Autosomal dominant VCP hypomorph mutation impairs disaggregation of PHF-tau
Neurodegeneration in Alzheimer’s disease (AD) is closely associated with the accumulation of pathologic tau aggregates in the form of neurofibrillary tangles. We found that a p.Asp395Gly mutation in VCP (valosin-containing protein) was associated with dementia characterized neuropathologically by neuronal vacuoles and neurofibrillary tangles. Moreover, VCP appeared to exhibit tau disaggregase activity in vitro, which was impaired by the p.Asp395Gly mutation. Additionally, intracerebral microinjection of pathologic tau led to increased tau aggregates in mice in which p.Asp395Gly VCP mice was knocked in, as compared wi...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Darwich, N. F., Phan, J. M., Kim, B., Suh, E., Papatriantafyllou, J. D., Changolkar, L., Nguyen, A. T., ORourke, C. M., He, Z., Porta, S., Gibbons, G. S., Luk, K. C., Papageorgiou, S. G., Grossman, M., Massimo, L., Irwin, D. J., McMillan, C. T., Nasrallah Tags: Biochemistry, Medicine, Diseases, Online Only r-articles Source Type: news
Gene regulatory networks controlling vertebrate retinal regeneration
Injury induces retinal Müller glia of certain cold-blooded vertebrates, but not those of mammals, to regenerate neurons. To identify gene regulatory networks that reprogram Müller glia into progenitor cells, we profiled changes in gene expression and chromatin accessibility in Müller glia from zebrafish, chick, and mice in response to different stimuli. We identified evolutionarily conserved and species-specific gene networks controlling glial quiescence, reactivity, and neurogenesis. In zebrafish and chick, the transition from quiescence to reactivity is essential for retinal regeneration, whereas in mice, a dedicat...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Hoang, T., Wang, J., Boyd, P., Wang, F., Santiago, C., Jiang, L., Yoo, S., Lahne, M., Todd, L. J., Jia, M., Saez, C., Keuthan, C., Palazzo, I., Squires, N., Campbell, W. A., Rajaii, F., Parayil, T., Trinh, V., Kim, D. W., Wang, G., Campbell, L. J., Ash, J Tags: Neuroscience, Online Only r-articles Source Type: news
Comment on "Ancient origins of allosteric activation in a Ser-Thr kinase"
Hadzipasic et al. (Reports, 21 February 2020, p. 912) used ancestral sequence reconstruction to identify historical sequence substitutions that putatively caused Aurora kinases to evolve allosteric regulation. We show that their results arise from using an implausible phylogeny and sparse sequence sampling. Addressing either problem reverses their inferences: Allostery and the amino acids that confer it were not gained during the diversification of eukaryotes but were lost in a subgroup of Fungi. (Source: ScienceNOW)
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Park, Y., Patton, J. E. J., Hochberg, G. K. A., Thornton, J. W. Tags: Evolution t-comment Source Type: news
Architecture of the photosynthetic complex from a green sulfur bacterium
The photosynthetic apparatus of green sulfur bacteria (GSB) contains a peripheral antenna chlorosome, light-harvesting Fenna-Matthews-Olson proteins (FMO), and a reaction center (GsbRC). We used cryo–electron microscopy to determine a 2.7-angstrom structure of the FMO-GsbRC supercomplex from Chlorobaculum tepidum. The GsbRC binds considerably fewer (bacterio)chlorophylls [(B)Chls] than other known type I RCs do, and the organization of (B)Chls is similar to that in photosystem II. Two BChl layers in GsbRC are not connected by Chls, as seen in other RCs, but associate with two carotenoid derivatives. Relatively long d...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Chen, J.-H., Wu, H., Xu, C., Liu, X.-C., Huang, Z., Chang, S., Wang, W., Han, G., Kuang, T., Shen, J.-R., Zhang, X. Tags: Biochemistry, Botany, Online Only r-articles Source Type: news
Rotavirus induces intercellular calcium waves through ADP signaling
Rotavirus causes severe diarrheal disease in children by broadly dysregulating intestinal homeostasis. However, the underlying mechanism(s) of rotavirus-induced dysregulation remains unclear. We found that rotavirus-infected cells produce paracrine signals that manifested as intercellular calcium waves (ICWs), observed in cell lines and human intestinal enteroids. Rotavirus ICWs were caused by the release of extracellular adenosine 5'-diphosphate (ADP) that activated P2Y1 purinergic receptors on neighboring cells. ICWs were blocked by P2Y1 antagonists or CRISPR-Cas9 knockout of the P2Y1 receptor. Blocking the ADP signal re...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Chang-Graham, A. L., Perry, J. L., Engevik, M. A., Engevik, K. A., Scribano, F. J., Gebert, J. T., Danhof, H. A., Nelson, J. C., Kellen, J. S., Strtak, A. C., Sastri, N. P., Estes, M. K., Britton, R. A., Versalovic, J., Hyser, J. M. Tags: Microbiology, Molecular Biology, Online Only r-articles Source Type: news
Divergent impacts of warming weather on wildlife disease risk across climates
Disease outbreaks among wildlife have surged in recent decades alongside climate change, although it remains unclear how climate change alters disease dynamics across different geographic regions. We amassed a global, spatiotemporal dataset describing parasite prevalence across 7346 wildlife populations and 2021 host-parasite combinations, compiling local weather and climate records at each location. We found that hosts from cool and warm climates experienced increased disease risk at abnormally warm and cool temperatures, respectively, as predicted by the thermal mismatch hypothesis. This effect was greatest in ectothermi...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Cohen, J. M., Sauer, E. L., Santiago, O., Spencer, S., Rohr, J. R. Tags: Ecology, Medicine, Diseases, Online Only r-articles Source Type: news
Sponsored Collection | The Human Protein Atlas: A 20-year journey into the body
Source: ScienceNOW - November 19, 2020 Category: Science Tags: Cell Biology, Medicine, Diseases From the AAAS Office of Publishing Source Type: news
Technology Feature | Can patients' gut microbes help fight cancer?
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Powell, K. Tags: From the AAAS Office of Publishing Source Type: news
Enhanced Zika virus susceptibility of globally invasive Aedes aegypti populations
The drivers and patterns of zoonotic virus emergence in the human population are poorly understood. The mosquito Aedes aegypti is a major arbovirus vector native to Africa that invaded most of the world’s tropical belt over the past four centuries, after the evolution of a "domestic" form that specialized in biting humans and breeding in water storage containers. Here, we show that human specialization and subsequent spread of A. aegypti out of Africa were accompanied by an increase in its intrinsic ability to acquire and transmit the emerging human pathogen Zika virus. Thus, the recent evolution and global...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Aubry, F., Dabo, S., Manet, C., Filipovic, I., Rose, N. H., Miot, E. F., Martynow, D., Baidaliuk, A., Merkling, S. H., Dickson, L. B., Crist, A. B., Anyango, V. O., Romero-Vivas, C. M., Vega-Rua, A., Dusfour, I., Jiolle, D., Paupy, C., Mayanja, M. N., Lut Tags: Microbiology reports Source Type: news
Tissue topography steers migrating Drosophila border cells
Moving cells can sense and respond to physical features of the microenvironment; however, in vivo, the significance of tissue topography is mostly unknown. Here, we used Drosophila border cells, an established model for in vivo cell migration, to study how chemical and physical information influences path selection. Although chemical cues were thought to be sufficient, live imaging, genetics, modeling, and simulations show that microtopography is also important. Chemoattractants promote predominantly posterior movement, whereas tissue architecture presents orthogonal information, a path of least resistance concentrated nea...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Dai, W., Guo, X., Cao, Y., Mondo, J. A., Campanale, J. P., Montell, B. J., Burrous, H., Streichan, S., Gov, N., Rappel, W.-J., Montell, D. J. Tags: Cell Biology, Development reports Source Type: news
Oceanic plateau of the Hawaiian mantle plume head subducted to the uppermost lower mantle
The Hawaiian-Emperor seamount chain that includes the Hawaiian volcanoes was created by the Hawaiian mantle plume. Although the mantle plume hypothesis predicts an oceanic plateau produced by massive decompression melting during the initiation stage of the Hawaiian hot spot, the fate of this plateau is unclear. We discovered a megameter-scale portion of thickened oceanic crust in the uppermost lower mantle west of the Sea of Okhotsk by stacking seismic waveforms of SS precursors. We propose that this thick crust represents a major part of the oceanic plateau that was created by the Hawaiian plume head ~100 million years ag...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Wei, S. S., Shearer, P. M., Lithgow-Bertelloni, C., Stixrude, L., Tian, D. Tags: Geochemistry, Geophysics reports Source Type: news
Experimental observation of the liquid-liquid transition in bulk supercooled water under pressure
We prepared bulk samples of supercooled liquid water under pressure by isochoric heating of high-density amorphous ice to temperatures of 205 ± 10 kelvin, using an infrared femtosecond laser. Because the sample density is preserved during the ultrafast heating, we could estimate an initial internal pressure of 2.5 to 3.5 kilobar in the high-density liquid phase. After heating, the sample expanded rapidly, and we captured the resulting decompression process with femtosecond x-ray laser pulses at different pump-probe delay times. A discontinuous structural change occurred in which low-density liquid domains appeared a...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Kim, K. H., Amann-Winkel, K., Giovambattista, N., Späh, A., Perakis, F., Pathak, H., Parada, M. L., Yang, C., Mariedahl, D., Eklund, T., Lane, T. J., You, S., Jeong, S., Weston, M., Lee, J. H., Eom, I., Kim, M., Park, J., Chun, S. H., Poole, P. H. Tags: Chemistry, Physics reports Source Type: news
A marine microbiome antifungal targets urgent-threat drug-resistant fungi
New antifungal drugs are urgently needed to address the emergence and transcontinental spread of fungal infectious diseases, such as pandrug-resistant Candida auris. Leveraging the microbiomes of marine animals and cutting-edge metabolomics and genomic tools, we identified encouraging lead antifungal molecules with in vivo efficacy. The most promising lead, turbinmicin, displays potent in vitro and mouse-model efficacy toward multiple-drug–resistant fungal pathogens, exhibits a wide safety index, and functions through a fungal-specific mode of action, targeting Sec14 of the vesicular trafficking pathway. The efficacy...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Zhang, F., Zhao, M., Braun, D. R., Ericksen, S. S., Piotrowski, J. S., Nelson, J., Peng, J., Ananiev, G. E., Chanana, S., Barns, K., Fossen, J., Sanchez, H., Chevrette, M. G., Guzei, I. A., Zhao, C., Guo, L., Tang, W., Currie, C. R., Rajski, S. R., Audhya Tags: Chemistry, Medicine, Diseases reports Source Type: news
An extremely metal-deficient globular cluster in the Andromeda Galaxy
We report a massive GC in the Andromeda Galaxy (M31), RBC EXT8, that is extremely depleted in heavy elements. Its iron abundance is about 1/800 that of the Sun and about one-third that of the most iron-poor GCs previously known. It is also strongly depleted in magnesium. These measurements challenge the notion of a metallicity floor for GCs and theoretical expectations that massive GCs could not have formed at such low metallicities. (Source: ScienceNOW)
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Larsen, S. S., Romanowsky, A. J., Brodie, J. P., Wasserman, A. Tags: Astronomy reports Source Type: news
Nanomesh pressure sensor for monitoring finger manipulation without sensory interference
Monitoring of finger manipulation without disturbing the inherent functionalities is critical to understand the sense of natural touch. However, worn or attached sensors affect the natural feeling of the skin. We developed nanomesh pressure sensors that can monitor finger pressure without detectable effects on human sensation. The effect of the sensor on human sensation was quantitatively investigated, and the sensor-applied finger exhibits comparable grip forces with those of the bare finger, even though the attachment of a 2-micrometer-thick polymeric film results in a 14% increase in the grip force after adjusting for f...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Lee, S., Franklin, S., Hassani, F. A., Yokota, T., Nayeem, M. O. G., Wang, Y., Leib, R., Cheng, G., Franklin, D. W., Someya, T. Tags: Engineering reports Source Type: news
Artificial multimodal receptors based on ion relaxation dynamics
We present a deformable artificial multimodal ionic receptor that can differentiate thermal and mechanical information without signal interference. Two variables are derived from the analysis of the ion relaxation dynamics: the charge relaxation time as a strain-insensitive intrinsic variable to measure absolute temperature and the normalized capacitance as a temperature-insensitive extrinsic variable to measure strain. The artificial receptor with a simple electrode-electrolyte-electrode structure simultaneously detects temperature and strain by measuring the variables at only two measurement frequencies. The human skin&n...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: You, I., Mackanic, D. G., Matsuhisa, N., Kang, J., Kwon, J., Beker, L., Mun, J., Suh, W., Kim, T. Y., Tok, J. B.- H., Bao, Z., Jeong, U. Tags: Physics, Applied, Materials Science reports Source Type: news
Control of long-distance motion of single molecules on a surface
Spatial control over molecular movement is typically limited because motion at the atomic scale follows stochastic processes. We used scanning tunneling microscopy to bring single molecules into a stable orientation of high translational mobility where they moved along precisely defined tracks. Single dibromoterfluorene molecules moved over large distances of 150 nanometers with extremely high spatial precision of 0.1 angstrom across a silver (111) surface. The electrostatic nature of the effect enabled the selective application of repulsive and attractive forces to send or receive single molecules. The high control allows...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Civita, D., Kolmer, M., Simpson, G. J., Li, A.-P., Hecht, S., Grill, L. Tags: Chemistry, Physics reports Source Type: news
Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms
We report the isolation and characterization of two ultrapotent SARS-CoV-2 human neutralizing antibodies (S2E12 and S2M11) that protect hamsters against SARS-CoV-2 challenge. Cryo–electron microscopy structures show that S2E12 and S2M11 competitively block angiotensin-converting enzyme 2 (ACE2) attachment and that S2M11 also locks the spike in a closed conformation by recognition of a quaternary epitope spanning two adjacent receptor-binding domains. Antibody cocktails that include S2M11, S2E12, or the previously identified S309 antibody broadly neutralize a panel of circulating SARS-CoV-2 isolates and activate effec...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Tortorici, M. A., Beltramello, M., Lempp, F. A., Pinto, D., Dang, H. V., Rosen, L. E., McCallum, M., Bowen, J., Minola, A., Jaconi, S., Zatta, F., De Marco, A., Guarino, B., Bianchi, S., Lauron, E. J., Tucker, H., Zhou, J., Peter, A., Havenar-Daughton, C. Tags: Biochemistry, Immunology r-articles Source Type: news
Fetal mast cells mediate postnatal allergic responses dependent on maternal IgE
We report a role for MCs within the developing fetus and demonstrate that fetal MCs may contribute to antigen-specific vertical transmission of allergic disease. (Source: ScienceNOW)
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Msallam, R., Balla, J., Rathore, A. P. S., Kared, H., Malleret, B., Saron, W. A. A., Liu, Z., Hang, J. W., Dutertre, C. A., Larbi, A., Chan, J. K. Y., St. John, A. L., Ginhoux, F. Tags: Cell Biology, Immunology r-articles Source Type: news
A human tissue screen identifies a regulator of ER secretion as a brain-size determinant
Loss-of-function (LOF) screens provide a powerful approach to identify regulators in biological processes. Pioneered in laboratory animals, LOF screens of human genes are currently restricted to two-dimensional cell cultures, which hinders the testing of gene functions requiring tissue context. Here, we present CRISPR–lineage tracing at cellular resolution in heterogeneous tissue (CRISPR-LICHT), which enables parallel LOF studies in human cerebral organoid tissue. We used CRISPR-LICHT to test 173 microcephaly candidate genes, revealing 25 to be involved in known and uncharacterized microcephaly-associated pathways. W...
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Esk, C., Lindenhofer, D., Haendeler, S., Wester, R. A., Pflug, F., Schroeder, B., Bagley, J. A., Elling, U., Zuber, J., von Haeseler, A., Knoblich, J. A. Tags: Development, Medicine, Diseases r-articles Source Type: news
Functional screen for microcephaly genes
Source: ScienceNOW - November 19, 2020 Category: Science Authors: Purnell, B. A. Tags: Development, Medicine, Diseases twis Source Type: news