bluuebunny/crossref_metadata_2025_split huggingface dataset:
Distinct B cell profiles characterise healthy weight and obesity pre- and post-bariatric surgery
Authors: Šlisere B. , Arisova M. , Aizbalte O. , Salmiņa M. M. , Zolovs M. , Levenšteins M. , Mukāns M. , Troickis I. , Meija L. , Lejnieks A. , Bīlande G. , Rosser E. C. , Oļeiņika K. 
Published: July 2023

Abstract
Background/Objectives
Obesity-associated metabolic dysfunction and inflammation can be ameliorated by bariatric surgery. While obesity is also linked to impaired B cell activation, differentiation, and persistence in response to infection and vaccination little is known about post-operative immune B cell compartment and to what extent dysregulation in B cell pathways can be reversed. To bridge this gap in knowledge, we carried out in-depth evaluation of B cell composition in individuals with obesity prior to and following bariatric surgery compared to lean controls.

Subjects/Methods
We recruited individuals with obesity (BMI at least 35 kg/m2) before bariatric surgery (n = 21) and followed them up 6 months post-operatively (n = 17). As controls we recruited age- and sex-matched lean (BMI < 25) individuals (n = 18). We carried out comprehensive immunophenotyping of peripheral blood B cells as well as interrogated their association with inflammatory and metabolic parameters.

Results
In obesity the balance of antigen-inexperienced and memory B cells in the peripheral blood is altered, with an expansion of naïve and a reduction in total memory B cells. 6 months following bariatric surgery this balance is restored. However, post-operative patients are uniquely characterised by an increase in B cell subsets associated with chronic inflammation – CD11c+CXCR5-IgD-CD27- double negative 2 (DN2) B cells and CD27+CD38++ plasmablasts. Correlations between B cells subsets, inflammatory and metabolic parameters were distinct in lean people and individuals with obesity pre- and post-bariatric surgery.

Conclusions
Bariatric surgery patients display a unique B cell profile 6 months post-operatively; this bears minimal resemblance to that of pre-operative patients and only partially overlaps with that of lean controls. Post-operative differences in the B cell compartment compared to lean controls are detected despite global amelioration of inflammation and restoration of metabolic health. Collectively, this indicates that bariatric surgery creates a specific immunometabolic state with potential implications for health outcomes.
The potential preventive effect of dietary phytochemicals In Vivo
Authors: Saleh Mai M. , Darwish Zeinab E. , El Nouaem Manal I. , Fayed Nesrin A. , Mourad Ghada M. , Ramadan Omneya R. 
Published: July 2023

Abstract
Introduction
Chemoprevention refers to using specific substances during oncogenesis. Curcumin and catechins are both polyphenol types of phytochemicals present in curcuma longa and green tea. The effect of curcumin is synergistic with epigallocatechin gallate, the most abundant polyphenol in tea.

Aim
To evaluate and compares the chemopreventive effect of both green tea and curcumin (each individually and in combination) through induction of hamster buccal pouch carcinoma.

Materials and methods
Squamous cell carcinoma was chemically induced in fifty Syrian golden hamsters divided into 5 groups (10 each). The first group was used as a normal control group. The second group received the carcinogenic agent only. The other three groups received green tea, curcumin, and a combination of both, respectively. Flow cytometry, immunofluorescence, and immunohistochemical assays were used to evaluate apoptosis, proliferation, and angiogenesis. ANOVA test was used to analyze the results between the study groups.

Results
The cells of the positive control group (B) resulted in 11.57% apoptosis. In the study groups, treatment of the cells with green tea (C), and curcumin (D) and both of them (E) showed increased apoptosis. The fluorescent image in group B showed an increase of the red fluorescence in the nucleus and cytoplasm of the squamous cell carcinoma cells while groups C, D, and E showed a decrease of the red fluorescence in the nuclei of the squamous cell carcinoma cells. The microvessel density was higher in the positive control group as compared to the treated groups.

Conclusions
The combination of green tea and curcumin has a significant chemopreventive effect against oral carcinogenesis.
Evolutionary history of the Arctic flora
Authors: Zhang Jun , Li Xiao-Qian , Peng Huan-Wen , Hai Lisi , Erst Andrey S. , Jabbour Florian , Ortiz Rosa del C. , Xia Fu-Cai , Soltis Pamela S. , Soltis Douglas E. , Wang Wei 
Published: July 2023

AbstractThe Arctic tundra is a relatively young and new type of biome and is especially sensitive to the impacts of global warming. However, little is known about how the Arctic flora was shaped over time. Here we investigate the origin and evolutionary dynamics of the Arctic flora by sampling 32 angiosperm clades that together encompass 3626 species. We show that dispersal into the Arctic and in situ diversification within the Arctic have similar trends through time, initiating at approximately 10–9 Ma, increasing sharply around 2.6 Ma, and peaking around 1.0–0.7 Ma. Additionally, we discover the existence of a long-term dispersal corridor between the Arctic and western North America. Our results suggest that the initiation and diversification of the Arctic flora might have been jointly driven by progressive landscape and climate changes and sea-level fluctuations since the early Late Miocene. These findings have important conservation implications given rapidly changing climate conditions in the Arctic.
Allosteric activation of vinculin by talin
Authors: Franz Florian , Tapia-Rojo Rafael , Winograd-Katz Sabina , Boujemaa-Paterski Rajaa , Li Wenhong , Unger Tamar , Albeck Shira , Aponte-Santamaria Camilo , Garcia-Manyes Sergi , Medalia Ohad , Geiger Benjamin , Gräter Frauke 
Published: July 2023

AbstractThe talin-vinculin axis is a key mechanosensing component of cellular focal adhesions. How talin and vinculin respond to forces and regulate one another remains unclear. By combining single-molecule magnetic tweezers experiments, Molecular Dynamics simulations, actin-bundling assays, and adhesion assembly experiments in live cells, we here describe a two-ways allosteric network within vinculin as a regulator of the talin-vinculin interaction. We directly observe a maturation process of vinculin upon talin binding, which reinforces the binding to talin at a rate of 0.03 s−1. This allosteric transition can compete with force-induced dissociation of vinculin from talin only at forces up to 10 pN. Mimicking the allosteric activation by mutation yields a vinculin molecule that bundles actin and localizes to focal adhesions in a force-independent manner. Hence, the allosteric switch confines talin-vinculin interactions and focal adhesion build-up to intermediate force levels. The ‘allosteric vinculin mutant’ is a valuable molecular tool to further dissect the mechanical and biochemical signalling circuits at focal adhesions and elsewhere.
Cancer-associated fibroblast classification in single-cell and spatial proteomics data
Authors: Cords Lena , Tietscher Sandra , Anzeneder Tobias , Langwieder Claus , Rees Martin , de Souza Natalie , Bodenmiller Bernd 
Published: July 2023

AbstractCancer-associated fibroblasts (CAFs) are a diverse cell population within the tumour microenvironment, where they have critical effects on tumour evolution and patient prognosis. To define CAF phenotypes, we analyse a single-cell RNA sequencing (scRNA-seq) dataset of over 16,000 stromal cells from tumours of 14 breast cancer patients, based on which we define and functionally annotate nine CAF phenotypes and one class of pericytes. We validate this classification system in four additional cancer types and use highly multiplexed imaging mass cytometry on matched breast cancer samples to confirm our defined CAF phenotypes at the protein level and to analyse their spatial distribution within tumours. This general CAF classification scheme will allow comparison of CAF phenotypes across studies, facilitate analysis of their functional roles, and potentially guide development of new treatment strategies in the future.
Manipulating microRNA miR408 enhances both biomass yield and saccharification efficiency in poplar
Authors: Guo Yayu , Wang Shufang , Yu Keji , Wang Hou-Ling , Xu Huimin , Song Chengwei , Zhao Yuanyuan , Wen Jialong , Fu Chunxiang , Li Yu , Wang Shuizhong , Zhang Xi , Zhang Yan , Cao Yuan , Shao Fenjuan , Wang Xiaohua , Deng Xin , Chen Tong , Zhao Qiao , Li Lei , Wang Guodong , Grünhofer Paul , Schreiber Lukas , Li Yue , Song Guoyong , Dixon Richard A. , Lin Jinxing 
Published: July 2023

AbstractThe conversion of lignocellulosic feedstocks to fermentable sugar for biofuel production is inefficient, and most strategies to enhance efficiency directly target lignin biosynthesis, with associated negative growth impacts. Here we demonstrate, for both laboratory- and field-grown plants, that expression of Pag-miR408 in poplar (Populus alba × P. glandulosa) significantly enhances saccharification, with no requirement for acid-pretreatment, while promoting plant growth. The overexpression plants show increased accessibility of cell walls to cellulase and scaffoldin cellulose-binding modules. Conversely, Pag-miR408 loss-of-function poplar shows decreased cell wall accessibility. Overexpression of Pag-miR408 targets three Pag-LACCASES, delays lignification, and modestly reduces lignin content, S/G ratio and degree of lignin polymerization. Meanwhile, the LACCASE loss of function mutants exhibit significantly increased growth and cell wall accessibility in xylem. Our study shows how Pag-miR408 regulates lignification and secondary growth, and suggest an effective approach towards enhancing biomass yield and saccharification efficiency in a major bioenergy crop.
Regulation of Rad52-dependent replication fork recovery through serine ADP-ribosylation of PolD3
Authors: Richards Frederick , Llorca-Cardenosa Marta J. , Langton Jamie , Buch-Larsen Sara C. , Shamkhi Noor F. , Sharma Abhishek Bharadwaj , Nielsen Michael L. , Lakin Nicholas D. 
Published: July 2023

AbstractAlthough Poly(ADP-ribose)-polymerases (PARPs) are key regulators of genome stability, how site-specific ADP-ribosylation regulates DNA repair is unclear. Here, we describe a novel role for PARP1 and PARP2 in regulating Rad52-dependent replication fork repair to maintain cell viability when homologous recombination is dysfunctional, suppress replication-associated DNA damage, and maintain genome stability. Mechanistically, Mre11 and ATM are required for induction of PARP activity in response to replication stress that in turn promotes break-induced replication (BIR) through assembly of Rad52 at stalled/damaged replication forks. Further, by mapping ADP-ribosylation sites induced upon replication stress, we identify that PolD3 is a target for PARP1/PARP2 and that its site-specific ADP-ribosylation is required for BIR activity, replication fork recovery and genome stability. Overall, these data identify a critical role for Mre11-dependent PARP activation and site-specific ADP-ribosylation in regulating BIR to maintain genome integrity during DNA synthesis.
HCK induces macrophage activation to promote renal inflammation and fibrosis via suppression of autophagy
Authors: Chen Man , Menon Madhav C. , Wang Wenlin , Fu Jia , Yi Zhengzi , Sun Zeguo , Liu Jessica , Li Zhengzhe , Mou Lingyun , Banu Khadija , Lee Sui-Wan , Dai Ying , Anandakrishnan Nanditha , Azeloglu Evren U. , Lee Kyung , Zhang Weijia , Das Bhaskar , He John Cijiang , Wei Chengguo 
Published: July 2023

AbstractRenal inflammation and fibrosis are the common pathways leading to progressive chronic kidney disease (CKD). We previously identified hematopoietic cell kinase (HCK) as upregulated in human chronic allograft injury promoting kidney fibrosis; however, the cellular source and molecular mechanisms are unclear. Here, using immunostaining and single cell sequencing data, we show that HCK expression is highly enriched in pro-inflammatory macrophages in diseased kidneys. HCK-knockout (KO) or HCK-inhibitor decreases macrophage M1-like pro-inflammatory polarization, proliferation, and migration in RAW264.7 cells and bone marrow-derived macrophages (BMDM). We identify an interaction between HCK and ATG2A and CBL, two autophagy-related proteins, inhibiting autophagy flux in macrophages. In vivo, both global or myeloid cell specific HCK-KO attenuates renal inflammation and fibrosis with reduces macrophage numbers, pro-inflammatory polarization and migration into unilateral ureteral obstruction (UUO) kidneys and unilateral ischemia reperfusion injury (IRI) models. Finally, we developed a selective boron containing HCK inhibitor which can reduce macrophage pro-inflammatory activity, proliferation, and migration in vitro, and attenuate kidney fibrosis in the UUO mice. The current study elucidates mechanisms downstream of HCK regulating macrophage activation and polarization via autophagy in CKD and identifies that selective HCK inhibitors could be potentially developed as a new therapy for renal fibrosis.
Structures of p53/BCL-2 complex suggest a mechanism for p53 to antagonize BCL-2 activity
Authors: Wei Hudie , Wang Haolan , Wang Genxin , Qu Lingzhi , Jiang Longying , Dai Shuyan , Chen Xiaojuan , Zhang Ye , Chen Zhuchu , Li Youjun , Guo Ming , Chen Yongheng 
Published: July 2023

AbstractMitochondrial apoptosis is strictly controlled by BCL-2 family proteins through a subtle network of protein interactions. The tumor suppressor protein p53 triggers transcription-independent apoptosis through direct interactions with BCL-2 family proteins, but the molecular mechanism is not well understood. In this study, we present three crystal structures of p53-DBD in complex with the anti-apoptotic protein BCL-2 at resolutions of 2.3–2.7 Å. The structures show that two loops of p53-DBD penetrate directly into the BH3-binding pocket of BCL-2. Structure-based mutations at the interface impair the p53/BCL-2 interaction. Specifically, the binding sites for p53 and the pro-apoptotic protein Bax in the BCL-2 pocket are mostly identical. In addition, formation of the p53/BCL-2 complex is negatively correlated with the formation of BCL-2 complexes with pro-apoptotic BCL-2 family members. Defects in the p53/BCL-2 interaction attenuate p53-mediated cell apoptosis. Overall, our study provides a structural basis for the interaction between p53 and BCL-2, and suggests a molecular mechanism by which p53 regulates transcription-independent apoptosis by antagonizing the interaction of BCL-2 with pro-apoptotic BCL-2 family members.
Characterization of crAss-like phage isolates highlights Crassvirales genetic heterogeneity and worldwide distribution
Authors: Ramos-Barbero María Dolores , Gómez-Gómez Clara , Sala-Comorera Laura , Rodríguez-Rubio Lorena , Morales-Cortes Sara , Mendoza-Barberá Elena , Vique Gloria , Toribio-Avedillo Daniel , Blanch Anicet R. , Ballesté Elisenda , Garcia-Aljaro Cristina , Muniesa Maite 
Published: July 2023

AbstractCrassvirales (crAss-like phages) are an abundant group of human gut-specific bacteriophages discovered in silico. The use of crAss-like phages as human fecal indicators is proposed but the isolation of only seven cultured strains of crAss-like phages to date has greatly hindered their study. Here, we report the isolation and genetic characterization of 25 new crAss-like phages (termed crAssBcn) infecting Bacteroides intestinalis, belonging to the order Crassvirales, genus Kehishuvirus and, based on their genomic variability, classified into six species. CrAssBcn phage genomes are similar to ΦCrAss001 but show genomic and aminoacidic differences when compared to other crAss-like phages of the same family. CrAssBcn phages are detected in fecal metagenomes around the world at a higher frequency than ΦCrAss001. This study increases the known crAss-like phage isolates and their abundance and heterogeneity open the question of what member of the Crassvirales group should be selected as human fecal marker.
Multi-reward reinforcement learning based development of inter-atomic potential models for silica
Authors: Koneru Aditya , Chan Henry , Manna Sukriti , Loeffler Troy D. , Dhabal Debdas , Bertolazzo Andressa A. , Molinero Valeria , Sankaranarayanan Subramanian K. R. S. 
Published: July 2023

AbstractSilica is an abundant and technologically attractive material. Due to the structural complexities of silica polymorphs coupled with subtle differences in Si–O bonding characteristics, the development of accurate models to predict the structure, energetics and properties of silica polymorphs remain challenging. Current models for silica range from computationally efficient Buckingham formalisms (BKS, CHIK, Soules) to reactive (ReaxFF) and more recent machine-learned potentials that are flexible but computationally costly. Here, we introduce an improved formalism and parameterization of BKS model via a multireward reinforcement learning (RL) using an experimental training dataset. Our model concurrently captures the structure, energetics, density, equation of state, and elastic constants of quartz (equilibrium) as well as 20 other metastable silica polymorphs. We also assess its ability in capturing amorphous properties and highlight the limitations of the BKS-type functional forms in simultaneously capturing crystal and amorphous properties. We demonstrate ways to improve model flexibility and introduce a flexible formalism, machine-learned ML-BKS, that outperforms existing empirical models and is on-par with the recently developed 50 to 100 times more expensive Gaussian approximation potential (GAP) in capturing the experimental structure and properties of silica polymorphs and amorphous silica.
Mechanism and therapeutic implications of pomalidomide-induced immune surface marker upregulation in EBV-positive lymphomas
Authors: Jaeger Hannah K. , Davis David A. , Nair Ashwin , Shrestha Prabha , Stream Alexandra , Yaparla Amulya , Yarchoan Robert 
Published: July 2023

AbstractEpstein-Barr virus (EBV) downregulates immune surface markers to avoid immune recognition. Pomalidomide (Pom) was previously shown to increase immune surface marker expression in EBV-infected tumor cells. We explored the mechanism by which Pom leads to these effects in EBV-infected cells. Pom increased B7-2/CD86 mRNA, protein, and surface expression in EBV-infected cells but this was virtually eliminated in EBV-infected cells made resistant to Pom-induced cytostatic effects. This indicates that Pom initiates the upregulation of these markers by interacting with its target, cereblon. Interestingly, Pom increased the proinflammatory cytokines IP-10 and MIP-1∝/β in EBV infected cells, supporting a possible role for the phosphoinositide 3-kinase (PI3K)/AKT pathway in Pom’s effects. Idelalisib, an inhibitor of the delta subunit of PI3 Kinase, blocked AKT-Ser phosphorylation and Pom-induced B7-2 surface expression. PU.1 is a downstream target for AKT that is expressed in EBV-infected cells. Pom treatment led to an increase in PU.1 binding to the B7-2 promoter based on ChIP analysis. Thus, our data indicates Pom acts through cereblon leading to degradation of Ikaros and activation of the PI3K/AKT/PU.1 pathway resulting in upregulation of B7-2 mRNA and protein expression. The increased immune recognition in addition to the increases in proinflammatory cytokines upon Pom treatment suggests Pom may be useful in the treatment of EBV-positive lymphomas.
Selective isotropic etching of SiO2 over Si3N4 using NF3/H2 remote plasma and methanol vapor
Authors: Gil Hong Seong , Kim Doo San , Jang Yun Jong , Kim Dea Whan , Kwon Hea In , Kim Gyoung Chan , Kim Dong Woo , Yeom Geun Young 
Published: July 2023

AbstractIn this study, an isotropic etching process of SiO2 selective to Si3N4 using NF3/H2/methanol chemistry was investigated. HF was formed using a NF3/H2 remote plasma, and in order to remove the F radicals, which induces spontaneous etching of Si-base material, methanol was injected outside the plasma discharge region. Through this process, etch products were formed on the surface of SiO2, and then the (NH4)2SiF6 was removed by following heating process. When the H and F radicals were abundant, the highest SiO2 etch per cycle (EPC) was obtained. And, the increase of H2 and methanol percentage in the gas chemistry increased the etch selectivity by decreasing the F radicals. The etch products such as (NH4)2SiF6 were formed on the surfaces of SiO2 and Si3N4 during the reaction step and no noticeable spontaneous etching by formation of SiF4 was observed. By optimized conditions, the etch selectivity of SiO2 over Si3N4 and poly Si higher than 50 and 20, respectively, was obtained while having SiO2 EPC of ~ 13 nm/cycle. It is believed that the cyclic process using NF3/H2 remote plasma and methanol followed by heating can be applied to the selective isotropic SiO2 etching of next generation 3D device fabrication.
Tagasaste silvopastures in steep-hill country. 2. Effect of increasing proximity to tagasaste on growth and survival of companion pasture species
Authors: Tozer Katherine , Noakes Emma , Douglas Grant , Greenfield Rose , Cameron Catherine 
Published: July 2023

Context Tagasaste (Cytisus proliferus), a fast-growing leguminous tree, has potential to supplement pasture production in steep-hill country and to increase pasture resilience. Aims In the companion paper, we quantified tagasaste production characteristics. Here, we determine the effect of proximity of 10-year-old tagasaste trees on productivity of eight pasture species including grasses (perennial ryegrass, Lolium perenne; cocksfoot, Dactylis glomerata; prairie grass, Bromus willdenowii; microlaena, Microlaena stipoides), perennial legumes (white clover, Trifolium repens; red clover, T. pratense; lotus, Lotus pedunculatus), and an annual legume (subterranean clover, T. subterraneum). Methods A site was established in the East Coast region of the North Island of New Zealand on steep-hill country (>20° slope). Herbage production, nutritive value and survival of pasture species established as spaced transplants were measured over 3 years. Results Cocksfoot had high survival, herbage production and metabolisable energy content but was negatively affected by proximity to tagasaste. Microlaena was not significantly affected by proximity to tagasaste; however, it was much less productive and had lower nutritive values than the other grasses. Only 40% of perennial ryegrass transplants survived 3 years, and survival of perennial legumes was negligible. Subterranean clover was able to set seed in the open and in shade. Conclusions Cocksfoot was the most productive grass species, and microlaena was least affected by proximity to tagasaste. Given the poor persistence of perennial clovers, annual clovers may be better suited to a tagasaste silvopasture on steep, dry hillsides. Implications Mixtures of cocksfoot and subterranean clover may be well suited to summer-dry hillsides, between and under trees in a tagasaste silvopasture. Microlaena may provide some forage and can maintain groundcover despite shade.