bluuebunny/crossref_metadata_2025 huggingface dataset:
The neural basis of ideological differences in race categorization
Authors: Krosch Amy R. , Jost John T. , Van Bavel Jay J.
Published: February 2021

Multiracial individuals are often categorized as members of their ‘socially subordinate’ racial group—a form of social discrimination termed hypodescent—with political conservatives more likely than liberals to show this bias. Although hypodescent has been linked to racial hierarchy preservation motives, it remains unclear
how
political ideology influences categorization: Do conservatives and liberals see, feel or think about mixed-race faces differently? Do they differ in sensitivity to Black prototypicality (i.e. skin tone darkness and Afrocentric features) or racial ambiguity (i.e. categorization difficulty) of Black/White mixed-race faces? To help answer these questions, we collected a politically diverse sample of White participants and had them categorize mixed-race faces as Black or White during functional neuroimaging. We found that conservatism was related to greater anterior insula activity to racially ambiguous faces, and this pattern of brain activation mediated conservatives' use of hypodescent. This demonstrates that conservatives' greater sensitivity to racial ambiguity (rather than Black prototypicality) gives rise to greater categorization of mixed-race individuals into the socially subordinate group and tentatively suggests that conservatives may differ from liberals in their affective reactions to mixed-race faces. Implications for the study of race categorization and political psychology are discussed.

This article is part of the theme issue ‘The political brain: neurocognitive and computational mechanisms'.
Proposal to reclassify four Lactobacillus species as Apilactobacillus bombintestini, Companilactobacillus suantsaicola, Lactiplantibacillus garii and Levilactobacillus suantsaiihabitans
Authors: Mattarelli Paola , Felis Giovanna , Franz Charles M. A. P. , Gänzle Michael G.
Published: February 2021

The taxonomy of the genus

Lactobacillus

was revised in April 2020 to reclassify species that were originally described as

Lactobacillus

species into 25 genera that comprise phylogenetically related micro-organisms. The species in these 25 genera also share major metabolic traits and generally have a shared ecology. A total of four comb. nov. names, however, were not considered validly published because the valid publication of the corresponding basonyms was published in later issues of the International Journal of Systematic and Evolutionary Microbiology. This communication aims to validly publish the names Apilactobacillus bombintestini,

Companilactobacillus suantsaicola

,

Lactiplantibacillus garii

and

Levilactobacillus suantsaiihabitans

.
Pseudorhodobacter turbinis sp. nov., isolated from the gut of the Korean turban shell, Turbo cornutus
Authors: Jeong Yun-Seok , Kang Woorim , Lee June-Young , Sung Hojun , Kim Hyun Sik , Han Jeong-Eun , Tak Euon Jung , Lee So-Yeon , Lee Jae-Yun , Kim Pil Soo , Hyun Dong-Wook , Jung Mi-Ja , Bae Jin-Woo
Published: February 2021

A novel Gram-stain-negative, coccus-shaped, aerobic and motile bacterial strain, designated S12M18T, was isolated from the gut of the Korean turban shell, Turbo cornutus. Phylogenetic analysis based on 16S rRNA gene sequences showed that strain S12M18T belonged to the genus

Pseudorhodobacter

and had the highest 16S rRNA gene sequence similarity twith

Pseudorhodobacter aquimaris

HDW-19T (98.63 %). The phylogenomic tree congruently verified that strain S12M18T occupies a taxonomic position within the genus

Pseudorhodobacter

. The OrthoANIu value between strain S12M18T and

P. aquimaris

HDW-19T was 87.22 %. The major cellular fatty acid of strain S12M18T was summed feature 8 (C18 : 1 ω7c or C18 : 1 ω6c). The major components of the polar lipids were phosphatidylcholine, phosphatidylglycerol and phosphatidylethanolamine. The predominant isoprenoid quinone was Q-10. The DNA G＋C content was 57.8 mol%. The polyphasic analyses indicated that strain S12M18T represents a novel species of the genus

Pseudorhodobacter

, for which the name Pseudorhodobacter turbinis sp. nov. is proposed. The type strain is S12M18T (=KCTC 62742T=JCM 33168T).
Profile of SARS-CoV-2-specific CD4 T cell response: Relationship with disease severity and impact of HIV-1 and activeMycobacterium tuberculosisco-infection
Authors: Riou Catherine , Bruyn Elsa du , Stek Cari , Daroowala Remy , Goliath Rene T. , Abrahams Fatima , Said-Hartley Qonita , Allwood Brian W. , Hsiao Marvin , Wilkinson Katalin A. , Arlehamn Cecilia S. Lindestam , Sette Alessandro , Wasserman Sean , Wilkinson Robert J.
Published: February 2021

T cells are involved in control of COVID-19, but limited knowledge is available on the relationship between antigen-specific T cell response and disease severity. Here, we assessed the magnitude, function and phenotype of SARS-CoV-2-specific CD4 T cells in 95 hospitalized COVID-19 patients (38 of them being HIV-1 and/or tuberculosis (TB) co-infected) and 38 non-COVID-19 patients, using flow cytometry. We showed that SARS-CoV-2-specific CD4 T cell attributes, rather than magnitude, associates with disease severity, with severe disease being characterized by poor polyfunctional potential, reduced proliferation capacity and enhanced HLA-DR expression. Moreover, HIV-1 and TB co-infection skewed the SARS-CoV-2 T cell response. HIV-1 mediated CD4 T cell depletion associated with suboptimal T cell and humoral immune responses to SARS-CoV-2; and a decrease in the polyfunctional capacity of SARS-CoV-2-specific CD4 T cells was observed in COVID-19 patients with active TB. Our results also revealed that COVID-19 patients displayed reduced frequency of Mtb-specific CD4 T cells, with possible implications for TB disease progression. There results corroborate the important role of SARS-CoV-2-specific T cells in COVID-19 pathogenesis and support the concept of altered T cell functions in patients with severe disease.
Targeting the Coronavirus Nucleocapsid Protein through GSK-3 Inhibition
Authors: Liu Xiaolei , Verma Anurag , Garcia Gustavo , Ramage Holly , Myers Rebecca L. , Lucas Anastasia , Michaelson Jacob J. , Coryell William , Kumar Arvind , Charney Alexander W. , Kazanietz Marcelo G. , Rader Daniel J , Ritchie Marylyn D , Berrettini Wade H. , Schultz David C. , Cherry Sara , Damoiseaux Robert , Arumugaswami Vaithilingaraja , Klein Peter S.
Published: February 2021

The coronaviruses responsible for severe acute respiratory syndrome (SARS-CoV), COVID-19 (SARS-CoV-2), Middle East respiratory syndrome (MERS-CoV), and other coronavirus infections express a nucleocapsid protein (N) that is essential for viral replication, transcription, and virion assembly. Phosphorylation of N from SARS-CoV by glycogen synthase kinase 3 (GSK-3) is required for its function and inhibition of GSK-3 with lithium impairs N phosphorylation, viral transcription, and replication. Here we report that the SARS-CoV-2 N protein contains GSK-3 consensus sequences and that this motif is conserved in diverse coronaviruses, raising the possibility that SARS-CoV-2 may be sensitive to GSK-3 inhibitors including lithium. We conducted a retrospective analysis of lithium use in patients from three major health systems who were PCR tested for SARS-CoV-2. We found that patients taking lithium have a significantly reduced risk of COVID-19 (odds ratio = 0.51 [0.35 - 0.74], p = 0.005). We also show that the SARS-CoV-2 N protein is phosphorylated by GSK-3. Knockout of GSK3A and GSK3B demonstrates that GSK-3 is essential for N phosphorylation. Alternative GSK-3 inhibitors block N phosphorylation and impair replication in SARS-CoV-2 infected lung epithelial cells in a cell-type dependent manner. Targeting GSK-3 may therefore provide a new approach to treat COVID-19 and future coronavirus outbreaks.

Significance

COVID-19 is taking a major toll on personal health, healthcare systems, and the global economy. With three betacoronavirus epidemics in less than 20 years, there is an urgent need for therapies to combat new and existing coronavirus outbreaks. Our analysis of clinical data from over 300,000 patients in three major health systems demonstrates a 50% reduced risk of COVID-19 in patients taking lithium, a direct inhibitor of glycogen synthase kinase-3 (GSK-3). We further show that GSK-3 is essential for phosphorylation of the SARS-CoV-2 nucleocapsid protein and that GSK-3 inhibition blocks SARS-CoV-2 infection in human lung epithelial cells. These findings suggest an antiviral strategy for COVID-19 and new coronaviruses that may arise in the future.
Accessible LAMP-Enabled Rapid Test (ALERT) for detecting SARS-CoV-2
Authors: Bektaş Ali , Covington Michael F. , Aidelberg Guy , Arce Anibal , Matute Tamara , Núñez Isaac , Walsh Julia , Boutboul David , Lindner Ariel B. , Federici Fernán , Jayaprakash Anitha
Published: February 2021

The COVID-19 pandemic has highlighted bottlenecks in large-scale, frequent testing of populations for infections. PCR-based diagnostic tests are expensive, reliant on expensive centralized labs, can take days to deliver results, and are prone to backlogs and supply shortages. Antigen tests, that bind and detect the surface proteins of a virus, are rapid and inexpensive but suffer from high false negative rates. To address this problem, we have created an inexpensive, simple, and robust 60-minute Do-It-Yourself (DIY) workflow to detect viral RNA from nasal swabs or saliva with high sensitivity (0.1 to 2 viral particles/µl) and specificity (>97% True Negative Rate) utilizing reverse transcription loop-mediated isothermal amplification (RT-LAMP).

Our workflow, ALERT (Accessible LAMP-Enabled Rapid Test), incorporates the following features: 1) Increased shelf-life and ambient temperature storage by using wax layers to isolate enzymes from reaction, 2) Improved specificity by using sequence-specific QUASR reporters, 3) Increased sensitivity through use of a magnetic wand to enable pipette-free concentration of sample RNA and cell debris removal, 4) Quality control with a nasopharyngeal-specific mRNA target, and 5) Co-detection of other respiratory viruses, such as Influenza B, by duplexing QUASR-modified RT-LAMP primer sets.

The flexible nature of the ALERT workflow allows easy, at-home and point-of-care testing for individuals and higher-throughput processing for centralized labs and hospitals. With minimal effort, SARS-CoV-2-specific primer sets can be swapped out for other targets to repurpose ALERT to detect other viruses, microorganisms or nucleic acid-based markers.
Essential hypertension is associated with changes in gut microbial metabolic pathways: A multi-site analysis of ambulatory blood pressure
Authors: Nakai Michael , Ribeiro Rosilene V , Stevens Bruce R. , Gill Paul , Muralitharan Rikeish R. , Yiallourou Stephanie , Muir Jane , Carrington Melinda , Head Geoffrey A. , Kaye David M. , Marques Francine Z.
Published: February 2021

Recent evidence supports a role for the gut microbiota in hypertension, but whether ambulatory blood pressure (BP) is associated with gut microbiota and their metabolites remains unclear. We characterised the function of the gut microbiota, their metabolites and receptors in untreated human hypertensive participants in Australian metropolitan and regional areas. Ambulatory BP, faecal microbiome predicted from 16S rRNA gene sequencing, plasma and faecal metabolites called short-chain fatty acid (SCFAs), and expression of their receptors were analysed in 70 untreated and otherwise healthy participants from metropolitan and regional communities. Most normotensives were female (66%) compared to hypertensives (35%, P<0.01), but there was no difference in age between the groups (59.2±7.7 versus 60.3±6.6-years-old). Based on machine-learning multivariate covariance analyses of de-noised amplicon sequence variant prevalence data, we determined that there were no significant differences in predicted gut microbiome α- and β-diversity metrics between normotensives versus essential, white coat or masked hypertensives. However, select taxa were specific to these groups, notablyAcidaminococcus spp., Eubacterium fissicatena and Muribaculaceaewere higher, whileRuminococcusandEubacterium eligenswere lower in hypertensives. Importantly, normotensive and essential hypertensive cohorts could be differentiated based on gut microbiome gene pathways and metabolites. Specifically, hypertensive participants exhibited higher plasma acetate and butyrate, but their immune cells expressed reduced levels of SCFA-activated G-protein coupled re1ceptor 43 (GPR43). In conclusion, gut microbial diversity did not change in essential hypertension, but we observed a significant shift in microbial gene pathways. Hypertensive subjects had lower levels of GPR43, putatively blunting their response to BP-lowering metabolites.
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

Correctional 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

Several 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.

Highlights

NAMPT 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

Coronavirus 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

Since 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

Alfalfa (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

Hyperscanning 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

Loss 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 Statement

Although 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

Gram-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.

IMPORTANCE

Gram-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

Despite 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

HIV-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

Abstract

Behavioural 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.
Spanish non-financial corporations and the COVID pandemic: vulnerability, resilience and transformation
Authors: Salas-Fumás Vicente
Published: February 2021

Purpose

This paper aims to assess the vulnerability and resilience of the Spanish non-financial corporations (NFC) to the shock from the COVID pandemic with consolidated income accounts data, and shows comparative labor productivity and endowment of organizational capital of Spanish firms, as indicators of their capabilities at the outset of the new digital transformation wave proposed by the next generation EU program.

Design/methodology/approach

The paper first describes the recent evolution (quarterly 2020 data) of the Spanish non-financial corporate sector (gross value added, labor cost, capital formation, profits) in the assessment of the vulnerability and resilience of the sector to the shock of the COVID pandemic. Then second, it estimates a probit model to evaluate the EU country effects in the explanation of the different propensity firms in the European Company Survey database to adopt innovative management and organization practices.

Findings

In the Spring of 2020, the Spanish NFC were still recovering from the great recession (low resilience), and the severe contraction in value-added and profits of the corporate sector in the first three quarters of the year evidences its high vulnerability. The proved complementarity between organizational and information related assets implies that the low endowment of organizational capital of Spanish firms, could be a severe limitation for the advancement toward digitalization.

Research limitations/implications

The aggregate corporate sector data used in the analysis of vulnerability and resilience of Spanish firms does not account for the heterogeneous effects of the pandemic across economic sectors (manufacturing and services, for example) and across firms (large versus small ones).

Originality/value

The paper complements the country-level analysis of the impact of the COVID pandemic in the Spanish economy with the analysis of the impact of the pandemic in the performance of the corporate sector. It provides one of the first analysis of the current endowment of organization capital of Spanish firms and highlights its relevance for productivity growth.
Empirical investigation of factors that enhance development of technology in design process improvement in architecture education: analyses of students' views
Authors: Imani Elnaz , Asefi Maziar
Published: February 2021

Purpose

Technology development quality in architectural design is affected by the quality of the process and factors used to develop it. The purpose of this study is to investigate the factors for effective enhancement (EE) of technologies in design process improvement (DPI).

Design/methodology/approach

Major databases have been explored to identify a list of factors affecting technology development in DPI because of the main elements of architecture design education. Then, a survey-based empirical study has been done in two high-rank architecture schools (one in a developing country and one in a developed country), during the years 2015–2018. Data have been collected from analyzing the design process, design reviews, design team viewpoints, researchers' observations and organizations' features about the development of production, conceptualization and communication technologies in DPI initiatives. Both quantitative and qualitative approaches have been utilized to provide deep contextual data.

Findings

Comparative analysis of the groups showed that high levels of EE of technologies lead to high levels of DPI, and these are because of the positive performance of conceptualization, communication and production technologies.

Originality/value

Comparing two groups, the category of design process and the factors related to the design stages of ask, imagine and improve approved to be the right factors to use technologies in more effective ways. Efficiency in collecting information and doing research, efficiency in developing solutions, efficiency in communicating results, team processes and organization communications have been rated top most effective factors based upon overall categories.
Successful health-promoting leadership – A question of synchronisation
Authors: Skott Pia
Published: February 2021

Purpose

The aim of this paper is to identify the role of the principal in establishing a whole school approach for health and wellbeing. Two questions are asked: (1) What do successful Swedish principals do when they take on a whole school approach? (2) How do these results relate to previous research on successful school leadership?

Design/methodology/approach

This paper focuses on the complexity of organisational processes and considers the role of successful leadership in managing a whole school approach to health promotion. It presents findings from two different but interlinked projects, and draws on document studies and interviews with principals, student health team members and teachers in Sweden.

Findings

This paper argues that successful school leaders are crucial in establishing a whole school approach, because of the work they do to synchronise the health-promoting activities in schools. The study identifies four aspects of coordination that need to be enacted simultaneously when leading health-promoting processes. The fifth aspect identified is that a whole school approach is not limited to the school, but the whole local school context, i.e. a synchronisation between different system levels.

Originality/value

Although limited in scale, this paper reports key findings that could have practical implications for school leaders. The study suggests that successful school leadership research needs to use a health-promoting lens in order to make leadership practices health-promoting practices. It also proposes extended comparative research from different fields and contexts.
Quality management practices as a driver of employee satisfaction: exploring the mediating role of organizational image
Authors: Babu Faisal , Thomas Sam
Published: February 2021

Purpose

Total quality management (TQM) has been a universally applienod management strategy to improve organizational performance and thereby to achieve competitiveness. Compared with the scholarly and practical attention paid to identify the consequences of implementing TQM practices, little is known about how those practices enhance organizational image and employee satisfaction. This paper aims to address that research gap and is designed to empirically prove the relationship between TQM practices, organizational image and employee satisfaction.

Design/methodology/approach

A questionnaire-based survey of 285 employees including administrators, managers and heads of departments of 21 National Accreditation Board for Hospital and Healthcare providers-accredited hospitals in India was conducted. The proposed research model was tested using partial least squares based structural equation modelling.

Findings

The results revealed that TQM practices have positive direct and indirect effects on employee satisfaction, confirming the partial mediation role played by organizational image in the relationship between TQM practices and employee satisfaction.

Research limitations/implications

From the findings, leaders can understand that by implementing TQM practices, organizations can enhance image of the organization and bring high level of employee satisfaction.

Originality/value

The study tries to answer questions largely ignored in the TQM literature: the effect of TQM practices on organizational image and employee satisfaction, and the mediating role of organizational image on TQM practices and employee satisfaction.
Research constituents and citation analysis of theJournal of Business and Industrial Marketing(1986–2019)
Authors: Donthu Naveen , Kumar Satish , Sureka Riya , Joshi Rohit
Published: February 2021

Purpose

This study aims to map the major research constituents and trends for theJournal of Business and Industrial Marketing(JBIM) during its 34-year history (1986–2019). It also identifies JBIM’s thematic structure and the key factors affecting the impact of its articles.

Design/methodology/approach

The Scopus database is used to identify the bibliographic data of JBIM. The most prolific authors, institutions and countries in the journal are analyzed through weighted distributions of articles. The thematic structure of the journal is evaluated by means of bibliographic coupling analysis. The study also examines the factors influencing citations of JBIM articles through regression modeling.

Findings

JBIM publishes contributions from around the world, though the most prolific contributors are affiliated with the USA, UK and Finland. Thematic analysis divided JBIM articles into five major themes. Citation analysis reveals that article age, special issue appearance, number of author keywords and number of references are prominent factors explaining an article’s impact.

Research limitations/implications

This study uses data from the Scopus database, and limitations of the database have implications for the findings.

Originality/value

This is the first comprehensive study to identify the thematic structure and the factors affecting citations of JBIM articles.
Technology as infrastructure for change: district leader understandings of 1:1 educational technology initiatives and educational change
Authors: Lamb Alexandra J. , Weiner Jennie Miles
Published: February 2021

Purpose

While educational infrastructure is consistently identified as a key lever for educational change, it is often overlooked in research and practice and specifically in relation to technology in schools. By using educational infrastructure as a lens to examine a group of districts' implementation of 1:1 programs, this work provides opportunities for understanding and approaching technology programs in new, and potentially more effective, ways.

Design/methodology/approach

Using the concept of educational infrastructure (Mehta and Fine, 2015; Peurach and Neumerski, 2015), this multiple-case study explores the ways superintendents and district technology leaders understand and enact 1:1 technology initiatives to support educational change.

Findings

The authors find these leaders see 1:1 technology as both embedded in, and engaged in changing, the physical, cultural, instructional and leadership infrastructures. This suggests that 1:1 technology can act as an infrastructure itself and has the potential to support changes to teaching and learning across the system.

Originality/value

This study offers a new perspective to understand and enact the opportunities of 1:1 technology. Specifically, it helps to reframe technology programs away from discrete classroom or school-based interventions to consider and attend to the system-level resources they require and thus increase benefits they can produce. While always useful, such considerations are particularly important in the current context and the proliferation of online learning for so many.