bluuebunny/crossref_metadata_2025 huggingface dataset:
Conserved and novel enhancers in theAedes aegypti single-mindedlocus recapitulate embryonic ventral midline gene expression
Authors: Schember Isabella , Reid William , Sterling-Lentsch Geyenna , Halfon Marc S.
Published: August 2023

Transcriptionalcis-regulatory modules, e.g., enhancers, control the time and location of metazoan gene expression. While changes in enhancers can provide a powerful force for evolution, there is also significant deep conservation of enhancers for developmentally important genes, with function and sequence characteristics maintained over hundreds of millions of years of divergence. Not well understood, however, is how the overall regulatory composition of a locus evolves, with important outstanding questions such as how many enhancers are conserved vs. novel, and to what extent are the locations of conserved enhancers within a locus maintained? We begin here to address these questions with a comparison of the respectivesingle-minded (sim)loci in the two dipteran speciesDrosophila melanogaster(fruit fly) andAedes aegypti(mosquito).simencodes a highly conserved transcription factor that mediates development of the arthropod embryonic ventral midline. We identify two enhancers in theA. aegypti simlocus and demonstrate that they function equivalently in both transgenic flies and transgenic mosquitoes. OneA. aegyptienhancer is highly similar to knownDrosophilacounterparts in its activity, location, and autoregulatory capability. The other differs from any knownDrosophila simenhancers with a novel location, failure to autoregulate, and regulation of expression in a unique subset of midline cells. Our results suggest that the conserved pattern ofsimexpression in the two species is the result of both conserved and novel regulatory sequences. Further examination of this locus will help to illuminate how the overall regulatory landscape of a conserved developmental gene evolves.

AUTHOR SUMMARY

The expression patterns and roles of genes, especially those involved in core developmental processes, are often conserved over vast evolutionary distances. Paradoxically, the DNA sequences surrounding these genes, which contain thecis-regulatory sequences (enhancers) that regulate gene expression, tend to be highly diverged. The manner and extent to which enhancers are functionally conserved, and how the overall organization of regulatory sequences within a locus is preserved or restructured, is not well understood. In this paper, we investigate these questions by identifying enhancers controlling expression of a master nervous system regulatory gene namedsimin the mosquitoAedes aegypti, and comparing their functions and locations to those in the well-characterizedsimlocus of the fruit flyDrosophila melanogaster. Our results suggest that the two species generate identical patterns ofsimexpression through a mix of conserved and novel regulatory sequences. Continued exploration of thesimlocus in these two species will help to build a comprehensive picture of how a regulatory locus for a master developmental regulator has evolved.
Polyadenylation of mRNAs encoding secreted proteins by TENT5 family of enzymes is essential for gametogenesis in mice
Authors: Brouze Michał , Czarnocka-Cieciura Agnieszka , Gewartowska Olga , Kusio-Kobiałka Monika , Jachacy Kamil , Szpila Marcin , Tarkowski Bartosz , Gruchota Jakub , Krawczyk Paweł , Mroczek Seweryn , Borsuk Ewa , Dziembowski Andrzej
Published: August 2023

Cytoplasmic polyadenylation plays a vital role in gametogenesis, however, the participating enzymes and substrates in mammals remain unclear. Using knockout and knock-in mouse models, we describe the essential role of 4 TENT5 poly(A) polymerases in mice fertility and gametogenesis.

TENT5B and TENT5C play crucial, but redundant roles in oogenesis, with double knockout of both genes leading to oocyte degeneration. Additionally, TENT5B-GFP knock-in females display gain-of-function infertility effect with multiple chromosomal aberrations in ovulated oocytes. TENT5C and TENT5D both regulate different stages of spermatogenesis, shown by sterility of males with either gene’s knockout mutation. Finally,Tent5aknockout significantly lowers fertility, although the underlying mechanism is not directly related to gametogenesis.

Through Direct RNA sequencing we discovered that TENT5s polyadenylate mRNAs encoding endoplasmic reticulum-targeted proteins essential for gametogenesis. Sequence motives analysis and reporter mRNA assay revealed that the presence of endoplasmic reticulum-leader represents the primary determinant of TENT5-mediated regulation.
A unified molecular theory of sweet taste: revisit, update and beyond
Authors: Liu Bo
Published: August 2023

The molecular mechanism for the generation of sweet taste is still elusive, mainly because there has no common feature revealed imparting sweetness to various sweeteners1-2, although many principles and models have been proposed to interpret their structure and activity relationships (SARs)3-8. In this research, the SARs of sweet compounds of widely different chemical families were surveyed from a “trace to the source” view on the molecular organization of their components and their interaction with the sweet taste receptor (STR). This leads to a disclosure of intrinsic connectivity patterns in both sweeteners and STR: charge complementarity and compatibility between components, which afford the complementary sweetener-receptor interaction that induces receptor activation, accounting for the molecular origin of sweet taste. Herein, the analogous topology between glucophores in sweeteners and its counterparts in receptor, and their befitting orientated interaction, which is the common molecular feature of sweeteners, are firstly revealed. This paradigm not only provides a meaningful framework and helpful guidelines for further exploring SARs and molecular modification/design of sweeteners, but also has significant implications to illuminate the underlying mechanisms of molecular origin/evolution of both sweeteners and sweet taste receptors.
Oral administration of GnRH via a cricket vehicle stimulates spermiation in tiger salamanders (Ambystoma tigrinum)
Authors: Chen Devin M. , Chen Li-Dunn , Kouba Carrie K. , Songsasen Nucharin , Roth Terri L. , Allen Peter J. , Kouba Andrew J.
Published: August 2023

More than 50% of caudates are threatened with extinction and are in need ofex-situbreeding programs to support conservation efforts and species recovery. Unfortunately, many salamander populations under human care can experience reproductive failure, primarily due to missing environmental cues necessary for breeding. Assisted reproductive technologies (ARTs) are a useful suite of techniques for overcoming or bypassing these missing environmental cues to promote breeding. Exogenous hormones are used to stimulate natural breeding behaviors or gamete expression forin-vitrofertilization or biobanking and are typically administered intramuscularly in caudates. While effective, intramuscular injection is risky to perform in smaller-bodied animals, resulting in health and welfare risks. This research investigated the spermiation response to hormone administration through a non-invasive oral route using the tiger salamander (Ambystoma tigrinum) as a model species. Male salamanders were randomly rotated six weeks apart through four treatments (n = 11 males/treatment) in which animals received a resolving dose of gonadotropin-releasing hormone (GnRH) as follows: (1) Prime-Only (0.0 µg/g); (2) Low (0.25 µg/g); (3) Medium (1.0 µg/g); and (4) High (2.0 µg/g). All males were given a GnRH priming dose (0.25 µg/g) 24 hours prior to the resolving dose. Exogenous hormone was delivered inside of a cricket (Gryllodes sigillatus) that was presented as a food item by tweezers. Sperm samples were collected at 1, 3, 6, 9, 12, and 24 hours after the resolving dose and analyzed for quantity and quality. For all treatments, sperm concentration was produced in an episodic pattern over time. The Prime-Only treatment had a lower (p < 0.05) percent of sperm exhibiting normal morphology compared to treatments utilizing a resolving dose of GnRH. Overall, oral administration of GnRH is a feasible route of inducing spermiation in salamanders, yielding sperm of sufficient quantity and quality forin-vitrofertilization and biobanking efforts.
Neuron-specific chromatin disruption at CpG islands and aging-related regions in Kabuki syndrome mice
Authors: Boukas Leandros , Luperchio Teresa Romeo , Razi Afrooz , Hansen Kasper D. , Bjornsson Hans T.
Published: August 2023

Many Mendelian developmental disorders caused by coding variants in epigenetic regulators have now been discovered. Epigenetic regulators are broadly expressed, and each of these disorders typically exhibits phenotypic manifestations from many different organ systems. An open question is whether the chromatin disruption – the root of the pathogenesis – is similar in the different disease-relevant cell types. This is possible in principle, since all these cell-types are subject to effects from the same causative gene, that has the same kind of function (e.g. methylates histones) and is disrupted by the same germline variant. We focus on mouse models for Kabuki syndrome types 1 and 2, and find that the chromatin accessibility abnormalities in neurons are mostly distinct from those in B or T cells. This is not because the neuronal abnormalities occur at regulatory elements that are only active in neurons. Neurons, but not B or T cells, show preferential chromatin disruption at CpG islands and at regulatory elements linked to aging. A sensitive analysis reveals that the regions disrupted in B/T cells do exhibit chromatin accessibility changes in neurons, but these are very subtle and of uncertain functional significance. Finally, we are able to identify a small set of regulatory elements disrupted in all three cell types. Our findings reveal the cellular-context-specific effect of variants in epigenetic regulators, and suggest that blood-derived “episignatures” may not be well-suited for understanding the mechanistic basis of neurodevelopment in Mendelian disorders of the epigenetic machinery.
Chromatin structure from high resolution microscopy: scaling laws and microphase separation
Authors: Remini Loucif , Segers Midas , Palmeri John , Walter Jean-Charles , Parmeggiani Andrea , Carlon Enrico
Published: August 2023

Recent advances in experimental fluorescence microscopy allow high accuracy determination (resolution of 50nm) of the 3D physical location of multiple (up to ∼ 102) tagged regions of the chromosome. We investigate publicly available microscopy data for two loci of the human Chr.21 obtained from multiplexed FISH methods for different cell lines and treatments. Inspired by polymer physics models, our analysis centers around distance distributions between different tags, aiming to unravel the chromatin conformational arrangements. We show that for any specific genomic site, there are (at least) two different conformational arrangements of chromatin, implying coexisting distinct topologies which we refer to as phaseαand phaseβ. These two phases show different scaling behaviors: the former is consistent with a crumpled globule while the latter indicates a confined, but more extended conformation, as a looped domain. The identification of these distinct phases sheds light on the coexistence of multiple chromatin topologies and provides insights into the effects of cellular context and/or treatments on chromatin structure.
Multivalent GU-rich oligonucleotides sequester TDP-43 in the nucleus by inducing high molecular weight RNP complexes
Authors: Zhang Xi , Das Tanuza , Chao Tiffany F. , Trinh Vickie , Carmen Rogger , Ling Jonathan , Kalab Petr , Hayes Lindsey R.
Published: August 2023

TDP-43 nuclear clearance and cytoplasmic aggregation are hallmarks of TDP-43 proteinopathies. We recently demonstrated that binding to endogenous nuclear GU-rich RNAs sequesters TDP-43 in the nucleus by restricting its passive nuclear export. Here, we tested the feasibility of synthetic RNA oligonucleotide-mediated augmentation of TDP-43 nuclear localization. Using biochemical assays, we compared the ability of GU-rich oligonucleotides to engage in multivalent, RRM-dependent binding with TDP-43. When transfected into cells, (GU)16 attenuated TDP-43 mislocalization induced by transcriptional blockade or RanGAP1 ablation. Clip34nt and (GU)16 accelerated TDP-43 nuclear re-import after cytoplasmic mislocalization. RNA pulldowns confirmed that multivalent GU-oligonucleotides induced high molecular weight RNP complexes, incorporating TDP-43 and possibly other GU-binding proteins. Transfected GU-repeat oligos disrupted TDP-43 cryptic exon repression, likely by diverting TDP-43 from endogenous RNAs, except for Clip34nt which contains interspersed A and C. Thus, exogenous multivalent GU-RNAs can promote TDP-43 nuclear localization, though pure GU- repeat motifs impair TDP-43 function.
Anopheles gambiaemosGILT regulates innate immune genes andzpgexpression
Authors: Arora Gunjan , Tang Xiaotian , Cui Yingjun , Yang Jing , Chuang Yu-Min , Joshi Jayadev , Sajid Andaleeb , Dong Yuemei , Cresswell Peter , Dimopoulos George , Fikrig Erol
Published: August 2023

Gene-edited mosquitoes lacking agamma-interferon-inducible lysosomal thiol reductase-like protein, namely (mosGILTnull) have lowerPlasmodiuminfection, which is linked to impaired ovarian development and immune activation. The transcriptome ofmosGILTnullA. gambiaewas therefore compared to wild type (WT) by RNA-sequencing to delineate mosGILT-dependent pathways. Compared to WT mosquitoes,mosGILTnullA. gambiaedemonstrated altered expression of genes related to oogenesis, 20-hydroxyecdysone synthesis, as well as immune-related genes. Serendipitously, the zero population growth gene,zpg, an essential regulator of germ cell development was found to be one of the most downregulated genes inmosGILTnullmosquitoes. These results provide the crucial missing link between two previous studies on the role ofzpgandmosGILTin ovarian development. This study further demonstrates that mosGILT has the potential to serve as a target for the biological control of mosquito vectors and to influence thePlasmodiumlife cycle within the vector.
Characterization ofN-glycosylation and its Functional Role in SIDT1-Mediated RNA Uptake
Authors: Yang Tingting , Xiao Haonan , Chen Xiulan , Zheng Le , Guo Hangtian , Wang Jiaqi , Jiang Xiaohong , Zhang Chen-Yu , Yang Fuquan , Ji Xiaoyun
Published: August 2023

The mammalian SID-1 transmembrane family members, SIDT1 and SIDT2, are multi-pass transmembrane proteins that mediate the cellular uptake and intracellular trafficking of nucleic acids, playing important roles in the immune response and tumorigenesis. Previous work has suggested that human SIDT1 and SIDT2 areN-glycosylated, but the precise site-specificN-glycosylation information and its functional contribution remain unclear. In this study, we employ high-resolution liquid chromatography tandem mass spectrometry to comprehensively map theN-glycosites and quantify theN-glycosylation profiles of SIDT1 and SIDT2. Further molecular mechanistic probing elucidates the essential role ofN-linked glycans in regulating cell surface expression, RNA binding, protein stability, and RNA uptake of SIDT1. Our results provide crucial information about the potential functional impact ofN-glycosylation in the regulation of SIDT1-mediated RNA uptake and provide insights into the molecular mechanisms of this promising nucleic acid delivery system, with potential implications for therapeutic applications.
A patchwork pathway for catabolism of the sulfosugar sulfofucose
Authors: Li Jinling , Lee Mihwa , Yang Shuxin , Lewis Jessica M. , Herisse Marion , Pidot Sacha J. , Scott Nichollas E. , Williams Spencer J.
Published: August 2023

We report the isolation ofParacoccus onubensisstrain Merri, which can grow on the rare sulfosugar sulfofucose (6-deoxy-6-sulfo-D-galactose) as sole carbon source, leading to its breakdown and release of sulfite. Genome sequencing and comparative proteomics of samples grown on glucose versus sulfofucose identified a genetic locus containing most of the genes for a sulfoglycolytic pathway for breakdown of sulfofucose to the 3-carbon organosulfonate sulfolactaldehyde, and a biomineralization pathway for catabolism of sulfolactaldehyde to pyruvate and sulfite. A candidate sulfotagatose-1-phosphate aldolase was expressed and was active on the epimeric substrate sulfofructose-1-phosphate. Its 3D X-ray structure revealed a close homology to sulfofructose-1-phosphate aldolase from the sulfoglycolytic Embden-Meyerhof-Parnas pathway. A patchwork sulfofucose catabolism pathway is proposed involving a sulfofucolytic Embden-Meyerhof-Parnas and short-chain organosulfonate biomineralization pathway.

Significance

Sulfosugars are important compounds in the biogeochemical sulfur cycle and are produced by a wide range of photosynthetic plants, algae and cyanobacteria. While the pathways for the biosynthesis and catabolism of sulfoquinovose are well studied, much less is known about the rarer sulfosugar sulfofucose. We report a bacterium that can use sulfofucose as sole carbon source and achieve its complete breakdown to produce sulfite. We propose that sulfofucose catabolism is achieved using enzymes of the sulfoglycolytic Embden-Meyerhof-Parnas pathway that tolerate a change in stereochemistry at C4 of the sulfosugar. The sulfolactaldehyde output of this pathway is broken down to sulfite through a biomineralization pathway via sulfolactate. Microbial metabolism of this rare sulfosugar can be achieved through repurposing enzymes within known sulfosugar and short-chain organosulfonate catabolism catabolism.
A sum of its parts: A systematic review evaluating biopsychosocial and behavioral determinants of perinatal depression
Authors: Longoria Kayla D. , Nguyen Tien C. , Franco-Rocha Oscar , Garcia Sarina R. , Lewis Kimberly A. , Gandra Sreya , Cates Frances , Wright Michelle L.
Published: August 2023

Introduction

Depression is one of the most common yet underdiagnosed perinatal complications and our understanding of the pathophysiology remains limited. Though perinatal depression is considered to have a multifactorial etiology, integrative approaches to investigation are minimal. This review takes an integrative approach to systematically evaluate determinants and potential interactions among determinants of perinatal depression across four domains (i.e., biological, behavioral, environmental, social) and appraise the quality of methods applied.

Methods

Four databases (i.e., PubMed, CINAHL, APA PsycInfo, and Web of Science) were systematically searched to identify studies examining determinants of perinatal depression in adult perinatal persons (≥ 18 years). Articles were excluded if the outcomes were not focused on perinatal persons and depression or depression symptoms, the evaluation of depression was specific to a discrete facet of the perinatal period with probable psychological consequences (e.g., abortion, fetal/infant loss, adoption), or was considered grey literature. The Critical Appraisal Skills Programme and AXIS tools were used to guide and standardize quality appraisal assessments and determine the level of risk of bias.

Results

Of the 454 articles identified, 25 articles were included for final review. A total of 14 categories of determinants were investigated: biological (5), behavioral (4), social and environmental (5). Though only 28% of studies simultaneously considered determinants under more than one domain, a pattern of interactions with the tryptophan pathway emerged when determinants across domains were aggregated. Concerns for risk of bias were noted or were unclear for three types of bias: 13 (52%) selection bias, 3 (12%) recall bias, and 24 (96%) measurement bias.

Conclusions

Future research is needed to explore interactions among determinants and the tryptophan pathway; to strengthen the methods applied to this area of inquiry; and to generate evidence for best practices in reporting, selecting, and applying methods for measuring determinants and perinatal depression.
Neo-epitope identification by weakly-supervised peptide-TCR binding prediction
Authors: Gao Yuli , Gao Yicheng , Li Wannian , Wu Siqi , Xing Feiyang , Zhou Chi , Fu Shaliu , Chuai Guohui , Chen Qinchang , Zhang He , Liu Qi
Published: August 2023

The identification of T cell neo-epitopes is fundamental and computational challenging in tumor immunotherapy study. As the binding of pMHC - T cell receptor (TCR) is the essential condition for neo-epitopes to trigger the cytotoxic T cell reactivity, several computational studies have been proposed to predict neo-epitopes from the perspective of pMHC-TCR binding recognition. However, they often failed with the inaccurate binding prediction for a single pMHC -TCR pair due to the highly diverse TCR space. In this study, we proposed a novel weakly-supervised learning framework,i.e.,TCRBagger, to facilitate the personalized neo-epitope identification with weakly-supervised peptide-TCR binding prediction by bagging a sample-specific TCR profile.TCRBaggerintegrates three carefully designed learning strategies,i.e. a self-supervised learning strategy, a denoising learning strategy and a Multi-Instance Learning (MIL) strategy in the modeling of peptide-TCR binding. Our comprehensive tests revealed thatTCRBaggerexhibited great advances over existing tools by modeling interactions between peptide and TCR profiles. We further appliedTCRBaggerin different clinical settings, including (1) facilitating the peptide-TCR binding prediction under MIL using single-cell TCR-seq data. (2) improving the patient-specific neoantigen prioritization compared to the existing neoantigen identification tools. Collectively,TCRBaggerprovides novel perspectives and contributions for identifying neo-epitopes as well as discovering potential pMHC-TCR interactions in personalized tumor immunotherapy.
MethanotrophicMethanoperedensarchaea host diverse and interacting extrachromosomal elements
Authors: Shi Ling-Dong , West-Roberts Jacob , Schoelmerich Marie C. , Penev Petar I. , Chen LinXing , Amano Yuki , Lei Shufei , Sachdeva Rohan , Banfield Jillian F.
Published: August 2023

Methane emissions that contribute to climate change can be mitigated by anaerobic methane-oxidizing archaea such asMethanoperedens. SomeMethanoperedenshave huge extrachromosomal genetic elements (ECEs) called Borgs that may modulate their activity, yet the broader diversity ofMethanoperedensECEs is little studied. Here, we report small enigmatic linear ECEs, circular viruses and unclassified ECEs, that we predict replicate withinMethanoperedens. The linear ECEs have features such as inverted terminal repeats, pervasive tandem repeats, and coding patterns that are strongly reminiscent of Borgs, but they are only 52 kb to 145 kb in length. They share proteins with Borgs andMethanoperedens. Thus, we refer to them as mini-Borgs. Mini-Borgs are genetically diverse and we assign them to at least five family-level groups. We also identify eight novel families ofMethanoperedensviruses, some of which encode multiheme cytochromes, and unclassified circular ECEs that encode TnpB genes. A population-heterogeneous CRISPR array is in close proximity to the TnpB and has spacers that target otherMethanoperedensECEs including previously reported plasmids. The diverse groups of ECEs exchange genetic information with each other and withMethanoperedens, likely impacting the activity and evolution of these environmentally important archaea.
The Calcium-sensing receptor is an important regulator of female visceral and perivascular adipocyte function
Authors: Higgins Erin , Galofre Zaniah Gonzalez , McAbney John , Leiper James , Dowsett Laura
Published: August 2023

The Calcium-sensing receptor (CaSR) is a G protein-coupled receptor activated by fluctuations in extracellular calcium concentrations. Its importance in calcium homeostasis has long been established, though its role in other tissues is not well understood. Obesity is a major epidemic with both clinical and social consequences, therefore, understanding the full function and regulation of adipocytes is of critical importance. Adipocyte CaSR has previously been linked to lipolysis and inflammationin vitro. In this study, we set out to further our understanding of adipocyte CaSRin vivovia the generation of an adipocyte specific CaSR knockout mouse (CaSRAd-/-). We found female CaSRAd-/-mice weighed less than wildtype littermates with a significant reduction in visceral adipocyte size potentially due to increased expression of brown fat markers UCP-1 and Cidea. We also established that CaSR is expressed in perivascular adipose tissue (PVAT) and that its deletion protects female mice from PVAT driven hypercontractility. In contrast CaSR deletion had no effect on male body mass, adipocyte size or vascular reactivity. In conclusion, CaSR seems to be of importance in female but not male visceral and perivascular adipose tissue.
Alzheimer’s disease linked Aβ42 exerts product feedback inhibition on γ-secretase impairing downstream cell signaling
Authors: Zoltowska Katarzyna Marta , Das Utpal , Lismont Sam , Enzlein Thomas , Maesako Masato , Houser Mei CQ , Franco María Luisa , Özcan Burcu , Moreira Diana Gomes , Karachentsev Dmitry , Becker Ann , Hopf Carsten , Vilar Marçal , Berezovska Oksana , Mobley William , Chávez-Gutiérrez Lucía
Published: August 2023

Amyloid β (Aβ) peptides accumulating in the brain are proposed to trigger Alzheimer’s disease (AD). However, molecular cascades underlying their toxicity are poorly defined.

Here, we explored a novel hypothesis for Aβ42 toxicity that arises from its proven affinity for γ-secretases. We hypothesized that the reported increases in Aβ42, particularly in the endolysosomal compartment, promote the establishment of a product feedback inhibitory mechanism on γ-secretases, and thereby impair downstream signaling events.

We show that human Aβ42 peptides, but neither murine Aβ42 nor human Aβ17-42 (p3), inhibit γ-secretases and trigger accumulation of unprocessed substrates in neurons, including C-terminal fragments (CTFs) of APP, p75 and pan-cadherin. Moreover, Aβ42 treatment dysregulated cellular homeostasis, as shown by the induction of p75-dependent neuronal death in two distinct cellular systems.

Our findings raise the possibility that pathological elevations in Aβ42 contribute to cellular toxicity via the γ-secretase inhibition, and provide a novel conceptual framework to address Aβ toxicity in the context of γ-secretase-dependent homeostatic signaling.
Genome-based metabolic and phylogenomic analysis of the type strains ofTerrisporobactermayombei,Terrisporobacter petroleariusandTerrisporobacter glycolicus
Authors: Böer Tim , Bengelsdorf Frank R. , Bömeke Mechthild , Daniel Rolf , Poehlein Anja
Published: August 2023

To date, three validly published type strains of the genusTerrisporobacterare covered by draft genome sequences, and the genes and pathway responsible for acetogenesis have not been analyzed. Here, we report complete genome sequences of the bacterial type strainsTerrisporobacter petroleariusJCM 19845T,Terrisporobacter mayombeiDSM 6539TandTerrisporobacter glycolicusDSM 1288T. Functional annotation, KEGG pathway module reconstructions and screening for virulence factors were performed. Various species-specific vitamin, cofactor and amino acid auxotrophies were identified and a model for acetogenesis ofTerrisporobacterwas constructed. The complete genomes harbored a gene cluster for the reductive proline-dependent branch of the Stickland reaction located on an approximately 21 kb plasmid, which is exclusively found in theTerrisporobactergenus. Phylogenomic analysis of availableTerrisporobactergenomes suggested a reclassification of most isolates asT. glycolicusintoT. petrolearius.
Influence of Temperate Forest Autumn Leaf Phenology on Segmentation of Tree Species from UAV Imagery Using Deep Learning
Authors: Cloutier Myriam , Germain Mickaël , Laliberté Etienne
Published: August 2023

Remote sensing of forests has become increasingly accessible with the use of unoccupied aerial vehicles (UAV), along with deep learning, allowing for repeated high-resolution imagery and the capturing of phenological changes at larger spatial and temporal scales. In temperate forests during autumn, leaf senescence occurs when leaves change colour and drop. However, the influence of leaf senescence in temperate forests on tree species segmentation using a Convolutional Neural Network (CNN) has not yet been evaluated. Here, we acquired high-resolution UAV imagery over a temperate forest in Quebec, Canada on seven occasions between May and October 2021. We segmented and labelled 23,000 tree crowns from 14 different classes to train and validate a CNN for each imagery acquisition. The CNN-based segmentation showed the highest F1-score (0.72) at the start of leaf colouring in early September and the lowest F1-score (0.61) at peak fall colouring in early October. The timing of the events occurring during senescence, such as leaf colouring and leaf fall, varied substantially between and within species and according to environmental conditions, leading to higher variability in the remotely sensed signal. Deciduous and evergreen tree species that presented distinctive and less temporally-variable traits between individuals were better classified. While tree segmentation in a heterogenous forest remains challenging, UAV imagery and deep learning show high potential in mapping tree species. Our results from a temperate forest with strong leaf colour changes during autumn senescence show that the best performance for tree species segmentation occurs at the onset of this colour change.
Essential role of proline synthesis and the one-carbon metabolism pathways for systemic virulence ofStreptococcus pneumoniae
Authors: Ramos-Sevillano Elisa , Ercoli Giuseppe , Guerra-Assunção José Afonso , Betts Modupeh , Partridge Frederick , Fernandes Vitor E. , Wall Emma , Gordon Stephen B. , Ferreira Daniela M. , Heyderman Rob , Brown Jeremy S.
Published: August 2023

Previous virulence screens have indicated potential roles duringStreptococcus pneumoniaeinfection for the one-carbon metabolism pathway component Fhs and proline synthesis mediated by ProABC. To define how these metabolic pathways affectS. pneumoniaevirulence we have investigated phenotypes and transcription profiles of Δfhsand ΔproABCstrain mutants.S. pneumoniaecapsular serotype 6B BHN418 Δfhsand ΔproABCmutant strains were markedly reduced virulence in mouse models of systemic infection and pneumonia, but were still able to colonise the nasopharynx. Although the Δfhsand ΔproABCmutant strains grew normally in complete media, both mutant strains had markedly impaired growth in chemically defined medium, human serum and human CSF. The ΔproABCstrain also had impaired growth under conditions of osmotic and oxidative stress. When transferred to the serotype 2 D39S. pneumoniaestrain background, the Δfhsmutation replicated the virulence and growth in serum phenotype of the BHN418 mutation. In contrast, the D39 ΔproABCmutant could cause septicaemia and grow in human serum, indicating the role of this genetic locus during virulence is strain-specific. In human sera the Δfhsand ΔproABCmutants both had major derangements in global gene transcription affecting multiple but different metabolic pathways, identifying the correspondingS. pneumoniaemetabolic functions affected by these genes under infection-related conditions. Our data demonstrate an essential role for theS. pneumoniaeone- carbon metabolism and a strain-conditional role for proline biosynthesis for growth in physiological fluids and therefore systemic infection, and further demonstrate the vital importance of bacterial metabolism for disease pathogenesis.

Importance

Rapid adaptation to grow within the physiological conditions found in the host environment is an essential but poorly understood virulence requirement for systemic pathogens such asStreptococcus pneumoniae. We have now demonstrated an essential role for the one-carbon metabolism pathway and a conditional role depending on strain background for proline biosynthesis forS. pneumoniaegrowth in serum or CSF and therefore for systemic virulence. RNAseq data demonstrated that loss of one carbon metabolism or proline biosynthesis both have profound but differing effects onS. pneumoniaemetabolism in human serum, identifying the metabolic processes dependent on each pathway during systemic infection. These data provide a more detailed understanding of the adaptations required by systemic bacterial pathogens in order to cause infection, and demonstrate that the requirement for some of these adaptations vary between strains from the same species and could therefore underpin strain variations in virulence potential.
Invariant point message passing for protein side chain packing
Authors: Randolph Nicholas Z. , Kuhlman Brian
Published: August 2023

Protein side chain packing (PSCP) is a fundamental problem in the field of protein engineering, as high-confidence and low-energy conformations of amino acid side chains are crucial for understanding (and designing) protein folding, protein-protein interactions, and protein-ligand interactions. Traditional PSCP methods (such as the Rosetta Packer) often rely on a library of discrete side chain conformations, or rotamers, and a forcefield to guide the structure to low-energy conformations. Recently, deep learning (DL) based methods (such as DLPacker, AttnPacker, and DiffPack) have demonstrated state-of-the-art predictions and speed in the PSCP task. Building off the success of geometric graph neural networks for protein modeling, we present the Protein Invariant Point Packer (PIPPack) which effectively processes local structural and sequence information to produce realistic, idealized side chain coordinates using χ-angle distribution predictions and geometry-aware invariant point message passing (IPMP). On a test set of ∼1,400 high-quality protein chains, PIPPack is highly competitive with other state-of-the-art PSCP methods in rotamer recovery and per-residue RMSD but is significantly faster.
Regulation of the trade-off between cold stress and growth byBcGSTF10
Authors: Shen Yunlou , Wang Guangpeng , Ran Jiajun , Li Yiran , Wang Huiyu , Ding Qiang , Li Ying , Hou Xilin
Published: August 2023

Cold stress represents a significant threat to global agricultural productivity and food security. Typically, plant resistance to cold stress is accompanied by a growth deficit and a reduction in yield. In this study, we have discovered a novel gene,BcGSTF10, which has not been previously reported to be involved in low-temperature stress. On the one hand, biochemical and genetic analyses have demonstrated that BcGSTF10 interacts with BcICE1 to promote the expression ofCBFgenes, thereby enhancing freezing stress tolerance in non-heading Chinese cabbage [NHCC,Brassica campestris (syn. Brassica rapa)ssp.chinensis] andArabidopsis. On the other hand, the expression of theBcGSTF10gene is directly repressed by BcCBF2, whileBcGSTF10exhibits a positive role in growth in both NHCC andArabidopsis. This dual function ofBcGSTF10indicates its pivotal role in balancing low-temperature stress and growth, which will inform the development of strategies to breed climate-resilient and high-yield crops, thereby contributing to sustainable agriculture.
The ketamine metabolite (2R,6R)-hydroxynorketamine rescues hippocampal mRNA translation, synaptic plasticity and memory in mouse models of Alzheimer’s disease
Authors: Ribeiro Felipe C. , Cozachenco Danielle , Argyrousi Elentina K. , Staniszewski Agnieszka , Wiebe Shane , Calixtro Joao D. , Soares-Neto Rubens , Al-Chami Aycheh , Sayegh Fatema El , Bermudez Sara , Arsenault Emily , Cossenza Marcelo , Lacaille Jean-Claude , Nader Karim , Sun Hongyu , De Felice Fernanda G. , Lourenco Mychael V. , Arancio Ottavio , Aguilar-Valles Argel , Sonenberg Nahum , Ferreira Sergio T.
Published: August 2023

Impaired synaptic plasticity and progressive memory deficits are major hallmarks of Alzheimer’s disease (AD). Hippocampal mRNA translation, required for memory consolidation, is defective in AD. Here, we show that systemic treatment with (2R,6R)- hydroxynorketamine (HNK), an active metabolite of the antidepressant ketamine, prevented deficits in hippocampal mRNA translation, long-term potentiation (LTP) and memory induced by AD-linked amyloid-β oligomers (AβOs) in mice. HNK activated hippocampal extracellular signal-regulated kinase 1/2 (ERK1/2), mechanistic target of rapamycin (mTOR), and p70S6 kinase 1 (S6K1)/ribosomal protein S6 (S6), which promote protein synthesis and synaptic plasticity. Stimulation of S6 phosphorylation by HNK was mTORC1-dependent, while rescue of hippocampal LTP and memory in HNK-treated AβO-infused mice was ERK1/2-dependent and, partially, mTORC1- dependent. Remarkably, treatment with HNK corrected LTP and memory deficits in aged APP/PS1 mice. Transcriptomic analysis further showed that HNK rescued signaling pathways that are aberrant in APP/PS1 mice, including inflammatory and hormonal responses, and programmed cell death. Taken together, our findings demonstrate that HNK induces signaling and transcriptional responses that correct deficits in hippocampal synaptic plasticity and memory in AD mouse models. These results raise the prospect that HNK could serve as a therapeutic to prevent or reverse memory decline in AD.
How much does an employer's attractiveness matter to youth employment? Evidence from a developing country
Authors: Buitek Elvira К. , Kaliyeva Saule A. , Turginbayeva Ardak N. , Meldakhanova Marziya K. , Shaikh Aijaz A.
Published: August 2023

Purpose

Drawing on the contemporary literature and the theory of employer attractiveness, the authors aimed to examine key antecedents and consequences of employer attractiveness by proposing functional hypotheses and relationships between some endogenous variables.

Design/methodology/approach

Using the quota-cum-purposive sampling method, the unit of analysis selected for this study was millennials aged 18–35 years and working in the hospitality, travel, tourism and leisure (HTTL) sectors for the last two years. A total of 218 responses were collected in three months (June–August 2022). The data were analysed using partial least squares structural equation modelling (PLS-SEM).

Findings

For young employees, company recruitment behaviour, company image and source credibility are significantly and directly related to company attractiveness. The relationship between company image and employee word of mouth (WOM) was significantly positive. Company recruitment behaviour was found to significantly influence employee commitment. Company attractiveness was found to be directly related to young employees' WOM about the company and commitment to it.

Originality/value

The study establishes the significance of company attractiveness because a company's success largely depends on the company's ability to attract and retain a talented and skilled workforce. Moreover, the present study provides much-needed insights to policymakers and regulators that can help the policymakers define and implement favourable policies to promote and protect the country's job market and offer directions to youth employment.
Survival still in dilemma: an empirical analysis of factors influencing the performance and survival of eateries in COVID-19-prone world
Authors: Dhillon Dilpreet Kaur , Mahajan Pranav , Kaur Kuldip
Published: August 2023

Purpose

Distancing people socially as a precautionary measure against the mushrooming of COVID-19’s health and economic crisis has deleteriously affected the performance of the eatery industry to a great extent. Many food outlets failed to cope up with crisis and opted to move out, and many still vie to survive through pandemic. It becomes vital for researchers to understand what factors influence the performance and survival of eateries during the pandemic? The study makes an attempt to fabricate new factors which affect the performance and contribute significantly towards the survival of eateries in this new COVID-19-prone world.

Design/methodology/approach

The present study is a cross-sectional analysis with the sample of 150 eateries from the walled city of Punjab (India), i.e. Amritsar. Factor analysis is employed to scrutinise the factors which influence the performance of eateries during the pandemic, and to analyse factors which contribute significantly for the survival of eateries, logistic regression is performed.

Findings

The empirical analysis reveals that at prior psychological factor, followed by turnover factor, external factor, financial factor and marketing factor influence the performance of eateries during the pandemic. Only three factors, namely turnover factor, external factor and financial factor, turned up to be significant towards the survival rate of an eatery. The marketing factor which is a crucial contributor for survival of business in literature has turned out to be insignificant during the times of pandemic.

Originality/value

With the arrival of pandemic, the preference of people has changed, and the business environment in which entities operate has turned more complex. The present study is one of the pioneer attempts to evaluate whether the factors responsible for performance or survival of an eatery during normal times is relevant during the pandemic as well. The study contributes to the literature of eatery industry by adding a new variable namely psychological factor, i.e. changes witnessed in customers’ preference to visit an eatery.
An empirical study on Lean and its impact on sustainability in services
Authors: Lizarelli Fabiane Letícia , Chakraborty Ayon , Antony Jiju , Furterer Sandy , Maalouf Maher , Carneiro Matheus Borges
Published: August 2023

Purpose

Lean implementation has become popular over the past three decades in the industry and is becoming more prevalent in, service organizations. The objective of this study is to evaluate the impact of social and technical Lean practices on sustainable performance (i.e. economic, environmental and social) in service organizations.

Design/methodology/approach

The methodology includes the analysis of global results obtained from 139 managers from the service sector.

Findings

The results demonstrate that Lean practices have a positive effect on the three perspectives of sustainable performance, regardless of the company size and duration of Lean implementation. Furthermore, both social and technical Lean practices have a similar impact on environmental and economic performance, but their impact on social performance differs, since social Lean practices have a stronger impact on social performance.

Practical implications

This study has a significant contribution to Lean practitioners in service sectors, as it demonstrates that efforts to apply Lean practices can benefit economic results as well as environmental and social performance.

Originality/value

Majority of existing studies focused on the isolated impact of Lean on one of the triple bottom line performance aspects and with a scarcity of studies within the context of services. The intersection of these three strategic areas – Lean, sustainability and services – has not been extensively addressed. There is also a lack of studies that observe sustainability in environmental, social and economic performance, mainly in the service sector.
From “intimate-insider” to “relative-outsider”: an autoethnographic account of undertaking social work research in one’s own “backyard”
Authors: Murphy Ciarán
Published: August 2023

Purpose

This study aims to explore the challenges of being simultaneously “intimate insider” and “relative outsider” whilst undertaking an ethnography into a statutory child protection team. As a novice researcher seeking to explore a world of which he was already part, ethnography was considered the most suitable means for exploring child protection social workers’ discretion. However, by subscribing to binary notions of “insider” and “outsider” at the commencement of the study, the author underplayed the dilemma of reconciling friendships with his researcher role, as well as the barriers that his more junior organisational status could create.

Design/methodology/approach

This study provides an autoethnographic account of these challenges, and the author’s evolving status and movement between “insider” and “outsider” relative to different groups within the children’s services department.

Findings

The implications include the potential for being simultaneously “insider” and “outsider” when undertaking research within one’s employing organisation; the need to reconcile challenging social work tasks with researcher responsibilities; and the difficulty of maintaining pre-existing relationships, whilst also cultivating an objective research profile.

Originality/value

This paper offers an important contribution to the limited accounts of conducting research from “inside” a statutory children’s services department and will be of benefit to early career researchers considering a research project within their own “backyard”.
Abnormal returns and anti-leverage effect in the time of Russo-Ukrainian War 2022: evidence from oil, wheat and natural gas markets
Authors: Vasileiou Evangelos
Published: August 2023

Purpose

This study examines the impact of the Russo-Ukrainian War on the commodity markets of oil, wheat, and natural gas, in which these two countries play/have a dominant role. The author examines if during these extreme events an anti-leverage effect emerges and indicates the abnormal conditions of the markets.

Design/methodology/approach

The author uses daily returns from the future prices of brent oil, wheat, and natural gas for the period 31.3.2020–31.3.2022 and applies the exponential and the threshold asymmetry GARCH models.

Findings

The empirical findings confirm the existence of anti-leverage effect in the wheat and natural gas commodity markets and point to the existence of the leverage effect in the Brent market.

Practical implications

The existence of the anti-leverage effect means that stock prices and volatility present a positive relationship which is in contrast to the normal/conventional stylized facts which suggest the opposite. These findings could be useful for scholars and practitioners because they enable them to examine market abnormalities using the anti-leverage effect as a criterion and explore its relationship with extreme conditions and strategies that lead to skyrocketing increases in prices.

Originality/value

This study investigates the anti-leverage effect in commodity markets under extreme conditions, which has received little attention in the literature. Moreover, this paper links the existence of the anti-leverage effect with abnormal growth in asset prices, which shows a new direction for the behavior of assets when extreme conditions emerge.