bluuebunny/crossref_metadata_2025_split huggingface dataset:
Endothelial cell dysfunction: a key determinant for the outcome of allogeneic stem cell transplantation
Authors: Luft Thomas , Dreger Peter , Radujkovic Aleksandar 
Published: July 2021

AbstractAllogeneic hematopoietic stem cell transplantation (alloSCT) carries the promise of cure for many malignant and non-malignant diseases of the lympho-hematopoietic system. Although outcome has improved considerably since the pioneering Seattle achievements more than 5 decades ago, non-relapse mortality (NRM) remains a major burden of alloSCT. There is increasing evidence that endothelial dysfunction is involved in many of the life-threatening complications of alloSCT, such as sinusoidal obstruction syndrome/venoocclusive disease, transplant-associated thrombotic microangiopathy, and refractory acute graft-versus host disease. This review delineates the role of the endothelium in severe complications after alloSCT and describes the current status of search for biomarkers predicting endothelial complications, including markers of endothelial vulnerability and markers of endothelial injury. Finally, implications of our current understanding of transplant-associated endothelial pathology for prevention and management of complications after alloSCT are discussed.
TAZ inhibits osteoclastogenesis by attenuating TAK1/NF-κB signaling
Authors: Yang Wanlei , Lu Xuanyuan , Zhang Tan , Han Weiqi , Li Jianlei , He Wei , Jia Yewei , Zhao Kangxian , Qin An , Qian Yu 
Published: July 2021

AbstractOsteoporosis is an osteolytic disorder commonly associated with excessive osteoclast formation. Transcriptional coactivator with PDZ-binding motif (TAZ) is a key downstream effector of the Hippo signaling pathway; it was suggested to be involved in the regulation of bone homeostasis. However, the exact role of TAZ in osteoclasts has not yet been established. In this study, we demonstrated that global knockout and osteoclast-specific knockout of TAZ led to a low-bone mass phenotype due to elevated osteoclast formation, which was further evidenced by in vitro osteoclast formation assays. Moreover, the overexpression of TAZ inhibited RANKL-induced osteoclast formation, whereas silencing of TAZ reduced it. Mechanistically, TAZ bound to TGF-activated kinase 1 (TAK1) and reciprocally inhibited NF-κB signaling, suppressing osteoclast differentiation. Collectively, our findings highlight an essential role of TAZ in the regulation of osteoclastogenesis in osteoporosis and its underlying mechanism.
Molecular subtype-specific efficacy of anti-EGFR therapy in colorectal cancer is dependent on the chemotherapy backbone
Authors: ten Hoorn Sanne , Sommeijer Dirkje W. , Elliott Faye , Fisher David , de Back Tim R. , Trinh Anne , Koens Lianne , Maughan Tim , Seligmann Jenny , Seymour Matthew T. , Quirke Phil , Adams Richard , Richman Susan D. , Punt Cornelis J. A. , Vermeulen Louis 
Published: July 2021

Abstract
Background
Patient selection for addition of anti-EGFR therapy to chemotherapy for patients with RAS and BRAF wildtype metastatic colorectal cancer can still be optimised. Here we investigate the effect of anti-EGFR therapy on survival in different consensus molecular subtypes (CMSs) and stratified by primary tumour location.

Methods
Retrospective analyses, using the immunohistochemistry-based CMS classifier, were performed in the COIN (first-line oxaliplatin backbone with or without cetuximab) and PICCOLO trial (second-line irinotecan with or without panitumumab). Tumour tissue was available for 323 patients (20%) and 349 (41%), respectively.

Results
When using an irinotecan backbone, anti-EGFR therapy is effective in both CMS2/3 and CMS4 in left-sided primary tumours (progression-free survival (PFS): HR 0.44, 95% CI 0.26–0.75, P = 0.003 and HR 0.12, 95% CI 0.04–0.36, P < 0.001, respectively) and in CMS4 right-sided tumours (PFS HR 0.17, 95% CI 0.04–0.71, P = 0.02). Efficacy using an oxaliplatin backbone was restricted to left-sided CMS2/3 tumours (HR 0.57, 95% CI 0.36–0.96, P = 0.034).

Conclusions
The subtype-specific efficacy of anti-EGFR therapy is dependent on the chemotherapy backbone. This may provide the possibility of subtype-specific treatment strategies for a more optimal use of anti-EGFR therapy.
Tissue-specific 5-hydroxymethylcytosine landscape of the human genome
Authors: He Bo , Zhang Chao , Zhang Xiaoxue , Fan Yu , Zeng Hu , Liu Jun’e , Meng Haowei , Bai Dongsheng , Peng Jinying , Zhang Qian , Tao Wei , Yi Chengqi 
Published: July 2021

Abstract5-Hydroxymethylcytosine (5hmC) is an important epigenetic mark that regulates gene expression. Charting the landscape of 5hmC in human tissues is fundamental to understanding its regulatory functions. Here, we systematically profiled the whole-genome 5hmC landscape at single-base resolution for 19 types of human tissues. We found that 5hmC preferentially decorates gene bodies and outperforms gene body 5mC in reflecting gene expression. Approximately one-third of 5hmC peaks are tissue-specific differentially-hydroxymethylated regions (tsDhMRs), which are deposited in regions that potentially regulate the expression of nearby tissue-specific functional genes. In addition, tsDhMRs are enriched with tissue-specific transcription factors and may rewire tissue-specific gene expression networks. Moreover, tsDhMRs are associated with single-nucleotide polymorphisms identified by genome-wide association studies and are linked to tissue-specific phenotypes and diseases. Collectively, our results show the tissue-specific 5hmC landscape of the human genome and demonstrate that 5hmC serves as a fundamental regulatory element affecting tissue-specific gene expression programs and functions.
The Welwitschia genome reveals a unique biology underpinning extreme longevity in deserts
Authors: Wan Tao , Liu Zhiming , Leitch Ilia J. , Xin Haiping , Maggs-Kölling Gillian , Gong Yanbing , Li Zhen , Marais Eugene , Liao Yiying , Dai Can , Liu Fan , Wu Qijia , Song Chi , Zhou Yadong , Huang Weichang , Jiang Kai , Wang Qi , Yang Yong , Zhong Zhixiang , Yang Ming , Yan Xue , Hu Guangwan , Hou Chen , Su Yingjuan , Feng Shixiu , Yang Ji , Yan Jijun , Chu Jinfang , Chen Fan , Ran Jinhua , Wang Xiaoquan , Van de Peer Yves , Leitch Andrew R. , Wang Qingfeng 
Published: July 2021

AbstractThe gymnosperm Welwitschia mirabilis belongs to the ancient, enigmatic gnetophyte lineage. It is a unique desert plant with extreme longevity and two ever-elongating leaves. We present a chromosome-level assembly of its genome (6.8 Gb/1 C) together with methylome and transcriptome data to explore its astonishing biology. We also present a refined, high-quality assembly of Gnetum montanum to enhance our understanding of gnetophyte genome evolution. The Welwitschia genome has been shaped by a lineage-specific ancient, whole genome duplication (~86 million years ago) and more recently (1-2 million years) by bursts of retrotransposon activity. High levels of cytosine methylation (particularly at CHH motifs) are associated with retrotransposons, whilst long-term deamination has resulted in an exceptionally GC-poor genome. Changes in copy number and/or expression of gene families and transcription factors (e.g. R2R3MYB, SAUR) controlling cell growth, differentiation and metabolism underpin the plant’s longevity and tolerance to temperature, nutrient and water stress.
Energy efficiency and biological interactions define the core microbiome of deep oligotrophic groundwater
Authors: Mehrshad Maliheh , Lopez-Fernandez Margarita , Sundh John , Bell Emma , Simone Domenico , Buck Moritz , Bernier-Latmani Rizlan , Bertilsson Stefan , Dopson Mark 
Published: July 2021

AbstractWhile oligotrophic deep groundwaters host active microbes attuned to the low-end of the bioenergetics spectrum, the ecological constraints on microbial niches in these ecosystems and their consequences for microbiome convergence are unknown. Here, we provide a genome-resolved, integrated omics analysis comparing archaeal and bacterial communities in disconnected fracture fluids of the Fennoscandian Shield in Europe. Leveraging a dataset that combines metagenomes, single cell genomes, and metatranscriptomes, we show that groundwaters flowing in similar lithologies offer fixed niches that are occupied by a common core microbiome. Functional expression analysis highlights that these deep groundwater ecosystems foster diverse, yet cooperative communities adapted to this setting. We suggest that these communities stimulate cooperation by expression of functions related to ecological traits, such as aggregate or biofilm formation, while alleviating the burden on microorganisms producing compounds or functions that provide a collective benefit by facilitating reciprocal promiscuous metabolic partnerships with other members of the community. We hypothesize that an episodic lifestyle enabled by reversible bacteriostatic functions ensures the subsistence of the oligotrophic deep groundwater microbiome.
Chemotherapy-induced transposable elements activate MDA5 to enhance haematopoietic regeneration
Authors: Clapes Thomas , Polyzou Aikaterini , Prater Pia , Sagar  , Morales-Hernández Antonio , Ferrarini Mariana Galvao , Kehrer Natalie , Lefkopoulos Stylianos , Bergo Veronica , Hummel Barbara , Obier Nadine , Maticzka Daniel , Bridgeman Anne , Herman Josip S. , Ilik Ibrahim , Klaeylé Lhéanna , Rehwinkel Jan , McKinney-Freeman Shannon , Backofen Rolf , Akhtar Asifa , Cabezas-Wallscheid Nina , Sawarkar Ritwick , Rebollo Rita , Grün Dominic , Trompouki Eirini 
Published: July 2021

AbstractHaematopoietic stem cells (HSCs) are normally quiescent, but have evolved mechanisms to respond to stress. Here, we evaluate haematopoietic regeneration induced by chemotherapy. We detect robust chromatin reorganization followed by increased transcription of transposable elements (TEs) during early recovery. TE transcripts bind to and activate the innate immune receptor melanoma differentiation-associated protein 5 (MDA5) that generates an inflammatory response that is necessary for HSCs to exit quiescence. HSCs that lack MDA5 exhibit an impaired inflammatory response after chemotherapy and retain their quiescence, with consequent better long-term repopulation capacity. We show that the overexpression of ERV and LINE superfamily TE copies in wild-type HSCs, but not in Mda5−/− HSCs, results in their cycling. By contrast, after knockdown of LINE1 family copies, HSCs retain their quiescence. Our results show that TE transcripts act as ligands that activate MDA5 during haematopoietic regeneration, thereby enabling HSCs to mount an inflammatory response necessary for their exit from quiescence.
Protein engineering of the aldoxime dehydratase from Bacillus sp. OxB-1 based on a rational sequence alignment approach
Authors: Oike Keiko , Sproß Jens , Matsui Daisuke , Asano Yasuhisa , Gröger Harald 
Published: July 2021

AbstractRecently, the program INTMSAlign_HiSol for identifying aggregation hotspots in proteins only requiring secondary structure data was introduced. We explored the utility of this program further and applied it for engineering of the aldoxime dehydratase from Bacillus sp. OxB-1. Towards this end, the effect of inverting the hydropathy at selected positions of the amino acid sequence on the enzymatic activity was studied leading to 60% of our constructed variants, which showed improved activity. In part, this activity increase can be rationalised by an improved heme incorporation of the variants. For example, a single mutation gave a 1.8 fold increased enzymatic activity and 30% improved absolute heme incorporation.
Quantum inspired community detection for analysis of biodiversity change driven by land-use conversion and climate change
Authors: Akbar Sana , Saritha Sri Khetwat 
Published: July 2021

AbstractCommunity detection remains little explored in the analysis of biodiversity change. The challenges linked with global biodiversity change have also multiplied manifold in the past few decades. Moreover, most studies concerning biodiversity change lack the quantitative treatment central to species distribution modeling. Empirical analysis of species distribution and abundance is thus integral to the study of biodiversity loss and biodiversity alterations. Community detection is therefore expected to efficiently model the topological aspect of biodiversity change driven by land-use conversion and climate change; given that it has already proven superior for diverse problems in the domain of social network analysis and subgroup discovery in complex systems. Thus, quantum inspired community detection is proposed as a novel technique to predict biodiversity change considering tiger population in eighteen states of India; leading to benchmarking of two novel datasets. Elements of land-use conversion and climate change are explored to design these datasets viz.—Landscape based distribution and Number of tiger reserves based distribution respectively; for predicting regions expected to maximize Tiger population growth. Furthermore, validation of the proposed framework on the said datasets is performed using standard community detection metrics like—Modularity, Normalized Mutual Information (NMI), Adjusted Rand Index (ARI), Degree distribution, Degree centrality and Edge-betweenness centrality. Quantum inspired community detection has also been successful in demonstrating an association between biodiversity change, land-use conversion and climate change; validated statistically by Pearson’s correlation coefficient andpvalue test. Finally, modularity distribution based on parameter tuning establishes the superiority of the second dataset based on the number of Tiger reserves—in predicting regions maximizing Tiger population growth fostering species distribution and abundance; apart from scripting a stronger correlation of biodiversity change with land-use conversion.
Stage-dependent choriocapillaris impairment in Best vitelliform macular dystrophy characterized by optical coherence tomography angiography
Authors: Jauregui Ruben , Parmann Rait , Nuzbrokh Yan , Tsang Stephen H. , Sparrow Janet R. 
Published: July 2021

AbstractCharacterization of vascular impairment in Best vitelliform macular dystrophy (BVMD) is essential for the development of treatment modalities and therapy trials. As such, we seek to characterize the choriocapillaris (CC) at each stage of the disease process in 22 patients (44 eyes) with a diagnosis of BVMD confirmed by genetic sequencing. We utilize optical coherence tomography angiography (OCTA) images to characterize the CC and correlate our findings to the status of the retinal pigment epithelium (RPE) as observed on short-wavelength fundus autofluorescence (SW-AF) images. We observed that in the vitelliruptive stage, the CC appeared as bright and granular in the area where the vitelliform lesion was present. In the atrophic stage, varying degrees of CC atrophy were observed within the lesion area, with the regions of CC atrophy appearing as hypoautofluorescent on SW-AF images. Our results suggest that the CC impairment observed in the vitelliruptive stage of BVMD progressively culminates in the CC atrophy observed at the atrophic stage. As such, OCTA imaging can be used to characterize CC impairment in BVMD patients as part of diagnosis and tracking of disease progression. Our findings suggest that the best window of opportunity for therapeutic approaches is before the atrophic stage, as it is during this stage that CC atrophy is observed.
Uptake and release characteristics of serotonin hydrochloride by natural Cuban zeolite containing clinoptilolite and mordenite
Authors: Grass Jan-Paul , Pals Ulrike , Inayat Alexandra , Schwieger Wilhelm , Hartmann Martin , Dathe Wilfried 
Published: July 2021

AbstractSerotonin (5-HT) plays an important role in human physiology. An excess of this native regulator within the human gut can be partially controlled by orally consuming zeolite. Therefore, this study focuses on the kinetics of the uptake and release of serotonin hydrochloride (5-HT-hc) by natural Cuban zeolite containing clinoptilolite and mordenite at different pH levels using UV–Vis spectroscopy. 5-HT-hc is stable under the following investigated experimental conditions: incubation temperature of 36 °C; and at a pH of 5, 7, and 9. Independent of the zeolite framework, the 5-HT-hc is adsorbed without changing its molecular structure. The uptake and release of 5-HT-hc were not correlated to the textural properties of these aluminosilicates. The investigated zeolites adsorbed 5-HT-hc at about 14 mg per gram zeolite with no large differences observed between different samples. Release studies of 5-HT-hc-loaded zeolite revealed that the 5-HT-hc is strongly bound to the zeolite, and independent of the pH value and zeolite framework only up to 12.7% was released into the water.
Effects of illuminance and correlated color temperature of indoor light on emotion perception
Authors: Li Yun , Ru Taotao , Chen Qingwei , Qian Liu , Luo Xianghang , Zhou Guofu 
Published: July 2021

AbstractThe acute non-image forming (NIF) effects of daytime light on momentary mood had been-although not always-established in the current literature. It still remains largely unknown whether short-time light exposure would modulate emotion perception in healthy adults. The current study (N = 48) was conducted to explore the effects of illuminance (100 lx vs. 1000 lx at eye level) and correlated color temperature (CCT, 2700 K vs. 6500 K) on explicit and implicit emotion perception that was assessed with emotional face judgment task and emotional oddball task respectively. Results showed that lower CCT significantly decreased negative response bias in the face judgment task, with labeling ambiguous faces less fearful under 2700 K vs. 6500 K condition. Moreover, participants responded slightly faster for emotional pictures under 6500 K vs. 2700 K condition, but no significant effect of illuminance or CCT on negativity bias was revealed in the emotional oddball task. These findings highlighted the differential role of illuminance and CCT in regulating instant emotion perception and suggested a task-dependent moderation of light spectrum on negativity bias.
Analyses of Gnai3-iresGFP reporter mice reveal unknown Gαi3 expression sites
Authors: Leiss Veronika , Reisinger Ellen , Speidel Annika , Beer-Hammer Sandra , Nürnberg Bernd 
Published: July 2021

AbstractInhibitory G proteins (Giproteins) are highly homologous but play distinct biological roles. However, their isoform-specific detection remains challenging. To facilitate the analysis of Gαi3expression, we generated aGnai3﻿﻿-﻿iresGFP reporter mouse line. An internal ribosomal entry site (IRES) was inserted behind the stop-codon of theGnai3gene to initiate simultaneous translation of the GFP cDNA together with Gαi3. The expression of GFP was confirmed in spleen and thymus tissue by immunoblot analysis. Importantly, the GFP knock-in (ki) did not alter Gαi3expression levels in all organs tested including spleen and thymus compared to wild-type littermates. Flow cytometry of thymocytes, splenic and blood cell suspensions revealed significantly higher GFP fluorescence intensities in homozygous ki/ki animals compared to heterozygous mice (+/ki). Using cell-type specific surface markers GFP fluorescence was assigned to B cells, T cells, macrophages and granulocytes from both splenic and blood cells and additionally blood-derived platelets. Moreover, immunofluorescent staining of the inner ear from knock-in mice unraveled GFP expression in sensory and non-sensory cell types, with highest levels in Deiter’s cells and in the first row of Hensen’s cells in the organ of Corti, indicating a novel site for Gαi3expression. In summary, theGnai3-﻿﻿iresGFP reporter mouse represents an ideal tool for precise analyses of Gαi3expression patterns and sites.
Visualization of three-dimensional microcirculation of rodents’ retina and choroid for studies of critical illness using optical coherence tomography angiography
Authors: Park Jang Ryul , Lee ByungKun , Lee Min Ji , Kim Kyuseok , Oh Wang-Yuhl 
Published: July 2021

AbstractWe developed a method to measure the relative blood flow speed using optical coherence tomography angiography (OCTA) in retina and choroid, and investigated the feasibility of this method for assessing microcirculatory function in rat models of sepsis and hemorrhagic shock. Two sepsis models, 6-h severe sepsis without treatment and 30-h moderate sepsis maintaining mean arterial pressure, and volume controlled hemorrhagic shock and fluid resuscitation model were used to see the change of microcirculation. The blood flow index (BFI), which was calculated from the OCTA images to represent the average relative blood flow, was decreasing during the 6-h severe sepsis model. Its change is in parallel with the mean arterial blood pressure (MAP) and blood lactate levels. In the 30-h moderate sepsis model, the BFI was decreased while maintaining MAP, and lactate was increased. In the hemorrhagic shock model, the change of BFI is in line with MAP and lactate levels. In all models, BFI change is more sensitive in choroid than in retina. This study presents the OCTA-based retinal and choroidal microcirculatory blood flow monitoring method and shows its utility for assessment of critical illness.
Emergent topological fields and relativistic phonons within the thermoelectricity in topological insulators
Authors: Faílde Daniel , Baldomir Daniel 
Published: July 2021

AbstractTopological edge states are predicted to be responsible for the high efficient thermoelectric response of topological insulators, currently the best thermoelectric materials. However, to explain their figure of merit the coexistence of topological electrons, entropy and phonons can not be considered independently. In a background that puts together electrodynamics and topology, through an expression for the topological intrinsic field, we treat relativistic phonons within the topological surface showing their ability to modulate the Berry curvature of the bands and then playing a fundamental role in the thermoelectric effect. Finally, we show how the topological insulators under such relativistic thermal excitations keep time reversal symmetry allowing the observation of high figures of merit at high temperatures. The emergence of this new intrinsic topological field and other constraints are suitable to have experimental consequences opening new possibilities of improving the efficiency of this topological effect for their based technology.
Untargeted metabolomics analysis of Ralstonia eutropha during plant oil cultivations reveals the presence of a fucose salvage pathway
Authors: Gutschmann Björn , Bock Martina C. E. , Jahns Stefan , Neubauer Peter , Brigham Christopher J. , Riedel Sebastian L. 
Published: July 2021

AbstractProcess engineering of biotechnological productions can benefit greatly from comprehensive analysis of microbial physiology and metabolism. Ralstonia eutropha (syn. Cupriavidus necator) is one of the best studied organisms for the synthesis of biodegradable polyhydroxyalkanoate (PHA). A comprehensive metabolomic study during bioreactor cultivations with the wild-type (H16) and an engineered (Re2058/pCB113) R. eutropha strain for short- and or medium-chain-length PHA synthesis has been carried out. PHA production from plant oil was triggered through nitrogen limitation. Sample quenching allowed to conserve the metabolic states of the cells for subsequent untargeted metabolomic analysis, which consisted of GC–MS and LC–MS analysis. Multivariate data analysis resulted in identification of significant changes in concentrations of oxidative stress-related metabolites and a subsequent accumulation of antioxidative compounds. Moreover, metabolites involved in the de novo synthesis of GDP-l-fucose as well as the fucose salvage pathway were identified. The related formation of fucose-containing exopolysaccharides potentially supports the emulsion-based growth of R. eutropha on plant oils.