bluuebunny/crossref_metadata_2025_split huggingface dataset:
L-tyrosine-bound ThiH structure reveals C–C bond break differences within radical SAM aromatic amino acid lyases
Authors: Amara Patricia , Saragaglia Claire , Mouesca Jean-Marie , Martin Lydie , Nicolet Yvain 
Published: April 2022

Abstract2-iminoacetate synthase ThiH is a radical S-adenosyl-L-methionine (SAM) L-tyrosine lyase and catalyzes the L-tyrosine Cα–Cβ bond break to produce dehydroglycine and p-cresol while the radical SAM L-tryptophan lyase NosL cleaves the L-tryptophan Cα–C bond to produce 3-methylindole-2-carboxylic acid. It has been difficult to understand the features that condition one C–C bond break over the other one because the two enzymes display significant primary structure similarities and presumably similar substrate-binding modes. Here, we report the crystal structure of L-tyrosine bound ThiH from Thermosinus carboxydivorans revealing an unusual protonation state of L-tyrosine upon binding. Structural comparison of ThiH with NosL and computational studies of the respective reactions they catalyze show that substrate activation is eased by tunneling effect and that subtle structural changes between the two enzymes affect, in particular, the hydrogen-atom abstraction by the 5´-deoxyadenosyl radical species, driving the difference in reaction specificity.
Gene co-expression architecture in peripheral blood in a cohort of remitted first-episode schizophrenia patients
Authors: Rodríguez Natalia , Gassó Patricia , Martínez-Pinteño Albert , Segura Àlex-González , Mezquida Gisela , Moreno-Izco Lucia , González-Peñas Javier , Zorrilla Iñaki , Martin Marta , Rodriguez-Jimenez Roberto , Corripio Iluminada , Sarró Salvador , Ibáñez Angela , Butjosa Anna , Contreras Fernando , Bioque Miquel , Cuesta Manuel-Jesús , Parellada Mara , González-Pinto Ana , Berrocoso Esther , Bernardo Miquel , Mas Sergi ,   2EPS group, Amoretti S Silvia , Moren Constanza , Stella Carol , Gurriarán Xaquin , Alonso-Solís Anna , Grasa Eva , Fernandez Jessica , Gonzalez-Ortega Itxaso , Casanovas Francesc , Bulbuena Antoni , Núñez-Doyle Ágatha , Jiménez-Rodríguez Olga , Pomarol-Clotet Edith , Feria-Raposo Isabel , Usall Judith , Muñoz-Samons Daniel , Ilundain Jose L. , Sánchez-Torres Ana Maria , Saiz-Ruiz Jeronimo , López-Torres Isabel , Nacher Juan , De-la-Cámara Concepción , Gutiérrez Miguel , Sáiz Pilar Alejandra 
Published: April 2022

AbstractA better understanding of schizophrenia subtypes is necessary to stratify the patients according to clinical attributes. To explore the genomic architecture of schizophrenia symptomatology, we analyzed blood co-expression modules and their association with clinical data from patients in remission after a first episode of schizophrenia. In total, 91 participants of the 2EPS project were included. Gene expression was assessed using the Clariom S Human Array. Weighted-gene co-expression network analysis (WGCNA) was applied to identify modules of co-expressed genes and to test its correlation with global functioning, clinical symptomatology, and premorbid adjustment. Among the 25 modules identified, six modules were significantly correlated with clinical data. These modules could be clustered in two groups according to their correlation with clinical data. Hub genes in each group showing overlap with risk genes for schizophrenia were enriched in biological processes related to metabolic processes, regulation of gene expression, cellular localization and protein transport, immune processes, and neurotrophin pathways. Our results indicate that modules with significant associations with clinical data showed overlap with gene sets previously identified in differential gene-expression analysis in brain, indicating that peripheral tissues could reveal pathogenic mechanisms. Hub genes involved in these modules revealed multiple signaling pathways previously related to schizophrenia, which may represent the complex interplay in the pathological mechanisms behind the disease. These genes could represent potential targets for the development of peripheral biomarkers underlying illness traits in clinical remission stages after a first episode of schizophrenia.
Insight into impact of sewage discharge on microbial dynamics and pathogenicity in river ecosystem
Authors: Xie Yuyang , Liu Xiaolin , Wei Haiwei , Chen Xue , Gong Ningji , Ahmad Shakeel , Lee Taeho , Ismail Sherif , Ni Shou-Qing 
Published: April 2022

AbstractDirect sewage discharge could cause copious numbers of serious and irreversible harm to the environment. This study investigated the impacts of treated and raw sewage on the river ecosystem. Through our analysis, sewage carried various nutrients into the river, leading to changes in the microbial community in the river and reducing the diversity and richness of bacteria. The relative abundances of Hydrogenophaga, Thauera, Planctomyces, Zoogloea, and Pseudomonas boosted from 0.25, 0.01, 0.00, 0.05, and 0.08% to 3.33, 3.43, 0.02, 6.28, and 2.69%, before and after raw sewage discharge, respectively. The gene abundance of pathogenic bacteria significantly increased after raw sewage discharge. For instance, the gene abundance of Vibrio, Helicobacter, Tuberculosis, and Staphylococcus augmented from 4055, 3797, 13,545, 33 reads at Site-1 to 23,556, 13,163, 19,887, 734 reads at Site-2, respectively. In addition, according to the redundancy analysis (RDA), the infectious pathogens were positively related to the environmental parameters, in which COD showed the highest positive correlation with Mycobacterium tuberculosis. Additionally, river self-purification may contribute to improving water quality and reducing pathogenicity. The outcomes of this study showed that direct discharge brought pathogens and changed microbial community structure of the river.
2 deoxy-D-glucose augments the mitochondrial respiratory chain in heart
Authors: Aiestaran-Zelaia Irati , Sánchez-Guisado María Jesús , Villar-Fernandez Marina , Azkargorta Mikel , Fadon-Padilla Lucia , Fernandez-Pelayo Uxoa , Perez-Rodriguez Diego , Ramos-Cabrer Pedro , Spinazzola Antonella , Elortza Félix , Ruíz-Cabello Jésus , Holt Ian J. 
Published: April 2022

Abstract2-Deoxy-D-glucose (2DG) has recently received emergency approval for the treatment of COVID-19 in India, after a successful clinical trial. SARS-CoV-2 infection of cultured cells is accompanied by elevated glycolysis and decreased mitochondrial function, whereas 2DG represses glycolysis and stimulates respiration, and restricts viral replication. While 2DG has pleiotropic effects on cell metabolism in cultured cells it is not known which of these manifests in vivo. On the other hand, it is known that 2DG given continuously can have severe detrimental effects on the rodent heart. Here, we show that the principal effect of an extended, intermittent 2DG treatment on mice is to augment the mitochondrial respiratory chain proteome in the heart; importantly, this occurs without vacuolization, hypertrophy or fibrosis. The increase in the heart respiratory chain proteome suggests an increase in mitochondrial oxidative capacity, which could compensate for the energy deficit caused by the inhibition of glycolysis. Thus, 2DG in the murine heart appears to induce a metabolic configuration that is the opposite of SARS-CoV-2 infected cells, which could explain the compound’s ability to restrict the propagation of the virus to the benefit of patients with COVID-19 disease.
Proteomic networks associated with tumor-educated macrophage polarization and cytotoxicity potentiated by heat-killed tuberculosis
Authors: Putri Denise U. , Feng Po-Hao , Lin Chiou-Feng , Haryana Sofia M. , Soesatyo Marsetyawan H. N. E. , Lee Kang-Yun , Han Chia-Li 
Published: April 2022

AbstractLocal administration of attenuated mycobacterium has been used as a cancer treatment adjuvant to re-boost patient immune responses with variable clinical outcomes. We aimed to clarify the impact of attenuated heat-killed tuberculosis (HKTB) on tumor-associated macrophages which play critical roles in shaping immunological regulation in the tumor microenvironment. Upon HKTB stimulation, both primary macrophages derived from the peripheral blood of healthy subjects and from lung cancer patients as well as THP1-derived classically activated macrophages (Ms) and tumor-educated macrophages (TEMs) were polarized into the proinflammatory phenotype, as characterized by increased expression cluster of differentiation 86. A quantitative proteomic analysis revealed that stimulated TEMs were unable to activate the toll-like receptor 2, signal transducer and activator of transcription 1, or nuclear factor-κB signaling. Instead, they showed distinct intercellular adhesion molecule 1 signaling, impaired cell adhesion, and mitochondrial dysfunction. These molecular mechanisms might contribute to lower cytotoxicity of HKTB-stimulated TEMs against A549 cells via the release of distinct inflammatory cytokines compared to HKTB-stimulated Ms. Our study provides an unbiased and systematic interpretation of cellular and molecular alterations of HKTB-reeducated macrophages which should help illuminate potential strategies of HKTB-stimulated macrophage-based combination therapy for cancer treatment.
Network analysis reveals dysregulated functional patterns in type II diabetic skin
Authors: Liu Chunan , Ram Sudha , Hurwitz Bonnie L. 
Published: April 2022

AbstractSkin disorders are one of the most common complications of type II diabetes (T2DM). Long-term effects of high blood glucose leave individuals with T2DM more susceptible to cutaneous diseases, but its underlying molecular mechanisms are unclear. Network-based methods consider the complex interactions between genes which can complement the analysis of single genes in previous research. Here, we use network analysis and topological properties to systematically investigate dysregulated gene co-expression patterns in type II diabetic skin with skin samples from the Genotype-Tissue Expression database. Our final network consisted of 8812 genes from 73 subjects with T2DM and 147 non-T2DM subjects matched for age, sex, and race. Two gene modules significantly related to T2DM were functionally enriched in the pathway lipid metabolism, activated by PPARA and SREBF (SREBP). Transcription factors KLF10, KLF4, SP1, and microRNA-21 were predicted to be important regulators of gene expression in these modules. Intramodular analysis and betweenness centrality identified NCOA6 as the hub gene while KHSRP and SIN3B are key coordinators that influence molecular activities differently between T2DM and non-T2DM populations. We built a TF-miRNA-mRNA regulatory network to reveal the novel mechanism (miR-21-PPARA-NCOA6) of dysregulated keratinocyte proliferation, differentiation, and migration in diabetic skin, which may provide new insights into the susceptibility of skin disorders in T2DM patients. Hub genes and key coordinators may serve as therapeutic targets to improve diabetic skincare.
The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults
Authors: Fry Jean L. , Munson Brooke D. , Thompson Katherine L. , Fry Christopher S. , Paddon-Jones Douglas , Arentson-Lantz Emily J. 
Published: April 2022

AbstractInpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model was a simulated inpatient hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) in a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose < 100 mg/dL. Participants completed a standard 75 g oral glucose tolerance test (OGTT) at baseline and post-bed rest. Bed rest increased 2-h OGTT blood glucose and insulin independent of genetic variant. In multiple regression modeling, the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele predicted increases in 2-h OGTT blood glucose (p = 0.039). We showed that the TCF7L2 rs7903146 T allele confers risk for loss of glucose tolerance in nondiabetic older adults following 7 days of bed rest.
Spatial epidemiology of hemorrhagic disease in Illinois wild white-tailed deer
Authors: Dorak Sheena J. , Varga Csaba , Ruder Mark G. , Gronemeyer Peg , Rivera Nelda A. , Dufford Douglas R. , Skinner Daniel J. , Roca Alfred L. , Novakofski Jan , Mateus-Pinilla Nohra E. 
Published: April 2022

AbstractEpizootic hemorrhagic disease (EHD) and bluetongue (BT) are vector-borne viral diseases that affect wild and domestic ruminants. Clinical signs of EHD and BT are similar; thus, the syndrome is referred to as hemorrhagic disease (HD). Syndromic surveillance and virus detection in North America reveal a northern expansion of HD. High mortalities at northern latitudes suggest recent incursions of HD viruses into northern geographic areas. We evaluated the occurrence of HD in wild Illinois white-tailed deer from 1982 to 2019. Our retrospective space–time analysis identified high-rate clusters of HD cases from 2006 to 2019. The pattern of northward expansion indicates changes in virus-host-vector interactions. Serological evidence from harvested deer revealed prior infection with BTV. However, BTV was not detected from virus isolation in dead deer sampled during outbreaks. Our findings suggest the value of capturing the precise geographic location of outbreaks, the importance of virus isolation to confirm the cause of an outbreak, and the importance of expanding HD surveillance to hunter-harvested wild white-tailed deer. Similarly, it assists in predicting future outbreaks, allowing for targeted disease and vector surveillance, helping wildlife agencies communicate with the public the cause of mortality events and viral hemorrhagic disease outcomes at local and regional scales.
Changes to the gut microbiota of a wild juvenile passerine in a multidimensional urban mosaic
Authors: Maraci Öncü , Corsini Michela , Antonatou-Papaioannou Anna , Jünemann Sebastian , Sudyka Joanna , Di Lecce Irene , Caspers Barbara A. , Szulkin Marta 
Published: April 2022

AbstractUrbanisation is a major anthropogenic perturbation presenting novel ecological and evolutionary challenges to wild populations. Symbiotic microorganisms residing in the gastrointestinal tracts (gut) of vertebrates have mutual connections with host physiology and respond quickly to environmental alterations. However, the impact of anthropogenic changes and urbanisation on the gut microbiota remains poorly understood, especially in early development. To address this knowledge gap, we characterised the gut microbiota of juvenile great tits (Parus major) reared in artificial nestboxes and in natural cavities in an urban mosaic, employing two distinct frameworks characterising the urban space. Microbial diversity was influenced by cavity type. Alpha diversity was affected by the amount of impervious surface surrounding the breeding location, and positively correlated with tree cover density. Community composition differed between urban and rural sites: these alterations covaried with sound pollution and distance to the city centre. Overall, the microbial communities reflect and are possibly influenced by the heterogeneous environmental modifications that are typical of the urban space. Strikingly, the choice of framework and environmental variables characterising the urban space can influence the outcomes of such ecological studies. Our results open new perspectives to investigate the impact of microbial symbionts on the adaptive capacity of their hosts.
The use of renin angiotensin aldosterone system inhibitors may be associated with decreased mortality after cancer surgery
Authors: Oh Ah Ran , Park Jungchan , Lee Jong-Hwan , Min Jeong Jin , Gook Joonhee , Jang Jae Ni , Lee Seung-Hwa , Kim Kyunga , Ahn Joonghyun 
Published: April 2022

AbstractRenin–angiotensin–aldosterone system (RAAS) inhibitors are antihypertensive agents with conflicting results on protective effects against some types of cancer. In light of these controversies, we aimed to study the effects of RAAS inhibitors in patients undergoing cancer surgery. From March 2010 to December 2019, consecutive adult patients with antihypertensive drug prescription at discharge after cancer surgery were enrolled and divided into two groups according to RAAS inhibitors prescription. The primary outcome was 5-year mortality after surgery. Secondary outcomes included mortalities during 3-year and 1-year follow-ups and cancer-specific mortality and recurrence rates during 5-, 3-, and 1-year follow-ups. A total of 19,765 patients were divided into two groups according to RAAS inhibitor prescription at discharge: 8,374 (42.4%) patients in the no RAAS inhibitor group and 11,391 (57.6%) patients in the RAAS inhibitor group. In 5022 pairs of propensity-score matched population, 5-year mortality was significantly lower in the RAAS inhibitor group (11.4% vs. 7.4%, hazard ratio [HR] 0.73, 95% confidence interval [CI] 0.64–0.83, P < 0.001), and 5-year recurrence rate was also lower for the RAAS inhibitor group (5.3% vs. 3.7%, HR 0.82, 95% CI 0.68–0.99, P = 0.04). In our analysis, RAAS inhibitor was associated with decreased 5-year mortality in hypertensive patients who underwent cancer surgery. Prescription of RAAS inhibitor in accordance with current guidelines may be associated with improved mortality after cancer surgery.
Super-strong magnetic field-dominated ion beam dynamics in focusing plasma devices
Authors: Morace A. , Abe Y. , Honrubia J. J. , Iwata N. , Arikawa Y. , Nakata Y. , Johzaki T. , Yogo A. , Sentoku Y. , Mima K. , Ma T. , Mariscal D. , Sakagami H. , Norimatsu T. , Tsubakimoto K. , Kawanaka J. , Tokita S. , Miyanaga N. , Shiraga H. , Sakawa Y. , Nakai M. , Azechi H. , Fujioka S. , Kodama R. 
Published: April 2022

AbstractHigh energy density physics is the field of physics dedicated to the study of matter and plasmas in extreme conditions of temperature, densities and pressures. It encompasses multiple disciplines such as material science, planetary science, laboratory and astrophysical plasma science. For the latter, high energy density states can be accompanied by extreme radiation environments and super-strong magnetic fields. The creation of high energy density states in the laboratory consists in concentrating/depositing large amounts of energy in a reduced mass, typically solid material sample or dense plasma, over a time shorter than the typical timescales of heat conduction and hydrodynamic expansion. Laser-generated, high current–density ion beams constitute an important tool for the creation of high energy density states in the laboratory. Focusing plasma devices, such as cone-targets are necessary in order to focus and direct these intense beams towards the heating sample or dense plasma, while protecting the proton generation foil from the harsh environments typical of an integrated high-power laser experiment. A full understanding of the ion beam dynamics in focusing devices is therefore necessary in order to properly design and interpret the numerous experiments in the field. In this work, we report a detailed investigation of large-scale, kilojoule-class laser-generated ion beam dynamics in focusing devices and we demonstrate that high-brilliance ion beams compress magnetic fields to amplitudes exceeding tens of kilo-Tesla, which in turn play a dominant role in the focusing process, resulting either in a worsening or enhancement of focusing capabilities depending on the target geometry.
Automated estimation of cancer cell deformability with machine learning and acoustic trapping
Authors: Lee O-Joun , Lim Hae Gyun , Shung K. Kirk , Kim Jin-Taek , Kim Hyung Ham 
Published: April 2022

AbstractCell deformability is a useful feature for diagnosing various diseases (e.g., the invasiveness of cancer cells). Existing methods commonly inflict pressure on cells and observe changes in cell areas, diameters, or thickness according to the degree of pressure. Then, the Young’s moduli (i.e., a measure of deformability) of cells are estimated based on the assumption that the degrees of the changes are inversely proportional to Young’s moduli. However, manual measurements of the physical changes in cells are labor-intensive, and the subjectivity of the operators can intervene during this step, thereby causing considerable uncertainty. Further, because the shapes of cells are nonuniform, we cannot ensure the assumption for linear correlations of physical changes in cells with their deformability. Therefore, this study aims at measuring non-linear elastic moduli of live cells (degrees of cell deformability) automatically by employing conventional neural networks (CNN) and multilayer perceptrons (MLP) while preserving (or enhancing) the accuracy of the manual methods. First, we obtain photomicrographs of cells on multiple pressure levels using single-beam acoustic tweezers, and then, we suggest an image preprocessing method for emphasizing changes in cell areas on the photomicrographs. The CNN model is trained to measure the ratios of the cell area change at each pressure level. Then, we apply the multilayer perceptron (MLP) to learn the correlations of the cell area change ratios according to the pressure levels with cell deformability. The accuracy of the CNN was evaluated using two types of breast cancer cells: MDA-MB-231 (invasive) and MCF-7 (noninvasive). The MLP was assessed using five different beads (Young’s moduli from 0.214 to 9.235 kPa), which provides standardized reference data of the non-linear elastic moduli of live cells. Finally, we validated the practicality of the proposed system by examining whether the non-linear elastic moduli estimated by the proposed system can distinguish invasive breast cancer cells from noninvasive ones.
Efficacy of electromechanical-assisted gait training on clinical walking function and gait symmetry after brain injury of stroke: a randomized controlled trial
Authors: Nam Yeon Gyo , Ko Mun Jung , Bok Soo Kyung , Paik Nam-Jong , Lim Chi-Yeon , Lee Jin Won , Kwon Bum Sun 
Published: April 2022

AbstractElectromechanical-assisted gait training may be an effective intervention to promote motor recovery after brain injury. However, many studies still have difficulties in clarifying the difference between electromechanical-assisted gait training and conventional gait training. To evaluate the effectiveness of electromechanical-assisted gait training compared to that of conventional gait training on clinical walking function and gait symmetry of stroke patients. We randomly assigned patients with stroke (n = 144) to a control group (physical therapist-assisted gait training) and an experimental group (electromechanical gait training). Both types of gait training were done for 30 min each day, 5 days a week for 4 weeks. The primary endpoint was the change in functional ambulatory category (FAC). Secondary endpoints were clinical walking functions and gait symmetries of swing time and step length. All outcomes were measured at baseline (pre-intervention) and at 4 weeks after the baseline (post-intervention). FAC showed significant improvement after the intervention, as did clinical walking functions, in both groups. The step-length asymmetry improved in the control group, but that in the experimental group and the swing-time asymmetry in both groups did not show significant improvement. In the subgroup analysis of stroke duration of 90 days, FAC and clinical walking functions showed more significant improvement in the subacute group than in the chronic group. However, gait symmetries did not show any significant changes in either the subacute or the chronic group. Electromechanically assisted gait training by EXOWALK was as effective as conventional gait training with a physiotherapist. Although clinical walking function in the subacute group improved more than in the chronic group, gait asymmetry did not improve for either group after gait training.Trial registration: KCT0003411 Clinical Research Information Service (CRIS), Republic of Korea.