bluuebunny/crossref_metadata_2025 huggingface dataset:
Stability of One-Step Spray-on Splint for Lower Extremity Fractures During Splinting, MEDEVAC, and Impact
Authors: Hobayan C Grace P , Bates Nathaniel A , Heyniger John , Alzouhayli Kenan , Piscitani Franco , Haider Clifton R , Felton Christopher , Groth Adam T , Martin Kevin D
Published: January 2024

Introduction

Military transport can induce whole-body vibrations, and combat almost always involves high impact between lower extremities and the ground. Therefore, robust splinting technology is necessary for lower extremity fractures in these settings. Our team compared a novel one-step spray-on foam splint (FastCast) to the current military standard structured aluminum malleable (SAM) splint.

Materials and Methods

Ten cadaveric specimens were subjected to complete tibia/fibula osteotomy. Specimens were fitted with custom accelerometer and gyroscope sensors superior and inferior to the fracture line. Each specimen underwent fracture and splinting from a standard of care SAM splint and an experimental FastCast spray foam splint in a randomized order. Each specimen was manually transported to an ambulance and then released from a 1 meter height to simulate impact. The custom sensors recorded accelerations and rotations throughout each event. Repeated-measures Friedman tests were used to assess differences between splint method within each event and between sensors within each splint method.

Results

During splinting, overall summation of change and difference of change between sensors for accelerations and rotations were greater for SAM splints than FastCast across all axes (P ≤ 0.03). During transport, the range of acceleration along the linear superior/inferior axis was greater for SAM splint than FastCast (P = 0.02), as was the range of rotation along the transverse plane (P < 0.01). On impact, the summation of change observed was greater for SAM splint than FastCast with respect to acceleration and rotation on the posterior/anterior and superior/inferior axes (P ≤ 0.03), and the cumulative difference between superior and inferior sensors was greater for SAM than FastCast with respect to anterior-axis rotation (P < 0.05).

Conclusion

FastCast maintains stabilization of fractured lower extremities during transport and impacts to a significantly greater extent than SAM splints. Therefore, FastCast can potentially reduce the risk of fracture complications following physical stressors associated with combat and extraction.
COVID-19 lockdowns weigh heavily on youth: an analysis of the impact on BMI for Age Z scores in children and adolescents
Authors: Abed Alah Muna , Abdeen Sami , Bougmiza Iheb , Selim Nagah
Published: January 2024

Background

The COVID-19 pandemic has significantly impacted the lifestyle and health of children and adolescents. This study aimed to assess the lifestyle changes brought about by COVID-19-related school closures and their impact on the Body Mass Index for Age Z (BAZ) scores of governmental school students in Qatar.

Methods

An analytical cross-sectional study was conducted between June and August 2022 targeting students aged 8–15 years. Data on lifestyle behaviors were gathered through telephone interviews with parents of selected students. The BAZ scores before and after school closures that were automatically calculated by the electronic health records system were extracted.

Results

We completed 1546 interviews. We found a significant increase in unhealthy food categories, a reduction in physical activity and an increase in the screen time over the period of schools’ closure. The BAZ increased significantly by 0.30 (95% CI 0.26–0.35). The increase in BAZ scores was significantly higher among male students and the younger age group compared to females and older counterparts, respectively. The student’s age group, sex, nationality and change in physical activity were significant predictors of the change in BAZ scores.

Conclusions

School closures during the COVID-19 pandemic negatively impacted the lifestyle of students in Qatar and resulted in a significant increase in the BAZ scores.
Impact of Biologics and Small Molecule Agents on Postoperative Complications in Inflammatory Bowel Disease: A Systematic Review
Authors: Lee Kate E. , Sizemore J. Alexander , Kim Grace , Shen Bo , Sands Bruce E.
Published: January 2024

BACKGROUND:

Patients with inflammatory bowel disease may require colectomy for severe disease unresponsive or refractory to pharmacological therapy. The question of the impact of biologic use on postoperative complications is a topic of active investigation.

OBJECTIVE:

A systematic literature review was performed to describe the current state of knowledge of the impact of perioperative biologic and tofacitinib use on postoperative complications in patients with inflammatory bowel disease.

DATA SOURCES:

PubMed and Cochrane databases were searched.

STUDY SELECTION:

Studies between January 2000 and January 2023, in any language, were searched, followed by a snowball search identifying further studies, in accordance with preferred reporting items for systematic reviews and meta-analyses guidelines. Articles regarding pediatric or endoscopic management were excluded.

INTERVENTIONS:

Preoperative or perioperative exposure to biologics in inflammatory bowel disease was included.

MAIN OUTCOME MEASURES:

Infectious and noninfectious complications, including anastomotic leaks, surgical site infections, urinary tract infections, pneumonia, sepsis, septic shock, postoperative length of stay, readmission, and reoperation, were the main outcomes measured.

RESULTS:

A total of 28 studies were included for analysis in this review, including 7 meta-analyses or systematic reviews, and 5 randomized studies. Snowball search identified 11 additional studies providing topical information. Overall, tumor necrosis factor inhibitors likely do not increase risk of postoperative adverse outcomes, while data on other biologics and small molecule agents are emerging.

LIMITATIONS:

This is a qualitative review including all study types. The varied nature of study types precludes quantitative comparison.

CONCLUSIONS:

Although steroids increase postoperative infectious and noninfectious complications, tumor necrosis factor inhibitors do not appear to increase postoperative infectious and non-infectious complications. There is a need for further perioperative data for other agents. See Video.
Obesity/cardiometabolic phenotype of heart failure with preserved ejection fraction: mechanisms to recent trials
Authors: Verma Raj , Dhingra Nitish K. , Connelly Kim A.
Published: January 2024

Purpose of review

Heart failure with preserved ejection fraction (HFpEF) is a leading and growing cause of morbidity and mortality globally. Of the various phenotypes identified, the obesity (or cardiometabolic) phenotype appears to be most common. The purpose of this review is to provide the clinician with an abridged understanding of recent developments that have elucidated obesity/visceral adiposity as a central mechanism linking inflammation/immune dysregulation to the development of the HFpEF syndrome. Recent clinical trials examining the efficacy of pharmacological treatments that target obesity in HFpEF will also be discussed.

Recent findings

Recent data indicate that visceral adiposity and insulin resistance in HFpEF serve as key mechanisms driving inflammation and immune dysregulation, which play a critical role in the development of cardiac stiffness, diastolic dysfunction and fibrosis in HFpEF. In obesity, alterations in macrophage polarization, changes in innate and adaptive immune systems and altered myocardial energetics promote metabolic inflammation in HFpEF. Finally, emerging data suggest that inflammatory biomarkers, specifically, IL-6, may provide useful information about HFpEF severity and symptom burden in obesity.

The obesity phenotype of HFpEF is seen in upward of 80% with HFpEF. Obesity is not just a bystander, but plays an essential role in the pathobiology and clinical course of HFpEF. Targeting overweight/obesity in HFpEF with GLP-1 receptor agonists holds promise in these patients.
Strategies to Obtain and Deliver Blood Products Into Critically Injured Children
Authors: Sullivan Travis M. , Sippel Genevieve J. , Gestrich-Thompson Waverly V. , Burd Randall S.
Published: January 2024

Objectives

Timely transfusion is associated with improved survival and a reduction in in-hospital morbidity. The benefits of early hemorrhagic shock recognition may be limited by barriers to accessing blood products and their timely administration. We examined how pediatric trauma programs obtain blood products, the types of rapid infusion models used, and the metrics tracked to improve transfusion process efficiency in their emergency department (ED).

Methods

We developed and distributed a self-report survey to members of the Pediatric Trauma Society. The survey consisted of 6 initial questions, including the respondent's role and institution, whether a blood storage refrigerator was present in their ED, the rapid infuser model used to transfuse critically injured children in their ED, if their program tracked 4 transfusion process metrics, and if a video recording system was present in the trauma bay. Based on these responses, additional questions were prompted with an option for a free-text response.

Results

We received 137 responses from 77 institutions. Most pediatric trauma programs have a blood storage refrigerator in the ED (n = 46, 59.7%) and use a Belmont rapid infuser to transfuse critically injured children (n = 45, 58.4%). The American College of Surgeons Level 1 designated trauma programs, or state-based equivalents, and “pediatric” trauma programs were more likely to have video recording systems for performance improvement review compared with lower designated trauma programs and “combined pediatric and adult” trauma programs, respectively.

Conclusions

Strategies to improve the timely acquisition and infusion of blood products to critically injured children are underreported. This study examined the current practices that pediatric trauma programs use to transfuse critically injured children and may provide a resource for trauma programs to cite for transfusion-related quality improvement.
Prevalence, antibiotic resistance, and genomic characterisation of Campylobacter spp. in retail chicken in Hanoi, Vietnam
Authors: Huong Luu Quynh , Chisnall Thomas , Rodgers John D. , Cawthraw Shaun A. , Card Roderick M.
Published: January 2024

Campylobacter

spp. are a leading cause of bacterial foodborne zoonosis worldwide, with poultry meat and products recognised as a significant source of human infection. In Vietnam there are few data regarding the occurrence, antimicrobial resistance, and genomic diversity of

Campylobacter

in poultry and poultry meat. The aim of this study was to estimate the prevalence of

Campylobacter

in chicken meat at retail in Hanoi, determine antimicrobial sensitivities of the

Campylobacter

isolated, and assess their genetic diversity. A total of 120 chicken meat samples were collected from eight traditional retail markets (n=80) and four supermarkets (n=40).

Campylobacter

was isolated following ISO 10272-1 : 2017 and identification verified by PCR. The prevalence of

Campylobacter

was 38.3 % (46/120) and

C. coli

was the most prevalent species in both retail markets (74 %) and supermarkets (88 %). The minimum inhibitory concentrations for ciprofloxacin, erythromycin, gentamicin, nalidixic acid, streptomycin, and tetracycline were determined by broth microdilution for 32 isolates. All characterised

Campylobacter

were resistant to ciprofloxacin, nalidixic acid, and tetracycline, with corresponding resistance determinants detected in the sequenced genomes. Most

C. coli

were multidrug resistant (24/28) and two harboured the erythromycin resistance gene ermB on a multiple drug-resistance genomic island, a potential mechanism for dissemination of resistance. The 32 isolates belonged to clonal complexes associated with both poultry and people, such as CC828 for

C. coli

. These results contribute to the One Health approach for addressing

Campylobacter

in Vietnam by providing detailed new insights into a main source of human infection and can inform the design of future surveillance approaches.
Rubisco supplies pyruvate for the 2-C-methyl-D-erythritol-4-phosphate pathway
Authors: Evans Sonia E. , Xu Yuan , Bergman Matthew E. , Ford Scott A. , Liu Yingxia , Sharkey Thomas D. , Phillips Michael A.
Published: January 2024

Ribulose-1,5-bisphosphate carboxylase/oxygenase (rubisco) produces pyruvate in the chloroplast through beta-elimination of the aci-carbanion intermediate. Here we show that this side reaction supplies pyruvate for isoprenoid, fatty acid, and branched chain amino acid biosynthesis in photosynthetically active tissue. 13C labeling studies of whole Arabidopsis plants demonstrate that the total carbon commitment to pyruvate is too large for phosphoenolpyruvate (PEP) to serve as precursor. Low oxygen stimulates rubisco carboxylase activity and increased pyruvate production and flux through the 2-C-methyl-D-erythritol-4-phosphate (MEP) pathway, which supplies the precursors for plastidic isoprenoid biosynthesis. Metabolome analysis of mutants defective in PEP or pyruvate import further supported rubisco as the main source of pyruvate in chloroplasts. Rubisco beta-elimination leading to pyruvate constituted 0.7% of the product profile in in vitro assays, which translates to 2% of the total carbon leaving the Calvin-Benson-Bassham cycle (CBC). These insights solve the so-called pyruvate paradox, improve the fit of metabolic models for central metabolism, and connect the MEP pathway directly to carbon assimilation.
Evaluation of homologous recombination repair status in metastatic prostate cancer by next-generation sequencing and functional tissue-based immunofluorescence assays
Authors: Arce-Gallego Sara , Morgado Pablo Cresta , Delgado-Serrano Luisa , Simonetti Sara , Gonzalez Macarena , Marmolejo David , Morales-Barrera Rafael , Mir Gisela , Semidey Maria Eugenia , Lozano Paula Romero , Cordoba-Terreros Sarai , Mast Richard , de Albert Matias , Planas Jacques , Cuadras Mercè , Maldonado Xavier , Suarez Cristina , Casanova-Salas Irene , Nonell Lara , Dienstmann Rodrigo , Nuciforo Paolo , Vivancos Ana , Llop-Guevara Alba , Carles Joan , Serra Violeta , Mateo Joaquin
Published: January 2024

Purpose

Metastatic prostate cancer (mPC) is enriched for homologous recombination repair (HRR) gene alterations; these biomarkers have prognostic and predictive value. Next-generation sequencing (NGS) allows for patient stratification based on these biomarkers, but widespread clinical implementation is still limited. Moreover, not all mutations in HRR genes result in functional HRR loss in the tumor. We investigated the correlation between genomic and functional loss of HRR, using NGS and an optimized RAD51 immunofluorescence (RAD51-IF) assay in mPC clinical biopsies.

Experimental design

Observational study including patients with stage IV prostate cancer. Biopsies from either primary tumor or metastatic biopsies underwent NGS (targeted sequencing and/or whole-exome sequencing), and RAD51-IF. Clinical data was extracted from electronic patient records.

Results

219 biopsies from 187 patients were acquired, including primary (151/219) and metastatic (68/219) tumor biopsies collected either in the metastatic hormone- sensitive (169/219) or castration-resistant (50/219) setting. NGS (181 biopsies from 157 patients) showed frequent genomic alterations inTP53(40%),AR(15%),PTEN(14%), MYC (10%),BRCA2(9%),ATM(8%) andBRCA1(2%). Tissue for RAD51 IF was available for 206 samples; of those, 140/206 (68%) were evaluable for RAD51- IF. Based on a previously defined threshold of 10% RAD51-positive cells, 21% samples had RAD51-low results compatible with HRR deficiency (HRD). Sample matched RAD51-IF and genomics data were obtained for 128 biopsies (117 patients): RAD51-IF had a high sensitivity (68%) and specificity (85%) to identify cases withBRCA1/2alterations. Additionally, the RAD51-IF assay was able to identify restoration of HRR function in selected cases withBRCA2reversion mutations or BRCA1 expression.

Conclusions

RAD51-IF is feasible in routine clinical samples from mPC patients and associates strongly with clinically relevant HRR gene alterations.
BERTE: High-precision hierarchical classification of transposable elements by a transfer learning method with BERT pre-trained model and convolutional neural network
Authors: Chen Yiqi , Qi Yang , Wu Yingfu , Zhang Fuhao , Liao Xingyu , Shang Xuequn
Published: January 2024

Transposable Elements (TEs) are abundant repeat sequences found in living organisms. They play a pivotal role in biological evolution and gene regulation and are intimately linked to human diseases. Existing TE classification tools can classify classes, orders, and superfamilies concurrently, but they often struggle to effectively extract sequence features. This limitation frequently results in subpar classification results, especially in hierarchical classification. To tackle this problem, we introduced BERTE, a tool for TE hierarchical classification. BERTE encoded TE sequences into distinctive features that consisted of both attentional and cumulativek-merfrequency information. By leveraging the multi-head self-attention mechanism of the pre-trained BERT model, BERTE transformed sequences into attentional features. Additionally, we calculated multiplek-merfrequency vectors and concatenate them to form cumulative features. Following feature extraction, a parallel Convolutional Neural Network (CNN) model was employed as an efficient sequence classifier, capitalizing on its capability for high-dimensional feature transformation. We evaluated BERTE’s performance on filtered datasets collected from 12 eukaryotic databases. Experimental results demonstrated that BERTE could improve the F1-score at different levels by up to 21% compared to current state-of-the-art methods. Furthermore, the results indicated that not only could BERT better characterize TE sequences in feature extraction, but also that CNN was more efficient than other popular deep learning classifiers. In general, BERTE classifies TE sequences with greater precision. BERTE is available athttps://github.com/yiqichen-2000/BERTE.
A taxonomy based on acoustic features of some Iranian cicadas and calling song description ofChloropsalta smaragdulaHaupt, 1920 (Hem: Cicadidae) from Isfahan, Iran
Authors: Mehdipour Maedeh , Riede Klaus , Sendi Jalal Jalali , Zamanian Hossein , Mohammadi-Mobarakeh Akbar
Published: January 2024

This paper compiles parameters of calling songs from 14 cicada species inhabiting Iran. In addition, calling song parameters ofChloropsalta smaragdulawere analyzed for the first time. A taxonomy based on song parameters was designed, including Iranian cicadasTibicen plebejus,Cicadatra lorestanica,Cicadivetta tibialis,Tettigetta golestani,Pagiphora annulata,Tibicina haematodes,Cicada orni, Pagiphora annulata,Chloropsalta smaragdula,Cicadatra hyalina,Psalmocharias querula,Cicadatra persica,Cicadatra alhageos,Cicadatra atraandCicadatra barbodiout of 44 species reported from Iran. In addition to common acoustic parameters, four new complex spectral features such as variance, kurtosis, spectral centroid and short time energy were used. These additional features were necessary to construct a comprehensive identification key based on acoustic parameters. Our acoustic identification system provides a highly accurate species recognition method, which could be of general relevance in cicada taxonomy.
Mitochondrial fission surveillance is coupled toCaenorhabditis elegansDNA and chromosome segregation integrity
Authors: Yang Xiaomeng , Meng Fanfan , Wei Ruichen , Liu Dianchen , Gong Xuan , Ruvkun Gary , Wei Wei
Published: January 2024

Mitochondrial fission and fusion are tightly regulated to specify mitochondrial abundance, localization, and arrangement during cell division as well as in the diverse differentiated cell types and physiological states. However, the regulatory pathways for such mitochondrial dynamics are less explored than the mitochondrial fission and fusion components. Here we report a large-scale screen for genes that regulate mitochondrial fission. Mitochondrial fission defects cause a characteristic asymmetric fluorescent pattern in embryos carrying mitochondrial stress reporter genes. Using this asymmetric activation, we performed RNAi screens that identified 3 kinase genes from a ∼500-kinase library and another 11 genes from 3,300 random genes that function in mitochondrial fission. Many of these identified genes play roles in chromosome segregation. We find that chromosome missegregation and genome instability lead to dysregulation of mitochondrial fission in a manner independent of Drp-1. ATL-1, theC. elegansATR orthologue, plays a protective role in alleviating the mitochondrial fission defect caused by chromosome missegregation. This establishes a screening paradigm for identifying mitochondrial fission regulators which reveals the role of ATR in surveilling mitochondrial fission to mitigate dysregulation caused by improper chromosome segregation.
Floria: Fast and accurate strain haplotyping in metagenomes
Authors: Shaw Jim , Gounot Jean-Sebastien , Chen Hanrong , Nagarajan Niranjan , Yu Yun William
Published: January 2024

Shotgun metagenomics allows for direct analysis of microbial community genetics, but scalable computational methods for the recovery of bacterial strain genomes from microbiomes remains a key challenge. We introduce Floria, a novel method designed for rapid and accurate recovery of strain haplotypes from short and long-read metagenome sequencing data, based on minimum error correction (MEC) read clustering and a strain-preserving network flow model. Floria can function as a standalone haplotyping method, outputting alleles and reads that co-occur on the same strain, as well as an end-to-end read-to-assembly pipeline (Floria-PL) for strain-level assembly. Benchmarking evaluations on synthetic metagenomes showed that Floria is>3×faster and recovers 21% more strain content than base-level assembly methods (Strainberry), while being over an order of magnitude faster when only phasing is required. Applying Floria to a set of 109 deeply sequenced nanopore metagenomes took<20 minutes on average per sample, and identified several species that have consistent strain heterogeneity. Applying Floria’s short-read haplotyping to a longitudinal gut metagenomics dataset revealed a dynamic multi-strainAnaerostipes hadruscommunity with frequent strain loss and emergence events over 636 days. With Floria, accurate haplotyping of metagenomic datasets takes mere minutes on standard workstations, paving the way for extensive strain-level metagenomic analyses.

Availability

Floria is available athttps://github.com/bluenote-1577/floria, and the Floria-PL pipeline is available athttps://github.com/jsgounot/Floria_analysis_workflow.
Clinical progression of Parkinson’s disease in the early 21st century: Insights from AMP-PD dataset
Authors: Lewis Mechelle M. , Cheng Xinyi Vivian , Du Guangwei , Zhang Lijun , Li Changcheng , De Jesus Sol , Tabbal Samer D. , Mailman Richard , Li Runze , Huang Xuemei
Published: January 2024

Background

Parkinson’s disease (PD) therapeutic strategies have evolved since the introduction of levodopa in the 1960s, but there is limited data on their impact on disease progression markers.

Objective

Delineate the current landscape of PD progression at tertiary subspecialty care and research centers.

Method

Using Accelerating Medicine Partnership-PD (AMP-PD) data harmonized from seven biomarker discovery studies (2010-2020), we extracted: overall [Schwab and England (S&E), PD Questionnaire (PDQ-39)]; motor [Movement Disorders Society Unified PD Rating Scale (MDS-UPDRS)-II and -III and Hoehn & Yahr (HY)]; and non-motor [MDS-UPDRS-I, University of Pennsylvania Smell Identification Test (UPSIT), Montreal Cognitive Assessment (MoCA), and Epworth Sleepiness Scale (ESS)] scores. Age at diagnosis was set as 0 years, and data were tracked for 15 subsequent years.

Results

Subjects’ (3,001 PD cases: 2,838 white, 1,843 males) mean age at diagnosis was 60.2±10.3 years and disease duration was 9.9±6.0 years at the baseline evaluation. Participants largely reported independence (S&E,5y: 86.6±12.3;10y: 78.9±19.3;15y: 78.5±17.0) and good quality of life (PDQ-39,5y: 15.5±12.3;10y: 22.1±15.8;15y: 24.3±14.4). Motor scores displayed a linear progression, whereas non-motor scores plateaued ∼10-15 years. Younger onset age correlated with slower overall (S&E), motor (MDS-UPDRS-III), and non-motor (UPSIT/MoCA) progression, and females had better overall motor (MDS-UPDRS-II-III) and non-motor (UPSIT) scores than males.

Conclusions

Twenty-first century PD patients remain largely independent in the first decade of disease. Female and young age of diagnosis were associated with better clinical outcomes. There are data gaps for non-whites and metrics that gauge non-motor progression for >10 years after diagnosis.
Orthology inference at scale with FastOMA
Authors: Majidian Sina , Nevers Yannis , Yazdizadeh Kharrazi Ali , Warwick Vesztrocy Alex , Pascarelli Stefano , Moi David , Glover Natasha , Altenhoff Adrian M , Dessimoz Christophe
Published: January 2024

The surge in genome data, with ongoing efforts aiming to sequence 1.5M eukaryotes in a decade, could revolutionise genomics, revealing the origins, evolution, and genetic innovations of biological processes. Yet, traditional genomics methods scale poorly with such large datasets. Addressing this, “FastOMA” provides linear scalability, enabling the processing of thousands of eukaryotic genomes within a day. FastOMA maintains the high accuracy and resolution of the well-established OMA approach in benchmarks. FastOMA is available athttps://github.com/DessimozLab/FastOMA/.
Inheritance of old mitochondria controls early CD8+T cell fate commitment and is regulated by autophagy
Authors: Borsa Mariana , Lechuga-Vieco Ana Victoria , Kayvanjoo Amir H. , Yazicioglu Yavuz , Compeer Ewoud B. , Richter Felix C. , Bui Hien , Dustin Michael L. , Katajisto Pekka , Simon Anna Katharina
Published: January 2024

T cell immunity is impaired during ageing, particularly in memory responses needed for efficient vaccination. Autophagy and asymmetric cell division (ACD) are cell biological mechanisms key to memory formation, which undergo a decline upon ageing. However, despite the fundamental importance of these processes in cellular function, the link between ACD andin vivofate decisions has remained highly correlative in T cells and in the field of mammalian ACD overall. Here we provide robust causal evidence linking ACD toin vivoT cell fate decisions and our data are consistent with the concept that initiation of asymmetric T cell fates is regulated by autophagy. Analysing the proteome of first-daughter CD8+T cells following TCR-triggered activation, we reveal that mitochondrial proteins rely on autophagy for their asymmetric inheritance and that damaged mitochondria are polarized upon first division. These results led us to evaluate whether mitochondria were asymmetrically inherited and to functionally address their impact on T cell fate. For this we used a novel mouse model that allows sequential tagging of mitochondria in mother and daughter cells, enabling their isolation and subsequentin vivoanalysis of CD8+T cell progenies based on pre-mitotic cell cargo. Autophagy-deficient CD8+T cells showed impaired clearance and symmetric inheritance of old mitochondria, suggesting that degradation events promote asymmetry and are needed to generate T cells devoid of old organelles. Daughter cells inheriting old mitochondria are more glycolytic and upon adoptive transfer show reduced memory potential, whereas daughter cells that have not inherited old mitochondria from the mother cell are long-lived and expand upon cognate-antigen challenge. Proteomic and single-cell transcriptomic analysis of cells inheriting aged mitochondria suggest that their early fate divergence relies on one carbon metabolism as a consequence of poor mitochondrial quality and function. These findings increase our understanding of how T cell diversity is early-imprinted during division and will help foster the development of strategies to modulate T cell function.

Abstract Figure

The MitoSnap model allows tracking of pre-mitotic and post-mitotic cell cargoes.

Both segregation and degradation (autophagy) contribute to the asymmetric inheritance of old mitochondria.

Old mitochondria impact cell metabolism and function.

Cells devoid of old mitochondria exhibit better memory potentialin vivo.
Conway-Bromage-Lyndon (CBL): an exact, dynamic representation ofk-mer sets
Authors: Martayan Igor , Cazaux Bastien , Limasset Antoine , Marchet Camille
Published: January 2024

In this paper, we introduce the Conway-Bromage-Lyndon (CBL) structure, a compressed, dynamic and exact method for representingk-mer sets. Originating from Conway and Bromage’s concept, CBL innovatively employs the smallest cyclic rotations ofk-mers, akin to Lyndon words, to leverage lexicographic redundancies. In order to support dynamic operations and set operations, we propose a dynamic bit vector structure that draws a parallel with Elias-Fano’s scheme. This structure is encapsulated in a Rust library, demonstrating a balanced blend of construction efficiency, cache locality, and compression. Our findings suggest that CBL outperforms existing dynamick-mer set methods. Unique to this work, CBL stands out as the only known exactk-mer structure offering in-place set operations. Its different combined abilities position it as a flexible Swiss knife structure fork-mer set management. Availability:https://github.com/imartayan/CBL
Assessing the effects of acute temperature changes of sea water temperature due to climate change on Scottish farmed Atlantic salmon and investigating genetic mitigation
Authors: Tsairidou Smaragda , van den Berg Jarl , Tapping Stephen , Sobolewska Halina , Hamilton Alastair
Published: January 2024

Changes in growth, survival, maturation and health in Atlantic salmon post-smolts were observed under moderate and more extreme heat-wave conditions for the west coast of Scotland. A Scottish Atlantic salmon breeding programme population of 518 salmon of age 13-14 months, was observed for 4 weeks in summer, in tanks with ambient water temperature or ∼ 4 degrees and ∼ 8 degrees above ambient temperature. Data were recorded for the fish before and after the challenge. All fish were genotyped using a custom SNP (single nucleotide polymorphism) array (8,978 SNP genotypes after quality control). Temperature-dependant genotype-by-environment interactions and the potential for selective breeding to improve resilience were investigated. Statistical analyses revealed significant differences between thermal environments for body weight, average daily weight gain, and survival, while higher temperature induced earlier maturation, and an increase of gill health scores. QPCR (quantitative polymerase chain reaction) analyses revealed the presence ofAeromonas hydrophila, a pathogen typically more prevalent in warmer climates. Using genomic relationships and animal mixed models, body weight and average daily weight gain provided moderate heritabilities, while between-tank genetic correlations were close to 1, indicating no significant re-ranking of genotypes between the different thermal environments. These findings suggest that even short-term exposure to heat stress may be sufficient to negatively impact survival and gill health, and induce earlier maturation. However, observations took place within a commercial farm where having replicates for each thermal environment was not possible, hence further experiments with larger populations, exposed to more prolonged heat stress are needed.
A study on tomato brown rugose fruit virus longevity in soil and virion susceptibility to various pH treatments contributes to optimization of a soil disinfection protocol
Authors: Molad Ori , Smith Elisheva , Luria Neta , Bakelman Elena , Lachman Oded , Reches Meital , Dombrovsky Aviv
Published: January 2024

Background and aims

Tobamoviruses are highly stable soil-borne pathogens posing a challenge to a monoculture practice. Biochemical and physical properties of tobamovirus virions were studied by analyses of tobacco mosaic virus (TMV). Little is known about tomato brown rugose fruit tobamovirus (ToBRFV) regarding longevity in soil and virion stability. Our aims were to determine ToBRFV longevity in naturally-contaminated soil and study virion stability in a range of acidic and alkaline conditions to promote new strategies for soil remediation.

Methods

ToBRFV longevity in naturally-contaminated soil was tested by collecting an earth pile after a growth-cycle of ToBRFV-infected tomato plants. The soil was sampled at different time points and root-truncated tomato seedlings were planted. Virion stability at a range of pH values was determined by testing virus infectivity onNicotiana glutinosa; by amplifying large genome segments using RT-PCR; and by transmission electron microscopy (TEM) visualization.

Results

ToBRFV-infectivity in naturally-contaminated soil was profoundly reduced by day 184 of pile-age and was abolished between 205-385 days of pile-age. Virion stability and genome integrity were preserved over the pH range of 2-10. At pH 1, ToBRFV-infectivity and efficiency of large genome segment amplifications were reduced. At pH values above 10, modified particle morphologies were visualized by TEM, and virus infectivity was abolished. Treatment of ToBRFV-contaminated soil with an alkaline chlorinated-trisodium phosphate solution profoundly reduced soil-mediated virus infection of root-truncated tomato seedlings.

Conclusions

pH values above 10, compromised ToBRFV particle morphology genome integrity and virus infectivity. Alkaline disinfectant enhanced soil remediation following natural ToBRFV contamination.
Efficient CRISPR genome editing and integrative genomic analyses reveal the mosaicism of Cas-induced mutations and pleiotropic effects ofscarletgene in an emerging model system
Authors: Xu Sen , Neupane Swatantra , Wang Hongjun , Pham Thinh Phu , Snyman Marelize , Huynh Trung V. , Wang Li
Published: January 2024

Despite the revolutionary impacts of CRISPR-Cas gene editing systems, the effective and widespread use of CRISPR technologies in emerging model organisms still faces significant challenges. These include the inefficiency in generating heritable mutations at the organismal level, limited knowledge about the genomic consequences of gene editing, and an inadequate understanding of the inheritance patterns of CRISPR-Cas-induced mutations. This study addresses these issues by 1) developing an efficient microinjection delivery method for CRISPR editing in the microcrustaceanDaphnia pulex; 2) assessing the editing efficiency of Cas9 and Cas12a nucleases, examining mutation inheritance patterns, and analyzing the local and global mutation spectrum in thescarletmutants; and 3) investigating the transcriptomes ofscarletmutants to understand the pleiotropic effects ofscarletunderlying their swimming behavior changes. Our reengineered CRISPR microinjection method results in efficient biallelic editing with both nucleases. While indels are dominant in Cas-induced mutations, a few on-site large deletions (>1kb) are observed, most likely caused by microhomology-mediated end joining repair. Knock-in of a stop codon cassette to thescarletlocus was successful, despite complex induced mutations surrounding the target site. Moreover, extensive germline mosaicism exists in some mutants, which unexpectedly produce different phenotypes/genotypes in their asexual progenies. Lastly, our transcriptomic analyses unveil significant gene expression changes associated with scarlet knock-out and altered swimming behavior in mutants, including several genes (e.g., NMDA1, ABAT, CNTNAP2) involved in human neurodegenerative diseases. This study expands our understanding of the dynamics of gene editing in the tractable model organismDaphniaand highlights its promising potential as a neurological disease model.
Harnessing the regenerative potential ofinterleukin11to enhance heart repair
Authors: Shin Kwangdeok , Rodriguez-Parks Anjelica , Kim Chanul , Silaban Isabella M. , Xia Yu , Sun Jisheng , Dong Chenyang , Keles Sunduz , Wang Jinhu , Cao Jingli , Kang Junsu
Published: January 2024

Balancing between regenerative processes and fibrosis is crucial for heart repair, yet strategies regulating this balance remain a barrier to developing therapies. While Interleukin11 (IL11) is known as a fibrotic factor, its contribution to heart regeneration is poorly understood. We uncovered thatil11a, an Il11homolog in zebrafish, can trigger robust regenerative programs in zebrafish hearts, including cardiomyocytes proliferation and coronary expansion, even in the absence of injury. However, prolongedil11ainduction in uninjured hearts causes persistent fibroblast emergence, resulting in fibrosis. While deciphering the regenerative and fibrotic effects ofil11a, we found thatil11-dependent fibrosis, but not regeneration, is mediated through ERK activity, suggesting to potentially uncoupleil11adual effects on regeneration and fibrosis. To harness theil11a’s regenerative ability, we devised a combinatorial treatment throughil11ainduction with ERK inhibition. This approach enhances cardiomyocyte proliferation with mitigated fibrosis, achieving a balance between regenerative processes and fibrosis. Thus, we unveil the mechanistic insights into regenerativeil11roles, offering therapeutic avenues to foster cardiac repair without exacerbating fibrosis.
TIPPo: A User-Friendly Tool for De Novo Assembly of Organellar Genomes with HiFi Data
Authors: Xian Wenfei , Bezrukov Ilja , Bao Zhigui , Vorbrugg Sebastian , Gautam Anupam , Weigel Detlef
Published: January 2024

Plant cells have two major organelles with their own genomes: chloroplasts and mitochondria. While chloroplast genomes tend to be structurally conserved, the mitochondrial genomes of plants, which are much larger than those of animals, are characterized by complex structural variation. We introduce TIPPo, a user-friendly, reference-free assembly tool that uses PacBio high-fidelity (HiFi) long-read data and that does not rely on genomes from related species or nuclear genome information for the assembly of organellar genomes. TIPPo employs a deep learning model for initial read classification and leverages k-mer counting for further refinement, significantly reducing the impact of nuclear insertions of organellar DNA on the assembly process. We used TIPPo to completely assemble a set of 54 complete chloroplast genomes. No other tool was able to completely assemble this set. TIPPo is comparable to PMAT in assembling mitochondrial genomes from most species, but does achieve even higher completeness for some species. We also used the assembled organelle genomes to identify instances of nuclear plastid DNA (NUPTs) and nuclear mitochondrial DNA (NUMTs) insertions. The cumulative length of NUPTs/NUMTs positively correlates with the size of the nuclear genome, suggesting that insertions occur stochastically. NUPTs/NUMTs show predominantly C:G to T:A changes, with the mutated cytosines typically found in CG and CHG contexts, suggesting that degradation of NUPT and NUMT sequences is driven by the known elevated mutation rate of methylated cytosines. siRNA loci are enriched in NUPTs and NUMTs, consistent with the RdDM pathway mediating DNA methylation in these sequences.
Application of the thermal death time model in predicting thermal damage accumulation in plants
Authors: Faber Andreas H , Ørsted Michael , Ehlers Bodil Kirstine
Published: January 2024

The thermal death time (TDT) model suggests that the duration an organism can tolerate thermal stress decreases exponentially as the intensity of the temperature becomes more extreme. This model has been used to predict damage accumulation in ectotherm animals and plants under fluctuating thermal conditions. However, the critical assumption of the TDT model, which is additive damage accumulation, remains unverified for plants.

We assessed thermal damage inThymus vulgarisunder different heat and cold treatments and used TDT models to predict time to thermal failure of PSII. Additionally, thermal tolerance estimates from previous studies were used to create TDT models to assess the applicability of this framework in plants.

We show that thermal damage obtained at different stress intensities and durations is additive for both heat and cold stress, and that the TDT model can predict damage accumulation at both temperature extremes. Data from previous studies indicate a broad applicability of this approach across species, traits, and environments.

The TDT framework reveals a thermal tolerance landscape describing the exponential relationship between exposure duration, stress intensity and damage accumulation in plants. This thermal sensitivity emphasizes the potential impact of future thermal extremes on the mortality and distribution of plant species.

Highlight

This study highlights the applicability of the thermal death time model to plants, unveiling a distinct thermal tolerance landscape, extending across species and traits for assessing thermal stress impacts.
AC-BioSD : A biomolecular signal differentiator module with enhanced performance (extended version)
Authors: Alexis Emmanouil , Avalos José L. , Cardelli Luca , Papachristodoulou Antonis
Published: January 2024

Temporal gradient estimation is a pervasive phenomenon in natural biological systems and holds great promise for synthetic counterparts with broad-reaching applications. Here, we advance the concept ofBioSD(Biomolecular Signal Differentiators) by introducing a novel biomolecular topology, termedAutocatalytic-BioSDorAC-BioSD. Its structure allows for insensitivity to input signal changes and high precision in terms of signal differentiation, even when operating far from nominal conditions. Concurrently, disruptive high-frequency signal components are effectively attenuated. In addition, the usefulness of our topology in biological regulation is highlighted via a PID (Proportional-Integral-Derivative) bio-control scheme withset point weightingand filtered derivative action in both the deterministic and stochastic domains.
From small to tall: breed-varied household pet dogs can be trained to detect Parkinson’s Disease
Authors: Holt Lisa , Johnston Samuel V
Published: January 2024

Objective

Parkinson’s Disease (PD) is a clinically diagnosed disease that carries a reported misdiagnosis rate of 10–20%. Recent scientific discoveries have provided evidence of volatile organic compounds in sebum that are unique to patients with PD. The purpose of this study was to determine if companion dogs could be trained to distinguish between sebum samples provided by PD-positive patients and PD-negative human controls.

Methods

This was a randomized, handler-blind, controlled study. Twenty-three canines of varying breeds, ages, and environmental backgrounds were included. The two-year study period reported here was the final two years of a seven-year program which started in January of 2016. This study encompassed 200 total working session days from 2021 and 2022.

Results

When averaged as a group over two years, the 23 dogs were 89% sensitive and 87% specific to an olfactory distinction between PD-positive and PD-negative human donor samples. Ten of the twenty-three dogs averaged 90% or higher in both sensitivity and specificity.

In 161 separate instances, dogs were presented with both unique PD-positive and PD-negative samples (the dogs had not previously encountered any of the samples presented). For these first-time exposures, the 23 dogs collectively averaged 86% sensitivity and 89% specificity.

When comparing the sensitivity and specificity of PD-positive samples from donors who reported levodopa usage to PD-positive samples from donors who reported no levodopa usage, the dogs showed no statistical difference in sensitivity or specificity at the 95% significance level, indicating levodopa usage is not a factor in PD canine detection. Other factors investigated as part of this study included sample donor gender, canine breed, age, duration of time in the program, and training.

Conclusions

Companion dogs can be trained with reward-biased detection methodologies to distinguish between PD-positive and PD-negative donor sebum samples in a controlled setting. This study provides further evidence of one or more volatile organic compounds in the sebum of PD-positive patients that can be detected by canines. Summarily, study findings support the application of trained companion dogs for the screening of PD-positive and PD-negative samples in which numbers of samples are limited and the dogs are worked in short intervals, followed by recovery training.
The interaction of relative age with maturation and body size in female handball talent selection based on only sport-specific criteria
Authors: Tróznai Zsófia , Utczás Katinka , Pápai Júlia , Pálinkás Gergely , Szabó Tamás , Petridis Leonidas
Published: January 2024

Talent identification is often affected by the relative age effects (RAEs) and/or maturation. Previous research has suggested that talent selection should include sport-specific technical tasks instead of body size and/or physical test measurements, assuming that the technical tasks are less influenced by interindividual variability in maturation. Our purpose was to examine the prevalence of RAEs and how biological maturity, body size, and body composition in relation to relative age affect talent selection among female handball players. Handball-specific drills and in-game performance were the criteria of a single talent selection program. Birth distribution of U14 female (N= 3198) handball players were analyzed. Body size, body composition, and bone age were assessed on 264 selected and 266 not-selected players. Body composition was assessed with InBody 720, whereas biological age from bone age. Chi-square was used to examine quartile distributions, and logistic regression to determine the effects of the predictors on the selection. In terms of all registered players, there was no difference in birth distribution. RAEs appeared at the first selection level and were evident at all levels. Quartiles differed only between the first and the last quartiles in body size and muscle mass. Only bone age differed between consecutive quartile or semi-year groups. Body size, body composition, and maturity had a significant, but of moderate power, effect on the selection. Larger body height increased selection odds by about 12%, larger muscle mass by 12% to 25%, larger percent body fat decreased selection odds by 7%, while larger bone age by 3.5-4 times. RAEs affected talent selection when applying sport-specific drills as selection criteria. Relative age was connected to bone age, but not convincingly to body size and muscle mass. Bone age had the largest effect on the selection, but this was not associated with larger body size or muscle mass.