bluuebunny/crossref_metadata_2025 huggingface dataset:
Does eating less or exercising more to reduce energy availability produce distinct metabolic responses?
Authors: Halsey Lewis G. , Areta José L. , Koehler Karsten
Published: July 2023

When less energy is available to consume, people often lose weight, which reduces their overall metabolic rate. Their cellular metabolic rate may also decrease (metabolic adaptation), possibly reflected in physiological and/or endocrinological changes. Reduced energy availability can result from calorie restriction or increased activity energy expenditure, raising the following question that our review explores: do the body's metabolic and physiological responses to this reduction differ or not depending on whether they are induced by dietary restriction or increased activity? First, human studies offer indirect, contentious evidence that the body metabolically adapts to reduced energy availability, both in response to either a calorie intake deficit or increased activity (exercise; without a concomitant increase in food intake). Considering individual aspects of the body's physiology as constituents of whole-body metabolic rate, similar responses to reduced energy availability are observed in terms of reproductive capacity, somatic maintenance and hormone levels. By contrast, tissue phenotypic responses differ, most evidently for skeletal tissue, which is preserved in response to exercise but not calorie restriction. Thus, while in many ways ‘a calorie deficit is a calorie deficit’, certain tissues respond differently depending on the energy deficit intervention.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Obesity and environments external to the body
Authors: Ulijaszek Stanley
Published: July 2023

Studies of environment and obesity usually use epidemiologically tractable measures that are proxies for energy balance or macronutrient composition intake, mostly to identify individual behavioural changes for prevention or reduction of obesity, or inform policy. Of environments external to the body as they relate to obesity, the built environment and the food environment are considered among the most important. Incorporating human sociality into obesity and environments research enriches the field by offering possible ways for understanding obesity production via social stress, dietary preference, food consumption and physical activity. External environments are in flux, however, especially with changing urban form and social environmental hybridity since Web 2.0, with urban polycentricity and networked and online activity influencing obesity production in new ways. While the world's rural populations are experiencing the fastest increases in obesity, large urban populations benefit from scale in setting the physical conditions for physical activity and healthy food availability, with larger and polycentric cities having lower rates of obesity than smaller monocentric or dispersed cities. It is argued that built, food and social environments set the context for obesity production or its amelioration, with sociodemographic factors being more important than new phenomena such as digital and smart technologies.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
The fructose survival hypothesis for obesity
Authors: Johnson Richard J. , Lanaspa Miguel A. , Sanchez-Lozada L. Gabriela , Tolan Dean , Nakagawa Takahiko , Ishimoto Takuji , Andres-Hernando Ana , Rodriguez-Iturbe Bernardo , Stenvinkel Peter
Published: July 2023

The fructose survival hypothesis proposes that obesity and metabolic disorders may have developed from over-stimulation of an evolutionary-based biologic response (survival switch) that aims to protect animalsin advanceof crisis. The response is characterized by hunger, thirst, foraging, weight gain, fat accumulation, insulin resistance, systemic inflammation and increased blood pressure. The process is initiated by the ingestion of fructose or by stimulating endogenous fructose production via the polyol pathway. Unlike other nutrients, fructose reduces the active energy (adenosine triphosphate) in the cell, while blocking its regeneration from fat stores. This is mediated by intracellular uric acid, mitochondrial oxidative stress, the inhibition of AMP kinase and stimulation of vasopressin. Mitochondrial oxidative phosphorylation is suppressed, and glycolysis stimulated. While this response is aimed to be modest and short-lived, the response in humans is exaggerated due to gain of ‘thrifty genes’ coupled with a western diet rich in foods that contain or generate fructose. We propose excessive fructose metabolism not only explains obesity but the epidemics of diabetes, hypertension, non-alcoholic fatty liver disease, obesity-associated cancers, vascular and Alzheimer's dementia, and even ageing. Moreover, the hypothesis unites current hypotheses on obesity. Reducing activation and/or blocking this pathway and stimulating mitochondrial regeneration may benefit health-span.

This article is part of a discussion meeting issue ‘Causes of obesity: theories, conjectures and evidence (Part I)’.
Deciphering the interaction surface between the West Nile virus NS3 and NS5 proteins
Authors: Brand Carolin , Geiss Brian , Bisaillon Martin
Published: July 2023

West Nile virus (WNV) is the most prevalent mosquito-borne disease and the leading cause of viral encephalitis in the continental United States. It belongs to the Flavivirus family which includes other important human pathogens such as dengue virus (DENV), Japanese encephalitis virus (JEV), and Zika viruses (ZIKV). Despite several decades of research, no specific antiviral drugs are available to treat Flavivirus infections. The present study characterizes the interaction between the WNV NS3 and NS5 proteins for the purpose of identifying hotspots in the protein-protein interaction which could be targeted for the development of antiviral therapeutics. We previously developed an interaction model in silico based on data available in the literature. Here, potential interacting residues on NS3 and NS5 were mutated in a WNV replicon, and seven mutations in the NS3 protein were found to drastically reduce viral replication. In addition to being well conserved among mosquito-borne Flaviviruses, these residues are located on the protein’s surface in two clusters which might be interesting new targets for future drug development.
11-month SARS-CoV-2 immunogenicity decay, and associated factors, among mRNA vaccinees: Implications for Booster Vaccination
Authors: Asamoah-Boaheng Michael , Grunau Brian , Haig Scott , Karim Mohammad Ehsanul , Kirkham Tracy , Lavoie Pascal M. , Sediqi Sadaf , Drews Steven J. , O'Brien Sheila F , Barakauskas Vilte , Marquez Ana Citlali , Jassem Agatha , Goldfarb David
Published: July 2023

BackgroundWe examined the 11-month longitudinal antibody decay among 2-dose mRNA vaccinees, and identified factors associated with faster decay.MethodsThe study included samples from the CORSIP longitudinal observational study of paramedics in Canada. Participants were included if they had received two mRNA vaccines without prior SARS-CoV-2 infection and provided two blood samples post-vaccination. The outcomes of interest were quantitative SARS-CoV-2 antibody concentrations. We employed spaghetti and scatter plots (with kernel-weighted local polynomial smoothing curve) to describe the trend of the antibody decay over 11-months post vaccine and fit a mixed effect exponential decay model to examine the loss of immunogenicity and factors associated with antibody waning over time.ResultsThis analysis included 652 blood samples from 326 adult paramedics. Total anti-spike antibody levels peaked on the 21st day (antibody level 9,042U/mL) after the second mRNA vaccine dose. Total anti-spike antibody levels declined thereafter, with a half-life of 94 [95% CI: 70, 143] days, with levels plateauing at 295 days (antibody level 1021 U/mL). Older age, vaccine dosing interval <35 days, and the BNT162b2 vaccine (compared to mRNA-1273 vaccine) were associated with faster antibody decay.ConclusionAntibody levels declined after the initial mRNA series with a half-life of 94 days, plateauing at 295 days. These findings may inform the timing of booster vaccine doses and identifying individuals with faster antibody decay.
Nocardioides potassii sp. nov., isolated from weathered potash tailings soil
Authors: Liu Lingxiao , Zhang Ya , Chen Qiuyu , Shen Qi , Li Ludan , Cao Chengliang , Li Rongpeng , Jiang Jihong , Liu Jinjuan
Published: July 2023

A Gram-positive, aerobic actinomycete, designated strain KLBMP 9356T, was isolated from weathered potash tailings soil sampled in Xuzhou, Jiangsu Province, PR China. The colonies were cream-coloured, convex and rounded. The optimal growth conditions of strain KLBMP 9356T were 1 % (w/v) NaCl, 28 °C and pH 7. Phylogenetic analysis based on 16S rRNA gene sequences indicated that strain KLBMP 9356T showed the highest similarity to

Nocardioides zhouii

CGMCC 1.11084T (98.9 %) and

Nocardioides glacieisoli

CGMCC 1.11097T (98.7 %). Results from two tree-making algorithms supported the position that strain KLBMP 9356T forms a stable clade with

N. zhouii

CGMCC 1.11084T and

N. glacieisoli

CGMCC 1.11097T. Strain KLBMP 9356T exhibited low digital DNA-DNA hybridization values with

N. zhouii

CGMCC 1.11084T (27.6 %) and

N. glacieisoli

CGMCC 1.11097T (31.4 %). The average nucleotide identity values between strain KLBMP 9356T and

N. zhouii

CGMCC 1.11084T and

N. glacieisoli

CGMCC 1.11097T were 83.8% and 85.9%, respectively. The peptidoglycan in the cell wall of the novel strain was ll-2,6-diaminopimelic acid and the predominant menaquinone was MK-8(H4). The major fatty acids (>10 %) were C17:1ω8c and C18:1ω9c. The major polar lipids were diphosphatidylglycerol, phosphatidylglycerol, lyso-phospatidylglycerol and phosphatidylinositol. The genomic DNA G+C content was 71.6 mol%. Based on its morphological, chemotaxonomic and phylogenetic characteristics, strain KLBMP 9356T represents a novel species of the genus

Nocardioides

, for which the name Nocardioides potassii sp. nov. is proposed. The type strain is KLBMP 9356T (=CGMCC 4.7738T=NBRC 115493T).
Rhizobium brockwellii sp. nov., Rhizobium johnstonii sp. nov. and Rhizobium beringeri sp. nov., three genospecies within the Rhizobium leguminosarum species complex
Authors: Young J. Peter W. , Jorrin Beatriz , Moeskjær Sara , James Euan K.
Published: July 2023

Genomic evidence indicates that the

Rhizobium leguminosarum

species complex comprises multiple distinct species, perhaps 18 or more. Of the five earliest genospecies (gs) to be described, only two have formal names: R. leguminosarum sensu stricto (gsE) and

Rhizobium ruizarguesonis

(gsC). Here, we provide formal descriptions and names for the other three genospecies, based on the publicly available genome sequences for multiple strains of each species: Rhizobium brockwellii sp. nov. (gsA, 37 strains, type strain CC275eT=LMG 6122T = ICMP 2163T=NZP 561T = PDDCC 2163T=HAMBI 13T), Rhizobium johnstonii sp. nov. (gsB, 54 strains, type strain 3841T = LMG 32736T=DSM 114642T) and Rhizobium beringeri sp. nov. (gsD, 8 strains, type strain SM51T = LMG 32895T = DSM 115206T). Each species forms a well-supported clade in a phylogeny based on 120 concatenated core genes. All strains have average nucleotide identity (ANI) above 96 % with the relevant type strain and below 96 % with all other type strains. Each species is characterised by a number of genes that are absent or rare in other species.
Prevalence of and risk factors for peripheral artery disease in rural South Africa: A cross-sectional analysis of the HAALSI cohort
Authors: Beidelman Erika Teresa , Rosenberg Molly , Wade Alisha N. , Crowther Nigel , Kalbaugh Corey A.
Published: July 2023

Introduction

The burden of peripheral artery disease (PAD) is increasing in low- and middle-income countries. Existing literature from sub-Saharan Africa is limited and lacks population-representative estimates. We estimated the burden and risk factor profile of PAD for a rural South African population.

Methods

We used data from 1,883 participants of the HAALSI cohort of South African adults aged 40-69 years with available ankle-brachial index (ABI) measurements. We defined clinical PAD as ABI ≤0.90 or >1.40 and borderline PAD as ABI >0.90 & ≤1.00. We compared the distribution of sociodemographic variables, biomarkers, and comorbidities across PAD classifications. To identify associated factors, we calculated unadjusted and age-sex-adjusted prevalence ratios with log-binomial models.

Results

Overall, 6.6% (95% CI: 5.6-7.7) of the sample met the diagnostic criteria for clinical PAD while 44.7% (95% CI: 42.4-47.0) met the diagnostic criteria for borderline PAD. Age (PR: 1.9, 95% CI: 1.2-3.1 for ages 50-59 compared to 40-49; PR: 2.5, 95% CI: 1.5-4.0 for ages 60-69 compared to 40-49) and C-reactive protein (PR: 1.08, 95% CI: 1.03-1.12) were associated with increased prevalence of clinical PAD. All other examined factors were not associated with clinical PAD.

Conclusions

We found high PAD prevalence for younger age groups compared to previous research and a lack of evidence for the influence of traditional risk factors for this rural, low-income population. Future research should focus on identifying the underlying risk factors for PAD in this setting. South African policymakers and clinicians should consider expanded screening for early PAD detection in rural areas.
Invasion of the stigma by the pollen tube or an oomycete pathogen: striking similarities and differences
Authors: Riglet Lucie , Hok Sophie , Kebdani-Minet Naïma , Berre Joëlle Le , Gourgues Mathieu , Rozier Frédérique , Bayle Vincent , Bancel-Vallée Lesli , Allasia Valérie , Keller Harald , Rocha Martine Da , Gaude Thierry , Attard Agnés , Fobis-Loisy Isabelle
Published: July 2023

The epidermis is the first barrier that protects organisms from surrounding stresses. Similar to the hyphae of filamentous pathogens that penetrate and invade the outer tissues of the host, the pollen germinates and grows a tube within epidermal cells of the stigma. Early responses of the epidermal layer are therefore decisive for the outcome of these two-cell interaction processes. Here, we aim at characterizing and comparing how the papillae of the stigma respond to intrusion attempts, either by hypha of the hemibiotrophic oomycete root pathogen,Phytophthora parasiticaor by the pollen tube. We found thatP. parasiticaspores attach to the papillae and hyphae subsequently invade the entire pistil. Using transmission electron microscopy, we examined in detail the invasive growth characteristics ofP. parasiticaand found that the hypha passed through the stigmatic cell wall to grow in contact with the plasma membrane, contrary to the pollen tube that advanced engulfed within the two cell wall layers of the papilla. Further quantitative image analysis revealed that the pathogen and the pollen tube trigger reorganization of the endomembrane system (trans Golgi network, late endosome) and the actin cytoskeleton. Some of these remodeling processes are common to both invaders, while others appear to be more specific showing that the stigmatic cells trigger an appropriate response to the invading structure and somehow can recognize the invader that attempts to penetrate.
Protective role of N-acetylcysteine and Sulodexide on endothelial cells after SARS-CoV-2 infection
Authors: Rajewska-Tabor Justyna , Sosińska-Zawierucha Patrycja , Pyda Malgorzata , Bręborowicz Andrzej
Published: July 2023

Severe acute respiratory syndrome coronavirus-2 causes hyperinflammation and activation of coagulation cascade and in the result aggravates endothelial cell dysfunction. N-acetylcysteine and Sulodexide have been found to mitigate endothelial damage. The influence on coronary artery endothelial cells of serum collected after 4+/-1 months from coronavirus infection was studied. The concentrations of serum samples of interleukin 6, von Willebrand Factor, tissue Plasminogen Activator and Plasminogen Activator Inhibitor-1 were studied. The cultures with serum of patients after coronavirus infection were incubated with N-acetylocysteine and Sulodexide to estimate their potential protective role. The blood inflammatory parameters were increased in the group of cultures incubated with serum from patients after coronavirus infection. Supplementation of the serum from patients after coronavirus infection with N-acetylcysteine or Sulodexide reduced the synthesis of interleukin 6, von Willebrand Factor. No changes in the synthesis of tissue Plasminogen Activator were observed. N-acetylcysteine reduced the synthesis of Plasminogen Activator Inhibitor-1. N-acetylcysteine and Sulodexide increased the tPA/PAI-1 ratio. N-acetylcysteine may have a role in reducing the myocardial injury occurring in the post-COVID-19 syndrome. Sulodexide can also play a protective role in post-COVID-19 patients.
Improving Gonorrhoea Molecular Diagnostics: Genome Mining-Based Identification of Identical Multi-Repeat Sequences (IMRS) inNeisseria gonorrhoeaeGenome
Authors: Shiluli Clement , Kamath Shwetha , Kanoi Bernard N. , Kimani Rachael , Maina Michael , Waweru Harrison , Kamita Moses , Ndirangu Ibrahim , Abkallo Hussein M. , Oduor Bernard , Pamme Nicole , Dupaty Joshua , Klapperich Catherine M. , Lolabattu Srinivasa Raju , Gitaka Jesse
Published: July 2023

Purpose

Curable sexually transmitted infections (STIs) such asNeisseria gonorrhoeae(N. gonorrhoeae) is a major cause of poor pregnancy outcome. The infection is often asymptomatic in pregnant women and a syndrome-based approach of testing leads to missed diagnosis. Culture followed by microscopy is inadequate and time-consuming. The gold standard Nucleic Acid Amplification Tests (NAATs) require advanced infrastructure settings whilst point of care tests are limited to immunoassays with sensitivities and specificities insufficient to accurately diagnose asymptomatic cases. This necessitates the development and validation of assays that are fit for purpose.

Materials and methods

Here, we have identified new diagnostic target biomarker regions forN. gonorrhoeaeusing an algorithm for genome mining of identical multi repeat sequences (IMRS). These were then developed as DNA amplification primers to design better diagnostic assays. To test the primer pair, genomic DNA was 10-fold serially diluted (100pg/μL to 1×10-3pg/μL) and used as DNA template for PCR reactions. The gold standard PCR using 16S rRNA primers was also run as a comparative test, and both assay products resolved on 1% agarose gel.

Results

Our newly developedN. gonorrhoeaeIMRS-PCR assay had an analytical sensitivity of 6 fg/μL representing better sensitivity compared to the 16S rRNA PCR assay with analytical sensitivity of 4.3096 pg/μL. The assay was also successfully validated with clinical urethral swab samples. We further advanced this technique by developing an iso-thermal IMRS, which was both reliable and sensitive for detecting culturedN. gonorrhoeaeisolates at a concentration of 38 ng/μL. Combining the iso-thermal IMRS with a low-cost Lateral Flow Assay, we were able to detectN. gonorrhoeaeamplicons at a starting concentration of 100 pg/μL.

Conclusion

Therefore, there is a potential to implement this concept within miniaturized, isothermal, microfluidic platforms, and laboratory-on-a-chip diagnostic devices for highly reliable point-of-care testing.
AMPK targets PDZD8 to trigger carbon source shift to glutamine
Authors: Li Mengqi , Wang Yu , Wei Xiaoyan , Cai Wei-Feng , Zhu Mingxia , Yao Luming , Wang Yongliang , Liu Yan-Hui , Wu Jianfeng , Xiong Jinye , Tian Xiao , Qu Qi , Xie Renxiang , Li Xiaomin , Chen Siwei , Huang Xi , Zhang Cixiong , Xie Changchuan , Wu Yaying , Xu Zheni , Zhang Baoding , Jiang Bin , Yu Yong , Wang Zhi-Chao , Li Qinxi , Li Gang , Lin Shu-Yong , Yu Li , Piao Hai-Long , Deng Xianming , Zhang Chen-Song , Lin Sheng-Cai
Published: July 2023

The shift of carbon utilisation from glucose to other nutrients is a fundamental metabolic adaptation to cope with the decreased glucose oxidation during fasting or starvation1. AMP-activated protein kinase (AMPK) plays crucial roles in manifesting physiological benefits accompanying glucose starvation or calorie restriction2. However, the underlying mechanisms are unclear. Here, we show that low glucose-induced activation of AMPK plays a decisive role in the shift of carbon utilisation from glucose to glutamine. We demonstrate that endoplasmic reticulum (ER)-localised PDZD8, which we identify to be a new substrate of AMPK, is required for the glucose starvation-promoted glutaminolysis. AMPK phosphorylates PDZD8 at threonine 527 (T527), and promotes it to interact with and activate the mitochondrial glutaminase 1 (GLS1), a rate-limiting enzyme of glutaminolysis3–5, and as a result the ER-mitochondria contact is strengthened. In vivo, PDZD8 enhances glutaminolysis, and triggers mitohormesis that is required for extension of lifespan and healthspan inCaenorhabditis eleganssubjected to glucose starvation or caloric restriction. Muscle-specific re-introduction of wildtype PDZD8, but not the AMPK-unphosphorylable PDZD8-T527A mutant, toPDZD8−/−mice is able to rescue the increase of glutaminolysis, and the rejuvenating effects of caloric restriction in aged mice, including grip strength and running capacity. Together, these findings reveal an AMPK-PDZD8-GLS1 axis that promotes glutaminolysis and executes the anti-ageing effects of calorie restriction by promoting inter-organelle crosstalk between ER and mitochondria.
Impaired biogenesis of basic proteins impacts multiple hallmarks of the aging brain
Authors: Di Fraia Domenico , Marino Antonio , Lee Jae Ho , Kelmer Sacramento Erika , Baumgart Mario , Bagnoli Sara , Tomaz da Silva Pedro , Kumar Sahu Amit , Siano Giacomo , Tiessen Max , Terzibasi-Tozzini Eva , Gagneur Julien , Frydman Judith , Cellerino Alessandro , Ori Alessandro
Published: July 2023

Aging and neurodegeneration entail diverse cellular and molecular hallmarks. Here, we studied the effects of aging on the transcriptome, translatome, and multiple layers of the proteome in the brain of a short-lived killifish. We reveal that aging causes widespread reduction of proteins enriched in basic amino acids that is independent of mRNA regulation, and it is not due to impaired proteasome activity. Instead, we identify a cascade of events where aberrant translation pausing leads to reduced ribosome availability resulting in proteome remodeling independently of transcriptional regulation. Our research uncovers a vulnerable point in the aging brain’s biology – the biogenesis of basic DNA/RNA binding proteins. This vulnerability may represent a unifying principle that connects various aging hallmarks, encompassing genome integrity and the biosynthesis of macromolecules.

One-Sentence Summary

Translation pausing reshapes the aging brain proteome, revealing vulnerabilities in the biogenesis of nucleic-acid protein.
Robust inference of historical human generation times
Authors: Wang Richard J. , Rogers Jeffrey , Hahn Matthew W.
Published: July 2023

Ragsdale and Thornton (2023) raise concerns about our recent estimates of historical human generation times, concluding that our results were “predominantly driven by nonbiological artifacts.” While we believe these authors have pointed out several important sources of uncertainty, we show here that their main concerns are either not relevant to our study or support our conclusions as much as they cast doubt on them. In particular, the demographic simulations carried out by Ragsdale and Thornton assume all individuals with recent African ancestry are from West Africa, which is not appropriate for our sample. In contrast to the lack of visual concordance between predictions and data cited by these authors as evidence for a lack of fit, we demonstrate that our model provides a good statistical fit to data on the overall historical mutation spectrum, though one particular mutation type is an outlier. Furthermore, we show that the historical generation times inferred when using alternative methods for estimating the ages of individual alleles are largely in agreement with our results, particularly so when using results from Relate. Importantly, these analyses, as well as recent work from an independent group, confirm the idea that a model built onde novomutations and applied to polymorphism data provides useful and reliable estimates of generation times in widely distant mammals.
Epigenetic insights into neuropsychiatric and cognitive symptoms in Parkinson’s disease: A DNA co-methylation network analysis
Authors: Harvey Joshua , Smith Adam R. , Weymouth Luke S. , Smith Rebecca G. , Castanho Isabel , Hubbard Leon , Creese Byron , Bresner Kate , Williams Nigel , Pishva Ehsan , Lunnon Katie
Published: July 2023

Parkinson’s disease is a highly heterogeneous disorder, encompassing a complex spectrum of clinical presentation including motor, sleep, cognitive and neuropsychiatric symptoms. We aimed to investigate genome-wide DNA methylation networks in post-mortem Parkinson’s disease brain samples and test for region-specific association with common neuropsychiatric and cognitive symptoms. Of traits tested, we identify a co-methylation module in the substantia nigra with significant correlation to depressive symptoms and with ontological enrichment for terms relevant to neuronal and synaptic processes. Notably, expression of the genes annotated to the methylation loci present within this module are found to be significantly enriched in neuronal subtypes within the substantia nigra. These findings highlight the potential involvement of neuronal-specific changes within the substantia nigra with regard to depressive symptoms in Parkinson’s disease.
Investigating the effects of age and hearing loss on speech intelligibility and amplitude modulation frequency selectivity
Authors: Regev Jonathan , Zaar Johannes , Relaño-Iborra Helia , Dau Torsten
Published: July 2023

The perception of amplitude modulation (AM), characterized by a frequency-selective process in the modulation domain, is considered critical for speech intelligibility. Previous literature has provided evidence of an age-related decline in AM frequency selectivity. Additionally, a notable sharpening of AM tuning with hearing loss has been observed, which was proposed to be related to a perceptual advantage resulting from peripheral compression loss. This study explores whether such changes in AM tuning with age and hearing loss contribute to the speech intelligibility challenges that older listeners often face in noisy environments. Young (n=10, 22-28 years) and older (n=9, 57-77 years) listeners with normal hearing as well as older listeners with hearing impairment (n=9, 64-77 years) participated in the study. All had previously taken part in studies on AM tuning. Speech-reception thresholds (SRTs) were collected in conditions including stationary, fluctuating, and competing-speech maskers. The results revealed an age-related increase in SRTs, with an additional negative impact of hearing loss. Beyond age and audibility, a measure of AM tuning significantly contributed to explaining the variance in SRTs across listeners for specific maskers. These findings motivate further exploration of the relationship between AM frequency selectivity and speech intelligibility in noise.
A Novel Genome Optimization Tool for Chromosome-Level Assembly across Diverse Sequencing Techniques
Authors: Chuang Wei-Hsuan , Cheng Hsueh-Chien , Chang Yu-Jung , Fu Pao-Yin , Huang Yi-Chen , Hsieh Ping-Heng , Chen Shu-Hwa , Kwok Pui-Yan , Lin Chung-Yen , Ho Jan-Ming
Published: July 2023

This paper introduces a novel genome assembly optimization tool named LOCLA, which stands for “Local Optimization for Chromosome-Level Assembly”. It identifies reads and contigs aligned locally with high quality on gap flanks or scaffold boundaries of draft assemblies for gap filling and scaffold connection. LOCLA applies to both de novo and reference-based assemblies. It can also utilize reads produced by diverse sequencing techniques, e.g., 10x Genomics (10xG) Linked-Reads, and PacBio HiFi reads.

We validated LOCLA on three human samples and one non-model organism. For the first two human samples, LLD0021C and CHM13, we generated de novo draft assemblies from 10xG Linked-Reads. On LLD0021C, LOCLA improves the draft assembly by adding 23.3 million bases using only 10xG Linked-Reads. These additional bases cover 28,746 protein-coding regions, particularly in pericentromeric and telomeric regions. On the CHM13 sample, we took 10xG Linked-Reads and PacBio HiFi reads as input. As a result, LOCLA added 46.2 million bases to the draft assembly. The increased content enables us to identify genes linked to complex diseases (e.g., ARHGAP11A) and critical biological pathways. We created two reference-guided draft assemblies on the third human sample, HG002, using contigs assembled from PacBio HiFi reads. LOCLA enhances the two draft assemblies by recovering 27.9 million bases (22.26%) and 35.7 million bases (30.93%) of the sequences discarded by the reference-guided assembly tool. The results indicate the robustness of LOCLA’s contig detection algorithm on gap flanks. Furthermore, we show that 95% of the sequences filled in by LOCLA have over 80% accuracy compared with the HG002 reference genome published by the Human Pan-genome Reference Consortium. On the non-model organism, LOCLA enhanced the genome assembly of Bruguiera sexangula (JAHLGP000000000) by decreasing 41.4% of its gaps and raising the Benchmarking Universal Single-Copy Orthologs (BUSCO) analysis score to 98.10%.

LOCLA can optimize de novo and reference-guided assemblies using varied sequencing reads. The final assemblies produced by LOCLA have improved in both quantity and quality. The increased gene content may provide a valuable resource in advancing personalized medicine.
A molecular toolbox to study progesterone receptor signaling
Authors: Aarts Marleen T. , Wagner Muriel , van der Wal Tanne , van Boxtel Antonius L. , van Amerongen Renée
Published: July 2023

Progesterone receptor (PR) signaling is required for mammary gland development and homeostasis. A major bottleneck in studying PR signaling is the lack of sensitive assays to measure and visualize PR pathway activity both quantitatively and spatially. Here, we develop new tools to study PR signaling in human breast epithelial cells. First, we generate optimized Progesterone Responsive Element (PRE)-luciferase constructs and demonstrate that these new reporters are a powerful tool to quantify PR signaling activity across a wide range of progesterone concentrations in two luminal breast cancer cell lines, MCF7 and T47D. We also describe a fluorescent lentiviral PRE-GFP reporter as a novel tool to visualize PR signaling at the single-cell level. Our reporter constructs are sensitive to physiological levels of progesterone. Second, we show that low background signaling, and high levels of PR expression are a prerequisite for robustly measuring PR signaling. Increasing PR expression by transient transfection, stable overexpression in MCF7 or clonal selection in T47D, drastically improves both the dynamic range of luciferase reporter assays, and the induction of endogenous PR target genes as measured by qRT-PCR. We find that the PR signaling response differs per cell line, target gene and hormone concentration used. Taken together, our tools allow a more rationally designed approach for measuring PR signaling in breast epithelial cells.
Physical fitness and motor competence performance characteristics of elite Chinese youth athletes from four track and field throwing disciplines – a cross sectional study
Authors: Zhao Kewei , Siener Maximilian , Zhao Yifan , Hohmann Andreas
Published: July 2023

Purpose

Systematic athletic training during adolescence may facilitate the development of sport-specific skills and the expression of sport-specific physical characteristics in young athletes. The aim of this study was to differentiate male athletes aged 14-17 years from four different throwing disciplines using anthropomorphic measurements and motor competence performance tests, in order to test whether athletes from different disciplines have physical form and fitness characteristics consistent with the sport-specific demands of each throwing discipline.

Methods

The sample consisted of 289 male youth athletes belonging to the four different throwing disciplines: shot put (n=101), hammer throw (n=16), discus throw (n=63), and javelin throw (n=109). The performance diagnosis comprised three anthropometric measurements, and twelve physical fitness tests. Discriminant analysis and neural network (Multilayer Perceptron) were used to test whether it is possible to discriminate between athletes of the four sports.

Results

The results of this study show that for male throwing athletes aged 14-17 years, differences in generic anthropometric and sport performance tests distinguish the talent of more than two-thirds of young athletes based on individual sport (DA: 68.7%; MLP: 72.2%), regardless of the classification method used.

Conclusion

The relevance of the three anthropometric parameters and twelve physical fitness measures for talent identification and training monitoring in the track and field throwing disciplines was confirmed. The discus throwers had a height advantage, the shot putters and hammer throwers had better arm strength, while the javelin throwers had better explosive strength and sprint speed. All events, except the hammer throwers, showed a high level of explosive power in the medicine ball forward or backward throw test. This was particularly important for the shot put and discus athletes.
Development of selection strategies for genetic improvement in production traits of Mecheri sheep based on a Bayesian multi trait evaluation
Authors: Balasundaram Balakrishnan , Muralidharan Jaganadhan , Murali Nagarajan , Cauveri Doraiswamy , Raja Angamuthu , Okpeku Moses , Thiruvenkadan Aranganoor Kannan
Published: July 2023

The progression of genetic selection techniques to enhance farm animal performance traits is guided by the present level of genetic variation and maternal impact in each trait, as well as the genetic association between traits. This study was conducted on a population of Mecheri sheep maintained from 1980 to 2018 at Mecheri Sheep Research Station, Pottaneri, India, to determine variance and covariance components, as well as genetic parameters for various production performance traits. The production traits of Mecheri sheep assessed include: birth weight (BW), weaning weight (WW), six-month weight (SMW), nine-month weight (NMW) and yearling weight (YW). The Bayesian approach using the Gibbs sampler analyzed six animal models with different combinations of additive direct and maternal additive effects was used. Direct genetics, maternal genetics and residual effects models were the major significantly contributors to total phenotypic variation for all the production traits studied. Direct heritability estimates of birth weight, WW, SMW, NMW and YW were 0.25, 0.20, 0.12, 0.14 and 0.13, respectively. The maternal heritability estimated for BW, WW, SMW, NMW and YW were 0.17, 0.10, 0.12, 0.14 and 0.14, respectively. The maternal effects had a major impact on the pre-weaning production traits. The genetic correlations estimated between different pairs of production traits studied ranged from 0.19 to 0.93. The body weight at birth exhibited higher genetic relationship with weaning weight than post-weaning growth characteristics, and the genetic correlation between weaning weight and post-weaning attributes was moderate to high (0.52 to 0.72). Based on the additive genetic variance in weaning weight and the correlation estimates of weaning weight with post-weaning traits, the weaning weight was proposed as a selection criterion for improving growth traits in Mecheri sheep.
Mitochondrial dysfunction underlies impaired neurovascular coupling following traumatic brain injury
Authors: van Hameren Gerben , Muradov Jamil , Minarik Anna , Aboghazleh Refat , Orr Sophie , Cort Shayna , Andrews Keiran , McKenna Caitlin , Pham Nga Thy , MacLean Mark A. , Friedman Alon
Published: July 2023

Traumatic brain injury (TBI) involves an acute injury (primary damage), which may evolve in the hours to days after impact (secondary damage). Seizures and cortical spreading depolarization (CSD) are metabolically demanding processes that may worsen secondary brain injury. Metabolic stress has been associated with mitochondrial dysfunction, including impaired calcium homeostasis, reduced ATP production, and elevated ROS production. However, the association between mitochondrial impairment and vascular function after TBI is poorly understood. Here, we explored this association using a rodent closed head injury model. CSD resulted in neurobehavioral decline after TBI. Craniotomy was performed to elicit CSD via electrical stimulation or to induce seizures via 4-aminopyridine application. We measured vascular dysfunction following CSDs and seizures in TBI animals using laser doppler flowmetry. We observed a more profound reduction in local cortical blood flow in TBI animals compared to healthy controls. Following TBI, CSD resulted in mitochondrial dysfunction and pathological signs of increased oxidative stress adjacent to the vasculature. We explored these findings further using electron microscopy and found that TBI and CSDs resulted in vascular morphological changes and mitochondrial cristae damage in astrocytes, pericytes and endothelial cells. Overall, we provide evidence that CSDs induce mitochondrial dysfunction, impaired cortical blood flow, and neurobehavioral deficits in the setting of TBI.

Highlights

Cortical spreading depolarization after TBI causes behavioral decline in rats.

Vasoconstriction and oligemia after cortical spreading depolarization is worse in TBI brains.

Spreading depolarization causes impaired mitochondrial function.

TBI and spreading depolarization result in constricted vessels and increased pericyte size.

TBI and spreading depolarization result in mitochondrial damage in vascular cells.

Graphical abstract
The balance between shear flow and extracellular matrix in ovarian cancer-on-chip
Authors: Chen Changchong , Boché Alphonse , Lopez Elliot , Peng Juan , Carreiras Franck , Schanne-Klein Marie-Claire , Chen Yong , Lambert Ambroise , Aimé Carole
Published: July 2023

Ovarian cancer is the most lethal gynecologic cancer in developed countries. Silent onset of the metastatic activity of ovarian tumor cells is factor for poor outcomes. In the tumor microenvironment, the extracellular matrix (ECM) and flow shear stress are known to play key roles in directing cell invasion. Hence, acute and tunable tools are critical to mimic scaffold and fluid for building clinically relevantin vitromodels. We have built an ovarian tumor-on-chip where tunable ECM models are easily seeded with tumor spheroids and integrated within a microfluidic chip. This allows the investigation of the crosstalk between the characteristics of the ECM models and shear stress on the migratory behavior and cellular heterogeneity of ovarian tumor cells. We vary the composition of the ECM playing with type I and IV collagens and laminin, and control the shear stress in the chip. This work shows that in the shear stress regime of the peritoneal cavity, the ECM plays a major role in driving individual or collective modes of migration. In the presence of basement membrane proteins, migration is more collective that on type I collagen regardless of shear stress level. In addition, with increasing shear stress, individual cell migration was enhanced, while no significant impact on collective migration could be measured. This highlights our ability to discriminate relevant parameters for onset and shifts of cell behavior using our in vitro models. Furthermore, we described the ability to shift cells from an epithelial phenotype to a more mesenchymal phenotype, which could allow us to describe the role of these parameters during epithelial-to-mesenchymal (EMT) transition as a continuous process. Finally, we conclude that the ECM should hold a central position inin vitrocancer models, to understand cell response and develop platforms for therapeutic development.
Detection and localization of conspecifics in ghost knifefish are influenced by the relationship between the spatial organization of receptors and signals
Authors: Ramachandra Keshav L , Milam Oak E , Pedraja Federico , Cornett Jenna , Marsat Gary
Published: July 2023

The detection and localization of signals relies on arrays of receptors and their spatial organization plays a key role in setting the accuracy of the system. Electrosensory signals in weakly electric ghost knifefish are captured by an array of receptors covering their body. While we know that spatial resolution for small objects, such as prey, is enhanced near the head due to a high receptor density, it is not clear how receptor organization influences the processing of global and diffuse signals from conspecifics. We investigated the detection and localization accuracy for conspecific signals and determined how they are influenced by the organization of receptors. To do so we modeled the signal, its spatial pattern as it reaches the sensory array, and the responses of the heterogeneous population of receptors. Our analysis provides a conservative estimate of the accuracy of detection and localization (specifically azimuth discrimination) of a conspecific signal. We show that beyond 20 cm the conspecific signal is less than a few percent the strength of the baseline self-generated signal. As a result, detection and localization accuracy decreases quickly for more distant sources. Detection accuracy at distances above 40 cm decreases rapidly and detection at the edge of behaviorally observed ranges might require attending to the signal for several seconds. Angular resolution starts to decrease at even shorter distances (30 cm) and distant signals might require behavioral or neural coding mechanisms that have not been considered here. Most importantly, we show that the higher density of receptors rostrally enhances detection accuracy for signal sources in front of the fish, but contributes little to the localization accuracy of these conspecific signals. We discuss parallels with other sensory systems and suggest that our results highlight a general principle. High receptor convergence in systems with spatially diffuse signals contributes to detection capacities, whereas in systems with spatially delineated signals, receptor density is associated with better spatial resolution.
Sensory symptoms across the lifespan in people with cerebral palsy
Authors: Lyons-Warren Ariel M , Guez-Barber Danielle , Thomas Sruthi P. , Tantry Evelyne K , Mahat Aditya , Aravamuthan Bhooma ,   Cerebral Palsy Research Network
Published: July 2023

Structured Abstract

AIM

To estimate prevalence of sensory symptoms in people with cerebral palsy (CP) across the lifespan.

METHOD

In this cross-sectional study, the self-reported Sensory Processing Scale Inventory (SPS-I) was administered via REDCap between 2/1/22 and 8/15/22 to people with CP or their caregivers enrolled in the online MyCP Community Registry. We determined the association between SPS-I scores and age (Pearson correlation) and functional status as assessed using five validated functional classification systems for CP (ANOVA). We hypothesized that sensory symptoms would differ between younger and older individuals with CP.

RESULTS

Of 155 responses (28% response rate, age 1-76 years, 34% male), 97% reported at least one bothersome sensory symptom. Total sensory symptoms decreased with age (R2=0.12, p<0.0001), driven by decreases in hyposensitivity symptoms (R2=0.32, p<0.0001), primarily tactile hyposensitivity (R2=0.29, p<0.0001). Sensory symptoms increased with greater functional impairment across all functional domains (ANOVA, p<0.0001). However, the age-specific decrease in hypo-sensitivities was most pronounced in people with the greatest gross motor functional impairment (R2=0.70, p=0.0004).

INTERPRETATION

Our findings suggest that hypo-sensitivity, primarily tactile sensitivity, decreases with age in people with CP. Future work should assess whether decreased hyposensitivity contributes to other age-related changes in CP like increased pain.

What this paper adds

Individuals with CP exhibit both hyper- and hypo-sensitivity across all sensory modalities

Hyposensitivity decreases with age in people with CP, independent of GMFCS level

Less hyposensitivity correlates with greater functional ability in people with CP

Of all sensory modalities, tactile hyposensitivity correlates most strongly with age.
A Natural Language Processing Algorithm for Classifying Suicidal Behaviors in Alzheimer’s Disease and Related Dementia Patients: Development and Validation Using Electronic Health Records Data
Authors: Zandbiglari Kimia , Hasanzadeh Hamid Reza , Kotecha Pareeta , Sajdeya Ruba , Goodin Amie J , Jiao Tianze , Adiba Farzana I , Mardini Mamoun T. , Bian Jiang , Rouhizadeh Masoud
Published: July 2023

This study aimed to develop a natural language processing algorithm (NLP) using machine learning (ML) and Deep Learning (DL) techniques to identify and classify documentation of suicidal behaviors in patients with Alzheimer’s disease and related dementia (ADRD). We utilized MIMIC-III and MIMIC-IV datasets and identified ADRD patients and subsequently those with suicide ideation using relevant International Classification of Diseases (ICD) codes. We used cosine similarity with ScAN (Suicide Attempt and Ideation Events Dataset) to calculate semantic similarity scores of ScAN with extracted notes from MIMIC for the clinical notes. The notes were sorted based on these scores, and manual review and categorization into eight suicidal behavior categories were performed. The data were further analyzed using conventional ML and DL models, with manual annotation as a reference. The tested classifiers achieved classification results close to human performance with up to 98% precision and 98% recall of suicidal ideation in the ADRD patient population. Our NLP model effectively reproduced human annotation of suicidal ideation within the MIMIC dataset. These results establish a foundation for identifying and categorizing documentation related to suicidal ideation within ADRD population, contributing to the advancement of NLP techniques in healthcare for extracting and classifying clinical concepts, particularly focusing on suicidal ideation among patients with ADRD. Our study showcased the capability of a robust NLP algorithm to accurately identify and classify documentation of suicidal behaviors in ADRD patients.