Dental anatomy of the apex predator Sinraptor Dongi (Theropoda: Allosauroidea) from the late Jurassic of China

The dental morphology of the holotype of the theropod Sinraptor dongi from the Jurassic Shishugou Formation of China is comprehensively described. We highlight a combination of dental features that appear to be restricted to Sinraptor: (i) crowns with denticulated mesial and distal carinae extending from the root and an irregular surface texture on the enamel; (ii) a D- to salinon-shaped cross-sectional outline at the crown base in mesialmost teeth; (iii) mesial crowns with mesial carinae spiraling mesiolingually and lingually positioned longitudinal groove adjacent to the mesial carina; and (iv) particularly labiolingually compressed lateral teeth with weakly labially deflected distal carinae, flat to concave basocentral surfaces of the labial margins of the crowns, and horizontally elongated distal denticles showing short to well-developed interdenticular sulci. Using cladistic, multivariate, discriminant, and cluster analyses, we demonstrate that the dentition of Sinraptor is relatively similar to that of ceratosaurids, megalosauroids, and other allosauroids and is particularly close to that of Allosaurus. The dental anatomy of Sinraptor and Allosaurus, which differs mainly in the labiolingual compression of the lateral crowns and in the number of premaxillary teeth, shows adaptations towards a predatory lifestyle, including premaxillary teeth capable of enduring tooth-tobone contact and crowns with widely separated mesial and distal carinae capable of inflicting widely open wounds.Fil: Hendrickx, Christophe Marie Fabian. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico - Tucumán. Unidad Ejecutora Lillo; ArgentinaFil: Stiegler, Josef. The George Washington University; Estados UnidosFil: Currie, Philip J.. University of Alberta; CanadáFil: Han, Fenglu. University of Geoscience; ChinaFil: Xu, Xing. Chinese Academy of Sciences; República de ChinaFil: Choiniere, Jonah N.. University of the Witwatersrand; SudáfricaFil: Wu, Xiao Chung. Canadian Museum of Nature; Canad

Insulin-Resistant Subjects Have Normal Angiogenic Response to Aerobic Exercise Training in Skeletal Muscle, but Not in Adipose Tissue

Reduced vessel density in adipose tissue and skeletal muscle is associated with obesity and may result in decreased perfusion, decreased oxygen consumption, and insulin resistance. In the presence of VEGFA, Angiopoietin-2 (Angpt2) and Angiopoietin-1 (Angpt1) are central determinants of angiogenesis, with greater Angpt2:Angpt1 ratios promoting angiogenesis. In skeletal muscle, exercise training stimulates angiogenesis and modulates transcription of VEGFA, Angpt1, and Angpt 2. However, it remains unknown whether exercise training stimulates vessel growth in human adipose tissue, and it remains unknown whether adipose angiogenesis is mediated by angiopoietin signaling. We sought to determine whether insulin-resistant subjects would display an impaired angiogenic response to aerobic exercise training. Insulin-sensitive (IS, N = 12) and insulin-resistant (IR, N = 14) subjects had subcutaneous adipose and muscle (vastus lateralis) biopsies before and after 12 weeks of cycle ergometer training. In both tissues, we measured vessels and expression of pro-angiogenic genes. Exercise training did not increase insulin sensitivity in IR Subjects. In skeletal muscle, training resulted in increased vessels/muscle fiber and increased Angpt2:Angpt1 ratio in both IR and IS subjects. However, in adipose, exercise training only induced angiogenesis in IS subjects, likely due to chronic suppression of VEGFA expression in IR subjects. These results indicate that skeletal muscle of IR subjects exhibits a normal angiogenic response to exercise training. However, the same training regimen is insufficient to induce angiogenesis in adipose tissue of IR subjects, which may help to explain why we did not observe improved insulin sensitivity following aerobic training

Human Galectin-9 Is a Potent Mediator of HIV Transcription and Reactivation.

Identifying host immune determinants governing HIV transcription, latency and infectivity in vivo is critical to developing an HIV cure. Based on our recent finding that the host factor p21 regulates HIV transcription during antiretroviral therapy (ART), and published data demonstrating that the human carbohydrate-binding immunomodulatory protein galectin-9 regulates p21, we hypothesized that galectin-9 modulates HIV transcription. We report that the administration of a recombinant, stable form of galectin-9 (rGal-9) potently reverses HIV latency in vitro in the J-Lat HIV latency model. Furthermore, rGal-9 reverses HIV latency ex vivo in primary CD4+ T cells from HIV-infected, ART-suppressed individuals (p = 0.002), more potently than vorinostat (p = 0.02). rGal-9 co-administration with the latency reversal agent "JQ1", a bromodomain inhibitor, exhibits synergistic activity (p<0.05). rGal-9 signals through N-linked oligosaccharides and O-linked hexasaccharides on the T cell surface, modulating the gene expression levels of key transcription initiation, promoter proximal-pausing, and chromatin remodeling factors that regulate HIV latency. Beyond latent viral reactivation, rGal-9 induces robust expression of the host antiviral deaminase APOBEC3G in vitro and ex vivo (FDR<0.006) and significantly reduces infectivity of progeny virus, decreasing the probability that the HIV reservoir will be replenished when latency is reversed therapeutically. Lastly, endogenous levels of soluble galectin-9 in the plasma of 72 HIV-infected ART-suppressed individuals were associated with levels of HIV RNA in CD4+ T cells (p<0.02) and with the quantity and binding avidity of circulating anti-HIV antibodies (p<0.009), suggesting a role of galectin-9 in regulating HIV transcription and viral production in vivo during therapy. Our data suggest that galectin-9 and the host glycosylation machinery should be explored as foundations for novel HIV cure strategies

Comparative assessment of seller’s staining test (SST) and direct fluorescent antibody test for rapid and accurate laboratory diagnosis of rabies

Background: Rabies causes 55, 000 annual human deaths globally and about 10,000 people are exposed annually in Nigeria. Diagnosis of animal rabies in most African countries has been by direct microscopic examination. In Nigeria, the Seller’s stain test (SST) was employed until 2009. Before then, both SST and dFAT were used concurrently until the dFAT became the only standard method.Objective: This study was designed to assess the sensitivity and specificity of the SST in relation to the ‘gold standard’ dFAT in diagnosis of rabies in Nigeria.Methods: A total of 88 animal specimens submitted to the Rabies National Reference Laboratory, Nigeria were routinely tested for rabies by SST and dFAT.Results: Overall, 65.9% of the specimens were positive for rabies by SST, while 81.8% were positive by dFAT. The sensitivity of SST in relation to the gold standard dFAT was 81.0% (95% CIs; 69.7% - 88.6%), while the specificity was 100% (95% CIs; 76% - 100%).Conclusion: The relatively low sensitivity of the SST observed in this study calls for its replacement with the dFAT for accurate diagnosis of rabies and timely decisions on administration of PEP to prevent untimely deaths of exposed humans.Keywords: Seller’s Staining Test, direct fluorescent antibody test, rabies, diagnosis, Nigeri

Rationale, experience and ethical considerations underpinning integrated actions to further global goals for health and land biodiversity in Papua New Guinea

The SURFACES project is integrating action on good health and wellbeing (Sustainable Development Goal [SDG] 3) and conservation of life on land (SDG 15) in the threatened rainforests of Papua New Guinea (PNG), and mapping evidence of similar projects worldwide. Our approach is framed by Planetary Health, aiming to safeguard both human health and the natural systems that underpin it. Our rationale is demonstrated through a summary of health needs and forest conservation issues across PNG, and how these play out locally. We outline differing types of integrated conservation and health interventions worldwide, providing examples from Borneo, Uganda, India and elsewhere. We then describe what we are doing on-the-ground in PNG, which includes expansion of a rainforest conservation area alongside the establishment of a nurse-staffed aid post, and an educational intervention conceptually linking forest conservation and health. Importantly, we explore some ethical considerations on the conditionality of medical provision, and identify key challenges to successful implementation of such projects. The latter include: avoiding cross-sectoral blindness and achieving genuine interdisciplinary working; the weak evidence base justifying projects; and temporal-spatial issues. We conclude by suggesting how projects integrating actions on health and conservation SDGs can benefit from (and contribute to) the energy of the emerging Planetary Health movement

Omega-3 Fatty Acids Reduce Adipose Tissue Macrophages in Human Subjects with Insulin Resistance

Fish oils (FOs) have anti-inflammatory effects and lower serum triglycerides. This study examined adipose and muscle inflammatory markers after treatment of humans with FOs and measured the effects of ω-3 fatty acids on adipocytes and macrophages in vitro. Insulin-resistant, nondiabetic subjects were treated with Omega-3-Acid Ethyl Esters (4 g/day) or placebo for 12 weeks. Plasma macrophage chemoattractant protein 1 (MCP-1) levels were reduced by FO, but the levels of other cytokines were unchanged. The adipose (but not muscle) of FO-treated subjects demonstrated a decrease in macrophages, a decrease in MCP-1, and an increase in capillaries, and subjects with the most macrophages demonstrated the greatest response to treatment. Adipose and muscle ω-3 fatty acid content increased after treatment; however, there was no change in insulin sensitivity or adiponectin. In vitro, M1-polarized macrophages expressed high levels of MCP-1. The addition of ω-3 fatty acids reduced MCP-1 expression with no effect on TNF-α. In addition, ω-3 fatty acids suppressed the upregulation of adipocyte MCP-1 that occurred when adipocytes were cocultured with macrophages. Thus, FO reduced adipose macrophages, increased capillaries, and reduced MCP-1 expression in insulin-resistant humans and in macrophages and adipocytes in vitro; however, there was no measureable effect on insulin sensitivity. Diabetes 62:1709–1717, 201