[Research Articles] Genomic epidemiology of superspreading events in Austria reveals mutational dynamics and transmission properties of SARS-CoV-2
In conclusion, this study illustrates the power of combining epidemiological analysis with deep viral genome sequencing to unravel the spread of SARS-CoV-2 and to gain fundamental insights into mutational dynamics and transmission properties. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Popa, A., Genger, J.-W., Nicholson, M. D., Penz, T., Schmid, D., Aberle, S. W., Agerer, B., Lercher, A., Endler, L., Colaco, H., Smyth, M., Schuster, M., Grau, M. L., Martinez-Jimenez, F., Pich, O., Borena, W., Pawelka, E., Keszei, Z., Senekowitsch, M., L Tags: Research Articles Source Type: research
[Research Articles] An epoxide hydrolase inhibitor reduces neuroinflammation in a mouse model of Alzheimers disease
We report that sEH is predominantly expressed in astrocytes and is elevated in postmortem brain tissue from patients with AD and in the 5xFAD β amyloid mouse model of AD. The amount of sEH expressed in AD mouse brains correlated with a reduction in brain EpFA concentrations. Using a specific small-molecule sEH inhibitor, 1-trifluoromethoxyphenyl-3-(1-propionylpiperidin-4-yl) urea (TPPU), we report that TPPU treatment protected wild-type mice against LPS-induced inflammation in vivo. Long-term administration of TPPU to the 5xFAD mouse model via drinking water reversed microglia and astrocyte reactivity and immune pathw...
Source: Science Translational Medicine - December 9, 2020 Category: Biomedical Science Authors: Ghosh, A., Comerota, M. M., Wan, D., Chen, F., Propson, N. E., Hwang, S. H., Hammock, B. D., Zheng, H. Tags: Research Articles Source Type: research
[Research Articles] Evidence for a protective role of placental growth factor in cardiovascular disease
Placental growth factor (PlGF) is a mitogen for endothelial cells, but it can also act as a proinflammatory cytokine. Because it promotes early stages of plaque formation in experimental models of atherosclerosis and was implicated in epidemiological associations with risk of cardiovascular disease (CVD), PlGF has been attributed a pro-atherogenic role. Here, we investigated whether PlGF has a protective role in CVD and whether elevated PlGF reflects activation of repair processes in response to vascular stress. In a population cohort of 4742 individuals with 20 years of follow-up, high baseline plasma PlGF was associated ...
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Chen, Y., Nilsson, A. H., Goncalves, I., Edsfeldt, A., Engström, G., Melander, O., Orho-Melander, M., Rauch, U., Tengryd, C., Venuraju, S. M., Lahiri, A., Liang, C., Nilsson, J. Tags: Research Articles Source Type: research
[Research Articles] Chronic embedded cortico-thalamic closed-loop deep brain stimulation for the treatment of essential tremor
Deep brain stimulation (DBS) is an approved therapy for the treatment of medically refractory and severe movement disorders. However, most existing neurostimulators can only apply continuous stimulation [open-loop DBS (OL-DBS)], ignoring patient behavior and environmental factors, which consequently leads to an inefficient therapy, thus limiting the therapeutic window. Here, we established the feasibility of a self-adjusting therapeutic DBS [closed-loop DBS (CL-DBS)], fully embedded in a chronic investigational neurostimulator (Activa PC + S), for three patients affected by essential tremor (ET) enrolled in a longitudinal ...
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Opri, E., Cernera, S., Molina, R., Eisinger, R. S., Cagle, J. N., Almeida, L., Denison, T., Okun, M. S., Foote, K. D., Gunduz, A. Tags: Research Articles Source Type: research
[Editors' Choice] A charged NET accelerates atherosclerosis in acute infections
Neutrophil extracellular traps (NETs) accelerate vascular inflammation in a model of endotoxinemia. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Giannarelli, C. Tags: Editors ' Choice Source Type: research
[Editors' Choice] A triple threat for cancer treatment
Coupling a photosensitizer to camptothecin enhances selectivity and potency of the chemotherapy to kill cancer cells in vitro and in vivo. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Ankrum, J. Tags: Editors ' Choice Source Type: research
[Editors' Choice] Can your diet change your clock?
High-fat diets disturb circadian metabolic rhythms in the brain. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Hurley, J. M. Tags: Editors ' Choice Source Type: research
[Research Articles] Reactivation of dormant tumor cells by modified lipids derived from stress-activated neutrophils
Tumor recurrence years after seemingly successful treatment of primary tumors is one of the major causes of mortality in patients with cancer. Reactivation of dormant tumor cells is largely responsible for this phenomenon. Using dormancy models of lung and ovarian cancer, we found a specific mechanism, mediated by stress and neutrophils, that may govern this process. Stress hormones cause rapid release of proinflammatory S100A8/A9 proteins by neutrophils. S100A8/A9 induce activation of myeloperoxidase, resulting in accumulation of oxidized lipids in these cells. Upon release from neutrophils, these lipids up-regulate the f...
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Perego, M., Tyurin, V. A., Tyurina, Y. Y., Yellets, J., Nacarelli, T., Lin, C., Nefedova, Y., Kossenkov, A., Liu, Q., Sreedhar, S., Pass, H., Roth, J., Vogl, T., Feldser, D., Zhang, R., Kagan, V. E., Gabrilovich, D. I. Tags: Research Articles Source Type: research
[Research Articles] Slowing late infantile Batten disease by direct brain parenchymal administration of a rh.10 adeno-associated virus expressing CLN2
Late infantile Batten disease (CLN2 disease) is an autosomal recessive, neurodegenerative lysosomal storage disease caused by mutations in the CLN2 gene encoding tripeptidyl peptidase 1 (TPP1). We tested intraparenchymal delivery of AAVrh.10hCLN2, a nonhuman serotype rh.10 adeno-associated virus vector encoding human CLN2, in a nonrandomized trial consisting of two arms assessed over 18 months: AAVrh.10hCLN2-treated cohort of 8 children with mild to moderate disease and an untreated, Weill Cornell natural history cohort consisting of 12 children. The treated cohort was also compared to an untreated European natural history...
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Sondhi, D., Kaminsky, S. M., Hackett, N. R., Pagovich, O. E., Rosenberg, J. B., De, B. P., Chen, A., Van de Graaf, B., Mezey, J. G., Mammen, G. W., Mancenido, D., Xu, F., Kosofsky, B., Yohay, K., Worgall, S., Kaner, R. J., Souwedaine, M., Greenwald, B. M. Tags: Research Articles Source Type: research
[Research Articles] Transcriptomic profiling across the nonalcoholic fatty liver disease spectrum reveals gene signatures for steatohepatitis and fibrosis
This study provides insights into the pathophysiology of progressive fibrosing steatohepatitis, and proof of principle that transcriptomic changes represent potentially tractable and clinically relevant markers of disease progression. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Govaere, O., Cockell, S., Tiniakos, D., Queen, R., Younes, R., Vacca, M., Alexander, L., Ravaioli, F., Palmer, J., Petta, S., Boursier, J., Rosso, C., Johnson, K., Wonders, K., Day, C. P., Ekstedt, M., Oresic, M., Darlay, R., Cordell, H. J., Marra, F., Vi Tags: Research Articles Source Type: research
[Research Articles] Glycine-based treatment ameliorates NAFLD by modulating fatty acid oxidation, glutathione synthesis, and the gut microbiome
In conclusion, impaired glycine metabolism may play a causative role in NAFLD. Glycine-based treatment attenuates experimental NAFLD by stimulating hepatic FAO and glutathione synthesis, thus warranting clinical evaluation. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Rom, O., Liu, Y., Liu, Z., Zhao, Y., Wu, J., Ghrayeb, A., Villacorta, L., Fan, Y., Chang, L., Wang, L., Liu, C., Yang, D., Song, J., Rech, J. C., Guo, Y., Wang, H., Zhao, G., Liang, W., Koike, Y., Lu, H., Koike, T., Hayek, T., Pennathur, S., Xi, C., Wen, Tags: Research Articles Source Type: research
[Reviews] A blueprint for translational regenerative medicine
The past few decades have produced a large number of proof-of-concept studies in regenerative medicine. However, the route to clinical adoption is fraught with technical and translational obstacles that frequently consign promising academic solutions to the so-called "valley of death." Here, we present a proposed blueprint for translational regenerative medicine. We offer principles to help guide the selection of cells and materials, present key in vivo imaging modalities, and argue that the host immune response should be considered throughout design and development. Last, we suggest a pathway to navigate the often complex...
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Armstrong, J. P. K., Keane, T. J., Roques, A. C., Patrick, P. S., Mooney, C. M., Kuan, W.-L., Pisupati, V., Oreffo, R. O. C., Stuckey, D. J., Watt, F. M., Forbes, S. J., Barker, R. A., Stevens, M. M. Tags: Reviews Source Type: research
[Focus] Endosomal recycling reconciles the Alzheimers disease paradox
A hub-and-spoke model with endosomal recycling as the hub can reconcile the pathogenic contribution of amyloid precursor protein to Alzheimer’s disease. (Source: Science Translational Medicine)
Source: Science Translational Medicine - December 2, 2020 Category: Biomedical Science Authors: Small, S. A., Petsko, G. A. Tags: Focus Source Type: research
[Research Articles] Obesity induces gut microbiota alterations and augments acute graft-versus-host disease after allogeneic stem cell transplantation
The efficacy of allogeneic hematopoietic stem cell transplantation (allo-HSCT) is limited by acute and chronic graft-versus-host disease (GVHD). The impact of obesity on allo-HSCT outcomes is poorly understood. Here, we report that obesity had a negative and selective impact on acute gut GVHD after allo-HSCT in mice with diet-induced obesity (DIO). These animals exhibited increased gut permeability, endotoxin translocation across the gut, and radiation-induced gastrointestinal damage after allo-HSCT. After allo-HSCT, both male and female DIO mouse recipients showed increased proinflammatory cytokine production and expressi...
Source: Science Translational Medicine - November 25, 2020 Category: Biomedical Science Authors: Khuat, L. T., Le, C. T., Pai, C.-C. S., Shields-Cutler, R. R., Holtan, S. G., Rashidi, A., Parker, S. L., Knights, D., Luna, J. I., Dunai, C., Wang, Z., Sturgill, I. R., Stoffel, K. M., Merleev, A. A., More, S. K., Maverakis, E., Raybould, H. E., Chen, M. Tags: Research Articles Source Type: research
[Editors' Choice] Modeling the impact of genetic heterogeneity on immunotherapy
A panel of genetically engineered mouse models recapitulates genotype-driven responses to immunotherapy and uncovers a driver of immunotherapy resistance in ovarian cancer. (Source: Science Translational Medicine)
Source: Science Translational Medicine - November 25, 2020 Category: Biomedical Science Authors: Zervantonakis, I. Tags: Editors ' Choice Source Type: research
