28 research outputs found

    Replication in Cells of Hematopoietic Origin Is Necessary for Dengue Virus Dissemination

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    Dengue virus (DENV) is a mosquito-borne pathogen for which no vaccine or specific therapeutic is available. Although it is well established that dendritic cells and macrophages are primary sites of DENV replication, it remains unclear whether non-hematopoietic cellular compartments serve as virus reservoirs. Here, we exploited hematopoietic-specific microRNA-142 (miR-142) to control virus tropism by inserting tandem target sites into the virus to restrict replication exclusively in this cell population. In vivo use of this virus restricted infection of CD11b+, CD11c+, and CD45+ cells, resulting in a loss of virus spread, regardless of the route of administration. Furthermore, sequencing of the targeted virus population that persisted at low levels, demonstrated total excision of the inserted miR-142 target sites. The complete conversion of the virus population under these selective conditions suggests that these immune cells are the predominant sources of virus amplification. Taken together, this work highlights the importance of hematopoietic cells for DENV replication and showcases an invaluable tool for the study of virus pathogenesis

    Elasmobranch conservation, challenges and management strategy in India: recommendations from a national consultative meeting

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    Historically, India has been projected as one of the major elasmobranch fishing nations in the world. However, management and conservation efforts are not commensurate with this trend. Along with the Wildlife (Protection) Act, 1972, several generic conservation measures are in place at the regional/local level. But India is still a long way from meeting global conservation commitments. We present here the status of elasmobranch management and conservation in India, with the specific objec-tive of identifying the gaps in the existing set-up. We also present recommendations based on a national consultative workshop held at the Central Marine Fisheries Research Institute, Kochi, in February 2020. We recommend the implementation of a National Plan of Action (NPOA-Sharks) and more in-clusive governance and policymaking for elasmobranch conservation in India

    The Beaker phenomenon and the genomic transformation of northwest Europe

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    From around 2750 to 2500 bc, Bell Beaker pottery became widespread across western and central Europe, before it disappeared between 2200 and 1800 bc. The forces that propelled its expansion are a matter of long-standing debate, and there is support for both cultural diffusion and migration having a role in this process. Here we present genome-wide data from 400 Neolithic, Copper Age and Bronze Age Europeans, including 226 individuals associated with Beaker-complex artefacts. We detected limited genetic affinity between Beaker-complex-associated individuals from Iberia and central Europe, and thus exclude migration as an important mechanism of spread between these two regions. However, migration had a key role in the further dissemination of the Beaker complex. We document this phenomenon most clearly in Britain, where the spread of the Beaker complex introduced high levels of steppe-related ancestry and was associated with the replacement of approximately 90% of Britain’s gene pool within a few hundred years, continuing the east-to-west expansion that had brought steppe-related ancestry into central and northern Europe over the previous centuries

    Structural basis for the initiation of eukaryotic transcription-coupled DNA repair

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    Eukaryotic transcription-coupled repair (TCR) is an important and well-conserved sub-pathway of nucleotide excision repair that preferentially removes DNA lesions from the template strand that block translocation of RNA polymerase II (Pol II). Cockayne syndrome group B (CSB, also known as ERCC6) protein in humans (or its yeast orthologues, Rad26 in Saccharomyces cerevisiae and Rhp26 in Schizosaccharomyces pombe) is among the first proteins to be recruited to the lesion-arrested Pol II during the initiation of eukaryotic TCR. Mutations in CSB are associated with the autosomal-recessive neurological disorder Cockayne syndrome, which is characterized by progeriod features, growth failure and photosensitivity1. The molecular mechanism of eukaryotic TCR initiation remains unclear, with several long-standing unanswered questions. How cells distinguish DNA lesion-arrested Pol II from other forms of arrested Pol II, the role of CSB in TCR initiation, and how CSB interacts with the arrested Pol II complex are all unknown. The lack of structures of CSB or the Pol II–CSB complex has hindered our ability to address these questions. Here we report the structure of the S. cerevisiae Pol II–Rad26 complex solved by cryo-electron microscopy. The structure reveals that Rad26 binds to the DNA upstream of Pol II, where it markedly alters its path. Our structural and functional data suggest that the conserved Swi2/Snf2-family core ATPase domain promotes the forward movement of Pol II, and elucidate key roles for Rad26 in both TCR and transcription elongation

    Demographics and length and weight relationships of commercially important sharks along the north-western coast of India

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    Biological data including size, sex ratios, male maturity, and length and weight relationships for four commercially important shark species, including the milk shark (Rhizoprionodon acutus Ruppell, 1837), the grey sharpnose shark (Rhizoprionodon oligolinx Springer, 1964), the spadenose shark (Scoliodon laticaudus Muller & Henle, 1838), and the bigeye smoothhound shark (Iago omanensis Norman, 1939), landed in Porbandar, Gujarat, India, are provided. All four species were landed by trawlers and gill-netters across three defined seasons, with seasonal differences. Higher proportions of mature R. acutus and S. laticaudus were observed in the pre-monsoon season, with neonates caught throughout the year, whereas higher proportions of mature R. oligolinx and I. omanensis were recorded during the monsoon season, with neonates caught in post-monsoon and pre-monsoon, respectively, showing important species-level differences. These small-bodied shark species (less than 1 m in total length) showed positive allometry in their length and weight relationships. Unlike the other three species, I. omanensis showed high disparity in total lengths (L-T) between the sexes, with females being larger than males, and with males maturing faster, with the smallest mature male of 33.58 cm L-T. Females outnumbered males except in R. acutus, and pregnant females of all species were recorded at least once. Of the 971 males recorded across species, 55.1% were mature and 44.9% were immature. Results from this study indicate that there is substantial overlap between the distributions of these species and fishing activities, and show that most, if not all, life stages are susceptible to mortality as a result of fishing. This study provides managers with a better understanding of the life-history traits of these commercially important species to support future quantitative population assessments, and provides a baseline of trends in fishing-related mortality

    Insights from elastic thermobarometry into exhumation of high-pressure metamorphic rocks from Syros, Greece

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    Retrograde metamorphic rocks provide key insights into the pressure–temperature (P–T) evolution of exhumed material, and resultant P–T constraints have direct implications for the mechanical and thermal conditions of subduction interfaces. However, constraining P–T conditions of retrograde metamorphic rocks has historically been challenging and has resulted in debate about the conditions experienced by these rocks. In this work, we combine elastic thermobarometry with oxygen isotope thermometry to quantify the P–T evolution of retrograde metamorphic rocks of the Cycladic Blueschist Unit (CBU), an exhumed subduction complex exposed on Syros, Greece. We employ quartz-in-garnet and quartz-in-epidote barometry to constrain pressures of garnet and epidote growth near peak subduction conditions and during exhumation, respectively. Oxygen isotope thermometry of quartz and calcite within boudin necks was used to estimate temperatures during exhumation and to refine pressure estimates. Three distinct pressure groups are related to different metamorphic events and fabrics: high-pressure garnet growth at ∼1.4–1.7 GPa between 500–550 ∘C, retrograde epidote growth at ∼1.3–1.5 GPa between 400–500 ∘C, and a second stage of retrograde epidote growth at ∼1.0 GPa and 400 ∘C. These results are consistent with different stages of deformation inferred from field and microstructural observations, recording prograde subduction to blueschist–eclogite facies and subsequent retrogression under blueschist–greenschist facies conditions. Our new results indicate that the CBU experienced cooling during decompression after reaching maximum high-pressure–low-temperature conditions. These P–T conditions and structural observations are consistent with exhumation and cooling within the subduction channel in proximity to the refrigerating subducting plate, prior to Miocene core-complex formation. This study also illustrates the potential of using elastic thermobarometry in combination with structural and microstructural constraints, to better understand the P–T-deformation conditions of retrograde mineral growth in high-pressure–low-temperature (HP/LT) metamorphic terranes.ISSN:1869-9510ISSN:1869-952

    Subduction, Underplating, and Return Flow Recorded in the Cycladic Blueschist Unit Exposed on Syros, Greece

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    Exhumed high-pressure/low-temperature (HP/LT) metamorphic rocks provide insights into deep (∼20–70 km) subduction interface dynamics. On Syros Island (Cyclades, Greece), the Cycladic Blueschist Unit preserves blueschist-to-eclogite facies oceanic- and continental-affinity rocks that record the structural and thermal evolution linked to Eocene subduction. Despite decades of research, the metamorphic and deformation history (P-T-D) and timing of subduction and exhumation are matters of ongoing discussion. We suggest that Syros comprises three coherent tectonic slices and that each slice underwent subduction, underplating, and syn-subduction return flow along similar P-T trajectories, but at progressively younger times. Subduction and exhumation are distinguished by lineations and ductile fold axis orientations, and are kinematically consistent with previous studies that document top-to-the-S-SW shear (prograde-to-peak subduction), top-to-the-NE shear (blueschist facies exhumation), and then E-W coaxial stretching (greenschist facies exhumation). Amphibole zonations record cooling during decompression, indicating return flow above a cold slab. Multi-mineral Rb-Sr isochrons and compiled metamorphic geochronology show that the three slices record distinct stages of peak subduction (53–52, ∼50, and 45 Ma) that young with structural depth. Retrograde blueschist and greenschist facies fabrics span ∼50–40 and ∼43–20 Ma, respectively, and also young with structural depth. Synthesized data sets support a revised tectonic framework for Syros, involving subduction of structurally distinct coherent slices and simultaneous return flow of previously accreted tectonic slices in the subduction channel shear zone. Distributed, ductile, dominantly coaxial return flow in an Eocene-Oligocene subduction channel proceeded at rates of ∼1.5–5 mm/yr and accommodated ∼80% of the total exhumation of this HP/LT complex
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