bluuebunny/crossref_metadata_2025 huggingface dataset:
Inserting Quantitative Literacy into the Human Physiology Lab Curriculum
Authors: Krontiris‐Litowitz Johanna
Published: November 2023

The practice of biology involves collection and interpretation of data sets that frequently require mathematical analysis or statistical tests. Therefore, it is important for students to build the skill set that enables them to analyze data, develop predicative numeric relationships, create models mathematical models the mimic physiological events and communicate ideas about data. Educators have identified a gap in the quantitative literacy (QL) or mathematical and computational preparation of future scientists. These skills are not part of the learning outcomes of traditional college math courses, however, they can be taught in the contextual situations found in discipline‐specific lab courses.

The objective of this study was to: 1) identify a set of QL learning objectives that could be embedded in a physiology lab curriculum and 2) develop pre‐test that could be used to probe student QL skill level. A set of five QL learning objectives framed the curriculum of a one semester undergraduate human physiology laboratory course (n=33). On the first day of class students were given a 7 question pretest that evaluated their understanding of quantitative scale, ability to develop computational strategies, capacity to communicate quantitative ideas in a text or tabular format, and their proficiency in extracting information and trends from graphs. For the remainder of the course, students performed lab protocols that supported content and QL learning objectives. At the end of the course student learning was assessed by comparing the results of the pre‐test to student performance on the lab notebooks and final exam. Analysis of the pre‐test scores showed that the instrument identified gaps in basic QL skills. Approximately 20–30 % of the students could not apply concepts of scale in order to correctly answer a question, extract information or inferences from a complex graph, or readily develop a computational strategy for a rate calculation. Analysis of student performance at the end of the course showed learning gains in these areas. These results indicate that the pretest was effective at disclosing disparities in student QL skills and serving as a benchmark for evaluating student learning gains.
Understanding how we understand: promoting research literacy during PhUn Week
Authors: Crecelius Anne R
Published: November 2023

Physiology Understanding (PhUn) Week is an outreach program that encourages connections between scientists and their local schools. Students (n=23) enrolled in a combined undergraduate and graduate Research in Sport and Health Science course served as visiting scientist teachers for a high school anatomy course at a non‐traditional charter school (24 participants). University students identified an original research article in the literature and a popular press source that mentioned that primary source and brought these to the classroom. The university students also designed a brief lesson to address: 1) the components of the primary research article, and 2) how well the popular press source translated the findings to a lay audience. Pairings of high school students spent approximately 30 min each with two different sets of university students. High school students were given a worksheet to record knowledge gained and university students were anonymously surveyed after the experience. Based on these quantitative survey results, university students enjoyed the experience, did not find it difficult to translate knowledge to an age‐appropriate level, learned something about themselves from the experience, and thought the high school students enjoyed and learned from the activity. Open‐ended responses supported these findings and addressed the willingness of the high school students to engage in conversations about the research process and future career plans. These results suggest that activities designed to promote research literacy can be enjoyable and engaging in this setting. Future work should address the effectiveness of this type of programing. In addition, this project successfully piloted PhUn Week activities into a non‐physiology specific course.

Support or Funding Information

The American Physiological Society provided PhUn Week promotional materials.
The Mechanisms of Gut‐dependent Protection against Cardiac Injury
Authors: Pier Marissa Lopez
Published: November 2023

The gut is the main location for immunological regulation and is influenced by the flora that reside there. This flora, also known as the gut microbiome, is necessary for maintaining immune health and disruptions in the microbiome result in systemic, metabolic and inflammatory disorders including obesity, diabetes, and cardiovascular disease. Therefore a possible approach to treat these disorders involves modulating the gut microbiome through the administration of probiotics. Probiotics are defined by the World Health Organization as, “live microorganisms that confer a health benefit to the host when consumed in adequate amounts.” Data from our laboratory indicate that a specific strain of probiotic, Bifidobacterium animalis sub‐species lactis 420 (B420), reduces the extent of cardiac injury following ischemia/reperfusion in a mouse model of myocardial infarction. This cardioprotection is attributed to a reduction in cardiac inflammation, however, it is unclear precisely how B420 mediates this effect. Here, we hypothesize that the mechanism of gut‐dependent cardioprotection observed in vivo is through epigenetic and post‐translational regulation of intestinal, epithelial and immune cell function. We further hypothesize that the initiation of this mechanism is not uniform throughout the GI tract, and may be regionally localized. To this end, we developed a system to track the probiotic in the gut to better understand where and how they interact with the gut microbiome. Indocyanine Green (ICG) is a near infrared(NIR) stable aqueous, sterile, fluorescent, and clinically effective agent. In this study we aim to develop an inexpensive and effective method to track B420 bacteria in the gut‐microbiome. ICG was cultured with B420 and analyzed with LagoX imaging software at NIR wavelengths. ICG did not inhibit growth of B420 culture, and was a suitable reagent for labeling B420 bacteria. The ICG‐B420 co‐culture was gavaged in a treatment group of C57BL/6 mice at 2mg/kg, while control mice received B420 only. The GI tract was imaged in vivo and ex vivo bioluminescence. Bacterial genomic DNA from C57BL/6 treated and untreated mice gut epithelia was quantified using B420 primers and quantitative PCR(qPCR), and verified localization of bacteria colonization observed during fluorescent imaging.

Support or Funding Information

Cardiovascular Training Grant in Biomedical Engineering NIH T32 training grant
The Calcineurin Homologous Protein‐1 Facilitates the Na+/H+ exchanger‐3 Traffic through the Golgi Complex and Impedes Traffic to the Early Endosomes
Authors: Crosby Garrett S , Babich Victor , Di Sole Francesca
Published: November 2023

Hypertension is a leading risk factor for cardiovascular and renal diseases, and a major burden for the health care system. It is characterized by disturbance in kidney function that increases sodium (Na+) re‐absorption and decreases Na+ output below Na+ intake. The Na+/H+ exchanger‐3 (NHE3) is a major regulator of body Na+, and blood volume and pressure. Physiological functions of NHE3 are dependent on NHE3 trafficking and precise localization to the cell surface. The Calcineurin Homologous Protein‐1 (CHP1) is a calcium‐binding protein and binding partner of NHE3. Defect in CHP1 action leads to hypotension and reduced cell surface NHE3 activity and protein expression. The goal of this study was to determine whether CHP1 effect on NHE3 function is via a control on NHE3 trafficking to and from the cell surface. NHE3‐mGFP alone or in combination with CHP1‐mRFP was expressed in opossum kidney (OK) cells and NHE3 localization to specific cellular compartments (determined using biomarkers) was analyzed by immunofluorescence. NHE3 co‐localized with biomarkers of the endoplasmic reticulum (PDI), Golgi Complex (GM130) and early endosomes (EEA1) after 24hrs, 48hrs, 72hrs and 96hrs of transfection (measured by the Mander's co‐localization coefficient). NHE3 and PDI co‐localization was steady for 48hrs after transfection but was rapidly reduced after 72hrs and 96hrs of transfection. NHE3 and GM130 co‐localization was abruptly increased after 48 hrs of transfection and reversed back to the 24hrs value after 96hrs of transfection. NHE3 co‐localization with EEA1 was steady through the time points under study. When NHE3 was co‐expressed with CHP1, NHE3 co‐localization with PDI did not change, while NHE3 co‐localization with GM130 or EEA1 was consistently reduced starting from 48hrs (30% reduction, NHE3 co‐localized with GM130) or 24hrs (20% reduction, NHE3 co‐localized with EEA1) of transfection. NHE3 and CHP1 co‐localization was constant through the time points under study. These findings suggest that CHP1: 1. co‐localized with NHE3 during its early steps in the biosynthetic pathway 2. facilitated NHE3 traffic through the Golgi Complex, while it impeded NHE3 traffic to the early endosomes. This study advances our understanding on the role of CHP1 in the control of NHE3 function and blood pressure.
Lipid droplets in steatotic liver disease
Authors: Bilson Josh , Scorletti Eleonora
Published: November 2023

Purpose of review

This review aims to discuss the most recent evidence exploring the role of lipid droplets in steatotic liver disease (SLD). We highlight the breadth of mechanisms by which lipid droplets may contribute to the progression of SLD with a particular focus on the role of lipid droplets as inducers of mechanical stress within hepatocytes and genetic mutations in lipid droplet associated proteins. Finally, this review provides an update on clinical trials exploring the therapeutic potential and strategies targeting lipid droplets.

Recent findings

The size, composition and location of hepatic lipid droplets strongly influence the pathological role of these organelles in SLD. Emerging studies are beginning to elucidate the importance of lipid droplet induced hepatocyte mechanical stress. Novel strategies targeting lipid droplets, including the effects of lipid droplet associated protein mutations, show promising therapeutic potential.

Much more than a histological feature, lipid droplets are complex heterogenous organelles crucial to cellular metabolism with important causative roles in the development and progression of SLD. Lipid droplet induced mechanical stress may exacerbate hepatic inflammation and fibrogenesis and potentially contribute to the development of a pro-carcinogenic hepatic environment. The integration of advancements in genetics and molecular biology in upcoming treatments aspires to transcend symptomatic alleviation and address the fundamental causes and pathological development of SLD.
Vibrio methylphosphonaticus sp. nov., a methylphosphonate-decomposing bacterium isolated from surface seawater in the Xisha Islands, PR China
Authors: Wang Wei , Liu Mei , Cao Bingbing , Liu Yi , Huang Keyi , Ding Yunqi , Xu Ziqing , Sun Fucheng , Zhang Yunxiao , Niu Wentao , Tian Peng , Huang Dingyong , Wang Xiaolei , Xiao Jiaguang
Published: November 2023

A Gram-stain-negative, facultative anaerobic, methylphosphonate-decomposing, motile by a polar flagellum and rod-shaped marine bacterium, designated S4B1T, was isolated from the surface seawater collected from the Yongle Atoll (Xisha Islands, PR China). The pairwise alignment showed the highest sequence similarity of 97.5 and 96.6 % to

Vibrio aestuarianus

subsp.

cardii

12_122_3T3T and

Vibrio atypicus

HHS02T, respectively. Phylogenetic analysis based on 16S rRNA gene and the phylogenomic analysis of single-copy genes showed that strain S4B1T belonged to the genus

Vibrio

and formed a close branch with Vibrio qingdaonensis ZSDZ65T. Growth of strain S4B1T occurred at 4–30 °C (optimum, 28 °C), at pH 6.0–8.0 (optimum, pH 7.0) and in the presence of 2–7 % (w/v) NaCl (optimum, 3 %). The predominant fatty acids (>10 %) were C16 : 0, iso-C16 : 0 and summed feature 3 (C16 : 1

 ω7c or/and C16 : 1
 ω6c). The DNA G+C content of the assembled genomic sequence was 44.3 mol%. Average nucleotide identity (ANI) values between S4B1T and its reference species were lower than the threshold for species delineation (95–96 %), in which its highest ANI value with V. qingdaonensis ZSDZ65T was 87.0 %. In silico DNA–DNA hybridization further showed that strain S4B1T had less than 70 % similarity to its relatives. On the basis of the polyphasic evidence, strain S4B1T is proposed to represent a novel species of the genus

Vibrio

, for which the name Vibrio methylphosphonaticus sp. nov. is proposed. The type strain is S4B1T (=KCTC 92311T=MCCC 1K06168T).
An online tool for correcting verification bias when validating electronic phenotyping algorithms
Authors: Bhasin Ajay , Bielinski Suzette J. , Kho Abel N. , Larson Nicholas B. , Rasmussen-Torvik Laura
Published: November 2023

Computable or electronic phenotypes of patient conditions are becoming more commonplace in quality improvement and clinical research. During phenotyping algorithm validation, standard classification performance measures (i.e., sensitivity, specificity, positive predictive value, negative predictive value, and accuracy) are commonly employed. When validation is performed on a randomly sampled patient population, direct estimates of these measures are valid. However, it is common that studies will sample patients conditional on the algorithm result, leading to a form of bias known as verification bias. The presence of verification bias requires adjustment of performance measure estimates to account for this sampling bias. Herein, we describe the appropriate formulae for valid estimates of sensitivity, specificity, and accuracy to account for verification bias. We additionally present an online tool to adjust algorithm performance measures for verification bias by directly taking the sampling strategy into consideration and recommend use of this tool to properly estimate algorithm performance for phenotyping validation studies.
Predictors of High-grade Squamous Intraepithelial Lesion treatment failure
Authors: Botting-Provost S. , Koushik A. , Trottier H. , Coutlée F. , Mayrand MH
Published: November 2023

Objective

To estimate the association between several risk factors and high-grade squamous intraepithelial lesions (HSIL) treatment failure in order to identify predictors.

Methods

The study population included 1,548 Canadian women treated for HSIL who participated in a randomized control trial. HSIL treatment failure was the presence of histologically confirmed HSIL or worse during the two-year follow-up period. This nested-case control study included all 101 cases of treatment failure and controls that were matched 1:1 on treatment center and date of failure. Conditional logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) between each potential predictor and HSIL treatment failure. Independent variables that were examined included age, parity, smoking status, number of sexual partners, condom use, method of contraception, margins, number of passes, diagnosis on conisation, genotype, and number of infecting types. Interactions between smoking and margins and genotype were evaluated.

Results

Having positive vs. negative margins (adjusted OR=4.05, 95% CI 1.57-10.48) and being positive forHuman Papillomavirus(HPV)16 and/or HPV18 vs. any other type (adjusted OR=2.69, 95% CI 1.32-5.49) were predictors of HSIL treatment failure in multivariable models. ORs suggested that older age, more severe lesions, and single-type infections may be at a higher risk of treatment failure but were not statistically significant. The ORs for smoking status, number of sexual partners, condom use, contraception, parity, and number of passes were near the null value. We did not observe any evidence of interaction between smoking and genotype, nor between margins and genotype.

Conclusion

Only positive margins and HPV16/18 positivity were predictors for being diagnosed with HSIL or worse within two years of treatment. However, we do not recommend automatic retreatment of those with positive margins because over 90% of those with positive margins did not fail treatment. The predictive value of HPV16 and HPV18 for HSIL treatment failure suggests that high coverage vaccination programs should contribute to a significant reduction in residual/recurrent disease.
Using electronic health record data to determine the safety of aqueous humor liquid biopsies for molecular analyses
Authors: Wolf Julian , Chemudupati Teja , Kumar Aarushi , Franco Joel A. , Montague Artis A. , Lin Charles C. , Lee Wen-Shin , Fisher A. Caroline , Goldberg Jeffrey L. , Mruthyunjaya Prithvi , Chang Robert T. , Mahajan Vinit B.
Published: November 2023

Purpose

Knowing the surgical safety of anterior chamber liquid biopsies will support the increased use of proteomics and other molecular analyses to better understand disease mechanisms and therapeutic responses in patients and clinical trials. Manual review of operative notes from different surgeons and procedures in electronic health records (EHR) is cumbersome, but free-text software tools could facilitate efficient searches.

Design

Retrospective case series.

Participants

1418 aqueous humor (AH) liquid biopsies from patients undergoing intraocular surgery.

Methods

Natural language unstructured free-text EHR searches were performed using the Stanford Research Repository (STARR) cohort discovery tool to identify complications associated with anterior chamber paracentesis and subsequent endophthalmitis. Complications of the surgery unrelated to the biopsy were not reviewed.

Main Outcome Measures

Biopsy associated intraoperative complications and endophthalmitis.

Results

1418 AH liquid biopsies were performed by 17 experienced surgeons. EHR free-text searches were 100% error-free for surgical complications, >99% for endophthalmitis (<1% false positive), and >93.6% for anesthesia type, requiring manual review for only a limited number of cases. More than 85% of cases were performed under local anesthesia without ocular muscle akinesia. Although the most common indication was cataract (50.1%), other diagnoses included glaucoma, diabetic retinopathy, uveitis, age-related macular degeneration, endophthalmitis, retinitis pigmentosa, and uveal melanoma. A 50-100μL sample was collected in all cases using either a 30-gauge needle or a blunt cannula via a paracentesis. The median follow-up was more than seven months. There was only one minor complication (0.07%) identified: a case of a small tear in Descemet’s membrane without long-term sequelae. No other complications occurred, including other corneal injuries, lens or iris trauma, hyphema, or suprachoroidal hemorrhage. There was no case of postoperative endophthalmitis.

Conclusions

Anterior chamber liquid biopsy during intraocular surgery is a safe procedure and may be considered for large-scale collection of AH samples for molecular analyses. Natural language free-text EHR searches are an efficient approach to reviewing intraoperative procedures.
TREVIXMBD: A Transcriptional Regulation-driven Variational Inference Model to Speculate Gene Expression Mechanism with Integration of Single-cell Multi-omics
Authors: Cao Lan , Zhang Wenhao , Zeng Feng , Wang Ying
Published: November 2023

Single-cell multi-omics technology enables the concurrent measurement of multiple molecular entities, making it critical for unraveling the inherent gene regulation mechanisms driving cell heterogeneity. However, existing multi-omics techniques have limitations in capturing the intricate regulatory interactions among these molecular components. In this study, we introduce TREVIXMBD(Transcriptional REgulation-driven Variational Inference), a novel method that integrates the well-established gene regulation structure with scRNA-seq and scATAC-seq data through an advanced Bayesian framework. TREVIXMBDmodels the generation of gene expression profiles in individual cells by considering the integrated influence of three fundamental biological factors: accessibility of cis-regulatory elements regions, transcription factor (TF) activities and regulatory weights. TF activities and regulatory weights are probabilistically represented as latent variables, which capture the inherent gene regulatory significance. Hence, in contrast to gene expression, TF activities and regulatory weights that depict the cell states from a more intrinsic perspective, can keep consistent across diverse datasets. TREVIXMBDexhibits superior performance when compared to baseline methods in a variety of biological analyses, including cell typing, cell development tracking, and batch effect correction, as validated through comprehensive benchmarking. Moreover, TREVIXMBDcan reveal variations in TF-gene regulation relationships across cells. The pretrained TREVIXMBDmodel can work even when only scRNA-seq is available. Overall, TREVIXMBDintroduces a pioneering biological-mechanism-driven framework for elucidating cell states at a gene regulatory level. The model’s structure is adaptable for the inclusion of additional biological factors, allowing for flexible and more comprehensive gene regulation analysis.
scCross: A Deep Generative Model for Unifying Single-cell Multi-omics with Seamless Integration, Cross-modal Generation, and In-silico Exploration
Authors: Yang Xiuhui , Mann Koren K. , Wu Hao , Ding Jun
Published: November 2023

Single-cell multi-omics illuminate intricate cellular states, yielding transformative insights into cellular dynamics and disease. Yet, while the potential of this technology is vast, the integration of its multifaceted data presents challenges. Some modalities have not reached the robustness or clarity of established scRNA-seq. Coupled with data scarcity for newer modalities and integration intricacies, these challenges limit our ability to maximize single-cell omics benefits. We introduce scCross: a tool adeptly engineered using variational autoencoder, generative adversarial network principles, and the Mutual Nearest Neighbors (MNN) technique for modality alignment. This synergy ensures seamless integration of varied single-cell multi-omics data. Beyond its foundational prowess in multi-omics data integration, scCross excels in single-cell cross-modal data generation, multi-omics data simulation, and profound in-silico cellular perturbations. Armed with these capabilities, scCross is set to transform the field of single-cell research, establishing itself in the nuanced integration, generation, and simulation of complex multi-omics data.
Intellectual disability and neurogenesis defects associated with increased turnover of an O-GlcNAcase variant
Authors: Authier Florence , Attianese Benedetta , Bartual Sergio Galan , Mitchell Conor W. , Ferenbach Andrew T. , Doummar Diane , Charles Perrine , Mignot Cyril , Keren Boris , van Aalten Daan M. F.
Published: November 2023

Intellectual Disability (ID) is characterised by substantial limitations in cognitive function and adaptive behaviour, affecting 1-3% of the population. Protein O-GlcNAcylation is a posttranslational modification of nucleocytoplasmic proteins regulated by two opposing enzymes: O-GlcNAc transferase (OGT) and O-GlcNAcase (OGA). Recently, missense mutations inOGThave been shown to segregate with ID, associated with compensatory reduction of OGA expression, although it is unclear whether this is mechanistically linked to the disease. Here, we report a patient with a K885Nde novomissense mutation in the C-terminal pseudo histone acetyltransferase domain of OGA, associated with ID, infantile spasms and autism. While the K885N mutation does not affect protein stability or activityin vitro, this residue sits in the canonical GCN5 acetyltransferase family acceptor binding cleft. Strikingly, mouse embryonic stem cells edited to harbour the K885N mutation show increased OGA turnover and defects in neurogenesis. Taken together, these data suggest a link between missense mutations in OGA and ID.
A distinct T cell receptor signature associates with cardiac outcome in myocardial infarction patients
Authors: Le Gouge Kenz , Ashour DiyaaElDin , Heinrichs Margarete , Stys Paul , Barennes Pierre , Stangl Verena , Rech Lavinia , Hoefler Gerald , Kashofer Karl , Gassenmaier Tobias , Boivin-Jahns Valerie , Jahns Roland , Hofmann Ulrich , Schmitt Dominik , Frey Anna , Störk Stefan , Frantz Stefan , Rainer Peter P. , Ramos Gustavo Campos , Mariotti-Ferrandiz Encarnita
Published: November 2023

Myocardial infarction (MI) is associated with an inflammatory process mainly attributed to innate immune components. Very recently, the role of T-cells in both inflammation and healing has been suggested through various human and mouse studies. Previous studies showed that CD4+ and CD8+ T cells affect post-MI repair but did not investigate how to leverage T cell biology to predict post-MI outcomes in patients. For instance, the antigenic trigger of T-cells is still unknown in human. Indeed, others and we identified T-cell specific for myosin infiltrating the myocardium in mouse models of MI, recent studies identified expanded clones in human myocardium, altogether suggesting a tissue-specific T-cell activation. However, it is still unclear how acute post-MI immune responses shape long-term cardiac functional outcomes in individual patients. In this study, we analyzed the role of T-cell in predicting post-MI repair by analyzing the T-cell receptor (TCR) repertoire. Indeed, the TCR repertoire is now considered as a marker of the clinical status of individuals. Previous studies in infectious but also autoimmune contexts showed the potential of the TCR repertoire to predict the disease. Therefore, assessing the dynamic changes in global TCR repertoires may provide valuable information about the antigen-specific immune responses underlying post-MI healing. In our study, we carefully selected patients that suffered from MI on a prospective cohort. The TCR repertoire has been analyzed by next generation sequencing at the index hospitalization with the aim to identify features predict of their healing outcome assessed at 12 months post-MI. While no major variations have been found in diversity of TCR gene usage, we identified unique TCR signatures predicting one-year cardiac functional outcomes. Our result enables early immune-based risk stratification of MI patients and calls for larger studies to develop novel predictive biomarkers and possibly new therapeutics.
Diverging the anthracycline class of anti-cancer drugs for superior survival of acute myeloid leukemia patients
Authors: Qiao Xiaohang , van der Zanden Sabina Y. , Li Xiaoyang , Tan Minkang , Zhang Yunxiang , Song Ji-Ying , van Gelder Merle A. , Hamoen Feija L. , Janssen Lennert , Zuur Charlotte L. , Pang Baoxu , van Tellingen Olaf , Li Junmin , Neefjes Jacques
Published: November 2023

The efficacy of anthracycline-based chemotherapeutics, which include doxorubicin and its structural relatives daunorubicin and idarubicin, remains almost unmatched in oncology, despite a side effect profile including cumulative dose-dependent cardiotoxicity, therapy-related malignancies and infertility. Detoxification of anthracyclines while preserving their anti-neoplastic effects is arguably a major unmet need in modern oncology, as cardiovascular complications that limit anti-cancer treatment are now a leading cause of morbidity and mortality among the 17 million cancer survivors in the U.S.. To address this, we examined different clinically relevant anthracycline drugs with respect to a series of features including mode of action (chromatin and DNA damage), bio-distribution, anti-tumor efficacy and cardiotoxicity in pre-clinical models and patients. We show that different anthracycline drugs have surprisingly individual efficacy and toxicity profiles. In particular, aclarubicin stands out in pre-clinical models and clinical trials as it potently kills cancer cells, does not induce therapy-related malignancies or cardiotoxicity, and can be safely administered even after a maximum cumulative dose of either ida- or doxorubicin has been reached. Retrospective analysis of aclarubicin used in second-line treatment of relapsed/refractory AML patients showed similar survival effects to its use in first line, leading to an almost 25% increase in 5-year overall survival. Considering individual anthracyclines as different drugs provides new treatment options that strongly improve survival of cancer patients while limiting the toxic side-effects.

Abstract Figure
Natural immune boosting can cause synchrony in susceptibility and outbreaks of respiratory infections with rapidly waning immunity
Authors: Pritchard Mark G. , Cavany Sean M. , Dunachie Susanna J. , Medley Graham F. , Turtle Lance , Donnelly Christl A. , Horby Peter W. , Cooper Ben S.
Published: November 2023

Natural immune boosting is a mechanism in which re-exposure to a pathogen while immunity is waning can prolong protection against reinfection. Its role in viral respiratory-tract infections with rapidly waning immunity has not been studied in mathematical models. Here we use a deterministic compartmental model to investigate the effect of immune boosting on such infections, and how the reduction in transmission due to non-pharmaceutical interventions during the covid-19 pandemic could affect immune waning and boosting. We find that immune boosting can introduce unstable equilibria into the model, and we show in simulations that this can amplify, or even cause, oscillations in infections and disease outbreaks. After periods of reduced transmissibility, representing non-pharmaceutical interventions, simulations with more immune boosting exhibit larger rebound outbreaks that occurred sooner. Observed incidence of respiratory syncytial virus infection in Scotland between 2016 and 2023 can be equally explained by models with high levels of immune boosting, and models without natural immune boosting. To produce the same incidence, models with more immune boosting require a greater mean transmissibility, suggesting that models underestimating natural immune boosting will also underestimate transmissibility.
Improving SARS-CoV-2 variants monitoring in the absence of genomic surveillance capabilities: a serological study in Bolivian blood donors in October 2021 and June 2022
Authors: Inchauste Lucia , Nurtop Elif , Bautista Machicado Lissete , Leigue Roth Yanine , Lenz Gonzales Shirley , Herrera Maria Luisa , Mina Villafan Katty , Mamani Mamani Pedro , Ramos Espinoza Marcelo , Pavel Suarez Juan Carlos , Garcia Copa Juan Cansio , Leigue Zabala Yitzhak , Arancibia Cardozo Etzel , Gallian Pierre , de Lamballerie Xavier , Priet Stéphane
Published: November 2023

Unlike genomic data, serological data have not been previously leveraged to evaluate the SARS-CoV-2 variants circulation. In Bolivia, sustained genomic surveillance capacities were lacking especially at the beginning of the pandemic. In 2021 and 2022 we estimated the prevalence of anti-SARS-CoV-2 antibodies in Bolivian blood donors and explored the feasibility of using virus serum neutralization data for variants thought to have circulated to map their circulation across all departments over a year-long follow-up period. Anti-S1 and anti-NCP SARS-CoV-2 IgGs were studied, along with virus neutralization tests for ancestral-D614G, Gamma, Delta, and Omicron BA.1 lineages of SARS-CoV-2. Between 2021 and 2022, the overall prevalence of anti-S1 and anti-NCP antibodies increased reaching values over 90%, demonstrating that a large proportion of the Bolivian population was no longer naïve to the virus. Viral neutralization data, analyzed through multiple approaches, revealed the spread of the Gamma variant up to 2021, particularly impacting northern departments. In 2022, Gamma continued to circulate in southernmost departments of the country and the emergence of Omicron BA.1 was detected. These trends align with publicly available genomic data from neighboring countries. Our serological analyses successfully identified both new antigenic groups, such as Omicron BA.1, and individual variants related to previously circulating groups, such as Delta. The study contributes insights into overall population immunity to SARS-CoV-2 and variant-specific immunity levels across different regions of Bolivia. It also emphasizes the potency of seroprevalence studies in informing public health decisions and underscore their value in capturing the initial phases of emerging epidemics when variant diversity is limited, facilitating timely genomic surveillance setup.
The association between parental, obstetric, socioeconomic, and lifestyle factors and the development of childhood obesity: A Danish Cohort Study
Authors: Christiansen Elizabeth la Cour , Thagaard Ida Näslund , Hedley Paula L. , Lautrup Hansen Majbrit Johanne , Frithioff-Bøjsøe Christine , Larsen Torben , Holm Jens-Christian , Christiansen Michael , Krebs Lone
Published: November 2023

Background

Childhood obesity is a multifactorial disease with complex etiology. Obstetrical factors are seldom taken into considerations.

Objectives

To investigate the association between parental, obstetric and lifestyle characteristics, and childhood overweight and obesity.

Methods

This retrospective cohort study evaluated associations between birthweight, pre-pregnancy BMI, birth mode, paternal BMI, family history of obesity, parental status, and maternal socioeconomic status and the outcome variable childhood overweight and obesity using logistic regression. Data regarding parental and childhood characteristics were collected through self-administered questionnaires, and obstetric information was retrieved from the Danish Medical Birth Registry.

Results

The incidence of childhood overweight and obesity was 11.3 % at a median (IQR) age of 6.51 years (IQR = 2.84). In obese mothers and children who were macrosomic at birth (birthweight ≥4,500 g), the incidence was 21.6% and 23.4%, respectively.

Risk factors for childhood overweight and obesity were macrosomia, (aOR 2.34, 95% CI 1.24-2.19), maternal- and (aOR 2.48, 95% CI 1.78-3.45) paternal overweight and obesity (aOR 2.17, 95% CI 1.44-3.34) and birthweight z-score (aOR 1.13, 95% CI 1.03-1.23). Combining maternal obesity and a macrosomic child gave the highest risk (aOR 7.49, 95% CI 2.05-24.86) Other predictors were divorced-(aOR 2.04, 95% CI 1.13-3.57) and living as a single parents (aOR 3.80, 95% CI 1.31-10.16).

Conclusions

Macrosomia combined with maternal obesity was the strongest risk factor for childhood overweight and obesity. Other individual risk factors are parental obesity and socioeconomic factors. This supports the role of lifestyle modification, education-based policies and interventions to prevent high birth weight in counteracting childhood obesity.
Genetic analysis of 104 pregnancy phenotypes in 39,194 Chinese women
Authors: Xiao Han , Li Linxuan , Yang Meng , Zeng Jingyu , Zhou Jieqiong , Tao Ye , Zhou Yan , Cai Mingzhi , Liu Jiuying , Huang Yushan , Zhong Yuanyuan , Liu Panhong , Cao Zhongqiang , Mei Hong , Cai Xiaonan , Hu Liqin , Zhou Rui , Xu Xun , Yang Huanming , Wang Jian , Zhu Huanhuan , Zhou Aifen , Jin Xin
Published: November 2023

Maternity is a special period in a woman’s life that involves substantial physiological, psychological, and hormonal changes. These changes may cause alterations in many clinical measurements during pregnancy, which can be used to monitor and diagnose maternal disorders and adverse postnatal outcomes. Exploring the genetic background of these phenotypes is key to elucidating the pathogenesis of pregnancy disorders. In this study, we conducted a large-scale molecular biology analysis of 104 pregnancy phenotypes based on genotype data from 39,194 Chinses women. Genome- wide association analysis identified a total of 407 trait-locus associations, of which 75.18% were previously reported. Among the 101 novel associations for 37 phenotypes, some were potentially pregnancy-specific and worth further experimental investigation. For example,ESR1with fasting glucose, hemoglobin, hematocrit, and several leukocytoses;ZSCAN31with blood urea nitrogen. We further performed pathway- based analysis and uncovered at least one significant pathway for 24 traits, in addition to previously known functional pathways, novel findings included birthweight with “Reactome signaling by NODAL”, twin pregnancy with “Reactome mitotic G1-G1/S phases”. The partitioning heritability analysis recapitulated known trait-relevant tissue/cell types, and also discovered interesting results including twin pregnancy with “embryoid bodies” cell-type enrichment, the delivery type cesarean section with “fallopian tube”, and birth weight with “ovary and embryonic stem cells”. In terms of both sample size and the variety of phenotypes, our work is one of the largest genetic studies of pregnancy phenotypes across all populations. We believe that this study will provide a valuable resource for exploring the genetic background of pregnancy phenotypes and also for further research on pregnancy-related diseases and adverse neonatal outcomes.
Unveiling the Impact of Arsenic Toxicity on Immune Cells in Atherosclerotic Plaques: Insights from Single-Cell Multi-Omics Profiling
Authors: Makhani Kiran , Yang Xiuhui , Dierick France , Subramaniam Nivetha , Gagnon Natascha , Ebrahimian Talin , Wu Hao , Ding Jun , Mann Koren K.
Published: November 2023

Millions worldwide are exposed to elevated levels of arsenic. This significantly increases their risk of developing atherosclerosis, a pathology primarily driven by immune cells. While the impact of arsenic on immune cell populations in atherosclerotic plaques has been broadly characterized, cellular heterogeneity is a substantial barrier to in-depth examinations of the cellular dynamics for varying immune cell populations. Here, we present one of the first single-cell multi-omics profiling of atherosclerotic plaques in apolipoprotein E knockout (apoE-/-) mice to understand the transcriptomic and epigenetic changes in various immune cells induced by arsenic. Our data reveal that arsenic alters the transcriptional profile of macrophages in a subtype-specific manner with implicated shifts in cell-cell interaction and cell fate predictions. Additionally, our data suggest that arsenic-mediated changes in chromosome accessibility are more profound than their effects on the transcriptome, hence revealing markers of arsenic exposure and potential targets of interventions.

Teaser

Arsenic changes gene expression and epigenome primarily of macrophages in atherosclerotic plaque, suggesting intervention targets.
A Unified Approach to Investigating 4 dpf Zebrafish Larval Behaviour through a Standardised Light/Dark Assay
Authors: Hillman Courtney , Kearn James , Parker Matthew O.
Published: November 2023

Zebrafish have emerged as a dynamic research model in the domains of neuropsychopharmacology, biological psychiatry and behaviour. Working with larvae ≤ 4 days post-fertilisation (dpf) offers an avenue for high-throughput investigation whilst aligning with the 3Rs principles of animal research. The light/dark assay, which is the most used behavioural assay for larval neuropharmacology research, lacks experimental reliability and standardisation. This study aimed to formulate a robust, reproducible and standardised light/dark behavioural assay using 4 dpf zebrafish larvae. Considerable between-batch and inter-individual variability was found, which we rectified with a normalisation approach to ensure a reliable foundation for analysis. We then identified that 5-minute light/dark transition periods are optimal for locomotor activity. We also found that a 30-minute acclimation in the light was found to produce significantly increased dark phase larval locomotion. Next, we confirmed the pharmacological predictivity of the standardised assay using ethanol which, as predicted, caused hyperlocomotion at low concentrations and hypolocomotion at high concentrations. Finally, the assay was validated by assessing the behavioural phenotype of hyperactive transgenic (adgrl3.1-/-) larvae, which was rescued with psychostimulant medications. Our standardised assay not only provides a clear experimental and analytical framework to work with 4 dpf larvae, but also facilitates between-laboratory collaboration using our normalisation approach.
Population genomic history of the endangered Anatolian and Cyprian mouflons in relation to worldwide wild, feral and domestic sheep lineages
Authors: Atağ Gözde , Kaptan Damla , Yüncü Eren , Vural Kıvılcım Başak , Mereu Paolo , Pirastru Monica , Barbato Mario , Leoni Giovanni Giuseppe , Güler Merve N. , Er Tuğçe , Eker Elifnaz , Yazıcı Tunca Deniz , Kılıç Muhammed Sıddık , Altınışık N. Ezgi , Çelik Ecem Ayşe , Miranda Pedro Morell , Dehasque Marianne , Floridia Viviana , Götherström Anders , Bilgin C. Can , Togan İnci , Günther Torsten , Özer Füsun , Hadjisterkotis Eleftherios , Somel Mehmet
Published: November 2023

Once widespread in their homelands, Anatolian mouflon (Ovis gmelini anatolica) and Cyprian mouflon (Ovis gmelini ophion) were driven to near extinction during the 20th century and are currently listed as endangered populations by the IUCN. While the exact origins of these lineages remain unclear, they have been suggested to be close relatives of domestic sheep or remnants of proto-domestic sheep groups. Here, we study whole genome sequences of n=5 Anatolian mouflons and n=10 Cyprian mouflons in terms of population history and diversity, relative to eight other extant sheep lineages. We find reciprocal genetic affinity between Anatolian and Cyprian mouflons and domestic sheep, higher than all other studied wild sheep genomes, including the Iranian mouflon (Ovis gmelini). Despite similar recent population dynamics, Anatolian and Cyprian mouflons exhibit disparate diversity levels, which can potentially be attributed to founder effects, island isolation, introgression from domestic lineages, or different bottleneck dynamics. The lower relative mutation load found in Cyprian compared to Anatolian mouflons suggests the purging of recessive deleterious variants in the former. This agrees with estimates of a long-term small effective population size in the Cyprian mouflon. Both subspecies harbor considerable numbers of runs of homozygosity (ROH) blocks <2 Mb, which reflects the effect of small population size. Expanding our analyses to worldwide wild and feralOvisgenomes, we observe varying viability metrics among different lineages, and a limited consistency between viability metrics and conservation status. Factors such as recent inbreeding, introgression, and unique population dynamics may contribute to the observed disparities.
Bioconversion of Glucose-Rich Lignocellulosic Wood Hydrolysates to 3-Hydroxypropionic Acid and Succinic Acid using EngineeredSaccharomyces cerevisiae
Authors: Bottoms Scott , Mürk Christina , Peng Huadong , Ledesma-Amaro Rodrigo , Loog Mart
Published: November 2023

Background

3-hydroxypropionic acid (3-HP) and succinic acid (SA) were announced as two of the top twelve value-added platform chemicals from biomass out of a group of over 300 potential compounds that could be made from biomass in a government report in 2004 (Werpy and Petersen, 2004) and in an updated report in 2010 (Bozell and Petersen, 2010). The screening criteria used in the report classified 3-HP and SA as direct petroleum replacement building block chemicals. 3-HP is a precursor to several high-value compounds, such as acrylic acid, 1,3-propanediol, acrylamide, and methyl acrylates, that ultimately end up in products such as fibers, contact lenses, diapers, fabric coatings, and other super absorbent polymers (SAPs). SA is a high-value platform chemical used in polyester production and a precursor for nylon and other bioplastics. Additionally, these reports identified pathways to building block compounds from sugars. Yeast fermentations were identified in these reports as a preferred potential pathway to 3-HP and SA production from sugars because of yeasts’ natural low pH tolerance.

Results

The laboratory strainSaccharomyces cerevisiaeBY4741 was engineered to produce either 3-HP or SA. These yeasts can convert fermentable sugars from glucose-rich lignocellulosic hardwood feedstocks into organic acid products such as 3-HP and SA under low pH conditions using exponential fed-batch cultivation strategies. Glucose-rich wood sugars provided a better growth environment for the engineered yeast strains, increasing production titers by 6.1 and 6.5 times for SA and 3-HP, respectively.

Conclusions

This study shows the potential of locally produced glucose-rich wood sugars to increase the production of platform chemicals necessary in the production of biobased polymers by engineered yeast cell factories.
Benchmarking sample pooling for epigenomics of natural populations
Authors: Daniels Ryan J. , Meyer Britta S. , Giulio Marco , Signorini Silvia G. , Riccardi Nicoletta , Torre Camilla Della , Weber Alexandra A.-T.
Published: November 2023

Interest in the role of DNA methylation (DNAm) has grown in ecological and evolutionary research of natural populations. While researchers are typically interested in comparing population-level variation, individual sequencing is the current standard. Natural populations have low effect sizes and thus need large sample sizes to detect differences. The cost of sequencing the necessary samples can be prohibitive in DNAm work. Pooling DNA before library preparation is a powerful tool to reduce costs but no recommendations exist for DNAm pooling in ecology-epigenetics research. We test if pooled and individual libraries provide similar global and region-specific DNA methylation signals in a natural system of response to pollution. We generated whole-epigenome data for two freshwater invasive molluscs (Corbicula fluminaandDreissena polymorpha) collected from a polluted and unpolluted locality, Lake Maggiore, Italy. Our results support that pooling effectively captures the same genome-wide and global treatment-level signals as individual libraries but we note that pooled libraries yielded orders of magnitude more input data and differentially-methylated regions (DMRs) detected compared with individual libraries. We estimated greatly lower power for regions from individual libraries compared with pooled libraries. The post-hoc process of computationally pooling data from individual libraries produced results comparable to pooled libraries in volumes but had discrepancies between DMRs. We discuss the possible causes for the discrepancies and put our results in the context of the benefits and drawbacks of sample pooling for epigenomics of natural populations.