bluuebunny/crossref_metadata_2025_split huggingface dataset:
Isolated anemia in patients with large granular lymphocytic leukemia (LGLL)
Authors: Salama Youssef , Zhao Fang , Oliveira Jennifer L. , Yuan Ji , Jevremovic Dragan , Go Ronald S. , Ding Wei , Parikh Sameer A. , Shah Mithun V. , Hampel Paul J. , Al-Kali Aref , Morice William G. , Shi Min 
Published: February 2022

AbstractPatients with large granular lymphocytic leukemia (LGLL) frequently present with neutropenia. When present, anemia is usually accompanied by neutropenia and/or thrombocytopenia and isolated anemia is uncommon. We evaluated a cohort of 244 LGLL patients spanning 15 years and herein report the clinicopathologic features of 34 (14%) with isolated anemia. The patients with isolated anemia showed a significantly male predominance (p = 0.001), a lower level of hemoglobulin (p < 0.0001) and higher MCV (p = 0.017) and were less likely to have rheumatoid arthritis (p = 0.023) compared to the remaining 210 patients. Of the 34 LGLL patients with isolated anemia, 13 (38%) presented with pure red cell aplasia (PRCA), markedly decreased reticulocyte count and erythroid precursors, and more transfusion-dependence when compared to non-PRCA patients. There was no other significant clinicopathologic difference between PRCA and non-PRCA patients. 32 patients were followed for a median duration of 51 months (6–199). 24 patients were treated (11/11 PRCA and 13/21 non-PRCA patients,p < 0.02). The overall response rate to first-line therapy was 83% [8/11 (72.7%) for PRCA, 12/13 (92.3%) for non-PRCA], including 14 showing complete response and 6 showing partial response with a median response duration of 48 months (12–129). Half of non-PRCA patients who were observed experienced progressive anemia. During follow-up, no patients developed neutropenia; however, 5/27 (18.5%) patients developed thrombocytopenia. No significant difference in overall survival was noted between PRCA and non-PRCA patients. In summary, this study demonstrates the unique features of LGLL with isolated anemia and underscores the importance of recognizing LGLL as a potential cause of isolated anemia, which may benefit from disease-specific treatment. LGLL patients with PRCA were more likely to require treatment but demonstrated similar clinicopathologic features, therapeutic responses, and overall survival compared to isolated anemia without PRCA, suggesting PRCA and non-PRCA of T-LGLL belong to a common disease spectrum.
FXR1 can bind with the CFIm25/CFIm68 complex and promote the progression of urothelial carcinoma of the bladder by stabilizing TRAF1 mRNA
Authors: Deng Minhua , Wang Ning , Li Zhiyong , Chen Rixin , Duan Jinling , Peng Yulu , Wu Zeshen , Zhang Zhiling , Jiang Lijuan , Zheng Xianchong , Xie Dan , Wei Wensu , Liu Zhuowei , Zhou Fangjian 
Published: February 2022

AbstractRNA-binding proteins (RBPs) are key regulators of gene expression. RBP dysregulation is reported to play essential roles in tumorigenesis. However, the role of RBPs in urothelial carcinoma of the bladder (UCB) is only starting to be unveiled. Here, we comprehensively assessed the mRNA expression landscape of 104 RBPs from two independent UCB cohorts, Sun Yat-sen University Cancer Center (SYSUCC) and The Cancer Genome Atlas (TCGA). Fragile X-related gene 1 (FXR1) was identified as a novel cancer driver gene in UCB. FXR1 overexpression was found to be related to the poor survival rate in the SYSUCC and TCGA cohorts. Functionally, FXR1 promotes UCB proliferation and tumorigenesis. Mechanistically, FXR1 serves as a platform to recruit CFIm25 and CFIm68, forming a novel 3′ processing machinery that functions in sequence-specific poly(A) site recognition. FXR1 affects the 3′ processing of Tumor necrosis factor receptor-associated factor 1 (TRAF1) mRNA, which leads to nuclear stabilization. The novel regulatory relationship between FXR1 and TRAF1 can enhance cell proliferation and suppress apoptosis. Our data collectively highlight the novel regulatory role of FXR1 in TRAF1 3′ processing as an important determinant of UCB oncogenesis. Our study provides new insight into RBP function and provides a potential therapeutic target for UCB.
Encoding gene RAB3B exists in linear chromosomal and circular extrachromosomal DNA and contributes to cisplatin resistance of hypopharyngeal squamous cell carcinoma via inducing autophagy
Authors: Lin Changwei , Chen Yifei , Zhang Fan , Liu Baiying , Xie Canbin , Song Yexun 
Published: February 2022

AbstractCisplatin (DDP) resistance is an important factor that decreases the effect of chemotherapy, thus leading to local recurrence and lymph node metastasis of hypopharyngeal squamous cell carcinoma (HSCC). We aimed to explore the role and mechanism of extrachromosomal circular DNA (eccDNA) in the DDP resistance of HSCC. In our research, the HSCC cell line FaDu and the DDP-resistant cell line FaDu/DDP were used as subjects. eccDNA sequencing and whole transcriptome sequencing were conducted, followed by a combined analysis of the two sequencing profiles. Outward PCR, inward PCR and Sanger sequencing were used to verify sequences of the eccDNAs. Bioinformatics analysis based on TCGA/GEO was performed in addition to plasmid transfection, RNA interference, qRT-PCR and Western blot experiments to verify the expression level of RAB3B amplified from eccDNA. mRFP-GFP-LC3 adenoviral particle transfection and transmission electron microscopy were used to detect autophagic flux. Finally, we evaluated the role of RAB3B in FaDu/DDP cells and patient-derived organoids. Our results showed that we purified and sequenced more than 10 thousand eccDNAs from the two cell lines, and the size of the eccDNAs was distributed from 0.01 kb to 1000 kb. The combined analysis between eccDNA and transcript sequencing indicated that there were some highly expressed genes that were completely or partially transcribed from related sequences of eccDNAs and not from genome linear DNA. We further screened and verified the encoding gene RAB3B using full-length sequences that might be amplified from eccDNA [chr1circle 46219-52682 kb]. Finally, we confirmed that RAB3B could promote DDP resistance in HSCC by inducing autophagy. The eccDNA might play significant roles in DDP resistance in HSCC by amplifying related functional genes. Further study is needed to explore the novel mechanisms of eccDNA in the drug resistance of HSCC.
Short- and long-read metagenomics of urban and rural South African gut microbiomes reveal a transitional composition and undescribed taxa
Authors: Tamburini Fiona B. , Maghini Dylan , Oduaran Ovokeraye H. , Brewster Ryan , Hulley Michaella R. , Sahibdeen Venesa , Norris Shane A. , Tollman Stephen , Kahn Kathleen , Wagner Ryan G. , Wade Alisha N. , Wafawanaka Floidy , Gómez-Olivé F. Xavier , Twine Rhian , Lombard Zané ,   H3Africa AWI-Gen Collaborative Centre, Agongo Godfred , Alberts Marianne , Ali Stuart , Asiki Gershim , Baloyi Vukosi , Boua Palwendé Romuald , Brandenburg Jean-Tristan , Ceballos Francisco Camiña , Chikowore Tinashe , Choma Solomon , Choudhury Ananyo , Crowther Nigel , Debpuur Cornelius , Gondwe Mwawi , Hazelhurst Scott , Kahn Kathleen , Khayeka-Wandabwa Christopher , Kisiangani Isaac , Kyobutungi Catherine , Lombard Zané , Mashaba Given , Mashinya Felistas , Mathema Theo , Micklesfield Lisa , Mohamed Shukri , Mthembu Busisiwe , Mukomana Freedom , Nonterah Engelbert , Norris Shane A. , Oduaran Ovokeraye , Oduro Abraham R. , Gómez-Olivé F. Xavier , Ramsay Michèle , Sankoh Osman , Sengupta Dhriti , Smyth Natalie , Soo Cassandra , Soodyall Himla , Sorgho Herman , Swiel Yaniv , Tambo Ernest , Tindana Pauline , Tinto Halidou , Tluway Furahini , Tollman Stephen , Twine Rhian , Wade Alisha , Wagner Ryan , Wandera Henry , Kabudula Chodziwadziwa , Ohene-Kwofie Daniel , Wafawanaka Floidy , Hazelhurst Scott , Bhatt Ami S. 
Published: February 2022

AbstractHuman gut microbiome research focuses on populations living in high-income countries and to a lesser extent, non-urban agriculturalist and hunter-gatherer societies. The scarcity of research between these extremes limits our understanding of how the gut microbiota relates to health and disease in the majority of the world’s population. Here, we evaluate gut microbiome composition in transitioning South African populations using short- and long-read sequencing. We analyze stool from adult females living in rural Bushbuckridge (n = 118) or urban Soweto (n = 51) and find that these microbiomes are taxonomically intermediate between those of individuals living in high-income countries and traditional communities. We demonstrate that reference collections are incomplete for characterizing microbiomes of individuals living outside high-income countries, yielding artificially low beta diversity measurements, and generate complete genomes of undescribed taxa, includingTreponema, Lentisphaerae, andSuccinatimonas. Our results suggest that the gut microbiome of South Africans does not conform to a simple “western-nonwestern” axis and contains undescribed microbial diversity.
White matter myelination during early infancy is linked to spatial gradients and myelin content at birth
Authors: Grotheer Mareike , Rosenke Mona , Wu Hua , Kular Holly , Querdasi Francesca R. , Natu Vaidehi S. , Yeatman Jason D. , Grill-Spector Kalanit 
Published: February 2022

AbstractDevelopment of myelin, a fatty sheath that insulates nerve fibers, is critical for brain function. Myelination during infancy has been studied with histology, but postmortem data cannot evaluate the longitudinal trajectory of white matter development. Here, we obtained longitudinal diffusion MRI and quantitative MRI measures of longitudinal relaxation rate (R1) of white matter in 0, 3 and 6 months-old human infants, and developed an automated method to identify white matter bundles and quantify their properties in each infant’s brain. We find that R1 increases from newborns to 6-months-olds in all bundles. R1 development is nonuniform: there is faster development in white matter that is less mature in newborns, and development rate increases along inferior-to-superior as well as anterior-to-posterior spatial gradients. As R1 is linearly related to myelin fraction in white matter bundles, these findings open new avenues to elucidate typical and atypical white matter myelination in early infancy.
Black carbon footprint of human presence in Antarctica
Authors: Cordero Raúl R. , Sepúlveda Edgardo , Feron Sarah , Damiani Alessandro , Fernandoy Francisco , Neshyba Steven , Rowe Penny M. , Asencio Valentina , Carrasco Jorge , Alfonso Juan A. , Llanillo Pedro , Wachter Paul , Seckmeyer Gunther , Stepanova Marina , Carrera Juan M. , Jorquera Jose , Wang Chenghao , Malhotra Avni , Dana Jacob , Khan Alia L. , Casassa Gino 
Published: February 2022

AbstractBlack carbon (BC) from fossil fuel and biomass combustion darkens the snow and makes it melt sooner. The BC footprint of research activities and tourism in Antarctica has likely increased as human presence in the continent has surged in recent decades. Here, we report on measurements of the BC concentration in snow samples from 28 sites across a transect of about 2,000 km from the northern tip of Antarctica (62°S) to the southern Ellsworth Mountains (79°S). Our surveys show that BC content in snow surrounding research facilities and popular shore tourist-landing sites is considerably above background levels measured elsewhere in the continent. The resulting radiative forcing is accelerating snow melting and shrinking the snowpack on BC-impacted areas on the Antarctic Peninsula and associated archipelagos by up to 23 mm water equivalent (w.e.) every summer.
Boron isotopes in boninites document rapid changes in slab inputs during subduction initiation
Authors: Li Hong-Yan , Li Xiang , Ryan Jeffrey G. , Zhang Chao , Xu Yi-Gang 
Published: February 2022

AbstractHow subduction-related magmatism starts at convergent plate margins is still poorly understood. Here we show that boron isotope variations in early-formed boninites from the Izu-Bonin arc, combined with radiogenic isotopes and elemental ratios document rapid (~0.5 to 1 Myr) changes in the sources and makeup of slab inputs as subduction begins. Heterogeneous hornblende-granulite facies melts from ocean crust gabbros ± basalts fluxed early melting to generate low silica boninites. Hydrous fluids from slab sediments and basalts later fluxed the low silica boninites mantle source to produce high silica boninites. Our results suggest that initially the uppermost parts of the slab were accreted near the nascent trench, perhaps related to early low-angle subduction. The rapid changes in slab inputs recorded in the boninites entail a steepening subduction angle and cooling of the plate interface, allowing for subduction of slab sediment and basalt, and generating hydrous fluids at lower slab temperatures.
Earthquake breakdown energy scaling despite constant fracture energy
Authors: Ke Chun-Yu , McLaskey Gregory C. , Kammer David S. 
Published: February 2022

AbstractIn the quest to determine fault weakening processes that govern earthquake mechanics, it is common to infer the earthquake breakdown energy from seismological measurements. Breakdown energy is observed to scale with slip, which is often attributed to enhanced fault weakening with continued slip or at high slip rates, possibly caused by flash heating and thermal pressurization. However, seismologically inferred breakdown energy varies by more than six orders of magnitude and is frequently found to be negative-valued. This casts doubts about the common interpretation that breakdown energy is a proxy for the fracture energy, a material property which must be positive-valued and is generally observed to be relatively scale independent. Here, we present a dynamic model that demonstrates that breakdown energy scaling can occur despite constant fracture energy and does not require thermal pressurization or other enhanced weakening. Instead, earthquake breakdown energy scaling occurs simply due to scale-invariant stress drop overshoot, which may be affected more directly by the overall rupture mode – crack-like or pulse-like – rather than from a specific slip-weakening relationship.
Cooperative multivalent receptor binding promotes exposure of the SARS-CoV-2 fusion machinery core
Authors: Pak Alexander J. , Yu Alvin , Ke Zunlong , Briggs John A. G. , Voth Gregory A. 
Published: February 2022

AbstractThe molecular events that permit the spike glycoprotein of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to bind and enter cells are important to understand for both fundamental and therapeutic reasons. Spike proteins consist of S1 and S2 domains, which recognize angiotensin-converting enzyme 2 (ACE2) receptors and contain the viral fusion machinery, respectively. Ostensibly, the binding of spike trimers to ACE2 receptors promotes dissociation of the S1 domains and exposure of the fusion machinery, although the molecular details of this process have yet to be observed. We report the development of bottom-up coarse-grained (CG) models consistent with cryo-electron tomography data, and the use of CG molecular dynamics simulations to investigate viral binding and S2 core exposure. We show that spike trimers cooperatively bind to multiple ACE2 dimers at virion-cell interfaces in a manner distinct from binding between soluble proteins, which processively induces S1 dissociation. We also simulate possible variant behavior using perturbed CG models, and find that ACE2-induced S1 dissociation is primarily sensitive to conformational state populations and the extent of S1/S2 cleavage, rather than ACE2 binding affinity. These simulations reveal an important concerted interaction between spike trimers and ACE2 dimers that primes the virus for membrane fusion and entry.
Menin directs regionalized decidual transformation through epigenetically setting PTX3 to balance FGF and BMP signaling
Authors: Liu Mengying , Deng Wenbo , Tang Lu , Liu Meng , Bao Haili , Guo Chuanhui , Zhang Changxian , Lu Jinhua , Wang Haibin , Lu Zhongxian , Kong Shuangbo 
Published: February 2022

AbstractDuring decidualization in rodents, uterine stroma undergoes extensive reprograming into distinct cells, forming the discrete regions defined as the primary decidual zone (PDZ), the secondary decidual zone (SDZ) and the layer of undifferentiated stromal cells respectively. Here we show that uterine deletion of Men1, a member of the histone H3K4 methyltransferase complex, disrupts the terminal differentiation of stroma, resulting in chaotic decidualization and pregnancy failure. Genome-wide epigenetic profile reveals that Men1 binding in chromatin recapitulates H3K4me3 distribution. Further transcriptomic investigation demonstrates that Men1 directly regulates the expression of PTX3, an extra-cellular trap for FGF2 in decidual cells. Decreased Ptx3 upon Men1 ablation leads to aberrant activation of ERK1/2 in the SDZ due to the unrestrained FGF2 signal emanated from undifferentiated stromal cells, which blunt BMP2 induction and decidualization. In brief, our study provides genetic and molecular mechanisms for epigenetic rewiring mediated decidual regionalization by Men1 and sheds new light on pregnancy maintenance.
Multimodal investigation of the association between shift work and the brain in a population-based sample of older adults
Authors: Bittner Nora , Korf Horst-Werner , Stumme Johanna , Jockwitz Christiane , Moebus Susanne , Schmidt Börge , Dragano Nico , Caspers Svenja 
Published: February 2022

AbstractNeuropsychological studies reported that shift workers show reduced cognitive performance and circadian dysfunctions which may impact structural and functional brain networks. Here we tested the hypothesis whether night shift work is associated with resting-state functional connectivity (RSFC), cortical thickness and gray matter volume in participants of the 1000BRAINS study for whom information on night shift work and imaging data were available. 13 PRESENT and 89 FORMER night shift workers as well as 430 control participants who had never worked in shift (NEVER) met these criteria and were included in our study. No associations between night shift work, three graph-theoretical measures of RSFC of 7 functional brain networks and brain morphology were found after multiple comparison correction. Preceding multiple comparison correction, our results hinted at an association between more years of shift work and higher segregation of the visual network in PRESENT shift workers and between shift work experience and lower gray matter volume of the left thalamus. Extensive neuropsychological investigations supplementing objective imaging methodology did not reveal an association between night shift work and cognition after multiple comparison correction. Our pilot study suggests that night shift work does not elicit general alterations in brain networks and affects the brain only to a limited extent. These results now need to be corroborated in studies with larger numbers of participants.
Proteome analysis of the Gram-positive fish pathogen Renibacterium salmoninarum reveals putative role of membrane vesicles in virulence
Authors: Kroniger Tobias , Flender Daniel , Schlüter Rabea , Köllner Bernd , Trautwein-Schult Anke , Becher Dörte 
Published: February 2022

AbstractBacterial kidney disease (BKD) is a chronic bacterial disease affecting both wild and farmed salmonids. The causative agent for BKD is the Gram-positive fish pathogen Renibacterium salmoninarum. As treatment and prevention of BKD have proven to be difficult, it is important to know and identify the key bacterial proteins that interact with the host. We used subcellular fractionation to report semi-quantitative data for the cytosolic, membrane, extracellular, and membrane vesicle (MV) proteome of R. salmoninarum. These data can aid as a backbone for more targeted experiments regarding the development of new drugs for the treatment of BKD. Further analysis was focused on the MV proteome, where both major immunosuppressive proteins P57/Msa and P22 and proteins involved in bacterial adhesion were found in high abundance. Interestingly, the P22 protein was relatively enriched only in the extracellular and MV fraction, implicating that MVs may play a role in host–pathogen interaction. Compared to the other subcellular fractions, the MVs were also relatively enriched in lipoproteins and all four cell wall hydrolases belonging to the New Lipoprotein C/Protein of 60 kDa (NlpC/P60) family were detected, suggesting an involvement in the formation of the MVs.
Strain-induced quantum Hall phenomena of excitons in graphene
Authors: Berman Oleg L. , Kezerashvili Roman Ya. , Lozovik Yurii E. , Ziegler Klaus G. 
Published: February 2022

AbstractWe study direct and indirect pseudomagnetoexcitons, formed by an electron and a hole in the layers of gapped graphene under strain-induced gauge pseudomagnetic field. Since the strain-induced pseudomagnetic field acts on electrons and holes the same way, it occurs that the properties of single pseudomagnetoexcitons, their collective effects and phase diagram are cardinally different from those of magnetoexcitons in a real magnetic field. We have derived wave functions and energy spectrum of direct in a monolayer and indirect pseudomagnetoexcitons in a double layer of gapped graphene. The quantum Hall effect for direct and indirect excitons was predicted in the monolayers and double layers of gapped graphene under strain-induced gauge pseudomagnetic field, correspondingly.
Role of TRPC6 in kidney damage after acute ischemic kidney injury
Authors: Zheng Zhihuang , Tsvetkov Dmitry , Bartolomaeus Theda Ulrike Patricia , Erdogan Cem , Krügel Ute , Schleifenbaum Johanna , Schaefer Michael , Nürnberg Bernd , Chai Xiaoning , Ludwig Friedrich-Alexander , N’diaye Gabriele , Köhler May-Britt , Wu Kaiyin , Gollasch Maik , Markó Lajos 
Published: February 2022

AbstractTransient receptor potential channel subfamily C, member 6 (TRPC6), a non-selective cation channel that controls influx of Ca2+ and other monovalent cations into cells, is widely expressed in the kidney. TRPC6 gene variations have been linked to chronic kidney disease but its role in acute kidney injury (AKI) is unknown. Here we aimed to investigate the putative role of TRPC6 channels in AKI. We used Trpc6−/− mice and pharmacological blockade (SH045 and BI-749327), to evaluate short-term AKI outcomes. Here, we demonstrate that neither Trpc6 deficiency nor pharmacological inhibition of TRPC6 influences the short-term outcomes of AKI. Serum markers, renal expression of epithelial damage markers, tubular injury, and renal inflammatory response assessed by the histological analysis were similar in wild-type mice compared to Trpc6−/− mice as well as in vehicle-treated versus SH045- or BI-749327-treated mice. In addition, we also found no effect of TRPC6 modulation on renal arterial myogenic tone by using blockers to perfuse isolated kidneys. Therefore, we conclude that TRPC6 does not play a role in the acute phase of AKI. Our results may have clinical implications for safety and health of humans with TRPC6 gene variations, with respect to mutated TRPC6 channels in the response of the kidney to acute ischemic stimuli.