bluuebunny/crossref_metadata_2025 huggingface dataset:
Trends, changes and determinants of medical attention received before death among deceased adults in India: Evidence from pooled cross-sectional survey data (2004-2018)
Authors: Akhtar Saddaf Naaz , Saikia Nandita
Published: May 2022

Background

India is coping an ageing population without an adequate medical care service. However, trends, changes and factors of receiving medical attention before death remains unknown. Therefore, we intend to examine the trends, changes and determinants of medical attention received before death among the deceased adults in India.

Methods

Our study has used a nationally representative pooled-cross-sectional survey data from2004 to 2017-18. We performed univariate, bivariate and multivariate analyses. We have examined the trends from 2004 to 2017-18. Then we estimated the absolute changes in medical attention rate (MAR) received before death by the 45+ deceased adults for the time period between 2004-2005 & 2017-2018 and 2014 & 2017-2018. Lastly, we applied binary logistic regression analysis to identify the effect of significant predictor variables on the medical attention received before death.

Results

Our study has revealed that there has been marginal increase (0.74%) in the overall trend in medical attention received before death among 45+ adults from 2004 to 2017-18. Females, rural residence are showing negative change in receiving medical attention. However, our finding has showed that young-old, middle-old and oldest-old have significantly lower odds of receiving medical attention compared to middle-aged adults. Surprisingly, our result has revealed that Southern and Western regions are found to have significantly less likely to receive medical attention before death among deceased adults which is a striking finding.

Conclusions

Therefore, there is an urgent need to establish a primary health center at community level that play an important role in order to meet the comprehensive requirements of middle-aged and older adults in India. It would be helpful to develop and execute the health policies and programs that would enable India to achieve healthy aging in India at national and subnational levels, as it is a key element of public health challenges.
Socio-economic and demographic determinants of all-cause, main-cause and sub-cause mortality among 45+ adults: Evidence from Longitudinal Ageing Study in India
Authors: Akhtar Saddaf Naaz , Saikia Nandita
Published: May 2022

Background

Studies on cause-specific mortality among 45+ adults remain unknown in Indian settings. However, understanding the epidemiology of this public health problem can guide policy development for premature and old-age mortality prevention. Therefore, we intend to examine the socio-economic and demographic determinants of all-cause, main-cause and sub-cause mortality among 45+ adults in India.

Methods

We adopted the cross-sectional data from the Longitudinal Ageing Study of India (LASI-wave-I) conducted in 2017-18. We performed descriptive, bivariate and multivariate analysis.

Results

Females, young-old, middle-old, oldest-old showed lower odds of all-cause, main-cause and sub-cause mortality than males and middle-aged adults. Central region showed significantly greater odds of all-cause mortality risks than Northern region. Christians have lower odds of all-cause mortality risk than Hindus. With the increase in household income, the odds of NCD-related mortality risks also increase. Central (OR=1.54; p<0.01), Eastern (OR=1.28; p<0.01) and Western regions (OR=1.18; p<0.1) have greater odds of non-NCD-related mortality-risks than Northern regions. Urban residence (OR=01.34; p<0.05) has significantly higher odds of CVD-related mortality-risk than rural residence. OBC (OR=0.59; p<0.01) has lower odds of cancer-related mortality risks than general caste. North-eastern region (OR=2.00; p<0.01) has significantly greater odds of diabetes-related mortality risks.

Conclusions

The premature and old-age mortality components would help formulate and execute integrated interventions aimed at specific age groups and causes-specific mortality. Medical care, pollution management, environmental control, more involvement in physical activity and a healthy lifestyle could assist in lowering the CVD, cancer & diabetes-related mortality. A new strategy is needed to avoid future deaths and burdens from ageing-related CVD.

Highlights

This is the first-ever study that provides the socio-economic and demographic factors association of all-cause, main-cause and sub-cause mortality by characteristics among 45+ adults in India.

Females, young-old, middle-old, and oldest-old showed lower odds of all-cause, main-cause and sub-cause mortality than males and middle-aged adults.

With the increase in household income, the odds of NCD-related mortality risks also increase.

Urban residents have significantly higher odds of CVD-related mortality risk than rural residents.

OBC has lower odds of cancer-related mortality risks than general caste.
An improved TurboID pipeline in C. elegans by biochemical depletion of endogenously biotinylated carboxylases
Authors: Artan Murat , Hartl Markus , Chen Weiqiang , de Bono Mario
Published: May 2022

Proximity-dependent protein labeling provides a powerful in vivo strategy to characterize the interactomes of specific proteins. We previously optimized a proximity labeling protocol for C. elegans using the highly active biotin ligase TurboID. A significant constraint on the sensitivity of TurboID is the presence of abundant, endogenously biotinylated proteins that take up bandwidth in the mass spectrometer, notably carboxylases that use biotin as a co-factor. In C. elegans, these comprise POD-2/acetyl-CoA carboxylase alpha, PCCA-1/propionyl-CoA carboxylase alpha, PYC-1/pyruvate carboxylase and MCCC-1/methylcrotonyl-CoA carboxylase alpha. We developed ways to remove these carboxylases prior to streptavidin purification and mass spectrometry, by engineering their corresponding genes to add a C-terminal His10 tag. This allows us to deplete them from C. elegans lysates using immobilized metal affinity chromatography (IMAC). To demonstrate the method’s efficacy, we use it to expand the interactome map of the presynaptic active zone protein ELKS-1. We identify many known active zone proteins, as well as previously uncharacterized potentially synaptic proteins. Our approach provides a quick and inexpensive solution to a common contaminant problem in biotin- dependent proximity labeling. The approach may be applicable to other model organisms and will enable deeper and more complete analysis of interactors for proteins of interest.
Molecular evidence of chemical disguise by the socially parasitic spiny ant Polyrhachis lamellidens (Hymenoptera: Formicidae) when invading a host colony
Authors: Iwai Hironori , Mori Masaru , Tomita Masaru , Kono Nobuaki , Arakawa Kazuharu
Published: May 2022

While most ant species establish a colony independently, some socially parasitic ants build the foundation of their colony by invading other ant (host) colonies and utilizing their labour forces. Many socially parasitic ants disguise their cuticular hydrocarbon (CHC) profile, which is also known as nestmate discrimination pheromones, when invading the host colony. Since the strategy of chemical disguise is widespread in socially parasitic ants, elucidating the mechanism of chemical disguise will promote knowledge on the evolutionary history of social parasitism. However, detailed knowledge is still lacking, as the relevant information has only originated from circumstantial evidence, which was obtained from ecological observations. In this study, we investigated the mechanism of chemical disguise in a new queen of a temporary socially parasitic spiny ant (Polyrhachis lamellidens) by measuring its CHC profile, performing a tracing assay with labelled substances, and analysing gene expression levels. First, after rubbing behaviour was observed against the host workers, the CHC profile in P. lamellidens shifted to pronounced peaks that closely resembling that of the host workers. We also observed a reduction in aggressive behaviours by the host ant against P. lamellidens after rubbing behaviour was performed. In addition, P. lamellidens acquired artificially-applied labelling substances from host workers through their rubbing behaviours, while gene expression profiling showed the expression of CHC synthesis-related genes did not change during this behaviour. These results suggest that P. lamellidens directly obtains host CHCs through rubbing behaviour, and these host CHCs enables P. lamellidens to remain disguised during colony invasion.
Lasting consequences on physiology and social behavior following cesarean delivery in prairie voles
Authors: Kenkel William , Kingsbury Marcy , Reinhart John , Cetinbas Murat , Sadreyev Ruslan I. , Carter C. Sue , Perkeybile Allison
Published: May 2022

Cesarean delivery is associated with diminished plasma levels of several ‘birth-signaling’ hormones, such as oxytocin and vasopressin. These same hormones have been previously shown to exert organizational effects when acting in early life. For example, our previous work found a broadly gregarious phenotype in prairie voles exposed to oxytocin at birth. Meanwhile, cesarean delivery has been previously associated with changes in social behavior and metabolic processes related to oxytocin and vasopressin. In the present study, we investigated the long-term neurodevelopmental consequences of cesarean delivery in prairie voles. After cross-fostering, vole pups delivered either via cesarean or vaginal delivery were studied throughout development. Cesarean-delivered pups responded to isolation differently in terms of their vocalizations (albeit in opposite directions in the two experiments), huddled in less cohesive groups under warmed conditions, and shed less heat. As young adults, we observed no differences in anxiety-like or alloparental behavior. However, in adulthood, cesarean-delivered voles of both sexes failed to form partner preferences with opposite sex conspecifics. In a follow-up study, we replicated this deficit in partner-preference formation among cesarean-delivered voles and were able to normalize pair-bonding behavior by treating cesarean-delivered vole pups with oxytocin (0.25 mg/kg) at delivery. Finally, we detected minor differences in regional oxytocin receptor expression within the brains of cesarean-delivered voles, as well as microbial composition of the gut. Gene expression changes in the gut epithelium indicated that cesarean-delivered male voles have altered gut development. These results speak to the possibility of unintended developmental consequences of cesarean delivery, which currently accounts for 32.9% of deliveries in the U.S. and suggest that further research should be directed at whether hormone replacement at delivery influences behavioral outcomes in later life.
A Murine Model of Abductor Insufficiency Accelerates the Development of Hip Osteoarthritis
Authors: Geary Michael B. , Orner Caitlin A. , Shammas Helen , Reuter John M. , Loiselle Alayna E. , Wu Chia-Lung , Giordano Brian D.
Published: May 2022

Osteoarthritis (OA) of the hip is a common and debilitating painful joint disease. A growing body of evidence suggests that there may be an association between periarticular myotendinous pathology and the development of hip OA. Thus, we hypothesized that a murine model of hip OA could be achieved through selective injury of the abductor complex around the hip. C57BL6/J mice were randomized to sham surgery or abductor injury, in which the myotendinous insertion at the third trochanter and greater trochanter were surgically detached. Mice were allowed free, active movement until sacrifice at either 3 weeks or 20 weeks post-injury. Histologic analyses and immunohistochemical staining (IHC) of the femoral head articular cartilage were performed, along with μCT analysis to assess subchondral bone remodeling. We observed that mice receiving abductor injury exhibited significant OA severity with loss of Type II Collagen staining compared to sham control mice at 20 weeks post-surgery, comparable MMPI13 expression was observed between injury and sham groups. No significant differences in subchondral bone were found on μCT after 20 weeks following injury. Our study suggests a link between abductor dysfunction and the development of hip OA, which are common pathomorphologies encountered in routine orthopaedic clinical practice. Further, this novel animal model may provide a valuable tool for future investigations into the pathogenesis and treatment of hip OA.
A bifunctional kinase-phosphatase module integrates mitotic checkpoint and error-correction signalling to ensure mitotic fidelity
Authors: Corno Andrea , Cordeiro Marilia H , Allan Lindsey A , Wei Qian , Harrington Elena , Smith Richard J , Saurin Adrian T.
Published: May 2022

Two major mechanisms have evolved to safeguard genome stability during mitosis: the mitotic checkpoint delays mitosis until all chromosomes have attached to microtubules, and the kinetochore-microtubule error-correction pathway keeps this attachment process free from errors. We demonstrate here that the optimal strength and dynamics of both processes is set by a kinase-phosphatase pair (PLK1-PP2A) that engage in negative feedback on the BUB complex. Uncoupling this homeostatic feedback to skew the balance towards PLK1 produces a strong checkpoint, weak microtubule attachments, and mitotic delays. Conversely, skewing the balance towards PP2A causes a weak checkpoint, strong microtubule attachments, and chromosome segregation errors. The number of MELT motifs on the KNL1 signalling scaffold sets the optimal levels of each enzyme, because engineering KNL1 to recruit too many BUB complexes increases KNL1-PLK1/PP2A levels, and enhances checkpoint/microtubule attachment strength. In contrast, recruiting too few BUB complexes lowers KNL1-PLK1/PP2A, and decreases checkpoint/microtubule attachment strength. Both of these situations are associated with chromosome segregation errors. Together, these data demonstrate how a single bifunctional kinase-phosphatase module integrates two major mitotic processes to help preserve genome stability.
Single Nucleus RNA Sequencing of Human Pancreatic Islets In Vitro and In Vivo Identifies New Gene Sets and Three β-Cell Subpopulations with Different Transcriptional Profile
Authors: Kang Randy B. , Li Yansui , Rosselot Carolina , Zhang Tuo , Siddiq Mustafa , Rajbhandari Prashant , Stewart Andrew F. , Scott Donald K. , Garcia-Ocana Adolfo , Lu Geming
Published: May 2022

Single-cell RNA sequencing (scRNA-seq) has provided valuable insights into human islet cell types and their corresponding stable gene expression profiles. However, this approach requires cell dissociation that complicates its utility in vivo and provides limited information on the active transcriptional status of islet cells. On the other hand, single-nucleus RNA sequencing (snRNA-seq) does not require cell dissociation and affords enhanced information from intronic sequences that can be leveraged to identify actively transcribing genes in islet cell populations. Here, we first sought to compare scRNA-seq and snRNA-seq analysis of human islets in vitro using exon reads or combined exon and intron reads, respectively. Datasets reveal similar human islet cell clusters using both approaches. In the snRNA-seq data, however, the top differentially expressed genes in human islet endocrine cells are not the canonical genes but a new set of non-canonical gene markers including ZNF385D, TRPM3, LRFN2, PLUT (β cells), PTPRT, FAP, PDK4, LOXL4 (α cells), LRFN5, ADARB2, ERBB4, KCNT2 (δ cells) and CACNA2D3, THSD7A, CNTNAP5, RBFOX3 (γ cells). Notably, these markers also accurately define endocrine cell populations in human islet grafts in vivo. Further, by integrating the information from nuclear and cytoplasmic transcriptomes, we identify three β-cell sub-clusters: an active INS mRNA transcribing cluster (β1), an intermediate INS mRNA-transcribing cluster (β2), and a mature INS mRNA rich cluster (β3). These display distinct gene expression patterns representing different biological dynamic states both in vitro and in vivo. Interestingly, the INS mRNA rich cluster (β3) becomes the predominant sub-cluster in vivo. In summary, snRNA-seq analysis of human islet cells is a previously unrecognized tool that can be accurately employed for improved identification of human islet cell types and their transcriptional status in vivo.
Cooperative assembly confers regulatory specificity and long-term genetic circuit stability
Authors: Bragdon Meghan D. J. , Patel Nikit , Chuang James , Levien Ethan , Bashor Caleb J. , Khalil Ahmad S.
Published: May 2022

In eukaryotes, links in gene regulatory networks are often maintained through cooperative self-assembly between transcriptional regulators (TRs) and DNA cis-regulatory motifs, a strategy widely thought to enable highly specific regulatory connections to be formed between otherwise weakly-interacting, low-specificity molecular components. Here, we directly test whether this regulatory strategy can be used to engineer regulatory specificity in synthetic gene circuits constructed in yeast. We show that circuits composed of artificial zinc-finger TRs can be effectively insulated from aberrant misregulation of the host cell genome by using cooperative multivalent TR assemblies to program circuit connections. As we demonstrate in experiments and mathematical models, assembly-mediated regulatory connections enable mitigation of circuit-driven fitness defects, resulting in genetic and functional stability of circuits in long-term continuous culture. Our naturally-inspired approach offers a simple, generalizable means for building evolutionarily robust gene circuits that can be scaled to a wide range of host organisms and applications.
PP6 regulation of Aurora A-TPX2 limits NDC80 phosphorylation and mitotic spindle size
Authors: Sobajima Tomoaki , Kowalczyk Katarzyna M. , Skylakakis Stefanos , Hayward Daniel , Fulcher Luke J. , Neary Colette , Batley Caleb , Kurlekar Samvid , Roberts Emile , Gruneberg Ulrike , Barr Francis A.
Published: May 2022

Amplification of the mitotic kinase Aurora A or loss of its regulator protein phosphatase 6 (PP6) have emerged as drivers of genome instability. Cells lacking PPP6C, the catalytic subunit of PP6, have amplified Aurora A activity and as we show here, enlarged mitotic spindles which fail to hold chromosomes tightly together in anaphase, causing defective nuclear structure. Using functional genomics to shed light on the processes underpinning these changes, we discover synthetic lethality between PPP6C and the kinetochore protein NDC80. We find that NDC80 is phosphorylated on multiple N-terminal sites during spindle formation by Aurora A-TPX2, exclusively at checkpoint-silenced, microtubule-attached kinetochores. NDC80 phosphorylation persists until spindle disassembly in telophase, is increased in PPP6C-knockout cells and, and is Aurora B-independent. An Aurora-phosphorylation-deficient NDC80-9A mutant reduces spindle size and suppresses defective nuclear structure in PPP6C-knockout cells. By regulating NDC80 phosphorylation by Aurora A-TPX2, PP6 plays an important role in mitotic spindle formation and size control, and thus the fidelity of cell division.
Phenotypic variation and quantitative trait loci for resistance to southern anthracnose and clover rot in red clover
Authors: Frey Lea A. , Vleugels Tim , Ruttink Tom , Schubiger Franz X. , Pegard Marie , Skøt Leif , Grieder Christoph , Studer Bruno , Roldán-Ruiz Isabel , Kölliker Roland
Published: May 2022

Red clover (Trifolium pratense L.) is an important forage legume of temperate regions, particularly valued for its high yield potential and its high forage quality. Despite substantial breeding progress during the last decades, continuous improvement of cultivars is crucial to ensure yield stability in view of newly emerging diseases or changing climatic conditions. The high amount of genetic diversity present in red clover ecotypes, landraces and cultivars provides an invaluable, but often unexploited resource for the improvement of key traits such as yield, quality, and resistance to biotic and abiotic stresses.

A collection of 397 red clover accessions was genotyped using a pooled genotyping-by-sequencing approach with 200 plants per accession. Resistance to the two most pertinent diseases in red clover production, southern anthracnose caused by Colletotrichum trifolii, and clover rot caused by Sclerotinia trifoliorum, was assessed using spray inoculation. The mean survival rate for southern anthracnose was 22.9% and the mean resistance index for clover rot was 34.0%. Genome-wide association analysis revealed several loci significantly associated with resistance to southern anthracnose and clover rot. Most of these loci are in coding regions. One quantitative trait locus (QTL) on chromosome 1 explained 16.8% of the variation in resistance to southern anthracnose. For clover rot resistance we found eight QTL, explaining together 80.2% of the total phenotypic variation. The SNPs associated with these QTL provide, once validated, a promising resource for marker-assisted selection in existing breeding programs, facilitating the development of novel cultivars with increased resistance against two devastating fungal diseases of red clover.

Key message

High variability for and candidate loci associated with resistance to southern anthracnose and clover rot in a worldwide collection of red clover provide a first basis for genomics-assisted breeding.
Loss of heterozygosity spectrum varies with ploidy levels in natural yeast populations
Authors: Dutta Abhishek , Dutreux Fabien , Schacherer Joseph
Published: May 2022

The appearance of genomic variations such as loss of heterozygosity (LOH) has a significant impact on phenotypic diversity observed in a population. Recent large-scale yeast population genomic surveys have shown a high frequency of these events in natural isolates and more particularly in polyploids. However, the frequency, extent, and spectrum of LOH in polyploid organisms have never been explored and is poorly characterized to date. Here, we accumulated 5,163 LOH events over 1,875 generations in 76 mutation accumulation (MA) lines comprising nine natural heterozygous diploid, triploid, and tetraploid natural S. cerevisiae isolates from different ecological and geographical origins. We found that the rate and spectrum of LOH are variable across ploidy levels. Of the total accumulated LOH events, 8.5%, 21%, and 70.5% of them were found in diploid, triploid, and tetraploid MA lines, respectively. Our results clearly shows that the frequency of generated LOH events increases with ploidy level. In fact, the cumulative LOH rates were estimated to be 9.3 × 10−3, 2.2 × 10−2, and 8.4 × 10−2 events per division for diploids, triploids, and tetraploids, respectively. In addition, a clear bias towards the accumulation of interstitial and short LOH tracts is observed in triploids and tetraploids compared to diploids. The variation of the frequency and spectrum of LOH events across ploidy level could be related to the genomic instability, characterizing higher ploidy isolates.

Highlights

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Yeast isolates with a high ploidy level (e.g., 3n and 4n) accumulate a larger number of LOH events compared to diploids.

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The type of events and the LOH spectrum are both variable according to the ploidy levels.

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A clear bias towards the accumulation of short LOH tracts is observed in polyploids compared to diploids.

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The variation in LOH spectrum is most likely related to genomic instability present in higher ploidy strains.
Glucocorticoid receptor activation during human microglial differentiation leads to genomic instability and senescence
Authors: Wei Jingzhang , Arber Charles , Wray Selina , Hardy John , Piers Thomas M , Pocock Jennifer M
Published: May 2022

Early life stress, prenatal exposure to glucocorticoids (GCs), confers a higher risk of psychiatric and neurodevelopmental disorders in children. Increasingly, the importance of microglia in these disorders has been recognised. Studies on GCs exposure during microglial development have been limited, and there are few, if any, human studies. We established an in vitro model of ELS by continuous pre-expoure of human iPS-microglia to GCs during primitive haematopoiesis (the critical stage of iPS-microglial differentiation) and then examined how this exposure affected the microglial phenotype as they differentiated and matured to microglia. The iPS-microglia predominately expressed glucocorticoid receptors over mineralocorticoid receptors, and the GR-α splice variant. Chronic GCs exposure during primitive haematopoiesis was able to recapitulate in vivo ELS effects. Thus pre-exposure to prolonged GCs resulted in increased type I interferon signalling, the presence of Cyclic GMP-AMP synthase-positive (cGAS) micronuclei, and cellular senescence in the matured iPS-microglia. The findings from this in vitro ELS model have ramifications for the responses of microglia in the pathogenesis of GC-mediated ELS- associated disorders such as schizophrenia, attention-deficit hyperactivity disorder and autistic spectrum disorder.

Highlights

Human iPS-derived-microglia predominantly express glucocorticoid receptor NR3C1 compared with mineralocorticoid receptor NR3C2, and a predominant splice variant of the NR3C1 of GR-α.

GC expression shows a differentiation-linked increment from iPSC to iPS-microglia.

An early-life stress model was established by exposing iPSC to glucocorticoids during primitive haematopoiesis.

RNA-seq analysis revealed that this early glucocorticoid exposure led to enhanced type I interferon inducible gene expression in the subsequent iPS-microglia.

Furthermore, micronuclei formation and cellular senescence markers were upregulated in the iPSC-microglia, indicating genomic instability due to early chronic GC exposure.

These findings have ramifications for the microglial responses in ELS linked neurodevelopmental disorders such as schizophrenia, attention-deficit hyperactivity disorder and autistic spectrum disorder.

Graphical abstract
MPS1 localizes to microtubule-attached kinetochores and actively promotes microtubule release
Authors: Hayward Daniel , Roberts Emile , Gruneberg Ulrike
Published: May 2022

In eukaryotes, the spindle assembly checkpoint protects genome stability in mitosis by preventing anaphase onset until incorrect microtubule-kinetochore attachment geometries have been eliminated and chromosome biorientation has been completed. These error correction and checkpoint processes are linked by two conserved serine/threonine kinases, Aurora B and MPS1 1, 2. In the prevailing model for spindle checkpoint signaling, MPS1 detects microtubule-free kinetochores generated by the Aurora B-dependent error correction pathway, and initiates spindle checkpoint signaling. However, we find that MPS1 initially localizes to microtubule-attached kinetochores in a manner dependent on the relative activities of Aurora B and its counteracting phosphatase PP2A-B56, and then actively promotes microtubule release. Thus, MPS1 is not a passive sensor for the microtubule binding state of kinetochores but actively generates microtubule-free checkpoint signaling kinetochores. MPS1 is thus instrumental for both the initial resolution of incorrect microtubule-kinetochore attachments and the downstream propagation of spindle checkpoint signaling.
Identification and characterisation of potent anti-MRSA phloroglucinol derivatives of Dryopteris crassirhizoma Nakai
Authors: Bhowmick Sumana , Beckmann Manfred , Shen Jianying , Mur Luis A.J.
Published: May 2022

Traditional Chinese Medicine (TCM) has been used to treat infectious diseases and could offer potential drug leads. This study evaluates the in vitro antimicrobial activities commercially sourced Dryopteris crassirhizoma Nakai whose authenticity was confirmed by DNA barcoding based on the ribulose bisphosphate carboxylase (rbcL) gene. Powdered rhizomes were sequentially extracted using n-hexane, dichloromethane, ethyl acetate and methanol at ambient temperature. The dried extracts at different concentrations were tested for antimicrobial activities against Escherichia coli, Pseudomonas aeruginosa, Staphylococcus aureus, Methicillin-resistant Staphylococcus aureus (MRSA), and Mycobacterium smegmatis. D. crassirhizoma extracts exhibited significant antimicrobial activities only against MRSA. Activity-led fractionations of D. crassirhizoma and characterisation by Ultra performance liquid chromatography - tandem mass spectrometry (UPLC-MS/MS) identified two potent anti-MRSA phloroglucinol derivatives: Norflavaspidic acid AB and flavaspidic acid AB. The impact of norflavaspidic acid AB on MRSA cells was examined using untargeted metabolomic analysis and compared to that of other established antibiotics (all treatments normalized to MIC50 at 6 h). This suggested that norflavaspidic acid AB had a distinctive effect which involved targeting bioenergetic transformation, metabolism, and particularly acetyl CoA, in MRSA cells. No cytotoxicity was observed for norflavaspidic acid AB against murine HepG2 cells. This study requires further experimental validation but can have indicated a naturally available compound that could help counter the threat of clinically relevant strains with antibiotic resistance.
Bayesian species distribution models integrate presence-only and presence-absence data to predict deer distribution and relative abundance
Authors: Morera-Pujol Virginia , Mostert Philip S. , Murphy Kilian , Burkitt Tim , Coad Barry , McMahon Barry J. , Nieuwenhuis Maarten , Morelle Kevin , Ward Alastair , Ciuti Simone
Published: May 2022

The use of georeferenced information on the presence of a species to predict its distribution across a geographic area is one of the most common tools in management and conservation. The collection of high-quality presence-absence data through structured surveys is, however, expensive, and managers usually have more abundant low-quality presence-only data collected by citizen scientists, opportunistic observations, and culling returns for game species. Integrated Species Distribution Models (ISDMs) have been developed to make the most of the data available by combining the higher-quality, but usually less abundant and more spatially restricted presence-absence data, with the lower quality, unstructured, but usually more extensive and abundant presence-only data. Joint-likelihood ISDMs can be run in a Bayesian context using INLA (Integrated Nested Laplace Approximation) methods that allow the addition of a spatially structured random effect to account for data spatial autocorrelation. These models, however, have only been applied to simulated data so far. Here, for the first time, we apply this approach to empirical data, using presence-absence and presence-only data for the three main deer species in Ireland: red, fallow and sika deer. We collated all deer data available for the past 15 years and fitted models predicting distribution and relative abundance at a 25 km2resolution across the island. Models’ predictions were associated to spatial estimate of uncertainty, allowing us to assess the quality of the model and the effect that data scarcity has on the certainty of predictions. Furthermore, we validated the three species-specific models using independent deer hunting returns. Our work clearly demonstrates the applicability of spatially-explicit ISDMs to empirical data in a Bayesian context, providing a blueprint for managers to exploit unused and seemingly unusable data that can, when modelled with the proper tools, serve to inform management and conservation policies.
Deconstructing cold-induced brown adipocyte neogenesis in mice
Authors: Burl Rayanne B. , Rondini Elizabeth A. , Wei Hongguang , Pique-Regi Roger , Granneman James G.
Published: May 2022

Cold-exposure triggers neogenesis in classic interscapular brown adipose tissue (BAT) that involves activation of b1-adrenergic receptors, proliferation of PDGFRA+ adipose tissue stromal cells (ASCs), and recruitment of immune cells whose phenotypes are presently unknown. Single- cell RNA-sequencing (scRNA-seq) identified three ASC subpopulations that occupied distinct tissue locations. Of these, interstitial ASC1 were found to be direct precursors of new brown adipocytes (BA). Surprisingly, knockout of b1-adrenergic receptors in ASCs did not prevent cold- induced neogenesis, whereas pharmacological activation of the b3-adrenergic receptor on BAs was sufficient, suggesting that signals derived from mature BAs indirectly trigger ASC proliferation and differentiation. In this regard, cold exposure induced the delayed appearance of multiple macrophage and dendritic cell populations whose recruitment strongly correlated with the onset and magnitude of neogenesis across diverse experimental conditions. High resolution immunofluorescence and single molecule fluorescence in situ hybridization demonstrated that cold-induced neogenesis involves dynamic interactions between ASC1 and recruited immune cells that occur on the micrometer scale in distinct tissue regions. Our results indicate that neogenesis is not a reflexive response of progenitors to b-adrenergic signaling, but rather is a complex adaptive response to elevated metabolic demands within brown adipocytes.
Unbiased proteomic and forward genetic screens reveal that mechanosensitive ion channel MSL10 functions at ER-plasma membrane contact sites in Arabidopsis thaliana
Authors: Codjoe Jennette M. , Richardson Ryan A. , Haswell Elizabeth S.
Published: May 2022

Mechanosensitive (MS) ion channels are an evolutionarily conserved way for cells to sense mechanical forces and transduce them into ionic signals. The channel properties of Arabidopsis thaliana MscS-Like (MSL)10 have been well studied, but how MSL10 signals remains largely unknown. To uncover signaling partners of MSL10, we employed both a proteomic screen and a forward genetic screen; both unexpectedly implicated ER-plasma membrane contact sites (EPCSs) in MSL10 function. The proteomic screen revealed that MSL10 associates with multiple proteins associated with EPCSs. Of these, only VAMP-associated proteins (VAP)27-1 and VAP27-3 interacted directly with MSL10. The forward genetic screen, for suppressors of a gain-of-function MSL10 allele (msl10-3G, MSL10S640L), identified mutations in the synaptotagmin (SYT)5 and SYT7 genes. We also found that EPCSs were expanded in leaves of msl10-3G plants compared to the wild type. Taken together, these results indicate that MSL10 can be found at EPCSs and functions there, providing a new cell-level framework for understanding MSL10 signaling. In addition, placing a mechanosensory protein at EPCS provides new insight into the function and regulation of this type of subcellular compartment.
A critical role for touch neurons in a skin-brain pathway for stress resilience
Authors: Schaffler Melanie D , Johnson Micah , Hing Ben , Kahler Paul , Hultman Ian , Srivastava Sanvesh , Arnold Justin , Blendy Julie N , Hultman Rainbo , Abdus-Saboor Ishmail
Published: May 2022

Social touch can act as a stress buffer, reducing behavioral and physiological responses to stressful scenarios. However, skin-brain touch pathways that promote stress resilience remain unknown. Here, we show that mice with an early life genetic ablation of Mrgprb4-lineage touch neurons display stress vulnerability behaviors in adulthood. Chemogenetic activation of these touch neurons reduced corticosterone levels under mild acute stress conditions. In addition, whole-brain c-Fos activity mapping while chemogenetically turning on these neurons uncovered differential neural activity patterns in brain areas relevant to somatosensation, reward, and affect. To gain mechanistic insight into this skin-brain touch pathway for stress susceptibility, we used multi-circuit neurophysiological recordings across seven brain regions at baseline and after stress in mice that had Mrgprb4-lineage touch neurons ablated in early life. Interestingly, the Mrgprb4-lineage neuron-ablated mice have alterations in local field potential phase directionality and power in the theta frequencies in mesolimbic reward regions, which may underlie our observed stress susceptibility phenotype. Together, these studies revealed that sensory neurons in the skin engage networks across the brain to promote stress resilience.
A Well-Characterized Polycistronic-Like Gene Expression System in Yeast
Authors: Mukherjee Minakshi , Wang Zhen Q.
Published: May 2022

Efficient expression of multiple genes is critical to yeast metabolic engineering because of the increasing complexity of engineered pathways. A yeast polycistronic expression system is of particular interest because one promoter can drive the expression of multiple genes. Polycistronic expression thus requires less genetic material and minimizes undesirable recombination due to repeated use of the same promoter. It also decreases the number of DNA parts necessary for cloning a multi-gene construct. 2A viral peptides enable the co-translation of multiple proteins from one mRNA by ribosomal skipping. However, the wide adaptation of this strategy for polycistronic-like gene expression in yeast awaits in-depth characterizations. Additionally, a one-step assembly of such a polycistronic-like system is highly desirable. To this end, we have developed a MoClo compatible 2A peptide-based polycistronic-like system capable of expressing multiple genes from a single promoter in yeast. Characterizing the bi-, tri, and quad-cistronic expression of fluorescent proteins showed high cleavage efficiencies of three 2A peptides. The expression level of each protein decreases as it moves away from the promoter. Additionally, the impact of a C-terminal 2A peptide on protein function is dependent on the protein sequence. Applying the polycistronic-like system for geraniol production resulted in similar or higher titers compared to a conventional monocistronic construct. In summary, this highly-characterized polycistronic-like gene expression system is another tool to facilitate multi-gene expression in yeast.
Oxytocin Activity in the Paraventricular and Supramammillary Nuclei of the Hypothalamus is Essential for Social Recognition Memory in Rats
Authors: Rajamani Keerthi Thirtamara , Barbier Marie , Lefevre Arthur , Niblo Kristi , Cordero Nicholas , Netser Shai , Grinevich Valery , Wagner Shlomo , Harony-Nicolas Hala
Published: May 2022

Oxytocin plays an important role in modulating social recognition memory. However, the direct implication of oxytocin neurons of the paraventricular nucleus of the hypothalamus (PVH) and their downstream hypothalamic targets in regulating short- and long-term forms of social recognition memory has not been fully investigated. In this study, we employed a chemogenetic approach to target the activity of PVH oxytocin neurons in male rats and found that specific silencing of this neuronal population led to an impairment in short- and long-term social recognition memory. We combined viral mediated fluorescent labeling of oxytocin neurons with immunohistochemical techniques and identified the supramammillary nucleus (SuM) of the hypothalamus as a target of PVH oxytocinergic axonal projections in rats. We used multiplex fluorescence in-situ hybridization to label oxytocin receptors in the SuM and determined that they are predominantly expressed in glutamatergic neurons, including those that project to the CA2 region of the hippocampus. Finally, we used a highly selective oxytocin receptor antagonist in the SuM to examine the involvement of oxytocin signaling in modulating short- and long-term social recognition memory and found that it is necessary for the formation of both. This study discovered a previously undescribed role for the SuM in regulating social recognition memory via oxytocin signaling and reinforced the specific role of PVH oxytocin neurons in regulating this form of memory.
Rapid evolution and strain turnover in the infant gut microbiome
Authors: Chen Daisy W. , Garud Nandita R.
Published: May 2022

Although the ecological dynamics of the infant gut microbiome have been intensely studied, relatively little is known about evolutionary dynamics in the infant gut microbiome. Here we analyze longitudinal fecal metagenomic data from more than 700 infants and their mothers over the first year of life and find that the evolutionary dynamics in infant gut microbiomes are distinct from those of adults. We find evidence for more than a 10-fold increase in the rate of evolution and strain turnover in the infant gut compared with healthy adults, with the mother–infant transition at delivery being a particularly dynamic period in which gene loss dominates. Within a few months after birth, these dynamics stabilize, and gene gains become increasingly frequent as the microbiome matures. We furthermore find that evolutionary changes in infants show signatures of being seeded by a mixture of de novo mutations and transmissions of pre-evolved lineages from the broader family. Several of these evolutionary changes occur in parallel across infants, highlighting candidate genes that may play important roles in the development of the infant gut microbiome. Our results point to a picture of a volatile infant gut microbiome characterized by rapid evolutionary and ecological change in the early days of life.
Ad hoc government payments impact on non-real estate farm debt
Authors: Martinez Charles , Boyer Christopher N. , Yu Tun-Hsiang , Smith S. Aaron , Rabinowitz Adam
Published: May 2022

Purpose

The authors examined the impact of the Market Facilitation Program (MFP) and Coronavirus Food Assistance Program (CFAP) payments to United States agricultural producers on non-real estate agricultural loans.

Design/methodology/approach

The authors used quarterly, state-level commercial bank data from 2016–2020 to estimate dynamic panel models.

Findings

The authors found MFP and CFAP payments not associated with the percentage of non-real estate agricultural loans with payments over 90 days late. However, these payments associated with the percentage of non-real estate agricultural loans with payments between 30 and 89 days late. The available data utilized cannot consider when producers received the actual payment and what they specifically did with those funds.

Originality/value

The contribution of this study is for US policymakers and agricultural lenders. The findings could be helpful in designing and implementing future ad hoc payment programs and provide an understanding of potential shortcomings of the current safety net for agricultural producers in the Farm Bill. Additionally, findings can assist agricultural lenders in predicting the impact of ad hoc payments on their distressed loan portfolios.
What influences students’ food waste behaviour in campus canteens?
Authors: Wang Hong , Ma Baolong , Cudjoe Dan , Farrukh Muhammad , Bai Rubing
Published: May 2022

Purpose

Reducing food waste is one of the critical challenges of campus canteens. This study aims to test an extended theory of planned behaviour that incorporates moral norm, food taste and campus food-saving climate to understand the influence factors of food waste behaviour on campuses.

Design/methodology/approach

To evaluate the proposed model, an online survey was utilized to collect 513 valid questionnaires.

Findings

The findings suggest that (1) attitudes towards food waste, subjective norm and perceived behavioural control have a significant influence on intention to reduce food waste; (2) Moral norm and food taste are shown to have a favourable effect on the intention to reduce food waste; (3) Food waste behaviour is significantly determined by intention to reduce food waste; (4) Campus food-saving climate negatively moderates the relationship between intention to reduce food waste and food waste behaviour.

Originality/value

This study paves the way to enhance the understanding of the factors of food waste among college students. In addition, this study develops practical strategies to prevent large amounts of food from being wasted on campus.
Multinational orchestration: a meta-theoretical approach toward competitive advantage
Authors: Kaur Vaneet
Published: May 2022

Purpose

The purpose of this study is to critically evaluate the canonical contribution of the classical theories of multinational enterprises (MNE) and complement them with congruous multi-theoretical lenses to a propose a meta-theoretical view for competitive advantage. The proposed framework is applied to fundamental questions of MNE, and exploratory insights are revealed.

Design/methodology/approach

This study sought to review the literature on various paradigms such as resource-based view, knowledge-based view, attention-based view, relational view, dynamic capability view and institution-based view to propose a meta-theoretical approach explicating the phenomenon of competitiveness.

Findings

This study proffers that the key to global competitiveness lies in building micro-foundational, multidimensional and multilevel multinational orchestration capabilities. The requisite orchestration capabilities are capabilities par excellence that explain: how organizational capabilities originate through the cognition of individual employees at the micro level; how individual-level abilities are amplified when they are harnessed through relational capabilities to form knowledge capabilities at the meso-level; and how the confluence of knowledge capabilities and higher order dynamic capabilities gives rise to heterogeneous firm-level knowledge-based dynamic capabilities that can be combined with institution capabilities to aggrandize the prediction of competitive advantage for MNEs.

Originality/value

The successful development of MNE competitiveness as a field of academic inquiry, brought about by an increasing amount of theoretical specialization, has come at the price of significant fragmentation of the overall scientific quest. The abovementioned paradigms and their underlying constructs have primarily been conceptualized in silos. The classical theories of MNE have been used a starting point to which complementary multidisciplinary views have been scaffolded to gain a more nuanced understanding of global competitiveness.