bluuebunny/crossref_metadata_2025_split huggingface dataset:
IDSL.GOA: Gene Ontology Analysis for Interpreting Metabolomic datasets
Authors: Mahajan Priyanka , Fiehn Oliver , Barupal Dinesh 
Published: March 2023

AbstractBiological interpretation of metabolomic datasets often ends at a pathway analysis step to find the over-represented metabolic pathways in the list of statistically significant metabolites. However, definitions of biochemical pathways and metabolite coverage vary among different curated databases, leading to missed interpretations. For the lists of genes, transcripts and proteins, Gene Ontology (GO) terms over-presentation analysis has become a standardized approach for biological interpretation. But, GO analysis has not been achieved for metabolomic datasets. We present a new knowledgebase (KB) and the online tool, Gene Ontology Analysis by the Integrated Data Science Laboratory for Metabolomics and Exposomics (IDSL.GOA) to conduct GO over-representation analysis for a metabolite list. The IDSL.GOA KB covers 2,393 metabolic GO terms and associated 3,144 genes, 1,492 EC annotations, and 2,621 metabolites. IDSL.GOA analysis of a case study of older vs young female brain cortex metabolome highlighted 82 GO terms being significantly overrepresented (FDR <0.05). We showed how IDSL.GOA identified key and relevant GO metabolic processes that were not yet covered in other pathway databases. Overall, we suggest that interpretation of metabolite lists should not be limited to only pathway maps and can also leverage GO terms as well. IDSL.GOA provides a useful tool for this purpose, allowing for a more comprehensive and accurate analysis of metabolite pathway data. IDSL.GOA tool can be accessed athttps://goa.idsl.me/
Lepidoptera proboscis pollens are mainly derived from nectar
Authors: Ma Baiwei , Chen Qi , Lin Fei , Wang Guirong , Ren Bingzhong 
Published: March 2023

SummaryThe pollens which are rejected or ignored by the dry stigma can’t germinate since they haven’t acquired sugar solution from dry stigmas. But almost all research has ignored the participation of insects which may transport pollens from the nectar to stigmas, and that pollens may germinate on the dry stigma since they have soaked in the nectar. So, the key question is that whether insects carry pollens from nectar to the stigma.Since the adult Lepidoptera are important to the plant pollination and there is a general consensus that pollens are mainly deposited on the proboscis of adult Lepidoptera, and pollens are ubiquitous in the nectar of field flowers, we simulated the flower environment to conduct several groups of behavioral experiments in the adultMythimna separataby controlling the presence, absence or movement of pollens in nectar, then counted and compared the proboscis pollens.We found that the pollens on the proboscis were mainly derived from the nectar.Our conclusion may contributes to the research of pollen germination on stigmas, especially the dry stigma, and also shows the importance of adult Lepidoptera to pollination, even supports the coevolution of Lepidoptera and angiosperm.
Designer grass pea for transgene-free minimal neurotoxin-containing seeds with CRISPR-Cas9
Authors: Saha Tanushree , Shee Ranjana , Sahid Salman , Shee Dibyendu , Roy Chandan , Sharma Rajni , Pandey Ashutosh , Paul Soumitra , Datta Riddhi 
Published: March 2023

AbstractGrass pea seeds are consumed as food in several South Asian and Sub-Saharan African nations. However, the presence of the neurotoxic compound N-oxalyl-L-diamino propionic acid (β-ODAP) has restricted its cultivation. Although various cultivars with low β-ODAP levels have been developed, their cultivation is still limited due to the risk of neurolathyrism from long-term grass pea seed ingestion. In this study, we employed the CRISPR-Cas9-mediated gene editing technique to generate grass pea seeds with zero or minimal β-ODAP levels. We targeted theBAHD-AT3gene that encodes a key enzyme in the β-ODAP biosynthesis pathway. We developedbahd-at3knock-out lines using three gRNAs targeting different regions of this gene and characterized them. Cas9-free independent lines from each event carrying the desired on-target mutation were selected and backcrossed twice with the wild-type to eliminate any off-target mutation present therein. Various agronomical parameters were analyzed from the backcrossed mutant lines and they displayed no phenotypic abnormalities. Interestingly, the seed β-ODAP content ranged between 0.001 % - 0.002 % of dry weight which is 99 % lower than the wild-type. Together, our study reports the development of transgene-free, genome-edited grass peas with insignificant levels of β-ODAP in seeds for safer food in the future.
Identification of two novel polygalacturonase-inhibiting proteins (PGIPs) and their genomic reorganization in chickpea (Cicer arietinum)
Authors: Ellur Vishnutej , Wei Wei , Ghogare Rishikesh , Solanki Shyam , Vandemark George , Brueggeman Robert , Chen Weidong 
Published: March 2023

AbstractPolygalacturonase inhibiting proteins (PGIPs) are cell wall-anchored proteins that inhibit pathogen polygalacturonases (PGs). PGIPs, like other resistance genes, contain extracytoplasmic leucine-rich repeats (eLRRs), which are required for pathogen PG recognition. The importance of these PGIPs in plant defense has been well documented. This study focuses on chickpea (Cicer arietinum) PGIPs (CaPGIPs) owing to limited information available on this important crop. In this study, we identified and characterized two novelCapgips(Capgip3andCapgip4) in addition to the previously reportedCapgip1andCapgip2. Our analysis showed that CaPGIP1, CaPGIP3, and CaPGIP4 proteins contain N-terminal signal peptides, ten LRRs, theoretical molecular mass, and isoelectric points like other legume PGIPs. However, the previously reported CaPGIP2 cannot be classified as a true PGIP since it lacked a signal peptide, more than half of the LRRs, and other characteristics of a typical PGIP. Phylogenetic analysis and multiple sequence alignment revealed that theCapgipamino acid sequences are similar to the other reported legumes. Several cis-acting elements that are typical of pathogen response, tissue-specific activity, hormone response, and abiotic stress-related are present in the promoters ofCapgip1, Capgip3, andCapgip4. Localization experiments showed thatCapgip1, Capgip3, andCapgip4are located in the cell wall or membrane, whereasCapgip2is found in the endoplasmic reticulum.Capgiptranscript levels analyzed at normal conditions show constitutive tissue specific expression and heterozygous expression patterns analogous to other defense related gene families. All these findings suggest that CaPGIPs could have the potential to combat chickpea pathogens.
Within population plastic responses to combined thermal-nutritional stress differ from those in response to single stressors, and are genetically independent across traits in both males and females
Authors: Choy Yeuk Man Movis , Walter Greg M. , Mirth Christen K. , Sgrò Carla M. 
Published: March 2023

AbstractPhenotypic plasticity helps animals to buffer the effects of increasing thermal and nutritional stress created by climate change. Plastic responses to single and combined stressors can vary among genetically diverged populations. However, less is known about how plasticity in response to combined stress varies among individuals within a population or whether such variation changes across life-history traits. This is important because individual variation within populations shapes population-level responses to environmental change. Here, we used isogenic lines ofDrosophila melanogasterto assess plasticity of egg-to-adult viability and sex-specific body size for combinations of two temperatures (25°C or 28°C) and three diets (standard diet, low caloric diet, or low protein:carbohydrate ratio diet). Our results reveal substantial within-population genetic variation in plasticity for egg-to-adult viability and wing size in response to combined thermal-nutritional stress. This genetic variation in plasticity was a result of cross-environment genetic correlations that were often < 1 for both traits, as well as changes in the expression of genetic variation across environments for egg-to-adult viability. Cross-sex genetic correlations for body size were weaker when the sexes were reared in different conditions, suggesting that the genetic basis of traits may change with the environment. Further, our results suggest that plasticity in egg-to-adult viability is genetically independent from plasticity in body size. Importantly, plasticity in response to diet and temperature individually differed from plastic shifts in response to diet and temperature in combination. By quantifying plasticity and the expression of genetic variance in response to combined stress across traits, our study reveals the complexity of animal responses to environmental change, and the need for a more nuanced understanding of the potential for populations to adapt to ongoing climate change.
Chromosomal Duplications of MurZ (MurA2) or MurA (MurA1), Amino Acid Substitutions in MurZ (MurA2), and Absence of KhpAB Obviate the Requirement for Protein Phosphorylation inStreptococcus pneumoniaeD39
Authors: Tsui Ho-Ching Tiffany , Joseph Merrin , Zheng Jiaqi J. , Perez Amilcar J. , Manzoor Irfan , Rued Britta E. , Richardson John D. , Branny Pavel , Doubravová Linda , Massidda Orietta , Winkler Malcolm E. 
Published: March 2023

ABSTRACTGpsB links peptidoglycan synthases to other proteins that determine the shape of the respiratory pathogenStreptococcus pneumoniae(pneumococcus;Spn) and other low-GC Gram-positive bacteria. GpsB is also required for phosphorylation of proteins by the essential StkP(Spn) Ser/Thr protein kinase. Here we report three classes of frequently arising chromosomal duplications (≈21-176 genes) containingmurZ(MurZ-family homolog of MurA) ormurAthat suppress ΔgpsBor ΔstkP. These duplications arose from three different repeated sequences and demonstrate the facility of pneumococcus to modulate gene dosage of numerous genes. Overproduction of MurZ or MurA alone or overexpression of MurZ caused by ΔkhpABmutations suppressed ΔgpsBor ΔstkPphenotypes to varying extents. ΔgpsBand ΔstkPwere also suppressed by MurZ amino-acid changes distant from the active site, including one in commonly studied laboratory strains, and by truncation or deletion of the homolog of IreB(ReoM). Unlike in other Gram-positive bacteria, MurZ is predominant to MurA in pneumococcal cells. However, ΔgpsBand ΔstkPwere not suppressed by ΔclpCP, which did not alter MurZ or MurA amounts. These results support a model in which regulation of MurZ and MurA activity, likely by IreB(Spn), is the only essential requirement for protein phosphorylation in exponentially growing D39 pneumococcal cells.
Inducing an oxidized redox-balance improves anti-tumor CD8+T cell function
Authors: Oh Ju Hee , Cederberg Rachel A. , Tanaka Erin , Bopp Luisa , Ser Terri , Niyyati Sara , Patterson Annette E. , Amanat Neeku , Dutra Jared , Ye Patricia , Clark Meredith , Ward-Hartstonge Kirsten , Archambault Anne-Sophie , Tsui Janice , Lange Philipp F. , Tsai Sue , Verchere C. Bruce , Park Yongjin , Fabri Mario , Bennewith Kevin L. , Geltink Ramon I. Klein 
Published: March 2023

SUMMARYCancer immunotherapy using antigen-specific CD8+T cells depends on long-lasting anti-tumor function of thein vitroexpanded T cells. T cell function is intricately linked to the activity of many metabolic pathways directly impacting the ability of CD8+T cells to kill tumor cells. Metabolic conditioningin vitrobetter prepares CD8+T cells forin vivosurvival, tumor infiltration and tumor clearance. The mechanism underlyingin vitrometabolic conditioning-induced augmentedin vivoT cell function remains poorly understood. Here we show that metabolic conditioning of CD8+effector T cells induces an oxidized cellular redox balance at least in part mediated by increased mitochondrial reactive oxygen species (ROS). This redox shift contributes to enhancedin vivopersistence and tumor clearance. In human tumour-infiltrating T cells, altering the redox balanceex-vivoreinvigorated pro-inflammatory cytokine production. Therefore, we believe that redox alterations present a targetable pathway to increase T cell-based anti-tumor immunotherapy efficacy.
Significant reduction in blackfly bites following implementation of Slash and Clear: An option to consider for onchocerciasis elimination in areas of persistent transmission
Authors: Domche André , Nana Djeunga Hugues C. , Nwane Philippe B. , Njitchouang Guy R. , Fesuh Betrand Nono , Njiokou Flobert , Jacob Benjamin , Pion Sébastien D. , Kamgno Joseph 
Published: March 2023

AbstractBackgroundAlthough “Slash and Clear” has proven effective in reducing blackfly densities in low transmission foci, the impact of this strategy in high transmission settings with large rivers and important vector densities remains to be demonstrated.Methods/Principal findingsA controlled before-and-after community-based intervention comprising two arms (Bayomen as control site and Biatsota as intervention site) was carried out in the Mbam Valley (Centre Region, Cameroon). In each arm, baseline blackfly densities were collected over one year using the human landing method. The intervention consisted of destroying the trailing vegetation where blackflies breed. Blackfly densities were collected post-intervention to assess the impact of the intervention. Before the intervention, a total of 36,273 and 29,041 blackflies were collected in Bayomen and Biatsota, respectively. After the intervention period, the total blackfly density in the intervention site decreased from 29,041 to 20,011 (31.1% reduction), while an increase of 2·7% was observed in the control site (from 36,273 to 37,248). The Poisson mixed regression model shows that the reduction was significantly greater in the intervention site than in the control site (p<0.0005).Conclusions/SignificanceThis study showed that “Slash and Clear” approach is feasible and has a significant impact on vector densities in a high transmission setting. Further studies are needed to investigate the long-term impact of this vector control approach, and how this promising strategy can be scaled-up and sustained until elimination of onchocerciasis.Author summaryRiver blindness persists in some foci in Cameroon despite more than two decades of ivermectin-based preventive chemotherapy. Mass drug administration (MDA) appears insufficient to interrupt onchocerciasis transmission in these hotspots, and should be complemented by vector control, the most promising alternative strategy to date. In 2018, the effectiveness of a new community-based vector control approach, known as slash and clear, was demonstrated. This strategy involves the removal of trailing vegetation at breeding sites, a primary attachment points for blackfly larvae. In this study, we show that this environment-friendly intervention is feasible and has a significant impact on blackfly densities in high transmission settings. This promising intervention can be combined with regular annual ivermectin-based preventive chemotherapy to accelerate onchocerciasis elimination.
Wat1/mLst8, a TOR complex protein regulates mitochondrial integrity and calcium ion homeostasis in fission yeastS. pombe
Authors: Anjum Simmi , Srivastava Swati , Panigrahi Lalita , Ansari Uzair Ahmad , Trivedi Arun Kumar , Ahmed Shakil 
Published: March 2023

AbstractThe mTOR complexes play a fundamental role in mitochondrial biogenesis and cellular homeostasis. Wat1, an ortholog of mammalian Lst8 is an important component of TOR complex and is essential for the regulation of downstream signaling. Earlier we reported the role of Wat1 in oxidative stress response. Here, we show that the inactivation ofwat1leads to respiratory defects and mitochondrial depolarization leading to decrease in ATP production. The confocal and electron microscopy inwat1Δ cells revealed the fragmented mitochondrial morphology implying its role in mitochondrial fission. Furthermore, we also showed its role in autophagy and the maintenance of calcium ion homeostasis. Additionally,tor2-287mutant cells also exhibit defects in mitochondrial integrity indicating the TORC1-dependent involvement of Wat1 in the maintenance of mitochondrial homeostasis. The interaction studies of Wat1 and Tor2 with Por1 and Mmm1 proteins revealed a cross-talk between mitochondria and endoplasmic reticulum through the Mitochondria-associated membranes (MAM) and endoplasmic reticulum-mitochondria encounter structure (ERMES) complex, involving TORC1. Taken together, this study demonstrates involvement of Wat1/mLst8 in harmonizing various mitochondrial functions, redox status, and Ca2+homeostasis.
Bacteriophage-mediated decolonization ofEnterobacteriaceaein a novelGalleria mellonellagut colonization model
Authors: Mirza Kamran A. , Jacob Sebastian , Nietzsche Sandor , Makarewicz Oliwia , Pletz Mathias W. , Thieme Lara 
Published: March 2023

SummaryPurposeGalleria mellonellalarvae have emerged as an invertebrate model for studying bacterial pathogenesis and novel therapeutic options due to ethical concerns associated with the use of mammalian models such as mice. The benefits of usingG. mellonellalarvae include a less complex microbiome in the gut, making it suitable for gut colonization studies. The intestinal colonization ofKlebsiella pneumoniae(Kp) andEscherichia coli(Ec), two of the most antibiotic-resistant bacteria on the World Health Organization’s (WHO) priority list, plays a key role in the spread of antibiotic resistance. Bacteriophage therapy is emerging as a promising alternative for antibiotic-resistant bacteria due to its ability to specifically target and infect bacterial hosts, making it suitable for gut decontamination. This study aimed to establish a novelEnterobacteriaceae G. mellonellalarvae gut colonization model and compare the efficacy of conventional antibiotic treatment with a one-time phage cocktail in decolonizing the gut.ApproachLarvae were force-fed with different concentrations of bacterial doses ofK. pneumoniaeandE. coliat 0 h, 24 h, and 48 h, followed by survival monitoring at 24 h intervals. After 48 h and 120 h of the last force feed, the colony forming unit (CFU) count in the gut was evaluated. After successful colonization, larvae were one-time force-fed with either a 107PFU/larvae bacteriophage cocktail or with ciprofloxacin 4 mg/L or meropenem 2 mg/L. After 24 h post phage feeding, CFU counts were determined.Main findingsThree bacterial doses of 106CFU/larvae led to a stable gut colonization in the larvae gut regardless of theK. pneumoniaeandE. colistrains. Bacteriophage force-feeding reduced bacterial colonization by 4 log10CFU/larvae whereas antibiotic treatment led to a 2 log10CFU/larvae reduction compared to the control. The novel alternativeG. mellonellamodel for gut colonization studies can be used for proof-of-concept studies, reducing or even obviating the number of follow-up experiments in vertebrate models.
Placental Cell Conditioned Media Modifies Hematopoietic Stem Cell Transcriptome In Vitro
Authors: Harris Sean M. , Su Anthony L. , Dou John F. , Loch-Caruso Rita , Elkin Elana R. , Jaber Sammy , Bakulski Kelly M. 
Published: March 2023

AbstractBackgroundHematopoietic stem cells are cells that differentiate into all blood cell types. Although the placenta secretes hormones, proteins and other factors important for maternal and fetal health, cross-talk between placental cells and hematopoietic stem cells is poorly understood. Moreover, toxicant impacts on placental-hematopoietic stem cell communication is understudied. The goals of this study were to determine if factors secreted from placental cells alter transcriptomic responses in hematopoietic stem cells and if monoethylhexyl phthalate (MEHP), the bioactive metabolite of the pollutant diethylhexyl phthalate, modifies these effects.MethodsWe used K-562 and BeWo cells asin vitromodels of hematopoietic stem cells and placental syncytiotrophoblasts, respectively. We treated K-562 cells with medium conditioned by incubation with BeWo cells, medium conditioned with BeWo cells treated with 10 μM MEHP for 24 hours, or controls treated with unconditioned medium. We extracted K-562 cell RNA, performed RNA sequencing, then conducted differential gene expression and pathway analysis by treatment group.ResultsRelative to controls, K-562 cells treated with BeWo cell conditioned medium differentially expressed 173 genes (FDR<0.05 and fold-change>2.0), including 2.4 fold upregulatation ofTPM4and 3.3 fold upregulatation ofS1PR3. Upregulated genes were enriched for pathways including stem cell maintenance, cell proliferation and immune processes. Downregulated genes were enriched for terms involved in protein translation and transcriptional regulation. MEHP treatment differentially expressed eight genes (FDR<0.05), including genes involved in lipid metabolism (PLIN2, fold-change: 1.4;CPT1A, fold-change: 1.4).ConclusionK-562 cells, a model of hematopoietic stem cells, are responsive to media conditioned by placental cells, potentially impacting pathways like stem cell maintenance and proliferation.
Enhanced niche colonisation and competition during bacterial adaptation to a fungus
Authors: Richter Anne , Blei Felix , Hu Guohai , Schwitalla Jan W. , Lozano-Andrade Carlos N. , Jarmusch Scott A , Wibowo Mario , Kjeldgaard Bodil , Surabhi Surabhi , Jautzus Theresa , Phippen Christopher B. W. , Tyc Olaf , Arentshorst Mark , Wang Yue , Garbeva Paolina , Larsen Thomas Ostenfeld , Ram Arthur F.J. , van den Hondel Cees A.M. , Maróti Gergely , Kovács Ákos T. 
Published: March 2023

AbstractBacterial-fungal interactions (BFIs) influence microbial community performance of most ecosystems and elicit specific microbial behaviours, including stimulating specialised metabolite production. Using a simple BFI system encompassing the Gram-positive bacteriumBacillus subtilisand the black mould fungusAspergillus niger, we established a co-culture experimental evolution method to investigate bacterial adaptation to the presence of a fungus. In the evolving populations,B. subtiliswas rapidly selected for enhanced production of the lipopeptide surfactin and accelerated surface spreading ability, leading to inhibition of fungal expansion and acidification of the environment. These phenotypes were explained by specific mutations in the DegS-DegU two-component system. In the presence of surfactin, fungal hyphae exhibited bulging cells with delocalised secretory vesicles and RlmA-dependent cell wall stress induction. Increased surfactin production typically enhances the competitive success of bacteria against fungi, which likely explains the primary adaption path in the presence ofA. niger.Significance statementExperimental evolution and co-cultivation of different microbes are important and useful techniques for discovering new traits and unravelling cryptic regulatory connections. We combined these methods by evolving the Gram-positive bacteriumBacillus subtilisin the presence of the black mould fungusAspergillus nigerthat were previously shown to engage in an intricate and physical interaction. Both are ubiquitous, environmentally and industrially relevant model microbes in the colonisation of rhizo- and endosphere and in the production of enzymes. Our results demonstrate how laboratory adaptation can be exploited to improve biocontrol properties of bacteria.