured adherence to such medication. Here we examine patterns of analgesic use and their relationships to pain, self-efficacy and demographic factors. Methods: Consecutive patients were approached in a hospital rheumatology out-patient clinic. Pattern of analgesic use was assessed by response to statements such as 'I always take my tablets every day.' Pain and self-efficacy (SE) were measured using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) and Arthritis Self-Efficacy Scale (ASES). Influence of factors on pain level and regularity of analgesic use were investigated using linear regression. Differences in pain between those agreeing and disagreeing with statements regarding analgesic use were assessed using t-tests. Results: 218 patients (85% of attendees) completed the study. Six (2.8%) patients reported no current pain, 26 (12.3%) slight, 100 (47.4%) moderate, 62 (29.4%) severe and 17 (8.1%) extreme pain. In multiple linear regression self efficacy and regularity of analgesic use were significant (p < 0.01) with lower self efficacy and more regular use of analgesics associated with more pain. Low SE was associated with greater pain: 40 (41.7%) people with low SE reported severe pain versus 22 (18.3%) people with high SE, p < 0.001. Patients in greater pain were significantly more likely to take analgesics regularly; 13 (77%) of those in extreme pain reported always taking their analgesics every day, versus 9 (35%) in slight pain. Many patients, including 46% of those in severe pain, adjusted analgesic use to current pain level. In simple linear regression, pain was the only variable significantly associated with regularity of analgesic use: higher levels of pain corresponded to more regular analgesic use (p = 0.003). Conclusion: Our study confirms that there is a strong inverse relationship between self-efficacy and pain severity. Analgesics are often used irregularly by people with arthritis, including some reporting severe pain

Export of functional Streptomyces coelicolor alditol oxidase to the periplasm or cell surface of Escherichia coli and its application in whole-cell biocatalysis

Streptomyces coelicolor A3(2) alditol oxidase (AldO) is a soluble monomeric flavoprotein in which the flavin cofactor is covalently linked to the polypeptide chain. AldO displays high reactivity towards different polyols such as xylitol and sorbitol. These characteristics make AldO industrially relevant, but full biotechnological exploitation of this enzyme is at present restricted by laborious and costly purification steps. To eliminate the need for enzyme purification, this study describes a whole-cell AldO biocatalyst system. To this end, we have directed AldO to the periplasm or cell surface of Escherichia coli. For periplasmic export, AldO was fused to endogenous E. coli signal sequences known to direct their passenger proteins into the SecB, signal recognition particle (SRP), or Twin-arginine translocation (Tat) pathway. In addition, AldO was fused to an ice nucleation protein (INP)-based anchoring motif for surface display. The results show that Tat-exported AldO and INP-surface-displayed AldO are active. The Tat-based system was successfully employed in converting xylitol by whole cells, whereas the use of the INP-based system was most likely restricted by lipopolysaccharide LPS in wild-type cells. It is anticipated that these whole-cell systems will be a valuable tool for further biological and industrial exploitation of AldO and other cofactor-containing enzymes.

The effects of linkage disequilibrium in large scale SNP datasets for MDR

<p>Abstract</p> <p>Background</p> <p>In the analysis of large-scale genomic datasets, an important consideration is the power of analytical methods to identify accurate predictive models of disease. When trying to assess sensitivity from such analytical methods, a confounding factor up to this point has been the presence of linkage disequilibrium (LD). In this study, we examined the effect of LD on the sensitivity of the Multifactor Dimensionality Reduction (MDR) software package.</p> <p>Results</p> <p>Four relative amounts of LD were simulated in multiple one- and two-locus scenarios for which the position of the functional SNP(s) within LD blocks varied. Simulated data was analyzed with MDR to determine the sensitivity of the method in different contexts, where the sensitivity of the method was gauged as the number of times out of 100 that the method identifies the correct one- or two-locus model as the best overall model. As the amount of LD increases, the sensitivity of MDR to detect the correct functional SNP drops but the sensitivity to detect the disease signal and find an indirect association increases.</p> <p>Conclusions</p> <p>Higher levels of LD begin to confound the MDR algorithm and lead to a drop in sensitivity with respect to the identification of a direct association; it does not, however, affect the ability to detect indirect association. Careful examination of the solution models generated by MDR reveals that MDR can identify loci in the correct LD block; though it is not always the functional SNP. As such, the results of MDR analysis in datasets with LD should be carefully examined to consider the underlying LD structure of the dataset.</p

Incorporating prior knowledge improves detection of differences in bacterial growth rate

BACKGROUND: Robust statistical detection of differences in the bacterial growth rate can be challenging, particularly when dealing with small differences or noisy data. The Bayesian approach provides a consistent framework for inferring model parameters and comparing hypotheses. The method captures the full uncertainty of parameter values, whilst making effective use of prior knowledge about a given system to improve estimation. RESULTS: We demonstrated the application of Bayesian analysis to bacterial growth curve comparison. Following extensive testing of the method, the analysis was applied to the large dataset of bacterial responses which are freely available at the web-resource, ComBase. Detection was found to be improved by using prior knowledge from clusters of previously analysed experimental results at similar environmental conditions. A comparison was also made to a more traditional statistical testing method, the F-test, and Bayesian analysis was found to perform more conclusively and to be capable of attributing significance to more subtle differences in growth rate. CONCLUSIONS: We have demonstrated that by making use of existing experimental knowledge, it is possible to significantly improve detection of differences in bacterial growth rate