bluuebunny/crossref_metadata_2025 huggingface dataset:
Genome-wide identification of the LexA-mediated DNA damage response inStreptomyces venezuelae
Authors: Stratton Kathryn J. , Bush Matthew J. , Chandra Govind , Stevenson Clare E. M. , Findlay Kim C. , Schlimpert Susan
Published: March 2022

DNA damage triggers a widely conserved stress response in bacteria called the SOS response that involves two key regulators, the activator RecA and the transcriptional repressor LexA. Despite the wide conservation of the SOS response, the number of genes controlled by LexA varies considerably between different organisms. The filamentous soil-dwelling bacteria of the genusStreptomycescontain LexA and RecA homologs but their roles inStreptomyceshave not been systematically studied. Here, we demonstrate that RecA and LexA are required for the survival ofStreptomyces venezuelaeduring DNA damaging conditions and for normal development during unperturbed growth. Monitoring the activity of a fluorescentrecApromoter fusion and LexA protein levels revealed that the activation of the SOS response is delayed inS. venezuelae. By combining global transcriptional profiling and ChIP-seq analysis, we determined the LexA regulon and defined the core set of DNA damage repair genes that are expressed in response to treatment with the DNA alkylating agent mitomycin C. Our results show that DNA damage-induced degradation of LexA results in the differential regulation of LexA target genes. Using Surface Plasmon Resonance, we further confirm the LexA DNA binding motif (SOS box) and demonstrate that LexA displays tight but distinct binding affinities to its target promoters, indicating a graded response to DNA damage.

IMPORTANCE

The transcriptional regulator LexA functions as a repressor of the bacterial SOS response, which is induced during DNA damaging conditions. This results in the expression of genes important for survival and adaptation. Here, we report the regulatory network controlled by LexA in the filamentous antibiotic producingStreptomycesbacteria and establish the existence of the SOS response inStreptomyces. Collectively, our work reveals significant insights into the DNA damage response inStreptomycesthat will promote further studies to understand how these important bacteria adapt to their environment.
Inflammaging in human photoexposed skin: Early onset of senescence and imbalanced epidermal homeostasis across the decades
Authors: Jarrold Bradley B. , Ru Tan Christina Yan , Ho Chin Yee , Soon Ai Ling , Lam TuKiet T. , Yang Xiaojing , Nguyen Calvin , Guo Wei , Chew Yap Ching , DeAngelis Yvonne M. , Costello Lydia , De Los Santos Gomez Paola , Przyborski Stefan , Bellanger Sophie , Dreesen Oliver , Kimball Alexa B. , Oblong John E.
Published: March 2022

Inflammaging is a theory of aging which purports that low-level chronic inflammation leads to cellular dysfunction and premature aging of surrounding tissue. Skin is susceptible to inflammaging because it is the first line of defense from the environment, particularly solar radiation. To better understand the impact of aging and photoexposure on epidermal biology we performed a systems biology-based analysis of photoexposed face and arm and photoprotected buttock sites from women between the ages of 20’s to 70’s. Biopsies were analyzed by histology, transcriptomics, and proteomics and skin surface biomarkers collected from tape strips. We identified morphological changes with age of epidermal thinning, rete ridge pathlength loss, and stratum corneum thickening. The SASP biomarkers IL-8 and IL-1RA/IL1-α were consistently elevated in face across age and cis/trans-urocanic acid were elevated in arms and face with age. In older arms, the DNA damage response biomarker 53BP1 showed higher puncti numbers in basal layers and epigenetic aging was accelerated. Genes associated with differentiation and senescence show increasing expression in the 30’s whereas genes associated with hypoxia and glycolysis increase in the 50’s. Proteomics comparing 60’s vs 20’s confirmed elevated levels of differentiation and glycolytic related proteins. Representative immunostaining for proteins of differentiation, senescence, and oxygen sensing/hypoxia shows similar relationships. This systems biology-based analysis provides a body of evidence that young photoexposed skin is undergoing inflammaging. We propose the presence of chronic inflammation in young skin contributes to an imbalance of epidermal homeostasis that leads to a prematurely aged appearance during later life.
Age-related differences in functional network segregation in the context of sex and reproductive stage
Authors: Ballard Hannah K. , Jackson T. Bryan , Miller Abigail C. , Hicks Tracey H. , Bernard Jessica A.
Published: March 2022

Age is accompanied by differences in the organization of functional brain networks, which impact behavior in adulthood. Functional networks tend to become less segregated and more integrated with age. However, sex differences in network segregation declines with age are not well-understood. Further, network segregation in the context of female reproductive stage is relatively understudied, though unmasking such relationships would be informative for elucidating biological mechanisms that contribute to sex-specific differences in aging. In the current work, we used data from the Cambridge Centre for Ageing and Neuroscience (Cam-CAN) repository to evaluate differences in resting-state network segregation as a product of sex and reproductive stage. Reproductive stage was categorized using the Stages of Reproductive Aging Workshop (STRAW+10) criteria. Replicating prior work, we investigated the following functional networks: auditory, cerebellar-basal ganglia, cingulo-opercular task control, default mode, dorsal attention, fronto-parietal task control, salience, sensory somatomotor mouth, sensory somatomotor hand, ventral attention, and visual. First, our results mirror findings from previous work indicating that network segregation is lower with increasing age. Second, when analyzing associations between network segregation and age within each sex separately, we find differences between females and males. Finally, we report significant effects of reproductive stage on network segregation, though these findings are likely driven by age. Broadly, our results suggest that impacts of sex are important to evaluate when investigating network segregation differences across adulthood, though further work is needed to determine the unique role of menopause and sex hormones on the organization of functional brain networks within aging females.

Key Points

Segregation of functional brain networks declines with increasing age

Age-segregation relationships are modified by biological sex

Reproductive stage may impact sex differences in brain network organization
A novel cis-element enabled bacterial uptake by plant cells
Authors: Cathebras Chloé , Gong Xiaoyun , Andrade Rosa Elena , Vondenhoff Ksenia , Keller Jean , Delaux Pierre-Marc , Hayashi Makoto , Griesmann Maximilian , Parniske Martin
Published: March 2022

The root nodule symbiosis (RNS) of plants with nitrogen-fixing bacteria is phylogenetically restricted to a single clade of flowering plants, which calls for yet unidentified trait acquisitions and genetic changes in the last common ancestor. Here we discovered – within the promoter of the transcription factor gene Nodule Inception (NIN) – a cis-regulatory element (PACE), exclusively present in members of this clade. PACE was essential for restoring infection threads (ITs) in nin mutants of the legume Lotus japonicus. PACE sequence variants from RNS-competent species appeared functionally equivalent. Evolutionary loss or mutation of PACE is associated with loss of this symbiosis. During early stages of nodule development, PACE dictates gene expression in a spatially restricted domain containing cortical cells carrying ITs. Consistent with its expression domain, PACE-driven NIN expression restored the formation of cortical ITs, also when engineered into the NIN promoter of tomato. Our data pinpoint PACE as a key evolutionary invention that connected NIN to a pre-existing symbiosis signal transduction cascade that governs the intracellular accommodation of arbuscular mycorrhiza fungi and is conserved throughout land plants. This connection enabled bacterial uptake into plant cells via intracellular support structures like ITs, a unique and unifying feature of this symbiosis.
Cells with Stochastically Increased Methyltransferase to Restriction Endonuclease Ratio Provide an Entry for Bacteriophage into Protected Cell Population
Authors: Kirillov Alexander , Morozova Natalia , Polinovaskaya Vasilisa , Smirnov Sergey , Khodorkovskii Mikhail , Zeng Lanying , Ispolatov Yaroslav , Severinov Konstantin
Published: March 2022

The action of type II restriction-modification (RM) systems depends on restriction endonuclease (REase), which cleaves foreign DNA at specific sites, and methyltransferase (MTase), which protects host genome from restriction by methylating the same sites. We show that protection from phage infection increases as the copy number of plasmids carrying the Esp1396l RM system is increased. However, since increased plasmid copy number leads to both increased absolute intracellular REase and MTase levels and decreased MTase to REase ratio, it is impossible to determine which factor determines resistance/susceptibility to infection. By controlled expression of Esp1396I MTase or REase genes in cells carrying the Esp1396I system, we show that a shift in the MTase to REase ratio caused by overproduction of MTase or REase leads, respectively, to decreased or increased protection from infection. Consistently, due to stochastic variation of MTase and REase amount in individual cells, bacterial cells that are productively infected by bacteriophage have significantly higher MTase to REase ratios than cells that ward off the infection. Our results suggest that cells with transiently increased MTase to REase ratio at the time of infection serve as entry points for unmodified phage DNA into protected bacterial populations.
Pangenomics provides insights into the role of synanthropy in barn swallow evolution
Authors: Secomandi Simona , Gallo Guido Roberto , Sozzoni Marcella , Iannucci Alessio , Galati Elena , Abueg Linelle , Balacco Jennifer , Caprioli Manuela , Chow William , Ciofi Claudio , Collins Joanna , Fedrigo Olivier , Ferretti Luca , Fungtammasan Arkarachai , Haase Bettina , Howe Kerstin , Kwak Woori , Lombardo Gianluca , Masterson Patrick , Messina Graziella , Møller Anders Pape , Mountcastle Jacquelyn , Mousseau Timothy A. , Ferrer-Obiol Joan , Olivieri Anna , Rhie Arang , Rubolini Diego , Saclier Marielle , Stanyon Roscoe , Stucki David , Thibaud-Nissen Françoise , Torrance James , Torroni Antonio , Weber Kristina , Ambrosini Roberto , Bonisoli-Alquati Andrea , Jarvis Erich D. , Gianfranceschi Luca , Formenti Giulio
Published: March 2022

Insights into the evolution of non-model organisms are often limited by the lack of reference genomes. As part of the Vertebrate Genomes Project, we present a new reference genome and a pangenome produced with High-Fidelity long reads for the barn swallow Hirundo rustica. We then generated a reference-free multialignment with other bird genomes to identify genes under selection. Conservation analyses pointed at genes enriched for transcriptional regulation and neurodevelopment. The most conserved gene is CAMK2N2, with a potential role in fear memory formation. In addition, using all publicly available data, we generated a comprehensive catalogue of genetic markers. Genome-wide linkage disequilibrium scans identified potential selection signatures at multiple loci. The top candidate region comprises several genes and includes BDNF, a gene involved in stress response, fear memory formation, and tameness. We propose that the strict association with humans in this species is linked with the evolution of pathways typically under selection in domesticated taxa.
GLOBAL HOST RESPONSES TO THE MICROBIOTA AT SINGLE CELL RESOLUTION IN GNOTOBIOTIC ZEBRAFISH
Authors: Massaquoi Michelle S. , Kong Garth , Chilin Daisy , Hamilton Mary K. , Melancon Ellie , Eisen Judith S. , Guillemin Karen
Published: March 2022

Resident microbes are a feature of vertebrate animals that influence diverse aspects of their biology from tissue development to metabolism. Here we describe transcriptional responses to the microbiota across all the cells of a model developing vertebrate, the larval zebrafish. By performing single cell transcriptomic analysis of whole germ free and conventionalized larvae, we show that the impacts of the microbiota are sensed by all major organ systems but that responses are highly specific to different cell types. The presence of microbiota stimulates the expansion of progenitor-like cells in epithelial tissues and increases proliferation gene expression in progenitor-like cell populations of the immune and nervous systems. Across many cell types, including enterocytes, immune cells, and neurons, the microbiota upregulates expression of genes involved in microbial responses, cell type-specific activities, and cell type-specific deployment of ATP metabolism genes. These combined transcriptional patterns demonstrate how the microbiota simultaneously modulate cellular immune and metabolic programs. The impacts of the microbiota on tissue development are illustrated by the exocrine pancreas, which in the absence of the microbiota is smaller and composed of uniformly differentiated acinar cells. The presence of the microbiota results in exocrine pancreas enlargement and heterogeneous cellular expression of digestive enzyme and secretion genes, demonstrating how the microbiota promotes plasticity in tissue development and function. This single cell transcriptional dataset demonstrates the impacts of the microbiota on vertebrate development across the body and provides a foundation for dissecting cell type specific responses to microbial consortia members or molecules.

Animal development proceeds in the presence of intimate microbial associations, but the extent to which different host cells across the body respond to resident microbes remains to be fully explored. Using the vertebrate model organism, the larval zebrafish, we assessed transcriptional responses to the microbiota across the entire body at single cell resolution. We find that cell types across the body, not limited to tissues at host-microbe interfaces, respond to the microbiota. Responses are cell-type specific, but across many tissues the microbiota enhances cell proliferation, increases metabolism, and stimulates a diversity of cellular activities, revealing roles for the microbiota in promoting developmental plasticity. This work provides a resource for exploring transcriptional responses to the microbiota across all cell types of the vertebrate body and generating new hypotheses about the interactions between vertebrate hosts and their microbiota.
Lassa virus glycoprotein nanoparticles elicit a neutralizing antibody that defines a new site of vulnerability
Authors: Brouwer Philip J.M. , Antanasijevic Aleksandar , Ronk Adam J. , Müller-Kräuter Helena , Watanabe Yasunori , Claireaux Mathieu , Lloyd Nicole M. , Bijl Tom. P. L. , Perrett Hailee R. , Steijaert Thijs , Burger Judith A. , van Haaren Marlies M. , Sliepen Kwinten , van Gils Marit J. , Crispin Max , Strecker Thomas , Bukreyev Alexander , Ward Andrew B. , Sanders Rogier W.
Published: March 2022

Lassa virus is endemic in large parts of West Africa and causes a hemorrhagic fever. Recent years have seen several serious outbreaks of Lassa fever with high mortality rates. A vaccine to curtail infection is urgently needed. The development of a recombinant protein vaccine has been hampered by the instability of soluble Lassa virus glycoprotein complex (GPC) trimers, which disassemble into monomeric subunits after expression. Here we use two-component protein nanoparticles to stabilize GPC in a trimeric conformation and present twenty prefusion GPC trimers on the surface of an icosahedral nanoparticle. Cryo-EM studies of assembled GPC nanoparticles demonstrated a well-ordered structure and yielded a high-resolution structure of an unliganded GPC. These nanoparticles induced potent humoral immune responses in rabbits and protective immunity against a lethal Lassa virus challenge in guinea pigs. We isolated a neutralizing antibody which was mapped to the putative receptor-binding site, revealing a novel site of vulnerability on GPC.
Systemic ablation of Camkk2 impairs metastatic colonization and improves insulin sensitivity in TRAMP mice: Evidence for cancer cell-extrinsic CAMKK2 functions in prostate cancer
Authors: Pulliam Thomas L. , Awad Dominik , Han Jenny J. , Murray Mollianne M. , Ackroyd Jeffrey J. , Goli Pavithr , Oakhill Jonathan S. , Scott John W. , Ittman Michael M. , Frigo Daniel E.
Published: March 2022

Despite early studies linking calcium-calmodulin protein kinase kinase 2 (CAMKK2) to prostate cancer cell migration and invasion, the role of CAMKK2 in metastasis in vivo remains unclear. Moreover, while CAMKK2 is known to regulate systemic metabolism, whether CAMKK2’s effects on whole body metabolism would impact prostate cancer progression and/or related comorbidities is not known. Here, we demonstrate that germline ablation of Camkk2 slows, but does not stop, primary prostate tumorigenesis in the TRansgenic Adenocarcinoma Mouse Prostate (TRAMP) genetic mouse model. Consistent with prior epidemiological reports supporting a link between obesity and prostate cancer aggressiveness, TRAMP mice fed a high-fat diet exhibited a pronounced increase in the colonization of lung metastases. We demonstrated that this effect on metastatic spread was dependent on CAMKK2. Notably, diet-induced lung metastases exhibited a highly aggressive neuroendocrine phenotype. Concurrently, Camkk2 deletion improved insulin sensitivity in the same mice. Histological analyses revealed that cancer cells were smaller in the TRAMP;Camkk2-/- mice compared to TRAMP;Camkk2+/+ controls. Given the differences in circulating insulin levels, a known regulator of cell growth, we hypothesized that systemic CAMKK2 could promote prostate cancer cell growth and disease progression in part through cancer cell-extrinsic mechanisms. Accordingly, host deletion of Camkk2 impaired the growth of syngeneic murine prostate tumors in vivo, confirming nonautonomous roles for CAMKK2 in prostate cancer. Cancer cell size and mTOR signaling was diminished in tumors propagated in Camkk2-null mice. Together, these data indicate that, in addition to cancer cell-intrinsic roles, CAMKK2 promotes prostate cancer progression via tumor-extrinsic mechanisms. Further, we propose that CAMKK2 inhibition may also help combat common metabolic comorbidities in men with advanced prostate cancer.
ACSF2: A MEDIUM-CHAIN ACYL-CoA SYNTHETASE WITH A POTENTIAL ROLE IN NEURONAL DIFFERENTIATION
Authors: Maiguel Dony , Morita Masashi , Pei Zhengtong , Jia Zhenzhen , Watkins Paul A.
Published: March 2022

By activating fatty acids to their CoA derivatives, acyl-CoA synthetases (ACS) play an essential role in fatty acid metabolism. We previously identified ACSF2 as an ACS that was phylogenetically distinct from known families of short-chain, medium-chain, long-chain, very long-chain, and bubblegum ACSs. Functionally, ACSF2 preferentially activated medium-chain fatty acids. In this work, we provide further characterization of this unique ACS. ACSF2 mRNA expression was found in most tissues, although immunohistochemical analysis revealed differences in protein expression between various cell types in each tissue. Endogenous ACSF2 was found in the Golgi region in Neuro2a and P19 cells, and disruption of the Golgi in Neuro2a cells with nocodazole disrupted ACSF2 localization. In contrast, MA-10, HepG2, and skin fibroblasts had a mitochondrial ACSF2 localization. ACSF2 activated saturated fatty acids containing 6 to 10 carbons when overexpressed in COS-1 cells. The Kmapp for C10:0 was 24.4 μM and Vmaxapp was 385 nmol/20min/mg COS cell protein. Knockdown by RNA interference revealed that ACSF2 was responsible for most of the medium-chain ACS activity in Neuro2a cells. A lysine residue critical for activity in bacterial short-chain ACSs was found in ACSF2, and mutation of this residue to alanine abolished enzyme activity. Neurite outgrowth results when Neuro2a cells are induced to differentiate with retinoic acid, and ACSF2 migrated to nodes and points of neurite-neurite contact along with the presynaptic marker, synaptophysin. ACSF2-deficient Neuro2a cells showed significantly blunted neurite outgrowth in response to retinoic acid. These results suggest that this medium-chain ACS may play an important role in neuronal development.
Natural variation identifies new effectors of water use efficiency inArabidopsis
Authors: Bhaskara Govinal Badiger , Lasky Jesse R , Razzaque Samsad , Zhang Li , Haque Taslima , Bonnette Jason E , Civelek Guzide Zeynep , Verslues Paul E , Juenger Thomas E
Published: March 2022

Water use efficiency (WUE) is the ratio of biomass gained per unit of water consumed; thus, it can be altered by genetic factors that affect either side of the ratio. In the present study, we exploited natural variation for WUE as an unbiased approach to discover loci affecting either biomass accumulation or water use as factors affecting WUE. Genome-wide association (GWAS) analysis using integrated WUE measured through carbon isotope discrimination (δ13C) ofArabidopsis thalianaaccessions identified genomic regions associated with WUE. Reverse genetic analysis of 70 candidate genes selected based on the GWAS results and transcriptome data identified 25 genes affecting WUE as measured by gravimetric and δ13C analyses. Mutants of four genes had higher WUE than wild type, while mutants of the other 21 genes had lower WUE. The differences in WUE were caused by either altered biomass or water consumption (or both). Stomatal density was not a primary cause of altered WUE in these mutants. Leaf surface temperatures indicated that transpiration differed for mutants of 16 genes, but generally biomass accumulation had greater effect on WUE. The genes we identified are involved in diverse cellular processes including hormone and calcium signaling, meristematic activity, photosynthesis, flowering time, leaf/vasculature development, and cell wall composition; however, none of them had been previously linked to WUE or traits related to plant water relations. Thus, our study successfully identified new effectors of WUE that can be used to understand the genetic basis of WUE and improve crop productivity.
Monitoring of urban ecological environment including air quality using satellite imagery
Authors: Wang Yuan , Cai Guoyin , Yang Liuzhong , Zhang Ning , Du Mingyi
Published: March 2022

Rapid urbanisation has highlighted problems in the urban ecological environment and stimulated research on the evaluation of urban environments. In previous studies, key factors such as greenness, wetness, and temperature were extracted from satellite images to assess the urban ecological environment. Although air pollution has become increasingly serious as urbanisation proceeds, information on air pollution is not included in existing models. The Sentinel-5P satellite launched by the European Space Agency in 2017 is a reliable data source for monitoring air quality. By making full use of images from Landsat 8, Sentinel-2A, and Sentinel-5P, this work attempts to construct a new remote sensing monitoring index for urban ecology by adding air quality information to the existing remote sensing ecological index. The proposed index was tested in the Beijing metropolitan area using satellite data from 2020. The results obtained using the proposed index differ greatly in the central urban region and near large bodies of water from those obtained using the existing remote sensing monitoring model, indicating that air quality plays a significant role in evaluating the urban ecological environment. Because the model constructed in this study integrates information on vegetation, soil, humidity, heat, and air quality, it can comprehensively and objectively reflect the quality of the urban ecological environment. Consequently, the proposed remote sensing index provides a new approach to effectively monitoring the urban ecological environment.
Deep selection shapes the intragenomic diversity of rRNA genes
Authors: Sultanov Daniel , Hochwagen Andreas
Published: March 2022

Ribosome biogenesis in eukaryotes is supported by hundreds of ribosomal RNA (rRNA) gene copies that are encoded in the ribosomal DNA (rDNA). The multiple copies of rRNA genes are thought to have low sequence diversity within one species. Here, we present species-wide rDNA sequence analysis inSaccharomyces cerevisiaethat challenges this view. We show that rDNA copies in this yeast are far from homogeneous, both among and within isolates, and that many variants avoided fixation or elimination over evolutionary time. The sequence diversity landscape across the rDNA shows clear functional stratification, suggesting different copy-number thresholds for selection that shape rDNA diversity. Notably, nucleotide variants in the most conserved rDNA regions are sufficiently deleterious to exhibit signatures of purifying selection even when present in only a small fraction of rRNA gene copies. Our results portray a complex evolutionary landscape that shapes rDNA sequence diversity within a single species and reveal unexpectedly deep purifying selection of multi-copy genes.
An ALS-associated KIF5A mutant forms oligomers and aggregates and induces neuronal toxicity
Authors: Nakano Juri , Chiba Kyoko , Niwa Shinsuke
Published: March 2022

KIF5A is a kinesin superfamily motor protein that transports various cargos in neurons. Mutations inKif5acause familial amyotrophic lateral sclerosis (ALS). These ALS mutations are in the intron ofKif5aand induce mis-splicing of KIF5A mRNA, leading to splicing out of exon 27, which in human KIF5A encodes the cargo-binding tail domain of KIF5A. Therefore, it has been suggested that ALS is caused by loss of function of KIF5A. However, the precise mechanisms regarding how mutations in KIF5A cause ALS remain unclear. Here, we show that an ALS-associated mutant of KIF5A, KIF5A(Δexon27), is predisposed to form oligomers and aggregates in cultured mouse cell lines. Interestingly, purified KIF5A(Δexon27) oligomers showed more active movement on microtubules than wild type KIF5Ain vitro. Purified KIF5A(Δexon27) was prone to form aggregatesin vitro. Moreover, KIF5A(Δexon27)-expressingCaenorhabditis elegansneurons showed morphological defects. These data collectively suggest that ALS-associated mutations of KIF5A are toxic gain-of-function mutations rather than simple loss-of-function mutations.
Safety assessment of insecticidal proteins: A case study utilizing His-tagged protein to determine the safety of Mpp75Aa1.1, a new ETX_MTX2 protein that controls western corn rootworm
Authors: Wang Cunxi , Bean Gregory J. , Chen Chun Ju , Kessenich Colton R. , Peng Jiexin , Visconti Nicolo R. , Milligan Jason S. , Moore Robert G. , Tan Jianguo , Edrington Thomas C. , Li Bin , Giddings Kara S. , Bowen David , Luo Jinhua , Ciche Todd , Moar William J.
Published: March 2022

The recently discovered insecticidal protein Mpp75Aa1.1 from Brevibacillus laterosporus is one member of the ETX_MTX family of beta-pore forming proteins (β-PFPs) expressed in genetically modified (GM) maize to control western corn rootworm (WCR; Diabrotica virgifera virgifera LeConte). In this paper, bioinformatic analysis establishes that although Mpp75Aa1.1 shares varying degrees of similarity to members of the ETX_MTX2 protein family, it is unlikely to contribute to any allergenic, toxic, or otherwise adverse biological effects. The safety of Mpp75Aa1.1 is further supported by a weight of evidence including evaluation of history of safe use (HOSU) of ETX_MTX2 proteins. Assessments using either purified Mpp75Aa1.1 protein or a poly-histidine-tagged (His-tagged) variant of the Mpp75Aa1.1 protein demonstrate that both forms of the protein are heat labile at temperatures at or above 55 °C, degraded by gastrointestinal proteases within 0.5 min, and have no adverse effects in acute mouse oral toxicity studies at a dose level of 1920 or 2120 mg/kg body weight. Results also indicate that the domain-based protein characterization should be considered as part of the weight of evidence for the safe consumption of food or feed. Furthermore, these results support the use of His-tagged proteins as suitable surrogates for assessing the safety of their non-tagged parent proteins.
Glial dysregulation in human brain in Fragile X-related disorders
Authors: Dias Caroline M. , Talukdar Maya , Akula Shyam K. , Walsh Katherine , Walsh Christopher A.
Published: March 2022

Abstract

While large trinucleotide repeat expansions at the FMR1 locus cause Fragile X Syndrome (FXS), smaller “premutations” are associated with the late-onset condition Fragile X-associated tremor/ataxia syndrome (FXTAS), which shows very different clinical and pathological features, with no clear molecular explanation for these marked differences. One prevailing theory posits that the premutation uniquely causes neurotoxic increases in FMR1 mRNA (i.e., 4-8-fold increases), but evidence to support this hypothesis is largely derived from analysis of peripheral blood. We applied single- nucleus RNA-sequencing to post-mortem frontal cortex and cerebellum from 9 individuals with Fragile X mutations as well as age and sex matched controls (n=6) to assess cell-type specific molecular neuropathology. We found robust reduction of FMR1 mRNA in FXS as expected, with modest but significant upregulation (∼1.3 fold) of FMR1 in glial clusters associated with premutation expansions. In premutation cases we identified alterations in glia number in cortex and cerebellum. Differential expression analysis demonstrated altered cortical oligodendrocyte development, while gene ontology analysis revealed alterations in neuroregulatory roles of glia, such as glial modulation of neurotransmission and synaptic structure. We identified significant enrichment of known FMR1 protein target genes in differentially expressed gene lists in FXS as well as the premutation, suggesting FMR1 protein target pathways may represent a shared source of dysfunction in both conditions despite opposite FMR1 mRNA changes. These findings challenge existing dogma regarding FXTAS and implicate glial dysregulation as a critical facet of premutation pathophysiology, representing novel therapeutic targets directly derived from the human condition.
Does the perception of organizational justice determine employees' affective commitment? The mediating role of organizational trust
Authors: Malla Sweta Srivastava , Malla Sanjay
Published: March 2022

Purpose

The purpose of this paper is to identify select antecedents for affective commitment (AC) and whether organizational trust (OT) mediates the relationship between dimensions of organizational justice (OJ) and AC.

Design/methodology/approach

Using a survey-based design, data were collected from employees across industry verticals who were working in various organizations and participated in an executive management program at an Indian management institute. Analysis was carried out using a partial least square-based package of ADANCO 2.2.1.

Findings

In line with cross-cultural research, the results indicated that distributive and informational justice contribute toward employees' AC. In addition, the findings confirmed that OT mediates the justice-AC relationship for distributive, interpersonal and informational justice. The role of job satisfaction (JS) as an important antecedent was also identified.

Practical implications

The evidence-based findings, as represented in importance–performance map analysis (IPMA), will help the organizational leaders understand the factors responsible for employees' AC. Leaders will appreciate the important role played by justice, fairness and OT in enhancing commitment. The importance of JS was also highlighted.

Originality/value

This is a pioneering study to provide empirical evidence of the moderating effect of trust on OJ and the AC relationship. It is also one of the first to consider all of the four dimensions of OJ as possible antecedents for AC in a non-Western context.
Univ Manufacturers: key account management for B2B
Authors: Dash Sadhna , Dam Leena B. , Pillai Deepa , Kumar Jitender
Published: March 2022

Learning outcomes

At the end of the case discussion, students would be able to: design key account selection criteria for the organization’s vast clients; analyse the application of key account management (KAM) strategies in a business-to-business (B2B) segment for revenue growth for a medium-scale enterprise; recognize the significance of KAM in a B2B space for a scale enterprise; and assess the proficiency of Univ Manufacturers (UM) for KAM in addressing the existing challenges and managing business growth.

Case overview/synopsis

Tarun, the proprietor of UM, has recently received two big orders, one from Ram Enterprise, a long-standing client since 2011 of INR 2m (10% profit margin) and another order from a new client based in Chennai, a growing pharmaceutical products company, of order size of INR 2.3m (15% profit margin). Both the orders were required to be completed within 15 days. The new client with higher value and better returns could help UM enter the south India market, whereas business from the existing client was also profitable. Despite both orders being necessary for business survival and expansion, fulfilling them on schedule posed a huge challenge. Tarun wanted to fulfil both orders. He knew similar situations might arise in future. He advocated prioritizing customers, which made him contemplate KAM. On what basis he should categorize his customers was a big question. Tarun felt that it was time for UM to strategize relationship management with his customers. He wanted to optimize the partnerships. Tarun knew he wanted to introduce KAM, but was firm-level internal capabilities were enough for key account execution. What would be the feasible outcomes if KAM is applied at UM? What must he do to prevent such situations in the future?

Complexity academic level

This case can be used in B2B marketing and sales management courses. The dilemma can be explained as part of a marketing course for postgraduate and executive programs.

Supplementary materials

Teaching notes are available for educators only.

Subject code

CSS 8: Marketing.
Robots can’t take my job: antecedents and outcomes of Gen Z employees’ service robot risk awareness
Authors: Yu Heyao , Shum Cass , Alcorn Michelle , Sun Jie , He Zhaoli
Published: March 2022

Purpose

There has been a dramatic increase in the adoption of service robots in hotels, potentially replacing the human workforce. Drawing on Social Amplification of Risk Framework, this study aims to examine the moderating effect of transformational leadership on the indirect relationships between Gen Z employees’ tech-savviness and social skills on industry turnover intention via service robot risk awareness (SRRA).

Design/methodology/approach

This study collected two-wave time-lagged multilevel data of 281 frontline Gen Z hotel employees from 54 departments in China. Participants were asked to rate their tech-savviness, social skills and SRRA in the first survey. They rated their supervisor’s transformational leadership and industry turnover intention one week later.

Findings

Multilevel path analysis results showed SRRA mediates the negative indirect relationship of Gen Z employee’s tech-savviness and social skills on industry turnover intention. Transformational leadership weakened the positive effect of SRRA on industry turnover intention.

Originality/value

This study contributes to the growing literature on service robots by investigating the antecedents and outcomes of employees’ SRRA. To the best of the authors’ knowledge, it is one of the first empirical studies investigating the role of leadership to mitigate the negative consequences of employee’s SRRA. Managers can use the results of this study to implement training programs and ensure that employees and service robots successfully coexist in the workplace.
Examining revisit intention from the basic foundation of Islam: the role of halal destination attributes and perceived value
Authors: Mursid Ali
Published: March 2022

Purpose

The rapid development of Muslim travelers traveling to halal destinations stimulated this study to elucidate revisit intention based on the fundamental aspects of Muslim behavior, namely, Islamic belief and practice. First, the purpose of this study is to shed light on how Islamic belief affects the Islamic practice of Muslim travelers. Second, it verifies the effects of Islamic practice on halal destination attributes and destination attractiveness. Third, this study also identifies halal destination attributes that affect destination attractiveness, functional value and emotional value. Fourth, it further explores the effects of destination attractiveness on both functional value and emotional value. Finally, this study examines how both functional value and emotional value affect revisit intention.

Design/methodology/approach

The respondents of this study are Muslim travelers who visited one of the four favorite halal destinations in Indonesia from 2019 to 2020. Using purposive sampling methods, this study successfully collected responses from 317 respondents, and then the data were analyzed using structural equation modeling.

Findings

The results of this study demonstrate, first, Islamic belief positively and significantly affects Islamic practice. Second, Islamic practice positively and significantly impacts halal destination attributes and destination attractiveness. Third, halal destination attributes positively and significantly affect destination attractiveness, as well as both functional value and emotional value. Fourth, destination attractiveness positively and significantly impacts both functional value and emotional value. Finally, this study that found only emotional value positively and significantly impacts revisit intention, while functional value does not successfully increase revisit intention.

Originality/value

This study contributes to the crucial aspects of Muslim travelers’ behavior based on the fundamental of Islamic teaching include Islamic belief and practice. Moreover, this framework also contributes to the explain Muslim travelers revisit intention to halal destination using the means-ends theory.
Consumer purchase of halal certified product: a quantitative systematic literature review
Authors: Fauzi Muhammad Ashraf
Published: March 2022

Purpose

This study aims to review relevant studies concerning consumer purchase of halal-certified products. A total of 35 studies related to the consumer purchasing behavior of halal-certified products in top-tier journals have been identified according to the recommended systematic literature review methodology.

Design/methodology/approach

A systematic literature review approach was implemented to examine, summarize and finally interpret the relevant research stream pertaining to consumer purchase of halal-certified products.

Findings

There are five research streams extracted from this systematic review, halal study context, theories adapted, covariance-based-structural equation modeling (SEM) vs partial least square-SEM, Muslim vs nonMuslim consumer and role of religiosity. Despite the growing interest in the quantitative approach in consumer purchase behavior in halal-certified products, scholars in halal consumer studies must have a greater extent of work. These include incorporating diverse theories in the framework, an advanced SEM approach, and relevant determinants to capture consumer purchasing of halal-certified products in the highly anticipated and profitable Muslim market.

Research limitations/implications

Findings would help researchers in halal studies to consider and contemplate critical issues, according to the research stream presented in this review.

Originality/value

To the best of the authors’ knowledge, this study is the first review of quantitative studies on consumer purchases of halal-certified products.
Do ownership structures and governance attributes matter for corporate sustainability reporting? An examination in the Indian context
Authors: Kumar Kishore , Kumari Ranjita , Nandy Monomita , Sarim Mohd , Kumar Rakesh
Published: March 2022

Purpose

Based on the essence of the legitimacy and agency theories, this study empirically investigates the influence of corporate governance attributes and ownership structures on sustainability reporting of companies listed on the National Stock Exchange (NSE), India.

Design/methodology/approach

The study is based on panel data regression analysis of sustainability reporting practices of 53 environmentally sensitive companies drawn from NIFTY100 Index at NSE. All data pertaining to sustainability information disclosure, ownership structure and corporate governance characteristics were sourced from sustainability report, business responsibility report, annual report and Centre for Monitoring Indian Economy (CMIE) database for the years 2015–2019.

Findings

The empirical result reveals that sustainability reporting scenario has been consistently improving in India. This study documents that government ownership and frequency of board meetings are the two most important factors significantly influencing the extent of sustainability information disclosure of companies. However, the present study failed to find any significant impact of board size and big4 auditing on sustainability reporting practices. Unexpectedly, a higher number of independent directors does not improve sustainability disclosure of companies in India.

Originality/value

This study is one of the first studies to investigate how the nature of ownership and corporate governance characteristics contribute to or impede sustainability reporting practices of companies in India. This study offers important insights to regulators, practitioners and investors to analyze whether sustainability disclosure of companies is influenced by corporate governance attributes. It also provides a perspective for regulators and corporate strategists to assess the impact of recent corporate governance reforms in India and consider how corporate governance mechanism can be used to improve sustainability reporting practices.
A review of the long-term care policies under COVID-19 in Thailand’s aging society: implications for ASEAN countries
Authors: Tejativaddhana Phudit , Chuakhamfoo Nalinee Nakittipha , Hue Vo Man Thi
Published: March 2022

Purpose

This paper aims to explore the aging society situation, long-term care (LTC) policy preparation, COVID-19’s impact on older people, and post-pandemic preparations in Thailand and the implications for The Association of Southeast Asian Nations (ASEAN) countries.

Design/methodology/approach

Online databases from international, national, academic agencies and SCOPUS database from January 2019 to July 2021 were utilized for analysis. Relevant literature and data were selected for review.

Findings

The evidence suggests that the proportion of the aging population is increasing due to declined fertility and rising life expectancy. Current and future demand for effective healthcare in ASEAN will be better achieved with policies like the Universal Health Coverage and Primary Health Care system. While some countries, specifically Thailand, are developing and expanding their LTC policies, some concerns regarding the active aging policy remain. Most ASEAN countries are using public domain for LTC policies. However, the COVID-19 pandemic has posed a major challenge in implementing LTC and affected the vulnerable aging population in many aspects, including social protection issues in Thailand.

Originality/value

With the support from international organizations, ASEAN countries have framed several policy strategies in response to the increasing aging population, such as providing more LTC in the community. The unexpected challenges from the COVID-19 pandemic compel policymakers to consider resource allocations and community-based services. On the positive side, as the pandemic has made the vulnerable group exposed, social protection issues have been brought to the forefront of the political debate and called for an appropriate policy response.
Cyclic di‐GMP triggers the hypoxic adaptation of Mycobacterium bovis through a metabolic switching regulator ArgR
Authors: Zhang Jiaxun , Hu Lihua , Zhang Hua , He Zheng‐Guo
Published: March 2022

During infection, intracellular pathogens inevitably face the pressure of hypoxia. Mycobacterium tuberculosis and Mycobacterium bovis represent two typical intracellular bacteria, but the signalling pathway of their adaptation to hypoxia remains unclear. Here, we report a new mechanism of the hypoxic adaptation in M. bovis driven by the second messenger molecule c‐di‐GMP. We found that c‐di‐GMP was significantly accumulated in bacterial cells under hypoxic stress and blocked the inhibitory activity of ArgR, an arginine metabolism gene cluster regulator, which increased arginine synthesis and slowed tricarboxylic acid cycle (TCA cycle) and aerobic respiration. Meanwhile, c‐di‐GMP relieved the self‐inhibition of argR expression, and ArgR could interact with the nitrite metabolic gene regulator Cmr, promoting the positive regulation of Cmr and, thereafter, the nitrite respiration. Consistently, c‐di‐GMP significantly induced the expression of arginine and nitrite metabolism gene clusters and increased the mycobacterial survival ability under hypoxia. Therefore, we found a new function of the second messenger molecule c‐di‐GMP and characterized ArgR as a metabolic switching regulator that can coordinate the c‐di‐GMP signal to trigger hypoxic adaptation in mycobacteria. Our findings provide a potential new target for blocking the life cycle of M. tuberculosis infection.
Oh No! Puncture!
Authors: Fletcher Michael
Published: March 2022

Oh no! Puncture! Plus the solution to “How many balls in the bag”. By Michael Fletcher.Oh no! Puncture! Plus the solution to “How many balls in the bag”. By Michael Fletcher.
Covid Lockdowns in the UK: Estimating Their Effects on Transmission
Authors: Prestige Emily , Stander Julian , Wei Yinghui
Published: March 2022

UK citizens have lived through three lockdowns over the course of the Covid-19 pandemic. What effect have these restrictions had on the transmission of the virus? Emily Prestige, Julian Stander and Yinghui Wei investigate
What is Cox's Proportional Hazards Model?
Authors: Tibshirani Robert
Published: March 2022

Robert Tibshirani gives an overview of one of David Cox's most widely applied ideas, for which he was awarded the International Prize in Statistics in 2017
On Sir David Cox's Publications
Authors: Borja Mario Cortina , Stander Julian , Sebastiani Giovanni
Published: March 2022

Mario Cortina Borja, Julian Stander, and Giovanni Sebastiani analyse some of the tens of thousands of citations for the hundreds of papers produced by David Cox in a publishing career that spanned more than 70 years
“I Want to be Ready to Answer Questions we Don't Yet Know we Need to Know”: An Interview with Alison Pritchard
Authors: Tarran Brian
Published: March 2022

The deputy national statistician and director general for data capability at the UK Office for National Statistics talks to Brian Tarran about putting new data sources to work, survey transformation, and the shape of the data landscape post-Covid
One More Thing...
Authors: Leach Michael
Published: March 2022

A prose poem for Florence Nightingale