bluuebunny/crossref_metadata_2025_split huggingface dataset:
Soil organic carbon stocks and stabilization mechanisms in tidal marshes along estuarine gradients
Authors: Neiske Friederike , Seedtke Maria , Eschenbach Annette , Wilson Monica , Jensen Kai , Becker Joscha N. 
Published: May 2024

AbstractTidal marshes store large amounts of soil organic carbon (SOC), however, little is known on SOC stabilization mechanisms in these ecosystems. In estuarine marshes, SOC storage is dominated by a complex interaction of tidal inundation and salinity with biotic ecosystem components, leading to strong spatio-temporal variations within estuaries. Our aim was to assess (i) SOC stocks, (ii) SOC stabilization mechanisms (aggregation and mineral-association), and (iii) their environmental drivers along estuarine gradients. We analyzed SOC stocks and SOC density fractions in topsoil (0-10 cm) and subsoil (10-30 cm) of three marsh zones representing three flooding regimes (daily, monthly, yearly) in three marsh types along the salinity gradient (salt, brackish, freshwater) of the Elbe Estuary, Germany.Increasing salinity and flooding reduced SOC stocks 0-30 cm (9.3-74.6 t ha-1), which was related to decreasing plant biomass and soil texture. Mineral-associated organic matter (CMAOM) was the largest SOC fraction (59% of total SOC), followed by aggregate-occluded organic matter (CoPOM) (24%) and free particulate organic matter (CfPOM) (16%). The CMAOMamount in topsoils decreased downstream with increasing salinity, reflecting decreasing fine-texture along the estuary. The amount of CoPOMwas higher in topsoils and high marshes, indicating negative effects of flooding on aggregation. The relative proportion of CfPOM(% of total SOC) increased with increasing flooding frequency and reducing soil conditions.Our results underline the importance of estuarine gradients as drivers of SOC storage and stabilization. Climate-change induced sea-level rise and variations in salinity might reduce SOC storage and stabilization in estuaries.
Overexpression of α-SNAPRhg1can improverhg1-amediated soybean resistance to soybean cyst nematode
Authors: Haarith Deepak , Das Soumita , Nelson Emma , Zaptocony Ryan , Bent Andrew 
Published: May 2024

(i)SummaryTherhg1-aandrhg1-bhaplotypes of the soybeanRhg1locus are economically effective tools for the control of soybean cyst nematode (SCN;Heterodera glycines), but ongoing SCN evolution requires improved sources of resistance. BothRhg1haplotypes carry multiple tandem repeat copies of a four-gene block encoding four disparate proteins; resistance efficacy scales with copy number. The haplotypes encode different variants of an unusual α-SNAP protein whose abundance increases in the nematode-reprogrammed plant cells that form the syncytium (nematode feeding site), which subsequently collapses. Simultaneous presence of the two α-SNAPRhg1protein types, or substantially elevated expression of either type, was hypothesized to improve SCN resistance but has not been achievable by conventional plant breeding methods. We accomplished both, by transgenic additions to anrhg1-a Rhg4soybean line. Existing resistance to HG type 0 and HG type 2.5.7 SCN was strengthened, but resistance was not improved against an HG type 1.3.6.7 SCN population that was already highly virulent on the parent line. No significant yield penalties from constitutive overexpression of transgenic α-SNAP genes were observed in greenhouse or initial field studies. Cisgenic combination or elevated expression of the different α-SNAP genes may extend the efficacy and/or durability ofRhg1-mediated resistance. We also observed differential protein abundances for some α-SNAPRhg1isoforms after inoculation with different HG type populations of SCN. These approaches provide opportunities to understand the different mechanisms of the twoRhg1haplotypes and to possibly fine-tune them for better management of SCN.
Hippocampal neuroinflammation causes sex-specific disruptions in action selection, food approach memories, and neuronal activation
Authors: Ganesan Kiruthika , Ghorbanpour Sahar , Kendall William , Broome Sarah Thomas , Gladding Joanne M. , Dhungana Amolika , Abiero Arvie Rodriguez , Mahmoudi Maedeh , Castorina Alessandro , Kendig Michael D. , Becchi Serena , Valova Veronika , Cole Louise , Bradfield Laura A. 
Published: May 2024

AbstractHippocampal neuroinflammation is present in multiple diseases and disorders that impact motivated behaviour in a sex-specific manner, but whether neuroinflammation alone is sufficient to disrupt such behaviour is unknown. We investigated this question here using mice. First, the application of an endotoxin to primary cultures containing only hippocampal neurons did not affect their activation. However, when the same endotoxin was applied to mixed neuronal/glial cultures it did increase neuronal activation, providing initial indications of how it might be able to effect behavioural change. We next demonstrated neuroinflammatory effects on behaviour directly, demonstrating that intra-hippocampal administration of the same endotoxin increased locomotor activity and accelerated goal-directed learning in both male and female mice. In contrast, hippocampal neuroinflammation caused sex-specific disruptions to the acquisition of instrumental actions and to Pavlovian food-approach memories. Finally, we showed that hippocampal neuroinflammation had a sexually dimorphic effect on neuronal activation: increasing it in females and decreasing it in males.
Production and functional verification of 8-gene (GGTA1, CMAH, β4GalNT2, hCD46, hCD55, hCD59, hTBM, hCD39)-edited donor pigs for xenotransplantation
Authors: Wang Jiaoxiang , Xu Kaixiang , Liu Tao , Zhao Heng , Jamal Muhammad Ameen , Chen Gen , Huo Xiaoying , Yang Chang , Jiao Deling , Wei Taiyun , Huang Hanfei , Zhao Hongfang , Guo Jianxiong , Wang Fengchong , Zhang Xiong , Liu Kai , Qu Siming , Wang Gang , Zhao Hong-Ye , Zeng Zhong , Wei Hong-Jiang 
Published: May 2024

AbstractGene-edited pig-to-human xenotransplantation continues to make breakthroughs and is expected to enter clinic to solve the global shortage of donor organs. However, which gene combination is suitable for which organ transplantation remains unclear. In this study, we utilized CRISPR/Cas9 gene editing technology, PiggyBac transposon system and somatic cell cloning to construct GTKO/CMAHKO/β4GalNT2KO/hCD46/hCD55/hCD59/hCD39/hTBM 8 gene-edited cloned (GEC) donor pigs, and performed pig to non-human primate (NHP) transplantation to evaluate the effectiveness of these GEC pigs. The multiple vectors were co-transfected into fetal fibroblasts of Diannan miniature pig with O blood type, and 25 colonies were screened out, and one of them carried GGTA1, CMAH and β4GalNT2 biallelic knockout and integration of hCD46, hCD55, hCD59, hTBM and hCD39 genes, which was used as a donor cell for cloning, and a 33-day-old viable fetus was obtained. The fetus was identified and confirmed for normal karyotype and the absence of three xenogeneic antigens α-Gal, Neu5Gc and Sda, and expression of hCD46, hCD55, hCD59, hTBM and hCD39 genes, then the recloning was carried out and 28 cloned piglets were obtained by natural delivery. Molecular identification at DNA, mRNA and protein levels showed that 8 gene editing (GE) was successful in these GEC piglets. Moreover, antigen-antibody binding assay and complement-dependent cytotoxicity assay demonstrated that 8GE effectively reduced the immune incompatibility and kidney xenograft survived up to 15 and 17 days into two NHPs, respectively. During this period, the recipient serum antibodies IgA and IgM, complements C3 and C4, coagulation indicators PT, APTT, TT and FIB, as well as most electrolytes and liver function indicators remained relatively stable. The 24-hour urine output and serum creatinine remained normal at a period of post-transplantation. These results indicated that the 8GEC pigs effectively alleviated immune rejection and exerted life-supporting kidney function in the recipient.
Regional Differences in the US in Outcomes with Preeclampsia
Authors: Rajendran Aardra , Liu Yisi , Boyer Theresa M. , Vaught Arthur J. , Hays Allison G. , Coresh Josef , Vaidya Dhananjay , Michos Erin D. , Minhas Anum S. 
Published: May 2024

AbstractThis study explores preeclampsia outcomes across US regions and examines regional differences in specific preeclampsia-associated pregnancy complications and disease management. Patient-reported measures were obtained from The Preeclampsia Registry, an open-access database composed of women with at least one pregnancy diagnosed with a hypertensive disorder of pregnancy. Pregnancies and associated outcomes were stratified by US region (Northeast, Midwest, South and West). Among 2,667 pregnancies of which 92% were in White women, maximum systolic blood pressure at any time in pregnancy was highest among women in the South and Midwest (p=0.039). Furthermore, more women in the South received pre-pregnancy anti- hypertensives (p=0.026) and antenatal steroids (p=0.025) and delivered at an earlier gestational age (p=0.014) compared to women in other regions. Pregnancy complications such as elevated liver enzymes were higher in women in the South (p=0.019), and women in the South and West had additional end-organ damage such as renal complications (p<0.001) and hemolysis (p=0.008) as compared to women in other regions. Further investigation is needed to assess whether healthcare access or policy could be contributing to these regional discrepancies.
The textures of sarcoidosis: quantifying lung disease through variograms
Authors: Lippitt William L. , Maier Lisa A. , Fingerlin Tasha E. , Lynch David A. , Yadav Ruchi , Rieck Jared , Hill Andrew C. , Liao Shu-Yi , Mroz Margaret M. , Barkes Briana Q. , Chae Kum Ju , Hwang Hye Jeon , Carlson Nichole E. 
Published: May 2024

AbstractObjectiveSarcoidosis is a granulomatous disease affecting the lungs in over 90% of patients. Qualitative assessment of chest CT by radiologists is standard clinical practice and reliable quantification of disease from CT would support ongoing efforts to identify sarcoidosis phenotypes. Standard imaging feature engineering techniques such as radiomics suffer from extreme sensitivity to image acquisition and processing, potentially impeding generalizability of research to clinical populations. In this work, we instead investigate approaches to engineering variogram-based features with the intent to identify a robust, generalizable pipeline for image quantification in the study of sarcoidosis.ApproachFor a cohort of more than 300 individuals with sarcoidosis, we investigated 24 feature engineering pipelines differing by decisions for image registration to a template lung, empirical and model variogram estimation methods, and feature harmonization for CT scanner model, and subsequently 48 sets of phenotypes produced through unsupervised clustering. We then assessed sensitivity of engineered features, phenotypes produced through unsupervised clustering, and sarcoidosis disease signal strength to pipeline.Main resultsWe found that variogram features had low to mild association with scanner model and associations were reduced by image registration. For each feature type, features were also typically robust to all pipeline decisions except image registration. Strength of disease signal as measured by association with pulmonary function testing and some radiologist visual assessments was strong (optimistic AUC ≈ 0.9,p≪ 0.0001 in models for architectural distortion, conglomerate mass, fibrotic abnormality, and traction bronchiectasis) and fairly consistent across engineering approaches regardless of registration and harmonization for CT scanner.SignificanceVariogram-based features appear to be a suitable approach to image quantification in support of generalizable research in pulmonary sarcoidosis.
Combining clinical and diagnostic surveillance to estimate the burden of measles disease: a modeling study
Authors: Leung Tiffany , Ferrari Matthew 
Published: May 2024

AbstractBackgroundThe clinical case definition for measles is highly sensitive and has low specificity. Diag-nostic confirmation can resolve this uncertainty for individual cases and is a crucial tool for confirmation of measles outbreaks. However, in under-resourced settings, it is prohibitive to confirm all suspected cases and routine measles surveillance comprises a combination of both clinically and diagnostically confirmed cases.MethodsWe developed a dynamic model of measles, rubella, and other sources of febrile rash to simulate time series of a suspected measles surveillance system. We simulated partial reporting of suspected cases and limited routine diagnostic testing using assays with sensitivity and specificity that correspond to current or proposed rapid diagnostic tests. We estimated the time series of reported measles cases as the product of suspected cases and the proportion of diagnostic positive cases. We then estimated the reporting rate and annual incidence for measles using the time-series SIR model.ResultsReconstructing the time series of reported measles cases using the fraction of diagnostic positive cases results in unbiased estimates of the reporting rate and the annual incidence at moderate vaccination levels for all reasonable levels of test sensitivity and specificity, even for low proportions tested. At high vaccination levels, diagnostic tests with low sensitivity (<90%) lead to slight bias in annual incidence. Temporal variation in the prevalence of measles among suspected cases require that the proportion of cases attributable to measles be estimated frequently (i.e., monthly) to avoid bias in estimates.ConclusionCombining routine, systematic diagnostic confirmation of suspected measles cases with suspected cases surveillance can improve estimates of the reporting rate and annual incidence using diagnostic tests with sensitivity and specificity consistent with proposed rapid diagnostic tests.
Clinical and genetic association studies reveal within-individual variability as an integral part of Huntington disease
Authors: Aziz N. Ahmad 
Published: May 2024

AbstractHuntington disease (HD) is one of the most common repeat expansion disorders. Clinically, HD patients exhibit considerable visit-to-visit variability in symptoms and signs independent of measuring method or rater, yet neither the precise nature nor the determinants of this clinical variability are known. Leveraging detailed genetic and longitudinal clinical data from large cohorts of HD patients, this work1)establishes within-individual variability in disease expression as an integral part of HD semiology, demonstrating that it increases with disease duration, mutation size, younger age-at-onset, and lower body weight,2)provides a mathematical framework linking higher phenotypic variability to increased predictive entropy, revealing a fundamental relation between within-individual variability and energy expenditure, and3)identifies novel genetic modifiers of both within-individual variability and age-at-onset in HD. Thus, accounting for within-individual variability in HD could facilitate the discovery of pathogenic mechanisms and outcomes directly relevant to the development of disease modifying therapies.
The nitrogen-fixing fernAzollahas a complex microbiome characterized by multiple modes of transmission
Authors: Song Michael J. , Li Fay-Wei , Freund Forrest , Tribble Carrie M. , Toffelmier Erin , Miller Courtney , Shaffer H. Bradley , Rothfels Carl J. 
Published: May 2024

AbstractAzollais a floating fern that has closely evolved with a vertically transmitted obligate cyanobacterium endosymbiont—Anabaena azollae—that performs nitrogen fixation in specializedAzollaleaf pockets. This cyanobac-terium has a greatly reduced genome and appears to be in the “advanced” stages of symbiosis, potentially evolving into a nitrogen-fixing organelle. However, there are also other lesser-known inhabitants of the leaf pocket whose role and mode of transmission are unknown. We sequenced 112Azollaspecimens collected across the state of California and characterized their metagenomes in order to identify the common bacterial endosymbionts of the leaf pocket and assess their patterns of co-diversification. Four taxa were found across all samples, establishing that there are multiple endosymbionts that consistently inhabit theAzollaleaf pocket. We found varying degrees of co-diversification across these taxa as well as varying degrees of isolation by distance and of pseudogenation, which implies that the endosymbiotic community is transmitted by a mix of horizontal and vertical mechanisms, and that some members of the microbiome are more facultative symbionts than others. These results show that theAzollasymbiotic community is complex, featuring members at potentially different stages of symbiosis evolution, further supporting the utility of theAzollamicrocosm as a system for studying the evolution of symbioses.
Transcriptional Signatures of Domestication Revealed by Meta-Analysis of Pig, Chicken, Wild Boar, and Red Junglefowl Gene Expression Data
Authors: Uno Motoki , Bono Hidemasa 
Published: May 2024

AbstractDomesticated animals have undergone significant changes in their behavior, morphology, and physiological functions during domestication. To identify the changes in gene expression associated with domestication, we collected RNA-seq data of pigs, chickens, wild boars, and red junglefowl from public databases and performed a meta-analysis. Gene expression was quantified and the expression ratio between domesticated animals and their wild ancestors (DW-ratio) was calculated. Genes were classified as “upregulated,” “downregulated,” or “unchanged” based on their DW-ratio, and DW-score was calculated for each gene. Gene set enrichment analysis revealed that genes upregulated in pigs were related to defense from viral infection, whereas those upregulated in chickens were associated with aminoglycan and carbohydrate derivative catabolic processes. Genes commonly upregulated in pigs and chickens are involved in the immune response, olfactory learning, epigenetic regulation, cell division, and extracellular matrix. In contrast, genes upregulated in wild boar and red junglefowl are related to stress response, cell proliferation, cardiovascular function, neural regulation, and energy metabolism. These findings provide valuable insights into the genetic basis of the domestication process and highlight potential candidate genes for breeding applications.Simple SummaryDomesticated animals, such as pigs and chickens, have undergone significant genetic changes compared to their wild ancestors. We collected gene expression data from pigs, chickens, wild boars, and red junglefowl, and performed a comprehensive analysis. We identified differentially expressed genes by comparing the gene expression patterns of domesticated animals and their wild counterparts. These genes are involved in various biological processes, including immune response, metabolism, and stress response. Notably, domesticated animals exhibited higher expression of genes related to viral resistance and bone weakness, whereas their wild ancestors showed higher expression of genes associated with stress response and energy metabolism. Identifying these differentially expressed genes provides valuable insights into the genetic changes that occurred during the domestication process. Furthermore, these findings have highlighted potential candidate genes that could be targeted in breeding programs to improve the health and productivity of domesticated animals, ultimately contributing to the development of sustainable livestock production and addressing the growing global food demand.
Biochemical and neurophysiological effects of deficiency of the mitochondrial import protein TIMM50
Authors: Paz Eyal , Jain Sahil , Gottfried Irit , Staretz-Chacham Orna , Mahajnah Muhammad , Bagchi Pritha , Seyfried Nicholas T. , Ashery Uri , Azem Abdussalam 
Published: May 2024

AbstractTIMM50, an essential TIM23 complex subunit, is suggested to facilitate the import of ∼60% of the mitochondrial proteome. In this study, we characterized aTIMM50disease causing mutation in human fibroblasts and noted significant decreases in TIM23 core protein levels (TIMM50, TIMM17A/B, and TIMM23). Strikingly, TIMM50 deficiency had no impact on the steady state levels of most of its putative substrates, suggesting that even low levels of a functional TIM23 complex are sufficient to maintain the majority of TIM23 complex-dependent mitochondrial proteome. As TIMM50 mutations have been linked to severe neurological phenotypes, we aimed to characterize TIMM50 defects in manipulated mammalian neurons. TIMM50 knockdown in mouse neurons had a minor effect on the steady state level of most of the mitochondrial proteome, supporting the results observed in patient fibroblasts. Amongst the few affected TIM23 substrates, a decrease in the steady state level of components of the intricate oxidative phosphorylation and mitochondrial ribosome complexes was evident. This led to declined respiration rates in fibroblasts and neurons, reduced cellular ATP levels and defective mitochondrial trafficking in neuronal processes, possibly contributing to the developmental defects observed in patients with TIMM50 disease. Finally, increased electrical activity was observed in TIMM50 deficient mice neuronal cells, which correlated with reduced levels of KCNJ10 and KCNA2 plasma membrane potassium channels, likely underlying the patients’ epileptic phenotype.
Canonical neurodevelopmental trajectories of structural and functional manifolds
Authors: Monaghan Alicja , Bethlehem Richard. A.I. , Akarca Danyal , Margulies Daniel ,   the Team CALM, Astle Duncan E. 
Published: May 2024

ABSTRACTOrganisational gradients refer to a continuous low-dimensional embedding of brain regions and can quantify core organisational principles of complex systems like the human brain. Mapping how these organisational principles are altered or refined across development and phenotypes is essential to understanding the relationship between brain and behaviour. Taking a developmental approach and leveraging longitudinal and cross-sectional data from two multi-modal neuroimaging datasets, spanning the full neurotypical-neurodivergent continuum, we charted the organisational variability of structural (N = 887) and functional (N = 728) gradients, across childhood and adolescence (6-19 years old). Across datasets, despite differing phenotypes, we observe highly similar structural and functional gradients. These gradients, or organisational principles, are highly stable across development, with the exact same ordering across early childhood into mid-adolescence. However, there is substantial developmental change in the strength of embedding within those gradients: by modelling developmental trajectories as non-linear splines, we show that structural and functional gradients exhibit sensitive periods and are refined across development. Specifically, structural gradients gradually contract in low-dimensional space as networks become more integrated, whilst the functional manifold expands, indexing functional specialisation. The coupling of these structural and functional gradients follows a unimodal-association axis and varies across individuals, with developmental effects concentrated in the more plastic higher-order networks. Importantly, these developmental effects on coupling, in these higher-order networks, are attenuated in the neurodivergent sample. Finally, we mapped structure-function coupling onto dimensions of psychopathology and cognition and demonstrate that coupling is a robust predictor of dimensions of cognition, such as working memory, but not psychopathology. In summary, across clinical and community samples, we demonstrate consistent principles of structural and functional brain organisation, with progressive structural integration and functional segregation. These are gradients are established early in life, refined through development, and their coupling is a robust predictor of working memory.