169 research outputs found

    Homogeneous low-molecular-weight heparins with reversible anticoagulant activity

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    Low-molecular-weight heparins (LMWHs) are carbohydrate-based anticoagulants clinically used to treat thrombotic disorders, but impurities, structural heterogeneity or functional irreversibility can limit treatment options. We report a series of synthetic LMWHs prepared by cost-effective chemoenzymatic methods. The high activity of one defined synthetic LMWH against human factor Xa (FXa) was reversible in vitro and in vivo using protamine, demonstrating that synthetically accessible constructs can have a critical role in the next generation of LMWHs

    Intention Understanding in Autism

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    When we observe a motor act (e.g. grasping a cup) done by another individual, we extract, according to how the motor act is performed and its context, two types of information: the goal (grasping) and the intention underlying it (e.g. grasping for drinking). Here we examined whether children with autistic spectrum disorder (ASD) are able to understand these two aspects of motor acts. Two experiments were carried out. In the first, one group of high-functioning children with ASD and one of typically developing (TD) children were presented with pictures showing hand-object interactions and asked what the individual was doing and why. In half of the “why” trials the observed grip was congruent with the function of the object (“why-use” trials), in the other half it corresponded to the grip typically used to move that object (“why-place” trials). The results showed that children with ASD have no difficulties in reporting the goals of individual motor acts. In contrast they made several errors in the why task with all errors occurring in the “why-place” trials. In the second experiment the same two groups of children saw pictures showing a hand-grip congruent with the object use, but within a context suggesting either the use of the object or its placement into a container. Here children with ASD performed as TD children, correctly indicating the agent's intention. In conclusion, our data show that understanding others' intentions can occur in two ways: by relying on motor information derived from the hand-object interaction, and by using functional information derived from the object's standard use. Children with ASD have no deficit in the second type of understanding, while they have difficulties in understanding others' intentions when they have to rely exclusively on motor cues

    Bazaar aesthetics: On excess and economic rationality

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    For more than a century, social theoretical writings on consumer culture and commodity aesthetics have concentrated on the world of capitalist commodities and commercial spaces: on brands, shopping malls and global media culture. Popular commodity aesthetics have had a marginal presence in the literature. However, today, as the popular masses are entering commercial culture to an unprecedented extent, through cheap electronics, ubiquitous internet connectivity and accessible knock-offs, popular commodity aesthetics have increased in importance. In this article, I use fieldwork in Delhi’s electronics bazaars to develop an inside perspective on the popular aesthetic of the bazaar. I argue that bazaars are characterized by excess: the excess of a seemingly chaotic architecture, household objects, and unhindered sociality. The excess is not simply a symptom of an underlying irrationality. It is deeply embedded in the social and economic life of bazaars and contributes towards the ability of small-scale commerce to endure and survive

    Microprocessor mediates transcriptional termination of long noncoding RNA transcripts hosting microRNAs

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    MicroRNA (miRNA) play a major role in the post-transcriptional regulation of gene expression. Mammalian miRNA biogenesis begins with co-transcriptional cleavage of RNA polymerase II (Pol II) transcripts by the Microprocessor complex. While most miRNA are located within introns of protein coding genes, a substantial minority of miRNA originate from long non coding (lnc) RNA where transcript processing is largely uncharacterized. Here, by detailed characterization of liver-specific lnc-pri-miR-122 and genome-wide analysis, we show that most lnc-pri-miRNA do not use the canonical cleavage and polyadenylation (CPA) pathway but instead use Microprocessor cleavage to terminate transcription. Microprocessor inactivation leads to extensive transcriptional readthrough of lnc-pri-miRNA and transcriptional interference with downstream genes. Consequently we define a novel RNase III-mediated, polyadenylation-independent mechanism of Pol II transcription termination in mammalian cells

    Neurexin-1 and Frontal Lobe White Matter: An Overlapping Intermediate Phenotype for Schizophrenia and Autism Spectrum Disorders

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    Background: Structural variation in the neurexin-1 (NRXN1) gene increases risk for both autism spectrum disorders (ASD) and schizophrenia. However, the manner in which NRXN1 gene variation may be related to brain morphology to confer risk for ASD or schizophrenia is unknown. Method/Principal Findings: 53 healthy individuals between 18–59 years of age were genotyped at 11 single nucleotide polymorphisms of the NRXN1 gene. All subjects received structural MRI scans, which were processed to determine cortical gray and white matter lobar volumes, and volumes of striatal and thalamic structures. Each subject’s sensorimotor function was also assessed. The general linear model was used to calculate the influence of genetic variation on neural and cognitive phenotypes. Finally, in silico analysis was conducted to assess potential functional relevance of any polymorphisms associated with brain measures. A polymorphism located in the 39 untranslated region of NRXN1 significantly influenced white matter volumes in whole brain and frontal lobes after correcting for total brain volume, age and multiple comparisons. Follow-up in silico analysis revealed that this SNP is a putative microRNA binding site that may be of functional significance in regulating NRXN1 expression. This variant also influenced sensorimotor performance, a neurocognitive function impaired in both ASD and schizophrenia. Conclusions: Our findings demonstrate that the NRXN1 gene, a vulnerability gene for SCZ and ASD, influences brai

    A new synaptic player leading to autism risk: Met receptor tyrosine kinase

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    The validity for assigning disorder risk to an autism spectrum disorder (ASD) candidate gene comes from convergent genetic, clinical, and developmental neurobiology data. Here, we review these lines of evidence from multiple human genetic studies, and non-human primate and mouse experiments that support the conclusion that the MET receptor tyrosine kinase (RTK) functions to influence synapse development in circuits relevant to certain core behavioral domains of ASD. There is association of both common functional alleles and rare copy number variants that impact levels of MET expression in the human cortex. The timing of Met expression is linked to axon terminal outgrowth and synaptogenesis in the developing rodent and primate forebrain, and both in vitro and in vivo studies implicate this RTK in dendritic branching, spine maturation, and excitatory connectivity in the neocortex. This impact can occur in a cell-nonautonomous fashion, emphasizing the unique role that Met plays in specific circuits relevant to ASD

    Partner in fat metabolism: role of KLFs in fat burning and reproductive behavior

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    The abnormalities caused by excess fat accumulation can result in pathological conditions which are linked to several interrelated diseases, such as cardiovascular disease and obesity. This set of conditions, known as metabolic syndrome, is a global pandemic of enormous medical, economic, and social concern affecting a significant portion of the world’s population. Although genetics, physiology and environmental components play a major role in the onset of disease caused by excessive fat accumulation, little is known about how or to what extent each of these factors contributes to it. The worm, Caenorhabditis elegans offers an opportunity to study disease related to metabolic disorder in a developmental system that provides anatomical and genomic simplicity relative to the vertebrate animals and is an excellent eukaryotic genetic model which enable us to answer the questions concerning fat accumulation which remain unresolved. The stored triglycerides (TG) provide the primary source of energy during periods of food deficiency. In nature, lipid stored as TGs are hydrolyzed into fatty acids which are broken down through β-oxidation to yield acetyl-CoA. Our recent study suggests that a member of C. elegans Krüppel-like factor, klf-3 regulates lipid metabolism by promoting FA β-oxidation and in parallel may contribute in normal reproduction and fecundity. Genetic and epigenetic factors that influence this pathway may have considerable impact on fat related diseases in human. Increasing number of studies suggest the role of mammalian KLFs in adipogenesis. This functional conservation should guide our further effort to explore C. elegans as a legitimate model system for studying the role of KLFs in many pathway components of lipid metabolism
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