bluuebunny/crossref_metadata_2025_split huggingface dataset:
Role of rs2282679 in 25-hydroxyvitamin D levels and insulin resistance after a sleeve gastrectomy
Authors: de Luis Daniel , Izaola Olatz , Primo David , López Gómez Juan José , Pacheco David 
Published: April 2024

Abstract
Background & aims
Some studies have reported links between 25-hydroxyvitamin D levels and the presence of obesity and some genetic variants. The aim of our design was to evaluate the effects of rs2282679 genetic variant of CG gene on 25-hydroxyvitamin D levels, weight loss and metabolic parameters after a robotic sleeve gastrectomy in premenopausal females with obesity.

Methods
76 participants were enrolled. 25-hydroxyvitamin D levels, biochemical evaluation and anthropometric parameters were registered before surgery and after 3, 6 and 12 months follow up. Genotype of rs2282679 CG gene was evaluated.

Results
The improvements in anthropometric parameters, blood pressure and lipid profile were similar in both genotypes (TT vs TG + GG). Basal insulin levels and HOMA-IR were greater in G allele carriers than non-carriers (Delta: 6.7 ± 1.2 mUI/L; p = 0.01) and (Delta: 1.3 ± 0.1 units; p = 0.02). 25-hydroxyvitamin D levels were lower in G allele carriers than non-carriers (Delta: 8.1 ± 1.1 ng/dl; p = 0.03). The levels of insulin and HOMA-IR remained greater in G allele carriers than non-carriers throughout all the visits. The levels of 25-hydroxyvitamin D remained lower in G allele carriers than non-G allele. The average level of 25-hydroxyvitamin D at 12 months in non-G allele carriers were above 30 ng/dl (36.0 ± 3.1 ng/dl) and the level in G allele carriers were below (24.9 ± 4.9 ng/dl).

Conclusions
rs 2282679 (GC) was related with low 25 hydroxyvitamin D levels and insulin resistance. In addition, the presence of G allele produced a decrease in the improvement of 25-hydroxyvitamin D levels and insulin resistance after weight loss during 12 months.
Acidovorax temperans skews neutrophil maturation and polarizes Th17 cells to promote lung adenocarcinoma development
Authors: Stone Joshua K. , von Muhlinen Natalia , Zhang Chenran , Robles Ana I. , Flis Amy L. , Vega-Valle Eleazar , Miyanaga Akihiko , Matsumoto Masaru , Greathouse K. Leigh , Cooks Tomer , Trinchieri Giorgio , Harris Curtis C. 
Published: April 2024

Abstract
Change within the intratumoral microbiome is a common feature in lung and other cancers and may influence inflammation and immunity in the tumor microenvironment, affecting growth and metastases. We previously characterized the lung cancer microbiome in patients and identified Acidovorax temperans as enriched in tumors. Here, we instilled A. temperans in an animal model driven by mutant K-ras and Tp53. This revealed A. temperans accelerates tumor development and burden through infiltration of proinflammatory cells. Neutrophils exposed to A. temperans displayed a mature, pro-tumorigenic phenotype with increased cytokine signaling, with a global shift away from IL-1β signaling. Neutrophil to monocyte and macrophage signaling upregulated MHC II to activate CD4+ T cells, polarizing them to an IL-17A+ phenotype detectable in CD4+ and γδ populations (T17). These T17 cells shared a common gene expression program predictive of poor survival in human LUAD. These data indicate bacterial exposure promotes tumor growth by modulating inflammation.
Cerebral blood flow dynamics during cardiac surgery in infants
Authors: Leth-Olsen Martin , Døhlen Gaute , Torp Hans , Nyrnes Siri Ann 
Published: April 2024

Abstract
Background
In this pilot study, we investigated continuous cerebral blood flow velocity measurements to explore cerebrovascular hemodynamics in infants with congenital heart disease undergoing cardiac surgery.

Methods
A non-invasive transfontanellar cerebral Doppler monitor (NeoDoppler) was used to monitor 15 infants (aged eight days to nine months) during cardiac surgery with cardiopulmonary bypass. Numerical and visual analyses were conducted to assess trends and events in Doppler measurements together with standard monitoring equipment. The mean flow index, calculated as the moving Pearson correlation between mean arterial pressure and time averaged velocity, was utilized to evaluate dynamic autoregulation. Two levels of impaired autoregulation were defined (Mean flow index >0.3/0.45), and percentage of time above these limits were calculated.

Results
High quality recordings were achieved during 90.6% of the monitoring period. There was a significant reduction in time averaged velocity in all periods of cardiopulmonary bypass. All patients showed a high percentage of time with impaired dynamic autoregulation, with Mean flow index >0.3 and 0.45: 73.71% ± 9.06% and 65.16% ± 11.27% respectively. Additionally, the system promptly detected hemodynamic events.

Conclusion
Continuous transfontanellar cerebral Doppler monitoring could become an additional tool in enhancing cerebral monitoring in infants during cardiac surgery.

Impact

This pilot study demonstrates the feasibility of continuous transfontanellar Doppler monitoring of cerebral blood flow velocities during cardiac surgery in infants.

It also demonstrates a high proportion of time with impaired cerebral autoregulation during cardiac surgery based on the Mean flow index.

Continuous transfontanellar Doppler could become a useful tool to improve cerebral monitoring and provide new pathophysiological insight.
Shared inflammatory glial cell signature after stab wound injury, revealed by spatial, temporal, and cell-type-specific profiling of the murine cerebral cortex
Authors: Koupourtidou Christina , Schwarz Veronika , Aliee Hananeh , Frerich Simon , Fischer-Sternjak Judith , Bocchi Riccardo , Simon-Ebert Tatiana , Bai Xianshu , Sirko Swetlana , Kirchhoff Frank , Dichgans Martin , Götz Magdalena , Theis Fabian J. , Ninkovic Jovica 
Published: April 2024

AbstractTraumatic brain injury leads to a highly orchestrated immune- and glial cell response partially responsible for long-lasting disability and the development of secondary neurodegenerative diseases. A holistic understanding of the mechanisms controlling the responses of specific cell types and their crosstalk is required to develop an efficient strategy for better regeneration. Here, we combine spatial and single-cell transcriptomics to chart the transcriptomic signature of the injured male murine cerebral cortex, and identify specific states of different glial cells contributing to this signature. Interestingly, distinct glial cells share a large fraction of injury-regulated genes, including inflammatory programs downstream of the innate immune-associated pathways Cxcr3 and Tlr1/2. Systemic manipulation of these pathways decreases the reactivity state of glial cells associated with poor regeneration. The functional relevance of the discovered shared signature of glial cells highlights the importance of our resource enabling comprehensive analysis of early events after brain injury.
Late Paleozoic oxygenation of marine environments supported by dolomite U-Pb dating
Authors: Ben-Israel Michal , Holder Robert M. , Nelson Lyle L. , Smith Emily F. , Kylander-Clark Andrew R. C. , Ryb Uri 
Published: April 2024

AbstractUnderstanding causal relationships between evolution and ocean oxygenation hinges on reliable reconstructions of marine oxygen levels, typically from redox-sensitive geochemical proxies. Here, we develop a proxy, using dolomite U–Pb geochronology, to reconstruct seawater U/Pb ratios. Dolomite samples consistently give U–Pb dates and initial 207Pb/206Pb ratios lower than expected from their stratigraphic ages. These observations are explained by resetting of the U–Pb system long after deposition; the magnitude of deviations from expected initial 207Pb/206Pb are a function of the redox-sensitive U/Pb ratios during deposition. Reconstructed initial U/Pb ratios increased notably in the late-Paleozoic, reflecting an increase in oxygenation of marine environments at that time. This timeline is consistent with documented shifts in some other redox proxies and supports evolution-driven mechanisms for the oxygenation of late-Paleozoic marine environments, as well as suggestions that early animals thrived in oceans that on long time scales were oxygen-limited compared to today.
Intrinsic exchange biased anomalous Hall effect in an uncompensated antiferromagnet MnBi2Te4
Authors: Chong Su Kong , Cheng Yang , Man Huiyuan , Lee Seng Huat , Wang Yu , Dai Bingqian , Tanabe Masaki , Yang Ting-Hsun , Mao Zhiqiang , Moler Kathryn A. , Wang Kang L. 
Published: April 2024

AbstractAchieving spin-pinning at the interface of hetero-bilayer ferromagnet/antiferromagnet structures in conventional exchange bias systems can be challenging due to difficulties in interface control and the weakening of spin-pinning caused by poor interface quality. In this work, we propose an alternative approach to stabilize the exchange interaction at the interface of an uncompensated antiferromagnet by utilizing a gradient of interlayer exchange coupling. We demonstrate this exchange interaction through a designed field training protocol in the odd-layer topological antiferromagnet MnBi2Te4. Our results reveal a remarkable field-trained exchange bias of up to ~ 400 mT, which exhibits high repeatability and can be easily reset by a large training field. Notably, this field-trained exchange bias effect persists even with zero-field initialization, presenting a stark contrast to the traditional field-cooled exchange bias. The highly tunable exchange bias observed in this single antiferromagnet compound, without the need for an additional magnetic layer, provides valuable insight into the exchange interaction mechanism. These findings pave the way for the systematic design of topological antiferromagnetic spintronics.
Genomic language model predicts protein co-regulation and function
Authors: Hwang Yunha , Cornman Andre L. , Kellogg Elizabeth H. , Ovchinnikov Sergey , Girguis Peter R. 
Published: April 2024

Abstract
Deciphering the relationship between a gene and its genomic context is fundamental to understanding and engineering biological systems. Machine learning has shown promise in learning latent relationships underlying the sequence-structure-function paradigm from massive protein sequence datasets. However, to date, limited attempts have been made in extending this continuum to include higher order genomic context information. Evolutionary processes dictate the specificity of genomic contexts in which a gene is found across phylogenetic distances, and these emergent genomic patterns can be leveraged to uncover functional relationships between gene products. Here, we train a genomic language model (gLM) on millions of metagenomic scaffolds to learn the latent functional and regulatory relationships between genes. gLM learns contextualized protein embeddings that capture the genomic context as well as the protein sequence itself, and encode biologically meaningful and functionally relevant information (e.g. enzymatic function, taxonomy). Our analysis of the attention patterns demonstrates that gLM is learning co-regulated functional modules (i.e. operons). Our findings illustrate that gLM’s unsupervised deep learning of the metagenomic corpus is an effective and promising approach to encode functional semantics and regulatory syntax of genes in their genomic contexts and uncover complex relationships between genes in a genomic region.
Dbf4-dependent kinase promotes cell cycle controlled resection of DNA double-strand breaks and repair by homologous recombination
Authors: Galanti Lorenzo , Peritore Martina , Gnügge Robert , Cannavo Elda , Heipke Johannes , Palumbieri Maria Dilia , Steigenberger Barbara , Symington Lorraine S. , Cejka Petr , Pfander Boris 
Published: April 2024

AbstractDNA double-strand breaks (DSBs) can be repaired by several pathways. In eukaryotes, DSB repair pathway choice occurs at the level of DNA end resection and is controlled by the cell cycle. Upon cell cycle-dependent activation, cyclin-dependent kinases (CDKs) phosphorylate resection proteins and thereby stimulate end resection and repair by homologous recombination (HR). However, inability of CDK phospho-mimetic mutants to bypass this cell cycle regulation, suggests that additional cell cycle regulators may be important. Here, we identify Dbf4-dependent kinase (DDK) as a second major cell cycle regulator of DNA end resection. Using inducible genetic and chemical inhibition of DDK in budding yeast and human cells, we show that end resection and HR require activation by DDK. Mechanistically, DDK phosphorylates at least two resection nucleases in budding yeast: the Mre11 activator Sae2, which promotes resection initiation, as well as the Dna2 nuclease, which promotes resection elongation. Notably, synthetic activation of DDK allows limited resection and HR in G1 cells, suggesting that DDK is a key component of DSB repair pathway selection.
Loss of CREBBP and KMT2D cooperate to accelerate lymphomagenesis and shape the lymphoma immune microenvironment
Authors: Li Jie , Chin Christopher R. , Ying Hsia-Yuan , Meydan Cem , Teater Matthew R. , Xia Min , Farinha Pedro , Takata Katsuyoshi , Chu Chi-Shuen , Jiang Yiyue , Eagles Jenna , Passerini Verena , Tang Zhanyun , Rivas Martin A. , Weigert Oliver , Pugh Trevor J. , Chadburn Amy , Steidl Christian , Scott David W. , Roeder Robert G. , Mason Christopher E. , Zappasodi Roberta , Béguelin Wendy , Melnick Ari M. 
Published: April 2024

AbstractDespite regulating overlapping gene enhancers and pathways, CREBBP and KMT2D mutations recurrently co-occur in germinal center (GC) B cell-derived lymphomas, suggesting potential oncogenic cooperation. Herein, we report that combined haploinsufficiency of Crebbp and Kmt2d induces a more severe mouse lymphoma phenotype (vs either allele alone) and unexpectedly confers an immune evasive microenvironment manifesting as CD8+ T-cell exhaustion and reduced infiltration. This is linked to profound repression of immune synapse genes that mediate crosstalk with T-cells, resulting in aberrant GC B cell fate decisions. From the epigenetic perspective, we observe interaction and mutually dependent binding and function of CREBBP and KMT2D on chromatin. Their combined deficiency preferentially impairs activation of immune synapse-responsive super-enhancers, pointing to a particular dependency for both co-activators at these specialized regulatory elements. Together, our data provide an example where chromatin modifier mutations cooperatively shape and induce an immune-evasive microenvironment to facilitate lymphomagenesis.
Hidden impacts of ocean warming and acidification on biological responses of marine animals revealed through meta-analysis
Authors: Alter Katharina , Jacquemont Juliette , Claudet Joachim , Lattuca María E. , Barrantes María E. , Marras Stefano , Manríquez Patricio H. , González Claudio P. , Fernández Daniel A. , Peck Myron A. , Cattano Carlo , Milazzo Marco , Mark Felix C. , Domenici Paolo 
Published: April 2024

AbstractConflicting results remain on the impacts of climate change on marine organisms, hindering our capacity to predict the future state of marine ecosystems. To account for species-specific responses and for the ambiguous relation of most metrics to fitness, we develop a meta-analytical approach based on the deviation of responses from reference values (absolute change) to complement meta-analyses of directional (relative) changes in responses. Using this approach, we evaluate responses of fish and invertebrates to warming and acidification. We find that climate drivers induce directional changes in calcification, survival, and metabolism, and significant deviations in twice as many biological responses, including physiology, reproduction, behavior, and development. Widespread deviations of responses are detected even under moderate intensity levels of warming and acidification, while directional changes are mostly limited to more severe intensity levels. Because such deviations may result in ecological shifts impacting ecosystem structures and processes, our results suggest that climate change will likely have stronger impacts than those previously predicted based on directional changes alone.
Enhanced polarization switching characteristics of HfO2 ultrathin films via acceptor-donor co-doping
Authors: Zhou Chao , Ma Liyang , Feng Yanpeng , Kuo Chang-Yang , Ku Yu-Chieh , Liu Cheng-En , Cheng Xianlong , Li Jingxuan , Si Yangyang , Huang Haoliang , Huang Yan , Zhao Hongjian , Chang Chun-Fu , Das Sujit , Liu Shi , Chen Zuhuang 
Published: April 2024

AbstractIn the realm of ferroelectric memories, HfO2-based ferroelectrics stand out because of their exceptional CMOS compatibility and scalability. Nevertheless, their switchable polarization and switching speed are not on par with those of perovskite ferroelectrics. It is widely acknowledged that defects play a crucial role in stabilizing the metastable polar phase of HfO2. Simultaneously, defects also pin the domain walls and impede the switching process, ultimately rendering the sluggish switching of HfO2. Herein, we present an effective strategy involving acceptor-donor co-doping to effectively tackle this dilemma. Remarkably enhanced ferroelectricity and the fastest switching process ever reported among HfO2 polar devices are observed in La3+-Ta5+ co-doped HfO2 ultrathin films. Moreover, robust macro-electrical characteristics of co-doped films persist even at a thickness as low as 3 nm, expanding potential applications of HfO2 in ultrathin devices. Our systematic investigations further demonstrate that synergistic effects of uniform microstructure and smaller switching barrier introduced by co-doping ensure the enhanced ferroelectricity and shortened switching time. The co-doping strategy offers an effective avenue to control the defect state and improve the ferroelectric properties of HfO2 films.
A modular organic neuromorphic spiking circuit for retina-inspired sensory coding and neurotransmitter-mediated neural pathways
Authors: Matrone Giovanni Maria , van Doremaele Eveline R. W. , Surendran Abhijith , Laswick Zachary , Griggs Sophie , Ye Gang , McCulloch Iain , Santoro Francesca , Rivnay Jonathan , van de Burgt Yoeri 
Published: April 2024

AbstractSignal communication mechanisms within the human body rely on the transmission and modulation of action potentials. Replicating the interdependent functions of receptors, neurons and synapses with organic artificial neurons and biohybrid synapses is an essential first step towards merging neuromorphic circuits and biological systems, crucial for computing at the biological interface. However, most organic neuromorphic systems are based on simple circuits which exhibit limited adaptability to both external and internal biological cues, and are restricted to emulate only specific the functions of an individual neuron/synapse. Here, we present a modular neuromorphic system which combines organic spiking neurons and biohybrid synapses to replicate a neural pathway. The spiking neuron mimics the sensory coding function of afferent neurons from light stimuli, while the neuromodulatory activity of interneurons is emulated by neurotransmitters-mediated biohybrid synapses. Combining these functions, we create a modular connection between multiple neurons to establish a pre-processing retinal pathway primitive.
ReLo is a simple and rapid colocalization assay to identify and characterize direct protein–protein interactions
Authors: Salgania Harpreet Kaur , Metz Jutta , Jeske Mandy 
Published: April 2024

AbstractThe characterization of protein-protein interactions (PPIs) is fundamental to the understanding of biochemical processes. Many methods have been established to identify and study direct PPIs; however, screening and investigating PPIs involving large or poorly soluble proteins remains challenging. Here, we introduce ReLo, a simple, rapid, and versatile cell culture-based method for detecting and investigating interactions in a cellular context. Our experiments demonstrate that ReLo specifically detects direct binary PPIs. Furthermore, we show that ReLo bridging experiments can also be used to determine the binding topology of subunits within multiprotein complexes. In addition, ReLo facilitates the identification of protein domains that mediate complex formation, allows screening for interfering point mutations, and it is sensitive to drugs that mediate or disrupt an interaction. In summary, ReLo is a simple and rapid alternative for the study of PPIs, especially when studying structurally complex proteins or when established methods fail.
Inverse relationship between species competitiveness and intraspecific trait variability may enable species coexistence in experimental seedling communities
Authors: Yang Jing , Wang Xiya , Carmona Carlos P. , Wang Xihua , Shen Guochun 
Published: April 2024

AbstractTheory suggests that intraspecific trait variability may promote species coexistence when competitively inferior species have higher intraspecific trait variability than their superior competitors. Here, we provide empirical evidence for this phenomenon in tree seedlings. We evaluated intraspecific variability and plastic response of ten traits in 6750 seedlings of ten species in a three-year greenhouse experiment. While we observed no relationship between intraspecific trait variability and species competitiveness in competition-free homogeneous environments, an inverse relationship emerged under interspecific competition and in spatially heterogeneous environments. We showed that this relationship is driven by the plastic response of the competitively inferior species: Compared to their competitively superior counterparts, they exhibited a greater increase in trait variability, particularly in fine-root traits, in response to competition, environmental heterogeneity and their combination. Our findings contribute to understanding how interspecific competition and intraspecific trait variability together structure plant communities.
RNA-seq analysis in simulated microgravity unveils down-regulation of the beta-rhizobial siderophore phymabactin
Authors: Golaz Daphné , Papenfuhs Chad K. , Bellés-Sancho Paula , Eberl Leo , Egli Marcel , Pessi Gabriella 
Published: April 2024

AbstractExploiting the symbiotic interaction between crops and nitrogen-fixing bacteria is a simple and ecological method to promote plant growth in prospective extraterrestrial human outposts. In this study, we performed an RNA-seq analysis to investigate the adaptation of the legume symbiont Paraburkholderia phymatum STM815T to simulated microgravity (s0-g) at the transcriptome level. The results revealed a drastic effect on gene expression, with roughly 23% of P. phymatum genes being differentially regulated in s0-g. Among those, 951 genes were upregulated and 858 downregulated in the cells grown in s0-g compared to terrestrial gravity (1 g). Several genes involved in posttranslational modification, protein turnover or chaperones encoding were upregulated in s0-g, while those involved in translation, ribosomal structure and biosynthesis, motility or inorganic ions transport were downregulated. Specifically, the whole phm gene cluster, previously bioinformatically predicted to be involved in the production of a hypothetical malleobactin-like siderophore, phymabactin, was 20-fold downregulated in microgravity. By constructing a mutant strain (ΔphmJK) we confirmed that the phm gene cluster codes for the only siderophore secreted by P. phymatum as assessed by the complete lack of iron chelating activity of the P. phymatum ΔphmJK mutant on chrome azurol S (CAS) agar plates. These results not only provide a deeper understanding of the physiology of symbiotic organisms exposed to space-like conditions, but also increase our knowledge of iron acquisition mechanisms in rhizobia.