bluuebunny/crossref_metadata_2025 huggingface dataset:
Pregnancy History and Estradiol Influence Spatial Memory, Hippocampal Plasticity, and Inflammation in Middle-aged Rats
Authors: Puri Tanvi A. , Lieblich Stephanie E. , Ibrahim Muna , Galea Liisa A. M.
Published: June 2024

Pregnancy and motherhood (parity) can have long-term effects on cognition and brain aging in both humans and rodents. Estrogens are related to cognitive function and neuroplasticity. Estrogens can improve cognition in postmenopausal women, but the evidence is mixed, in part due to differences in hormone therapy dose and composition. In addition, past pregnancy influences brain aging and cognition, with earlier age of first pregnancy being associated with poorer outcomes with aging. However, few studies have examined specific features of pregnancy history such as the age of first pregnancy or the possible mechanisms underlying these changes. We examined whether maternal age at first pregnancy and estradiol treatment differentially affected hippocampal neuroplasticity, inflammation, activation, and cognition in middle-age. Thirteen-month-old rats (who were nulliparous (never mothered) or previously primiparous (had a litter) at 3 months or 7 months) received daily injections of estradiol (or sesame oil vehicle) for sixteen days and were tested on the Morris Water Maze. An older age of first pregnancy was associated with impaired spatial memory but improved performance on reversal training, and increased new neurons in the ventral hippocampus compared to the other groups. Estradiol decreased total activation and percent activation of new neurons in the dorsal hippocampus, regardless of parity history. Estradiol also decreased the production of anti-inflammatory cytokines based on age of first pregnancy. This work suggests that estradiol affects neuroplasticity and neuroinflammation in middle age, and that pregnancy history can have long lasting effects on hippocampus structure and function.
Differential Gene Expression in MRI-classified Glioblastoma
Authors: Rhodes Christopher T. , Wang Yufeng , Lin Chin-Hsing Annie
Published: June 2024

Previous characterization of the genome and transcriptome of glioblastoma (GBM) has revealed molecular alterations that potentially drive GBM pathogenesis and heterogeneity1-6. These open-resources are evolving, such as The Cancer Genome Atlas (TCGA) and The Cancer Imaging Atlas (TCIA) at the National Institute of Health comprising a large cohort of molecular and MRI data. Yet, no report deciphers the link between molecular signatures and MRI-classified GBM. The necessity to re-form molecular and imaging data motivated our computational approach to integrate TCIA and TCGA datasets derived from GBM. We uncovered common and distinct molecular signatures across GBM patients and specific to tumor locations, respectively. Despite heterogeneity in GBM, the top 12 genes from our analysis highlights that the dysregulation of a subset of neurotransmitter receptor or transporter and synaptic activity is common across GBM patients. The coherent layer of imaging and molecular information would help us stratify precision neuro-oncology and treatment options in ways that are not possible through MRI or genomic data alone. Our findings provide molecular targets in the disrupted neurocircuit of GBM, suggesting imbalanced excitation and inhibition. Given the fact that GBM patients exhibit similar symptoms resembling patients with neurodegenerative diseases and seizures, our results supported the hypothesis-GBM in the context of neurological disorders beyond a solely cancerous disease.
Causal Cortical and Thalamic Connections in the Human Brain
Authors: Lyu Dian , Stiger James , Lusk Zoe , Buch Vivek , Parvizi Josef
Published: June 2024

The brain’s functional architecture is intricately shaped by causal connections between its cortical and subcortical structures. Here, we studied 27 participants with 4864 electrodes implanted across the anterior, mediodorsal, and pulvinar thalamic regions, and the cortex. Using data from electrical stimulation procedures and a data-driven approach informed by neurophysiological standards, we dissociated three unique spectral patterns generated by the perturbation of a given brain area. Among these, a novel waveform emerged, marked by delayed-onset slow oscillations in both ipsilateral and contralateral cortices following thalamic stimulations, suggesting a mechanism by which a thalamic site can influence bilateral cortical activity. Moreover, cortical stimulations evoked earlier signals in the thalamus than in other connected cortical areas suggesting that the thalamus receives a copy of signals before they are exchanged across the cortex. Our causal connectivity data can be used to inform biologically-inspired computational models of the functional architecture of the brain.
Coexistence despite competition: Vegetation structural complexity shapes bryophyte diversity over succession
Authors: Hanusch Maximilian
Published: June 2024

Vascular plants and bryophytes are key components driving the development of diverse ecosystems following glacial retreat. Unravelling biotic interaction mechanisms between both groups is crucial for understanding the generation of biodiversity under natural conditions. Focusing on a 170-year primary succession gradient in the Austrian Alps, this study examines mechanisms of competitive interaction between vascular plants and bryophytes during the initial phases of ecosystem establishment. Using data on vegetation structural complexity derived from multispectral 3D-scans of vegetation, the local habitat’s substrate diversity, and vascular plant and bryophyte taxonomic composition, this study provides a mechanistic understanding of plant-plant interactions within a natural ecosystem. Vascular plants dominate the vertical niche through complex growth structures, which negatively affect bryophyte diversity. A pattern that is uniquely detectable by estimates of vegetation structural complexity. Path analysis confirms that vegetation structural complexity drives competition through a reduction of realized niche sizes of bryophyte communities, a concept introduced here as ecological dispersion. This study demonstrates the advantages of 3D-laser-scanning approaches in capturing the complexity of vegetation structure and its impacts on ecosystem dynamics. The findings underscore the importance of vegetation structural complexity in the establishment and maintenance of natural ecosystems and underscore the potential of 3D-laser-scanning methods in future studies to inform biodiversity conservation and restoration approaches in similar environments.
Taking stock of selective logging in the Andaman Islands, India: recent & legacy effects of timber extraction, assisted natural regeneration and a revamped working plan
Authors: Surendra Akshay , Sridhar Vanjulavalli , Osuri Anand M. , Ratnam Jayashree
Published: June 2024

Forest management is an evolving balance between biodiversity conservation and economic needs. A shift in Andaman Islands’ Working Plan mandate in 2000s reflects this evolution. Our study independently assesses the impact of said policy change on post-logging recovery of forests in Baratang and Middle Andaman.

In 2017-18, we placed seventy-six 0.49ha plots across evergreen and deciduous patches and compared large-tree (≥180cm girth) density and diversity across forests that were logged after 2005 focussing on sustainability, logged in 1990s focussing on timber, logged twice in 1990s and after 2005, and unlogged forests. We assessed forest regeneration in thirty 0.01ha plots along a coupe road within forests logged after 2005.

Forests logged after 2005 had similar density of large trees as forests logged in 1990s (despite having 1/3rdthe recovery time), indicating reduced offtake or better recruitment. Along the unlogged—once-logged—twice-logged gradient, the dominance ofPterocarpus dalbergioidesin deciduous patches decreased while the dominance ofDiptercarpus sp.in evergreen patches increased. Compared to natural regeneration, proportionately more deciduous saplings were planted in both evergreen and deciduous patches.

The new working plan maintains timber stock but not diversity. We make six simple recommendations to better align practice with the Working Plan mandate.

Synthesis

Post-2005 timber extraction policy in the Andaman Islands is partially successful but long-term forest health, in line with the working plan mandate, requires (1) lower timber offtake from deciduous patches and (2) targeted assisted regeneration of non-timber tree species.
Aquatic plant mycobiomes change with watershed urbanization
Authors: Mora Jacob , Olson Matt , Rocks Sara S. , Zahn Geoffrey
Published: June 2024

Urban expansion, projected to triple globally from 2000 to 2030, significantly impacts biodiversity and ecosystem processes, including those of microbial communities. While extensive research has examined urbanization effects on macro-organisms, the impacts on microbial communities, particularly those associated with aquatic plants, remain underexplored. This study investigates the fungal endophyte communities in the pollution-tolerant aquatic plant Ranunculus aquatilis along an urbanization gradient in the Provo River, Utah, USA, a rapidly urbanizing region. We collected plant and adjacent water samples from ten locations along the river, spanning from rural to urbanized areas, and conducted DNA amplicon sequencing to characterize fungal community composition.

Our results show a significant decline in fungal alpha diversity downstream, correlated with increased urbanization metrics such as impervious surface area and developed land cover. Specifically, fungal ASV richness and Shannon diversity decreased as urbanization intensified, driven primarily by a reduction in rare taxa. Despite a stable core microbiome dominated by a few taxa, the overall community structure varied significantly along the urban gradient, with notable shifts in dominant fungal taxa. Contrary to expectations, no detectable levels of heavy metals were found in water samples, suggesting that other urbanization-related factors, potentially including organic pollutants or plant stress responses, influence fungal endophyte communities.

Our findings underscore the need for further investigation into the mechanisms driving these patterns, particularly the roles of organic pollution, nutrient loads, and plant stress. Understanding these interactions is crucial for predicting the impacts of continued urbanization on freshwater ecosystems and their associated microbial communities.
Insect-habitat-plant interaction networks provide guidelines to mitigate the risk of transmission of Xylella fastidiosa to grapevine in Southern France
Authors: Mesmin Xavier , Chartois Marguerite , Farigoule Pauline , Burban Christian , Streito Jean-Claude , Thuillier Jean-Marc , Pierre Eric , Lambert Maxime , Mellerin Yannick , Bonnard Olivier , van Halder Inge , Fried Guillaume , Rasplus Jean-Yves , Cruaud Astrid , Rossi Jean-Pierre
Published: June 2024

1. Xylella fastidiosa (Xf) is a xylem-limited bacterium that has been recorded in several European countries since its detection in 2013 in Apulia (Italy). Given the prominence of the wine industry in many southern European countries, a big threat is the development of Pierce's disease in grapevines. Yet, the insect-habitat and insect-plant interaction networks in which xylem feeders, possible vectors of Xf, are involved around European vineyards are largely unknown. 2. Here we describe these networks in three important wine-growing regions of southern France (Provence-Alpes-Cote d'Azur, Occitanie, Nouvelle-Aquitaine) to identify the main source habitats of xylem feeders, and to gather information about their specialization degree at the habitat, plant family, and plant species levels. A total of 92 landscapes (and 700 sites) were studied over three sampling sessions in the fall 2020, the spring 2021, and the fall 2021. 3. Among the habitats sampled, meadows hosted the largest xylem feeder communities, followed by alfalfa fields. Vineyard headlands and inter-rows hosted slightly smaller xylem feeder communities, indicating that potential Xf vectors were thriving in the close vicinity of vulnerable plants. Finally woody habitats in general and grapevines in particular hosted very few xylem feeders, showing that transfer on vulnerable plants are rare, but not inexistent. In terms of specialization degrees, Philaenus spumarius, Aphrophora alni, Lepyronia coleoptrata, and Cicadella viridis were all similarly generalists at the habitat, plant family or plant species level. The only specialist was Aphrophora grp. salicina, which was restricted to riparian forests, and more specifically to Salicaceae. Neophilaenus spp. were extremely specialist at the plant family level (Poaceae), but rather generalist at the habitat and plant species levels. All 1017 insects screened for the presence of Xf tested negative, showing that Xf is not widespread in the studied regions. 4. Our study provides new basic ecological information on potential vectors of Xf, especially on their specialization and feeding preferences, as well as practical information that may be relevant for the design of epidemiological surveillance plans.
Why didn’t the nudibranch cross the ocean? Understanding biogeographic and evolutionary relationships ofHermissenda(Nudibranchia: Myrrhinidae) Bergh, 1878
Authors: Montana Katherine O. , Gosliner Terrence M. , Crews Sarah C. , Bonomo Lynn J. , Carlton James T. , Johnson Rebecca F.
Published: June 2024

In the aftermath of the 2011 east Japanese earthquake and tsunami, anthropogenic debris from the east coast of Japan floated across the Pacific Ocean to the west coast of North America. One such vessel from Iwate Prefecture arrived on the coast of Oregon, and the fouling community included specimens identified as the nudibranchHermissenda crassicornis, which was previously thought to range from Japan to Baja California but has since been split into three species:H. crassicornis(Alaska to southern CA),H. opalescens(British Columbia to Baja California), andH. emurai(Japan, Korea, Russian Far East). Previous work suggested that all of the motile invertebrates found in the tsunami debris fouling community were either pelagic or Japanese in origin. Our study sought to determine whether the nudibranch specimens collected from the Iwate vessel were, according to the new classification system, onlyH. emuraior whether the Eastern PacificHermissendawere present as well. Results from DNA sequencing and morphological analysis suggest that specimens ofH. crassicornis, as it is currently recognized, andH. opalescenswere found on the vessel.This finding indicates either that these species settled after arrival to the west coast of North America or thatH. crassicornisandH. opalescensis found in Japan, suggestingHermissendaranges need to be investigated further.Occurrence data shared on the iNaturalist platform were also used to assess current ranges. Our phylogenetic tree and haplotype network constructed from COI data from allHermissendaspecies indicate thatH. opalescensandH. emuraiare most closely related withH. opalescenssister to the clade that containsH. opalescensandH. emurai. This study demonstrates the power of combining volunteer naturalist data with lab-collected data to understand evolutionary relationships, species ranges, and biogeography.
Milk Fat Globule Membrane-Containing Protein Powder Promotes Fitness inCaenorhabditis elegans
Authors: Pitkänen Miina , Matilainen Olli
Published: June 2024

Milk-derived peptides and milk fat globule membrane (MFGM) have gained interest as health-promoting food ingredients. However, the mechanisms by which these nutraceuticals modulate the function of biological systems often remain unclear. We utilizedCaenorhabditis elegansto elucidate how milk-derived Protein powders rich in MFGM, previously used in a clinical trial, affect the physiology of this model organism. Our results demonstrate that Protein powders do not affect lifespan but promote the fitness of the animals. Surprisingly, gene expression analysis revealed that Protein powders decrease the expression of genes functioning on innate immunity, which also translates into reduced survival on pathogenic bacteria. One of the innate immunity-associated genes showing reduced expression upon Protein powder supplementation iscpr-3, the homolog of human cathepsin B. Interestingly, knockdown ofcpr-3enhances fitness, but not in Protein powder-treated animals, suggesting that protein powders contribute to fitness by downregulating the expression of this gene. In summary, this research highlights the value ofC. elegansin testing the biological activity of food supplements and nutraceuticals. Furthermore, this study should encourage investigations into whether milk-derived peptides and MFGM mediate their beneficial effects through the modulation of cathepsin B expression in humans.
Hotwiring integrin endocytosis acutely modulates cell interactions
Authors: Kamboj Sahil , Boché Alphonse , Moret Anneline , Wang Zixu , Aimé Carole , Agniel Rémy , Leroy-Dudal Johanne , Carreiras Franck , Gallet Olivier , Royle Stephen J , Lambert Ambroise
Published: June 2024

Integrins are heterodimeric cell surface receptors that govern cell-cell interactions, which in turn can influence multiscale processes: cell migration, extracellular matrix remodeling and tissue formation. These processes occur over timescales which range from milliseconds to days. While various strategies exist to study integrin function across biological scales from cell to tissue, they are often chronic and fail to target specific cell-cell interactions acutely. We engineered cells to rapidly alter cell behavior by downregulating the surface population of α5β1 integrins through hot-wired clathrin-mediated endocytosis. This method allows for inducible, specific internalization of α5β1 integrins, achieving acute downregulation across various cell lines in 5-30 minutes. We show that induced internalization of α5β1 decreases the cell area, causes uptake of extracellular fibronectin, and decreases the rate of tumor spheroid compaction. This targeted control of multiscale processes by rapid downregulation of this important class of cell surface receptors demonstrates that hot-wired endocytosis is a useful tool to acutely modulate cell biology.
Instead of seeing it as a health care issue, you see it as you:Reasons for alcohol use, consequences of use, and barriers to help seeking among fathers in Kenya
Authors: Giusto Ali , Satinsky Emily N. , Jaguga Florence , Rono Wilter , Barasa Julius , Galán Chardée A. , Wainberg Milton L.
Published: June 2024

Introduction

Father alcohol use negatively impacts family systems, yet research in this area is scarce in low- and middle-income countries like Kenya. An understanding of why fathers drink, consequences of alcohol use, and barriers to care is needed to refine and adapt clinical and implementation approaches to treating fathers.

Methods

Community members, leaders, mental health providers, and fathers experiencing alcohol use problems in Eldoret, Kenya were recruited to participate in semi-structured qualitative interviews and focus groups. Participants were asked about why fathers engage in alcohol use, potential impacts of use, and barriers to accessing care. The frame method was employed to analyze the data. The study team read transcripts, iteratively memo-ed and discussed notes, developed a codebook, and coded transcripts. Broad codes were summarized and reviewed alongside transcripts.

Results

Participants noted reasons for and consequences of fathers’ drinking at individual, family and interpersonal, and sociocultural levels. At the individual level, alcohol use facilitated an escape from mental distress and acted as a means to cope with “idleness” due to unemployment. Consequences included poor physical and mental health, such as depression. At the family/interpersonal level, fathers used alcohol to distract themselves from family conflicts. Consequences included violence and poor child outcomes. Gender and drinking norms were drivers at the sociocultural level. Consequences at this level included stigmatization and loss of social status, which can drive shame and isolation. Salient barriers to care included fathers’ lack of awareness of their alcohol use problem, limited-service access, and social stigma.

Conclusions

Father motivations for drinking are influenced by multiple ecological levels, and drinking has a cascade of consequences on the family. These effects are worsened by barriers to care. Intervention and implementation strategies should consider masculinity norms, resources, and avoidant coping motivations in adaptation.
Diagnosis of the Beninese Health System: Progress, and Challenges for an Effective, Resilient, and Sustainable System
Authors: Nahini Amboise Tchando , Baranon Mouhamadou Djima , Sambieni Emmanuel N’Koé , Sanni Mouftaou Amadou
Published: June 2024

This work involved diagnosing the Beninese health system based on secondary data from several sources (statistical directories, surveys, censuses, and study reports). The descriptive analysis of the evolution of health indicators in Benin between 2002 and 2021 and in-depth interviews with resource people in the health sector made it possible to assess the efforts and progress made by those in power and system stakeholders. There have been many tangible efforts to improve accessibility to health services (the rates of health coverage and attendance at health facilities have increased from 86% to 96% and from 35% to 56% between 2002 and 2021). These efforts have significantly reduced morbidity and mortality rates. The results also indicate a drop in deaths due to malaria (141 deaths to 86 per 100,000 inhabitants between 2003 and 2021) and a drop in the prevalence of HIV AIDS up to 0.8% from 2019 ahead of several countries—neighbors of the sub-region. Early neonatal mortality fell from 10.1‰ to 4.7‰ as well as deaths of children under 5 years old, thus improving life expectancy at birth from 59.6 years in 2002 to 63.8 years in 2013. Despite these efforts, many challenges remain, adding to the strong demographic growth in the country, which clearly expresses the threats weighing on the daily state of health of the Beninese population and calling for a new way of thinking for a sustainable health system. The study ends with the prioritization of challenges and a proposal for strategies to have an efficient and resilient health system, capable of producing quality, healthy, and productive human capital.
Activity and function of the endothelial sodium channel is regulated by the effector domain of MARCKS like protein 1 in mouse aortic endothelial cells
Authors: Yu Ling , Bala Niharika , Nguyen Van-Anh L. , Kessler Leah , LaDisa John F. , Alli Abdel A.
Published: June 2024

The endothelial sodium channel (EnNaC) plays an important role in regulating vessel stiffness. Here, we investigated the regulation of EnNaC in mouse aortic endothelial cells (mAoEC) by the actin cytoskeleton and lipid raft association protein myristoylated alanine-rich C-kinase substrate like protein 1 (MLP1). We hypothesized that mutation of specific amino acid residues within the effector domain of MLP1 or loss of association between MLP1 and the anionic phospholipid phosphate PIP2 would significantly alter membrane association and EnNaC activity in mAoEC. mAoEC transiently transfected with a mutant MLP1 construct (three serine residues in the effector domain replaced with aspartate residues) showed a significant decrease in EnNaC activity compared to cells transfected with wildtype MLP1. Compared to vehicle treatment, mAoEC treated with the PIP2 synthesis blocker wortmannin showed less colocalization of EnNaC and MLP1. In other experiments, Western blot and densitometric analysis showed a significant decrease in MLP1 and caveloin-1 protein expression in mAoEC treated with wortmannin compared to vehicle. Finally, wortmannin treatment decreased sphingomyelin content and increased membrane fluidity in mAoEC. Taken together, our results suggest constitutive phosphorylation of MLP1 attenuates the function of EnNaC in aortic endothelial cells by a mechanism involving a decrease in association with MLP1 and EnNaC at the membrane, while deletion of PIP2 decreases MARCKS expression and overall membrane fluidity.
Scalable intracellular delivery via microfluidic vortex shedding enhances the function of chimeric antigen receptor T-cells
Authors: Sytsma Brandon J. , Allain Vincent , Bourke Struan , Faizee Fairuz , Fathi Mohsen , Berdeaux Rebecca , Ferreira Leonardo M.R. , Brewer W. Jared , Li Lian , Pan Fong L. , Rothrock Allison G. , Nyberg William A. , Li Zhongmei , Wilson Leah H. , Eyquem Justin , Pawell Ryan S.
Published: June 2024

Adoptive chimeric antigen receptor T-cell (CAR-T) therapy is transformative and approved for hematologic malignancies. It is also being developed for the treatment of solid tumors, autoimmune disorders, heart disease, and aging. Despite unprecedented clinical outcomes, CAR-T and other engineered cell therapies face a variety of manufacturing and safety challenges. Traditional methods, such as lentivirus transduction and electroporation, result in random integration or cause significant cellular damage, which can limit the safety and efficacy of engineered cell therapies. We present hydroporation as a gentle and effective alternative for intracellular delivery. Hydroporation resulted in 1.7- to 2-fold higher CAR-T yields compared to electroporation with superior cell viability and recovery. Hydroporated cells exhibited rapid proliferation, robust target cell lysis, and increased pro-inflammatory and regulatory cytokine secretion in addition to improved CAR-T yield by day 5 post-transfection. We demonstrate that scaled-up hydroporation can process 5 × 108cells in less than 10 s, showcasing the platform as a viable solution for high-yield CAR-T manufacturing with the potential for improved therapeutic outcomes.
Left-Right Brain-Wide Asymmetry of Neuroanatomy in the Mouse Brain
Authors: Silberfeld Andrew , Roe James M. , Ellegood Jacob , Lerch Jason P. , Qiu Lily , Kim Yongsoo , Lee Jong Gwan , Hopkins William D. , Grandjean Joanes , Ou Yangming , Pourquié Olivier
Published: June 2024

Left-right asymmetry of the human brain is widespread through its anatomy and function. However, limited microscopic understanding of it exists, particularly for anatomical asymmetry where there are few well-established animal models. In humans, most brain regions show subtle, population-average regional asymmetries in thickness or surface area, alongside a macro-scale twisting called the cerebral petalia in which the right hemisphere protrudes anteriorly past the left. Here, we ask whether neuroanatomical asymmetries can be observed in mice, leveraging 6 mouse neuroimaging cohorts from 5 different research groups (∼3,500 animals). We found an anterior-posterior pattern of volume asymmetry with anterior regions larger on the right and posterior regions larger on the left. This pattern appears driven by similar trends in surface area and positional asymmetries, with the results together indicating a small brain-wide twisting pattern, similar to the human cerebral petalia. Furthermore, the results show no apparent relationship to known functional asymmetries in mice, emphasizing the complexity of the structure-function relationship in brain asymmetry. By establishing a signature of anatomical brain asymmetry in mice, we aim to provide a foundation for future studies to probe the mechanistic underpinnings of brain asymmetry seen in humans – a feature of the brain with extremely limited understanding.

Significance Statement

The human brain shows significant left-right anatomical asymmetry. Understanding its microscopic basis has implications for studies of autism and schizophrenia, evolution, embryonic brain development, and the relationship between structure and function in the brain. One of the biggest challenges to understanding this aspect of the brain is that animal models are limited. Here we show a brain-wide twisting pattern of asymmetry in the mouse brain using over 3,500 animals from six independent cohorts. These findings provide a basis for using mice to interrogate the microscopic underpinnings of anatomical asymmetry in humans and a roadmap for exploring anatomical asymmetry in additional species.
Shallow sequencing (Shall-seq) procedure: A method for determining the genetic lineages and detecting antimicrobial resistance genes of antimicrobial-resistant bacteria using minimum Nanopore sequencing data
Authors: Yagi Nobuyoshi , Miyagi Nanase , Uechi Ayumi , Hirai Itaru
Published: June 2024

Antimicrobial-resistant bacteria could cause nosocomial infections and outbreaks in healthcare facilities. Phylogenetic analyses based on whole-genome sequencing (WGS) could become the gold-standard method for understanding the route of antimicrobial-resistant bacterial spreading. However, generally, the WGS needs to analyze much amount of data. Therefore, sufficient resources such as budget and data analysis system are needed and it is a burden for introduction of the WGS in the routine clinical examination of pathogenic bacterial isolates. In this study, we usedEscherichia colias a model and evaluated whether determination of the genetic background and detection of antimicrobial-resistance genes of 29E. coliclinical isolates were achieved by searching databases using sequence reads output by the Nanopore sequencer as the search keys. Consequently, only 66.2 MB data was sufficient to search for a genome sequence with ≥90% range of coverage rate. Importantly, AMR genes and plasmid replicon types were also detected with minimum data, and the detected AMR genes and phenotypes of theE. coliisolates did not present any discrepancy. Taken together, this shallow sequencing (Shall-seq) procedure consists of “shallow of coverage” sequencing using the Nanopore sequencer and data search using minimum data could be used to analyze bacterial isolates cost-effectively.
Increased Neonatal Deaths in Texas After SB8, a Cardiac Activity-Based Abortion Ban
Authors: Faust Jeremy Samuel , Chen Ji , Renton Benjamin , Otugo Onyekachi , Chen Alexander Junxiang , Yaver Miranda , Lin Zhenqiu , Rasmussen Sonja A. , Krumholz Harlan M.
Published: June 2024

Introduction

On September 1, 2021, Texas enacted Senate Bill 8 (SB8), a law banning abortions after the detection of fetal heart activity, without exceptions for early detectable fetal abnormalities with low survival probability. The effect on neonatal mortality is unknown.

Methods

We deployed difference-in-differences (primary analysis), and Joinpoint and seasonal autoregressive moving integrated averages (sensitivity analyses) to determine whether all-cause mortality among Texas neonates increased after SB8 was enacted, and compared the findings to states with permissive abortion laws. Changes in mortality due to congenital malformations, deformations and chromosomal abnormalities were also measured.

Results

Compared with states where abortion remained legal, approximately 177 all-cause excess neonatal deaths (2.3 per 10,000 births, interaction p<0.003) occurred in Texas. A sensitivity analysis using Joinpoint logistic regression spontaneously identified a mortality trend change in Texas coinciding with SB8 enactment. Approximately 113 excess deaths (1.5 per 10,000 births, interaction p<0.001) due to congenital malformations, deformations and chromosomal abnormalities occurred among Texas neonates after SB8 enactment. Compared to expected deaths based on prior internal trends (sARIMA), Texas recorded 289 (95% CI 18-559) excess neonatal deaths (3.7 per 10,000 births; 95% CI 0.2-7.2) in 2022-2023. A preliminary analysis of post-SB8 shares of neonates listed as “not alive” on birth certificates by race/ethnicity found increased relative contributions from non-Hispanic White and Hispanic populations.

Conclusion

Texas SB8 was responsible for between 177-289 excess neonatal deaths from Quarter 4, 2021-Quarter 4, 2023. These results suggest that if other SB8-like abortion bans are enacted, increases in neonatal mortality may occur elsewhere.
Prevalence of Anemia of Chronic Disease/Inflammation at a Tertiary Care Hospital in North India
Authors: Bhendekar Sidheshwar Vishnu , Kirtani Jay , Naithani Rahul
Published: June 2024

Background

There is lack of data from India on prevalence of anemia of chronic disease or inflammation (ACD).

Patients & methods

This was a prospective observational cross sectional prevalence study. Anemic patients underwent a complete blood count with peripheral smear, serum ferritin level, iron, total iron binding capacity, transferrin saturation, vitamin B12 and folic acid level, reticulocyte count and stool for occult blood. Other investigations were performed as required according to patient’s clinical profile.

Results

Three hundred fifty five patients were enrolled. A total of 109 patients (30.7%) had anemia of chronic disease ACD (30.7%). Sixty three/263 (24%) females had ACD compared to 46/95 (48.4%) males. ACD was four times more common in age group 80 years and above (56.5%) compared to age group 18 to 39 years (13.9%). Seventy two (66%) patients had mild anemia, 19 patients (17%) had moderate anemia and 18 patients (16%) had severe anemia. Diabetes mellitus (44%), hypertension (39%) and chronic kidney disease (25%) were the commonest underlying morbidity. Thirty six patients (33%) had no underlying comorbidity or cause.

Conclusion

The prevalence of anemia of chronic disease increases with age. Majority of anemia of chronic disease patients have mild anemia.
Risk factors in the first 1000 days of life associated with childhood obesity: a systematic review and risk factor quality assessment
Authors: Blaauwendraad Sophia M , Kamphuis Arwen SJ , Ruiz-Ojeda Francisco Javier , Brandimonte-Hernández Marco , Flores-Ventura Eduard , Abrahamse-Berkeveld Marieke , Collado Maria Carmen , van Diepen Janna A , Iozzo Patricia , Knipping Karen , van Loo-Bouwman Carolien A , Gil Ángel , Gaillard Romy
Published: June 2024

Background

Adverse early life exposures might negatively affect foetal and infant development, predisposing children to obesity. We aimed to systematically identify and evaluate risk factors for childhood obesity in preconception, pregnancy, and infancy, and assess their potential as targets for future prediction and prevention strategies.

Methods

This systematic review (PROSPERO, CRD42022355152) included longitudinal studies from selected electronic databases published between inception and August 17th, 2022, identifying maternal, paternal, or infant risk factors from preconception until infancy for childhood obesity between 2 and 18 years. Screening and data extraction was performed through standardized extraction forms. We assessed risk factor quality on modifiability and predictive power using a piloted criteria template from ILSI-Europe-Marker-Validation-Initiative.

Findings

We identified 172 observational and 5 intervention studies involving n=1.879.971 children from 37, predominantly high-income, countries. 59%, 25% and 16% of studies measured childhood obesity between 2- <6 years, 6-10 years, and >10 -18 years respectively. Average reported childhood obesity prevalence was 11·1%. Pregnancy and infancy risk factors were mostly studied. We identified 59 potential risk factors, 24 of which were consistently associated with childhood obesity risk. Higher maternal prepregnancy weight (n=28/31 positive associations from 31 studies, respectively), higher gestational weight gain (n=18/21), maternal smoking during pregnancy (n=23/29), higher birth weight (n=20/28), LGA (n=17/18), no breastfeeding (n=20/31), and higher infant weight gain (n=12/12) were the strongest risk factors, which may aid in prediction or be targets for prevention. Level of evidence was generally moderate due to unreliable exposure measurement, short follow-up/loss-to-follow up, and risk of confounding.

Interpretation

We identified 7 early life risk factors, which were strongly associated with a higher risk of childhood obesity, and can contribute to future prediction and prevention strategies. These findings support implementation of prevention strategies targeting these early-life risk factors from a clinical and population perspective, where possible integrated with implementation studies.

Funding

This work was conducted by an expert group of the European branch of the International Life Sciences Institute, ILSI Europe.
The yield of tuberculosis contact investigation in São Paulo, Brazil: a community-based cross-sectional study
Authors: Silva José Mário Nunes da , Diaz-Quijano Fredi Alexander
Published: June 2024

The strategy of tuberculosis (TB) contact investigation is essential for enhancing disease detection. We conducted a cross-sectional study to evaluate the yield of contact investigation for new TB cases, estimate the prevalence of TB, and identify characteristics of index cases associated with infection among contacts of new cases notified between 2010 and 2020 in São Paulo, Brazil. Out of 186,466 index TB cases, 131,055 (70.3%) underwent contact investigation. A total of 652,286 contacts were screened, of which 451,704 (69.2%) were examined. Of these, 12,243 were diagnosed with active TB (yield of 2.0%), resulting in a number needed to screen of 51 and a number needed to test of 37 to identify one new TB case. The weighted prevalence for the total contacts screened was 2.8% (95% confidence interval [CI]: 2.7%–2.9%), suggesting underreporting of 6,021 (95% CI: 5,269–6,673) cases. The likelihood of TB diagnosis was higher among contacts of cases with active case-finding, abnormal chest X-ray, pulmonary TB, or drug resistance, as well as among children, adults, women, individuals in socially vulnerable situations, and those with underlying clinical conditions. The study highlights significant TB underreporting among contacts, recommending strengthened contact investigation to promptly identify and treat new cases.
Lipid composition of the membrane governs the oligomeric organization of VDAC1
Authors: Lafargue Elodie , Duneau Jean-Pierre , Buzhinsky Nicolas , Ornelas Pamela , Ortega Alexandre , Ravishankar Varun , Sturgis James , Casuso Ignacio , Bergdoll Lucie
Published: June 2024

Mitochondrial physiology is intricately linked to the oligomerization of voltage-dependent anion channels (VDAC), acting as gatekeepers to mitochondria. However, the molecular determinants of VDAC oligomerization remain poorly understood. Here, we used atomic force microscopy to investigate the effects of three lipids of the Mitochondrial Outer Membrane (MOM) on VDAC assemblies. We observed that VDAC forms lipid-sensitive clusters, termed honeycombs, and their compaction is regulated by cholesterol. Molecular dynamics simulations revealed VDAC’s affinity for cholesterol and phosphatidylethanolamine, both of which affect the formation of these honeycombs. Although we identified honeycomb-like assemblies akin to those in the native MOM, deviations from the physiological lipid composition resulted in varying degrees of disruption of these native-like structures. This emphasizes the profound impact of the lipid environment on VDAC organization. These findings underscore the physiological significance of lipid heterogeneity and changes within biological membranes arising from membrane contacts or pathologies in modulating VDAC behavior.
Midline Assembloids Reveal Regulators of Human Axon Guidance
Authors: Onesto Massimo M. , Amin Neal D. , Pan Chenjie , Chen Xiaoyu , Reis Noah , Valencia Alfredo M. , Hudacova Zuzana , McQueen James P. , Tessier-Lavigne Marc , Paşca Sergiu P.
Published: June 2024

Organizers are specialized cell populations that orchestrate cell patterning and axon guidance in the developing nervous system. Although non-human models have led to fundamental discoveries about the organization of the nervous system midline by the floor plate, an experimental model of human floor plate would enable broader insights into regulation of human neurodevelopment and midline connectivity. Here, we have developed stem cell-derived organoids resembling human floor plate (hFpO) and assembled them with spinal cord organoids (hSpO) to generate midline assembloids (hMA). We demonstrate that hFpO promote Sonic hedgehog-dependent ventral patterning of human spinal progenitors and Netrin-dependent guidance of human commissural axons, paralleling non-human models. To investigate evolutionary-divergent midline regulators, we profiled the hFpO secretome and identified 27 evolutionarily divergent genes between human and mouse. Utilizing the hMA platform, we targeted these candidates in an arrayed CRISPR knockout screen and reveal thatGALNT2, a gene involved in O-linked glycosylation, impairs floor plate-mediated guidance of commissural axons in humans. This novel platform extends prior axon guidance discoveries into human-specific neurobiology with implications for mechanisms of nervous system evolution and neurodevelopmental disorders.
CryoEM Structure of the human THIK-1 K2P K+Channel Reveals a Lower ‘Y-gate’ Regulated by Lipids and Anaesthetics
Authors: Rödström Karin EJ , Eymsh Bisher , Proks Peter , Hayre Mehtab S , Madry Christian , Rowland Anna , Newstead Simon , Baukrowitz Thomas , Schewe Marcus , Tucker Stephen J
Published: June 2024

THIK-1 (KCNK13) is a halothane-inhibited and anionic lipid-activated Two-Pore Domain (K2P) K+channel implicated in microglial activation and neuroinflammation, and a current target for the treatment of neurodegenerative disorders such as Alzheimer’s and Amyothropic Lateral Sclerosis (ALS). However, compared to other K2P channels, little is known about the structural and functional properties of THIK-1. Here we present a 3.16 Å resolution cryoEM structure of human THIK-1 that reveals several unique features, in particular, a tyrosine in M4 (Y273) which contributes to a lower ‘Y-gate’ that opens upon activation by physiologically-relevant signalling pathways. We further demonstrate that binding of linoleic acid within a modulatory pocket adjacent to the filter also activates THIK-1, and that halothane inhibition involves a binding site within the inner cavity resulting in changes to the Y-gate. Finally, the extracellular cap domain contains positively-charged residues that line the ion exit pathway and which contribute to the unique biophysical properties of this channel. Overall, our results provide important insights into the structural basis of THIK1 function and identify distinct regulatory sites that expand its potential as a drug target for the modulation of microglial function.
Dietary protein from different sources escapes host digestion and is differentially modified by the microbiota
Authors: Awan Ayesha , Bartlett Alexandria , Blakeley-Ruiz J. Alfredo , Richie Tanner , Theriot Casey M. , Kleiner Manuel
Published: June 2024

Protein is an essential macronutrient and variations in its source and quantity have been shown to impact long-term health outcomes. Differential health impacts of dietary proteins from various sources are likely driven by differences in their digestibility by the host and subsequent availability to the intestinal microbiota. However, our current understanding regarding the fate of dietary proteins from different sources in the gut, specifically how component proteins within these sources interact with the host and the gut microbiota, is limited. To determine which dietary proteins are efficiently digested by the host and which proteins escape host digestion and are used by the gut microbiota, we used high-resolution mass spectrometry to quantify the proteins that make up different dietary protein sources before and after digestion in germ-free and conventionally raised mice. Contrary to expectation, we detected proteins from all sources in fecal samples of both germ-free and conventional mice suggesting that even protein sources with a high digestive efficiency make it in part to the colon where they can serve as a substrate for the microbiota. Additionally, we found clear patterns where specific component proteins of the dietary protein sources were used as a preferred substrate by the microbiota or were not as accessible to the microbiota. We found that specific proteins with functions that could impact host health and physiology were differentially enriched in germ-free or conventionally raised mice. These findings reveal large differences in the fate of dietary protein from various sources in the gut that could explain some of their differential health impacts.
A family of lanthipeptides with anti-phage function
Authors: Shomar Helena , Tesson Florian , Guillaume Marie , Ongenae Véronique , Le Bot Margot , Georjon Héloïse , Mordret Ernest , Zhang Le , van Wezel Gilles P. , Rozen Daniel , Briegel Ariane , Zirah Séverine , Claessen Dennis , Li Yanyan , Bernheim Aude
Published: June 2024

Bacteria synthesize natural products to adapt to their environment, where phage-bacteria interactions play a crucial role in bacterial ecology. Although a few natural products have been shown to protect bacteria from phage infection, the prevalence and diversity of chemical anti-phage defense remain largely unexplored. Here, we uncover a novel family of over 2000 lanthipeptide biosynthetic gene clusters from Actinobacteria that participate in anti-phage defense, which we named lanthiphages. Lanthiphages colocalize with other anti-phage systems in defense islands. We demonstrate that native lanthiphage expression protects the model strainStreptomyces coelicoloragainst diverse phages. Heterologous expression of four additional lanthiphage pathways shows that the anti-phage function is conserved across this family of biosynthetic gene clusters. Finally, we demonstrate that lanthiphage expression leads to the production of a novel compound and alters phage transcription. Our findings highlight that biosynthetic gene clusters with anti-phage functions can be successfully identified through genomic analysis. This work paves the way for the systematic mining of anti-phage natural products, which could constitute a novel reservoir of antiviral drugs.
Energy-based bond graph models of glucose transport with SLC transporters
Authors: Hunter Peter J. , Ai Weiwei , Nickerson David P.
Published: June 2024

The SLC (solutecarrier) superfamily mediates the passive transport of small molecules across apical and basolateral cell membranes in nearly all tissues. In this paper we employ bond graph approaches to develop models of SLC transporters that conserve mass, charge and energy, respectively, and which can be parameterised for a specific cell and tissue type for which the experimental kinetic data is available. We show how analytic expressions that preserve thermodynamic consistency can be derived for a representative four- or six-state model, given reasonable assumptions associated with steady-state flux conditions. We present details on fitting parameters forSLC2A2(a GLUT transporter) andSLC5A1(an SGLT transporter) to experimental data and show how well the steady-state flux expressions match the full kinetic analysis. Since the bond graph approach will not be familiar to many readers, we provide a detailed description of the approach and illustrate its application to a number of familiar biophysical processes.

SIGNIFICANCE

Physiological systems typically involve coupled mechanical, electrical and chemical processes, with energy acting as a universal currency across these domains. We propose a new visual representation for all components of these processes using bond graphs. Bringing all physical processes under one consistent framework greatly simplifies the task of understanding multiscale physiological processes. This energy-based framework, which is the 0D version of a more general 3D port-Hamiltonian theory, can be used to model all lumped parameter physiological processes. A small number of bond graph templates can be used to model all members of the large SLC transporter family, and reduced thermodynamically consistent steady-state flux models provide a useful simplification for many situations. Glucose transport is chosen here to illustrate the bond graph approach because it represents the first step in cell metabolic processes, where energy conservation needs to be a fundamental characteristic of quantitative models. Our future work on cell metabolism will build on the foundation established here.