bluuebunny/crossref_metadata_2025 huggingface dataset:
Suppressing upregulation of fibrinogen after polytrauma mitigates thrombosis in mice
Authors: Seadler Monica S. , Ferraresso Francesca , Bansal Muskan , Haugen Amber , Hayssen William G. , Flick Matthew J. , de Moya Marc , Dyer Mitchell R. , Kastrup Christian J.
Published: September 2024

BACKGROUND

Polytrauma results in systemic inflammation and increased circulating fibrinogen, which increases the risk of microvascular and macrovascular thrombosis that contributes to secondary organ damage and venous thromboembolism (VTE). There are no clinically approved agents to prevent hyperfibrinogenemia after polytrauma. We hypothesized that preventing the increase in fibrinogen levels after polytrauma would suppress thrombosis.

METHODS

Small-interfering ribonucleic acid (siRNA) against fibrinogen was encapsulated in lipid nanoparticles (siFibrinogen). Mice underwent a model of polytrauma and were then given varying doses of siFibrinogen, control siRNA, or no treatment. Fibrinogen was measured for 1 week via enxyme-linked immunosorbent assay (ELISA). To model postinjury VTE, the inferior vena cava was ligated 2 days after polytrauma in a portion of the mice. Thrombus weight was measured 48 hours after the inferior vena cava was ligated.

RESULTS

Treatment with siFibrinogen prevented hyperfibrinogenemia after trauma without exacerbating the hypofibrinogenemic state that occurs in the acute injury period (1 hour). In treated groups, fibrinogen was significantly lower from 6 hours postinjury through the 7-day monitoring period. Maximal fibrinogen reduction was observed at 72 hours. Here, mice that received 2.0 mg/kg of siFibrinogen had 1% of normal values relative to untreated mice, and mice that received 1.0 or 0.5 mg/kg had 4%. Mice treated with siFibrinogen that underwent the postinjury VTE model had significantly reduced thrombus weight compared with control siRNA-treated animals. More notably, among all siFibrinogen treated mice, 12 of 18 were completely protected from thrombosis, compared with 0 of 9 displaying protection in the control group.

CONCLUSION

The rise of fibrinogen and the size of thrombi after polytrauma can be mitigated via the administration of siRNA against fibrinogen. siFibrinogen represents a promising novel target for VTE prophylaxis posttrauma.
Update on eating disorders and disordered eating behaviors in metabolic bariatric surgery patients
Authors: Conceição Eva , Mitchell James E. , Sarwer David B.
Published: September 2024

Purpose of review

Recent literature suggests a potential causal link between metabolic bariatric surgery (MBS) and an increased risk of eating disorders. However, the available literature offers unclear results regarding the definition of eating problems among MBS patients, their potential impact on weight outcomes, and the efficacy of adjunctive treatment.

Recent findings

Although eating disorders may be rare phenomena after surgery, disordered eating behaviors are more common and tend to be more consistently associated with suboptimal weight loss. There also appear to be clear problems when using Diagnostic and Statistical Manual of Mental Disorders 5th edition (DSM-5) criteria to assess eating disorders among MBS patients, particularly for restrictive eating, binge-eating episodes, and the core psychopathology of eating disorders. Finally, preoperative interventions appear to offer effects limited to the presurgery period, and the evidence for the efficacy of postoperative interventions remains limited. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) offer promising benefits for weight loss and the treatment of binge-eating problems, but their potential risks must be carefully managed.

Recognizing the diverse presentations of these problems among individuals undergoing MBS is crucial. Clinical attention should focus on intensive specialized care during the postoperative period for those who develop eating-related problems.
Spencermartinsiella nicolii sp. nov., a potential opportunistic pathogenic yeast species isolated from rotting wood in Brazil
Authors: Barros Katharina O. , Valério Aline D. , Batista Thiago M. , Santos Ana Raquel O. , Souza Gisele F. L. , Alvarenga Flávia B. M. , Lopes Mariana R. , Morais Camila G. , Alves Cristina , Goes-Neto Aristóteles , Vital Marcos J. S. , Uetanabaro Ana Paula T. , Souza Daniela L. , Bai Feng-Yan , Franco Glória R. , Lachance Marc-André , Rosa Carlos A. , Johann Susana
Published: September 2024

Nineteen isolates representing a candidate for a novel yeast species belonging to the genus Spencermartinsiella were recovered from rotting wood samples collected at different sites in Atlantic Rainforest and Amazonian Forest ecosystems in Brazil. Similarity search of the nucleotide sequence of the intergenic spacer (ITS)-5.8S and large subunit D1/D2 regions of the ribosomal gene cluster showed that this novel yeast is closely related to Spencermartinsiella cellulosicola. The isolates differ by four nucleotide substitutions in the D1/D2 domain and six substitutions and 31 indels in the ITS region from the holotype of S. cellulosicola. Phylogenomic analysis based on 1474 single-copy orthologues for a set of Spencermartinsiella species whose whole genome sequences are available confirmed that the novel species is phylogenetically close to S. cellulosicola. The low average nucleotide identity value of 83% observed between S. cellulosicola and the candidate species confirms that they are distinct. The novel species produced asci with hemispherical ascospores. The name Spencermartinsiella nicolii sp. nov. is proposed. The holotype is CBS 14238T. The MycoBank number is MB855027. Interestingly, the D1/D2 sequence of the S. nicolii was identical to that of an uncultured strain of Spencermartinsiella causing systemic infection in a male adult crocodile (Crocodylus niloticus). The characterization of some virulence factors and antifungal susceptibility of S. nicolii isolates suggest that this yeast may be an opportunistic pathogen for animals, including humans; the isolates grow at 37 °C.
Additions to the list of arthropods of Reunion Island
Authors: Nibouche Samuel , Sadeyen Joëlle , Dervin Sébastien , Gauche Mirana , Merion Sabine , Minatchy Janice , Fontaine Romuald , Reynaud Philippe , Michel Bruno
Published: September 2024

Contribution to the inventory of arthropods of Reunion Island

This work is a synthesis of new taxa for the Reunion Island identified between 1963 and 2022 and not published to date. The collections were carried out mainly by researchers and technicians from CIRAD or FDGDON. Sampling mainly targeted at crop pests and their natural enemies. The list includes 101 taxa new for Reunion. The Hymenoptera and Hemiptera are the most represented orders.
Identification of leptolin as a novel anti-obesity adipokine
Authors: Liu Jiarui , Wang Bingwei , Su Zhijie , Han Xiaoxu , He Miao , Zhao Yun , Hou Yujia , Li Daotong , Zhang Weiguang , Qin Lihua , Wang Ke , Li Yanchun , Yan Yi , Yu Siwang , Huang Xiaoshuai , Yuwen Tairan , Zheng Ruimao
Published: September 2024

Adipokines are key factors in regulating energy homeostasis. We identified a novel adipokine; we named it Leptolin. In humans, leptolin levels in white adipose tissue were positively corrected with exercise, and negatively associated with body mass index. Leptolin levels were positively correlated with lipolysis-promoting gene expression. Elevated leptolin in plasma of athletes, whereas lowered leptolin in plasma of obese individuals were observed. Leptolin gene-knockout mice exhibited increased adiposity and body weight, and decreased energy expenditure. Leptolin gene-overexpression mice showed obesity-resistant phenotypes.Treatment with leptolin promoted fat mobilization and energy expenditure, and reduced body weight, without affecting food-intake and motor activity. Together, leptolin, a novel adipokine with a capacity to improve metabolic status, may serve as a new therapeutic agent for obesity and metabolic disorders.
A novel combination therapy for ER+ breast cancer suppresses drug resistance via an evolutionary double-bind
Authors: Emond Rena , West Jeffrey , Grolmusz Vince , Cosgrove Patrick , Nath Aritro , Anderson Alexander R.A. , Bild Andrea H.
Published: September 2024

Chemotherapy remains a commonly used and important treatment option for metastatic breast cancer. A majority of ER+ metastatic breast cancer patients ultimately develop resistance to chemotherapy, resulting in disease progression. We hypothesized that an “evolutionary double-bind”, where treatment with one drug improves the response to a different agent, would improve the effectiveness and durability of responses to chemotherapy. This approach exploits vulnerabilities in acquired resistance mechanisms. Evolutionary models can be used in refractory cancer to identify alternative treatment strategies that capitalize on acquired vulnerabilities and resistance traits for improved outcomes. To develop and test these models, ER+ breast cancer cell lineages sensitive and resistant to chemotherapy are grown in spheroids with varied initial population frequencies to measure cross-sensitivity and efficacy of chemotherapy and add-on treatments such as disulfiram combination treatment. Different treatment schedules then assessed the best strategy for reducing the selection of resistant populations. We developed and parameterized a game-theoretic mathematical model from this in vitro experimental data, and used it to predict the existence of a double-bind where selection for resistance to chemotherapy induces sensitivity to disulfiram. The model predicts a dose-dependent re-sensitization (a double-bind) to chemotherapy for monotherapy disulfiram.
Kontextual: Reframing analysis of spatial omics data reveals consistent cell relationships across images
Authors: Ameen Farhan , Robertson Nick , Lin David M. , Ghazanfar Shila , Patrick Ellis
Published: September 2024

State-of-the-art spatial proteomic and transcriptomic technologies can deeply pheno-type cells in their native tissue environment, providing a high throughput means to effectively quantify spatial relationships between diverse cell populations. However, the experimental design choice of which regions of a tissue will be imaged can greatly impact the interpretation of spatial quantifications. That is, spatial relationships identified in one region of interest may not be interpreted consistently across other regions. To address this challenge, we introduce Kontextual, a method which considers alternative frames of reference for contextualising spatial relationships. These contexts may represent landmarks, spatial domains, or groups of functionally similar cells which are consistent across regions. By modelling spatial relationships between cells relative to these contexts, Kontextual produces robust spatial quantifications that are not confounded by the region selected. We demonstrate in spatial proteomics and spatial transcriptomics datasets that modelling spatial relationships this way is biologically meaningful. We also demonstrate how this approach can be used in a classification setting to improve prediction of patient prognosis.
Development and Validation of Collaborative Robot-assisted Cutting Method for Iliac Crest Flap Raising: Randomized Crossover Trial
Authors: Becker Paulina , Li Yao , Drobinsky Sergey , Egger Jan , Xie Kunpeng , Rashad Ashkan , Radermacher Klaus , Röhrig Rainer , de la Fuente Matías , Hölzle Frank , Puladi Behrus
Published: September 2024

The current gold standard of computer-assisted jaw reconstruction includes raising microvascular bone flaps with patient-specific 3D-printed cutting guides. The downsides of cutting guides are invasive fixation, periosteal denudation, preoperative lead time and missing intraoperative flexibility. This study aimed to investigate the feasibility and accuracy of a robot-assisted cutting method for raising iliac crest flaps compared to a conventional 3D-printed cutting guide.

In a randomized crossover design, 40 participants raised flaps on pelvic models using conventional cutting guides and a robot-assisted cutting method. The accuracy was measured and compared regarding osteotomy angle deviation, Hausdorff Distance (HD) and Average Hausdorff Distance (AVD). Duration, workload and usability were further evaluated.

The mean angular deviation for the robot-assisted cutting method was 1.9±1.1° (mean±sd) and for the 3D-printed cutting guide it was 4.7±2.9° (p<0.001). The HD resulted in a mean value of 1.5±0.6mm (robot) and 2.0±0.9mm (conventional) (p<0.001). For the AVD, this was 0.8±0.5mm (robot) and 0.8±0.4mm (conventional) (p=0.320). Collaborative robot-assisted cutting is an alternative to 3D-printed cutting guides in experimental static settings, achieving slot design benefits with less invasiveness and higher intraoperative flexibility. In the next step, the results should be tested in a dynamic environment with a moving phantom and on the cadaver.
Religion and COVID 19 Pandemic for better or for worse?
Authors: Ranasinghe Sameera Upashantha , Ranasinghe Lakshitha Iroshan , Pathiraja Indika
Published: September 2024

COVID-19 has negative repercussions on psychological aspects of the individual. Provision of personalized assistance to each individual is a task which cannot be fulfilled by the health system. In this context religion remains to be an effective tool. A qualitative study was conducted to find the spiritual practices and coping mechanisms of COVID-19 infected people(N=15, mean age =46.3 years) in Kurunegala district. Data collection was conducted using in-depth interviews and thematic analysis was conducted. The main themes found were Fatalism and perceived risk of COVID 19, Adherence to health care guidelines despite fatalistic beliefs, Religious coping in COVID 19, Spiritual practices for coping with stress/ distress and Fatalism as a positive force for self-care. It is imperative to manage the pandemic with the assistance of religion and spiritual practices.
Humoral Immunity after mRNA Omicron JN.1 Vaccination
Authors: Happle Christine , Hoffmann Markus , Kempf Amy , Nehlmeier Inga , Stankov Metodi V. , Hampel Noemi Calderon , Witte Torsten , Pöhlmann Stefan , Behrens Georg M. N. , Dopfer-Jablonka Alexandra
Published: September 2024

In late June 2024, the European Medicines Agency (EMA) recommended market authorization for a monovalent COVID-19 mRNA-vaccine based on JN.1 spike. We assessed immune responses in n=42 health-care workers (median age 47 years, interquartile range, IQR 19·5 years, 48% male), who in August 2024 were vaccinated with 30 μg of the updated mRNA omicron JN.1 vaccine (bretovameran, BioNTech/Pfizer, Mainz, Germany). Humoral immune responses were analyzed directly prior to and 13 days after vaccination.

The omicron JN.1 vaccination resulted in a significant 1·2-fold increase of anti-S IgG and 1·2-fold increase of omicron anti-S IgG (p<0·0001). To assess plasma neutralisation capacity, we employed a pseudovirus particle (pp) neutralisation assay including S proteins of seven SARS-CoV-2 lineages. Baseline response rates were 100% for XBB.1.5pp, 90% for JN.1ppand KP.2pp, 82% for KP.2.3pp, 92% for KP.3pp, and 72% for LB.1pp. Before JN.1 vaccination, particles bearing KP sublineage S proteins were slightly less efficiently neutralised compared with JN.1pp(median change, 1·2-fold to 2·6-fold), while LB.1ppneutralisation was 3-fold reduced, indicating antibody evasion. After vaccination, the response rates increased significantly for all pseudoviruses except XBB.1.5ppand KP.3pp. Thus, we observed a significant increase in neutralisation of JN.1pp, KP.2pp, KP.2.3pp, and LB.1pp, showing a median change of 2.2-fold, 3.8-fold, 3.3-fold, and 4.9-fold, respectively.

In summary, bretovameran increased anti-S IgG and strengthened neutralising responses against circulating SARS-CoV-2-variants, except for KP.3. We wish to point out that our study population exhibited high pre-vaccination omicron-related hybrid immunity and may not be representative of other populations. Our data supports the notion that the new mRNA vaccine against omicron JN.1 most likely increases protection against hospitalization and post-COVID sequelae caused by most current variants.
Structure and inhibition mechanisms ofMycobacterium tuberculosisessential transporter efflux protein A
Authors: Khandelwal Nitesh Kumar , Gupta Meghna , Gomez James E. , Barkho Sulyman , Guan Ziqiang , Eng Ashley Y. , Kawate Tomo , Balasubramani Sree Ganesh , Sali Andrej , Hung Deborah T. , Stroud Robert M.
Published: September 2024

A broad chemical genetics screen inMycobacterium tuberculosis (Mtb)to identify inhibitors of established or previously untapped targets for therapeutic development yielded compounds (BRD-8000.3 and BRD-9327) that inhibit the essential efflux pump EfpA. To understand the mechanisms of inhibition by these compounds, we determined the structures of EfpA with inhibitors bound at 2.7 -3.4 Å resolution. Our structures reveal different mechanisms of inhibition for the two inhibitors. BRD-8000.3 binds in a tunnel making contact with the lipid bilayer and extending toward the central cavity to displace the fatty acid chain of a lipid molecule bound in the apo structure, suggesting its blocking of an access route for a natural lipidic substrate, in contrast to its uncompetitive mechanism for the small molecule substrate ethidium bromide which likely enters through an alternative tunnel. Meanwhile, BRD-9327 binds in the outer vestibule without complete blockade of the substrate path to the outside, suggesting its possible inhibition of the dynamical motion necessary for “alternate access” to the two different sides of the membrane, as is characteristic of major facilitator superfamily (MFS) transporters. Both inhibitors may have a role in inhibiting the “alternate access” mechanism that could account for the uncompetitive nature of their efflux of some substrates. Our results explain the basis of the synergy of these inhibitors and their potential for combination in a multi drug strategy for anti-tuberculosis therapy. They also potentially point to a possible function for this essential efflux pump as a lipid transporter. The structures provide a foundation for rational modification of these inhibitors to increase potency.
The Autonomous Cognitive Examination: Machine-Learning Based Cognitive Examination
Authors: Howard Calvin W. , Johnson Amy , Barotono Sheena , Faust Katharina , Peedicail Joseph , Ng Marcus
Published: September 2024

Structured Abstract

INTRODUCTION

The rising prevalence of dementia necessitates a scalable solution to cognitive screening and diagnosis. Digital cognitive assessments offer a solution but lack the extensive validation of older paper-based tests. Creating a digital cognitive assessment which recreates a paper-based assessment could have the strengths of both tests.

METHODS

We developed the Autonomous Cognitive Examination (ACoE), a fully remote and automated digital cognitive assessment which recreates the assessments of paper-based tests. We assessed its ability to reproduce entire cognitive screens in a comparison cohort (n = 35), and the ability to reproduce overall diagnoses with an additional validation cohort (n = 11).

RESULTS

The ACoE reproduced overall cognitive assessments with excellent agreement (intraclass correlation coefficient = 0.89) and reproduced overall diagnoses with excellent fidelity (area under the curve = 0.96).

DISCUSSION

The ACoE may reliably reproduce the evaluations of the ACE-3, which may help in accessible evaluation of patient cognition. Assessment in larger population of patients with specific diseases will be necessary to determine usefulness.
Disrupted developmental signaling induces novel transcriptional states
Authors: Patel Aleena , Gonzalez Vanessa , Menon Triveni , Shvartsman Stanislav Y. , Burdine Rebecca , Avdeeva Maria
Published: September 2024

Signaling pathways induce stereotyped transcriptional changes as stem cells progress into mature cell types during embryogenesis. Signaling perturbations are necessary to discover which genes are responsive or insensitive to pathway activity. However, gene regulation is additionally dependent on cell state-specific factors like chromatin modifications or transcription factor binding. Thus, transcriptional profiles need to be assayed in single cells to identify potentially multiple, distinct perturbation responses among heterogeneous cell states in an embryo. In perturbation studies, comparing heterogeneous transcriptional states among experimental conditions often requires samples to be collected over multiple independent experiments. Datasets produced in such complex experimental designs can be confounded by batch effects. We present Design-Aware Integration of Single Cell ExpEriments (DAISEE), a new algorithm that models perturbation responses in single-cell datasets with a complex experimental design. We demonstrate that DAISEE improves upon a previously available integrative non-negative matrix factorization framework, more efficiently separating perturbation responses from confounding variation. We use DAISEE to integrate newly collected single-cell RNA-sequencing datasets from 5-hour old zebrafish embryos expressing optimized photoswitchable MEK (psMEK), which globally activates the extracellular signal-regulated kinase (ERK), a signaling molecule involved in many cell specification events. psMEK drives some cells that are normally not exposed to ERK signals towards other wild type states and induces novel states expressing a mixture of transcriptional programs, including precociously activated endothelial genes. ERK signaling is therefore capable of introducing profoundly new gene expression states in developing embryos.

Significance Statement

Signaling perturbations produce heterogeneous transcriptional responses that must be measured at the single-cell level. Data integration techniques allow us to model these responses which, however, can be confounded by batch effects. We present a computational tool (DAISEE) for extracting the common and perturbation-specific features of single-cell datasets representing multiple experimental conditions while achieving efficient batch effect correction. DAISEE outperforms its predecessor and will enable accurate analysis of a broad range of single-cell datasets. DAISEE applied to new single-cell RNA sequencing data from zebrafish embryos shows that gain-of-function signaling perturbations can induce novel states. Our analysis suggests that a wild type endothelial cell-specification program can be activated in abnormal developmental contexts when the extracellular signal-regulated kinase (ERK) pathway is deregulated.
Application of barcode sequencing to increase the throughput and complexity ofPlasmodium falciparumgenetic screening
Authors: Muhwezi Allan , Ghorbal Mehdi , Sanderson Theo , Ivanova Maria , Ansari Rizwan , Harper Sarah , Wong Wesley , Schulte Reiner , Girling Gareth , Schwach Frank , Bushell Ellen , Beaver Charlotte , Billker Oliver , Rayner Julian C.
Published: September 2024

All the pathology and symptoms associated with malaria are caused by the growth ofPlasmodiumparasites inside human red blood cells. This process, which in the case of the major human malaria pathogenPlasmodium falciparumtakes place over a 48-hour period, involves multiple tightly regulated developmental transitions. Understanding theP. falciparumgenes that regulate these key processes could lead to the identification of targets for new drugs. However, while large-scale sequencing efforts have led to a good understanding of theP. falciparumgenome and how it evolves over time and space, a disconnect remains between the amount of genome sequence data available and the amount of data describing what exactly the genes contained within it do – the phenotype. We have generated a panel of 66P. falciparumlines carrying individual gene knockouts tagged with unique DNA barcodes. We then used these lines in a series of assays that combine flow cytometry, cell sorting and DNA barcode quantification using next generation sequencing (Barcode Sequencing or BarSeq) to phenotype key aspects of the parasite life cycle such as growth, replication capacity and cell cycle progression. This approach both yields new data about individual gene function, and outlines a new approach where barcodedP. falciparumlines are used in pooled BarSeq-based assays to generate more precise phenotype data at scale.
Transcription termination and antitermination are critical for the fitness and function of the integrative and conjugative element Tn916
Authors: Wirachman Erika S. , Grossman Alan D.
Published: September 2024

Premature expression of genes in mobile genetic elements can be detrimental to their bacterial hosts. Tn916, the founding member of a large family of integrative and conjugative elements (ICEs; aka conjugative transposons), confers tetracycline-resistance and is found in several Gram-positive bacterial species. We identified a transcription terminator near one end of Tn916that functions as an insulator that prevents expression of element genes when Tn916is integrated downstream from an active host promoter. The terminator blocked expression of Tn916genes needed for unwinding and rolling circle replication of the element DNA, and loss of the terminator caused a fitness defect for the host cells. Further, we identified an element-encoded antiterminator (namedcanTfor conjugation-associated antitermination) that is essential for transcription of Tn916genes after excision of the element from the host chromosome. We found that the antiterminator is orientation-specific, functions with heterologous promoters and terminators, is processive and is most likely acis-acting RNA. Insulating gene expression in conjugative elements that are integrated in the chromosome is likely a key feature of the interplay between mobile genetic elements and their hosts and appears to be critical for the function and evolution of the large family of Tn916-like elements.

AUTHOR SUMMARY

Horizontal gene transfer allows bacteria to rapidly acquire new traits that can enhance their adaptability to different conditions. Integrative and conjugative elements (ICEs) are mobile genetic elements that reside integrated in a bacterial chromosome and can transfer to another cell via cell-to-cell contact through the element-encoded secretion system. ICEs often confer beneficial traits to their hosts, including antibiotic resistances, symbiotic/pathogenic determinants, metabolic capabilities, and anti-phage defense systems. Tn916, the first-described ICE, was identified based on its ability to transfer tetracycline resistance in the pathogenEnterococcus faecalis, and is found in several Gram-positive species. Once transferred into a new cell, Tn916integrates into AT-rich sequences, sometimes downstream from a host promoter. We found that Tn916has a transcription terminator near one end of the element that blocks transcription from an upstream host promoter, thereby protecting cells from detrimental effects of premature expression of element genes. Further, we found that Tn916has a transcription antitermination system that is essential for expression of element genes after excision from the host chromosome. Our findings highlight the complex layers of transcriptional regulation that have evolved in ICEs, impacting host cell viability and the spread of the element.
Mapping the ultrastructural topology of the corynebacterial cell surface
Authors: Isbilir Buse , Yeates Anna , Alva Vikram , Bharat Tanmay A.M.
Published: September 2024

Corynebacterium glutamicumis a diderm bacterium extensively used in the industrial-scale production of amino acids. Corynebacteria belong to the bacterial familyMycobacteriaceae, which is characterized by a highly unusual cell envelope with an outer membrane consisting of mycolic acids. Despite the occurrence of this distinctive cell envelope in several bacterial pathogens, includingCorynebacterium diphtheriae, Mycobacterium tuberculosis, andMycobacterium leprae, its ultrastructural and molecular details remain elusive.

To address this, we investigated the cell envelope ofC. glutamicumusing electron cryotomography and cryomicroscopy of focused ion beam-milled cells. Our high-resolution images allowed us to accurately map the different components of the cell envelope into the tomographic density. Our data reveal thatC. glutamicumhas a variable cell envelope, with the outermost layer comprising the surface (S-)layer, which decorates the mycomembrane in a patchy manner. We further isolated and resolved the structure of the S-layer at 3.1 Å resolution using single particle electron cryomicroscopy. Our structure shows that the S-layer ofC. glutamicumis composed of a hexagonal array of the PS2 protein, which interacts directly with the mycomembrane via a coiled coil-containing anchoring segment. Bioinformatic analyses revealed that the PS2 S-layer is sparsely yet exclusively present within theCorynebacteriumgenus and absent in other genera of theMycobacteriaceaefamily, suggesting distinct evolutionary pathways in the development of their cell envelopes.

Our structural and cellular data collectively provide a high-resolution topography of the unusualC. glutamicumcell surface, features of which are shared by many pathogenic and microbiome-associated bacteria, as well as by several industrially significant bacterial species. This study, therefore, provides a strong experimental framework for understanding cell envelopes that contain mycolic acids.
Shared genetic architecture links energy metabolism, behavior and starvation resistance along a power-endurance axis
Authors: Erkosar Berra , Dupuis Cindy , Savary Loriane , Kawecki Tadeusz J.
Published: September 2024

Shared developmental, physiological and molecular mechanisms can generate strong genetic covariances across suites of traits, constraining genetic variability and evolvability to certain axes in multivariate trait space (“variational modules” or “syndromes”). Such trait suites will not only respond jointly to selection; they will also covary across populations that diverged from one another by genetic drift. We report evidence for such a genetically correlated trait suite inDrosophila melanogaster. It links high expression of glycolysis and TCA cycle genes, high abundance of mitochondria and high spontaneous locomotor activity with low degree of adiposity, and low endurance and early death under starvation. This “power-endurance” axis is also aligned with abundance of certain metabolites, notably low trehalose (blood sugar) and high levels of some amino acids and their derivatives, including creatine, a compound known to facilitate energy production in muscles. Our evidence comes from six replicate “Selected” populations adapted to a nutrient-poor larval diet regime during 250 generations of experimental evolution and six “Control” populations evolved in parallel on a standard diet regime. We found that, within each of these experimental evolutionary regime, the above traits strongly covaried along the power-endurance axis across replicate populations which diversified by drift, indicating a shared genetic architecture. The two evolutionary regimes also drove divergence along this axis, with Selected populations on average displaced towards the “power” direction compared to Controls. Aspects of this “power-endurance” axis resemble the “pace of life” syndrome and the “thrifty phenotype”; it may have evolved as part of a coordinated organismal response to nutritional conditions.
Mutation and recombination parameters in zebra finch are similar to those in mammals
Authors: Prentout Djivan , Bykova Daria , Hoge Carla , Hooper Daniel M. , McDiarmid Callum S. , Wu Felix , Griffith Simon C. , de Manuel Marc , Przeworski Molly
Published: September 2024

Most of our understanding of the fundamental processes of mutation and recombination stems from a handful of disparate model organisms and pedigree studies of mammals, with little known about other vertebrates. To gain a broader comparative perspective, we focused on the zebra finch (Taeniopygia castanotis), which, like other birds, differs from mammals in its karyotype (which includes many micro-chromosomes), in the mechanism by which recombination is directed to the genome, and in aspects of ontogenesis. We collected genome sequences from three generation pedigrees that provide information about 80 meioses, inferring 202 single-pointde novomutations, 1,174 crossovers, and 275 non-crossovers. On that basis, we estimated a sex-averaged mutation rate of 5.0 × 10−9per base pair per generation, on par with mammals that have a similar generation time (∼2-3 years). Also as in mammals, we found a paternal germline mutation bias at later stages of gametogenesis (of 1.7:1) but no discernible difference between sexes in early development. Examining recombination patterns, we found that the sex-averaged crossover rate on macro-chromosomes (1.05 cM/Mb) is again similar to values observed in mammals, as is the spatial distribution of crossovers, with a pronounced enrichment near telomeres. In contrast, non-crossover rates are more uniformly distributed. On micro-chromosomes, sex-averaged crossover rates are substantially higher (4.21 cM/Mb), as expected from crossover homeostasis, and both crossover and non-crossover events are more uniformly distributed. At a finer scale, recombination events overlap CpG islands more often than expected by chance, as expected in the absence of PRDM9. Despite differences in the mechanism by which recombination events are specified and the presence of many micro-chromosomes, estimates of the degree of GC-biased gene conversion (59%), the mean non-crossover conversion tract length (∼32 bp), and the non-crossover-to-crossover ratio (5.4:1) are all comparable to those reported in primates and mice. The similarity of mutation and recombination properties in zebra finch to those in mammals suggest that they are conserved by natural selection.
CRISPR-Cas9 target-strand nicking provides phage resistance by inhibiting replication
Authors: Nguyen Giang T. , Schelling Michael A. , Sashital Dipali G.
Published: September 2024

Cas endonucleases, like Cas9 and Cas12a, are RNA-guided immune effectors that provide bacterial defense against bacteriophages. Cas endonucleases rely on divalent metal ions for their enzymatic activities and to facilitate conformational changes that are required for specific recognition and cleavage of target DNA. While Cas endonucleases typically produce double-strand breaks (DSBs) in DNA targets, reduced, physiologically relevant Mg2+concentrations and target mismatches can result in incomplete second-strand cleavage, resulting in the production of a nicked DNA. It remains poorly understood whether nicking by Cas endonucleases is sufficient to provide protection against phage. To address this, we tested phage protection by Cas9 nickases, in which only one of two nuclease domains is catalytically active. By testing a large panel of guide RNAs, we find that target strand nicking can be sufficient to provide immunity, while non-target nicking does not provide any additional protection beyond Cas9 binding. Target-strand nicking inhibits phage replication and can reduce the susceptibility of Cas9 to viral escape when targeting non-essential regions of the genome. Cleavage of the non- target strand by the RuvC domain is strongly impaired at low Mg2+concentrations. As a result, fluctuations in the concentration of other biomolecules that can compete for binding of free Mg2+strongly influences the ability of Cas9 to form a DSB at targeted sites. Overall, our results suggest that Cas9 may only nick DNA during CRISPR-mediated immunity, especially under conditions of low Mg2+availability in cells.
Simultaneous extraction of the weak radius and the weak mixing angle from parity-violating electron scattering on
C12
Authors: Cadeddu M. , Cargioli N. , Erler J. , Gorchtein M. , Piekarewicz J. , Roca-Maza Xavier , Spiesberger H.
Published: September 2024

We study the impact of nuclear structure uncertainties on a measurement of the weak charge of C12 at the future Mainz Energy Recovering Superconducting Accelerator (MESA) facility in Mainz. Information from a large variety of nuclear models, accurately calibrated to the ground-state properties of selected nuclei, suggest that a 0.3% precision measurement of the parity-violating asymmetry at forward angles will not be compromised by nuclear structure effects, thereby allowing a world-leading determination of the weak charge of C12. Furthermore, we show that a combination of measurements of the parity-violating asymmetry at forward and backward angles for the same electron-beam energy can be used to extract information on the nuclear weak charge distribution. We conclude that a 0.34% precision on the weak radius of C12 may be achieved by performing a 3% precision measurement of the parity-violating asymmetry at backward angles.

Published by the American Physical Society
2024
Popping: A granular transition
Authors: Ghosh A. , Bandi M. M. , Ghosh S.
Published: September 2024

In experiments conducted on a weakly confined 2D assembly of deformable cylinders subject ed to rapid in-plane shear loading, we have identified the key obstacle in achieving compaction. This obstacle involves a dynamic transition between mechanical instabilities, progressing from in-plane rearrangement to out-of-plane popping as the density increases. The popping effect reinforces the frictional constraints from the confining wall and restricts particle mobility, impeding the system from attaining greater compaction. We quantify this transition and demonstrate that interparticle friction contributes to smoothing the transition.

Published by the American Physical Society
2024
Local order metrics for many-particle systems across length scales
Authors: Maher Charles Emmett , Torquato Salvatore
Published: September 2024

Formulating order metrics that sensitively quantify the degree of order/disorder in many-particle systems in d-dimensional Euclidean space Rd across length scales is an outstanding challenge in physics, chemistry, and materials science. Since an infinite set of n-particle correlation functions is required to fully characterize a system, one must settle for a reduced set of structural information, in practice. We initiate a program to use the local number variance σN2(R) associated with a spherical sampling window of radius R (which encodes pair correlations) and an integral measure derived from it ΣN(Ri,Rj) that depends on two specified radial distances Ri and Rj. Across the first three space dimensions (d=1,2,3), we find these metrics can sensitively describe and categorize the degree of order/disorder of 41 different models of antihyperuniform, nonhyperuniform, disordered hyperuniform, and ordered hyperuniform many-particle systems at a specified length scale R. Using our local variance metrics, we demonstrate the importance of assessing order/disorder with respect to a specific value of R. These local order metrics could also aid in the inverse design of structures with prescribed length-scale-specific degrees of order/disorder that yield desired physical properties. In future work, it would be fruitful to explore the use of higher-order moments of the number of points within a spherical window of radius R [S. Torquato , ] to devise even more sensitive order metrics.

Published by the American Physical Society
2024
catena-Poly[[(8-aminoquinoline)cobalt(II)]-di-μ-azido]
Authors: Setifi Fatima , Setifi Zouaoui , Geiger David K. , Al-Douh Mohammed Hadi , Addala Abderezak
Published: September 2024

The title coordination polymer, [Co(N3)2(C9H8N2)]
n
, was synthesized solvothermally. The CoII atom exhibits a distorted octahedral [CoN6] coordination geometry with a bidentate 8-aminoquinoline ligand and four azide ligands. Bridging azide ligands result in chains extending along [100]. N—H...N hydrogen bonds join the chains to give an extended structure with sheets parallel to (002).
Is OFDI persistence beneficial for firms' performance? Evidence from Chinese firms
Authors: Ding Sasa , Liu Yajun , Huang Yi
Published: September 2024

Purpose

Based on organizational learning theory, this study aims to investigate the performance consequences and potential contextual factors of outward foreign direct investment (OFDI) persistence.

Design/methodology/approach

A regression analysis was conducted on a sample of 19,950 OFDI events of 1,425 A-share listed Chinese enterprises from 2008 to 2022. The estimator used was ordinary least squares with residual analysis, which allowed us to obtain robust and reliable results.

Findings

The results indicated that persistence in both greenfield investments and cross-border M&As had a significant and positive impact on firm performance, and such relationship was positively moderated by organizational absorptive capacity.

Research limitations/implications

This study only tested the economic performance of OFDI persistence rather than innovation and social performance. Exploring the effects of OFDI persistence on other aspects may also add new insights to the persistence literature. Besides absorptive capacity, it might be useful to conduct a more comprehensive consideration of moderators in the future.

Originality/value

This paper contributes to the research on the temporal dimension of internationalization by introducing the concept of OFDI persistence. Additionally, we used the OFDI spell to capture the notion of OFDI persistence, which is an endeavor to overcome the shortcomings of the traditional indicator. Finally, this paper also contributes to the organizational learning perspective by applying it to analyze persistent OFDI operations.
The impact of information and communication technology infrastructure on divorce for a sample of developed countries for the period 2012-2021
Authors: Lakhdari Boulenouar
Published: September 2024

Purpose

This study aims to measure the impact of information and communication technology (ICT) infrastructure on divorce for a sample of developed countries for the period (2012-2021).

Design/methodology/approach

This paper uses fixed effect and generalized method of moments (GMM) estimation to delve into the impact of eight ICT infrastructure factors on divorce. The analyses are based on data collected from the World Bank Development Indicators.

Findings

The fixed effect analysis revealed that an increase in both fixed-telephone subscriptions and population covered by at least a 4G led to an increase in divorce. However, an increase in mobile cellular subscriptions and active mobile broadband subscriptions lead to a decrease in divorce. The results of the GMM estimator showed that fixed broadband internet prices, mobile broadband internet prices, the percentage of the population covered by the 4 G mobile network and fixed-telephone subscriptions had a substantial effect on divorce. While fixed broadband subscriptions, active mobile broadband subscriptions and mobile cellular basket were found to hinder divorce.

Research limitations/implications

The findings of this study contribute to the existing literature by highlighting the impact of ICT on divorce in a sample of developed countries. Furthermore, it helps decision-makers and families to understand the causes of divorce related to ICT infrastructure in these societies, so they can understand this phenomenon and provide proactive policies.

Originality/value

This study used multiple factors to measure ICT infrastructure as well as the GMM estimator to delve into the impact of ICT on divorce.
A scoping review on combating workplace violence against psychiatry residents
Authors: Oyetunji Aderonke , Bunte Kailee , Bellman Val
Published: September 2024

Purpose

This paper aims to illuminate the issue of workplace violence (WPV) against psychiatry residents. Workplace violence is known to negatively impact physical and emotional well-being, professional development and the quality of the care that mental health professionals provide to patients. The authors discuss the prevalence of, risk factors for and consequences of WPV against psychiatry residents, as well as the need for support and resources to help residents cope with the emotional challenges of their job.

Design/methodology/approach

This paper is a review of the literature on WPV against psychiatry residents, and includes studies on its prevalence, associated risk factors and consequences.

Findings

Psychiatry residents face a heightened risk of WPV, including physical and verbal attacks, which can harm their mental and physical health and disrupt their continuity of care. Factors that contribute to WPV against psychiatry residents include exposure to aggressive or violent behaviors, inadequate training in WPV, understaffing, the stigmatization of mental illnesses, and discriminatory treatment. Furthermore, psychiatry residents who encounter WPV may develop negative emotions and attitudes toward their patients, which can compromise the care they provide.

Research limitations/implications

The inherent heterogeneity of study designs highlighted in this review could hinder the establishment of definitive conclusions about the impact of workplace violence on psychiatry residents. A focus on studies published in English may inadvertently exclude relevant literature in other languages, potentially limiting the comprehensiveness of study findings.

Originality/value

This paper highlights resident physicians’ personal experiences with and perceptions of WPV encountered during residency training. In response, potential solutions are proposed to address WPV, including increased support for resident physicians, mandatory reporting of WPV incidents, and a cultural shift toward zero tolerance for WPV. In addition, the paper raises awareness of the limited research on this topic and the importance of further investigation.
Dissatisfaction with professional accountant training: the role of learning styles
Authors: Malthus Sue , Fowler Carolyn , Cordery Carolyn J.
Published: September 2024

Purpose

Prior research finds that early-career professional accountants (early PAs) are generally dissatisfied with the learning and training opportunities offered during their early employment years, which impacts their career progression. This paper aims to examine whether different learning styles between these early PAs and their qualified accounting employers and trainers diverge.

Design/methodology/approach

Using Kolb’s learning styles inventory and interviews, this study explores the learning styles of early PAs and their employers, examining changes in these learning styles over time.

Findings

This research shows the necessity for different learning styles to be integrated into early PA training and learning, as research participants’ learning styles tend to prefer active experimentation requiring practical examples and self-learning opportunities. In contrast, their senior, qualified accounting employers prefer conceptualisation-based learning styles. As early PAs’ career progression requires them to succeed in employer-supported training, some early PAs change their learning style preferences to progress, whereas others with incompatible learning styles either moved to different employers or reassessed their choice of profession.

Practical implications

To reduce career dissatisfaction, develop and retain competent accountants, early PAs must be supported to learn effectively. By reducing early PAs’ dissatisfaction early PA educators and employers will potentially increase the attractiveness of accounting as a profession.

Originality/value

Few studies interrogate how accounting professionals utilise learning and training post-graduation nor do they examine the learning styles of workplace trainers and learners. This exploratory study uniquely analyses the learning styles of both early PAs and their employers.