bluuebunny/crossref_metadata_2025_split huggingface dataset:
The COVID-19 Incarceration Model: a tool for corrections staff to analyze outbreaks of COVID-19
Authors: Kwon Jisoo A. , Bretaña Neil A. , Grant Luke , Galouzis Jennifer , Hoey Wendy , Blogg James , Lloyd Andrew R. , Gray Richard T. 
Published: February 2021

AbstractCorrectional facilities are at high risk of COVID-19 outbreaks due to the inevitable close contacts in the environment. Such facilities are a high priority in the public health response to the epidemic. We developed a user-friendly Excel spreadsheet model (building on the previously developed Recidiviz model) to analyze COVID-19 outbreaks in correctional facilities and the potential impact of prevention strategies - the COVID-19 Incarceration Model. The model requires limited inputs and can be used by non-modelers. The impact of a COVID-19 outbreak and mitigation strategies is illustrated for an example prison setting.
NAMPT-derived NAD+fuels PARP1 to promote skin inflammation through parthanatos
Authors: Martínez-Morcillo Francisco J. , Cantón-Sandoval Joaquín , Martínez-Navarro Francisco J. , Cabas Isabel , Martínez-Vicente Idoya , Armistead Joy , Hatzold Julia , López-Muñoz Azucena , Martínez-Menchón Teresa , Corbalán-Vélez Raúl , Lacal Jesús , Hammerschmidt Matthias , García-Borrón José C. , García-Ayala Alfonsa , Cayuela María L. , Pérez-Oliva Ana B. , García-Moreno Diana , Mulero Victoriano 
Published: February 2021

SummarySeveral studies have revealed a correlation between chronic inflammation and NAD+metabolism but the precise mechanism involved is unknown. Here we report that the genetic and pharmacological inhibition of nicotinamide phosphoribosyltransferase (Nampt), the rate-limiting enzyme in the salvage pathway of NAD+biosynthesis, reduced oxidative stress, inflammation, and keratinocyte DNA damage, hyperproliferation and cell death in zebrafish models of chronic skin inflammation, while all these effects were reversed by NAD+supplementation. Similarly, genetic and pharmacological inhibition of poly ADP-ribose (PAR) polymerase 1 (Parp1), overexpression of PAR glycohydrolase, inhibition of apoptosis-inducing factor 1, inhibition of NADPH oxidases and reactive oxygen species (ROS) scavenging, all phenocopied the effects of Nampt inhibition. Pharmacological inhibition of NADPH oxidases/NAMPT/PARP/AIFM1 axis decreased expression of pathology-associated genes in human organotypic 3D skin models of psoriasis. Consistently, an aberrant induction of both NAMPT amounts and PARP activity was observed in lesional skin from psoriasis patients. In conclusion, hyperactivation of PARP1 in response to ROS-induced DNA damage, fueled by NAMPT-derived NAD+, mediates skin inflammation through parthanatos cell death.HighlightsNAMPT inhibition alleviates inflammation in zebrafish and human epidermis organoid models of psoriasis.NADPH oxidase-derived ROS mediates keratinocyte DNA damage and Parp1 overactivation.Inhibition of parthanatos cell death phenocopies the effects of NAMPT inhibition in zebrafish and human psoriasis models.NAMPT and PAR metabolism is altered in psoriasis patients.
WIN 55,212-2 shows anti-inflammatory and survival properties in human iPSC-derived cardiomyocytes infected with SARS-CoV-2
Authors: Aragão Luiz Guilherme H. S. , Oliveira Júlia T. , Temerozo Jairo R. , Mendes Mayara A. , Salerno José Alexandre , Pedrosa Carolina da S. G. , Puig-Pijuan Teresa , Veríssimo Carla P. , Ornelas Isis M. , Torquato Thayana , Vitória Gabriela , Sacramento Carolina Q. , Fintelman-Rodrigues Natalia , Dias Suelen da Silva Gomes , Soares Vinicius Cardoso , Souza Leticia R. Q. , Karmirian Karina , Goto-Silva Livia , Biagi Diogo , Cruvinel Estela M. , Dariolli Rafael , Furtado Daniel R. , Bozza Patrícia T. , Borges Helena L. , Souza Thiago Moreno L. , Guimarães Marília Zaluar P. , Rehen Stevens 
Published: February 2021

AbstractCoronavirus disease 2019 (COVID-19) is caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which can infect several organs, especially impacting respiratory capacity. Among the extrapulmonary manifestations of COVID-19 is myocardial injury, which is associated with a high risk of mortality. Myocardial injury, caused directly or indirectly by SARS-CoV-2 infection, can be triggered by inflammatory processes that cause damage to the heart tissue. Since one of the hallmarks of severe COVID-19 is the “cytokine storm”, strategies to control inflammation caused by SARS-CoV-2 infection have been considered. Cannabinoids are known to have anti-inflammatory properties by negatively modulating the release of pro-inflammatory cytokines. Herein, we investigated the effects of the cannabinoid agonist WIN 55,212-2 (WIN) in human iPSC-derived cardiomyocytes (hiPSC-CMs) infected with SARS-CoV-2. WIN did not modify angiotensin-converting enzyme II protein levels, nor reduced viral infection and replication in hiPSC-CMs. On the other hand, WIN reduced the levels of interleukins 6, 8, 18 and tumor necrosis factor-alpha (TNF-α) released by infected cells, and attenuated cytotoxic damage measured by the release of lactate dehydrogenase (LDH). Our findings suggest that cannabinoids should be further explored as a complementary therapeutic tool for reducing inflammation in COVID-19 patients.
A novel glucocorticoid and androgen receptor modulator reduces viral entry and innate immune inflammatory responses in the Syrian Hamster model of SARS-CoV-2
Authors: Rocha Savannah M. , Fagre Anna C. , Latham Amanda S. , Popichak Katriana A. , McDermott Casey P. , Dawson Clinton C. , Cummings Jason E. , Lewis Juliette , Reigan Philip , Aboellail Tawfik A. , Kading Rebekah C. , Schountz Tony , Theise Neil D. , Slayden Richard A. , Tjalkens Ronald B. 
Published: February 2021

AbstractSince its initial discovery in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the cause of COVID19, has spread worldwide and despite significant research efforts, treatment options remain limited. Replication of SARS-CoV-2 in lung is associated with marked infiltration of macrophages and activation of innate immune inflammatory responses triggered, in part, by heightened production of interleukin-6 (IL-6) that recruits lymphocytes to the site of infection that amplify tissue injury. Antagonists of the glucocorticoid and androgen receptors have shown promise in experimental models of COVID19 and in clinical studies, because cell surface proteins required for viral entry, angiotensin converting enzyme 2 (ACE2) and the transmembrane serine protease 2 (TMPRSS2), are transcriptionally regulated by these receptors. We therefore postulated that the glucocorticoid (GR) and androgen receptor (AR) antagonist, PT150, would reduce infectivity of SARS-CoV-2 and prevent inflammatory lung injury in the Syrian golden hamster model of COVID19. Animals were infected intranasally with 2.5 × 104TCID50/ml equivalents of SARS-CoV-2 (strain 2019-nCoV/USA-WA1/ 2020) and PT150 was administered by oral gavage at 30 and 100 mg/Kg/day for a total of 7 days. Animals were then examined at days 3, 5 and 7 post-infection (DPI) for lung histopathology, viral load and production of proteins regulating the initiation and progression of SARS-CoV-2 infection. Results of these studies indicated that oral administration of PT150 decreased replication of SARS-CoV-2 in lung, as well as expression of ACE2 and TMPRSS2 protein. Hypercellularity and inflammatory cell infiltration driven by macrophage responses were dramatically decreased in PT150-treated animals, as was tissue damage and expression of IL-6. Molecular modeling suggested that PT150 binds to the co-activator interface of the ligand binding domain of both AR and GR and thereby acts as an allosteric modulator and transcriptional repressor of these receptors. Phylogenetic analysis of AR and GR across multiple species permissive to SARS-CoV-2 infection revealed a high degree of sequence identity maintained across species, including human, suggesting that the mechanism of action and therapeutic efficacy observed in Syrian hamsters would likely be predictive of positive outcomes in patients. PT150 is therefore a strong candidate for further clinical development for the treatment of COVID19 across variants of SARS-CoV-2.
Assembly of chromosome-scale and allele-aware autotetraploid genome of the Chinese alfalfa cultivar Zhongmu-4 and identification of SNP loci associated with 27 agronomic traits
Authors: Long Ruicai , Zhang Fan , Zhang Zhiwu , Li Mingna , Chen Lin , Wang Xue , Liu Wenwen , Zhang Tiejun , Yu Long-Xi , He Fei , Jiang Xueqian , Yang Xijiang , Yang Changfu , Wang Zhen , Kang Junmei , Yang Qingchuan 
Published: February 2021

AbstractAlfalfa (Medicago sativaL.), the most valuable perennial legume crop, referred to as “Queen of the Forages” for its high nutritional value and yield production among forage crops. Comprehensive genomic information of germplasm resources from different ecological regions and modern breeding strategies, such as molecular-marker assisted breeding are of great importance to breed new alfalfa varieties with environmental resilience. Here, we report assembly of the genome sequence of Zhongmu-4 (ZM-4), one of the most planted cultivars in China, and identification of SNPs associated with alfalfa agronomic traits by Genome-wide Association Studies (GWAS). Sequence of 32 allelic chromosomes was assembled successfully by single molecule real time sequencing and Hi-C technique with ALLHiC algorithm. About 2.74 Gbp contigs, accounting for 88.39% of the estimated genome, were assembled with 2.56 Gbp contigs anchored to 32 pseudo-chromosomes. In comparison withM. truncatulaA17, distinctive inversion and translocation on chromosome 1, and between chromosome 4 and 8, respectively, were detected. Moreover, we conducted resequencing of 220 alfalfa accessions collected globally and performed GWAS analysis based on our assembled genome. Population structure analysis demonstrated that alfalfa has a complex genetic relationship among germplasm with different geographic origins. GWAS identified 101 SNPs associated with 27 out of 93 agronomic traits. The updated chromosome-scale and allele-aware genome sequence, coupled with the resequencing data of most global alfalfa germplasm, provides valuable information for alfalfa genetic research, and further analysis of major SNP loci will accelerate unravelling the molecular basis of important agronomic traits and facilitate genetic improvement of alfalfa.
Synchrony of mind and body are distinct in mother-child dyads
Authors: Reindl Vanessa , Wass Sam , Leong Victoria , Scharke Wolfgang , Wistuba Sandra , Wirth Christina Lisa , Konrad Kerstin , Gerloff Christian 
Published: February 2021

AbstractHyperscanning studies have begun to unravel the brain mechanisms underlying social interaction, indicating a functional role for interpersonal neural synchronization (INS), yet the mechanisms that drive INS are poorly understood. While interpersonal synchrony is considered a multimodal phenomenon, it is not clear how different biological and behavioral synchrony markers are related to each other. The current study, thus, addresses whether INS is functionally-distinct from synchrony in other systems – specifically the autonomic nervous system (ANS) and motor behavior. To test this, we used a novel methodological approach, based on concurrent functional near-infrared spectroscopy-electrocardiography, recorded whileN= 34 mother-child and stranger-child dyads (child mean age 14 years) engaged in cooperative and competitive tasks. Results showed a marked differentiation between neural, ANS and behavioral synchrony. Importantly, only in the neural domain was higher synchrony for mother-child compared to stranger-child dyads observed. Further, ANS and neural synchrony were positively related during competition but not during cooperation. These results suggest that synchrony in different behavioral and biological systems may reflect distinct processes. Mother-child INS may arise due to neural processes related to social affiliation, which go beyond shared arousal and similarities in behavior.
Insulin-dependent maturation of newly generated olfactory sensory neurons after injury
Authors: Kuboki Akihito , Kikuta Shu , Otori Nobuyoshi , Kojima Hiromi , Matsumoto Ichiro , Reisert Johannes , Yamasoba Tatsuya 
Published: February 2021

AbstractLoss of olfactory sensory neurons (OSNs) after injury to the olfactory epithelium (OE) triggers the generation of OSNs that are incorporated into olfactory circuits to restore olfactory sensory perception. This study addresses how insulin receptor-mediated signaling affects the functional recovery of OSNs after OE injury. Insulin levels were reduced in mice by ablating the pancreatic beta cells via streptozotocin injections. These streptozotocin-induced diabetic and control mice were then intraperitoneally injected with the olfactotoxic drug methimazole to selectively ablate OSNs. The OE of diabetic and control mice regenerated similarly until day 14 after injury. Thereafter, the OE of diabetic mice contained fewer mature and more apoptotic OSNs than control mice. Functionally, diabetic mice showed reduced electro-olfactogram responses and their olfactory bulbs had fewer c-Fos-active cells following odor stimulation, as well as performed worse in an odor-guided task compared to control mice. Insulin administered intranasally during day 8 to 13 after injury was sufficient to rescue recovery of OSNs in diabetic mice compared to control levels, while insulin administration between days 1 – 6 did not. During this critical time window on day 8 – 13 after injury, insulin receptors are highly expressed and intranasal application of insulin receptor antagonist inhibits regeneration. Furthermore, an insulin-enriched environment could facilitate regeneration even in non-diabetic mice. These results indicate that insulin facilitates the regeneration of OSNs after injury and suggest a critical stage during recovery (8 – 13 days after injury) during which the maturation of newly generated OSNs is highly dependent on and promoted by insulin.Significance StatementAlthough insulin receptor signaling is known to influence on cellular processes such as proliferation and apoptosis, it is poorly understood whether the insulin influences the regeneration of olfactory sensory neurons (OSNs) after injury. We compared the maturation processes of new OSNs after the methimazole-induced loss of pre-existing OSNs between diabetic and control mice. The results show that the regeneration of new OSNs depend on sufficient insulin levels during a specific temporal window, when insulin receptor expression is highly upregulated. Furthermore, an insulin-enriched environment via nasal insulin application during the critical period facilitates OSNs regeneration even in non-diabetic mice. The present results have implications for intranasal application of insulin as potential clinical therapeutics to facilitate OSNs regeneration after the injury.
DpaA detaches Braun’s lipoprotein from peptidoglycan
Authors: Winkle Matthias , Hernández-Rocamora Víctor M. , Pullela Karthik , Goodall Emily C. A. , Martorana Alessandra M. , Gray Joe , Henderson Ian R. , Polissi Alessandra , Vollmer Waldemar 
Published: February 2021

ABSTRACTGram-negative bacteria have a unique cell envelope with a lipopolysaccharide-containing outer membrane that is tightly connected to a thin layer of peptidoglycan. The tight connection between the outer membrane and peptidoglycan is needed to maintain the outer membrane as an impermeable barrier for many toxic molecules and antibiotics. Enterobacteriaceae such asEscherichia colicovalently attach the abundant outer membrane-anchored lipoprotein Lpp (Braun’s lipoprotein) to tripeptides in peptidoglycan, mediated by the transpeptidases LdtA, LdtB and LdtC. LdtD and LdtE are members of the same family of LD-transpeptidases but they catalyse a different reaction, the formation of 3-3 cross-links in the peptidoglycan. The function of the sixth homologue inE. coli, LdtF remains unclear, although it has been shown to become essential in cells with inhibited LPS export to the outer membrane. We now show that LdtF hydrolyses the Lpp-peptidoglycan linkage, detaching Lpp from peptidoglycan, and have renamed LdtF to peptidoglycanmeso-diaminopimelicacid proteinamidase A (DpaA). We show that the detachment of Lpp from peptidoglycan is beneficial for the cell under certain stress conditions and that the deletion ofdpaAallows frequent transposon inactivation in thelapB (yciM)gene, whose product down-regulates lipopolysaccharide biosynthesis. DpaA-like proteins have characteristic sequence motifs and are present in many Gram-negative bacteria of which some have no Lpp, raising the possibility that DpaA has other substrates in these species. Overall, our data show that the Lpp-peptidoglycan linkage inE. coliis more dynamic than previously appreciated.IMPORTANCEGram-negative bacteria have a complex cell envelope with two membranes and a periplasm containing the peptidoglycan layer. The outer membrane is firmly connected to the peptidoglycan by highly abundant proteins. The outer membrane-anchored Braun’s lipoprotein (Lpp) is the most abundant protein inE. coliand about one third of the Lpp molecules become covalently attached to tripeptides in peptidoglycan. The attachment of Lpp to peptidoglycan stabilizes the cell envelope and is crucial for the outer membrane to function as a permeability barrier for a range of toxic molecules and antibiotics. So far the attachment of Lpp to peptidoglycan has been considered to be irreversible. We have now identified an amidase, DpaA, which is capable of detaching Lpp from PG and we show that the detachment of Lpp is important under certain stress conditions. DpaA-like proteins are present in many Gram-negative bacteria and may have different substrates in these species.
Analysis Of Molecular Networks In The Cerebellum In Chronic Schizophrenia: Modulation By Early Postnatal Life Stressors In Murine Models
Authors: Vera-Montecinos América , Rodríguez-Mias Ricard , MacDowell Karina S. , García-Bueno Borja , Leza Juan C. , Villén Judit , Ramos Belén 
Published: February 2021

ABSTRACTDespite the growing importance of the cortico-cerebellar-thalamo-cortical circuit in schizophrenia, limited information is available regarding altered molecular networks in cerebellum. To identify altered protein networks, we conducted proteomic analysis of grey matter of postmortem cerebellar cortex in chronic schizophrenia subjects (n=12) and healthy individuals (n=14) followed by an extensive bioinformatic analysis. Two double-hit postnatal stress murine models for SZ were used to validate the most robust candidates. The models were maternal deprivation combined with an additional stressor: social isolation or chronic restraint stress. We found that the individual proteomic profile allowed the segregation of most schizophrenia cases from healthy individuals. We found 250 proteins with altered levels. This group was enriched in proteins related to mental disorders, mitochondrial disease, stress, and a number of biological functions including energy, immune response, axonal cytoskeletal organization and vesicle-mediated transport. Network analysis identified three modules: energy metabolism, neutrophil degranulation and a mixed module of mainly axonal-related functions. We analysed the most robust candidates in the networks in two double-hit stress murine models. METTL7A from the degranulation pathway was reduced in both models, while NDUFB9 from the energy network and CLASP1 from the axonal module decreased in only one model. This work provides evidence for altered energy, immune and axonal-related networks in the cerebellum in schizophrenia, suggesting that the accumulation of molecular errors, some by an early postnatal stress exposure, could lead to a failure in the normal cerebellar functions, impairing synaptic response and the defence mechanisms of this region against external harmful injuries in schizophrenia.
Structural insight into host plasma membrane association and assembly of HIV-1 Matrix protein
Authors: Ciftci Halilibrahim , Tateishi Hiroshi , Koiwai Kotaro , Koga Ryoko , Anraku Kensaku , Monde Kazuaki , Dağ Çağdaş , Destan Ebru , Yuksel Busra , Ayan Esra , Yildirim Gunseli , Yigin Merve , Ertem F. Betul , Shafiei Alaleh , Guven Omur , Besler Sabri O. , Sierra Raymond G. , Yoon Chun Hong , Su Zhen , Liang Mengling , Acar Burcin , Haliloglu Turkan , Otsuka Masami , Yumoto Fumiaki , Fujita Mikako , Senda Toshiya , DeMirci Hasan 
Published: February 2021

ABSTRACTHIV-1 continues to be a global health concern since AIDS was first recognized by the World Health Organization (WHO). It is estimated that there were 38 million people infected with HIV-1 and 1.5 million deaths in 2019 alone. A better understanding of the details of the HIV late-stage life cycle, involving Pr55Gagattachment to the membrane for the further oligomerization to release virion, will provide us new avenues for potential treatment. Inositol hexakisphosphate (IP6) is an abundant endogenous cyclitol molecule and its binding was linked to the oligomerization of Pr55Gagvia the MA domain. However, the binding site of IP6 on MA was unknown and the structural details of this interaction were missing. Here, we present three high-resolution crystal structures of the MA domain in complex with IP6 molecules to reveal its binding mode. Additionally, extensive Differential Scanning Fluorimetry analysis combined with cryo- and ambient-temperature X-ray crystallography and computational biology identify the key residues that participate in IP6 binding. Our data provide novel insights about the multilayered HIV-1 virion assembly process that involves the interplay of IP6 with PIP2, a phosphoinositide essential for the membrane binding of Pr55Gag. IP6 and PIP2 have neighboring alternate binding sites within the same highly basic region (residues 18-33). This indicates that IP6 and PIP2 bindings are not mutually exclusive and may play a key role in coordinating virion particles’ membrane localization. Based on our three different IP6-MA complex crystal structures, we propose a new model that involves the IP6 coordination of the oligomerization of outer MA and inner CA domain 2D layers during assembly and budding.
Behavioural synchronization in a multilevel society of feral horses
Authors: Maeda Tamao , Sueur Cédric , Hirata Satoshi , Yamamoto Shinya 
Published: February 2021

AbstractBehavioural synchrony among individuals is essential for group-living organisms. It is still largely unknown how synchronization functions in a multilevel society, which is a nested assemblage of multiple social levels between many individuals. Our aim was to build a model that explained the synchronization of activity in a multilevel society of feral horses. We used multi-agent based models based on four hypotheses: A) horses do not synchronize, B) horses synchronize with any individual in any unit, C) horses synchronize only within units and D) horses synchronize across and within units, but internal synchronization is stronger. Our empirical data obtained from drone observations best supported hypothesis D. This result suggests that animals in a multilevel society coordinate with other conspecifics not only within a unit but at an inter-unit level. In this case, inter-individual distances are much longer than those in most previous models which only considered local interaction within a few body lengths.