bluuebunny/crossref_metadata_2025_split huggingface dataset:
Persistent legacy effects on soil microbiota facilitate plant adaptive responses to drought
Authors: Ginnan Nichole A. , Custódio Valéria , Gopaulchan David , Ford Natalie , Salas-González Isai , Jones Dylan H. , Wells Darren M. , Moreno Ângela , Castrillo Gabriel , Wagner Maggie R. 
Published: August 2024

AbstractBoth chronic and acute drought alter the composition and physiology of the soil microbiota, favoring the selection of microbes with functional traits that preserve fitness in these challenging conditions1. This drought-adapted microbiota may influence water-use efficiency mechanisms in host plants. Currently, it is largely unknown how this soil microbial drought legacy manifests at the molecular and physiological levels and how it influences microbe-dependent plant responses to drought in diverse natural soils. Here, to infer how drought legacy affects soil microbiota composition and function, we collected soils spanning two distinct and geographically distant precipitation gradients. By controlling for variation in numerous other soil properties including porosity and elemental profiles, we identified a group of bacterial taxa that are highly sensitive to water availability and critical for the formation of soil drought memory. Next, by imposing an acute experimental drought we show that this microbial drought legacy is robust to short-term perturbations. Furthermore, we reveal that soil microbiota from historically dry climates buffered a wild grass species native to the precipitation gradient, but not the domesticated crop species maize, from the negative effects of subsequent acute drought. In particular, microbiota with a legacy of chronic water limitation altered the expression of a small subset of host genes that mediate the effect of acute drought on transpiration and intrinsic water use efficiency. Our results reveal how long-term exposure to water stress alters soil microbial communities and demonstrate the resulting “legacy effects” on the drought responses of neighboring plants.
Characterizing features affecting local ancestry inference performance in admixed populations
Authors: Honorato-Mauer Jessica , Shah Nirav N. , Maihofer Adam X. , Zai Clement C. , Belangero Sintia , Nievergelt Caroline M. ,   Psychiatric Genomics Consortium for PTSD Ancestry Working Group, Santoro Marcos , Atkinson Elizabeth 
Published: August 2024

AbstractIn recent years, significant efforts have been made to improve methods for genomic studies of admixed populations using Local Ancestry Inference (LAI). Accurate LAI is crucial to ensure downstream analyses reflect the genetic ancestry of research participants accurately. Here, we test analytic strategies for LAI to provide guidelines for optimal accuracy, focusing on admixed populations reflective of Latin America’s primary continental ancestries – African (AFR), Amerindigenous (AMR), and European (EUR). Simulating LD-informed admixed haplotypes under a variety of 2 and 3-way admixture models, we implemented a standard LAI pipeline, testing three reference panel compositions to quantify their overall and ancestry-specific accuracy. We examined LAI miscall frequencies and true positive rates (TPR) across simulation models and continental ancestries. AMR tracts have notably reduced LAI accuracy as compared to EUR and AFR tracts in all comparisons, with TPR means for AMR ranging from 88-94%, EUR from 96-99% and AFR 98-99%. When LAI miscalls occurred, they most frequently erroneously called European ancestry in true Amerindigenous sites. Using a reference panel well-matched to the target population, even with a lower sample size, LAI produced true-positive estimates that were not statistically different from a high sample size but mismatched reference, while being more computationally efficient. While directly responsive to admixed Latin American cohort compositions, these trends are broadly useful for informing best practices for LAI across other admixed populations. Our findings reinforce the need for inclusion of more underrepresented populations in sequencing efforts to improve reference panels.
Proteome asymmetry in mouse and human embryos before fate specification
Authors: Iwamoto-Stohl Lisa K. , Petelski Aleksandra A. , Meglicki Maciej , Fu Audrey , Khan Saad , Specht Harrison , Huffman Gray , Derks Jason , Jorgensen Victoria , Weatherbee Bailey A.T. , Weberling Antonia , Gantner Carlos W. , Mandelbaum Rachel S. , Paulson Richard J. , Lam Lisa , Ahmady Ali , Vasquez Estefania Sanchez , Slavov Nikolai , Zernicka-Goetz Magdalena 
Published: August 2024

AbstractPre-patterning of the embryo, driven by spatially localized factors, is a common feature across several non-mammalian species1–4. However, mammals display regulative development and thus it was thought that blastomeres of the embryo do not show such pre-patterning, contributing randomly to the three lineages of the blastocyst: the epiblast, primitive endoderm and trophectoderm that will generate the new organism, the yolk sac and placenta respectively4–6. Unexpectedly, early blastomeres of mouse and human embryos have been reported to have distinct developmental fates, potential and heterogeneous abundance of certain transcripts7–12. Nevertheless, the extent of the earliest intra-embryo differences remains unclear and controversial. Here, by utilizing multiplexed and label-free single-cell proteomics by mass-spectrometry13, we show that 2-cell mouse and human embryos contain an alpha and a beta blastomere as defined by differential abundance of hundreds of proteins exhibiting strong functional enrichment for protein synthesis, transport, and degradation. Such asymmetrically distributed proteins include Gps1 and Nedd8, depletion or overexpression of which in one blastomere of the 2-cell embryo impacts lineage segregation. These protein asymmetries increase at 4-cell stage. Intriguingly, halved mouse zygotes display asymmetric protein abundance that resembles alpha and beta blastomeres, suggesting differential proteome localization already within zygotes. We find that beta blastomeres give rise to a blastocyst with a higher proportion of epiblast cells than alpha blastomeres and that vegetal blastomeres, which are known to have a reduced developmental potential, are more likely to be alpha. Human 2-cell blastomeres also partition into two clusters sharing strong concordance with clusters found in mouse, in terms of differentially abundant proteins and functional enrichment. To our knowledge, this is the first demonstration of intra-zygotic and inter-blastomere proteomic asymmetry in mammals that has a role in lineage segregation.
Exploring SNP Filtering Strategies: The Influence of Strict vs Soft Core
Authors: Taouk Mona L. , Featherstone Leo A. , Taiaroa George , Seemann Torsten , Ingle Danielle J. , Stinear Timothy P. , Wick Ryan R. 
Published: August 2024

ABSTRACTPhylogenetic analyses are crucial for understanding microbial evolution and infectious disease transmission. Bacterial phylogenies are often inferred from single nucleotide polymorphism (SNP) alignments, with SNPs as the fundamental signal within these data. SNP alignments can be reduced to a ‘strict core’ by removing those sites which do not have data present in every sample. However, as sample size and genome diversity increase, a strict core can shrink markedly, discarding potentially informative data. Here, we propose and provide evidence to support the use of a ‘soft core’ that tolerates some missing data, preserving more information for phylogenetic analysis. Using large datasets ofNeisseria gonorrhoeaeandSalmonella entericaserovar Typhi, we assess different core thresholds. Our results show that strict cores can drastically reduce informative sites compared to soft cores. In a 10,000-genome alignment ofSalmonella entericaserovar Typhi, a 95% soft core yielded 10 times more informative sites than a 100% strict core. Similar patterns were observed inNeisseria gonorrhoeae. We further evaluated the accuracy of phylogenies built from strict and soft-core alignments using datasets with strong temporal signals. Soft-core alignments generally outperformed strict cores in producing trees displaying clock-like behaviour; for instance, theNeisseria gonorrhoeae95% soft core phylogeny had a root-to-tip regressionR2of 0.50 compared to 0.21 for the strict-core phylogeny. This study suggests that soft-core strategies are preferable for large, diverse microbial datasets. To facilitate this, we developedCore-SNP-filter(github.com/rrwick/Core-SNP-filter), an open-source software tool for generating soft-core alignments from whole-genome alignments based on user-defined thresholds.IMPACT STATEMENTThis study addresses a major limitation in modern bacterial genomics – the significant data loss observed in large datasets for phylogenetic analyses, often due to strict-core SNP alignment approaches. As bacterial genome sequence datasets grow and diversity increases, a strict-core approach can greatly reduce the number of informative sites, compromising phylogenetic resolution. Our research highlights the advantages of soft-core alignment methods which tolerate some missing data and retain more genetic information. To streamline the processing of alignments, we developedCore-SNP-filter(github.com/rrwick/Core-SNP-filter), a publicly available resource-efficient tool that filters alignments to informative and core sites.DATA SUMMARYAll genomic sequence reads used in this study were already publicly available and accessions can be found in Supplementary Dataset 1. Supplementary methods and all code can be found in the accompanying GitHub repository: (github.com/mtaouk/Core-SNP-filter-methods).
Effects of maximal speed locomotor training on spatiotemporal gait changes in individuals with chronic stroke: A secondary analysis of a randomized controlled trial
Authors: Pressler Daria , Schwab-Farrell Sarah M. , Reisman Darcy S. , Billinger Sandra A. , Boyne Pierce 
Published: August 2024

ABSTRACTObjectiveTo investigate longitudinal changes in spatiotemporal gait parameters after maximal versus moderate speed locomotor training in chronic stroke, by comparing short-burst high-intensity interval training (HIIT) versus moderate-intensity aerobic training (MAT). Compared to MAT, short-burst HIIT was hypothesized to exhibit greater improvement in non-paretic step length.DesignSecondary analysis from the HIT-Stroke randomized controlled trialSettingThree rehabilitation research centersParticipantsIndividuals with chronic stroke and residual walking limitations (N=55)InterventionsParticipants were randomized to short-burst HIIT (N=27) or MAT (N=28) for 45 minutes of walking practice, 3 times weekly, over 12 weeks. HIIT involved 30-second bursts of maximum walking speed, targeting >60% heart rate reserve (HRR). MAT involved continuous walking, targeting 40%-60% HRR.Main Outcome Measure(s)Mean spatiotemporal gait parameter changes between groups, averaging the 4-week, 8-week, and 12-week estimates minus baseline. The primary measure of interest was non-paretic step length, an indicator of paretic propulsion and biomechanical efficiency.ResultsNon-paretic step length increased significantly more in the HIIT group (+4.4 cm [95% CI, 1.9, 6.9]) compared to the MAT group (+0.1 [-2.5, 2.7]; HIIT vs. MAT p = .01). Both groups demonstrated significant increases in cadence, paretic step length, and bilateral single support time, and significant decreases in the coefficient of variation (CV) for stride velocity, stride time, and stride length. Symmetry measures did not significantly change in either group.ConclusionsGreater increases in non-paretic step length with short-burst HIIT suggest that maximal speed training may yield greater increases in paretic propulsion, a marker of biomechanical efficiency. Both moderate and maximal speed training (MAT and HIIT) appear to reduce spatiotemporal variability, possibly indicating improved gait stability.
The post-viral GPNMB+immune niche persists in long-term Covid, asthma, and COPD
Authors: Wu Kangyun , Zhang Yong , Yin-DeClue Huiqing , Sun Kelly , Mao Dailing , Crouch Erika C. , Byers Derek E. , Holtzman Michael J. 
Published: August 2024

AbstractEpithelial injury calls for a regenerative response from a coordinated network of epithelial stem cells and immune cells. Defining this network is key to preserving the repair process for acute resolution, but also for preventing a remodeling process with chronic dysfunction. We recently identified an immune niche for basal-epithelial stem cells using mouse models of injury after respiratory viral infection. Niche function depended on an early sentinel population of monocyte-derived dendritic cells (moDCs) that provided ligand GPNMB to basal-ESC receptor CD44 for reprogramming towards chronic lung disease. These same cell and molecular control points worked directly in mouse and human basal-ESC organoids, but the findings were not yet validated in vivo in human disease. Further, persistence of GPNMB expression in moDCs and M2-macrophages in mouse models suggested utility as a long-term disease biomarker in humans. Here we show increased expression of GPNMB localized to moDC-macrophage populations in lung tissue samples from long-term Covid, asthma, and COPD. The findings thereby provide initial evidence of a persistent and correctable pathway from acute injury to chronic disease with implications for cellular reprogramming and inflammatory memory.New and noteworthyRecent work indicates that a sentinel immune niche provides GPNMB to epithelial stem cells to drive structural remodeling and disease as exemplified by the response to respiratory viral injury. The present study provides initial evidence that this niche can be detected in humans in the context of comparable diseases (long-term Covid, asthma, and COPD) also linked to viral infection. The results support a persistent mechanism for inflammatory disease that might be correctable with GPNMB blockade directly or indirectly through related signaling pathways.
Integrative multi-omics reveal glial signatures associated with accelerated cognitive decline in Alzheimer’s disease
Authors: Schneegans Eléonore , Fancy Nurun , Thomas Michael , Adair Emily , Willumsen Nanet , Papageorgopoulou Marianna , Chau Vicky , Cheung To Ka Dorcas , Muirhead Robert C.J. , Whitwell Harry , Yagoubi Riad , Zhang Xiaowen , McGarry Aisling , Schilder Brian M , Matthews Paul M. , Jackson Johanna S 
Published: August 2024

AbstractAlzheimer’s disease (AD) is a neurodegenerative disorder characterised by progressive cognitive decline and memory loss caused by both genetic and environmental factors. Synapse dysfunction and loss are strongly related to cognitive decline in AD. This study integrates genomic, transcriptomic, proteomic and immunohistological (multi-omics) data and longitudinal cognitive data across several AD cohorts to elucidate the molecular drivers associated with astrocytes and microglia involved in these processes. Our findings demonstrate that activation of microglia and astrocytes occurs in specific cell subsets that are enriched in AD risk genes. Transcriptomic evidence for early microglial activation precedes immunohistological expression of severe neuropathology. Proteomic markers of astrocytic response appear to be most strongly associated with accelerated cognitive decline. However, we also found that brains from donors with a history of more rapid cognitive decline showed evidence for reduced SNAP25-VAMP interactions indicative of synaptic dysfunction, exhibited higher neurotoxic astrocyte reactivity, and were associated with the expression of neuronal markers of injury. Related molecular signatures in cerebrospinal fluid and plasma may provide biomarkers to identify patients at higher risk for rapid cognitive decline. Together, our results connect glial activation to synaptic dysfunction and cognitive decline in AD and highlight roles for microglial activation in the genesis of AD and later astrocyte activation as a potential determinant of clinical symptom progression.
Repetitive Transcranial Magnetic Stimulation Modulates Brain Connectivity in Children with Self-limited Epilepsy with Centrotemporal Spikes
Authors: She Xiwei , Qi Wendy , Nix Kerry C. , Menchaca Miguel , Cline Christopher C. , Wu Wei , He Zihuai , Baumer Fiona M. 
Published: August 2024

AbstractObjectiveInterictal epileptiform discharges (IEDs) alter brain connectivity in children with epilepsy; this connectivity change may be a mechanism by which epilepsy induces cognitive deficits. Here, we test whether repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, modulates connectivity and reduces IEDs in children with epilepsy.MethodsNineteen children with self-limited epilepsy with centrotemporal spikes (SeLECTS) participated in a cross-over study comparing the impact of active vs. sham rTMS on IEDs and brain connectivity. SeLECTS is an epilepsy syndrome affecting the motor cortex, and prior studies show that motor cortices become pathologically hyper-connected to frontal and temporal language cortices. Using a crossover design, we compared the effect of single doses of active versus sham motor cortex rTMS. Connectivity, which was quantified by the weighted phase lag index (wPLI), was measured before and after rTMS using single pulses of TMS combined with EEG (spTMS-EEG). Analyses focused on six regions: bilateral motor cortices and bilateral inferior frontal and superior temporal regions. IEDs were counted in the five minutes before and after rTMS.ResultsActive, but not sham, rTMS significantly and globally decreased wPLI connectivity between multiple regions, with the greatest reductions seen in the superior temporal region connections in the stimulated hemisphere. Additionally, there was a trend suggesting that rTMS decreases IED frequency.InterpretationThese findings underscore the potential of low-frequency rTMS to target pathologic hyperconnectivity and reduce IEDs in children with SeLECTS and potentially other pediatric epilepsy syndromes, offering a promising avenue for therapeutic intervention.
Impact of unequal testing on vaccine effectiveness estimates across two study designs: a simulation study
Authors: Bodner Korryn , Wang Linwei , Kustra Rafal , Kwong Jeffrey C. , Sander Beate , Sbihi Hind , Irvine Michael A , Mishra Sharmistha 
Published: August 2024

AbstractObservational studies are essential for measuring vaccine effectiveness. Recent research has raised concerns about how a relationship between testing and vaccination may affect estimates of vaccine effectiveness against symptomatic infection (symptomatic VE). Using an agent-based network model and SARS-CoV-2 as an example, we investigated how differences in the likelihood of testing by vaccination could influence estimates of symptomatic VE across two common study designs: retrospective cohort and test-negative design. First, we measured the influence of unequal testing on symptomatic VE estimates across study designs and sampling periods. Next, we investigated if the magnitude of bias in VE estimates from unequal testing was shaped by the level of immune escape (vaccine efficacy against susceptibility and against infectiousness) and underlying epidemic potential (probability of transmission). We found that unequal testing led to larger biases in the cohort design than the test-negative design and that biases were largest with lower efficacy against susceptibility. We also found the magnitude of bias was moderated by the sampling period, efficacy against infectiousness, and probability of transmission, with more pronounced moderating effects in the test-negative design. Our study illustrates that VE estimates across study designs require careful interpretation, especially in the presence of epidemic and immunological heterogeneity.
No evidence that retinol is protective for skin cancer
Authors: Helder Marloes , Pandeya Nirmala , Seviiri Mathias , Olsen Catherine M. , Whiteman David C. , Law Matthew H. 
Published: August 2024

ABSTRACTWith over 1.5 million new cases annually, skin cancers are the most commonly diagnosed group of cancers worldwide. Among these, melanoma and keratinocyte cancers (KC), comprising squamous cell carcinoma (SCC) and basal cell carcinoma (BCC), are predominant. Retinol, a vitamin A derivative, is essential in the regulation of growth and differentiation of epidermal cells. Moreover, retinol exhibits antioxidant properties, protecting the skin against ultra-violet (UV) radiation induced oxidative damage.Existing research on the impact of retinol on melanoma, SCC and BCC development shows mixed results. Several dietary intake studies have suggested that higher retinol levels reduce skin cancer risk, however, others have failed to find this association.We used two-sample Mendelian randomization (MR) to explore if there is a causal relationship between retinol and the risk of developing melanoma, SCC or BCC. Genetically predicted circulating retinol levels were obtained from a genome wide association study (GWAS) meta-analysis of the INTERVAL (N=11,132) and METSIM (N=6,136) cohorts. Melanoma (30,134 cases and 375,188 controls), SCC (10,557 cases and 537,850 controls) and BCC (36,479 cases and 540,185 controls) risks were derived from published GWAS meta-analyses. We conducted two MR approaches. In the first MR we used a single SNP (rs10882283) that is associated with the levels of Retinol Binding Protein 4 (RBP4) as an instrument variable (IV) for circulating retinol levels. In the second MR we used all independent genetic variants that were strongly associated (P < 5 × 10−8) with retinol levels as IVs. Odds ratios (OR) for skin cancer were calculated for a one standard deviation (SD) increase in genetically predicted retinol levels.The single IV approach revealed that retinol levels were not significantly associated with risk of melanoma (OR = 1.04 [95% confidence interval 0.83, 1.31], P = 0.72), SCC (OR = 1.15[0.87, 1.51], P = 0.32) or BCC (OR = 1.06 [0.90, 1.23], P = 0.50). Similar null results were observed with the multiple IV approach for melanoma (OR = 1.03 [0.95, 1.11], P = 0.54), SCC (OR = 1.01 [0.91, 1.13], P = 0.83), and BCC (OR = 1.04 [0.96, 1.12], P = 0.38).In conclusion, we found no evidence that circulating retinol levels were causally associated with the development of melanoma, SCC and BCC.