bluuebunny/crossref_metadata_2025 huggingface dataset:
Loss of Rnf43 accelerates Kras-mediated neoplasia and remodels the tumor immune microenvironment in pancreatic adenocarcinoma
Authors: Hosein Abdel Nasser , Dangol Gita , Okumura Takashi , Roszik Jason , Rajapakshe Kimal , Siemann Megan , Ghosh Bidyut , Monberg Maria , Guerrero Paola A. , Zaid Mohamed , Singhi Aatur , Haymaker Cara L , Clevers Hans , Woermann Sonja M. , Abou-Elkacem Lotfi , Maitra Anirban
Published: May 2021

RNF43 is an E3 ubiquitin ligase that is recurrently mutated in pancreatic ductal adenocarcinoma (PDAC) and precursor cystic neoplasms of the pancreas. The impact of RNF43 mutations on PDAC is poorly understood and autochthonous models have not been sufficiently characterized. In this study we describe a genetically engineered mouse model (GEMM) of PDAC with conditional expression of oncogenic Kras and deletion of the catalytic domain of Rnf43 (KRC) in exocrine cells. We demonstrate that Rnf43 loss results in an increased incidence of high-grade cystic lesions of the pancreas and PDAC. Importantly, KRC mice have a significantly decreased survival compared to mice containing only an oncogenic Kras mutation. By use of single cell RNA sequencing we demonstrated that KRC tumor progression is accompanied by a decrease in macrophages, as well as an increase in T and B lymphocytes with evidence of increased immune checkpoint molecule expression and affinity maturation, respectively. This was in stark contrast to the tumor immune microenvironment observed in the Kras/Tp53 driven PDAC GEMM. Furthermore, expression of the chemokine, CXCL5, was found to be specifically decreased in KRC cancer cells by means of epigenetic regulation and emerged as a putative candidate for mediating the unique KRC immune landscape. This GEMM establishes RNF43 as a bona fide tumor suppressor gene in PDAC and puts forth a rationale for an immunotherapy approach in this subset of PDAC cases.
Lateral Preoptic Area Neurons Signal Cocaine Self-Administration Behaviors
Authors: Coffey Kevin R. , Venkat Vaishnavi , West Mark O. , Barker David J.
Published: May 2021

The lateral preoptic area is implicated in numerous aspects of substance use disorder. In particular, the lateral preoptic area is highly sensitive to the pharmacological properties of psychomotor stimulants, and its activity promotes drug-seeking in the face of punishment and reinstatement during abstinence. Despite the lateral preoptic areas complicity in substance use disorder, how precisely lateral preoptic area neurons encode the individual components of drug self-administration has not been ascertained. To bridge this gap, we examined how the firing of single lateral preoptic area neurons correlates with three discrete elements of cocaine self-administration: 1) drug-seeking (pre-response), 2) drug-taking (response), and 3) receipt of the cocaine infusion. A significant subset of lateral preoptic area neurons responded to each component with a mix of increases and decreases in firing-rate. A majority of these neurons encoded the operant response with increases in spiking, though responses during the drug-seeking, taking, and reciept windows were highly correlated.
Experimental demonstration of tethered gene drive systems for confined population modification or suppression
Authors: Metzloff Matthew , Yang Emily , Dhole Sumit , Clark Andrew G. , Messer Philipp W. , Champer Jackson
Published: May 2021

Homing gene drives hold great promise for the genetic control of natural populations. However, current homing systems are capable of spreading uncontrollably between populations connected by even marginal levels of migration. This could represent a substantial sociopolitical barrier to the testing or deployment of such drives and may generally be undesirable when the objective is only local population control, such as suppression of an invasive species outside of its native range. Tethered drive systems, in which a locally confined gene drive provides the CRISPR nuclease needed for a homing drive, could provide a solution to this problem, offering the power of a homing drive and confinement of the supporting drive. Here, we demonstrate the engineering of a tethered drive system inDrosophila, using a regionally confined CRISPR Toxin-Antidote Recessive Embryo (TARE) drive to support modification and suppression homing drives. Each drive was able to bias inheritance in its favor, and the TARE drive was shown to spread only when released above a threshold frequency in experimental cage populations. After the TARE drive had established in the population, it facilitated the spread of a subsequently released split homing modification drive (to all individuals in the cage) and of a homing suppression drive (to its equilibrium frequency). Our results show that the tethered drive strategy is a viable and easily engineered option for providing confinement of homing drives to target populations.
SARS-CoV-2-specific memory B cells can persist in the elderly despite loss of neutralising antibodies
Authors: Jeffery-Smith Anna , Burton Alice R , Lens Sabela , Rees-Spear Chloe , Patel Monika , Gopal Robin , Muir Luke , Aiano Felicity , Doores Katie J , Chow J. Yimmy , Ladhani Shamez N , Zambon Maria , McCoy Laura E , Maini Mala K
Published: May 2021

Memory B cells (MBC) can provide a recall response able to supplement waning antibodies with an affinity-matured response better able to neutralise variant viruses. We studied a cohort of vulnerable elderly care home residents and younger staff, a high proportion of whom had lost neutralising antibodies (nAb), to investigate their reserve immunity from SARS-CoV-2-specific MBC. Class-switched spike and RBD-tetramer-binding MBC with a classical phenotype persisted five months post-mild/asymptomatic SARS-CoV-2 infection, irrespective of age. Spike/RBD-specific MBC remained detectable in the majority who had lost nAb, although at lower frequencies and with a reduced IgG/IgA isotype ratio. Functional spike/S1/RBD-specific recall was also detectable by ELISpot in some who had lost nAb, but was significantly impaired in the elderly, particularly to RBD. Our findings demonstrate persistence of SARS-CoV-2-specific MBC beyond loss of nAb, but highlight the need for careful monitoring of functional defects in RBD-specific B cell immunity in the elderly.

One sentence summary

Circulating class-switched spike and RBD-specific memory B cells can outlast detectable neutralising antibodies but are functionally constrained in the elderly.
A role for ecologically-tuned chunking in the evolution of advanced cognition demonstrated by modelling the cleaner fish market problem
Authors: Prat Yosef , Bshary Redouan , Lotem Arnon
Published: May 2021

What makes cognition ‘advanced’ is an open and not precisely defined question. One perspective involves increasing the complexity of associative learning, from conditioning to learning sequences of events (‘chaining’) to representing various cue combinations as ‘chunks’. Here we develop a weighted-graph model to study the conditions for the evolution of chunking ability, based on the ecology of the cleaner fishLabroides dimidiatus. Cleaners must learn to serve visitor clients before resident clients, because a visitor leaves if not attended while a resident waits for service. This challenge has been captured in various versions of the ephemeral-reward task, which has been proven difficult for a range of cognitively capable species. We show that chaining is the minimal requirement for solving the laboratory task, that involves repeated simultaneous exposure to an ephemeral and permanent food source. Adding ephemeral-ephemeral and permanent-permanent combinations, as cleaners face in the wild, requires individuals to have chunking abilities to solve the task. Importantly, chunking parameters need to be calibrated to ecological conditions in order to produce adaptive decisions. Thus, it is the fine tuning of this ability which may be the major target of selection during the evolution of advanced associative learning.
Chronic PPARγ Stimulation Shifts Amyloidosis to Higher Fibrillarity but Improves Cognition
Authors: Blume Tanja , Deussing Maximilian , Biechele Gloria , Peters Finn , Zott Benedikt , Schmidt Claudio , Franzmeier Nicolai , Wind Karin , Eckenweber Florian , Sacher Christian , Shi Yuan , Ochs Katharina , Kleinberger Gernot , Xiang Xianyuan , Focke Carola , Lindner Simon , Gildehaus Franz-Josef , Beyer Leonie , von Ungern-Sternberg Barbara , Bartenstein Peter , Baumann Karlheinz , Adelsberger Helmuth , Rominger Axel , Cumming Paul , Willem Michael , Dorostkar Mario M. , Herms Jochen , Brendel Matthias
Published: May 2021

Background

We undertook longitudinal β-amyloid positron emission tomography (Aβ-PET) imaging as a translational tool for monitoring of chronic treatment with the peroxisome proliferator-activated receptor gamma (PPARγ) agonist pioglitazone in Aβ model mice. We thus tested the hypothesis this treatment would rescue from increases of the Aβ-PET signal while promoting spatial learning and preservation of synaptic density.

Methods

PS2APP mice (N=23; baseline age: 8 months) and AppNL-G-F mice (N=37; baseline age: 5 months) were investigated longitudinally for five months using Aβ-PET. Groups of mice were treated with pioglitazone or vehicle during the follow-up interval. We tested spatial memory performance and confirmed terminal PET findings by immunohistochemical and biochemistry analyses.

Results

Surprisingly, Aβ-PET and immunohistochemistry revealed a shift towards higher fibrillary composition of Aβ-plaques during upon chronic pioglitazone treatment. Nonetheless, synaptic density and spatial learning were improved in transgenic mice with pioglitazone treatment, in association with the increased plaque fibrillarity.

Conclusion

These translational data suggest that a shift towards higher plaque fibrillarity protects cognitive function and brain integrity. Increases in the Aβ-PET signal upon immunomodulatory treatments targeting Aβ aggregation can thus be protective.
The genetic and epigenetic landscape of the Arabidopsis centromeres
Authors: Naish Matthew , Alonge Michael , Wlodzimierz Piotr , Tock Andrew J. , Abramson Bradley W. , Lambing Christophe , Kuo Pallas , Yelina Natasha , Hartwick Nolan , Colt Kelly , Kakutani Tetsuji , Martienssen Robert A. , Bousios Alexandros , Michael Todd P. , Schatz Michael C. , Henderson Ian R.
Published: May 2021

Centromeres attach chromosomes to spindle microtubules during cell division and, despite this conserved role, show paradoxically rapid evolution and are typified by complex repeats. We used ultra-long-read sequencing to generate the Col-CEN Arabidopsis thaliana genome assembly that resolves all five centromeres. The centromeres consist of megabase-scale tandemly repeated satellite arrays, which support high CENH3 occupancy and are densely DNA methylated, with satellite variants private to each chromosome. CENH3 preferentially occupies satellites with least divergence and greatest higher-order repetition. The centromeres are invaded by ATHILA retrotransposons, which disrupt genetic and epigenetic organization of the centromeres. Crossover recombination is suppressed within the centromeres, yet low levels of meiotic DSBs occur that are regulated by DNA methylation. We propose that Arabidopsis centromeres are evolving via cycles of satellite homogenization and retrotransposon-driven diversification.

One-sentence summary

Long read sequencing and assembly of the Arabidopsis centromeres reveals their genetic and epigenetic topography.
Complete protection by a single dose skin patch delivered SARS-CoV-2 spike vaccine
Authors: McMillan Christopher L.D. , Choo Jovin J.Y. , Idris Adi , Supramaniam Aroon , Modhiran Naphak , Amarilla Alberto A. , Isaacs Ariel , Cheung Stacey T.M. , Liang Benjamin , Bielefeldt-Ohmann Helle , Azuar Armira , Acharya Dhruba , Kelly Gabrielle , Fernando Germain J.P. , Landsberg Michael J. , Khromykh Alexander A. , Watterson Daniel , Young Paul R. , McMillan Nigel A.J. , Muller David A.
Published: May 2021

SARS-CoV-2 has infected over 160 million people and resulted in more than 3.3 million deaths, and we still face many challenges in the rollout of vaccines. Here, we use the high-density microarray patch to deliver a SARS-CoV-2 spike subunit vaccine directly to the skin. We show the vaccine, dry-coated on the patch is thermostable, and delivery of spike via HD-MAP induced greater cellular and antibody immune responses, with serum able to potently neutralize clinically relevant isolates including those from the B.1.1.7 and B.1.351 lineages. Finally, a single dose of HD-MAP-delivered spike provided complete protection from a lethal virus challenge, demonstrating that HD-MAP delivery of a SARS-CoV-2 vaccine is superior to traditional needle-and-syringe vaccination and has the potential to greatly impact the ongoing COVID-19 pandemic.
Cryo-EM Structure of the Photosynthetic LH1-RC Complex from Rhodospirillum rubrum
Authors: Tani K. , Kanno R. , Ji X.-C. , Hall M. , Yu L.-J. , Kimura Y. , Madigan M. T. , Mizoguchi A. , Humbel B. M. , Wang-Otomo Z.-Y.
Published: May 2021

We present a cryo-EM structure of the light-harvesting-reaction center (LH1-RC) core complex from purple phototrophic bacterium Rhodospirillum (Rsp.) rubrum at 2.76 Å resolution. The LH1 complex forms a closed, slightly elliptical ring structure with 16 αβ-polypeptides surrounding the RC. Our biochemical analysis detected rhodoquinone (RQ) molecules in the purified LH1-RC, and the cryo-EM density map specifically positions RQ at the QA site in the RC. The geranylgeraniol sidechains of bacteriochlorophyll (BChl) aG coordinated by LH1 β-polypeptides exhibit a highly homologous tail-up conformation that allows for interactions with the bacteriochlorin rings of nearby LH1 α-associated BChls aG. The structure also revealed key protein–protein interactions in both N- and C-terminal regions of the LH1 αβ-polypeptides, mainly within a face-to-face structural subunit. Our findings enable to evaluate past experimental and computational results obtained with this widely used organism and provide crucial information for more detailed exploration of light-energy conversion, quinone transport, and structure–function relationships in pigment-protein complexes.
Multi-omics consensus ensemble refines the classification of muscle-invasive bladder cancer with stratified prognosis, tumour microenvironment and distinct sensitivity to frontline therapies
Authors: Lu Xiaofan , Meng Jialin , Su Liwen , Jiang Liyun , Wang Haitao , Zhu Junkai , Huang Mengjia , Cheng Wenxuan , Xu Li , Ruan Xinjia , Zhou Yujie , Yeh Shuyuan , Liang Chaozhao , Yan Fangrong
Published: May 2021

The molecular classification of muscle-invasive bladder cancer (MIBC) based on transcriptomic signatures has been extensively studied. The complementary nature of information provided by different molecular profiles motivated us to refine MIBC classification by aggregating multi-omics data. We generated a consensus ensemble through ten multi-omics integrative clustering approaches on 396 MIBCs from TCGA. A total of 701 MIBCs from different sequencing technologies were used for external validation. Associations between subtypes and prognosis, molecular profiles, the tumour microenvironment, and potential response to frontline therapies were further analyzed. Nearest template prediction and random forest classification were used to develop a predictive signature/classifier for MIBC refinement. We identified four integrative consensus subtypes of MIBC, which were further designated basal-inflamed, basal-noninflamed, luminal-excluded and luminal-desert by immune profiling. Of note, the refinement of basal-like MIBC classification adds to the literature by identifying a basal-noninflamed MIBC subtype presenting with a significantly poor outcome and a global immune-cold phenotype, which might be triggered by Chr4 deletion and high activation of the oncogenic NRF2 pathway. In contrast, basal-inflamed MIBC showed high immunocyte infiltration and high expression of potential targets for immunotherapy. Using an external metastatic MIBC cohort in which patients received anti-PD-L1 treatment, we suggested that basal-inflamed MIBC had a higher likelihood of responding to immunotherapy than other MIBCs. The R package “refineMIBC” was offered as a research tool to refine MIBC from a single-sample perspective (https://github.com/xlucpu/refineMIBC). This consensus ensemble refines the intrinsic MIBC subtypes, which provides a blueprint for the clinical development of rational targeted and immunotherapeutic strategies.
Single cell analysis of spondyloarthritis regulatory T cells identifies distinct synovial gene expression patterns and clonal fates
Authors: Simone Davide , Penkava Frank , Ridley Anna , Sansom Stephen , Al-Mossawi M Hussein , Bowness Paul
Published: May 2021

Regulatory T cells (Tregs) play an important role in controlling inflammation and limiting autoimmunity, but their phenotypes at inflammatory sites in human disease are poorly understood. We here analyze the single-cell transcriptome of >16,000 Tregs obtained from peripheral blood and synovial fluid of two patients with HLA-B27+ ankylosing spondylitis and three patients with psoriatic arthritis, closely related forms of inflammatory spondyloarthritis. We identify multiple Treg clusters with distinct transcriptomic profiles, including, among others, a regulatory CD8+subset expressing cytotoxic markers/genes, and a Th17-likeRORC+ Treg subset characterized by IL-10 and LAG-3 expression. Synovial Tregs show upregulation of interferon signature and TNF receptor superfamily genes, and marked clonal expansion, consistent with tissue adaptation and antigen contact respectively. Individual synovial Treg clones map to different clusters indicating cell fate divergence. Finally, we demonstrate that LAG-3 directly inhibits IL-12/23 and TNF secretion by patient-derived monocytes, a mechanism with translational potential in SpA. Our detailed characterization of Tregs at an important inflammatory site illustrates the marked specialization of Treg subpopulations.
Structural and functional connectivity reconstruction with CATO - A Connectivity Analysis TOolbox
Authors: de Lange Siemon C. , Helwegen Koen , van den Heuvel Martijn P.
Published: May 2021

We describe a Connectivity Analysis TOolbox (CATO) for the reconstruction of structural and functional brain connectivity based on diffusion weighted imaging and resting-state functional MRI data. CATO is a multimodal software package that enables researchers to run end-to-end reconstructions from MRI data to structural and functional connectome maps, customize their analyses and utilize various software packages to preprocess data. Structural and functional connectome maps can be reconstructed with respect to user-defined (sub)cortical atlases providing aligned connectivity matrices for integrative multimodal analyses. We outline the implementation and usage of the structural and functional processing pipelines in CATO. Performance was calibrated with respect to simulated diffusion weighted imaging from the ITC2015 challenge, test-retest diffusion weighted imaging data and resting-state functional MRI data from the Human Connectome Project. CATO is open-source software distributed under the MIT License and available as a MATLAB toolbox and as a stand-alone application atwww.dutchconnectomelab.nl/CATO.
Distinct gene regulatory signatures of dominance rank and social bond strength in wild baboons
Authors: Anderson Jordan A. , Lea Amanda J. , Voyles Tawni N. , Akinyi Mercy Y. , Nyakundi Ruth , Ochola Lucy , Omondi Martin , Nyundo Fred , Zhang Yingying , Campos Fernando A. , Alberts Susan C. , Archie Elizabeth A. , Tung Jenny
Published: May 2021

The social environment is a major determinant of morbidity, mortality, and Darwinian fitness in social animals. Recent studies have begun to uncover the molecular processes associated with these relationships, but the degree to which they vary across different dimensions of the social environment remains unclear. Here, we draw on a long-term field study of wild baboons to compare the signatures of affiliative and competitive aspects of the social environment in white blood cell gene regulation, under both immune stimulated and non-stimulated conditions. We find that the effects of dominance rank on gene expression are directionally opposite in males versus females, such that high-ranking males resemble low-ranking females, and vice-versa. Among females, rank and social bond strength are both reflected in the activity of cellular metabolism and proliferation genes. However, pronounced rank-related differences in baseline immune gene activity are near-absent for social bond strength, while only bond strength predicts the fold-change response to immune (lipopolysaccharide) stimulation. Together, our results indicate that the directionality and magnitude of social effects on gene regulation depend on the aspect of the social environment under study. This heterogeneity may help explain why social environmental effects on health and longevity can also vary between measures.
Co-expression patterns of microglia markers Iba1, TMEM119 and P2RY12 in Alzheimer’s disease
Authors: Kenkhuis Boyd , Somarakis Antonios , Kleindouwel Lynn RT , van Roon-Mom Willeke MC , Höllt Thomas , van der Weerd Louise
Published: May 2021

Microglia have been identified as key players in Alzheimer’s disease pathogenesis, and other neurodegenerative diseases. Iba1, and more specifically TMEM119 and P2RY12 are gaining ground as presumedly more specific microglia markers, but comprehensive characterization of the expression of these three markers individually as well as combined is currently missing. Here we used a multispectral immunofluorescence dataset, in which over seventy thousand microglia from both aged controls and Alzheimer patients have been analysed for expression of Iba1, TMEM119 and P2RY12 on a single-cell level. For all markers, we studied the overlap and differences in expression patterns and the effect of proximity to β-amyloid plaques. We found no difference in absolute microglia numbers between control and Alzheimer subjects, but the prevalence of specific combinations of markers (phenotypes) differed greatly. In controls, the majority of microglia expressed all three markers. In Alzheimer patients, a significant loss of TMEM119+-phenotypes was observed, independent of the presence of β-amyloid plaques in its proximity. Contrary, phenotypes showing loss of P2RY12, but consistent Iba1 expression were increasingly prevalent around β-amyloid plaques. No morphological features were conclusively associated with loss or gain of any of the markers or any of the identified phenotypes. All in all, none of the three markers were expressed by all microglia, nor can be wholly regarded as a pan- or homeostatic marker, and preferential phenotypes were observed depending on the surrounding pathological or homeostatic environment. This work could help select and interpret microglia markers in previous and future studies.
An ancient divide in outer membrane tethering systems in Bacteria
Authors: Witwinowski Jerzy , Sartori-Rupp Anna , Taib Najwa , Pende Nika , Tham To Nam , Poppleton Daniel , Ghigo Jean-Marc , Beloin Christophe , Gribaldo Simonetta
Published: May 2021

Recent data support the hypothesis that Gram-positive bacteria (monoderms) arose from Gram-negatives (diderms) through loss of the outer membrane (OM). However how this happened remains unknown. Considering that tethering of the OM is essential for cell envelope stability in diderm bacteria we hypothesize that its destabilization may have been involved in OM loss. Here, we present an in-depth analysis of the four main OM tethering systems across all Bacteria. We show that their distribution strikingly follows the bacterial phylogeny with a bimodal distribution matching the deepest phylogenetic cleavage between Terrabacteria (a clade encompassing Cyanobacteria, Deinococcus/Thermus, Firmicutes, etc.) and Gracilicutes (a clade encompassing Proteobacteria, Bacteroidetes, Spirochaetes, etc.). Diderm Terrabacteria display as the main system OmpM, a porin that attaches non-covalently to modified peptidoglycan or to secondary cell wall polymers. In contrast, the lipoprotein Pal is restricted to the Gracilicutes along with a more sporadic occurrence of OmpA. While Braun’s lipoprotein Lpp is largely considered as the textbook example of OM attachment, it is actually present only in a subclade of Gammaproteobacteria. We propose an evolutionary scenario whereby the last common bacterial ancestor used a system based on OmpM, which was later replaced by one based on the lipoprotein Pal concomitantly to the emergence of the Lol machinery to address lipoproteins to the OM, with OmpA as a possible transition state. We speculate that the existence of only one main OM tethering system in the Terrabacteria would have allowed the multiple emergences of the monoderm phenotype specifically observed in this clade through OmpM perturbation. We test this hypothesis by inactivating all four ompM gene copies in the genetically tractable diderm Firmicute Veillonella parvula. The resulting mutant is severely affected in growth and displays high sensitivity to OM stress. High resolution imaging and tomogram reconstructions reveal a dramatic - yet non-lethal - phenotype, in which vast portions of the OM detach, producing large vesicles surrounding multiple monoderm-like cells sharing a common periplasm. Complementation by a single OmpM rescues the phenotype to a normal cell envelope. Together, our results highlight an ancient shift in bacterial evolution involving OM tethering systems. They suggest a possible mechanism for OM loss and a high flexibility of the cell envelope in diderm Firmicutes, making them ideal models to further refine our understanding of the mechanisms involved in bacterial OM stability, and opening the way to recapitulate the monoderm/diderm transition in the laboratory.
A modular mathematical model of exercise-induced changes in metabolism, signaling, and gene expression in human skeletal muscle
Authors: Akberdin I.R. , Kiselev I.N. , Pintus S.S. , Sharipov R.N. , Vertyshev A.Yu. , Vinogradova O.L. , Popov D.V. , Kolpakov F.A.
Published: May 2021

Skeletal muscle is the principal contributor to exercise-induced changes in human metabolism. Strikingly, although it has been demonstrated that a lot of metabolites accumulating in blood and human skeletal muscle during an exercise activate different signaling pathways and induce expression of many genes in working muscle fibres, the system understanding of signaling-metabolic pathways interrelations with downstream genetic regulation in the skeletal muscle is still elusive. Herein, a physiologically based computational model of skeletal muscle comprising energy metabolism, Ca2+and AMPK signalling pathways, and expression regulation of genes with early and delayed responses has been developed based on a modular modeling approach. The integrated modular model validated on diverse including original experimental data and different exercise modes provides a comprehensivein silicoplatform in order to decipher and track cause-effect relationships between metabolic, signaling and gene expression levels in the skeletal muscle.
The molecular basis of ubiquitin-specific protease 8 autoinhibition by the WW-like domain
Authors: Kakihara Keijun , Asamizu Kengo , Moritsugu Kei , Kubo Masahide , Kitaguchi Tetsuya , Endo Akinori , Kidera Akinori , Ikeguchi Mitsunori , Kato Akira , Komada Masayuki , Fukushima Toshiaki
Published: May 2021

Ubiquitin-specific protease 8 (USP8) is a deubiquitinating enzyme involved in multiple membrane trafficking pathways. The enzyme activity is inhibited by binding to 14-3-3 proteins, and mutations of the 14-3-3 binding motif in USP8 are related to Cushing’s disease. However, the molecular basis of USP8 enzyme activity regulation remains unclear. Here, we identified amino acids 645–684 of USP8 as an autoinhibitory region, which our pull-down and single-molecule FRET assay results suggested interacts with the catalytic USP domain.In silicomodelling indicated that the region forms a WW-like domain structure, plugs the catalytic cleft, and narrows the entrance to the ubiquitin-binding pocket. Furthermore, 14-3-3 was found to inhibit USP8 enzyme activity partly by enhancing the interaction between the WW-like and USP domains. These findings provide the molecular basis of USP8 autoinhibition via the WW-like domain. Moreover, they suggest that the release of autoinhibition may underlie Cushing’s disease caused by USP8 mutations.
Evolution of brilliant iridescent feather nanostructures
Authors: Nordén Klara K. , Eliason Chad M. , Stoddard Mary Caswell
Published: May 2021

The brilliant iridescent plumage of birds creates some of the most stunning color displays known in the natural world. Iridescent plumage colors are produced by nanostructures in feathers and have evolved in a wide variety of birds. The building blocks of these structures—melanosomes (melanin-filled organelles)—come in a variety of forms, yet how these different forms contribute to color production across birds remains unclear. Here, we leverage evolutionary analyses, optical simulations and reflectance spectrophotometry to uncover general principles that govern the production of brilliant iridescence. We find that a key feature that unites all melanosome forms in brilliant iridescent structures is thin melanin layers. Birds have achieved this in multiple ways: by decreasing the size of the melanosome directly, by hollowing out the interior, or by flattening the melanosome into a platelet. The evolution of thin melanin layers unlocks color-producing possibilities, more than doubling the range of colors that can be produced with a thick melanin layer and simultaneously increasing brightness. We discuss the implications of these findings for the evolution of iridescent structures in birds and propose two evolutionary paths to brilliant iridescence.
Transcriptional characterization of the glial response due to chronic neural implantation of flexible microprobes
Authors: Joseph Kevin , Kirsch Matthias , Johnston Midori , Münkel Christian , Stieglitz Thomas , Haas Carola A. , Hofmann Ulrich G.
Published: May 2021

Long term implantation of (micro-)probes into neural tissue cause unique and disruptive responses to these foreign bodies. In this study, we present the transcriptional trajectory of glial cells responding to chronic implantation of flexible micro-probes for up to 18 weeks. Transcriptome analysis shows a rapid activation of microglial cells and a strong upregulation of reactive astrocytic genes, which is lost over the full duration of the implant period. Most interestingly, animals that were implanted for 18 weeks show a transcriptional profile similar to non-implanted controls, with increased expression of genes associated with wound healing and angiogenesis, which raises hope of a normalization of the neuropil to the pre-injury state when using flexible probes. Nevertheless, our data show, that a subset of genes upregulated after 18 weeks belong to the family of immediate early genes, which would indicate that structural and functional remodeling has not been completed at this time point. Our results confirm and extend previous work on the molecular changes resulting from the presence of intraneural probes and provide a rational basis for developing intervention strategies to control them.
Tetracycline exposure alters key gut microbiota in Africanized honey bees (Apis mellifera scutellatax spp.)
Authors: Soares Kilmer Oliveira , de Oliveira Celso José Bruno , Rodrigues Adriana Evangelista , Vasconcelos Priscylla Carvalho , da Silva Núbia Michelle Vieira , da Cunha Filho Octavio Gomes , Madden Christopher , Hale Vanessa L.
Published: May 2021

Honey bees play a critical role in ecosystem health, biodiversity maintenance, and crop yield. Antimicrobials, such as tetracyclines, are used widely used across agriculture, medicine, and in bee keeping, and bees can be directly or indirectly exposed to tetracycline residues in the environment. In European honey bees, tetracycline exposure has been linked with shifts in the gut microbiota that negatively impact bee health. However, the effects of antimicrobials on Africanized honey bee gut microbiota have not been examined. The aim of this study was to investigate the effects of tetracycline exposure on the gut microbial community of Africanized honey bees (Apis mellifera scutellatax spp), which are important pollinators in South, Central, and North America. Bees (n=1,000) were collected from hives in Areia-PB, Northeastern Brazil, placed into plastic chambers and kept under controlled temperature and humidity conditions. The control group (CON) was fed daily with syrup (10g) consisting of a 1:1 solution of demerara sugar and water, plus a solid protein diet (10g) composed of 60% soy extract and 40% sugar syrup. The tetracycline group (TET) was fed identically but with the addition of tetracycline hydrochloride (450 µg/g) to the sugar syrup. Bees were sampled from each group before (day 0), and after tetracycline exposure (days 3, 6 and 9). Abdominal contents dissected out of each bee underwent DNA extraction and 16S rRNA sequencing (V3-V4) on an Illumina MiSeq. Sequences were filtered and processed through QIIME2 and DADA2. Microbial community composition and diversity and differentially abundant taxa were evaluated by treatment and time. Bee gut microbial composition (Jaccard) and diversity (Shannon) differed significantly and increasingly over time and between CON and TET groups. Tetracycline exposure was associated with decreased relative abundances ofBombellaandFructobacillus, along with decreases in key core microbiota such asSnodgrassella, Gilliamella, Rhizobiaceae, andApibacter. These microbes are critical for nutrient metabolism and pathogen defense, and decreased abundances of these microbes could negatively affect bee health. Considering the global ecological and economic importance of honey bees as pollinators, it is critical to understand the effects of agrochemicals including antimicrobials on honey bees.
Successful intergeneric transfer of a major apple scab resistance gene (Rvi6) from apple to pear and precise comparison of the downstream molecular mechanisms of this resistance in both species
Authors: Perchepied L. , Chevreau E. , Ravon E. , Gaillard S. , Pelletier S. , Bahut M. , Berthelot P. , Cournol R. , Schouten H.J. , Vergne E.
Published: May 2021

Background

Scab is the most important fungal disease of apple and pear. Apple (Malus x domesticaBorkh.) and European pear (Pyrus communisL.) are genetically related but they are hosts of two different fungal species:Venturia inaequalisfor apple andV. pyrinafor European pear. The apple/V. inaequalispathosystem is quite well known, whereas knowledge about the pear/V. pyrinapathosystem is still limited. The aim of our study was to analyse the mode of action of a major resistance gene of apple (Rvi6) in transgenic apple and pear plants interacting with the two scab species (V. inaequalisandV. pyrina), in order to determine the degree of functional transferability between the two pathosystems.

Results

Transgenic pear clones constitutively expressing theRvi6gene from apple were compared to a scab transgenic apple clone carrying the same construct. After inoculation in greenhouse withV. pyrina, strong defense reactions and very limited sporulation were observed on all transgenic pear clones tested. Microscopic observations revealed frequent aborted conidiophores in theRvi6transgenic pear /V. pyrinainteraction. The macro- and microscopic observations were very comparable to theRvi6apple /V. inaequalisinteraction. However, this resistance in pear proved variable according to the strain ofV. pyrina, and one of the strains tested overcame the resistance of most of the transgenic pear clones. Comparative transcriptomic analyses of apple and pear resistant interactions withV. inaequalisandV. pyrina, respectively, revealed different cascades of molecular mechanisms downstream of the pathogen recognition byRvi6in the two species. Signal transduction was triggered in both species with calcium (and G-proteins in pear) and interconnected hormonal signaling (jasmonic acid in pear, auxins in apple and brassinosteroids in both species), without involvement of salicylic acid. This led to the induction of defense responses such as a remodeling of primary and secondary cell wall, lipids biosynthesis (galactolipids in apple and cutin and cuticular waxes in pear), systemic acquired resistance signal generation (in apple) or perception in distal tissues (in pear), and the biosynthesis of phenylpropanoids (flavonoids in apple but also lignin in pear).

Conclusion

This study is the first example of a successful intergeneric transfer of a resistance gene amongRosaceae, with a resistance gene functioning towards another species of pathogen.
Analyses of hierarchical structures in vulcanized SBR rubber by using contrast-variation USANS and SANS
Authors: Takenaka Mikihito , Nishitsuji Shotaro , Watanabe Yuki , Yamaguchi Daisuke , Koizumi Satoshi
Published: May 2021

The hierarchical structures of poly(styrene-ran-butadiene) (SBR) rubber vulcanized with sulfur in a swollen state were investigated by using the contrast-variation ultra-small-angle neutron scattering (USANS) and small-angle neutron scattering (SANS) techniques. The following three levels of hierarchical structure were found: (i) ZnO clusters surrounded by dense SBR networks of the order of 1000 Å in size, (ii) dense networks of SBR in the size range of 70–100 Å and (iii) a mesh size of the network of the order of 10 Å. In addition to the three kinds of structure, dense networks without ZnO of the order of 1000 Å were also observed. These last networks were formed by ZnO's reaction with sulfur. However, the ZnO clusters disappeared, which is associated with the diffusion of Zn.
The role of occupational meaningfulness and citizenship as mediators between occupational status and recovery: a cross-sectional study among residents with co-occurring problems
Authors: Nesse Linda , Aamodt Geir , Gonzalez Marianne Thorsen , Rowe Michael , Raanaas Ruth Kjærsti
Published: May 2021

Purpose

Engagement in meaningful occupations and being included as full citizens of the community, is essential in everyday life, and may be of considerable relevance for recovery and quality of life. However, persons with co-occurring substance use and mental health problems experience extensive obstacles to engagement in occupations and citizenship. The relationship between objective measures of occupational status and subjective experiences of occupational meaningfulness, citizenship and recovery, is scarcely researched in the context of co-occurring problems. As such, the purpose of this study is to examine associations between occupational status, occupational meaningfulness, citizenship and recovery and quality of life and to examine the roles of occupational meaningfulness and citizenship as possible mediators between occupational status and recovery and quality of life.

Design/methodology/approach

The study used a cross-sectional design with a sample of 104 residents at supported housing sites across six Norwegian cities.

Findings

Linear regression analyzes indicated that occupational status was significantly associated with the citizenship domains caring for others and community participation and with the quality of life measure positive affect. Occupational meaningfulness and citizenship were significantly associated with different domains of recovery and quality of life. Furthermore, mediation analyzes showed that the relationship between occupational status and recovery and quality of life was mediated by caring for others and community participation.

Originality/value

The results suggest that emphasizing opportunities for occupational meaningfulness and citizenship in practice may have positive implications for recovery among persons with co-occurring problems.
Innovation in banking: fusion of artificial intelligence and blockchain
Authors: R. Vedapradha , Ravi Hariharan
Published: May 2021

Purpose

This study aims to analyze the importance of disruptive technological innovations on qualitative service delivery and their impact on the investment banks’ employee performance.

Design/methodology/approach

The cluster sampling method has been used to collect the primary data from the 250 respondents from foreign investment banks. Variables used are employee performance, service delivery, technology, security, operations, strategy and quality through chi-square, linear stepwise multiple regression analysis and correlation.

Findings

Storage network, operating cost, client reporting, cloud system and money laundering are the highest and most significant predictors of employee performance. Employee performance multiplies every unit with a strategic solution owing to positive and robust correlation (0.944). Fusion technology-based banks offer quality service to their clients.

Originality/value

A combination of artificial intelligence and blockchain ensures increasing automation to improve efficiency and reduce the operating cost creating a seamless integration in fraud detection, customer support, risk management, security, digitization and automation process, algorithmic trading, wealth management, etc.
Exploring high amylose rice in combination with carboxymethyl cellulose for preparation of low glycemic index gluten-free shelf-stable cookies
Authors: Naseer Bazila , Naik Haroon Rashid , Hussain Syed Zameer , Bhat Tashooq , Rouf Abdul
Published: May 2021

Purpose

Low glycemic index gluten-free cookies from high amylose rice flour were prepared by modifying baking conditions and ingredient composition.

Design/methodology/approach

Baking temperature, baking time, and concentration of carboxymethyl cellulose (CMC) were varied between 170 and 190° C, 12–25 min, and 0.2–1%, respectively, using central composite rotatable design. The developed cookies were packed in metalized polyester pouches and stored under ambient conditions for a period of 90 days.

Findings

Width and bulk density of cookies increased significantly (p < 0.05) with an increase in baking temperature, while thickness, baking loss and yield decreased with an increase in baking temperature. Puffiness increased predominantly with the increase in the concentration of CMC. Design expert predicted baking temperature of 185° C, baking time of 22 min, and 0.8% concentration of CMC as desirable conditions for the development of gluten-free cookies from rice flour. Cookies developed after following optimized conditions recorded dietary fiber of 4.66%, resistant starch (RS) content of 7.20% and predicted glycemic index (pGI) of 44.60. RS, pGI, moisture, water activity, free fatty acids and peroxide value increased significantly, whereas hardness and overall acceptability decreased during storage.

RPractical implications

Gluten-free (GF) foods are in high demand globally due to the prevalence of celiac disease. Rice lacks gluten protein, and thus, can serve as a potential raw material for the development of GF cookies. In the present study, the ingredient modification and freezing interventions during baking were found to be crucial if the development of low GI gluten-free cookies having good RS content is targeted. Optimized GF cookies prepared via technological intervention and packed in metalized polyester were shelf stable for up to 3 months under ambient conditions. Furthermore, resistant starch content was enhanced while the predicted glycemic index was decreased during storage. Adoption of baking conditions and CMC level optimized in the present study can help to develop shelf-stable GF bakery products for people suffering from comorbidities like celiac disease and diabetes.

Originality/value

Resistant starch content was enhanced while predicted glycemic index was decreased during storage of gluten-free cookies prepared from high amylose rice flour. The developed cookies can be a complementary diet to people suffering from comorbidities like celiac disease and diabetes.
Hometown advantage? Exploring the relationship between location, CSR/CSI and stakeholders’ behavioral intentions
Authors: O'Connor Amy , Mitson Renee , Gilbert Cory
Published: May 2021

Purpose

The purpose of this exploratory study is to investigate the relationship between location (hometown or elsewhere), evaluation of corporations, expectations for corporations in their communities and likelihood to engage in pro-corporate behaviors in corporate social responsibility (CSR) scenarios or anti-corporate behaviors in corporate social irresponsibility (CSI) scenarios. The purpose of our exploratory study is to examine if the location of CSR or CSI activities influence pro and anti-corporation behavioral intentions.

Design/methodology/approach

A quantitative survey method is utilized (N = 1,450). Participants were Minnesota residents who volunteered to take the survey. Surveys were administered at the 2018 Minnesota State Fair.

Findings

Participants described corporations in their community more favorably than corporations located elsewhere and indicated a desire to have more corporations headquartered in their community. In instances of CSR, participants were more likely to engage in pro-corporate behaviors than if the corporation was located elsewhere. However, participants indicated a stronger likelihood of engaging in anti-corporate behaviors when CSI was enacted in their community than if the company was located elsewhere.

Originality/value

This study examines CSR and CSI concurrently, surveys community stakeholders rather than relying on existing databases (e.g. KLD Stats) that measure a limited set of CSR metrics, moves beyond descriptive accounts of CSR behaviors and financial outcomes associated with geography and extends stakeholder-organization relationship theorizing into the CSR/CSI context to interrogate the mutual interdependence between stakeholders and organizations.
Insecure people can eclipse your sun; so identify before it is too late: revisit to the nexus between job insecurity, organizational identification and employee performance behaviour
Authors: Dahiya Rinki
Published: May 2021

Purpose

With the enhancing notions of job insecurity in employees, the objective of this study is to revisit the association between job insecurity and employee performance behaviour (task performance and contextual performance) with the mediating role of organizational identification. Specifically, the study examines how and why there is a negative link between job insecurity and performance and whether organizational identification may serve as a mediating mechanism.

Design/methodology/approach

A time-lagged survey of 192 employees having heterogeneous working background was analysed using the structural equation modelling (SEM) technique.

Findings

The findings highlight that the nexus between job insecurity and organizational citizenship behaviour is fully mediated by organizational identification. However, the organizational identification partially mediated the association between job insecurity and task performance.

Originality/value

The tendency of job insecurity in India is on the rise. This investigation gives a more profound comprehension of behavioural responses of job insecurity on employee performance behaviour with the social identity theoretical perspective. The study contributes to the extant literature by revisiting the model proposed by Piccoli et al. (2017) and includes organizational identification as a mediating mechanism, which has remained unexplored till now in the context of Indian manufacturing industry.