156 research outputs found

    Status and conservation of lion-tailed macaque and other arboreal mammals in tropical rainforests of Sringeri forest range, Western ghats, Karnataka, India

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    The lion-tailed macaque (Macaca silenus), an endangered primate species, was surveyed in the tropical rainforests of Sringeri in the state of Karnataka, south India. A total of 10 groups and a solitary adult male were found in approximately 90 square kilometers of rainforest. The other sympatric arboreal mammals found included common langurs, bonnet macaques and Malabar giant squirrels. The liontailed macaques are sympatric with other primates and giant squirrels in the undisturbed core areas. More towards the human habitations and disturbed areas, the lion-tailed macaques are absent and the forest is occupied by commensal species. The habitat features and the population structure indicate that this region is a potential area for maintaining a biologically viable population of lion-tailed macaques. However, a number of factors such as extraction of fuel wood, collection of minor forest produce, grazing by domestic livestock and plantation of commercial tree species are causing a serious threat to the habitat. The effect of habitat degradation on arboreal wildlife is discussed and the steps are suggested to minimize the effect of human disturbance on habitat

    CrRLK1L receptor‐like kinases HERK1 and ANJEA are female determinants of pollen tube reception

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    Communication between the gametophytes is vital for angiosperm fertilisation. Multiple CrRLK1L‐type receptor kinases prevent premature pollen tube burst, while another CrRLK1L protein, FERONIA (FER), is required for pollen tube reception in the female gametophyte. We report here the identification of two additional CrRLK1L homologues, HERCULES RECEPTOR KINASE 1 (HERK1) and ANJEA (ANJ), which act redundantly to promote pollen tube growth arrest at the synergid cells. HERK1 and ANJ localise to the filiform apparatus of the synergid cells in unfertilised ovules, and in herk1 anj mutants, a majority of ovules remain unfertilised due to pollen tube overgrowth, together indicating that HERK1 and ANJ act as female determinants for fertilisation. As in fer mutants, the synergid cell‐specific, endomembrane protein NORTIA (NTA) is not relocalised after pollen tube reception; however, unlike fer mutants, reactive oxygen species levels are unaffected in herk1 anj double mutants. Both ANJ and HERK1 associate with FER and its proposed co‐receptor LORELEI (LRE) in planta. Together, our data indicate that HERK1 and ANJ act with FER to mediate female–male gametophyte interactions during plant fertilisation

    Comparative effectiveness of canagliflozin, SGLT2 inhibitors and non-SGLT2 inhibitors on the risk of hospitalization for heart failure and amputation in patients with type 2 diabetes mellitus: A real-world meta-analysis of 4 observational databases (OBSERVE-4D)

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    Aims: Sodium glucose co-transporter 2 inhibitors (SGLT2i) are indicated for treatment of type 2 diabetes mellitus (T2DM)some SGLT2i have reported cardiovascular benefit, and some have reported risk of below-knee lower extremity (BKLE) amputation. This study examined the real-world comparative effectiveness within the SGLT2i class and compared with non-SGLT2i antihyperglycaemic agents. Materials and methods: Data from 4 large US administrative claims databases were used to characterize risk and provide population-level estimates of canagliflozin's effects on hospitalization for heart failure (HHF) and BKLE amputation vs other SGLT2i and non-SGLT2i in T2DM patients. Comparative analyses using a propensity score–adjusted new-user cohort design examined relative hazards of outcomes across all new users and a subpopulation with established cardiovascular disease. Results: Across the 4 databases (142 800 new users of canagliflozin, 110 897 new users of other SGLT2i, 460 885 new users of non-SGLT2i), the meta-analytic hazard ratio estimate for HHF with canagliflozin vs non-SGLT2i was 0.39 (95% CI, 0.26-0.60) in the on-treatment analysis. The estimate for BKLE amputation with canagliflozin vs non-SGLT2i was 0.75 (95% CI, 0.40-1.41) in the on-treatment analysis and 1.01 (95% CI, 0.93-1.10) in the intent-to-treat analysis. Effects in the subpopulation with established cardiovascular disease were similar for both outcomes. No consistent differences were observed between canagliflozin and other SGLT2i. Conclusions: In this large comprehensive analysis, canagliflozin and other SGLT2i demonstrated HHF benefits consistent with clinical trial data, but showed no increased risk of BKLE amputation vs non-SGLT2i. HHF and BKLE amputation results were similar in the subpopulation with established cardiovascular disease. This study helps further characterize the potential benefits and harms of SGLT2i in routine clinical practice to complement evidence from clinical trials and prior observational studies

    The complex TIE between macrophages and angiogenesis

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    Macrophages are primarily known as phagocytic immune cells, but they also play a role in diverse processes, such as morphogenesis, homeostasis and regeneration. In this review, we discuss the influence of macrophages on angiogenesis, the process of new blood vessel formation from the pre-existing vasculature. Macrophages play crucial roles at each step of the angiogenic cascade, starting from new blood vessel sprouting to the remodelling of the vascular plexus and vessel maturation. Macrophages form promising targets for both pro- and anti-angiogenic treatments. However, to target macrophages, we will first need to understand the mechanisms that control the functional plasticity of macrophages during each of the steps of the angiogenic cascade. Here, we review recent insights in this topic. Special attention will be given to the TIE2-expressing macrophage (TEM), which is a subtype of highly angiogenic macrophages that is able to influence angiogenesis via the angiopoietin-TIE pathway

    Rare variant collapsing in conjunction with mean log p-value and gradient boosting approaches applied to Genetic Analysis Workshop 17 data

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    In addition to methods that can identify common variants associated with susceptibility to common diseases, there has been increasing interest in approaches that can identify rare genetic variants. We use the simulated data provided to the participants of Genetic Analysis Workshop 17 (GAW17) to identify both rare and common single-nucleotide polymorphisms and pathways associated with disease status. We apply a rare variant collapsing approach and the usual association tests for common variants to identify candidates for further analysis using pathway-based and tree-based ensemble approaches. We use the mean log p-value approach to identify a top set of pathways and compare it to those used in simulation of GAW17 dataset. We conclude that the mean log p-value approach is able to identify those pathways in the top list and also related pathways. We also use the stochastic gradient boosting approach for the selected subset of single-nucleotide polymorphisms. When compared the result of this tree-based method with the list of single-nucleotide polymorphisms used in dataset simulation, in addition to correct SNPs we observe number of false positives

    A proposal for a coordinated effort for the determination of brainwide neuroanatomical connectivity in model organisms at a mesoscopic scale

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    In this era of complete genomes, our knowledge of neuroanatomical circuitry remains surprisingly sparse. Such knowledge is however critical both for basic and clinical research into brain function. Here we advocate for a concerted effort to fill this gap, through systematic, experimental mapping of neural circuits at a mesoscopic scale of resolution suitable for comprehensive, brain-wide coverage, using injections of tracers or viral vectors. We detail the scientific and medical rationale and briefly review existing knowledge and experimental techniques. We define a set of desiderata, including brain-wide coverage; validated and extensible experimental techniques suitable for standardization and automation; centralized, open access data repository; compatibility with existing resources, and tractability with current informatics technology. We discuss a hypothetical but tractable plan for mouse, additional efforts for the macaque, and technique development for human. We estimate that the mouse connectivity project could be completed within five years with a comparatively modest budget.Comment: 41 page

    Functional dissection of the Drosophila Kallmann's syndrome protein DmKal-1

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    BACKGROUND: Anosmin-1, the protein implicated in the X-linked Kallmann's syndrome, plays a role in axon outgrowth and branching but also in epithelial morphogenesis. The molecular mechanism of its action is, however, widely unknown. Anosmin-1 is an extracellular protein which contains a cysteine-rich region, a whey acidic protein (WAP) domain homologous to some serine protease inhibitors, and four fibronectin-like type III (FnIII) repeats. Drosophila melanogaster Kal-1 (DmKal-1) has the same protein structure with minor differences, the most important of which is the presence of only two FnIII repeats and a C-terminal region showing a low similarity with the third and the fourth human FnIII repeats. We present a structure-function analysis of the different DmKal-1 domains, including a predicted heparan-sulfate binding site. RESULTS: This study was performed overexpressing wild type DmKal-1 and a series of deletion and point mutation proteins in two different tissues: the cephalopharyngeal skeleton of the embryo and the wing disc. The overexpression of DmKal-1 in the cephalopharyngeal skeleton induced dosage-sensitive structural defects, and we used these phenotypes to perform a structure-function dissection of the protein domains. The reproduction of two deletions found in Kallmann's Syndrome patients determined a complete loss of function, whereas point mutations induced only minor alterations in the activity of the protein. Overexpression of the mutant proteins in the wing disc reveals that the functional relevance of the different DmKal-1 domains is dependent on the extracellular context. CONCLUSION: We suggest that the role played by the various protein domains differs in different extracellular contexts. This might explain why the same mutation analyzed in different tissues or in different cell culture lines often gives opposite phenotypes. These analyses also suggest that the FnIII repeats have a main and specific role, while the WAP domain might have only a modulator role, strictly connected to that of the fibronectins

    J/ψ\psi suppression in In-In collisions at 158 GeV/nucleon

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    The NA60 experiment has studied J/ψ\psi production in Indium-Indium collisions at 158 A\cdotGeV. In this paper we present an updated set of results obtained with the complete set of available statistics and an improved alignment of the vertex tracker. The centrality dependence of the J/ψ\psi production, obtained with an analysis technique based only on the J/ψ\psi sample, indicates that a suppression beyond that induced by nuclear absorption is present in In-In collisions, setting in at \sim80 participant nucleons. A first study of the systematic errors related with this measurement is discussed. We also present preliminary results on the J/ψ\psi azimuthal distributions.Comment: 8 pages, 3 figures, proceedings of Hard Probes 2006 International Conferenc
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