bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pathways from performance monitoring to negative symptoms and functional outcomes in psychotic disorders
Authors: Foti Dan , Perlman Greg , Bromet Evelyn J. , Harvey Philip D. , Hajcak Greg , Mathalon Daniel H. , Kotov Roman 
Published: April 2020

AbstractBackgroundPerformance monitoring entails rapid error detection to maintain task performance. Impaired performance monitoring is a candidate pathophysiological process in psychotic disorders, which may explain the broader deficit in executive function and its known associations with negative symptoms and poor functioning. The current study models cross-sectional pathways bridging neurophysiological measures of performance monitoring with executive function, symptoms, and functioning.MethodsData were from the 20-year assessment of the Suffolk County Mental Health Project. Individuals with psychotic disorders (N= 181) were originally recruited from inpatient psychiatric facilities. Data were also collected from a geographically and demographically matched group with no psychosis history (N= 242). Neural measures were the error-related negativity (ERN) and error positivity (Pe). Structural equation modeling tested mediation pathways.ResultsBlunted ERN and Pe in the clinical cohort related to impaired executive function (r= 0.26–0.35), negative symptom severity (r= 0.17–0.25), and poor real-world functioning (r= 0.17–0.19). Associations with executive function were consistent across groups. Multiple potential pathways were identified in the clinical cohort: reduced ERN to inexpressivity was mediated by executive function (β= 0.10); reduced Pe to global functioning was mediated by executive function and avolition (β= 0.10).ConclusionsThis supports a transdiagnostic model of psychotic disorders by which poor performance monitoring contributes to impaired executive function, which contributes to negative symptoms and poor real-world functioning. If supported by future longitudinal research, these pathways could inform the development of targeted interventions to address cognitive and functional deficits that are central to psychotic disorders.
Vínculo Entre La Evaluación De Tecnologías Sanitarias y La Toma De Decisión Para La Asignación De Recursos Sanitarios en Latino-América
Authors: Pichon-Riviere Andrés , Augustovski Federico , García Martí Sebastián , Alfie Verónica , Sampietro-Colom Laura 
Published: April 2020

ResumenObjetivosUn vínculo claro entre la evaluación y la toma de decisión constituye un principio de buena práctica en evaluación de tecnologías sanitarias (ETESA) reconocido a nivel internacional. El objetivo del Foro de Políticas en Latino-América (LatamPF) 2019 de Health Technology Assessment International fue explorar los diferentes modelos que vinculan la ETESA y la toma de decisión y discutir su potencial aplicabilidad en Latino-América.MétodosEste manuscrito está basado en un documento base y en el trabajo deliberativo realizado por los miembros (54 participantes, 12 países) que asistieron al LatamPF, a través de la metodología design thinking.ResultadosLos participantes coincidieron en que la relación inapropiada entre la ETESA y la toma de decisión atenta hoy contra la legitimidad de las decisiones, expone al proceso de ETESA a una excesiva influencia política y judicial, y condiciona que algunos actores se sientan relegados del proceso de evaluación y toma de decisión. Se identificaron los atributos del proceso de ETESA más prioritarios y factibles de ser mejorados en la región, y con el mayor potencial para generar un cambio positivo en los sistemas de salud. La mayor parte de estos están vinculados con la apropiada institucionalización de la ETESA, ampliar la participación de los diferentes actores y mejorar la transparencia de los procesos de ETESA.ConclusionesEl LatamPF ha identificado barreras y recomendado acciones para reforzar el vínculo entre ETESA y la decisión. A su vez, existe en estos momentos una ventana de oportunidad en la región, ya que el tema es visualizado como una prioridad por gran parte de los actores de la sociedad. Por ello, los diferentes actores de los sistemas sanitarios deberían ahora tomar esta oportunidad para avanzar en el fortalecimiento del vínculo entre ETESA y toma de decisión.
BLOOD, FLOWERS, AND POWER: A NEW INTERPRETATION OF PLATE 44 OF THE CODEX BORGIA, A MEXICAN PRE-HISPANIC MANUSCRIPT
Authors: Olivier Guilhem 
Published: April 2020

AbstractIn this paper, I propose a new interpretation of Plate 44 of the Codex Borgia in the context of his central part, the most difficult to understand. The challenge is to demonstrate that Nowotny's (2005 [1961]) reading of this plate as a representation of a ritual of access to power can be combined with Boone's (2007) interpretation of the plate as a representation of a myth of the origin of flowers. In Mesoamerica, the nose-piercing ritual is part of a rite of passage in which the candidate appeared symbolically as a sacrificial victim, dying before his rebirth as a king. The myth of the origin of flowers is also a myth of the origin of menstruation and access to womanhood, thereby constituting a feminine equivalent of the nose-piercing rite of passage. Therefore, plate 44 of the Codex Borgia would illustrate the parallelism between women's fertility and men's access to power. This proposal will contribute to elucidate Frazer's (1981–1984 [1913–1924]) study, who, years ago, was wondering about the coincidence of menstruation taboos related to menarche and taboos that affected sacred kings in many parts of the world.
Hydropower Production Benefits More From 1.5 °C than 2 °C Climate Scenario
Authors: Meng Ying , Liu Junguo , Leduc Sylvain , Mesfun Sennai , Kraxner Florian , Mao Ganquan , Qi Wei , Wang Zifeng 
Published: April 2020

AbstractHydropower plays an important role as renewable and clean energy in the world's overall energy supply. Electricity generation from hydropower represented approximately 16.6% of the world's total electricity and 70% of all renewable electricity in 2015. Determining the different effects of 1.5 and 2 °C of global warming has become a hot spot in water resources research. However, there are still few studies on the impacts of different global warming levels on gross hydropower potential. This study used a coupled hydrological and techno‐economic model framework to assess hydropower production under global warming levels of 1.5 and 2 °C, while also considering gross hydropower potential, power consumption, and economic factors. The results show that both global warming levels will have a positive impact on the hydropower production of a tropical island (Sumatra) relative to the historical period; however, the ratio of hydropower production versus power demand provided by 1.5 °C of global warming is 40% higher than that provided by 2 °C of global warming under RCP6.0. The power generation by hydropower plants shows incongruous changing trends with hydropower potential under the same global warming levels. This inconformity occurs because the optimal sites for hydropower plants were chosen by considering not only hydropower potential but also economic factors. In addition, the reduction in CO2 emissions under global warming of 1.5 °C (39.06 × 106 t) is greater than that under global warming of 2 °C (10.20 × 106 t), which reveals that global warming decreases the benefits necessary to relieve global warming levels. However, the hydropower generation and the reduction in CO2 emissions will be far less than the energy demand when protected areas are excluded as potential sites for hydropower plants, with a sharp decrease of 40–80%. Thus, government policy‐makers should consider the trade‐off between hydropower generation and forest coverage area in nationally determined contributions.
Improving Hydrological Models With the Assimilation of Crowdsourced Data
Authors: Avellaneda P. M. , Ficklin D. L. , Lowry C. S. , Knouft J. H. , Hall D. M. 
Published: April 2020

AbstractSmall streams often lack reliable hydrological data. Environmental agencies play a key role in providing such data; however, these agencies are often challenged by the growing monitoring needs and lack of funding. Given the spatial mismatch between observed data and small watersheds/headwaters, local volunteers can act as potentially valuable research partners. We examine how CrowdHydrology, a citizen science program that collects stream stage and stream temperature observations, improves a hydrologic model of the Boyne River, Michigan, USA. Volunteers provided observations at four calibration sites with different interarrival times of the observations. We tested whether stream stage and stream temperature observations (measured by volunteers) improved the performance of a Soil and Water Assessment Tool (SWAT) model of the Boyne River. Observations were integrated into the model using the ensemble Kalman filter. This framework allowed us to integrate observation error, track the variability of model parameters, and simulate daily streamflow and stream temperature across the watershed. Measures of daily model performance included the Nash‐Sutcliffe efficiency, modified Nash‐Sutcliffe efficiency (Ef‐mod), refined index of agreement (dr), and relative bias (Bias). For all calibration sites, estimates of streamflow improved after data assimilation compared to simulations based on initial/default SWAT parameters. Different measures of model performance emerged based on the interarrival times of the observations. Results demonstrate that observations collected by local volunteers, with a certain temporal resolution, can improve SWAT hydrological models and capture central tendency.
New virus isolates from Italian hydrothermal environments underscore the biogeographic pattern in archaeal virus communities
Authors: Baquero Diana P , Contursi Patrizia , Piochi Monica , Bartolucci Simonetta , Liu Ying , Cvirkaite-Krupovic Virginija , Prangishvili David , Krupovic Mart 
Published: April 2020

Abstract
Viruses of hyperthermophilic archaea represent one of the least understood parts of the virosphere, showing little genomic and morphological similarity to viruses of bacteria or eukaryotes. Here, we investigated virus diversity in the active sulfurous fields of the Campi Flegrei volcano in Pozzuoli, Italy. Virus-like particles displaying eight different morphotypes, including lemon-shaped, droplet-shaped and bottle-shaped virions, were observed and five new archaeal viruses proposed to belong to families Rudiviridae, Globuloviridae and Tristromaviridae were isolated and characterized. Two of these viruses infect neutrophilic hyperthermophiles of the genus Pyrobaculum, whereas the remaining three have rod-shaped virions typical of the family Rudiviridae and infect acidophilic hyperthermophiles belonging to three different genera of the order Sulfolobales, namely, Saccharolobus, Acidianus, and Metallosphaera. Notably, Metallosphaera rod-shaped virus 1 is the first rudivirus isolated on Metallosphaera species. Phylogenomic analysis of the newly isolated and previously sequenced rudiviruses revealed a clear biogeographic pattern, with all Italian rudiviruses forming a monophyletic clade, suggesting geographical structuring of virus communities in extreme geothermal environments. Analysis of the CRISPR spacers suggests that isolated rudiviruses have experienced recent host switching across the genus boundary, potentially to escape the targeting by CRISPR-Cas immunity systems. Finally, we propose a revised classification of the Rudiviridae family, with the establishment of six new genera. Collectively, our results further show that high-temperature continental hydrothermal systems harbor a highly diverse virome and shed light on the evolution of archaeal viruses.
A novel PKC activating molecule promotes neuroblast differentiation and delivery of newborn neurons in brain injuries
Authors: Domínguez-García Samuel , Geribaldi-Doldán Noelia , Gómez-Oliva Ricardo , Ruiz Felix A. , Carrascal Livia , Bolívar Jorge , Verástegui Cristina , Garcia-Alloza Monica , Macías-Sánchez Antonio J. , Hernández-Galán Rosario , Nunez-Abades Pedro , Castro Carmen 
Published: April 2020

AbstractNeural stem cells are activated within neurogenic niches in response to brain injuries. This results in the production of neuroblasts, which unsuccessfully attempt to migrate toward the damaged tissue. Injuries constitute a gliogenic/non-neurogenic niche generated by the presence of anti-neurogenic signals, which impair neuronal differentiation and migration. Kinases of the protein kinase C (PKC) family mediate the release of growth factors that participate in different steps of the neurogenic process, particularly, novel PKC isozymes facilitate the release of the neurogenic growth factor neuregulin. We have demonstrated herein that a plant derived diterpene, (EOF2; CAS number 2230806-06-9), with the capacity to activate PKC facilitates the release of neuregulin 1, and promotes neuroblasts differentiation and survival in cultures of subventricular zone (SVZ) isolated cells in a novel PKC dependent manner. Local infusion of this compound in mechanical cortical injuries induces neuroblast enrichment within the perilesional area, and noninvasive intranasal administration of EOF2 promotes migration of neuroblasts from the SVZ towards the injury, allowing their survival and differentiation into mature neurons, being some of them cholinergic and GABAergic. Our results elucidate the mechanism of EOF2 promoting neurogenesis in injuries and highlight the role of novel PKC isozymes as targets in brain injury regeneration.
How does mTOR sense glucose starvation? AMPK is the usual suspect
Authors: Leprivier Gabriel , Rotblat Barak 
Published: April 2020

AbstractGlucose is a major requirement for biological life. Its concentration is constantly sensed at the cellular level, allowing for adequate responses to any changes of glucose availability. Such responses are mediated by key sensors and signaling pathway components that adapt cellular metabolism to glucose levels. One of the major hubs of these responses is mechanistic target of rapamycin (mTOR) kinase, which forms the mTORC1 and mTORC2 protein complexes. Under physiological glucose concentrations, mTORC1 is activated and stimulates a number of proteins and enzymes involved in anabolic processes, while restricting the autophagic process. Conversely, when glucose levels are low, mTORC1 is inhibited, in turn leading to the repression of numerous anabolic processes, sparing ATP and antioxidants. Understanding how mTORC1 activity is regulated by glucose is not only important to better delineate the biological function of mTOR, but also to highlight potential therapeutic strategies for treating diseases characterized by deregulated glucose availability, as is the case of cancer. In this perspective, we depict the different sensors and upstream proteins responsible of controlling mTORC1 activity in response to changes in glucose concentration. This includes the major energy sensor AMP-activated protein kinase (AMPK), as well as other independent players. The impact of such modes of regulation of mTORC1 on cellular processes is also discussed.
AAV-mediated cardiac gene transfer of wild-type desmin in mouse models for recessive desminopathies
Authors: Ruppert T. , Heckmann M. B. , Rapti K. , Schultheis D. , Jungmann A. , Katus H. A. , Winter L. , Frey N. , Clemen C. S. , Schröder R. , Müller O. J. 
Published: April 2020

AbstractMutations in the human desmin gene cause autosomal-dominant and recessive cardiomyopathies and myopathies with marked phenotypic variability. Here, we investigated the effects of adeno-associated virus (AAV)-mediated cardiac wild-type desmin expression in homozygous desmin knockout (DKO) and homozygous R349P desmin knockin (DKI) mice. These mice serve as disease models for two subforms of autosomal-recessive desminopathies, the former for the one with a complete lack of desmin protein and the latter for the one with solely mutant desmin protein expression in conjunction with protein aggregation pathology in striated muscle. Two-month-old mice were injected with either a single dose of 5 × 1012 AAV9-hTNT2-mDes (AAV-Des) vector genomes or NaCl as control. One week after injection, mice were subjected to a forced swimming exercise protocol for 4 weeks. Cardiac function was monitored over a period of 15 month after injection and before the mice were sacrificed for biochemical and morphological analysis. AAV-mediated cardiac expression of wild-type desmin in both the homozygous DKO and DKI backgrounds reached levels seen in wild-type mice. Notably, AAV-Des treated DKO mice showed a regular subcellular distribution of desmin as well as a normalization of functional and morphological cardiac parameters. Treated DKI mice, however, showed an aberrant subcellular localization of desmin, unchanged functional cardiac parameters, and a trend toward an increased cardiac fibrosis. In conclusion, the effect of a high-dose AAV9-based desmin gene therapy is highly beneficial for the heart in DKO animals, but not in DKI mice.
Proteasome inhibitor-induced modulation reveals the spliceosome as a specific therapeutic vulnerability in multiple myeloma
Authors: Huang Hector H. , Ferguson Ian D. , Thornton Alexis M. , Bastola Prabhakar , Lam Christine , Lin Yu-Hsiu T. , Choudhry Priya , Mariano Margarette C. , Marcoulis Makeba D. , Teo Chin Fen , Malato Julia , Phojanakong Paul J. , Martin Thomas G. , Wolf Jeffrey L. , Wong Sandy W. , Shah Nina , Hann Byron , Brooks Angela N. , Wiita Arun P. 
Published: April 2020

AbstractEnhancing the efficacy of proteasome inhibitors (PI) is a central goal in myeloma therapy. We proposed that signaling-level responses after PI may reveal new mechanisms of action that can be therapeutically exploited. Unbiased phosphoproteomics after treatment with the PI carfilzomib surprisingly demonstrates the most prominent phosphorylation changes on splicing related proteins. Spliceosome modulation is invisible to RNA or protein abundance alone. Transcriptome analysis after PI demonstrates broad-scale intron retention, suggestive of spliceosome interference, as well as specific alternative splicing of protein homeostasis machinery components. These findings lead us to evaluate direct spliceosome inhibition in myeloma, which synergizes with carfilzomib and shows potent anti-tumor activity. Functional genomics and exome sequencing further support the spliceosome as a specific vulnerability in myeloma. Our results propose splicing interference as an unrecognized modality of PI mechanism, reveal additional modes of spliceosome modulation, and suggest spliceosome targeting as a promising therapeutic strategy in myeloma.
Development of a thermophilic coculture for corn fiber conversion to ethanol
Authors: Beri Dhananjay , York William S. , Lynd Lee R. , Peña Maria J. , Herring Christopher D. 
Published: April 2020

AbstractThe fiber in corn kernels, currently unutilized in the corn to ethanol process, represents an opportunity for introduction of cellulose conversion technology. We report here that Clostridium thermocellum can solubilize over 90% of the carbohydrate in autoclaved corn fiber, including its hemicellulose component glucuronoarabinoxylan (GAX). However, Thermoanaerobacterium thermosaccharolyticum or several other described hemicellulose-fermenting thermophilic bacteria can only partially utilize this GAX. We describe the isolation of a previously undescribed organism, Herbinix spp. strain LL1355, from a thermophilic microbiome that can consume 85% of the recalcitrant GAX. We sequence its genome, and based on structural analysis of the GAX, identify six enzymes that hydrolyze GAX linkages. Combinations of up to four enzymes are successfully expressed in T. thermosaccharolyticum. Supplementation with these enzymes allows T. thermosaccharolyticum to consume 78% of the GAX compared to 53% by the parent strain and increases ethanol yield from corn fiber by 24%.
A BET family protein degrader provokes senolysis by targeting NHEJ and autophagy in senescent cells
Authors: Wakita Masahiro , Takahashi Akiko , Sano Osamu , Loo Tze Mun , Imai Yoshinori , Narukawa Megumi , Iwata Hidehisa , Matsudaira Tatsuyuki , Kawamoto Shimpei , Ohtani Naoko , Yoshimori Tamotsu , Hara Eiji 
Published: April 2020

AbstractAlthough cellular senescence acts primarily as a tumour suppression mechanism, the accumulation of senescent cells in vivo eventually exerts deleterious side effects through inflammatory/tumour-promoting factor secretion. Thus, the development of new drugs that cause the specific elimination of senescent cells, termed senolysis, is anticipated. Here, by an unbiased high-throughput screening of chemical compounds and a bio-functional analysis, we identify BET family protein degrader (BETd) as a promising senolytic drug. BETd provokes senolysis through two independent but integrated pathways; the attenuation of non-homologous end joining (NHEJ), and the up-regulation of autophagic gene expression. BETd treatment eliminates senescent hepatic stellate cells in obese mouse livers, accompanied by the reduction of liver cancer development. Furthermore, the elimination of chemotherapy-induced senescent cells by BETd increases the efficacy of chemotherapy against xenograft tumours in immunocompromised mice. These results reveal the vulnerability of senescent cells and open up possibilities for its control.
Deep learning enables structured illumination microscopy with low light levels and enhanced speed
Authors: Jin Luhong , Liu Bei , Zhao Fenqiang , Hahn Stephen , Dong Bowei , Song Ruiyan , Elston Timothy C. , Xu Yingke , Hahn Klaus M. 
Published: April 2020

AbstractStructured illumination microscopy (SIM) surpasses the optical diffraction limit and offers a two-fold enhancement in resolution over diffraction limited microscopy. However, it requires both intense illumination and multiple acquisitions to produce a single high-resolution image. Using deep learning to augment SIM, we obtain a five-fold reduction in the number of raw images required for super-resolution SIM, and generate images under extreme low light conditions (at least 100× fewer photons). We validate the performance of deep neural networks on different cellular structures and achieve multi-color, live-cell super-resolution imaging with greatly reduced photobleaching.
CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes
Authors: Shimokawa Chikako , Kato Tamotsu , Takeuchi Tadashi , Ohshima Noriyasu , Furuki Takao , Ohtsu Yoshiaki , Suzue Kazutomo , Imai Takashi , Obi Seiji , Olia Alex , Izumi Takashi , Sakurai Minoru , Arakawa Hirokazu , Ohno Hiroshi , Hisaeda Hajime 
Published: April 2020

AbstractType 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic β-cells are destroyed. Intestinal helminths can cause asymptomatic chronic and immunosuppressive infections and suppress disease in rodent models of T1D. However, the underlying regulatory mechanisms for this protection are unclear. Here, we report that CD8+regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes affects the intestinal microbiota and increases the abundance ofRuminococcusspp., resulting in the induction of CD8+Treg cells. Furthermore, trehalose has therapeutic effects on both streptozotocin-induced diabetes and in the NOD mouse model of T1D. In addition, compared with healthy volunteers, patients with T1D have fewer CD8+Treg cells, and the abundance of intestinalRuminococcuspositively correlates with the number of CD8+Treg cells in humans.