bluuebunny/crossref_metadata_2025 huggingface dataset:
Divergent trajectories to structural diversity impact patient survival in high grade serous ovarian cancer
Authors: Ewing Ailith , Meynert Alison , Silk Ryan , Aitken Stuart , Bendixsen Devin P. , Churchman Michael , Brown Stuart L. , Hamdan Alhafidz , Mattocks Joanne , Grimes Graeme R. , Ballinger Tracy , Hollis Robert L. , Herrington C. Simon , Thomson John P. , Sherwood Kitty , Parry Thomas , Esiri-Bloom Edward , Bartos Clare , Croy Ian , Ferguson Michelle , Lennie Mairi , McGoldrick Trevor , McPhail Neil , Siddiqui Nadeem , Glasspool Rosalind , Mackean Melanie , Nussey Fiona , McDade Brian , Ennis Darren ,   The Scottish Genomes Partnership, McMahon Lynn , Matakidou Athena , Dougherty Brian , March Ruth , Barrett J. Carl , McNeish Iain A. , Biankin Andrew V. , Roxburgh Patricia , Gourley Charlie , Semple Colin A.
Published: January 2024

Deciphering the structural variation across tumour genomes is crucial to determine the events driving tumour progression and better understand tumour adaptation and evolution. High grade serous ovarian cancer (HGSOC) is an exemplar tumour type showing extreme, but poorly characterised structural diversity. We comprehensively describe the mutational landscape driving HGSOC, exploiting a large (N=324), deeply whole genome sequenced dataset. We reveal two divergent evolutionary trajectories, affecting patient survival and involving differing genomic environments. One involves homologous recombination repair deficiency (HRD) while the other is dominated by whole genome duplication (WGD) with frequent chromothripsis, breakage-fusion-bridges and extra-chromosomal DNA. These trajectories contribute to structural variation hotspots, containing novel candidate driver genes with significantly altered expression. While structural variation predominantly drives tumorigenesis, we also find high mtDNA mutation loads associated with shorter patient survival, and acting in combination with alterations in the nuclear genome to impact prognosis and suggesting new strategies for patient stratification.
Reproductive innovation enabled radiation in the deep sea during an ecological crisis
Authors: Brownstein Chase D. , Zapfe Katerina L. , Lott Spencer , Harrington Richard , Ghezelayagh Ava , Dornburg Alex , Near Thomas J.
Published: January 2024

Major ecological transitions are thought to fuel evolutionary radiations, but whether they are contingent on the evolution of certain traits is unclear. We show that the rapid ecological transition of anglerfishes into pelagic habitats during a period of major global warming coincided with the origins of sexual parasitism, in which male anglerfishes temporarily attach or permanently fuse to females to mate. A phylogenomic reconstruction of the evolutionary history of anglerfishes provides a strong inference for the convergent evolution of permanently-fusing deep-sea anglerfishes and their degenerate immune genes. Our results support that sexual parasitism was enabled by the degeneration of adaptive immunity and ancestral sexual size dimorphism. The combination of these traits facilitated the transition of pelagic anglerfishes into novel ecologies available in the deep open oceans after evolving from benthic ancestors. These results show how seemingly unrelated physiological and reproductive traits interact synergistically to drive evolutionary radiation in novel environments.
Loss of calpain 3 dysregulates store-operated calcium entry and its exercise response in mice
Authors: Villani Katelyn R. , Zhong Renjia , Spencer Henley-Beasley C. , Rastelli Giorgia , Boncompagni Simona , Barton Elisabeth R. , Wei-LaPierre Lan
Published: January 2024

Limb-Girdle Muscular Dystrophy 2A (LGMD2A) is caused by mutations in theCAPN3gene encoding Calpain 3, a skeletal-muscle specific, Ca2+-dependent protease. Localization of Calpain 3 within the triad suggests it contributes to Ca2+homeostasis. Through live-cell Ca2+measurements, muscle mechanics, immunofluorescence, and electron microscopy (EM) inCapn3deficient (C3KO) and wildtype (WT) mice, we determined if loss of Calpain 3 altered Store-Operated Calcium Entry (SOCE) activity. Direct Ca2+influx measurements revealed loss ofCapn3elicits elevated resting SOCE and increased resting cytosolic Ca2+, supported by high incidence of calcium entry units (CEUs) observed by EM. C3KO and WT mice were subjected to a single bout of treadmill running to elicit SOCE. Within 1HR post-treadmill running, C3KO mice exhibited diminished force production inextensor digitorum longusmuscles and a greater decay of Ca2+transients inflexor digitorum brevismuscle fibers during repetitive stimulation. Striking evidence for impaired exercise-induced SOCE activation in C3KO mice included poor colocalization of key SOCE proteins, stromal-interacting molecule 1 (STIM1) and ORAI1, combined with disappearance of CEUs in C3KO muscles. These results demonstrate that Calpain 3 is a key regulator of SOCE in skeletal muscle and identify SOCE dysregulation as a contributing factor to LGMD2A pathology.
The Molecular Picture of the Local Environment in a Stable Model Coacervate
Authors: Baksi Atanu , Zerze Hasan , Agrawal Aman , Karim Alamgir , Zerze Gül H.
Published: January 2024

Polymers with electric charge, known as polyelectrolytes, are well known to form complex coacervates, which have vital implications in various biological processes and beyond. While significant advancements have been made in comprehending the molecular interactions thatdrivecomplex coacervation, the interactions thatstabilizethe coacervates against coalescence present an intricate experimental challenge and remain a subject of ongoing investigation. In a recent experimental study, polydiallyldimethylammonium chloride polycationic (PDDA) and anionic adenosine triphosphate (ATP) coacervates have been shown to stabilize upon transferring them to deionized water. Here, we perform molecular dynamics simulations of PDDA-ATP coacervates both in supernatant and in DI water, to understand the ion dynamics and structure within stable coacervates. We produced and analyzed an aggregated sum of 63μssimulation data of PDDA-ATP coacervates in explicit water when they are in supernatant and deionized (DI) water. We found that discarding the supernatant and transferring the coacervates to DI water causes an immediate ejection of a significant amount (more than 50%) of small ions (Na+andCl−) from the coacervates to the bulk solution. Subsequently, the DI water environment alters the ionic density profiles in coacervates and the surface ion dynamics. We calculated a notable slowdown for the coacervate ions when they were transferred to the DI water. These results suggest that the initial ejection of the ions from the coacervates in DI water potentially brings the outer layer of the coacervates to a physically bound state that prevents or slows down the further mobility of ions.

Significance Statement

Complex coacervates are promising agents for encapsulating and delivering various materials in living organisms, however, they are often prone to coalesce, limiting the range of their applications. Recently, these coacervates have been stabilized by transferring them to deionized water. However, a molecular understanding of this stability against coalescence remained elusive. This study utilizes computer simulations to model a stable coacervate system previously probed experimentally. When the coacervates were transferred to deionized water, a significant portion of the ions were immediately ejected into the solution, modifying the coacervates’ total charge and facilitating formation of possible surface crust. These molecular insights into the stable coacervates will enable their controllable design for encapsulation and delivery applications.
Pharmacological validation of an attention bias test for conventional broiler chickens
Authors: Lourenço da Silva Marconi Italo , Ulans Alexandra , Jacobs Leonie
Published: January 2024

Fear and anxiety are considered concerns for animal welfare as they are associated with negative affective states. This study aimed to pharmacologically validate an attention bias test (ABT) for broiler chickens (Gallus gallus domesticus) as a cognitive bias test to determine anxiety. Two-hundred-and-four male Ross 708 broiler chickens were arbitrarily allocated to either the anxiogenic or control treatment at day 25 of age, resulting in 102 birds per treatment. Birds from the anxiogenic group were administered with 2.5 mg/kg of β-CCM (β-carboline-3-carboxylic acid-N-methylamide [FG 7142]) through an intraperitoneal injection at a volume of 0.1 ml/100 g of body weight. Birds from the control group were administered with 9 mg/kg of a saline solution. During ABT, birds were tested in groups of three (n = 34 groups of three birds/treatment) with commercial feed and mealworms as positive stimuli and a conspecific alarm call as a negative stimulus. Control birds were 45 s faster to begin feeding than anxiogenic birds. Birds from the control group vocalized 40 s later and stepped 57 s later than birds from the anxiogenic group. The occurrence of vigilance behaviors did not differ between treatments. This study was successful in pharmacologically validating an attention bias test for fast-growing broiler chickens, testing three birds simultaneously. Our findings showed that latencies to begin feeding, first vocalization, and first step were valid measures to quantify anxiety.
2018-2019 human seasonal H3N2 influenza A virus spillovers into swine with demonstrated virus transmission in pigs were not sustained in the pig population
Authors: Powell Joshua D. , Thomas Megan N. , Anderson Tavis K. , Zeller Michael A. , Gauger Phillip C. , Baker Amy L. Vincent
Published: January 2024

Human seasonal H3 3C3a clade influenza A viruses (IAV) were detected in four U.S. pigs from commercial swine farms in Michigan, Illinois, and Virginia in 2019. To evaluate the relative risk of this spillover to the pig population, whole genome sequencing and phylogenetic characterization was conducted and revealed all eight viral gene segments were closely related to 2018-2019 H3N2 human seasonal IAV. Next, a series of in vitro viral kinetics, receptor binding, and antigenic characterization studies were performed using a representative A/swine/Virginia/A02478738/2018(H3N2) (SW/VA/19) isolate. Viral replication kinetic studies of SW/VA/19 demonstrated less efficient replication curves than all ten swine H3N2 viruses tested, but higher than three human H3N2 strains. Serial passaging experiments of SW/VA/19 in swine cells did not increase virus replication, but changes at HA amino acid positions 9 and 159 occurred. In swine transmission studies, wild type SW/VA/19 was shed in nasal secretions and transmitted to all indirect contact pigs, whereas the human seasonal strain A/Switzerland/9715293/2013(H3N2) from the same 3C3a clade failed to transmit. SW/VA/19 induced minimal macroscopic and microscopic lung lesions. Collectively these findings demonstrate that these human seasonal H3N2 3C3a-like viruses did not require reassortment with endemic swine IAV gene segments, impacting virus shedding and transmission in pigs. Limited detections in the U.S. pig population in the subsequent period of time suggests a yet unknown restriction factor likely limiting the spread of these viruses in the U.S. pig population.

IMPORTANCE

Interspecies human-to-swine IAV transmission occurs globally and contributes to increased IAV diversity in pig populations. We present data that a swine isolate from a 2018-2019 human-to-swine transmission event was shed for multiple days in challenged and contact pigs. By characterizing this introduction through bioinformatic, molecular, and animal experimental approaches, these findings better inform animal health practices and in vaccine decision-making. Since wholly human seasonal H3N2 viruses in the U.S. were not previously identified as being transmissible in pigs (i.e. reverse zoonosis), these findings reveal the interspecies barriers for transmission to pigs may not require significant changes to all human seasonal H3N2.
TransMEP: Transfer learning on large protein language models to predict mutation effects of proteins from a small known dataset
Authors: Hoffbauer Tilman , Strodel Birgit
Published: January 2024

Machine learning-guided optimization has become a driving force for recent improvements in protein engineering. In addition, new protein language models are learning the grammar of evolutionarily occurring sequences at large scales. This work combines both approaches to make predictions about mutational effects that support protein engineering. To this end, an easy-to-use software tool called TransMEP is developed using transfer learning by feature extraction with Gaussian process regression. A large collection of datasets is used to evaluate its quality, which scales with the size of the training set, and to show its improvements over previous fine-tuning approaches. Wet-lab studies are simulated to evaluate the use of mutation effect prediction models for protein engineering. This showed that TransMEP finds the best performing mutants with a limited study budget by considering the trade-off between exploration and exploitation.

Graphical TOC Entry
A user-friendly input–output (IO) curve analysis tool for variable brain stimulation responses, particularly evoked potentials in transcranial magnetic stimulation (TMS)
Authors: Ma Ke , Goetz Stephan M.
Published: January 2024

Background

Motor-evoked potentials (MEPs) are among the few readily observable direct responses to suprathreshold stimuli administered to the brain. They serve for a variety of applications, often in the form of dose–response curves, also called recruitment or input–output (IO) curves. However, MEPs and thus IO curves demonstrate extreme trial-to-trial variability that can exceed more than two decimal orders of magnitude. Recent studies have identified issues in previous statistical analysis of IO curves and introduced better methods, others could quantitatively separate several widely independent variability sources. However, research has failed providing the field with a user-friendly implementation of the methods for analysing such IO curves statistically sound and separating variability so that they were limited to a few research groups.

Objective

This work intends to provide the latest methods for analysing IO curves and extract variability information in an open-source package so that the community can easily use and adapt them to their own needs.

Methods

We implemented recent IO curve methods with a graphical user interface and provided the code as well as compiled versions for Mac, Linux, and Windows.

Results

The application imports typical IO data of individual stimulus–response sets, guides users step by step through the analysis, and allows exporting of the results including figures for post-hoc analysis and documentation.

Conclusion

This graphical application offers a user-friendly environment for analysing the variability of evoked potentials and its various contributions, catering to the needs of clinical and experimental neuroscientists.
Prediction of Post Traumatic Epilepsy using MRI-based Imaging Markers
Authors: Akrami Haleh , Cui Wenhui , Kim Paul E. , Heck Christianne N. , Irimia Andrei , Jebri Karim , Nair Dileep , Leahy Richard M. , Joshi Anand A.
Published: January 2024

Post-traumatic Epilepsy (PTE) is a debilitating neurological disorder that develops after traumatic brain injury (TBI). Despite the high prevalence of PTE, current methods for predicting its occurrence remain limited. In this study, we aimed to identify imaging-based markers for the prediction of PTE using machine learning. Specifically, we examined three imaging features: lesion volumes and resting-state fMRI-based measures of functional connectivity and amplitude of low-frequency fluctuation (ALFF). We employed three machine learning methods, namely, kernel support vector machine (KSVM), random forest, and a neural network, to develop predictive models. Our results showed that the KSVM classifier, with all three feature types as input, achieved the best prediction accuracy of 0.78 AUC (Area Under the Receiver Operating Characteristic (ROC) curve) using nested cross-validation. Furthermore, we performed voxel-wise and lobe-wise group difference analyses to investigate the specific brain regions and features that the model found to be most helpful in distinguishing PTE from non-PTE populations. Our statistical analysis uncovered significant differences in bilateral temporal lobes and cerebellum between PTE and non-PTE groups. Overall, our findings demonstrate the complementary prognostic value of MR-based markers in PTE prediction and provide new insights into the underlying structural and functional alterations associated with PTE.
Revisiting the invasion paradox: resistance-richness relationship is driven by augmentation and displacement trends
Authors: Zhu Yu , Momeni Babak
Published: January 2024

Host-associated resident microbiota can protect their host from pathogen—a community-level trait called colonization resistance. The effect of the diversity of the resident community in previous studies has shown contradictory results, with higher diversity either strengthening or weakening colonization resistance. To control the confounding factors that may lead to such contradictions, we use mathematical simulations that focus on species interactions and their impact on colonization resistance. We use a mediator-explicit model that accounts for metabolite-mediated interactions to performin silicoinvasion experiments. Our results state that colonization resistance often does not have a monotonic relationship with the species richness of the resident community. Instead, colonization outcomes are often the consequence of two underlying trends as the richness of the resident community increases: a decrease in instances of augmentation (invader species added, without driving out resident species) and an increase in instances of displacement (invader species added, driving out some of the resident species). We observe these two underlying trends hold consistently under different parameters, regardless of the number of compounds that mediate interactions between species or the proportion of the facilitative versus inhibitory interactions among species. Our results provide an explanation for the seemingly contradictory trend in the resistance-diversity relationship in previous reports.
Strategic Debulking of the Femoral Stem Promotes Load Sharing Through Controlled Flexural Rigidity of the Implant Wall: Optimization of Design by Finite Element Analysis
Authors: Sunavala-Dossabhoy Gulshan , Saba Brent M. , McCarthy Kevin
Published: January 2024

Hip arthroplasty prostheses are often constructed of metal alloys, and the inherent disparity in the modulus of elasticity between the implant and the femur is attributed to the altered stress-strain pattern in adjacent bone. Rigid implants shield surrounding bone from mechanical loading, and the reduction in skeletal stress required to maintain bone mass and density results in accelerated bone loss, the forerunner to implant loosening and implant failure. Femoral stems of various geometric profiles and surface modifications, materials and material distributions for graded functionality, and porous stem structures have been investigated to achieve mechanical properties of stems that are closer to bone to mitigate stress shielding. For improved load transfer from implant to femur, the proposed study investigated a strategic debulking effort to impart controlled flexibility while retaining sufficient strength and endurance properties of the femoral stem. Using an iterative design process, debulked configurations based on an internal skeletal truss framework were evaluated using finite element analysis as outlined in ISO 7206 standards, with implants offset in natural femur or potted in testing cylinders. The commonality across the debulked designs was the minimization of proximal stress shielding compared to conventional solid implants. Stem topography can influence performance, and the truss implants with and without the calcar collar were evaluated. Load sharing was equally effective irrespective of the collar however, the collar was critical to reducing the stresses in the implant. When bonded directly to bone or cemented in the femur, the truss stem was effective at limiting stress shielding. Nevertheless, a localized increase in principal stress at the lateral proximal junction could negatively affect cement integrity and the bonding of cemented implants. The study determined that superior biomechanical performance of the truss implant is realized with a collared stem that is placed in an interference fit. Mechanistically, the controlled accommodation of deformation of the implant wall provides contextual flexibility and load sharing characteristics to the truss implant.
Artificial intelligence–enabled electrocardiogram for mortality and cardiovascular risk estimation: An actionable, explainable and biologically plausible platform
Authors: Sau Arunashis , Pastika Libor , Sieliwonczyk Ewa , Patlatzoglou Konstantinos , Ribeiro Antonio H. , McGurk Kathryn A. , Zeidaabadi Boroumand , Zhang Henry , Macierzanka Krzysztof , Mandic Danilo , Sabino Ester , Giatti Luana , Barreto Sandhi M , do Valle Camelo Lidyane , Tzoulaki Ioanna , O’Regan Declan P. , Peters Nicholas S. , Ware James S. , Ribeiro Antonio Luiz P. , Kramer Daniel B. , Waks Jonathan W. , Ng Fu Siong
Published: January 2024

Background and Aims

Artificial intelligence-enhanced electrocardiograms (AI-ECG) can be used to predict risk of future disease and mortality but has not yet been adopted into clinical practice. Existing model predictions lack actionability at an individual patient level, explainability and biological plausibility. We sought to address these limitations of previous AI-ECG approaches by developing the AI-ECG risk estimator (AIRE) platform.

Methods and Results

The AIRE platform was developed in a secondary care dataset of 1,163,401 ECGs from 189,539 patients, using deep learning with a discrete-time survival model to create a subject-specific survival curve using a single ECG. Therefore, AIRE predicts not only risk of mortality, buttime-to-mortality. AIRE was validated in five diverse, transnational cohorts from the USA, Brazil and the UK, including volunteers, primary care and secondary care subjects. AIRE accurately predicts risk of all-cause mortality (C-index 0.775 (0.773-0.776)), cardiovascular (CV) death 0.832 (0.831-0.834), non-CV death (0.749 (0.747-0.751)), future ventricular arrhythmia (0.760 (0.756-0.763)), future atherosclerotic cardiovascular disease (0.696 (0.694-0.698)) and future heart failure (0.787 (0.785-0.889))). Through phenome- and genome-wide association studies, we identified candidate biological pathways for the prediction of increased risk, including changes in cardiac structure and function, and genes associated with cardiac structure, biological aging and metabolic syndrome.

Conclusion

AIRE is an actionable, explainable and biologically plausible AI-ECG risk estimation platform that has the potential for use worldwide across a wide range of clinical contexts for short- and long-term risk estimation.

Graphical Abstract
Assessing the Incidence of Postoperative Diabetes in Gastric Cancer Patients: A Comparative Study of Roux-en-Y Gastrectomy and Other Surgical Reconstruction Techniques
Authors: Onishi Tatsuki
Published: January 2024

Study objective

Sleeve gastrectomy is effective in morbid obesity, and it improves glucose homeostasis. In gastric cancer patients with type 2 diabetes mellitus, gastrectomy, including total gastrectomy (TG), is beneficial for glycaemic control. However, the effects of gastrectomy and different reconstructive techniques on the incidence of postoperative diabetes in gastric cancer patients are unclear. This study investigated the development of new-onset diabetes in these patients, focusing on different reconstruction methods.

Design

A comparative study

Setting

Electrical medical records

Patients

This study included 715 patients without diabetes who underwent TG at Tokyo Metropolitan Bokutoh Hospital between August 2005 and March 2019.

Interventions

Patients underwent reconstruction by Roux-en-Y (RY) or other surgical techniques (OT), with diabetes onset determined by HbA1c levels or medical records.

Measurements

Analyses included two-sample t-tests, chi-squared tests, and the Kaplan-Meier method with log-rank tests to compare the onset curves between the two groups.

Main Results

Stratified data analysis compared the RY and OT reconstruction methods. Log-rank test results (P=0.0217) indicated a statistically significant difference in the incidence of new-onset diabetes between RY and OT groups in gastric cancer patients.

Conclusion

This first-of-its-kind study provides insight into how different methods of gastric reconstruction affect postoperative diabetes. The results suggest significant differences in new-onset diabetes mellitus after surgery based on the reconstruction method. This research highlights the need for careful surgical planning to consider potential postoperative diabetes, particularly in patients with a family history of diabetes mellitus. Future studies should investigate the role of gut microbiota and other reconstructive techniques, such as laparoscopic jejunal interposition, in developing postoperative diabetes.
Genome assembly of the milky mangroveExcoecaria agallocha
Authors:   Hong Kong Biodiversity Genomics Consortium,   Project Coordinator and Co-Principal Investigators, Hui Jerome H.L. , Chan Ting Fung , Chan Leo L. , Cheung Siu Gin , Cheang Chi Chiu , Fang James K.H. , Gaitan-Espitia Juan Diego , Lau Stanley C.K. , Sung Yik Hei , Wong Chris K.C. , Yip Kevin Y.L. , Wei Yingying ,   DNA extraction, library preparation and sequencing, Law Sean T.S. , So Wai Lok ,   Genome assembly and gene model prediction, Nong Wenyan ,   Genome analysis and quality control, Nong Wenyan ,   Sample collector and logistics, Lau David T.W. , Law Sean T.S. , Lee Shing Yip , Yip Ho Yin
Published: January 2024

The milky mangroveExcoecaria agallochais a latex-secreting mangrove that are distributed in tropical and subtropical regions. While its poisonous latex is regarded as a potential source of phytochemicals for biomedical applications, the genomic resources ofE. agallocharemains limited. Here, we present a chromosomal level genome ofE. agallocha, assembled from the combination of PacBio long-read sequencing and Omni-C data. The resulting assembly size is 1,332.45 Mb and has high contiguity and completeness with a scaffold N50 of 58.9 Mb and a BUSCO score of 98.4 %. 73,740 protein-coding genes were also predicted. The milky mangrove genome provides a useful resource for further understanding the biosynthesis of phytochemical compounds inE. agallocha.
Spatio-temporal analysis of Vaccinia virus infection and host response dynamics using single-cell transcriptomics and proteomics
Authors: Matía Alejandro , McCarthy Frank , Woosley Hunter , Turon-Lagot Vincent , Platzer Sebastian W. , Liu Jonathan , Lorenzo María M. , Borja Michael , Shetty Kavya , Winkler Juliane , Elias Joshua E. , Blasco Rafael , Arias Carolina , Hein Marco Y.
Published: January 2024

Poxviruses are a large group of DNA viruses with exclusively cytoplasmic life cycles and complex gene expression programs. A number of systems-level studies have analyzed bulk transcriptome and proteome changes upon poxvirus infection, but the cell-to-cell heterogeneity of the transcriptomic response, and the subcellular resolution of proteomic changes have remained unexplored.

Here, we measured single-cell transcriptomes of Vaccinia virus-infected populations of HeLa cells and immortalized human fibroblasts, resolving the cell-to-cell heterogeneity of infection dynamics and host responses within those cell populations. We further integrated our transcriptomic data with changes in the levels and subcellular localization of the host and viral proteome throughout the course of Vaccinia virus infection.

Our findings from single-cell RNA sequencing indicate conserved transcriptome changes independent of the cellular context, including widespread host shutoff, heightened expression of cellular transcripts implicated in stress responses, the rapid accumulation of viral transcripts, and the robust activation of antiviral pathways in bystander cells. While most host factors were co-regulated at the RNA and protein level, we identified a subset of factors where transcript and protein levels were discordant in infected cells; predominantly factors involved in transcriptional and post-transcriptional mRNA regulation. In addition, we detected the relocalization of several host proteins such as TENT4A, NLRC5, and TRIM5, to different cellular compartments in infected cells. Collectively, our comprehensive data provide spatial and temporal resolution of the cellular and viral transcriptomes and proteomes and offer a robust foundation for in-depth exploration of virus-host interactions in poxvirus-infected cells.
Genomes ofAegilops umbellulataprovide new insights into unique structural variations and genetic diversity in the U-genome for wheat improvement
Authors: Singh Jatinder , Gudi Santosh , Maughan Peter J. , Liu Zhaohui , Kolmer James , Wang Meinan , Chen Xianming , Rouse Matthew , Lasserre-Zuber Pauline , Rimbert Helene , Sehgal Sunish , Fiedler Jason , Choulet Frédéric , Acevedo Maricelis , Gupta Rajeev , Gill Upinder
Published: January 2024

Aegilopsspp. serve as an important reservoir for novel sources of resistance or tolerance to biotic and abiotic stresses. To harness this reservoir, we have generated a high-quality chromosome-level genome assembly of anAe.umbellulataaccession PI 554389 using a combination of PacBio HiFi, Oxford nanopore, and chromosome conformation capture (Hi-C) sequencing technologies and resequenced 20Ae. umbellulatagenomes using Illumina sequencing. We assembled a 4.20 Gb genome spanned over seven chromosomes, rich in repetitive elements (∼84%), achieving a QV of 59.54 with 98.14% completeness. The phylogenetic analysis places the U-genome with D-lineage, but major and distinct rearrangements were revealed in the U-genome. Unique transposon landscape of diploid U-genome and complex chromosomal rearrangements, most prominently in 4U and 6U chromosomes uncovered a distinct evolutionary trajectory ofAe. umbellulata. Additionally, the resequencing of geographically and morphologically diverseAe. umbellulataaccessions revealed three distinctive evolutionary sub-populations. Resequencing also identified six new haplotypes forLr9, the first leaf rust resistance gene introgressed and cloned fromAe. umbellulata.These genomics resources along with high levels of resistance in the resequenced accessions against five devastating wheat diseases affirmed the genetic potential ofAe. umbellulatafor wheat improvement.
Development of a simple and highly sensitive method for the concentration and detection of African swine fever virus in oral fluids and its feasibility assessment on raised pigs in Northern Vietnam
Authors: Mai Thi Ngan , Tran Thi Huong Giang , Dong Van Hieu , Le Van Phan , Huynh Thi My Le , Bui Tran Anh Dao , Uemura Ryoko , Yamazaki Yasuko , Nguyen Thi Lan , Yamazaki Wataru
Published: January 2024

Background

Early detection and early slaughter through quarantine are essential to prevent the spread of the African swine fever virus (ASFV). Highly accurate testing is effective for early detection, but it is still difficult to establish a system, especially in the Global South. Pooled oral fluids tests have been used for simple pathogen monitoring, but compared to blood tests, the virus concentration in oral fluids is low, resulting in false negative and missing true positive cases. We collected oral fluids from raised pigs in northern Vietnam and attempted a highly sensitive ASFV survey using a newly developed virus concentration and detection method.

Results

In a spike test, the developed method showed up to 100 times greater sensitivity than a reference method. To compare and evaluate the performance of the developed method, a total of 68 pooled oral fluid samples were collected, 63 from northern Vietnam and 5 from southern Japan. Using real-time PCR, 9/68 (13.2%) were positive by the reference method, and 23/68 (33.8%) by the developed method. Using real-time LAMP, 1/68 (1.5%) were positive by the reference method and 6/68 (8.8%) by the developed method.

Conclusions

The developed method improved the sensitivity of ASFV detection from oral fluids and enabled early diagnosis of pigs before the onset of the disease. The developed method has the potential to enable simple and highly sensitive diagnosis of ASF, which is essential for its early diagnosis and effective surveillance.

Highlight

A method has been developed to detect ASFV in pig oral fluids with up to 100 times greater sensitivity than a reference method.

The developed method combines innovative pretreatment in less than 60 min with conventional nucleic acid extraction with a column kit followed by real-time PCR or LAMP.

Applied to feasibility assessment for ASF diagnosis on raised pigs, the developed method showed higher diagnostic sensitivity than the reference method.

The developed method can be a useful tool that contributes to early detection and surveillance of ASFV.
Protein kinase Sut1 from the CrenarchaeonSulfolobus acidocaldariusdisplays tyrosine phosphorylation activity
Authors: Maklad Hassan R. , Ruys Sébastien Pyr dit , Bervoets Indra , Vertommen Didier , Gutierrez Gustavo J. , Vranken Wim F. , Siebers Bettina , Peeters Eveline
Published: January 2024

Protein phosphorylation is a key cellular signaling mechanism that exists in all life forms. Unlike Bacteria and Eukarya, in which protein phosphorylation has thoroughly been studied, post-translational modification by means of phosphorylation have only been limitedly explored in Archaea. A previous study of the phosphoproteome of the model CrenarchaeonSulfolobus acidocaldariusrevealed a widespread occurrence of protein phosphorylation, especially on tyrosine residues. Moreover, several (putative) transcription factors, including AbfR1 and FadR, were previously shown to be phosphorylated on tyrosine residues, a phenomenon that is directly linked to a phosphorylation-mediated regulation of these transcription factors. Despite this potentially important role for tyrosine phosphorylation inS. acidocaldarius, to our knowledge, a kinase capable of directly phosphorylating tyrosine residues has not yet been identified in this organism, neither in Archaea as a whole. Here, we identify and characterize a protein kinase inS. acidocaldarius, Sut1, which displays tyrosine phosphorylation activityin vitroand represents a novel protein kinase family that is widespread in different archaeal organisms.
Denisovan admixture facilitated environmental adaptation in Papua New Guinean populations
Authors: Yermakovich Danat , André Mathilde , Brucato Nicolas , Kariwiga Jason , Leavesley Matthew , Pankratov Vasili , Mondal Mayukh , Ricaut François-Xavier , Dannemann Michael
Published: January 2024

Neandertals and Denisovans, having inhabited distinct regions in Eurasia and possibly Oceania for over 200,000 years, experienced ample time to adapt to diverse environmental challenges these regions presented. Among present-day human populations, Papua New Guineans (PNG) stand out as one of the few carrying substantial amounts of both Neandertal and Denisovan DNA, a result of past admixture events with these archaic human groups. This study investigates the distribution of introgressed Denisovan and Neandertal DNA within two distinct PNG populations, residing in the highlands of Mt Wilhelm and the lowlands of Daru Island. These locations exhibit unique environmental features, some of which may parallel the challenges that archaic humans once confronted and adapted to. Our results show that Denisovan-like haplotypes exhibit increased levels of population differentiation between PNG highlanders and lowlanders. The highly differentiated haplotypes, more common among highlanders, reside in genomic areas linked to brain development genes. Conversely, those more frequent in lowlanders overlap with genes enriched in immune response processes. Furthermore, Denisovan-like haplotypes displayed pronounced signatures of diversification within the major histocompatibility complex. Our findings suggest that Denisovan DNA has provided a valuable source of genetic variation to PNG genomes that facilitated adaptive responses to environmental challenges.
Biochemical characterization of theEscherichia colisurfaceome: A focus on type I fimbriae and flagella
Authors: Kavanaugh DW , Sivignon A , Rossez Y , Chouit Z , Chambon C , Beal L , Hébraud M , Guerardel Y , Nguyen H , Barnich N
Published: January 2024

TheEscherichia colisurfaceome consists mainly of the large surface organelles expressed by the organism to navigate and interact with the surrounding environment. The current study focuses on type I fimbriae and flagella. These large polymeric surface organelles are composed of hundreds to thousands of subunits, with their large size often preventing them from being studied in their native form. Recent studies are accumulating which demonstrate the glycosylation of surface proteins or virulence factors in pathogens, includingE. coli.

Using biochemical and glycobiological techniques, including biotin-hydrazide labelling of glycans and chemical and glycosidase treatments, we demonstrate i) the presence of a well-defined and chemically resistant FimA oligomer in several strains of pathogenic and non-pathogenicE. coli, ii) the major subunit of type I fimbriae, FimA, in pathogenic and laboratory strains is recognized by concanavalin A, iii) standard methods to removeN-glycans (PNGase F) or a broad-specificity mannosidase fail to remove the glycan structure, despite the treatments resulting in altered migration in SDS-PAGE, iv) PNGase F treatment results in a novel 32 kDa band recognized by anti-FliC antiserum.

While the exact identity of the glycan(s) and their site of attachment currently elude detection by conventional glycomics/glycoproteomics, the current findings highlight a potential additional layer of complexity of the surface (glyco)proteome of the commensal or adhesive and invasiveE. colistrains studied.
Astigmatism-based focus stabilisation with universal objective lens compatibility, extended operating range and nanometre precision
Authors: Rahmani Amir , Cox Tabitha , Thamaravelil Abhimanue Achary Akhila , Ponjavic Aleks
Published: January 2024

Focus stabilisation is vital for long-term fluorescence imaging, particularly in the case of high-resolution imaging techniques. Current stabilisation solutions either rely on fiducial markers that can be perturbative, or on beam reflection monitoring that is limited to high-numerical aperture objective lenses, making multimodal and large-scale imaging challenging. We introduce a beam-based method that relies on astigmatism, which offers advantages in terms of precision and the range over which focus stabilisation is effective. This approach is shown to be compatible with a wide range of objective lenses (10x-100x), typically achieving <10 nm precision with >10 μm operating range. Notably, our technique is largely unaffected by pointing stability errors, which in combination with implementation through a standalone Raspberry Pi architecture, offers a versatile focus stabilisation unit that can be added onto most existing microscope setups.
Mechanistic Insights into G-protein Activation via Phosphorylation Mediated Non-Canonical Pathway
Authors: Shewani Kunal , Madhu Midhun K. , Murarka Rajesh K.
Published: January 2024

Activation of heterotrimeric G-proteins (Gαβγ) downstream to receptor tyrosine kinases (RTKs) is a well-established crosstalk between the signaling pathways mediated by G-protein coupled receptors (GPCRs) and RTKs. While GPCR serves as a guanine exchange factor (GEF) in the canonical activation of Gαthat facilitates the exchange of GDP for GTP, the mechanism through which RTK phosphorylations induce Gαactivation remains unclear. Recent experimental studies revealed that the epidermal growth factor receptor (EGFR), a well-known RTK, phosphorylates the helical domain tyrosine residues Y154 and Y155 and accelerates the GDP release from the Gαi3, a subtype of Gα-protein. Using well-tempered metadynamics and extensive unbiased molecular dynamics simulations, we captured the GDP release event and identified the intermediates between bound and unbound states through Markov state models. The additional negative charges introduced by phosphorylations rewired the inter-residue interactions and significantly weakened the salt bridges at the domain interface, contributing to the increased separation of the Ras-like and helical domains of G-protein. Furthermore, the unfolding of helixαF resulted in greater flexibility near the hinge region, facilitating a greater distance between domains in the phosphorylated Gαi3. The release of GDP in the phosphorylated G-protein occurred at a faster rate compared to the unphosphorylated state, caused by increased fluctuations in conserved regions of P-loop, switch 1, and switch 2. Overall, this study provides atomistic insights into the activation of G-proteins induced by RTK phosphorylations and identifies the specific structural motifs involved in the process. The knowledge gained from the study could establish a foundation for targeting non-canonical signaling pathways and developing therapeutic strategies against the ailments associated with dysregulated G-protein signaling.
Fostering environmental preservation: exploring the synergy of green human resource management and corporate environmental ethics
Authors: Al-Swidi Abdullah Kaid , Al-Hakimi Mohammed A. , Al-Hattami Hamood Mohammed
Published: January 2024

Purpose

This study aims to explore the unique and synergistic effects of green human resource management (GHRM) and corporate environmental ethics (CEE) on the environmental performance (EP) of manufacturing small and medium-sized enterprises (SMEs) in Yemen, a less developed country (LDC).

Design/methodology/approach

Through a cross-sectional survey design, data were collected from 262 manufacturing SMEs in Yemen and analyzed using “hierarchical regression analysis” via PROCESS Macro.

Findings

The empirical results showed that GHRM and CEE positively affect EP and, more importantly, that CEE and GHRM have a synergistic effect on EP.

Research limitations/implications

This study makes a theoretical contribution by integrating GHRM, CEE and EP into a single framework, taking into account the perspectives of the resource-based view and the ethical theory of organizing. The results corroborate the unique and synergistic effects of GHRM and CEE on EP of SMEs in the manufacturing sector.

Practical implications

The results of this study offer valuable insights for SME managers/decision-makers, who are anticipated to become more interested in integrating environmental ethics into their companies. This has implications that with the consideration of CEE, SMEs can benefit from GHRM practices to improve their EP.

Social implications

The study highlights the positive economic and social impact of SMEs adopting eco-friendly practices like GRHM. In today’s economy, it is not sufficient to simply strive for economic growth. It is possible for SMEs to achieve well-rounded performance by implementing the recommended framework that emphasizes the importance of social and environmental well-being.

Originality/value

This study advances the existing work on the impact of GHRM on EP by demonstrating the crucial role of CEE in predicting EP of manufacturing SMEs in LDCs like Yemen. Previous research on GHRM has mainly been conducted on SMEs in developed nations, which may not be entirely applicable to LDCs. It is crucial to understand this aspect in the context of LDCs so that SMEs can adopt environmental practices effectively in the future: how SMEs conserve the environment through their environmental practices.
DAY NRLM scheme and its impact on women empowerment: a case of Morigaon district of Assam, India
Authors: Ningombam Sanjeev Kumar , Bordoloi Sudeshna
Published: January 2024

Purpose

This study aims to examine the political, economic, social and technological (PEST) factors of women empowerment in the context of rural development under the initiatives of the National Rural Livelihood Mission (NRLM).

Design/methodology/approach

The unit of analysis for this study is 459 samples. Non-probability sampling technique has been used for this study. Schedule/questionnaires have been circulated among the women in each block cluster. Frequencies have been used to represent the data against each statement. Non-parametric chi-square test has been used to examine the relationship between empowerment and political, economic, social, technological factors and interpersonal skills.

Findings

Statistical analysis shows that the Deendayal Antayodaya Yojana (DAY)-NRLM scheme has brought significant changes and development to women in political, social, economic and technological areas. It was observed that women are economically empowered and contribute to the economic upliftment of the family. Most of the respondents strongly felt that after being associated with DAY-NRLM, they were empowered to contribute efficiently to the social development process and activities.

Research limitations/implications

The findings of this study highlight the impact of DAY-NRLM implementation at block levels of a district in India. Subsequent research may be carried to measure the effectiveness of the capacity-building program conducted under the banner of DAY-NRLM.

Practical implications

Women empowerment is not limited to awareness, whereas it needs a complete set of initiatives backed with support systems. Few critical interventions could be building strong networks, enhancing financial management, encouraging the spirit of entrepreneurship among self-help group workers, providing easy access to credit, mentoring, handholding, continuous monitoring and evaluation.

Social implications

This study focuses on the impact of the DAY-NRLM scheme on women’s empowerment in the Morigaon district. The inferences from the study throw light on the empowerment of women vis-à-vis political, economic, social and technological factors.

Originality/value

This study is a primary study conducted in the Morigaon District of Assam. This is a new line of policy research that approaches the women empowerment with the PEST parameters.
Exchange rate and housing affordability in OECD countries
Authors: Salisu Afees Adebare , Rufai Aliyu Akorede , Nsonwu Modestus Chidi
Published: January 2024

Purpose

This study aims to construct alternative models to establish the dynamic relationship between exchange rates and housing affordability by estimating both the short- and long-run relationship between exchange rates and housing affordability for 18 OECD countries from 1975Q1 to 2022Q4. After that, this study demonstrates how this nexus behaves during high and low inflation regimes and turbulent times.

Design/methodology/approach

This study uses the panel autoregressive distributed lag technique to examine the nexus between housing affordability to capture the distinct characteristics of the sample countries and estimate various short- and long-run dynamics in the relationship between housing affordability and exchange rate.

Findings

Exchange rate appreciation improves housing affordability in the short run, whereas this connection tends to dissipate in the long run. Moreover, inflation can worsen housing affordability during turbulent times, such as the global financial crisis, in both the short and long run. Ignoring these changes in the relationship between exchange rates and housing affordability during turbulent times can lead to incorrect conclusions.

Originality/value

To the best of the authors’ knowledge, this study is the first to examine the association between exchange rates and housing affordability by demonstrating how these variables behave in high and low inflation regimes and turbulent times.