bluuebunny/crossref_metadata_2025 huggingface dataset:
MicroRNA-138 Regulates T-Cell Function by Targeting PD-1 in Patients with Hepatitis B Virus–Related Liver Diseases
Authors: Liu Wei , Zheng Xianzhao , Wang Jie , He Quanli , Li Junmin , Zhang Zengzeng , Liu Hongchun
Published: November 2020

Objective

T-cell exhaustion in hepatitis B virus (HBV) infection, which results from upregulation of programmed cell death-1 (PD-1), leads to persistent HBV infection and related disease progression. Therefore, agents targeting PD-1 may prove beneficial in the treatment of this condition. MicroRNA-138 (miR-138) possesses an anti-tumor ability in that it targets immune checkpoints, including PD-1. However, the function and underlying mechanisms of miR-138 in patients with HBV infection remains unclear.

Methods

Specimens were collected from healthy volunteers (n = 43) and patients with chronic hepatitis B (CHB; n = 52), liver cirrhosis (LC; n = 26), and hepatocellular carcinoma (HCC; n = 31); carriers of HBV who were asymptomatic (n = 51); and patients with CHB receiving antivirus treatment (n = 11). These specimens were then used to study the expression and relationship among miR-138, PD-1, and HBV DNA viral load. To investigate the role of miR-138 in regulating PD-1 expression and determine the effect of miR-138 in regulating T-cell function, a luciferase assay and a transfection assay were each performed with primary CD3+ T cells.

Results

We found that PD-1 was upregulated and miR-138 was downregulated in patients with CHB, LC, and HCC. Correlations analysis revealed that PD-1 expression was positively correlated with HBV DNA viral load whereas miR-138 was negatively correlated. Luciferase assay results showed that miR-138 directly inhibited PD-1 expression by interacting with the 3’-untranslated region of PD-1. As a result of miR-138 overexpression in primary T cells, PD-1 in these T cells was downregulated and antivirus cytokines secreted by T cells were significantly upregulated. In addition, the expression levels of PD-1 and miR-138 were reversed in patients with CHB who received antivirus treatments.

Conclusion

Results showed that miR-138 can promote T-cell responses within patients with HBV infection by inducing a PD-1 blockade. Such an effect suggests that miR-138 may serve as a new therapeutic target for the treatment of HBV infection.
Flanking sequence preference modulates de novo DNA methylation in the mouse genome
Authors: Mallona Izaskun , Ilie Ioana Mariuca , Karemaker Ino Dominiek , Butz Stefan , Manzo Massimiliano , Caflisch Amedeo , Baubec Tuncay
Published: November 2020

Mammalian de novo DNA methyltransferases (DNMT) are responsible for the establishment of cell-type-specific DNA methylation in healthy and diseased tissues. Through genome-wide analysis of de novo methylation activity in murine stem cells we uncover that DNMT3A prefers to methylate CpGs followed by cytosines or thymines, while DNMT3B predominantly methylates CpGs followed by guanines or adenines. These signatures are further observed at non-CpG sites, resembling methylation context observed in specialised cell types, including neurons and oocytes. We further show that these preferences result from structural differences in the catalytic domains of the two de novo DNMTs and are not a consequence of differential recruitment to the genome. Molecular dynamics simulations suggest that, in case of human DNMT3A, the preference is due to favourable polar interactions between the flexible Arg836 side chain and the guanine that base-pairs with the cytosine following the CpG. By exchanging arginine to a lysine, the corresponding side chain in DNMT3B, the sequence preference is reversed, confirming the requirement for arginine at this position. This context-dependent enzymatic activity provides additional insights into the complex regulation of DNA methylation patterns.
Management of Bloodstream Infections in Left Ventricular Assist Device Recipients: To Suppress, or Not to Suppress?
Authors: Esquer Garrigos Zerelda , Jandhyala Deeksha , Vijayvargiya Prakhar , Castillo Almeida Natalia E , Gurram Pooja , Corsini Campioli Cristina G , Stulak John M , Rizza Stacey A , O’Horo John C , DeSimone Daniel C , Baddour Larry M , Sohail M Rizwan
Published: November 2020

Background

Ascertaining involvement of left ventricular assist device (LVAD) in a patient presenting with bloodstream infection (BSI) can be challenging, frequently leading to use of chronic antimicrobial suppressive (CAS) therapy. We aimed to assess the efficacy of CAS therapy to prevent relapse of BSI from LVAD and non-LVAD sources.

Methods

We retrospectively screened adults receiving LVAD support from 2010 through 2018, to identify cases of BSI. Bloodstream infection events were classified into LVAD-related, LVAD-associated, and non-LVAD BSIs.

Results

A total of 121 episodes of BSI were identified in 80 patients. Of these, 35 cases in the LVAD-related, 14 in the LVAD-associated, and 46 in the non-LVAD BSI groups completed the recommended initial course of therapy and were evaluated for CAS therapy. Chronic antimicrobial suppressive therapy was prescribed in most of the LVAD-related BSI cases (32 of 35, 91.4%) and 12 (37.5%) experienced relapse. Chronic antimicrobial suppressive therapy was not prescribed in a majority of non-LVAD BSI cases (33, 58.9%), and most (31, 93.9%) did not experience relapse. Chronic antimicrobial suppressive therapy was prescribed in 9 of 14 (64.2%) cases of LVAD-associated BSI and none experienced relapse. Of the 5 cases in this group that were managed without CAS, 2 had relapse.

Conclusions

Patients presenting with LVAD-related BSI are at high risk of relapse. Consequently, CAS therapy may be a reasonable approach in the management of these cases. In contrast, routine use of CAS therapy may be unnecessary for non-LVAD BSIs.
On Christoph Deutschmann’s Disembedded Markets—Economic Theology and Global Capitalism, Abingdon and New York: Routledge, 2019
Authors: Jens Beckert
Published: November 2020

In this review symposium Jens Beckert, Greta Krippner and Elena Esposito discuss Christoph Deutschmann’s book Disembedded Markets—Economic Theology and Global Capitalism, Routledge 2019.
Development and validation of a highly sensitive and specific electrochemical assay to quantify anti-SARS-CoV-2 IgG antibodies to facilitate pandemic surveillance and monitoring of vaccine response
Authors: Chiang Samantha H. , Tu Michael , Cheng Jordan , Wei Fang , Li Feng , Chia David , Garner Omai , Chandrasekaran Sukantha , Bender Richard , Strom Charles M. , Wong David T.W.
Published: November 2020

Amperial™ is a novel assay platform that uses immobilized antigen in a conductive polymer gel followed by an electrochemical detection. A highly specific and sensitive assay was developed to quantify levels of IgG antibodies to SARS-CoV-2 in saliva. After establishing linearity and limit of detection we established a reference range of 5 standard deviations above the mean. There were no false positives in 667 consecutive saliva samples obtained prior to 2019. Saliva was obtained from 34 patients who had recovered from documented COVID-19 or had documented positive serologies. All of the patients with symptoms severe enough to seek medical attention had positive antibody tests and 88% overall had positive results.

We obtained blinded paired saliva and plasma samples from 14 individuals. The plasma was analyzed using an EUA-FDA cleared ELISA kit and the saliva was analyzed by our Amperial™ assay. All 5 samples with negative plasma titers were negative in saliva testing. Eight of the 9 positive plasma samples were positive in saliva and 1 had borderline results. A CLIA validation was performed as a laboratory developed test in a high complexity laboratory.

A quantitative non-invasive saliva based SARSCoV-2 antibody test was developed and validated with sufficient specificity to be useful for population-based monitoring and monitoring of individuals following vaccination.
Optimizing COVID-19 control with asymptomatic surveillance testing in a university environment
Authors: Brook Cara E. , Northrup Graham R. , Ehrenberg Alexander J. ,   the IGI SARS-CoV-2 Testing Consortium, Doudna Jennifer A. , Boots Mike
Published: November 2020

The high proportion of transmission events derived from asymptomatic or presymptomatic infections make SARS-CoV-2, the causative agent in COVID-19, difficult to control through the traditional non-pharmaceutical interventions (NPIs) of symptom-based isolation and contact tracing. As a consequence, many US universities developed asymptomatic surveillance testing labs, to augment NPIs and control outbreaks on campus throughout the 2020-2021 academic year (AY); several of those labs continue to support asymptomatic surveillance efforts on campus in AY2021-2022. At the height of the pandemic, we built a stochastic branching process model of COVID-19 dynamics at UC Berkeley to advise optimal control strategies in a university environment. Our model combines behavioral interventions in the form of group size limits to deter superspreading, symptom-based isolation, and contact tracing, with asymptomatic surveillance testing. We found that behavioral interventions offer a cost-effective means of epidemic control: group size limits of six or fewer greatly reduce superspreading, and rapid isolation of symptomatic infections can halt rising epidemics, depending on the frequency of asymptomatic transmission in the population. Surveillance testing can overcome uncertainty surrounding asymptomatic infections, with the most effective approaches prioritizing frequent testing with rapid turnaround time to isolation over test sensitivity. Importantly, contact tracing amplifies population-level impacts of all infection isolations, making even delayed interventions effective. Combination of behavior-based NPIs and asymptomatic surveillance also reduces variation in daily case counts to produce more predictable epidemics. Furthermore, targeted, intensive testing of a minority of high transmission risk individuals can effectively control the COVID-19 epidemic for the surrounding population. Even in some highly vaccinated university settings in AY2021-2022, asymptomatic surveillance testing offers an effective means of identifying breakthrough infections, halting onward transmission, and reducing total caseload. We offer this blueprint and easy-to-implement modeling tool to other academic or professional communities navigating optimal return-to-work strategies.
Prevalence of IgG antibodies against the severe acute respiratory syndrome coronavirus-2 among healthcare workers in Tennessee during May and June, 2020
Authors: Rebeiro Peter F. , Levinson Kara J. , Jolly Lindsay , Kassens Elizabeth , Dizikes George J. , Steece Richard S. , Metzger David C. , Loos Matthew , Buchheit Ron , Duncan Lisa D. , Rolando Lori A. , Schmitz Jonathan , Hart Heather A. , Aronoff David M.
Published: November 2020

SARS-CoV-2 seroprevalence was low (<1%) in this large population of healthcare workers (HCWs) across the state of Tennessee (n=11,787) in May-June 2020. Among those with PCR results, 81.5% of PCR and antibody test results were concordant. SARS-CoV-2 seroprevalence was higher among HCWs working in high-community-transmission regions and among younger workers.

Importance

These results may be seen as a baseline assessment of SARS-CoV-2 seroprevalence among HCWs in the American South during a period of growth, but not yet saturation, of infections among susceptible populations. In fact, this period of May-June 2020 was marked by the extension of renewed and sustained community-wide transmission after mandatory quarantine periods expired in several more populous regions of Tennessee. Where community transmission remains low, HCWs may still be able to effectively mitigate SARS-CoV-2 transmission, preserving resources for populations at high risk of severe disease, and these sorts of data help highlight such strategies.
Primate anterior insular cortex represents economic decision variables postulated by Prospect theory
Authors: Yang You-Ping , Li Xinjian , Stuphorn Veit
Published: November 2020

In humans, risk attitude is highly context-dependent, varying with wealth levels or for different potential outcomes, such as gains or losses. These behavioral effects are well described by Prospect Theory, with the key assumption that humans represent the value of each available option asymmetrically as gain or loss relative to a reference point. However, it remains unknown how these computations are implemented at the neuronal level. Using a new token gambling task, we found that macaques, like humans, change their risk attitude across wealth levels and gain/loss contexts. Neurons in their anterior insular cortex (AIC) encode the ‘reference point’ (i.e. the current wealth level of the monkey) and the ‘asymmetric value function’ (i.e. option value signals are more sensitive to change in the loss than in the gain context) as postulated by Prospect Theory. In addition, changes in the activity of a subgroup of AIC neurons are correlated with the inter-trial fluctuations in choice and risk attitude. Taken together, we find that the role of primate AIC in risky decision-making is to monitor contextual information used to guide the animal’s willingness to accept risk.
Implementation of CYP2D6 copy-number imputation panel and frequency of key pharmacogenetic variants in Finnish individuals with a psychotic disorder
Authors: Häkkinen K. , Kiiski JI. , Lähteenvuo M. , Jukuri T. , Suokas K. , Niemi-Pynttäri J. , Kieseppä T. , Männynsalo T. , Wegelius A. , Haaki W. , Lahdensuo K. , Kajanne R. , Kaunisto MA. , Tuulio-Henriksson A. , Kampman O. , Hietala J. , Veijola J. , Lönnqvist J. , Isometsä E. , Paunio T. , Suvisaari J. , Kalso E. , Niemi M. , Tiihonen J. , Daly M. , Palotie A. , Ahola-Olli AV.
Published: November 2020

Purpose

We constructed a CYP2D6 copy-number imputation panel by combining copy-number information to GWAS chip data. In addition, we report frequencies of key pharmacogenetic variants in individuals with a psychotic disorder from the genetically bottle-necked population of Finland.

Methods

We combined GWAS chip and CYP2D6 copy-number variation (CNV) data from the Breast Cancer Pain Genetics study (BrePainGen) to construct an imputation panel (N=902) for CYP2D6 CNV. The resulting data set was used as a CYP2D6 CNV imputation panel in 9,262 non-related individuals passing genotype data quality control procedures. The panel performance was evaluated by genotyping the CNV from a subset (N=297) of SUPER-Finland participants.

Results

CYP2D6 CNV was imputed correctly in 272 (92%) individuals. Sensitivity and specificity for detecting a duplication were 0.986 and 0.946, respectively. Sensitivity and specificity for detecting a deletion using imputation were 0.886 and 0.966, respectively. Based on imputation, the frequency of a CYP2D6 duplication and deletion in the whole SUPER-Finland sample with 9,262 non-related individuals passing quality control were 8.5% and 2.7%, respectively. We confirm the higher frequency of CYP2D6 ultrarapid metabolizers in Finland compared with non-Finnish Europeans. Additionally, we confirm a 21-fold enrichment of the UGT1A1 decreased function variant rs4148323 (also known as 211G>A, G71R or UGT1A1*6) in Finland compared with non-Finnish Europeans. Similarly, the NUDT15 variant rs116855232 was highly enriched in Finland.

Conclusion

Our results demonstrate that imputation of CYP2D6 CNV is possible. The methodology is not accurate enough to be used in clinical decision making, but it enables studying CYP2D6 in large biobanks with genome-wide data. In addition, it allows for researchers to recontact patients with certain pharmacogenetic variations through biobanks. We show that bottle-necked populations may have pharmacogenetically important variants with allele frequencies very different from the main ancestral group. Future studies should assess whether these differences are large enough to cause clinically significant changes in trial results across different ancestral groups.
Intra-host evolution during SARS-CoV-2 persistent infection
Authors: Voloch Carolina M , da Silva F Ronaldo , de Almeida Luiz G P , Brustolini Otavio J. , Cardoso Cynthia C , Gerber Alexandra L , Guimarães Ana Paula de C , Leitão Isabela de Carvalho , Mariani Diana , Ota Victor Akira ,   Covid19-UFRJ Workgroup,   LNCC-Workgroup, Lima Cristiano X , Teixeira Mauro M , Dias Ana Carolina F , Galliez Rafael Mello , Faffe Débora Souza , Pôrto Luís Cristóvão , Aguiar Renato S , Castiñeira Terezinha M P P , Ferreira Orlando C. , Tanuri Amilcar , de Vasconcelos Ana Tereza R
Published: November 2020

Prolonged infection of SARS-CoV-2 represents a challenge to the development of effective public health policies to control the COVID-19 pandemic. The reason why some people have persistent infection and how the virus survives for so long are still not fully understood. For this reason, we aimed to investigate the intra-host evolution of SARS-CoV-2 during persistent infection. Thirty-three patients who remained RT-PCR positive in the nasopharynx for at least 16 days were included in this study. Complete SARS-CoV-2 sequences were obtained for each patient at two time points. Phylogenetic, populational, and computational analysis of viral sequences confirmed persistent infection with evidence for a transmission cluster in health care professionals that shared the same workplace. A high number of missense variants targeting crucial structural and non-structural proteins such as Spike and Helicase was found. Interestingly, longitudinal acquisition of substitutions in Spike protein mapped many SARS-CoV-2 predicted T cell epitopes. Furthermore, the mutational profiles observed were suggestive of RNA editing enzyme activities, indicating innate immune mechanisms of the host cell. Viral quasispecies analysis corroborates persistent infection mainly by increasing richness and nucleotide diversity over time. Altogether, our findings highlight a dynamic and complex landscape of host and pathogen interaction during persistent infection suggesting that the host’s innate immunity shapes the increase of intra-host diversity with possible implications for therapeutic strategies and public health decisions during the COVID-19 pandemic.
Distance matters: barriers to antenatal care and safe childbirth in a migrant population on the Thailand-Myanmar border from 2007-2015, a pregnancy cohort study
Authors: Steinbrook Eric , Min Myo Chit , Kajeechiwa Ladda , Wiladphaingern Jacher , Paw Moo Kho , Pimanpanarak MuPawJay , Hiranloetthanyakit Woranit , Min Aung Myat , Tun Nay Win , Gilder Mary Ellen , Nosten François , McGready Rose , Parker Daniel M.
Published: November 2020

I.

Background

Antenatal care and delivery with skilled attendants substantially improve maternal health outcomes across the pregnancy spectrum, from conception to delivery. The Sustainable Development Goals recognize the need to expand these services to all pregnant women but there is limited data on access for migrants and in post-conflict regions.

II.

Methods

Using geographic information systems established for malaria elimination efforts in Kayin state, Myanmar and Tak Province, Thailand, retrospective estimates of travel distances from home villages to maternal health facilities between 2007-2015 were made. Multivariable regressions were used to assess the relationships between distance to healthcare and 1) presentation for early pregnancy care, 2) complications during pregnancy like malaria infections, and 3) eventual outcome of the pregnancy.

III.

Findings

Women who delayed antenatal care until the third trimester travelled 46% farther (DR: 1.46; CI: 1.39 – 1.53) compared to women who attended in the first trimester, and those with pregnancies complicated by Plasmodium falciparum malaria travelled 62% farther (DR: 1.62; CI: 1.44 – 1.82) than those without P. falciparum. Women did not deliver with skilled birth services and were lost to follow-up travelled 45% farther (distance ratio (DR): 1.45; CI: 1.40 – 1.51) than those who followed-up to deliver with skilled birth services.

IV.

Interpretation

This analysis supports substantial global evidence that travel distance disrupts access to care in limited resource regions. This is the first demonstration of empirical distance impacting maternal healthcare from early pregnancy to delivery of migrants living in post-conflict Thailand-Myanmar border regions, and future interventions should provide decentralized maternal healthcare to address these barriers.

V.

Funding

The Bill & Melinda Gates Foundation and the Wellcome Trust
Stimulus-specific plasticity of macaque V1 spike rates and gamma
Authors: Peter Alina , Stauch Benjamin J. , Shapcott Katharine , Kouroupaki Kleopatra , Schmiedt Joscha T. , Klein Liane , Klon-Lipok Johanna , Dowdall Jarrod R. , Schölvinck Marieke L. , Vinck Martin , Singer Wolf , Schmid Michael C. , Fries Pascal
Published: November 2020

When a visual stimulus is repeated, average neuronal responses typically decrease, yet they might maintain or even increase their impact through increased synchronization. Previous work has found that many repetitions of a grating lead to increasing gamma-band synchronization. Here we show in awake macaque area V1 that both, repetition-related reductions in firing rate and increases in gamma are specific to the repeated stimulus. These effects showed some persistence on the timescale of minutes. Further, gamma increases were specific to the presented stimulus location. Importantly, repetition effects on gamma and on firing rates generalized to natural images. These findings suggest that gamma-band synchronization subserves the adaptive processing of repeated stimulus encounters, both for generating efficient stimulus responses and possibly for memory formation.
Dissecting the role of glutamine in seeding peptide aggregation
Authors: Barrera Exequiel E. , Zonta Francesco , Pantano Sergio
Published: November 2020

Poly glutamine and glutamine-rich peptides play a central role in a plethora of pathological aggregation events. However, biophysical characterization of soluble oligomers —the most toxic species involved in these processes— remains elusive due to their structural heterogeneity and dynamical nature. Here, we exploit the high spatio-temporal resolution of simulations as a computational microscope to characterize the aggregation propensity and morphology of a series of polyglutamine and glutamine-rich peptides. Comparative analysis of ab-initio aggregation pinpointed a double role for glutamines. In the first phase, glutamines mediate seeding by pairing monomeric peptides, which serve as primers for higher-order nucleation. According to the glutamine content, these low molecular-weight oligomers may then proceed to create larger aggregates. Once within the aggregates, buried glutamines continue to play a role in their maturation by optimizing solvent-protected hydrogen bonds networks.

TOC / Abstract Figure
The single pass membrane protein MRAP2 regulates energy homeostasis by promoting primary cilia localization of the G protein-coupled receptor MC4R
Authors: Bernard Adélaïde , Naharros Irene Ojeda , Bourgain-Guglielmetti Florence , Ciprin Jordi , Yue Xinyu , Zhang Sumei , McDaid Erin , Nachury Maxence , Reiter Jeremy F. , Vaisse Christian
Published: November 2020

The G protein-coupled receptor MC4R (Melanocortin-4 Receptor) and its associated protein MRAP2 (Melanocortin Receptor-Associated Protein 2) are both essential for the regulation of food intake and body weight in humans and mice. MC4R localizes and functions at the neuronal primary cilium, a microtubule-based organelle that senses and relays extracellular signals. Here, we demonstrate that MRAP2 is critical for the ciliary localization and weight-regulating function of MC4R. Our data reveal that GPCR localization to primary cilia can require specific accessory proteins that may not be present in heterologous cell systems. Our findings also demonstrate the essential role of neuronal primary cilia localization of MC4R for adequate control of energy homeostasis and the obesity-promoting effect of genetic disruption of this pathway.
Hybrid Clustering of single-cell gene expression and cell spatial information via integrated NMF and k-means
Authors: Oh Sooyoun , Park Haesun , Zhang Xiuwei
Published: November 2020

Motivation

Recent advances in single cell transcriptomics have allowed us to examine the identity of single cells, which has led to the discovery of new cell types and high resolution maps of cell type composition in tissues. Technologies that measure multiple modalities of single cell data provide a more comprehensive picture of a cell, but they also create challenges for data integration tasks.

Results

In our work, we jointly consider the spatial location and gene expression profiles of cells to determine their identity. Specifically, we have developed scHybridNMF (single-cell Hybrid Nonnegative Matrix Factorization), which performs cell type identification by incorporating single cell gene expression data with cell location data. We combined nonnegative matrix factorization (NMF) with k-means clustering to cohesively represent high-dimensional gene expression data and low-dimensional location data, respectively. We show that scHybridNMF can utilize location data to improve cell type clustering. In particular, we show that under multiple scenarios, including the cases where there is a small number of genes profiled and the location data is noisy, scHybridNMF outperforms sparse NMF, k-means, and an existing method (HMRF) that also uses cell location and gene expression data for cell type identification.

Availability

https://github.com/soobleck/scHybridNMF

Contact

hpark@cc.gatech.edu,xiuwei.zhang@gatech.edu
DNA-SIP and repeated isolation corroborateVariovoraxas a key organism in maintaining the genetic memory for linuron biodegradation in an agricultural soil
Authors: Lerner Harry , Öztürk Başak , Dohrmann Anja B. , Thomas Joice , Marchal Kathleen , De Mot René , Dehaen Wim , Tebbe Christoph C. , Springael Dirk
Published: November 2020

The frequent exposure of agricultural soils to pesticides often leads to microbial adaptation, including the development of dedicated microbial populations that utilize the pesticide compound as a carbon and energy source. Soil from an agricultural field in Halen (Belgium) with a history of linuron exposure has been studied for its linuron-degrading bacterial populations at two time points over the past decade andVariovoraxwas appointed as a key linuron degrader. Like most studies on pesticide degradation, these studies relied on isolates that were retrieved through bias-prone enrichment procedures and therefore might not represent thein situactive pesticide-degrading populations. In this study, we revisited the Halen field and applied, in addition to enrichment-based isolation, DNA stable isotope probing (DNA-SIP), to identify thein situlinuron degrading bacteria. DNA-SIP unambiguously linkedVariovoraxand its linuron catabolic genes to linuron dissipation, likely through synergistic cooperation between two species. Additionally, two linuron mineralizingVariovoraxisolates were obtained with high 16S rRNA gene sequence similarity to strains isolated from the same field a decade earlier. The results confirmVariovoraxas thein situdegrader of linuron in the studied agricultural field and corroborate the genus as key in the maintenance of a robust genetic memory regarding linuron degradation functionality in the examined field.
A cortical circuit for audio-visual predictions
Authors: Garner Aleena R. , Keller Georg B.
Published: November 2020

Learned associations between stimuli in different sensory modalities can shape the way we perceive these stimuli (Mcgurk and Macdonald, 1976). During audio-visual associative learning, auditory cortex is thought to underlie multi-modal plasticity in visual cortex (McIntosh et al., 1998; Mishra et al., 2007; Zangenehpour and Zatorre, 2010). However, it is not well understood how processing in visual cortex is altered by an auditory stimulus that is predictive of a visual stimulus and what the mechanisms are that mediate such experience-dependent, audio-visual associations in sensory cortex. Here we describe a neural mechanism by which an auditory input can shape visual representations of behaviorally relevant stimuli through direct interactions between auditory and visual cortices. We show that the association of an auditory stimulus with a visual stimulus in a behaviorally relevant context leads to an experience-dependent suppression of visual responses in primary visual cortex (V1). Auditory cortex axons carry a mixture of auditory and retinotopically-matched visual input to V1, and optogenetic stimulation of these axons selectively suppresses V1 neurons responsive to the associated visual stimulus after, but not before, learning. Our results suggest that cross-modal associations can be stored in long-range cortical connections and that with learning these cross-modal connections function to suppress the responses to predictable input.
Tobramycin adaptation enhances policing of social cheaters inPseudomonas aeruginosa
Authors: Abisado Rhea G. , Kimbrough John H. , Mckee Brielle M. , Craddock Vaughn D. , Smalley Nicole E. , Dandekar Ajai A. , Chandler Josephine R.
Published: November 2020

ThePseudomonas aeruginosaLasR-I quorum sensing (QS) system regulates secreted proteases that can be exploited by cheaters, such as QS receptor-defective (lasR) mutants.lasRmutants emerge in populations growing on casein as a sole source of carbon and energy and increase in the population because they do not incur the substantial cost of engaging in QS. QS also increases resistance to some antibiotics, such as tobramycin. Here, we show that tobramycin suppresses the emergence oflasRmutants in casein-passaged populations. We also identify several mutations that accumulate in those populations indicating evidence of antibiotic adaptation. Mutations in one gene,ptsP, increase activity of the LasR-I system and production of a QS-controlled phenazine, pyocyanin. We find that mutations inptsPlead to suppression of cheaters independent of tobramycin. Cheater suppression relies on pyocyanin, which acts as a policing toxin by targeting cheaters. These results show that tobramycin suppresseslasRmutants through two mechanisms: first, by directly acting on tobramycin-susceptible cheaters and second, by selecting mutations inptsPthat lead to pyocyanin-dependent policing. This work demonstrates how adaptive mutations can alter the dynamics of cooperator-cheater relationships, which might be important for populations adapting to antibiotics during infections.
Inertia in value-driven attention
Authors: Liao Ming-Ray , Anderson Brian A.
Published: November 2020

Previously reward-associated stimuli persistently capture attention. We attempted to extinguish this attentional bias through a reversal learning procedure where the high-value color changed unexpectedly. Attentional priority shifted during training in favor of the currently high-value color, although a residual bias toward the original high-value color was still evident. Importantly, during a subsequent test phase, attention was initially more strongly biased toward the original high-value color, counter to the attentional priorities evident at the end of training. Our results show that value-based attentional biases do not quickly update with new learning and lag behind the reshaping of strategic attentional priorities by reward.
The maturational characteristics of the GABA input in the anterior piriform cortex may also contribute to the rapid learning of the maternal odor during the sensitive period
Authors: Oruro Enver Miguel , Pardo Grace V.E. , Lucion Aldo Bolten , Calcagnotto Maria Elisa , Idiart Marco A.P.
Published: November 2020

During the first ten postnatal days (P), infant rodents can learn olfactory preferences for novel odors if they are paired with thermo-tactile stimuli that mimic components of maternal care. After P10, the thermo-tactile pairing becomes ineffective for conditioning. The current explanation for this change in associative learning is the alteration in the norepinephrine (NE) inputs from the locus coeruleus (LC) to the olfactory bulb (OB) and the anterior piriform cortex (aPC). By combining patch-clamp electrophysiology and computational simulations, we showed in a recent work that a transitory high responsiveness of the OB-aPC circuit to the maternal odor is an alternative mechanism that could also explain early olfactory preference learning and its cessation after P10. That result relied solely on the maturational properties of the aPC pyramidal cells. However, the GABAergic system undergoes important changes during the same period. To address the importance of the maturation of the GABAergic system for early olfactory learning, we incorporated data from the GABA inputs, obtained from in vitro patch-clamp experiment in the aPC of rat pups aged P5–P7 reported here, to the model proposed in our previous publication. In the younger than P10 OB-aPC circuit with GABA synaptic input, the number of responsive aPC pyramidal cells to the conditioned maternal odor was amplified in 30% compared to the circuit without GABAergic input. When compared with the circuit with other younger than P10 OB-aPC circuit with adult GABAergic input profile, this amplification was 88%. Together, our results suggest that during the olfactory preference learning in younger than P10, the GABAergic synaptic input presumably acts by depolarizing the aPC pyramidal neurons in such a way that it leads to the amplification of the pyramidal neurons response to the conditioned maternal odor. Furthermore, our results suggest that during this developmental period, the aPC pyramidal cells themselves seem to resolve the apparent lack of GABAergic synaptic inhibition by a strong firing adaptation in response to increased depolarizing inputs.
Toward a supply chain risk identification and filtering framework using systems theory
Authors: Hou Jianrong , Zhao Xiaofeng
Published: November 2020

Purpose

The purpose of the paper is to develop a methodological framework for supply chain risk management using the hierarchical holographic modeling approach. It analyses supply chain risks in a systematic manner and develops a hierarchical methodology for identifying, prioritizing and managing the potential supply chain risks.

Design/methodology/approach

This research reviews supply chain risk management literature and develops a conceptual framework, which outlines general principles and guidelines for managing risks in a systematic manner. Through decomposition, the complexity of supply chain risk can be identified by analyzing smaller subsystems.

Findings

The paper provides a conceptual framework to identify supply chain risks from multiple overlapping perspectives. The structured filtering and ranking procedure enables decision-makers to focus on the most critical risks. The research shows that the supply chain risks associated with the sub-systems within the hierarchical structure contribute to and ultimately determine the risks of the overall supply chain system.

Research limitations/implications

The risks associated with each sub system within the hierarchical structure can contribute to and determine the risks of the overall supply chain system. Further applications in various companies and industry sectors would benefit supply chain managers on a case-by-case basis.

Practical implications

The hierarchical risk identification framework can serve as guidance for applications to specific supply chain systems and processes. The framework from a holistic overlapping perspective can efficiently and effectively help supply chain managers identify supply chain risks and facilitate the evaluation of the subsystem risks.

Originality/value

The paper applies system thinking in supply chain management and presents an efficient and practical framework for supply chain risk identification and evaluation.
The impact of intellectual capital and related party transactions on contractual costs
Authors: Salehi Mahdi , Ahmadzadeh Samira , Irvani Qale Sorkh Fahimeh
Published: November 2020

Purpose

The present study aims to assess the potential effects of intellectual capital (IC) and disclosure of firms' affiliate transactions on contractual costs (CC).

Design/methodology/approach

The statistical population of the study includes 768 firm-year observations listed on the Tehran Stock Exchange during 2012–2017. According to Pulic's model, the authors divide IC into three components, such as human capital (HC), relational capital and structural capital (SC). CC is also measured by utilising two variables of board cash compensation and unexpected reward of managers.

Findings

The results show that there is a negative and significant relationship between HC and CC. In contrast, the authors find that relational capital and SC have a positive impact on CC. The authors’ further analyses also demonstrate that disclosure of transactions with affiliates has a negative effect on unexpected rewards of managers.

Originality/value

Since there is no conducted study, which discusses the relationship between IC and contractual cost, this paper might be considered the primary studies conducted in this line of literature, specifically in emerging markets. Moreover, to the best of the authors' knowledge, this is the first study investigating the potential impact of disclosure of selling and purchasing transactions, separately, on the director's unexpected reward.
Workplace cyber abuse: challenges and implications for management
Authors: D'Souza Natalia , Forsyth Darryl , Blackwood Kate
Published: November 2020

Purpose

This paper offers a synopsis of workplace cyber abuse, identifying patterns of and responses to cyber abuse, as well as barriers to reporting and successful organisational intervention.

Design/methodology/approach

Using a pragmatic research paradigm, quantitative and qualitative survey data were collected from 205 targets of cyber abuse in New Zealand.

Findings

Nearly half of all respondents experienced more than one form of cyber abuse, with gendered patterns emerging. Workplace cyber abuse also frequently went unreported for varying reasons. Based on the descriptive analyses, four key challenges for the management of cyber abuse are identified: (1) multiple and gendered patterns of cyber abuse, (2) cyber abuse across organisational boundaries, (3) non-reporting and underreporting and (4) ineffective (or lack of) organisational interventions.

Practical implications

Implications for human resource management (HRM) and line managers include adopting a preventative approach to workplace cyber abuse by implementing clear policies, guidelines and resources to deal with cyber abuse, clarifying the boundaries of “workplace” cyber abuse and considering organisational protection measures for non-standard and vulnerable workers.

Social implications

Unique challenges with workplace cyber abuse emphasise the need for a coordinated, multilevel intervention approach involving organisations, policymakers, online platforms and academics.

Originality/value

This study provides an important overview of existing approaches to the management of workplace cyber abuse as well as a foundation upon which to base further research exploring good practice in its prevention and intervention and much-needed theoretical development.
Evaluating spatially explicit sharing‐sparing scenarios for multiple environmental outcomes
Authors: Finch Tom , Day Brett H. , Massimino Dario , Redhead John W. , Field Rob H. , Balmford Andrew , Green Rhys E. , Peach Will J.
Published: November 2020

Understanding how to allocate land for the sustainable delivery of multiple, competing objectives is a major societal challenge. The land sharing‐sparing framework presents a heuristic for understanding the trade‐off between food production and biodiversity conservation by comparing region‐wide land‐use scenarios which are equivalent in terms of overall food production.

Here, for two contrasting regions of lowland England (The Fens and Salisbury Plain), we use empirical data and predictive models to compare a suite of spatially explicit scenarios reflecting the full range of the sharing‐sparing continuum, including mixed scenarios which combine elements of both sharing and sparing. We evaluate a range of outcomes (bird populations, global warming potential (GWP), nitrogen and phosphorus pollution and outdoor recreation), to identify approaches to regional land‐use planning with the potential to deliver multiple societal benefits.

Land‐sharing scenarios (which reduce the dominance of productive agricultural land in farmed areas and the area of larger unfarmed areas) result in negative outcomes, particularly for birds and GWP. In contrast, many land‐sparing scenarios (including mixed scenarios which increase the area of lower‐yield farmland alongside larger unfarmed areas) resulted in improvements in all or most outcomes, although for recreation and nutrient export differences between scenarios were modest.

Importantly, environmental outcomes also depended on the spatial arrangement of spared land, the types of natural or semi‐natural habitat promoted on spared land, whether some lower‐yield farmland is delivered alongside larger unfarmed areas, and the overall region‐wide food production target.

Policy implications. Our study suggests that land‐sparing strategies which increase the area of natural and semi‐natural areas can improve environmental outcomes, despite the costs associated with high‐yield agriculture. However, high‐yield agriculture should not compromise future production or the conservation value of spared land, and explicit policies such as certification or payments for ecosystem services are required to link sustainable high‐yield production to habitat conservation. Our study also highlights the importance of mitigating projected increases in food demand.
A unique porin meditates iron‐selective transport through cyanobacterial outer membranes
Authors: Qiu Guo‐Wei , Jiang Hai‐Bo , Lis Hagar , Li Zheng‐Ke , Deng Bin , Shang Jin‐Long , Sun Chuan‐Yu , Keren Nir , Qiu Bao‐Sheng
Published: November 2020

Cyanobacteria are globally important primary producers and nitrogen fixers with high iron demands. Low ambient dissolved iron concentrations in many aquatic environments mean that these organisms must maintain sufficient and selective transport of iron into the cell. However, the nature of iron transport pathways through the cyanobacterial outer membrane remains obscure. Here we present multiple lines of experimental evidence that collectively support the existence of a novel class of substrate‐selective iron porin, Slr1908, in the outer membrane of the cyanobacterium Synechocystis sp. PCC 6803. Elemental composition analysis and short‐term iron uptake assays with mutants in Slr1908 reveal that this protein is primarily involved in inorganic iron uptake and contributes less to the accumulation of other metals. Homologues of Slr1908 are widely distributed in both freshwater and marine cyanobacteria, most notably in unicellular marine diazotrophs. Complementary experiments with a homologue of Slr1908 in Synechococcus sp. PCC 7002 restored the phenotype of Synechocystis knockdown mutants, showing that this siderophore producing species also possesses a porin with a similar function in Fe transport. The involvement of a substrate‐selective porins in iron uptake may allow cyanobacteria to tightly control iron flux into the cell, particularly in environments where iron concentrations fluctuate.
A US national randomized study to guide how best to reduce stigma when describing drug‐related impairment in practice and policy
Authors: Kelly John F. , Greene M. Claire , Abry Alexandra
Published: November 2020

Background and Aims

Drug‐related impairment is persistently stigmatized delaying and preventing treatment engagement. To reduce stigma, various medical terms (e.g. ‘chronically relapsing brain disease’, ‘disorder’) have been promoted in diagnostic systems and among national health agencies, yet some argue that over‐medicalization of drug‐related impairment lowers prognostic optimism and reduces personal agency. While intensely debated, rigorous empirical study is lacking. This study investigated whether random exposure to one of six common ways of describing drug‐related impairment induces systematically different judgments.

Design, Setting and Participants

Cross‐sectional survey, US general population, among a nationally representative non‐institutionalized sample (n = 3635; 61% response rate; December 2019–January 2020).

Intervention

Twelve vignettes (six terms × gender) describing someone treated for opioid‐related impairment depicted in one of six ways as a(n): ‘chronically relapsing brain disease’, ‘brain disease’, ‘disease’, ‘illness’, ‘disorder’ or ‘problem’.

Measurements

Multi‐dimensional stigma scale assessing: blame; social exclusion; prognostic optimism, continuing care, and danger (a = 0.70–0.83).

Findings

US adults [mean age = 47.81, confidence interval (CI) = 47.18–48.44; 52.4% female; 63.14% white] rated the same opioid‐impaired person differently across four of five stigma dimensions depending on which of six terms they were exposed to. ‘Chronically relapsing brain disease’ induced the lowest stigmatizing blame attributions (P < 0.05); at the same time, this term decreased prognostic optimism [mean difference (MD) = 0.18, 95% CI = 0.05, 0.30] and increased perceived need for continuing care (MD = –0.26, 95% CI = –0.43, –0.09) and danger (MD = –0.13, 95% CI = –0.25, –0.02) when compared with ‘problem’. Compared with a man, a woman was blamed more for opioid‐related impairment (MD = –0.08, 95% CI = –0.15, –0.01); men were viewed as more dangerous (MD = 0.13, 95% CI = 0.06, 0.19) and to be socially excluded (MD = 0.16, 95% CI = 0.09, 0.23).

Conclusions

There does not appear to be one single medical term for opioid‐related impairment that can meet all desirable clinical and public health goals. To reduce stigmatizing blame, biomedical ‘chronically relapsing brain disease’ terminology may be optimal; to increase prognostic optimism and decrease perceived danger/social exclusion use of non‐medical terminology (e.g. ‘opioid problem’) may be optimal.
Ecosystem diversity of mosquitoes (Diptera: Culicidae) in a remnant of Atlantic Forest, Rio de Janeiro state, Brazil
Authors: Alencar Jeronimo , de Mello Cecilia Ferreira , Rodríguez‐Planes Lucía , dos Santos Silva Júlia , Gil‐Santana Hélcio Reinaldo , Bastos Amanda Queiroz , Albuquerque Hermano Gomes , Rodrigues William Costa , Guimarães Anthony Érico
Published: November 2020

Understanding mosquito biodiversity in the Atlantic Forest is important for assessing changes in the distribution of mosquito populations, which have been considered predominantly to be sylvatic. An observational study of Culicidae was conducted in a remnant of the Atlantic Forest in the Poço das Antas Biological Reserve, Silva Jardim municipality, Rio de Janeiro state, Brazil, to evaluate species diversity and the influence of climatic factors (temperature, relative humidity and rainfall) on species distribution. Two types of light trap were used: an automatic CDC trap baited with CO2 and a Shannon trap. Collections were also made using a manual suction tube. Overall, 15 700 Culicidae specimens were collected belonging to two subfamilies, 12 genera and 41 species. The most common species were Coquillettidia chrysonotum, Mansonia titillans and Coquillettidia venezuelensis. Principal component analyses indicated a major association between sampling site six and the species Anopheles albitarsis, Mansonia titilllans, Cq. chrysonotum and Cq. venezuelensis. Furthermore, diversity indices indicated that sampling sites 1, 6 and 4 displayed higher diversity and a more uniform species abundance. Culicidae abundance was positively correlated with temperature. Landscape units exhibited contrasting community compositions of mosquitoes at multiple scales, with the community composition more similar in sites with similar landscape parameters. The importance of constant entomological monitoring is underscored by the diversity of mosquito species in this reserve and their potential role in the transmission of pathogens, combined with intermittent flow of visitors to the area.