Rivers,not refugia,drove diversification in arboreal,sub‐Saharan African snakes

The relative roles of rivers versus refugia in shaping the high levels of species diversity in tropical rainforests have been widely debated for decades. Only recently has it become possible to take an integrative approach to test predictions derived from these hypotheses using genomic sequencing and paleo‐species distribution modeling. Herein, we tested the predictions of the classic river, refuge, and river‐refuge hypotheses on diversification in the arboreal sub‐Saharan African snake genus Toxicodryas. We used dated phylogeographic inferences, population clustering analyses, demographic model selection, and paleo‐distribution modeling to conduct a phylogenomic and historical demographic analysis of this genus. Our results revealed significant population genetic structure within both Toxicodryas species, corresponding geographically to river barriers and divergence times from the mid‐Miocene to Pliocene. Our demographic analyses supported the interpretation that rivers are indications of strong barriers to gene flow among populations since their divergence. Additionally, we found no support for a major contraction of suitable habitat during the last glacial maximum, allowing us to reject both the refuge and river‐refuge hypotheses in favor of the river‐barrier hypothesis. Based on conservative interpretations of our species delimitation analyses with the Sanger and ddRAD data sets, two new cryptic species are identified from east‐central Africa. This study highlights the complexity of diversification dynamics in the African tropics and the advantages of integrative approaches to studying speciation in tropical regions.     

Molecular systematics of the Middle American genus Hypopachus (Anura: Microhylidae)

We present the first phylogenetic study on the widespread Middle American microhylid frog genus Hypopachus. Partial sequences of mitochondrial (12S and 16S ribosomal RNA) and nuclear (rhodopsin) genes (1275 bp total) were analyzed from 43 samples of Hypopachus, three currently recognized species of Gastrophryne, and seven arthroleptid, brevicipitid and microhylid outgroup taxa. Maximum parsimony (PAUP), maximum likelihood (RAxML) and Bayesian inference (MrBayes) optimality criteria were used for phylogenetic analyses, and BEAST was used to estimate divergence dates of major clades. Population-level analyses were conducted with the programs NETWORK and Arlequin. Results confirm the placement of Hypopachus and Gastrophryne as sister taxa, but the latter genus was strongly supported as paraphyletic. The African phrynomerine genus Phrynomantis was recovered as the sister taxon to a monophyletic Chiasmocleis, rendering our well-supported clade of gastrophrynines paraphyletic. Hypopachus barberi was supported as a disjunctly distributed highland species, and we recovered a basal split in lowland populations of Hypopachus variolosus from the Pacific versant of Mexico and elsewhere in the Mesoamerican lowlands. Dating analyses from BEAST estimate speciation within the genus Hypopachus occurred in the late Miocene/early Pliocene for most clades. Previous studies have not found bioacoustic or morphological differences among these lowland clades, and our molecular data support the continued recognition of two species in the genus Hypopachus.     

The electrostatic characteristics of G.U wobble base pairs

G·U wobble base pairs are the most common and highly conserved non-Watson–Crick base pairs in RNA. Previous surface maps imply uniformly negative electrostatic potential at the major groove of G·U wobble base pairs embedded in RNA helices, suitable for entrapment of cationic ligands. In this work, we have used a Poisson–Boltzmann approach to gain a more detailed and accurate characterization of the electrostatic profile. We found that the major groove edge of an isolated G·U wobble displays distinctly enhanced negativity compared with standard GC or AU base pairs; however, in the context of different helical motifs, the electrostatic pattern varies. G·U wobbles with distinct widening have similar major groove electrostatic potentials to their canonical counterparts, whereas those with minimal widening exhibit significantly enhanced electronegativity, ranging from 0.8 to 2.5kT/e, depending upon structural features. We propose that the negativity at the major groove of G·U wobble base pairs is determined by the combined effect of the base atoms and the sugar-phosphate backbone, which is impacted by stacking pattern and groove width as a result of base sequence. These findings are significant in that they provide predictive power with respect to which G·U sites in RNA are most likely to bind cationic ligands.     

Facultative response to a kleptoparasite by the cooperatively breeding pied babbler

In many cases of interspecific kleptoparasitism, hosts developdefensive behaviors to minimize the impact of kleptoparasites.Because vigilance and defensive behaviors are often costly,selection should favor hosts that adjust the amount of investmentneeded to minimize losses to kleptoparasitism. However, examplesof such facultative responses are rare. Here, we investigatethe response of cooperatively breeding pied babblers (Turdoidesbicolor) to the drongo (Dicrurus adsimilis), an avian kleptoparasitethat regularly follows pied babbler groups, often giving alarmcalls to alert the group to predators but also occasionallygiving false alarm calls in order to steal food items. We showthat pied babbler response to drongos varies markedly accordingto babbler group size. In small groups, where there are fewindividuals available to act as sentinels, babblers sentinelless when a drongo is present and respond strongly to drongoalarm calls. However, in large groups, where there are manyindividuals available to participate in predator vigilance,babblers sentinel more often when a drongo is present, rarelyrespond to drongo alarm calls, and aggressively displace drongos,with a consequent decline in the number of successful kleptoparasitismevents. This behavior represent a facultative response to akleptoparasite according to the costs versus benefits of toleratingtheir presence.     

Glucose-6-phosphate dehydrogenase deficiency in northern Mexico and description of a novel mutation

Glucose-6-phosphate dehydrogenase deficiency (G6PD) is the most common enzyme pathology in humans; it is X-linked inherited and causes neonatal hyperbilirubinaemia, chronic nonspherocytic haemolytic anaemia and drug-induced acute haemolytic anaemia. G6PD deficiency has scarcely been studied in the northern region of Mexico, which is important because of the genetic heterogeneity described in Mexican population. Therefore, samples from the northern Mexico were biochemically screened for G6PD-deficiency, and PCR-RFLPs, and DNA sequencing used to identify mutations in positive samples. The frequency of G6PD deficiency in the population was 0.95% (n = 1993); the mutations in 86% of these samples were G6PD A^?202A/376G , G6PD A^?376G/968C and G6PD Santamaria^376G/542T . Contrary to previous reports, we demonstrated that G6PD deficiency distribution is relatively homogenous throughout the country (P = 0.48336), and the unique exception with high frequency of G6PD deficiency does not involve a coastal population (Chihuahua: 2.4%). Analysis of eight polymorphic sites showed only 10 haplotypes. In one individual we identified a new G6PD mutation named Mexico DF^193A>G (rs199474830), which probably results in a damaging functional effect, according to PolyPhen analysis. Proteomic impact of the mutation is also described.     

Molecular phylogenetics of the arboreal Australian gecko genus Oedura Gray 1842 (Gekkota: Diplodactylidae): another plesiomorphic grade?

The family Diplodactylidae is the most ecologically diverse and geographically widespread radiation of geckos within Australasia. Herein we present a first comprehensive phylogenetic analysis of relationships of diplodactylid geckos currently assigned to the genus Oedura, a group of relatively generalised arboreal Australian geckos. Maximum Likelihood, bayesian and Maximum Parsimony analyses of a combination of over two and a half kilobases of nuclear (PDC, Rag-1) and mitochondrial (ND2, ND4, tRNA) sequence data all identified four distinctive lineages within Oedura s.l. Based on their deep divergences and a suite of diagnostic morphological characters we recognise each of these four lineages as genera, two of which are monotypic and newly described herein. Our molecular data also suggest that Oedura s.l. is not monophyletic, but is instead a plesiomorphic grade restricted to islands of rocky or forested habitat around coastal and central Australia. In contrast, combined analysis of all data suggests the Australian arid zone is dominated by a single comparatively derived and relatively species rich clade including most other genera of Australian Diplodactylidae. Additional data are required to properly resolve basal divergence events within the Diplodactylidae, however the emerging pattern of relationships and divergence is consistent with the hypothesis that monsoonal and temperate lineages are ancestral to the arid zone fauna, but also indicate that arid zone lineages and radiations are relatively old, and potentially date back to the mid Miocene or earlier.     

The effector T cells of diabetic subjects are resistant to regulation via CD4+ FOXP3+ regulatory T cells

Defects in immune regulation have been implicated in the pathogenesis of diabetes in mouse and in man. In vitro assays using autologous regulatory (Treg) and responder effector (Teff) T cells have shown that suppression is impaired in diabetic subjects. In this study, we addressed whether the source of this defect is intrinsic to the Treg or Teff compartment of diabetic subjects. We first established that in type 1 diabetes (T1D) individuals, similar levels of impaired suppression were seen, irrespective of whether natural (nTreg) or adaptive Treg (aTreg) were present. Then using aTreg, we examined the ability of T1D aTreg to suppress Teff of healthy controls, as compared with the ability of control aTreg to suppress Teff of diabetic subjects. Taking this approach, we found that the aTregs from T1D subjects function normally in the presence of control Teff, and that the T1D Teff were resistant to suppression in the presence of control aTreg. This escape from regulation was seen with nTreg as well and was not transferred to control Teff coincubated with T1D Teff. Thus, the "defective regulation" in T1D is predominantly due to the resistance of responding T cells to Treg and is a characteristic intrinsic to the T1D Teff. This has implications with respect to pathogenic mechanisms, which underlie the development of disease and the target of therapies for T1D.     

Burn injuries inflicted on children or the elderly: a framework for clinical and forensic assessment

LEARNING OBJECTIVES: After studying this article, the participant should be able to: 1. Understand the difference between battery and assault in U.S. law and the concepts of the phrase "child abuse" and "elder abuse." 2. Understand that state statutes vary and can define abuse narrowly or with great specificity, and that either definition has inherent problems for physicians treating victims of abuse and neglect. 3. Know where to find the state-specific legal criteria for child or elder abuse and neglect, along with the corresponding standards for mandatory reporting and physician accountability. 4. Understand the relevant law regarding physician-patient privilege and the repercussions of incorrect but good faith reporting and of failing to report suspected abuse or neglect of children or the elderly. 5. Understand that there are no pathognomic signs for inflicted burn injury. 6. Clinically assess burned pediatric or elderly patients within a framework that will minimize the risk of missing or inappropriately suspecting injuries that stem from abuse or neglect. SUMMARY: This article deals with burns inflicted on children and the elderly, two particularly vulnerable societal groups. Though inflicted burning is a relatively rare method of inflicting physical abuse, failure to diagnose it has far-reaching ramifications. These injuries pose both medical and forensic problems for physicians, along with unique ethical dilemmas. This article is a collaboration between surgeons and lawyers providing a holistic, workable approach to the management of inflicted burn injury. The authors first describe the legal considerations that must be appreciated by U.S. physicians, then they suggest a rational and balanced clinical approach to the assessment of burn injuries that may have been inflicted intentionally or negligently on children and the elderly.     

Out of the blue: a novel, trans-Atlantic clade of geckos (Gekkota, Squamata)

Phylogenetic relationships among gekkotan lizards were estimated from five nuclear protein-coding genes in separate and combined analyses using maximum parsimony, maximum likelihood and Bayesian analyses. All analyses recovered a monophyletic trans-Atlantic gecko clade (Phyllodactylidae) consisting of the genera Asaccus, Haemodracon, Homonota, Phyllodactylus, Phyllopezus, Ptyodactylus, Tarentola and Thecadactylus . No other phylogenetic or taxonomic hypotheses have proposed linking these genera, which have been consistently grouped with other taxa outside of the clade. In this paper, we determine the relationships of this new clade to other major gekkotan groups, evaluate previous phylogenetic hypotheses regarding constituent members of this novel clade, and critically examine the use of historically important morphological characters in gekkotan systematics as they relate to this novel clade, specifically — phalangeal formulae, hyoid morphology and external structure of the toe-pads.     

Structural basis of GC-1 selectivity for thyroid hormone receptor isoforms

Background

Multiple protein templates are commonly used in manual protein structure prediction. However, few automated algorithms of selecting and combining multiple templates are available.

Results

Here we develop an effective multi-template combination algorithm for protein comparative modeling. The algorithm selects templates according to the similarity significance of the alignments between template and target proteins. It combines the whole template-target alignments whose similarity significance score is close to that of the top template-target alignment within a threshold, whereas it only takes alignment fragments from a less similar template-target alignment that align with a sizable uncovered region of the target. We compare the algorithm with the traditional method of using a single top template on the 45 comparative modeling targets (i.e. easy template-based modeling targets) used in the seventh edition of Critical Assessment of Techniques for Protein Structure Prediction (CASP7). The multi-template combination algorithm improves the GDT-TS scores of predicted models by 6.8% on average. The statistical analysis shows that the improvement is significant (p-value < 10^-4). Compared with the ideal approach that always uses the best template, the multi-template approach yields only slightly better performance. During the CASP7 experiment, the preliminary implementation of the multi-template combination algorithm (FOLDpro) was ranked second among 67 servers in the category of high-accuracy structure prediction in terms of GDT-TS measure.

Conclusion

We have developed a novel multi-template algorithm to improve protein comparative modeling.