The major obstacle to a cure for HIV infection is the persistence of replication-competent viral reservoirs during antiretroviral therapy. HIV-specific chimeric antigen receptor (CAR) T cells have been developed to target latently infected CD4⁺ T cells that express virus either spontaneously or after intentional latency reversal. Whether HIV-specific CAR-T cells can recognize and eliminate the follicular dendritic cell (FDC) reservoir of HIV-bound immune complexes (ICs) is unknown. We created HIV-specific CAR-T cells using human peripheral blood mononuclear cells (PBMCs) and a CAR construct that enables the expression of CD4 (domains 1 and 2) and the carbohydrate recognition domain of mannose binding lectin (MBL) to target native HIV Env (CD4-MBL CAR). We assessed CAR-T cell cytotoxicity using a carboxyfluorescein succinimidyl ester (CFSE) release assay and evaluated CAR-T cell activation through interferon gamma (IFN-) production and CD107a membrane accumulation by flow cytometry. CD4-MBL CAR-T cells displayed potent lytic and functional responses to Env-expressing cell lines and HIV-infected CD4⁺ T cells but were ineffective at targeting FDC bearing HIV-ICs. CD4-MBL CAR-T cells were unresponsive to cell-free HIV or concentrated, immobilized HIV-ICs in cell-free experiments. Blocking intercellular adhesion molecule-1 (ICAM-1) inhibited the cytolytic response of CD4-MBL CAR-T cells to Env-expressing cell lines and HIV-infected CD4⁺ T cells, suggesting that factors such as adhesion molecules are necessary for the stabilization of the CAR-Env interaction to elicit a cytotoxic response. Thus, CD4-MBL CAR-T cells are unable to eliminate the FDC-associated HIV reservoir, and alternative strategies to eradicate this reservoir must be sought.

IMPORTANCE Efforts to cure HIV infection have focused primarily on the elimination of latently infected CD4⁺ T cells. Few studies have addressed the unique reservoir of infectious HIV that exists on follicular dendritic cells (FDCs), persists in vivo during antiretroviral therapy, and likely contributes to viral rebound upon cessation of antiretroviral therapy. We assessed the efficacy of a novel HIV-specific chimeric antigen receptor (CAR) T cell to target both HIV-infected CD4⁺ T cells and the FDC reservoir in vitro. Although CAR-T cells eliminated CD4⁺ T cells that express HIV, they did not respond to or eliminate FDC bound to HIV. These findings reveal a fundamental limitation to CAR-T cell therapy to eradicate HIV.

Discovery of the Breagh gas field in the Southern North Sea (SNS) has demonstrated the potential that the Lower Carboniferous (Visean, 346.7–330.9 Ma) Farne Group reservoirs have to contribute to the UK's future energy mix. New biostratigraphic correlations provide a basis to compare Asbian and Brigantian sedimentary cores from the Breagh Field and age-equivalent sediments exposed on the Northumberland Coast, which has proved critical in gaining an understanding of exploration and development opportunities. Thirteen facies associations characterize the mixed carbonate–siliciclastic system, grouped into: marine, delta front, delta shoreface, lower delta plain and upper delta plain gross depositional environments. The facies associations are interpreted as depositing in a mixed carbonate and siliciclastic fluvio-deltaic environment, and are arranged into coarsening- and cleaning-upward cycles (parasequences) bounded by flooding surfaces. Most cycles are characterized by mouth bars, distributary channels, interdistributary bays and common braided rivers, interpreted as river-dominated deltaic deposits. Some cycles include rare shoreface and tidally-influenced deposits, interpreted as river-dominated and wave- or tide-influenced deltaic deposits. The depositional processes that formed each cycle have important implications for the reservoir net/gross ratio (where this ratio indicates the proportion of sandstone beds in a cycle), thickness and lateral extent. The deltaic deposits were controlled by a combination of tectonic and eustatic (allocyclic) events and delta avulsion (autocyclic) processes, and are likely to reflect a changing tectonic regime, from extension within elongate fault-bounded basins (synrift) to passive regional thermal subsidence (post-rift). Deep incision by the Base Permian Unconformity across the Breagh Field has removed the Westphalian, Namurian and upper Visean, to leave the more prospective thicker clastic reservoirs within closure.

Thematic collection: This article is part of the Under-explored plays and frontier basins of the UK continental shelf collection available at: https://www.lyellcollection.org/cc/under-explored-plays-and-frontier-basins-of-the-uk-continental-shelf

Our photo of the day comes from Cornwall, England.

IWMI plans to use the data from Futurepump’s 4,000 pumps to calculate how much water is being extracted at any given time, which can help governments ensure it is used sustainably, with limits on extraction or a shift to less water-intensive crops.

Small reservoirs are a critical coping mechanism in water-stressed rural areas in Africa, providing immense livelihood benefits that include improved food and water security, entrepreneurial activities and climate resilience. Challenges associated with the implementation of investments in small reservoirs include appropriate site selection, weak institutions, insufficient maintenance and sedimentation. The findings from this study suggest […]

‘Fun and loving’ schoolboy Ben Thomson has died after a day out with friends at Glenburn Reservoir in Paisley, Renfrewshire.

Siltation studies of 27 dam-created reservoirs spanning the nation, obtained using the RTI law indicate that all is not well. Storage capacities of the reservoirs have been dropping and the loss is alarming; what's worse, little is being to done to stop the wastage, find Himanshu Thakkar & Swarup Bhattacharyya.

Michael Madsen will be playing the role of a Police Captain from Seattle PD in Nishabdham, which also stars Baahubali actress Anushka Shetty.

Khadakvasla Reservoir

Artificial Water Reservoirs

Koteshwar reservoir

A series of remarkable photographs from the library’s Geographic File (PR20) documents the construction of the Central Park Reservoir,  located between 86th and 96th streets.  Built between 1858 and 1862, the 106-acre reservoir is 40 feet deep and holds over a billion gallons of water. Once a critical part of the city’s fresh water system, it received water from the Croton...

The post Treasure Trove: Constructing the Central Park Reservoir appeared first on New-York Historical Society.

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Hayden Library - QE350.22.N67 R55 2018

Dewey Library - GB1201.R58 2019

Barker Library - TN858.L44 2019

Barker Library - TC540.R47 2019

Barker Library - TN870.53.E78 2019

Durham : Duke University Press, 2020.