bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genomic dissection of endemic carbapenem resistance: metallo-beta-lactamase gene dissemination through clonal, plasmid and integron transfer pathways
Authors: Macesic Nenad , Hawkey Jane , Vezina Ben , Wisniewski Jessica A. , Cottingham Hugh , Blakeway Luke V. , Harshegyi Taylor , Pragastis Katherine , Badoordeen Gnei Zweena , Dennison Amanda , Spelman Denis W. , Jenney Adam W.J. , Peleg Anton Y. 
Published: March 2023

AbstractInfections caused by metallo-beta-lactamase-producing organisms (MBLs) are a global health threat. Our understanding of transmission dynamics and how MBLs establish endemicity remains limited. We analysed two decades ofblaIMP-4evolution in a hospital using sequence data from 270 clinical and environmental isolates (including 169 completed genomes) and identified extreme gene promiscuity across 7 Gram-negative genera, 68 bacterial strains and 7 distinct plasmid types. An initial multi-species outbreak of conserved IncC plasmids (95 genomes across 37 strains) allowed endemicity to be established through the ability ofblaIMP-4to disseminate in successful strain-genetic setting pairs we termed ‘propagators’, in particularSerratia marcescensandEnterobacter hormaechei. From this reservoir,blaIMP-4persisted through diversification of genetic settings that resulted from transfer ofblaIMP-4plasmids between bacterial hosts and of the integron carryingblaIMP-4between plasmids. Our findings provide a framework for understanding endemicity and spread of MBLs and may have broader applicability to other carbapenemase-producing organisms.
An essential role for miR-15/16 in Treg suppression and restriction of proliferation
Authors: Johansson Kristina , Gagnon John D. , Zhou Simon , Fassett Marlys S. , Schroeder Andrew W. , Kageyama Robin , Bautista Rodriel A. , Pham Hewlett , Woodruff Prescott G. , Ansel K. Mark 
Published: March 2023

AbstractThe miR-15/16 family is a highly expressed group of tumor suppressor miRNAs that target a large network of genes in T cells to restrict their cell cycle, memory formation and survival. Upon T cell activation, miR-15/16 are downregulated, allowing rapid expansion of differentiated effector T cells to mediate a sustained immune response. Here, using conditional deletion of miR-15/16 in immunosuppressive regulatory T cells (Tregs) that express FOXP3, we identify new functions of the miR-15/16 family in T cell immunity. miR-15/16 are indispensable to maintain peripheral tolerance by securing efficient suppression by a limited number of Tregs. miR-15/16-deficiency alters Treg expression of critical functional proteins including FOXP3, IL2Rα/CD25, CTLA4, PD-1 and IL7Rα/CD127, and results in accumulation of functionally impaired FOXP3loCD25loCD127hiTregs. Excessive proliferation in the absence of miR-15/16 inhibition of cell cycle programs shifts Treg diversity and produces an effector Treg phenotype characterized by low expression of TCF1, CD25 and CD62L, and high expression of CD44. These Tregs fail to control immune activation of CD4+effector T cells, leading to spontaneous multi-organ inflammation and increased allergic airway inflammation in a mouse model of asthma. Together, our results demonstrate that miR-15/16 expression in Tregs is essential to maintain immune tolerance.HighlightsTreg-specific miR-15/16 expression is essential to prevent systemic tissue inflammationmiR-15/16 restrict Treg proliferation and regulate expression of the key functional Treg molecules FOXP3, IL2Rα, CTLA4, PD-1 and IL7RαmiR-15/16 limit formation of effector Tregs and is necessary for high suppressive capacity
SERODIAGNOSIS OF SALMONELLA INFECTION: USING A LOGISTIC REGRESSION MODEL
Authors: Ndako James A , Owolabi Iyanuoluwani J. , Junaid Surajudeen A. , Dojumo Victor T. , Ndako Christy J. , Abiodun Oluwakemi E. , Omoniyi Remilekun M. , Bello Sharon O. 
Published: March 2023

ABSTRACTSalmonella infection remains a major global health problem and worsened by lack of appropriate diagnostic tools to aid early detection and teatment, particularly in low-income nations.Salmonella typhiis the most common causative agent of typhoid fever and the prevalence of this illness has been on the increase specifically in areas of poor personal hygiene and sanitation. This study was carried out to further improve the diagnosis of salmonella infection, through a mathematical regression model. An analysis was performed using the logistic regression approach and the predictability of the model was done by extracting fifteen (15) typhoid observations from the obtained samples; for the model to predict their status. The model was able to accurately predict 66.7% of the observations. This study showed an increased prevalence in typhoid fever including a significant correlation between typhoid fever and other parameters. The global burden of this illness can be minimized by proper vaccination, and prompt but appropriate diagnosis and treatment.Further studies and test-meaasures also needs to be carried out to improve diagnosis and treatment regimen.
Sulfur disproportionating microbial communities in a dynamic, microoxic-sulfidic karst system
Authors: Aronson Heidi S. , Clark Christian E. , LaRowe Douglas E. , Amend Jan P. , Polerecky L. , Macalady Jennifer L. 
Published: March 2023

AbstractBiogeochemical sulfur cycling in sulfidic karst systems is largely driven by abiotic and biological sulfide oxidation, but the fate of elemental sulfur (S0) that accumulates in these systems is not well understood. The Frasassi Cave system (Italy) is intersected by a sulfidic aquifer that mixes with small quantities of oxygen-rich meteoric water, creating Proterozoic-like conditions and supporting a prolific ecosystem driven by sulfur-based chemolithoautotrophy. To better understand the cycling of S0in this environment, we examined the geochemistry and microbiology of sediments underlying widespread sulfide-oxidizing mats dominated byBeggiatoa. Sediment populations were dominated by uncultivated relatives of sulfur cycling chemolithoautotrophs related toSulfurovum,Halothiobacillus, Thiofaba, Thiovirga, Thiobacillus, andDesulfocapsa, as well as diverse uncultivated anaerobic heterotrophs affiliated withBacteroidota, Anaerolineaceae, Lentimicrobiaceae, and Prolixibacteraceae.DesulfocapsaandSulfurovumpopulations accounted for 12-26% of sediment 16S rRNA amplicon sequences and were closely related to isolates which carry out autotrophic S0disproportionation in pure culture. Gibbs energy (ΔGr) calculations revealed that S0disproportionation underin situconditions is energy yielding. Microsensor profiles through the mat-sediment interface showed thatBeggiatoamats consume dissolved sulfide and oxygen, but a net increase in acidity was only observed in the sediments below. Together, these findings suggest that disproportionation is an important sink for S0generated by microbial sulfide oxidation in this oxygen-limited system and may contribute to the weathering of carbonate rocks and sediments in sulfur- rich environments.
A genomic and structural bioinformatic pipeline identifies candidate type VI secretion antibacterial effector-immunity pairs
Authors: Geller Alexander Martin , Zlotkin David , Shalom Maor , Blum Noam , Levy Asaf 
Published: March 2023

AbstractType VI secretion systems (T6SS) are common bacterial contractile injection systems that inject toxic “effector” proteins into neighboring cells. We bioinformatically investigated T6SS core proteins in 11,832 genomes of Gram negative bacteria. Comparison of T6SS core proteins that are covalently attached to toxic T6SS effector proteins (T6Es) versus those that are not revealed differences in phylogenetic distribution, physical properties, and genomic position. Using the data generated from our bioinformatic analysis, we developed a new genomic- and Alphafold2-based pipeline for discovery of putative T6Es. We experimentally validated the toxic and immunity activities of four putative antibacterial T6SS effector proteins and four cognate immunity genes from diverse species, respectively. We used Foldseek to predict possible mechanisms of action of the putative T6Es, which was much more effective than sequence-based methods. Evidence of the possible mechanisms of action of the putative T6Es was explored through fluorescence microscopy, where we observed cell wall-targeting, DNA degradation, and cell filamentation. This study shows how combining genomic data mining with new structure-based bioinformatic tools can facilitate identification of novel antibacterial toxins.
A conserved RWP-RK transcription factor VSR1 controls gametic differentiation in volvocine algae
Authors: Geng Sa , Hamaji Takashi , Ferris Patrick J. , Gao Minglu , Nishimura Yoshiki , Umen James 
Published: March 2023

AbstractVolvocine green algae are a model for understanding the evolution of mating types and sexes. They are facultatively sexual, with gametic differentiation occurring in response to nitrogen starvation (-N) in most genera, and to sex inducer hormone (SI) inVolvox. The conserved RWP RK family transcription factor (TF) MID is encoded by theminusmating type (MT) locus or male sex-determining region (SDR) of heterothallic volvocine species and dominantly determinesminusor male gametic differentiation. However, the factor(s) responsible for establishing the defaultplusor female differentiation programs have remained elusive. We performed a phylo transcriptomic screen for autosomal RWP-RK TFs induced during gametogenesis in unicellular isogamousChlamydomonas reinhardtii(Chlamydomonas) and in multicellular oogamousVolvox carteri(Volvox) and identified a single conserved ortho-group we named Volvocine Sex Regulator 1 (VSR1). Chlamydomonasvsr1mutants of either mating type failed to mate and could not induce expression of key mating-type-specific genes. Similarly, Volvoxvsr1mutants in either sex could initiate sexual embryogenesis, but the presumptive eggs or androgonidia (sperm packet precursors) were infertile and unable to express key sex-specific genes. Yeast two-hybrid assays identified a conserved domain in VSR1 capable of self-interaction or interaction with the conserved N terminal domain of MID.In vivoco-immunoprecipitation experiments demonstrated association of VSR1 and MID in both Chlamydomonas and Volvox. These data support a new model for volvocine sexual differentiation where VSR1 homodimers activate expression ofplus/female gamete-specific-genes, but when MID is present MID-VSR1 heterodimers are preferentially formed and activateminus/male gamete-specific-genes.Significance StatementSex and recombination are conserved features of eukaryotic life cycles, but sex determination mechanisms are diverse, and are poorly understood in most major taxa. Our study identified a long-sought regulator of sexual differentiation in volvocine green algae—the RWP-RK family transcription factor (TF) VSR1— leading to the first complete paradigm for mating type or sex determination in this lineage. Our results support a model where gametically expressed VSR1 homodimerizes and activatesplus/female specific genes. When the dominant sex-linkedminus/male RWP-RK family TF MID is present MID-VSR1 heterodimers are preferentially formed and activateminus/male genes. The widespread association of RWP-RK TFs with gamete differentiation in the green lineage suggests that a similar paradigm may operate throughout the plant kingdom.
A local ATR-dependent checkpoint pathway is activated by a site-specific replication fork block in human cells
Authors: Ahmed-Seghir Sana , Jalan Manisha , Grimsley Helen E. , Sharma Aman , Twayana Shyam , Kosiyatrakul Settapong T , Thompson Christopher , Schildkraut Carl L. , Powell Simon N. 
Published: March 2023

AbstractWhen replication forks encounter DNA lesions that cause polymerase stalling a checkpoint pathway is activated. The ATR-dependent intra-S checkpoint pathway mediates detection and processing of sites of replication fork stalling to maintain genomic integrity. Several factors involved in the global checkpoint pathway have been identified, but the response to a single replication fork barrier (RFB) is poorly understood. We utilized theE.coli-based Tus-Tersystem in human MCF7 cells and showed that the Tus protein binding toTerBsequences creates an efficient site-specific RFB. The single fork RFB was sufficient to activate a local, but not global, ATR-dependent checkpoint response that leads to phosphorylation and accumulation of DNA damage sensor protein γH2AX, confined locally to within a kilobase of the site of stalling. These data support a model of local management of fork stalling, which allows global replication at sites other than the RFB to continue to progress without delay.
Parenting deficits inMagel2-null mice predicted from systematic investigation of imprinted gene expression in galanin neurons of the hypothalamus
Authors: Higgs M. J. , Webberley A. E. , John R. M. , Isles A. R. 
Published: March 2023

ABSTRACTImprinted genes are subject to germline epigenetic modification resulting in parental-specific allelic silencing. Although genomic imprinting is thought to be important for maternal behaviour, this idea is based on serendipitous findings from a small number of imprinted genes. Here, we undertook an unbiased systems biology approach, taking advantage of the recent delineation of specific neuronal populations responsible for controlling parental care, to test whether imprinted genes significantly converge to regulate parenting behaviour. Using single-cell RNA sequencing datasets, we identified a specific enrichment of imprinted gene expression in a recognised “parenting hub”, the galanin-expressing neurons of the preoptic area. We tested the validity of linking enriched expression in these neurons to function by focusing on MAGE family member L2(Magel2),an imprinted gene not previously linked to parenting behaviour. We confirmed expression ofMagel2in the preoptic area galanin expressing neurons. We then examined the parenting behaviour ofMagel2+/-null mice.Magel2-null mothers, fathers and virgin females demonstrated deficits in pup retrieval, nest building and pup-directed motivation, identifying a central role for this gene in parenting. Finally, we show thatMagel2-null mothers and fathers have a significant reduction in POA galanin expressing cells, which in turn contributes to a reducedc-Fosresponse in the POA upon exposure to pups. Our findings identify a novel imprinted gene that impacts parenting behaviour and, moreover, demonstrates the utility of using single-cell RNA sequencing data to predict gene function from expression and in doing so here, have identified a purposeful role for genomic imprinting in mediating parental behaviour.
A small number of human lineage mutations regulated RNA-protein binding of conserved genes and promoted human evolution
Authors: Song Weichen , Yu Shunying , Zhao Min , Lin Guan Ning 
Published: March 2023

AbstractWhether human lineage mutations (HLM) have contributed to human evolution via post-transcriptional modification remained unknown. We applied deep learning models Seqweaver to predict how HLM impacts RNA-binding protein affinity (RBP). At the threshold of the top 1% of human common variation, only 0.27% of HLM had large impacts on RBP. These HLMs enriched in a set of conserved genes that are highly expressed in adult excitatory neurons and prenatal Purkinje neurons, and involved in synapse organization and the GTPase pathway. These genes also carried excess damaging coding mutations that caused neurodevelopmental disorders, ataxia, and Schizophrenia. Among these genes, NTRK2 and ITPR1 had the most aggregated evidence of functional importance, pointing to an essential role in cognition and bipedalism. We concluded that a very small number of human-specific mutations have contributed to human speciation via impacts on post-transcriptional modification of critical brain-related genes.Author summaryPost-transcriptional modification has important functions in biological systems, but its role in evolution has long been a mystery due to the difficulty in predicting how a mutation could impact this process. Here we applied the newly developed deep learning model Seqweaver on human lineage mutations (HLM) to predict their effect on RNA-protein binding affinity profile (RBP). We found that only a very small number HLM are influential to RBP. Influential HLMs enriched in a set of conserved genes that are enriched in cells and functions critical for cognition and bipedal walking, and severe mutations on these genes cause the disruption of cognition (neurodevelopmental disorders) and bipedalism (ataxia). NTRK2 and ITPR1 had the most aggregated pieces of evidence of functional importance, pointing to an important role in cognition and bipedal walking. Taken together, our result demonstrated that there is a small number of human lineage mutations that modified the post-transcriptional modifications of conserved neuronal genes, which contributed to human speciation.
The influence of inter-regional delays in generating large-scale brain networks of phase synchronization
Authors: Williams N. , Ojanperä A. , Siebenhühner F. , Toselli B. , Palva S. , Arnulfo G. , Kaski S. , Palva J.M. 
Published: March 2023

AbstractLarge-scale networks of phase synchronization are considered to regulate the communication between brain regions fundamental to cognitive function, but the mapping to their structural substrates,i.e., the structure-function relationship, remains poorly understood. Biophysical Network Models (BNMs) have demonstrated the influences of local oscillatory activity and inter-regional anatomical connections in generating alpha-band (8–12 Hz) networks of phase synchronization observed with Electroencephalography (EEG) and Magnetoencephalography (MEG). Yet, the influence of inter-regional conduction delays remains unknown. In this study, we compared a BNM with standard “distance-dependent delays”, which assumes constant conduction velocity, to BNMs with delays specified by two alternative methods accounting for spatially varying conduction velocities, “isochronous delays” and “mixed delays”. We followed the Approximate Bayesian Computation (ABC) workflow, i) specifying neurophysiologically informed prior distributions of BNM parameters, ii) verifying the suitability of the prior distributions with Prior Predictive Checks, iii) fitting each of the three BNMs to alpha-band MEG resting-state data (N= 75) with Bayesian Optimisation for Likelihood-Free Inference (BOLFI), and iv) choosing between the fitted BNMs with ABC model comparison on a separate MEG dataset (N= 30). Prior Predictive Checks revealed the range of dynamics generated by each of the BNMs to encompass those seen in the MEG data, suggesting the suitability of the prior distributions. Fitting the models to MEG data yielded reliable posterior distributions of the parameters of each of the BNMs. Finally, model comparison revealed the BNM with “distance-dependent delays”, as the most probable to describe the generation of alpha-band networks of phase synchronization seen in MEG. These findings suggest that distance-dependent delays contribute significantly to the neocortical architecture of human alpha-band networks of phase synchronization. Hence, our study illuminates the role of inter-regional delays in generating the large-scale networks of phase synchronization that might subserve the communication between regions vital to cognition.HighlightsCompared methods to specify delays in Biophysical Network Models (BNMs)BNM with “distance-dependent” conduction delays more probable than alternativesBNMs with biologically informed prior distributions generate dynamics seen in MEGFitting BNMs yields reliable posterior distributions informed by MEG data (N= 75)
Discrimination of finger movements by magnetomyography with optically pumped magnetometers
Authors: Greco Antonino , Baek Sangyeob , Middelmann Thomas , Mehring Carsten , Braun Christoph , Marquetand Justus , Siegel Markus 
Published: March 2023

AbstractOptically pumped magnetometers (OPM) are quantum sensors that offer new possibilities to measure biomagnetic signals. In magnetomyography (MMG), compared to the current standard surface electromyography (EMG), OPM sensors offer the advantage of contactless measurements of muscle activity. However, little is known about the relative performance of OPM-MMG and EMG, e.g. in their ability to detect and classify finger movements. To address this, we recorded simultaneous OPM-MMG and EMG of finger flexor muscles for the discrimination of individual finger movements. Using a deep learning model for movement classification, we found that both sensor modalities were able to discriminate finger movements with above 89% accuracy. Furthermore, model predictions for the two sensor modalities showed high agreement in movement detection (85% agreement; Cohen’s kappa: 0.45). Our findings show that OPM sensors can be employed for reliable, contactless discrimination of finger movements and incentivize future applications of OPM in magnetomyography.
How do institutional environment and entrepreneurial cognition drive female and male entrepreneurship from a configuration perspective?
Authors: Chen Chengmeng , Huang Yongchun , Wu Shangshuo 
Published: March 2023

Purpose
The purpose of this paper is to examine the gender differences in entrepreneurship driven by configurations of institutional environment and entrepreneurial cognition, and provide theoretical guidance and practical reference for promoting female and male entrepreneurship.

Design/methodology/approach
Based on a configuration perspective, six antecedents of institutional environment and entrepreneurial cognition are integrated to explore multiple concurrent factors and causally complex relationships affecting female and male entrepreneurship.

Findings
This study indicates that the configurations of institutional environment and entrepreneurial cognition can achieve high female and male entrepreneurship. There are similarities and differences between female and male entrepreneurship from a configuration perspective. Perceived opportunity plays an important role in entrepreneurship for both women and men, and the absence of fear of failure is also important for male entrepreneurship. There is a complementary effect among entrepreneurial cognitions in the absence of institutional environment. In the configurations of institutional environment and entrepreneurial cognition, female entrepreneurship benefits more from informal institutions, whereas regulative and cognitive institutions play a greater role in male entrepreneurship.

Practical implications
Policymakers and individuals should take a holistic and complex view of the impact of institutional environment and entrepreneurial cognition, and differentiated measures should be taken for female and male entrepreneurship.

Originality/value
This research responds to the call for multilevel transnational entrepreneurship research, enriches research on institutional environment and entrepreneurial cognition, deepens the application of fuzzy-set qualitative comparative analysis to the field of entrepreneurship and strengthens the understanding of the similarities, differences and complexities of female and male entrepreneurship.