9 research outputs found

    A proposed mechanism for enhanced water-conservation in egg clutches of the Mexican Kingsnake, Lampropeltis mexicana (Serpentes: Colubridae)

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    A postura de ovos em um substrato úmido minimiza o estresse hídrico de ovos de répteis com casca coriácea, pois permite que absorvam água através da casca permeável. Esse ganho de água contribui para a redução da perda de água em ovos agregados. Demostramos aqui essa característica de conservação de água em ovos da serpente Lampropeltis mexicana em um experimento de balanco hídrico investigando tanto desovas naturais como ovos arranjados experimentalmente em grupos. As taxas de perda de água dos ovos continuam a diminuir à medida que mais ovos são adicionados ao agregado, com um limiar de aproximadamente 15 ovos. Não há redução adicional da taxa de perda de água em um agregado de 20 ovos, número maior que o tamanho típico máximo da desova natural dessa espécie. Correntes de ar seco dirigidas sobre a desova provocam o desaparecimento dessa característica de conservação de água, mas esta reaparece quando o ar está imóvel (desligando-se a corrente de ar). Essa é a primeira vez que um aumento na pressão de vapor de água em um agregado de ovos é demonstrado experimentalmente; os resultados sugerem que a postura de ovos agregados pode beneficiar o desenvolvimento por meio da conservação de umidade.Laying eggs on a wet substrate minimizes water stress for flexible-shelled reptile eggs because they absorb water through the permeable shell. This water gain contributes to reduced water-loss in aggregated eggs. This water-conserving feature is demonstrated in eggs of Lampropeltis mexicana in a water-balance experiment investigating both naturally laid clutches and eggs in arranged clusters. Water-loss rates of eggs decrease as more eggs are added to the aggregation, with a threshold at approximately 15 eggs. There is no further reduction in water-loss rate for eggs in an aggregation of 20, which exceeds the typical maximum for natural clutch size in this species. Blowing dry air over the egg clutch causes this water-conserving feature to disappear, but it re-appears when the air is still (air current turned off). This is the first time that an increase in water-vapor pressure in an aggregation of eggs has been demonstrated experimentally; the results suggest that laying aggregations of eggs may benefit development through moisture conservation

    SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

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    Kidney failure is frequently observed during and after COVID-19, but it remains elusive whether this is a direct effect of the virus. Here, we report that SARS-CoV-2 directly infects kidney cells and is associated with increased tubule-interstitial kidney fibrosis in patient autopsy samples. To study direct effects of the virus on the kidney independent of systemic effects of COVID-19, we infected human-induced pluripotent stem-cell-derived kidney organoids with SARS-CoV-2. Single-cell RNA sequencing indicated injury and dedifferentiation of infected cells with activation of profibrotic signaling pathways. Importantly, SARS-CoV-2 infection also led to increased collagen 1 protein expression in organoids. A SARS-CoV-2 protease inhibitor was able to ameliorate the infection of kidney cells by SARS-CoV-2. Our results suggest that SARS-CoV-2 can directly infect kidney cells and induce cell injury with subsequent fibrosis. These data could explain both acute kidney injury in COVID-19 patients and the development of chronic kidney disease in long COVID

    A proposed mechanism for enhanced water-conservation in egg clutches of the Mexican Kingsnake, Lampropeltis mexicana (Serpentes: Colubridae)

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    Laying eggs on a wet substrate minimizes water stress for flexible-shelled reptile eggs because they absorb water through the permeable shell. This water gain contributes to reduced water-loss in aggregated eggs. This water-conserving feature is demonstrated in eggs of Lampropeltis mexicana in a water-balance experiment investigating both naturally laid clutches and eggs in arranged clusters. Water-loss rates of eggs decrease as more eggs are added to the aggregation, with a threshold at approximately 15 eggs. There is no further reduction in water-loss rate for eggs in an aggregation of 20, which exceeds the typical maximum for natural clutch size in this species. Blowing dry air over the egg clutch causes this waterconserving feature to disappear, but it re-appears when the air is still (air current turned off). This is the first time that an increase in water-vapor pressure in an aggregation of eggs has been demonstrated experimentally; the results suggest that laying aggregations of eggs may benefit development through moisture conservation

    Open science discovery of potent noncovalent SARS-CoV-2 main protease inhibitors

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    We report the results of the COVID Moonshot, a fully open-science, crowdsourced, and structure-enabled drug discovery campaign targeting the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease. We discovered a noncovalent, nonpeptidic inhibitor scaffold with lead-like properties that is differentiated from current main protease inhibitors. Our approach leveraged crowdsourcing, machine learning, exascale molecular simulations, and high-throughput structural biology and chemistry. We generated a detailed map of the structural plasticity of the SARS-CoV-2 main protease, extensive structure-activity relationships for multiple chemotypes, and a wealth of biochemical activity data. All compound designs (>18,000 designs), crystallographic data (>490 ligand-bound x-ray structures), assay data (>10,000 measurements), and synthesized molecules (>2400 compounds) for this campaign were shared rapidly and openly, creating a rich, open, and intellectual property–free knowledge base for future anticoronavirus drug discovery

    Wearable sensors: modalities, challenges, and prospects

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    Wearable sensors have recently seen a large increase in both research and commercialization. However, success in wearable sensors has been a mix of both progress and setbacks. Most of commercial progress has been in smart adaptation of existing mechanical, electrical and optical methods of measuring the body. This adaptation has involved innovations in how to miniaturize sensing technologies, how to make them conformal and flexible, and in the development of companion software that increases the value of the measured data. However, chemical sensing modalities have experienced greater challenges in commercial adoption, especially for non-invasive chemical sensors. There have also been significant challenges in making significant fundamental improvements to existing mechanical, electrical, and optical sensing modalities, especially in improving their specificity of detection. Many of these challenges can be understood by appreciating the body's surface (skin) as more of an information barrier than as an information source. With a deeper understanding of the fundamental challenges faced for wearable sensors and of the state-of-the-art for wearable sensor technology, the roadmap becomes clearer for creating the next generation of innovations and breakthroughs

    SARS-CoV-2 infects the human kidney and drives fibrosis in kidney organoids

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    This work was supported by grants of the German Research Foundation (DFG: KR 4073/11-1; SFBTRR219, 322900939; and CRU344, 428857858, and CRU5011 InteraKD 445703531), a grant of the European Research Council (ERC-StG 677448), the Federal Ministry of Research and Education (BMBF NUM-COVID19, Organo-Strat 01KX2021), the Dutch Kidney Foundation (DKF) TASK FORCE consortium (CP1805), the Else Kroener Fresenius Foundation (2017_A144), and the ERA-CVD MENDAGE consortium (BMBF 01KL1907) all to R.K.; DFG (CRU 344, Z to I.G.C and CRU344 P2 to R.K.S.); and the BMBF eMed Consortium Fibromap (to V.G.P, R.K., R.K.S., and I.G.C.). R.K.S received support from the KWF Kankerbestrijding (11031/2017–1, Bas Mulder Award) and a grant by the ERC (deFiber; ERC-StG 757339). J.J. is supported by the Netherlands Organisation for Scientific Research (NWO Veni grant no: 091 501 61 81 01 36) and the DKF (grant no. 19OK005). B.S. is supported by the DKF (grant: 14A3D104) and the NWO (VIDI grant: 016.156.363). R.P.V.R. and G.J.O. are supported by the NWO VICI (grant: 16.VICI.170.090). P.B. is supported by the BMBF (DEFEAT PANDEMIcs, 01KX2021), the Federal Ministry of Health (German Registry for COVID-19 Autopsies-DeRegCOVID, www.DeRegCOVID.ukaachen.de; ZMVI1-2520COR201), and the German Research Foundation (DFG; SFB/TRR219 Project-IDs 322900939 and 454024652). S.D. received DFG support (DJ100/1-1) as well as support from VGP and TBH (SFB1192). M.d.B,R.R., N.S., and A.A. are supported by an ERC Advanced Investigator grant (H2020-ERC-2017-ADV-788982-COLMIN) to N.S. A.A. is supported by the NWO (VI.Veni.192.094). We thank Saskia de Wildt, Jeanne Pertijs (Radboudumc, Department of Pharmacology), and Robert M. Verdijk (Erasmus Medical Center, Department of Pathology) for providing tissue controls (Erasmus MC Tissue Bank) and Christian Drosten (Charite´ Universitatsmedizin Berlin, Institute of € Virology) and Bart Haagmans (Erasmus Medical Center, Rotterdam) for providing the SARS-CoV-2 isolate. We thank Kioa L. Wijnsma (Department of Pediatric Nephrology, Radboud Institute for Molecular Life Sciences, Amalia Children’s Hospital, Radboud University Medical Center) for support with statistical analysis regarding the COVID-19 patient cohort.Peer reviewedPublisher PD
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