bluuebunny/crossref_metadata_2025_split huggingface dataset:
Over-expression of an electron transport protein OmcS provides sufficient NADH for d-lactate production in cyanobacterium
Authors: Meng Hengkai , Zhang Wei , Zhu Huawei , Yang Fan , Zhang Yanping , Zhou Jie , Li Yin 
Published: April 2021

Abstract
Background
An efficient supply of reducing equivalent is essential for chemicals production by engineered microbes. In phototrophic microbes, the NADPH generated from photosynthesis is the dominant form of reducing equivalent. However, most dehydrogenases prefer to utilize NADH as a cofactor. Thus, sufficient NADH supply is crucial to produce dehydrogenase-derived chemicals in cyanobacteria. Photosynthetic electron is the sole energy source and excess electrons are wasted in the light reactions of photosynthesis.

Results
Here we propose a novel strategy to direct the electrons to generate more ATP from light reactions to provide sufficient NADH for lactate production. To this end, we introduced an electron transport protein-encoding gene omcS into cyanobacterium Synechococcus elongatus UTEX 2973 and demonstrated that the introduced OmcS directs excess electrons from plastoquinone (PQ) to photosystem I (PSI) to stimulate cyclic electron transfer (CET). As a result, an approximately 30% increased intracellular ATP, 60% increased intracellular NADH concentrations and up to 60% increased biomass production with fourfold increased d-lactate production were achieved. Comparative transcriptome analysis showed upregulation of proteins involved in linear electron transfer (LET), CET, and downregulation of proteins involved in respiratory electron transfer (RET), giving hints to understand the increased levels of ATP and NADH.

Conclusions
This strategy provides a novel orthologous way to improve photosynthesis via enhancing CET and supply sufficient NADH for the photosynthetic production of chemicals.
Evaluating the transcriptional fidelity of cancer models
Authors: Peng Da , Gleyzer Rachel , Tai Wen-Hsin , Kumar Pavithra , Bian Qin , Isaacs Bradley , da Rocha Edroaldo Lummertz , Cai Stephanie , DiNapoli Kathleen , Huang Franklin W. , Cahan Patrick 
Published: April 2021

Abstract
Background
Cancer researchers use cell lines, patient-derived xenografts, engineered mice, and tumoroids as models to investigate tumor biology and to identify therapies. The generalizability and power of a model derive from the fidelity with which it represents the tumor type under investigation; however, the extent to which this is true is often unclear. The preponderance of models and the ability to readily generate new ones has created a demand for tools that can measure the extent and ways in which cancer models resemble or diverge from native tumors.

Methods
We developed a machine learning-based computational tool, CancerCellNet, that measures the similarity of cancer models to 22 naturally occurring tumor types and 36 subtypes, in a platform and species agnostic manner. We applied this tool to 657 cancer cell lines, 415 patient-derived xenografts, 26 distinct genetically engineered mouse models, and 131 tumoroids. We validated CancerCellNet by application to independent data, and we tested several predictions with immunofluorescence.

Results
We have documented the cancer models with the greatest transcriptional fidelity to natural tumors, we have identified cancers underserved by adequate models, and we have found models with annotations that do not match their classification. By comparing models across modalities, we report that, on average, genetically engineered mice and tumoroids have higher transcriptional fidelity than patient-derived xenografts and cell lines in four out of five tumor types. However, several patient-derived xenografts and tumoroids have classification scores that are on par with native tumors, highlighting both their potential as faithful model classes and their heterogeneity.

Conclusions
CancerCellNet enables the rapid assessment of transcriptional fidelity of tumor models. We have made CancerCellNet available as a freely downloadable R package (https://github.com/pcahan1/cancerCellNet) and as a web application (http://www.cahanlab.org/resources/cancerCellNet_web) that can be applied to new cancer models that allows for direct comparison to the cancer models evaluated here.
The unusual structure of the PiggyMac cysteine-rich domain reveals zinc finger diversity in PiggyBac-related transposases
Authors: Guérineau Marc , Bessa Luiza , Moriau Séverine , Lescop Ewen , Bontems François , Mathy Nathalie , Guittet Eric , Bischerour Julien , Bétermier Mireille , Morellet Nelly 
Published: April 2021

AbstractBackgroundTransposons are mobile genetic elements that colonize genomes and drive their plasticity in all organisms. DNA transposon-encoded transposases bind to the ends of their cognate transposons and catalyze their movement. In some cases, exaptation of transposon genes has allowed novel cellular functions to emerge. The PiggyMac (Pgm) endonuclease of the ciliateParamecium tetraureliais a domesticated transposase from the PiggyBac family. It carries a core catalytic domain typical of PiggyBac-related transposases and a short cysteine-rich domain (CRD), flanked by N- and C-terminal extensions. During sexual processes Pgm catalyzes programmed genome rearrangements (PGR) that eliminate ~ 30% of germline DNA from the somatic genome at each generation. How Pgm recognizes its DNA cleavage sites in chromatin is unclear and the structure-function relationships of its different domains have remained elusive.ResultsWe provide insight into Pgm structure by determining the fold adopted by its CRD, an essential domain required for PGR. Using Nuclear Magnetic Resonance, we show that the Pgm CRD binds two Zn2+ions and forms an unusual binuclear cross-brace zinc finger, with a circularly permutated treble-clef fold flanked by two flexible arms. The Pgm CRD structure clearly differs from that of several other PiggyBac-related transposases, among which is the well-studied PB transposase fromTrichoplusia ni. Instead, the arrangement of cysteines and histidines in the primary sequence of the Pgm CRD resembles that of active transposases frompiggyBac-like elements found in other species and of human PiggyBac-derived domesticated transposases. We show that, unlike the PB CRD, the Pgm CRD does not bind DNA. Instead, it interacts weakly with the N-terminus of histone H3, whatever its lysine methylation state.ConclusionsThe present study points to the structural diversity of the CRD among transposases from the PiggyBac family and their domesticated derivatives, and highlights the diverse interactions this domain may establish with chromatin, from sequence-specific DNA binding to contacts with histone tails. Our data suggest that the Pgm CRD fold, whose unusual arrangement of cysteines and histidines is found in all PiggyBac-related domesticated transposases fromParameciumandTetrahymena, was already present in the ancestral active transposase that gave rise to ciliate domesticated proteins.
Sex differences in the consumption of over-the-counter analgesics among amateur volleyball players
Authors: Hager Lisa , Averbeck Beate , Voelcker-Rehage Claudia , Kutz Dieter F. 
Published: April 2021

AbstractBackgroundCompared with the normal adult population, athletes of several sport disciplines, such as endurance sports, ball sports, cycling and swimming, have higher use of over-the-counter analgesics (OTC analgesics). The aim of this study was to describe the epidemiology of OTC analgesic use in volleyball players as a typical competitive sport discipline. One particular focus was placed on the analysis whether the athletes’ use of OTC analgesics was influenced by their performance motivation.MethodsA cross-sectional survey among amateur volleyball players was carried out using a web-based sports questionnaire. The study included athletes of both sexes, 18 years and older, currently playing in a German volleyball league. The athletes’ sport-related complaints were evaluated regarding the use of OTC analgesics. The use of OTC analgesics by athletes was compared with their performance motivation, based on the „Achievement Motives Scale - Sport” (AMS-Sport) questionnaire.ResultsThe analysis of 114 completed questionnaires of amateur athletes revealed that the use of OTC analgesics was sex dependent, with a higher prevalence of use in female players (60%) versus male players (38%). The main reasons for consumption of OTC analgesics were pain in the head, knee and shoulder. The most frequently taken drug was ibuprofen, most often taken at competitions and over a period of 4 years (median). The analysis of the AMS-Sport questionnaire revealed that a logistic regression model for estimating the probability of drug use can be explained by the factorshope of successandyears of playing practisein female players but not male players. In females, an increase in the factorhope of successresulted in a lower probability of OTC analgesic use, while an increase inyears of playing practiseresulted in a higher probability of use.ConclusionThe average duration that volleyball players in this study took OTC analgesics was higher than that of the German population, and OTC analgesic use was more prevalent in female than male volleyball players. Thus, to reduce the prevalence of OTC analgesic use, educational programs should be implemented in sports teams; and, to reduce direct and indirect social pressure, sports teams should also receive sex-specific psychological support.
Associations of circulating folate, vitamin B12 and homocysteine concentrations in early pregnancy and cord blood with epigenetic gestational age: the Generation R Study
Authors: Monasso Giulietta S. , Küpers Leanne K. , Jaddoe Vincent W. V. , Heil Sandra G. , Felix Janine F. 
Published: April 2021

Abstract
Background
Circulating folate, vitamin B12 and homocysteine concentrations during fetal development have been associated with health outcomes in childhood. Changes in fetal DNA methylation may be an underlying mechanism. This may be reflected in altered epigenetic aging of the fetus, as compared to chronological aging. The difference between gestational age derived in clinical practice and gestational age predicted from neonatal DNA methylation data is referred to as gestational age acceleration. Differences in circulating folate, vitamin B12 and homocysteine concentrations during fetal development may be associated with gestational age acceleration.

Results
Up to 1346 newborns participating in the Generation R Study, a population-based prospective cohort study, had both cord blood DNA methylation data available and information on plasma folate, serum total and active B12 and plasma homocysteine concentrations, measured in early pregnancy and/or in cord blood. A subgroup of 380 newborns had mothers with optimal pregnancy dating based on a regular menstrual cycle and a known date of last menstrual period. For comparison, gestational age acceleration was calculated based the method of both Bohlin and Knight. In the total study population, which was more similar to Bohlin’s training population, one standard deviation score (SDS) higher maternal plasma homocysteine concentrations was nominally associated with positive gestational age acceleration [0.07 weeks, 95% confidence interval (CI) 0.02, 0.13] by Bohlin’s method. In the subgroup with pregnancy dating based on last menstrual period, the method that was also used in Knight’s training population, one SDS higher cord serum total and active B12 concentrations were nominally associated with negative gestational age acceleration [(− 0.16 weeks, 95% CI − 0.30, − 0.02) and (− 0.15 weeks, 95% CI − 0.29, − 0.01), respectively] by Knight’s method.

Conclusions
We found some evidence to support associations of higher maternal plasma homocysteine concentrations with positive gestational age acceleration, suggesting faster epigenetic than clinical gestational aging. Cord serum vitamin B12 concentrations may be associated with negative gestational age acceleration, indicating slower epigenetic than clinical gestational aging. Future studies could examine whether altered fetal epigenetic aging underlies the associations of circulating homocysteine and vitamin B12 blood concentrations during fetal development with long-term health outcomes.
Characteristics of epigenetic aging across gestational and perinatal tissues
Authors: Dieckmann Linda , Lahti-Pulkkinen Marius , Kvist Tuomas , Lahti Jari , DeWitt Peter E. , Cruceanu Cristiana , Laivuori Hannele , Sammallahti Sara , Villa Pia M. , Suomalainen-König Sanna , Eriksson Johan G. , Kajantie Eero , Raikkönen Katri , Binder Elisabeth B. , Czamara Darina 
Published: April 2021

AbstractBackgroundEpigenetic clocks have been used to indicate differences in biological states between individuals of same chronological age. However, so far, only few studies have examined epigenetic aging in newborns—especially regarding different gestational or perinatal tissues. In this study, we investigated which birth- and pregnancy-related variables are most important in predicting gestational epigenetic age acceleration or deceleration (i.e., the deviation between gestational epigenetic age estimated from the DNA methylome and chronological gestational age) in chorionic villus, placenta and cord blood tissues from two independent study cohorts (ITU, n = 639 and PREDO, n = 966). We further characterized the correspondence of epigenetic age deviations between these tissues.ResultsAmong the most predictive factors of epigenetic age deviations in single tissues were child sex, birth length, maternal smoking during pregnancy, maternal mental disorders until childbirth, delivery mode and parity. However, the specific factors related to epigenetic age deviation and the direction of association differed across tissues. In individuals with samples available from more than one tissue, relative epigenetic age deviations were not correlated across tissues.ConclusionGestational epigenetic age acceleration or deceleration was not related to more favorable or unfavorable factors in one direction in the investigated tissues, and the relative epigenetic age differed between tissues of the same person. This indicates that epigenetic age deviations associate with distinct, tissue specific, factors during the gestational and perinatal period. Our findings suggest that the epigenetic age of the newborn should be seen as a characteristic of a specific tissue, and less as a general characteristic of the child itself.
Characterization of the initial complaint and care pathways prior to diagnosis in very young sporadic Alzheimer’s disease
Authors: Olivieri Pauline , Hamelin Lorraine , Lagarde Julien , Hahn Valérie , Guichart-Gomez Elodie , Roué-Jagot Carole , Sarazin Marie 
Published: April 2021

Abstract
Background
Very-early-onset Alzheimer’s disease (young-AD) differentiates from late-onset AD (old-AD) by a predominant involvement of the parietal neocortex leading to atypical presentations. The diagnosis of AD is often not the first to be mentioned in such young patients.

Methods
We retrospectively reviewed the initial complaint and care pathways of 66 sporadic young-AD (age < 62) and 30 old-AD patients (age > 65) and compared their neuropsychological profiles at the time of diagnosis (based on clinical-biological criteria) with 44 amyloid-negative controls.

Results
The initial complaint of young-AD was non-cognitive and mimicked a burnout in 32% of cases. Their main cognitive complaints were memory (38% vs 87% in old-AD) and language (17% vs 13%) impairment. The referral to a psychiatrist prior to AD diagnosis was more frequent in young-AD than in old-AD (26% vs 0%). At the time of diagnosis, young-AD were at a more severe stage of dementia than old-AD (24% vs 10% with CDR ≥ 1) but had less anosognosia.

Conclusions
Better identifying the initial signs of very-early-onset AD is crucial to improve the early diagnosis and develop new treatments.
The safety and potential probiotic properties analysis of Streptococcus alactolyticus strain FGM isolated from the chicken cecum
Authors: Zhang Jingyan , Zhang Hong , Wang Lei , Zhang Kang , Qiu Zhengying , Zhang Kai , Yue Cong , Zhang Yong , Zhao Xingxu , Li Jianxi 
Published: April 2021

Abstract
Purpose
Streptococcus alactolyticus strain FGM is used to ferment Astragalus membranaceus to develop a novel feed additive for animals in China. This study aimed at characterizing the safety and potential probiotic features of the strain FGM in vitro.

Methods
The genome of S. alactolyticus strain FGM was sequenced and used for genomic in silico studies. It was evaluated for morphology, antibiotic susceptibility, hemolytic activity, acid tolerance, bile salt tolerance, adherence ability to Caco-2, and inhibitory pathogens activity.

Result
The GC content of the strain FGM was 40.38% and composed of 29 contigs. The annotation of coding genes revealed important characteristics of the germs, especially 151 genes annotated to biological adhesion. The strain FGM forecasted 43 amino acid sequences to be VF, but did not have a hemolytic gene, and neither did it show hemolytic activity in phenotypic analysis. Although 30 amino acid sequences were predicted to aid in resisting some antibiotics, the strain FGM just showed the resistance to trimoxazole and oxytetracycline, and intermediate resistance to kanamycin. FGM cells were showed the tolerance to pH 2 broth within 4 h, and 0.15~0.30% bile salt medium with the latter being attributed to the presence of bile-salt hydrolase. The strain FGM was shown to have the ability to adhere to Caco-2 cells and the adherence rate of 1.0 × 109 CFU/mL bacterial suspensions was 37.51%. Compared with Lactobacillus acidophilus, Lactobacillus reuteri, and Lactobacillus casei, the strain FGM showed a high capability to inhibit the diffusion of Escherichia coli O78 and reduce its adhesion on Caco-2 cells.

Conclusion
The results demonstrated the presence of probiotic potential and absence of adverse effects for the Streptococcus alactolyticus strain FGM in vitro, thus contributing to develop a safety and effective fermentation feed for animals.
Image-guided percutaneous ablation for the treatment of lung malignancies: current state of the art
Authors: Páez-Carpio Alfredo , Gómez Fernando M. , Isus Olivé Gemma , Paredes Pilar , Baetens Tarik , Carrero Enrique , Sánchez Marcelo , Vollmer Ivan 
Published: April 2021

AbstractImage-guided percutaneous lung ablation has proven to be a valid treatment alternative in patients with early-stage non-small cell lung carcinoma or oligometastatic lung disease. Available ablative modalities include radiofrequency ablation, microwave ablation, and cryoablation. Currently, there are no sufficiently representative studies to determine significant differences between the results of these techniques. However, a common feature among them is their excellent tolerance with very few complications. For optimal treatment, radiologists must carefully select the patients to be treated, perform a refined ablative technique, and have a detailed knowledge of the radiological features following lung ablation. Although no randomized studies comparing image-guided percutaneous lung ablation with surgery or stereotactic radiation therapy are available, the current literature demonstrates equivalent survival rates. This review will discuss image-guided percutaneous lung ablation features, including available modalities, approved indications, possible complications, published results, and future applications.
Different phenotypes and chondrogenic responses of human menstrual blood and bone marrow mesenchymal stem cells to activin A and TGF-β3
Authors: Uzieliene Ilona , Bagdonas Edvardas , Hoshi Kazuto , Sakamoto Tomoaki , Hikita Atsuhiko , Tachtamisevaite Zivile , Rakauskiene Greta , Kvederas Giedrius , Mobasheri Ali , Bernotiene Eiva 
Published: April 2021

Abstract
Background
Due to its low capacity for self-repair, articular cartilage is highly susceptible to damage and deterioration, which leads to the development of degenerative joint diseases such as osteoarthritis (OA). Menstrual blood-derived mesenchymal stem/stromal cells (MenSCs) are much less characterized, as compared to bone marrow mesenchymal stem/stromal cells (BMMSCs). However, MenSCs seem an attractive alternative to classical BMMSCs due to ease of access and broader differentiation capacity. The aim of this study was to evaluate chondrogenic differentiation potential of MenSCs and BMMSCs stimulated with transforming growth factor β (TGF-β3) and activin A.

Methods
MenSCs (n = 6) and BMMSCs (n = 5) were isolated from different healthy donors. Expression of cell surface markers CD90, CD73, CD105, CD44, CD45, CD14, CD36, CD55, CD54, CD63, CD106, CD34, CD10, and Notch1 was analyzed by flow cytometry. Cell proliferation capacity was determined using CCK-8 proliferation kit and cell migration ability was evaluated by scratch assay. Adipogenic differentiation capacity was evaluated according to Oil-Red staining and osteogenic differentiation according to Alizarin Red staining. Chondrogenic differentiation (activin A and TGF-β3 stimulation) was investigated in vitro and in vivo (subcutaneous scaffolds in nude BALB/c mice) by expression of chondrogenic genes (collagen type II, aggrecan), GAG assay and histologically. Activin A protein production was evaluated by ELISA during chondrogenic differentiation in monolayer culture.

Results
MenSCs exhibited a higher proliferation rate, as compared to BMMSCs, and a different expression profile of several cell surface markers. Activin A stimulated collagen type II gene expression and glycosaminoglycan synthesis in TGF-β3 treated MenSCs but not in BMMSCs, both in vitro and in vivo, although the effects of TGF-β3 alone were more pronounced in BMMSCs in vitro.

Conclusion
These data suggest that activin A exerts differential effects on the induction of chondrogenic differentiation in MenSCs vs. BMMSCs, which implies that different mechanisms of chondrogenic regulation are activated in these cells. Following further optimization of differentiation protocols and the choice of growth factors, potentially including activin A, MenSCs may turn out to be a promising population of stem cells for the development of cell-based therapies with the capacity to stimulate cartilage repair and regeneration in OA and related osteoarticular disorders.