PHYLOGENY OF SOME MIDDLE AMERICAN PITVIPERS BASED ON A CLADISTIC ANALYSIS OF MITOCHONDRIAL 12S AND 16S DNA SEQUENCE INFORMATION

The cladistic relationships of several Middle American pitvipers representing the genera Bothrops (sensu stricto), Bothriechis, Cerrophidion, Lachesis and Porthidium were determined using mitochondrial 12S and 16S DNA sequence information. Maximum parsimony analyses were performed using PAUP on aligned sequences that included published information for related taxa. Two sets of analyses were conducted: one disregarding gaps in the aligned matrix, and another with gaps treated as a fifth base. When gaps were excluded resolution declined, although the general arrangement of the taxa changed little. A consistent relationship was the grouping of ((Porthidium, Bothriechis) Lachesis). The placement of Lachesis, as nested within other bothropoid genera, is only partially supported by results of other authors. The arrangement of Crotalus, Bothrops and Cerrophidion was ambiguous when gaps were discounted. In both trees, Agkistrodon was basal to the New World forms. The remaining genera, Trimeresurus (Protobothrops), Vipera, Azemiops, and Coluber, were uniformly distant to the former taxa. Also of interest is the lack of close relationship, based on the DNA data here and elsewhere, between Bothrops and Porthidium. This is in striking contrast to results based on morphologic and allozymic analyses of previous studies. It is concluded that additional DNA sequence information from a larger sample of taxa will be necessary to better assess the phylogenetic relationships among Middle American and related pitvipers

The changing face of major trauma in the UK

Aim Major trauma (MT) has traditionally been viewed as a disease of young men caused by high-energy transfer mechanisms of injury, which has been reflected in the configuration of MT services. With ageing populations in Western societies, it is anticipated that the elderly will comprise an increasing proportion of the MT workload. The aim of this study was to describe changes in the demographics of MT in a developed Western health system over the last 20 years. Methods The Trauma Audit Research Network (TARN) database was interrogated to identify all cases of MT (injury severity score >15) between 1990 and the end of 2013. Age at presentation, gender, mechanism of injury and use of CT were recorded. For convenience, cases were categorised by age groups of 25 years and by common mechanisms of injury. Longitudinal changes each year were recorded. Results Profound changes in the demographics of recorded MT were observed. In 1990, the mean age of MT patients within the TARN database was 36.1, the largest age group suffering MT was 0–24 years (39.3%), the most common causative mechanism was road traffic collision (59.1%), 72.7% were male and 33.6% underwent CT. By 2013, mean age had increased to 53.8 years, the single largest age group was 25–50 years (27.1%), closely followed by those >75 years (26.9%), the most common mechanism was low falls (39.1%), 68.3% were male and 86.8% underwent CT. Conclusions This study suggests that the MT population identified in the UK is becoming more elderly, and the predominant mechanism that precipitates MT is a fall from <2 m. Significant improvements in outcomes from MT may be expected if services targeting the specific needs of the elderly are developed within MT centres

Intracellular Function of Interleukin-1 Receptor Antagonist in Ischemic Cardiomyocytes

Background: Loss of cardiac myocytes due to apoptosis is a relevant feature of ischemic heart disease. It has been described in infarct and peri-infarct regions of the myocardium in coronary syndromes and in ischemia-linked heart remodeling. Previous studies have provided protection against ischemia-induced cardiomyocyte apoptosis by the anti-inflammatory cytokine interleukin-1 receptor-antagonist (IL-1Ra). Mitochondria triggering of caspases plays a central role in ischemia-induced apoptosis. We examined the production of IL-1Ra in the ischemic heart and, based on dual intra/extracellular function of some other interleukins, we hypothesized that IL-1Ra may also directly inhibit mitochondria-activated caspases and cardiomyocyte apoptosis. Methodology/Principal Findings: Synthesis of IL-1Ra was evidenced in the hearts explanted from patients with ischemic heart disease. In the mouse ischemic heart and in a mouse cardiomyocyte cell line exposed to long-lasting hypoxia, IL-1Ra bound and inhibited mitochondria-activated caspases, whereas inhibition of caspase activation was not observed in the heart of mice lacking IL-1Ra (Il-1ra−/−) or in siRNA to IL-1Ra-interfered cells. An impressive 6-fold increase of hypoxia-induced apoptosis was observed in cells lacking IL-1Ra. IL-1Ra down-regulated cells were not protected against caspase activation and apoptosis by knocking down of the IL-1 receptor, confirming the intracellular, receptor-independent, anti-apoptotic function of IL-1Ra. Notably, the inhibitory effect of IL-1Ra was not influenced by enduring ischemic conditions in which previously described physiologic inhibitors of apoptosis are neutralized. Conclusions/Significance: These observations point to intracellular IL-1Ra as a critical mechanism of the cell self-protection against ischemia-induced apoptosis and suggest that this cytokine plays an important role in the remodeling of heart by promoting survival of cardiomyocytes in the ischemic regions

Minimum-weight perfect matching for non-intrinsic distances on the line

Consider a real line equipped with a (not necessarily intrinsic) distance. We deal with the minimum-weight perfect matching problem for a complete graph whose points are located on the line and whose edges have weights equal to distances along the line. This problem is closely related to one-dimensional Monge-Kantorovich trasnport optimization. The main result of the present note is a "bottom-up" recursion relation for weights of partial minimum-weight matchings.Comment: 13 pages, figures in TiKZ, uses xcolor package; introduction and the concluding section have been expande

PPARγ Variant Influences Angiographic Outcome and 10-Year Cardiovascular Risk in Male Symptomatic Coronary Artery Disease Patients

OBJECTIVE: Activation of peroxisome proliferator-activated receptor (PPAR)-gamma signaling influences metabolic profiles and the propensity toward inflammation. Small-molecule stimulation of PPARgamma is investigated for secondary prevention of cardiovascular disease. The common PPARgamma Pro12Ala variant has functional and prognostic consequences. A protective effect of the 12Ala-allele carriership on diabetes and myocardial infarction in healthy populations has been suggested. The relevance of this pathway also needs exploration in patients with manifest vascular disease. We investigated the effects of carriership of the Pro12Ala variant on angiographic and cardiovascular event outcomes in male patients with symptomatic coronary artery disease (CAD). RESEARCH DESIGN AND METHODS: The Regression Growth Evaluation Statin Study (REGRESS) cohort was genotyped for the Pro12Ala variant (rs1801282). Ten-year follow-up was derived from nation-wide registries, and risks were estimated using proportional hazards. Quantitative coronary angiography measurements were obtained and relations with genotype estimated using a generalized linear model. RESULTS: Genotypes ascertained (n = 679) comprised 540 (80%) Pro/Pro, 126 (19%) Pro/Ala, and 13 (2%) Ala/Ala subjects. The 12Ala allele was associated with less extensive focal (P = 0.001) and diffuse (P = 0.002) atherosclerosis and lower 10-year cardiovascular risk. Hazard ratios were 0.10 (95% CI 0.01-0.70, P = 0.02) for ischemic heart disease and 0.24 (0.08-0.74, P = 0.013) for vascular death, per each added copy of 12Ala, respectively. CONCLUSIONS: Carriers of the 12Ala allele of PPARgamma have less widespread CAD and are considerably protected against 10-year (cardio)vascular morbidity and mortality. These long-term findings in patients with manifest CAD support an important role of PPARgamma in determining vascular ris

The Mixed-Lineage Kinase DLK Is a Key Regulator of 3T3-L1 Adipocyte Differentiation

The mixed-lineage kinase (MLK) family member DLK has been proposed to serve as a regulator of differentiation in various cell types; however, its role in adipogenesis has not been investigated. In this study, we used the 3T3-L1 preadipocyte cell line as a model to examine the function of DLK in adipocyte differentiation.Immunoblot analyses and kinase assays performed on 3T3-L1 cells showed that the expression and activity of DLK substantially increase as differentiation occurs. Interestingly, DLK appears crucial for differentiation since its depletion by RNA interference impairs lipid accumulation as well as expression of the master regulators of adipogenesis C/EBPalpha and PPARgamma2 at both the mRNA and protein levels. In contrast, neither the expression nor the DNA binding activity of C/EBPbeta, an activator for C/EBPalpha and PPARgamma, is affected by DLK loss.Taken together, these results suggest that DLK is important for expression of mature adipocyte markers and that its action most likely takes place via regulation of C/EBPbeta transcriptional activity and/or initiation of C/EBPalpha and PPARgamma2 gene transcription