bluuebunny/crossref_metadata_2025_split huggingface dataset:
Minimal mitochondrial respiration is required to prevent cell death by inhibition of mTOR signaling in CoQ-deficient cells
Authors: Wang Ying , Hekimi Siegfried 
Published: August 2021

AbstractCoenzyme Q (CoQ) is a lipid-like mobile electron transporter of the mitochondrial respiratory chain. Patients with partial loss-of-function mutations in the CoQ biosynthesis pathway suffer from partial primary CoQ deficiency (MIM 607426). This leads to mitochondrial dysfunction, which presents like mitochondrial disease syndrome (MDS). In addition, many other conditions, including MDS itself, lead to secondary CoQ deficiency. We sought to identify drugs that can alleviate the consequences of the mitochondrial dysfunction that is associated with CoQ deficiency. Loss of the CoQ-biosynthetic enzyme COQ7 prevents CoQ synthesis but leads to the accumulation of the biosynthetic intermediate demethoxyubiquinone (DMQ). Coq7-knockout mouse embryonic fibroblasts (MEFs) die when rapid ATP generation from glycolysis is prevented. We screened for drugs that could rescue cell death under these conditions. All compounds that were identified inhibit mTOR signaling. In the CoQ-deficient cells, the beneficial action mTOR inhibition appears to be mediated by inhibition of protein translation rather than by stimulation of autophagy. We further studied the Coq7-knockout cells to better determine under which conditions mTOR inhibition could be beneficial. We established that Coq7-knockout cells remain capable of a low level of mitochondrial respiration mediated by DMQ. To obtain more profound mitochondrial dysfunction, we created double-knockout mutant MEFs lacking both Coq7, as well as Pdss2, which is required for sidechain synthesis. These cells make neither CoQ nor DMQ, and their extremely small residual respiration depends on uptake of CoQ from the culture medium. Although these cells are healthy in the presence of sufficient glucose for glycolysis and do not require uridine or pyruvate supplementation, mTOR inhibitors were unable to prevent their death in the absence of sufficient glycolysis. We conclude that, for reasons that remain to be elucidated, the energy-sparing benefits of the inhibition of mTOR signaling require a minimally functional respiratory chain.
Dysregulated hematopoiesis in bone marrow marks severe COVID-19
Authors: Wang Xin , Wen Yanling , Xie Xiaowei , Liu Yang , Tan Xiaohua , Cai Qingxian , Zhang Yawen , Cheng Lin , Xu Gang , Zhang Shengyuan , Wang Haiyan , Wei Lanlan , Tang Xian , Qi Furong , Zhao Juanjuan , Yuan Jing , Liu Lei , Zhu Ping , Ginhoux Florent , Zhang Shuye , Cheng Tao , Zhang Zheng 
Published: August 2021

AbstractSevere coronavirus disease 2019 (COVID-19) is often indicated by lymphopenia and increased myelopoiesis; however, the underlying mechanism is still unclear, especially the alteration of hematopoiesis. It is important to explore to what extent and how hematopoietic stem cells contribute to the impairment of peripheral lymphoid and myeloid compartments in COVID-19 patients. In this study, we used single-cell RNA sequencing to assess bone marrow mononuclear cells from COVID-19 patients with peripheral blood mononuclear cells as control. The results showed that the hematopoietic stem cells in these patients were mainly in the G1 phase and prone to apoptosis, with immune activation and anti-viral responses. Importantly, a significant accumulation of immature myeloid progenitors and a dramatic reduction of lymphoid progenitors in severe cases were identified, along with the up-regulation of transcription factors (such as SPI1, LMO4, ETS2, FLI1, and GATA2) that are important for the hematopoietic stem cell or multipotent progenitor to differentiate into downstream progenitors. Our results indicate a dysregulated hematopoiesis in patients with severe COVID-19.
Vertically transferred maternal immune cells promote neonatal immunity against early life infections
Authors: Stelzer Ina Annelies , Urbschat Christopher , Schepanski Steven , Thiele Kristin , Triviai Ioanna , Wieczorek Agnes , Alawi Malik , Ohnezeit Denise , Kottlau Julian , Huang Jiabin , Fischer Nicole , Mittrücker Hans-Willi , Solano Maria Emilia , Fehse Boris , Diemert Anke , Stahl Felix R. , Arck Petra Clara 
Published: August 2021

AbstractDuring mammalian pregnancy, immune cells are vertically transferred from mother to fetus. The functional role of these maternal microchimeric cells (MMc) in the offspring is mostly unknown. Here we show a mouse model in which MMc numbers are either normal or low, which enables functional assessment of MMc. We report a functional role of MMc in promoting fetal immune development. MMc induces preferential differentiation of hematopoietic stem cells in fetal bone marrow towards monocytes within the myeloid compartment. Neonatal mice with higher numbers of MMc and monocytes show enhanced resilience against cytomegalovirus infection. Similarly, higher numbers of MMc in human cord blood are linked to a lower number of respiratory infections during the first year of life. Our data highlight the importance of MMc in promoting fetal immune development, potentially averting the threats caused by early life exposure to pathogens.
Shear band-driven precipitate dispersion for ultrastrong ductile medium-entropy alloys
Authors: Jang Tae Jin , Choi Won Seok , Kim Dae Woong , Choi Gwanghyo , Jun Hosun , Ferrari Alberto , Körmann Fritz , Choi Pyuck-Pa , Sohn Seok Su 
Published: August 2021

AbstractPrecipitation strengthening has been the basis of physical metallurgy since more than 100 years owing to its excellent strengthening effects. This approach generally employs coherent and nano-sized precipitates, as incoherent precipitates energetically become coarse due to their incompatibility with matrix and provide a negligible strengthening effect or even cause brittleness. Here we propose a shear band-driven dispersion of nano-sized and semicoherent precipitates, which show significant strengthening effects. We add aluminum to a model CoNiV medium-entropy alloy with a face-centered cubic structure to form the L21 Heusler phase with an ordered body-centered cubic structure, as predicted by ab initio calculations. Micro-shear bands act as heterogeneous nucleation sites and generate finely dispersed intragranular precipitates with a semicoherent interface, which leads to a remarkable strength-ductility balance. This work suggests that the structurally dissimilar precipitates, which are generally avoided in conventional alloys, can be a useful design concept in developing high-strength ductile structural materials.
Plastic and low-cost axial zero thermal expansion alloy by a natural dual-phase composite
Authors: Yu Chengyi , Lin Kun , Jiang Suihe , Cao Yili , Li Wenjie , Wang Yilin , Chen Yan , An Ke , You Li , Kato Kenichi , Li Qiang , Chen Jun , Deng Jinxia , Xing Xianran 
Published: August 2021

AbstractZero thermal expansion (ZTE) alloys possess unique dimensional stability, high thermal and electrical conductivities. Their practical application under heat and stress is however limited by their inherent brittleness because ZTE and plasticity are generally exclusive in a single-phase material. Besides, the performance of ZTE alloys is highly sensitive to change of compositions, so conventional synthesis methods such as alloying or the design of multiphase to improve its thermal and mechanical properties are usually inapplicable. In this study, by adopting a one-step eutectic reaction method, we overcome this challenge. A natural dual-phase composite with ZTE and plasticity was synthesized by melting 4 atom% holmium with pure iron. The dual-phase alloy shows moderate plasticity and strength, axial zero thermal expansion, and stable thermal cycling performance as well as low cost. By using synchrotron X-ray diffraction, in-situ neutron diffraction and microscopy, the critical mechanism of dual-phase synergy on both thermal expansion regulation and mechanical property enhancement is revealed. These results demonstrate that eutectic reaction is likely to be a universal and effective method for the design of high-performance intermetallic-compound-based ZTE alloys.
Reversible gene silencing through frameshift indels and frameshift scars provide adaptive plasticity for Mycobacterium tuberculosis
Authors: Gupta Aditi , Alland David 
Published: August 2021

AbstractMycobacterium tuberculosis can adapt to changing environments by non-heritable mechanisms. Frame-shifting insertions and deletions (indels) may also participate in adaptation through gene disruption, which could be reversed by secondary introduction of a frame-restoring indel. We present ScarTrek, a program that scans genomic data for indels, including those that together disrupt and restore a gene’s reading frame, producing “frame-shift scars” suggestive of reversible gene inactivation. We use ScarTrek to analyze 5977 clinical M. tuberculosis isolates. We show that indel frequency inversely correlates with genomic linguistic complexity and varies with gene-position and gene-essentiality. Using ScarTrek, we detect 74 unique frame-shift scars in 48 genes, with a 3.74% population-level incidence of unique scar events. We find multiple scars in the ESX-1 gene cluster. Six scars show evidence of convergent evolution while the rest shared a common ancestor. Our results suggest that sequential indels are a mechanism for reversible gene silencing and adaptation in M. tuberculosis.
Phosphorus coordinated Rh single-atom sites on nanodiamond as highly regioselective catalyst for hydroformylation of olefins
Authors: Gao Peng , Liang Guanfeng , Ru Tong , Liu Xiaoyan , Qi Haifeng , Wang Aiqin , Chen Fen-Er 
Published: August 2021

AbstractSingle-atom Rh catalysts present superior activity relative to homogeneous catalyst in olefins hydroformylation, yet with limited success in regioselectivity control. In the present work, we develop a phosphorus coordinated Rh1 single-atom catalyst with nanodiamond as support. Benefiting from this unique structure, the catalyst exhibits excellent activity and regioselectivity in hydroformylation of arylethylenes with wide substrate generality, i.e., with high conversion (>99%) and high regioselectivity (>90%), which is comparable with the homogeneous counterparts. The coordination interaction between Rh1 and surface phosphorus species is clarified by 31P solid-state NMR and X-ray absorption spectroscopy (XAS). Rh single atoms are firmly anchored over nanodiamond through Rh-P bonds, guaranteeing good stability in the hydroformation of styrene even after six runs. Finally, by using this catalyst, two kinds of pharmaceutical molecules, Ibuprofen and Fendiline, are synthesized efficiently with high yields, demonstrating a new prospect of single-atom catalyst in pharmaceutical synthesis.
MiREDiBase, a manually curated database of validated and putative editing events in microRNAs
Authors: Marceca Gioacchino P. , Distefano Rosario , Tomasello Luisa , Lagana Alessandro , Russo Francesco , Calore Federica , Romano Giulia , Bagnoli Marina , Gasparini Pierluigi , Ferro Alfredo , Acunzo Mario , Ma Qin , Croce Carlo M. , Nigita Giovanni 
Published: August 2021

AbstractMicroRNAs (miRNAs) are regulatory small non-coding RNAs that function as translational repressors. MiRNAs are involved in most cellular processes, and their expression and function are presided by several factors. Amongst, miRNA editing is an epitranscriptional modification that alters the original nucleotide sequence of selected miRNAs, possibly influencing their biogenesis and target-binding ability. A-to-I and C-to-U RNA editing are recognized as the canonical types, with the A-to-I type being the predominant one. Albeit some bioinformatics resources have been implemented to collect RNA editing data, it still lacks a comprehensive resource explicitly dedicated to miRNA editing. Here, we present MiREDiBase, a manually curated catalog of editing events in miRNAs. The current version includes 3,059 unique validated and putative editing sites from 626 pre-miRNAs in humans and three primates. Editing events in mature human miRNAs are supplied with miRNA-target predictions and enrichment analysis, while minimum free energy structures are inferred for edited pre-miRNAs. MiREDiBase represents a valuable tool for cell biology and biomedical research and will be continuously updated and expanded at https://ncrnaome.osumc.edu/miredibase.
Global data set of long-term summertime vertical temperature profiles in 153 lakes
Authors: Pilla Rachel M. , Mette Elizabeth M. , Williamson Craig E. , Adamovich Boris V. , Adrian Rita , Anneville Orlane , Balseiro Esteban , Ban Syuhei , Chandra Sudeep , Colom-Montero William , Devlin Shawn P. , Dix Margaret A. , Dokulil Martin T. , Feldsine Natalie A. , Feuchtmayr Heidrun , Fogarty Natalie K. , Gaiser Evelyn E. , Girdner Scott F. , González María J. , Hambright K. David , Hamilton David P. , Havens Karl , Hessen Dag O. , Hetzenauer Harald , Higgins Scott N. , Huttula Timo H. , Huuskonen Hannu , Isles Peter D. F. , Joehnk Klaus D. , Keller Wendel Bill , Klug Jen , Knoll Lesley B. , Korhonen Johanna , Korovchinsky Nikolai M. , Köster Oliver , Kraemer Benjamin M. , Leavitt Peter R. , Leoni Barbara , Lepori Fabio , Lepskaya Ekaterina V. , Lottig Noah R. , Luger Martin S. , Maberly Stephen C. , MacIntyre Sally , McBride Chris , McIntyre Peter , Melles Stephanie J. , Modenutti Beatriz , Müller-Navarra Dörthe C. , Pacholski Laura , Paterson Andrew M. , Pierson Don C. , Pislegina Helen V. , Plisnier Pierre-Denis , Richardson David C. , Rimmer Alon , Rogora Michela , Rogozin Denis Y. , Rusak James A. , Rusanovskaya Olga O. , Sadro Steve , Salmaso Nico , Saros Jasmine E. , Sarvala Jouko , Saulnier-Talbot Émilie , Schindler Daniel E. , Shimaraeva Svetlana V. , Silow Eugene A. , Sitoki Lewis M. , Sommaruga Ruben , Straile Dietmar , Strock Kristin E. , Swain Hilary , Tallant Jason M. , Thiery Wim , Timofeyev Maxim A. , Tolomeev Alexander P. , Tominaga Koji , Vanni Michael J. , Verburg Piet , Vinebrooke Rolf D. , Wanzenböck Josef , Weathers Kathleen , Weyhenmeyer Gesa A. , Zadereev Egor S. , Zhukova Tatyana V. 
Published: August 2021

AbstractClimate change and other anthropogenic stressors have led to long-term changes in the thermal structure, including surface temperatures, deepwater temperatures, and vertical thermal gradients, in many lakes around the world. Though many studies highlight warming of surface water temperatures in lakes worldwide, less is known about long-term trends in full vertical thermal structure and deepwater temperatures, which have been changing less consistently in both direction and magnitude. Here, we present a globally-expansive data set of summertime in-situ vertical temperature profiles from 153 lakes, with one time series beginning as early as 1894. We also compiled lake geographic, morphometric, and water quality variables that can influence vertical thermal structure through a variety of potential mechanisms in these lakes. These long-term time series of vertical temperature profiles and corresponding lake characteristics serve as valuable data to help understand changes and drivers of lake thermal structure in a time of rapid global and ecological change.
A comprehensive analysis of gene expression changes in a high replicate and open-source dataset of differentiating hiPSC-derived cardiomyocytes
Authors: Grancharova Tanya , Gerbin Kaytlyn A. , Rosenberg Alexander B. , Roco Charles M. , Arakaki Joy E. , DeLizo Colette M. , Dinh Stephanie Q. , Donovan-Maiye Rory M. , Hirano Matthew , Nelson Angelique M. , Tang Joyce , Theriot Julie A. , Yan Calysta , Menon Vilas , Palecek Sean P. , Seelig Georg , Gunawardane Ruwanthi N. 
Published: August 2021

AbstractWe performed a comprehensive analysis of the transcriptional changes occurring during human induced pluripotent stem cell (hiPSC) differentiation to cardiomyocytes. Using single cell RNA-seq, we sequenced > 20,000 single cells from 55 independent samples representing two differentiation protocols and multiple hiPSC lines. Samples included experimental replicates ranging from undifferentiated hiPSCs to mixed populations of cells at D90 post-differentiation. Differentiated cell populations clustered by time point, with differential expression analysis revealing markers of cardiomyocyte differentiation and maturation changing from D12 to D90. We next performed a complementary cluster-independent sparse regression analysis to identify and rank genes that best assigned cells to differentiation time points. The two highest ranked genes between D12 and D24 (MYH7 and MYH6) resulted in an accuracy of 0.84, and the three highest ranked genes between D24 and D90 (A2M, H19, IGF2) resulted in an accuracy of 0.94, revealing that low dimensional gene features can identify differentiation or maturation stages in differentiating cardiomyocytes. Expression levels of select genes were validated using RNA FISH. Finally, we interrogated differences in cardiac gene expression resulting from two differentiation protocols, experimental replicates, and three hiPSC lines in the WTC-11 background to identify sources of variation across these experimental variables.
Monocyte to HDL cholesterol ratio as a marker of the presence and severity of obstructive sleep apnea in hypertensive patients
Authors: Sun Min , Liang Chao , Lin Hui , Meng Yuezhi , Tang Qunzhong , Shi Xiaoyu , Zhang Erming , Tang Qiang 
Published: August 2021

AbstractThis study aimed to investigate the correlation between monocyte to high-density lipoprotein cholesterol ratio (MHR) and obstructive sleep apnea (OSA) in patients with hypertension. A total of 246 hypertensive patients (67 controls, 65 mild, 51 moderate, and 63 severe OSA) were included. The relationship between MHR and OSA was analyzed. MHR correlated positively with apnea–hypopnea index (AHI), while negatively with mean SpO2 (P < 0.01). MHR was higher in OSA group than the control group (9.2 ± 2.6 vs. 10.8 ± 3.6, P < 0.001). Moreover, MHR in severe OSA group was the highest among all groups (9.2 ± 2.6, 10.2 ± 3.2, 10.4 ± 4.0, and 11.8 ± 3.4 in control, mild, moderate, and severe OSA group, respectively, P < 0.001). Logistic regression analysis demonstrated that MHR was an independent predictor of the presence of OSA (OR = 1.152, P < 0.01) and severe OSA (OR = 1.142, P < 0.01). Area under the curve of MHR was 0.634 (P < 0.05) and 0.660 (P < 0.05) for predicting OSA and severe OSA respectively in the ROC analysis. In conclusion, MHR increased with the severity of OSA. As a practical and cost-effective test, MHR was expected to be an available marker in evaluating OSA risk and severity in hypertensive patients.
Gastrin mediates cardioprotection through angiogenesis after myocardial infarction by activating the HIF-1α/VEGF signalling pathway
Authors: Wang Rui , Zhang Ziyue , Xu Zaicheng , Wang Na , Yang Dezhong , Liu Zhi Zhao , Liao Qiao , Xia Xuewei , Chen Caiyu , Shou Jialing , Li Liangpeng , Wang Wei Eric , Zeng Chunyu , Xia Tianyang , Wang Hongyong 
Published: August 2021

AbstractAcute myocardial infarction (MI) is one of the leading causes of death in humans. Our previous studies showed that gastrin alleviated acute myocardial ischaemia–reperfusion injury. We hypothesize that gastrin might protect against heart injury after MI by promoting angiogenesis. An MI model was simulated by ligating the anterior descending coronary artery in adult male C57BL/6J mice. Gastrin was administered twice daily by intraperitoneal injection for 2 weeks after MI. We found that gastrin reduced mortality, improved myocardial function with reduced infarct size and promoted angiogenesis. Gastrin increased HIF-1α and VEGF expression. Downregulation of HIF-1α expression by siRNA reduced the proliferation, migration and tube formation of human umbilical vein endothelial cells. These results indicate that gastrin restores cardiac function after MI by promoting angiogenesis via the HIF-1α/VEGF pathway.
The dielectric response of phenothiazine-based glass-formers with different molecular complexity
Authors: Rams-Baron M. , Jędrzejowska A. , Jurkiewicz K. , Matussek M. , Musiał M. , Paluch M. 
Published: August 2021

AbstractWe examined a series of structurally related glass-forming liquids in which a phenothiazine-based tricyclic core (PTZ) was modified by attaching n-alkyl chains of different lengths (n = 4, 8, 10). We systematically disentangled the impact of chemical structure modification on the intermolecular organization and molecular dynamics probed by broadband dielectric spectroscopy (BDS). X-ray diffraction (XRD) patterns evidenced that all PTZ-derivatives are not ‘ordinary’ liquids and form nanoscale clusters. The chain length has a decisive impact on properties, exerting a plasticizing effect on the dynamics. Its elongation decreases glass transition temperature with slight impact on fragility. The increase in the medium-range order was manifested as a broadening of the dielectric loss peak reflected in the lower value of stretching parameter βKWW. A disagreement with the behavior observed for non-associating liquids was found as a deviation from the anti-correlation between the value of βKWW and the relaxation strength of the α-process. Besides, to explain the broadening of loss peak in PTZ with the longest (decyl) chain a slow Debye process was postulated. In contrast, the sample with the shortest alkyl chain and a less complex structure with predominant supramolecular assembly through π–π stacking exhibits no clear Debye-mode fingerprints. The possible reasons are also discussed.
Effects of high rosuvastatin doses on hepatocyte mitochondria of hypercholesterolemic mice
Authors: Díaz-Zagoya Juan C. , Marín-Medina Alejandro , Zetina-Esquivel Alma M. , Blé-Castillo Jorge L. , Castell-Rodríguez Andrés E. , Juárez-Rojop Isela E. , Miranda-Zamora Rodrigo 
Published: August 2021

AbstractStatins are the cornerstone of therapy for individuals with hyperlipidemia. The aim of this study was to analyze the undesirable effects of mild, moderate and high doses of rosuvastatin in CD-1 male mice who received a cholesterol-rich diet, focusing on the morphological and functional changes on hepatocyte mitochondria. In a mouse model we studied the combined administration of a cholesterol-rich diet along with mild and moderate doses of rosuvastatin (1, 2.5 or 5 mg/kg/day) during several days. After the animals were sacrificed, liver mitochondria were isolated for microscopic studies and to analyze the respiratory function. The respiratory control (state-3/state-4) was evaluated in mice who received high doses of rosuvastatin. Rosuvastatin doses higher than 20 mg/kg/day induced premature death in mice with a hypercholesterolemic diet, but not in mice with a cholesterol-free diet. Doses from 2.5 to 5 mg/kg/day also induced morphological and functional alterations in mitochondria but these hypercholesterolemic animals survived longer. Giving 1 mg/kg/day, which is close to the maximal therapeutic dose for humans, did not affect mitochondrial architecture or respiratory function after two months of treatment. We analyzed the effect of rosuvastatin on hepatic tissue because it is where statins are mainly accumulated and it is the main site of endogenous cholesterol synthesis. Our results contribute to understand the side effects of rosuvastatin in hypercholesterolemic mice, effects that could also affect humans who are intolerant to statins.