1,255 research outputs found

    Rab4 Orchestrates a Small GTPase Cascade for Recruitment of Adaptor Proteins to Early Endosomes

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    SummaryBackgroundEarly, sorting endosomes are a major crossroad of membrane traffic, at the intersection of the endocytic and exocytic pathways. The sorting of endosomal cargo for delivery to different subcellular destinations is mediated by a number of distinct coat protein complexes, including adaptor protein 1 (AP-1), AP-3, and Golgi-localized, gamma adaptin ear-containing, Arf-binding (GGAs) protein. Ultrastructural studies suggest that these coats assemble onto tubular subdomains of the endosomal membrane, but the mechanisms of coat recruitment and assembly at this site remain poorly understood.ResultsHere we report that the endosomal Rab protein Rab4 orchestrates a GTPase cascade that results in the sequential recruitment of the ADP-ribosylation factor (Arf)-like protein Arl1; the Arf-specific guanine nucleotide exchange factors BIG1 and BIG2; and the class I Arfs, Arf1 and Arf3. Knockdown of Arf1, or inhibition of BIG1 and BIG2 activity with brefeldin A results in the loss of AP-1, AP-3, and GGA-3, but not Arl1, from endosomal membranes and the formation of elongated tubules. In contrast, depletion of Arl1 randomizes the distribution of Rab4 on endosomal membranes, inhibits the formation of tubular subdomains, and blocks recruitment of BIG1 and BIG2, Arfs, and adaptor protein complexes to the endosome.ConclusionsTogether these findings indicate that Arl1 links Rab4-dependent formation of endosomal sorting domains with downstream assembly of adaptor protein complexes that constitute the endosomal sorting machinery

    Confirming the existence of π-allyl-palladium intermediates during the reaction of meta photocycloadducts with palladium(ii) compounds

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    The transient existence of π-allyl-palladium intermediates formed by the reaction of Pd(OAc)2 and anisole-derived meta photocycloadducts has been demonstrated using NMR techniques. The intermediates tended to be short-lived and underwent rapid reductive elimination of palladium metal to form allylic acetates, however this degradation process could be delayed by changing the reaction solvent from acetonitrile to chloroform

    Chromosome-level reference genome of stinkwort, Dittrichia graveolens (L.) Greuter : A resource for studies on invasion, range expansion, and evolutionary adaptation under global change

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    This work was funded by the United States Department of Agriculture, National Institute of Food and Agriculture “Agriculture and Food Research Initiative Grant” [2020-67013-31856]. NL acknowledges support from the Swiss National Science Foundation [P2EZP3_178481] and Natural Environment Research Council [NE/W006553/1].Peer reviewedPublisher PD

    Oiling the bureaucracy? political spending, bureaucrats and the resource curse

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    What role do bureaucrats play in the development of the resource curse in countries that have recently discovered oil? Much of the resource curse literature argues that political leaders spend natural resource revenue in ways that entrench their political power but undermine longer-term economic development. This literature has largely overlooked the role of bureaucrats - those responsible for the day-to-day operations of the state. Bureaucrats may support or constrain political spending in ways that minimize the resource curse. Using results of a survey experiment with over 3,000 government employees in Ghana and Uganda, two countries with recent oil and gas discoveries, we find that bureaucrats treated with information on oil revenue are more likely to disapprove of spending practices that benefit political supporters. The results also suggest that material motivations may be at play: bureaucrats in Uganda who are secure in their jobs and outside of government patronage networks are most likely to oppose the political use of oil revenue. These findings challenge unitary state assumptions underlying much of the resource curse literature, especially for new oil producers. They also suggest that policymakers ought to engage civil servants in efforts to avoid or curtail the resource curse

    Podocytes Produce and Secrete Functional Complement C3 and Complement Factor H

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    Podocytes are an important part of the glomerular filtration barrier and the key player in the development of proteinuria, which is an early feature of complement mediated renal diseases. Complement factors are mainly liver-born and present in circulation. Nevertheless, there is a growing body of evidence for additional sites of complement protein synthesis, including various cell types in the kidney. We hypothesized that podocytes are able to produce complement components and contribute to the local balance of complement activation and regulation. To investigate the relevant balance between inhibiting and activating sides, our studies focused on complement factor H (CFH), an important complement regulator, and on C3, the early key component for complement activation. We characterized human cultured podocytes for the expression and secretion of activating and regulating complement factors, and analyzed the secretion pathway and functional activity. We studied glomerular CFH and C3 expression in puromycin aminonucleoside (PAN) -treated rats, a model for proteinuria, and the physiological mRNA-expression of both factors in murine kidneys. We found, that C3 and CFH were expressed in cultured podocytes and expression levels differed from those in cultivated glomerular endothelial cells. The process of secretion in podocytes was stimulated with interferon gamma and located in the Golgi apparatus. Cultured podocytes could initiate the complement cascade by the splitting of C3, which can be shown by the generation of C3a, a functional C3 split product. C3 contributed to external complement activation. Podocyte-secreted CFH, in conjunction with factor I, was able to split C3b. Podocytes derived from a patient with a CFH mutation displayed impaired cell surface complement regulation. CFH and C3 were synthesized in podocytes of healthy C57Bl/6-mice and were upregulated in podocytes of PAN treated rats. These data show that podocytes produce functionally active complement components, and could therefore influence the local glomerular complement activation and regulation. This modulating effect should therefore be considered in all diseases where glomerular complement activation occurs. Furthermore, our data indicate a potential novel role of podocytes in the innate immune system

    The response of perennial and temporary headwater stream invertebrate communities to hydrological extremes

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    The headwaters of karst rivers experience considerable hydrological variability, including spates and streambed drying. Extreme summer flooding on the River Lathkill (Derbyshire, UK) provided the opportunity to examine the invertebrate community response to unseasonal spate flows, flow recession and, at temporary sites, streambed drying. Invertebrates were sampled at sites with differing flow permanence regimes during and after the spates. Following streambed drying at temporary sites, dewatered surface sediments were investigated as a refugium for aquatic invertebrates. Experimental rehydration of these dewatered sediments was conducted to promote development of desiccation-tolerant life stages. At perennial sites, spate flows reduced invertebrate abundance and diversity, whilst at temporary sites, flow reactivation facilitated rapid colonisation of the surface channel by a limited number of invertebrate taxa. Following streambed drying, 38 taxa were recorded from the dewatered and rehydrated sediments, with Oligochaeta being the most abundant taxon and Chironomidae (Diptera) the most diverse. Experimental rehydration of dewatered sediments revealed the presence of additional taxa, including Stenophylax sp. (Trichoptera: Limnephilidae) and Nemoura sp. (Plecoptera: Nemouridae). The influence of flow permanence on invertebrate community composition was apparent despite the aseasonal high-magnitude flood events

    Neonatal motor functional connectivity and motor outcomes at age two years in very preterm children with and without high-grade brain injury

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    Preterm-born children have high rates of motor impairments, but mechanisms for early identification remain limited. We hypothesized that neonatal motor system functional connectivity (FC) would relate to motor outcomes at age two years; currently, this relationship is not yet well-described in very preterm (VPT; born \u3c32 weeks\u27 gestation) infants with and without brain injury. We recruited 107 VPT infants - including 55 with brain injury (grade III-IV intraventricular hemorrhage, cystic periventricular leukomalacia, post-hemorrhagic hydrocephalus) - and collected FC data at/near term-equivalent age (35-45 weeks postmenstrual age). Correlation coefficients were used to calculate the FC between bilateral motor and visual cortices and thalami. At two years corrected-age, motor outcomes were assessed with the Bayley Scales of Infant and Toddler Development, 3rd edition. Multiple imputation was used to estimate missing data, and regression models related FC measures to motor outcomes. Within the brain-injured group only, interhemispheric motor cortex FC was positively related to gross motor outcomes. Thalamocortical and visual FC were not related to motor scores. This suggests neonatal alterations in motor system FC may provide prognostic information about impairments in children with brain injury

    Religious revelation, secrecy and the limits of visual representation

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    This article seeks to contribute to a more adequate understanding of the adoption of modern audiovisual mass media by contemporary religious groups. It does so by examining Pentecostal-charismatic churches as well as the Christian mass culture instigated by its popularity, and so-called traditional religion in Ghana, which develop markedly different attitudes towards audiovisual mass media and assume different positions in the public sphere. Taking into account the complicated entanglement of traditional religion and Pentecostalism, approaching both religions from a perspective of mediation which regards media as intrinsic to religion, and seeking to avoid the pitfall of overestimating the power of modern mass media to determine the world, this article seeks to move beyond an unproductive recurrence to oppositions such as tradition and modernity, or religion and technology. It is argued that instead of taking as a point of departure more or less set ideas about the nexus of vision and modernity, the adoption of new mass media by religious groups needs to be analyzed by a detailed ethnographic investigation of how these new media transform existing practices of religious mediation. Special emphasis is placed on the tension between the possibilities of gaining public presence through new media, and the difficulty in authorizing these media, and the experiences they induce, as authentic. Copyright © 2006 SAGE Publications
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