bluuebunny/crossref_metadata_2025_split huggingface dataset:
CFAP61 is required for sperm flagellum formation and male fertility in human and mouse
Authors: Liu Siyu , Zhang Jintao , Kherraf Zine Eddine , Sun Shuya , Zhang Xin , Cazin Caroline , Coutton Charles , Zouari Raoudha , Zhao Shuqin , Hu Fan , Mustapha Selima Fourati Ben , Arnoult Christophe , Ray Pierre F , Liu Mingxi 
Published: March 2021

AbstractDefects in the structure or motility of cilia and flagella may lead to severe diseases such as primary ciliary dyskinesia (PCD), a multisystemic disorder with heterogeneous manifestations affecting primarily respiratory and reproductive functions. We report that CFAP61 is a conserved component of the Calmodulin and radial Spoke associated Complex (CSC) of cilia. We find that a CFAP61 splice variant, c.143+5G>A, causes exon skipping in human, inducing a multiple morphological abnormalities of the flagella (MMAF) phenotype. We generatedCfap61knockout mice that recapitulate the infertility phenotype of the human CFAP61 mutation, but without other symptoms usually observed in PCD. We find that CFAP61 interacts with the CSC, radial spoke stalk and RS head. During early stages ofCfap61−/−spermatid development, the assembly of RS components is impaired. With the progress of spermiogenesis, the axoneme inCfap61−/−cells becomes unstable and scatters, and the distribution of intraflagellar transport proteins is disrupted. This study reveals an organ specific mechanism of axoneme stabilization that is related to male infertility.
Diffusional Kurtosis Imaging in the Diffusion Imaging in Python Project
Authors: Neto Henriques Rafael , Correa Marta , Maralle Maurizio , Huber Elizabeth , Kruper John , Koudoro Serge , Yeatman Jason , Garyfallidis Eleftherios , Rokem Ariel 
Published: March 2021

ABSTRACTDiffusion-weighted magnetic resonance imaging (dMRI) measurements and models provide information about brain connectivity and are sensitive to the physical properties of tissue microstructure. Diffusional Kurtosis Imaging (DKI) quantifies the degree of non-Gaussian diffusion in biological tissue from dMRI. These estimates are of interest because they were shown to be more sensitive to microstructural alterations in health and diseases than measures based on the total anisotropy of diffusion which are highly confounded by tissue dispersion and fiber crossings. In this work, we implemented DKI in the Diffusion in Python (DIPY) project - a large collaborative open-source project which aims to provide well-tested, well-documented and comprehensive implementation of different dMRI techniques. We demonstrate the functionality of our methods in numerical simulations with known ground truth parameters and in openly available datasets. A particular strength of our DKI implementations is that it pursues several extensions of the model that connect it explicitly with microstructural models and the reconstruction of 3D white matter fiber bundles (tractography). For instance, our implementations include DKI-based microstructural models that allow the estimation of biophysical parameters, such as axonal water fraction. Moreover, we illustrate how DKI provides more general characterization of non-Gaussian diffusion compatible with complex white matter fiber architectures and grey matter, and we include a novel mean kurtosis index that is invariant to the confounding effects due to tissue dispersion. In summary, DKI in DIPY provides a well-tested, well-documented and comprehensive reference mplementation for DKI. It provides a platform for wider use of DKI in research on brain disorders and cognitive neuroscience research. It will ease the translation of DKI advantages into clinical applications.
Evolutionary optimization in classification of early-MCI patients from healthy controls using graph measures of resting-state fMRI
Authors: Zamani Jafar , Sadr Ali , Javadi Amir-Homayoun 
Published: March 2021

AbstractsIdentifying individuals with early mild cognitive impairment (EMCI) can be an effective strategy for early diagnosis and delay the progression of Alzheimer’s disease (AD). Many approaches have been devised to discriminate those with EMCI from healthy control (HC) individuals. Selection of the most effective parameters has been one of the challenging aspects of these approaches. In this study we suggest an optimization method based on five evolutionary algorithms that can be used in optimization of neuroimaging data with a large number of parameters. Resting-state functional magnetic resonance imaging (rs-fMRI) measures, which measure functional connectivity, have been shown to be useful in prediction of cognitive decline. Analysis of functional connectivity data using graph measures is a common practice that results in a great number of parameters. Using graph measures we calculated 1155 parameters from the functional connectivity data of HC (n=36) and EMCI (n=34) extracted from the publicly available database of the Alzheimer’s disease neuroimaging initiative database (ADNI). These parameters were fed into the evolutionary algorithms to select a subset of parameters for classification of the data into two categories of EMCI and HC using a two-layer artificial neural network. All algorithms achieved classification accuracy of 94.55%, which is extremely high considering single-modality input and low number of data participants. These results highlight potential application of rs-fMRI and efficiency of such optimization methods in classification of images into HC and EMCI. This is of particular importance considering that MRI images of EMCI individuals cannot be easily identified by experts.
A chemical screen based on an interruption of zebrafish gastrulation identifies the HTR2C inhibitor Pizotifen as a suppressor of EMT-mediated metastasis
Authors: Nakayama Joji , Tan Lora , Goh Boon Cher , Wang Shu , Makinoshima Hideki , Gong Zhiyuan 
Published: March 2021

AbstractMetastasis is responsible for approximately 90% of cancer-associated mortality but few models exist that allow for rapid and effective screening of anti-metastasis drugs. Current mouse models of metastasis are too expensive and time consuming to use for rapid and high-throughput screening. Therefore, we created a unique screening concept utilizing conserved mechanisms between zebrafish gastrulation and cancer metastasis for identification of potential anti-metastatic drugs. We hypothesized that small chemicals that interrupt zebrafish gastrulation might also suppress metastatic progression of cancer cells and developed a phenotype-based chemical screen to test the hypothesis. The screen used epiboly, the first morphogenetic movement in gastrulation, as a marker and enabled 100 chemicals to be tested in five hours. The screen tested 1280 FDA-approved drugs and identified Pizotifen, an antagonist for serotonin receptor 2C (HTR2C) as an epiboly-interrupting drug. Pharmacologic and genetic inhibition of HTR2C suppressed metastatic progression in a mouse model. Blocking HTR2C with Pizotifen restored epithelial properties to metastatic cells through inhibition of Wnt-signaling. In contrast, HTR2C induced epithelial to mesenchymal transition (EMT) through activation of Wnt-signaling and promoted metastatic dissemination of human cancer cells in a zebrafish xenotransplantation model. Taken together, our concept offers a novel platform for discovery of anti-metastasis drugs.
A bacterial signal transduction phosphorelay in the methanogenic archaeonMethanosarcina acetivorans
Authors: Sexauer Anne , Frankenberg-Dinkel Nicole 
Published: March 2021

AbstractSignal transduction via two-component systems is a powerful tool for microorganisms to respond to environmental changes. Histidine kinases originating from Bacteria are the most common signaling enzymes and are also present in Archaea, but not in all phyla. A total of 124 bacterial-type histidine kinases and/or regulators were identified in a screen of 149 Euryarchaeota genomes, but little is known about the signal transfer and molecular regulation of these systems (1).In this work, the hybrid kinase MA4377 from the methanogenic archaeonMethanosarcina acetivoranswas investigated (2, 3). MA4377 is a multidomain protein resembling a bacterial-type histidine kinase with two additional receiver domains at the C-terminus. Recombinant protein was employed to investigate the intra- and intermolecular phosphorelayin vitro. The kinase displays autophosphorylation activity of histidine residue 497. While no intramolecular phosphorelay was observed, the CheY-like receiver protein MA4376 was identified as part of the multi-component system that also seems to include the Msr-type transcription factor MA4375. This study reveals the presence andin vitrofunction of a bacterial-type hybrid histidine kinase integrated into an archaeal phosphorelay system.ImportanceSignal transduction enables organisms to rapidly react to changes in their surroundings. Different systems containing one-, two- or multiple-components are employed to sense and react to environmental changes. Most commonly, external perceived stimuli are converted into internal signals through protein phosphorylation. These systems are found in all domains of life but understood at different levels of complexity, the least being those from the domain of Archaea. By better elucidating the function of these early signal transduction systems, we will gain insight and understanding of the selection pressures on signal transduction pathways, and their evolution within the Archaea.
Recovery of high-qualitied Genomes from a deep-inland Salt Lake Using BASALT
Authors: Yu Ke , Qiu Zhiguang , Mu Rong , Qiao Xuejiao , Zhang Liyu , Lian Chun-Ang , Deng Chunfang , Wu Yang , Xu Zheng , Li Bing , Pan Baozhu , Zhang Yunzeng , Fan Lu , Liu Yong-xin , Cao Huiluo , Jin Tao , Chen Baowei , Wang Fan , Yan Yan , Xie Luhua , Zhou Lijie , Yi Shan , Chi Song , Zhang Chuanlun , Zhang Tong , Zhuang Weiqin 
Published: March 2021

AbstractMetagenomic binning enables the in-depth characterization of microorganisms. To improve the resolution and efficiency of metagenomic binning, BASALT (Binning Across a Series of AssembLies Toolkit), a novel binning toolkit was present in this study, which recovers, compares and optimizes metagenomic assembled genomes (MAGs) across a series of assemblies from short-read, long-read or hybrid strategies. BASALT incorporates self-designed algorithms which automates the separation of redundant bins, elongate and refine best bins and improve contiguity. Evaluation using mock communities revealed that BASALT auto-binning obtained up to 51% more number of MAGs with up to 10 times better MAG quality from microbial community at low (132 genomes) and medium (596 genomes) complexity, compared to other binners such as DASTool, VAMB and metaWRAP. Using BASALT, a case-study analysis of a Salt Lake sediment microbial community from northwest arid region of China was performed, resulting in 426 non-redundant MAGs, including 352 and 69 bacterial and archaeal MAGs which could not be assigned to any known species from GTDB (ANI < 95%), respectively. In addition, two Lokiarchaeotal MAGs that belong to superphylum Asgardarchaeota were observed from Salt Lake sediment samples. This is the first time that candidate species from phylum Lokiarchaeota was found in the arid and deep-inland environment, filling the current knowledge gap of earth microbiome. Overall, BASALT is proven to be a robust toolkit for metagenomic binning, and more importantly, expand the Tree of Life.
Public science data suggest that fish is the most important factor in reducing small pond biodiversity in Czechia
Authors: Hulcr Jiri , Gomez Demian F. 
Published: March 2021

AbstractThis project tested a public-science approach to the assessment of freshwater habitat quality via simple invertebrate sampling. We combined a mobile phone application and simple instruction to children to sample 50 ponds in Central Czechia, and we analyzed the data using a standard ecological statistics approach. Despite the limitation in scope and taxonomic precision, our data revealed the same patterns as academic studies of the same topic. Specifically, we conclude that the main cause of invertebrate community decline is fish overstocking, while diverse invertebrate communities require aquatic macrophytes. Pollution detectable by children has an effect on invertebrate community structure, but a different effect than fish has, and not as statistically robust. Importantly, almost all large ponds were found overstocked with fish; therefore, they support not more diversity than small ponds, but less, and serve as ecological traps. Our findings suggest that pond conservation should focus primarily on the restoration of aquatic vegetation, and that the most effective approach will be the removal of excessive fish.
Significance of the Wnt canonical pathway in radiotoxicity via oxidative stress of electron beam radiation and its molecular control in mice
Authors: Kumar Shashank , Fathima Eram , Khanum Farhath , S Malini Suttur 
Published: March 2021

AbstractRadiation triggers the cell death events through signaling proteins, but the combined mechanism of events is unexplored. We intend to investigate how the combined cascade works throughout the radiation process and its significance over radiotoxicity. Thirty adult mice were irradiated with electron beam radiation, and five were served as a control (Non treated). Mice were sacrificed after post 24 hours and 30 days of irradiation. We assessed the oxidative stress parameter and mRNA profile (Liver, Kidney, spleen, and germ cells), sperm viability, and motility. The mRNA profile study established the network of combined cascade work during radiation to combat oxidative response and cell survival. The quantitative examination of mRNA uncovers unique critical changes in all mRNA levels in all the cases, particularly in germ cells. Recuperation was likewise seen in post 30 days radiation in the liver, spleen, and kidney followed by oxidative stress parameters, however not in germ cells. It proposes reproductive physiology is exceptionally sensitive towards radiation, even at the molecular level. It also suggests the suppression of Lef1/axin2 could be the main reason for permanent failure in the sperm function process. Post irradiation likewise influences the morphology of sperms. The decrease in mRNA level of Lef1, Axin2, survivin, Ku70 suggests radiation inhibits the Wnt canonical pathway and failure in DNA repair mechanism in a coupled manner. Likewise, the increase in BAX and BCL2 suggests apoptosis activation followed by the decreased expression of enzymatic antioxidants. In summary, controlled several interlinked cascades execute when body exposure to radiation may further be used in a study to counterpart and better comprehend medication focus on radiation treatment.
Tract-specific statistics based on diffusion-weighted probabilistic tractography
Authors: Reid Andrew T. , Camilleri Julia A. , Hoffstaedter Felix , Eickhoff Simon B. 
Published: March 2021

AbstractDiffusion-weighted neuroimaging approaches provide rich evidence with which to estimate the structural integrity of white matter in vivo. Tract-based spatial statistics (TBSS), for instance, allows us to assess the spatial distribution of statistical tests performed on diffusion properties such as fractional anisotropy, which are proposed to reflect the integrity of white matter tracts. However, such methods do not provide a direct assessment of white matter integrity for connections between two specific regions of the brain. Here, we present a novel method for deriving tract-specific diffusion statistics, based upon arbitrarily-defined regions of interest. Our approach makes use of an empirically-derived population distribution based on probabilistic tractography, using the Nathan Kline Institute (NKI) Enhanced Rockland sample. We use a heuristic method to determine the most likely geometry of a path between two regions, if one exists, and express this as a spatial distribution. We then estimate the average orientation of streamlines traversing this path, at discrete distances along its trajectory, and compute the fraction of diffusion directed along this orientation for each participant. This allows us to obtain participant-wise metrics along the specific tract (tract-specific anisotropy; TSA), which can then be used to perform statistical analysis on any comparable population. Based on this method, we report both negative and positive associations between age and TSA for two networks derived from published meta-analytic studies (the “default mode” and “what-where” networks), along with more moderate sex differences and age-by-sex interactions in both networks.
In vivohigh-throughput screening of novel adeno-associated viral capsids targeting adult neural stem cells in the subventricular zone
Authors: Dehler Sascha , Kremer Lukas PM , Cerrizuela Santiago , Stiehl Thomas , Weinmann Jonas , Abendroth Heike , Kleber Susanne , Laure Alexander , Andari Jihad El , Anders Simon , Marciniak-Czochra Anna , Grimm Dirk , Martin-Villalba Ana 
Published: March 2021

AbstractThe adult mammalian brain entails a reservoir of neural stem cells (NSCs) generating glial cells and neurons. However, NSCs become increasingly quiescent with age, which hampers their regenerative capacity. New means are therefore required to genetically modify adult NSCs for re-enabling endogenous brain repair. Recombinant adeno-associated viruses (AAVs) are ideal gene therapy vectors due to an excellent safety profile and high transduction efficiency. We thus conducted a high-throughput screening of 177 intraventricularly injected barcoded AAV variants profiled by RNA sequencing. Quantification of barcoded AAV mRNAs identified two synthetic capsids, AAV9_A2 and AAV1_P5, both of which transduce active and quiescent NSCs. Further optimization of AAV1_P5 by judicious selection of promoter and dose of injected viral genomes enabled labeling of 30-60% of the NSC compartment, which was validated by FACS analyses and single cell RNA sequencing. Importantly, transduced NSC readily produced neurons. The present study identifies AAV variants with a high regional tropism towards the v-SVZ with high efficiency in targeting adult NSCs, thereby paving the way for preclinical testing of regenerative gene therapy.
Biosynthesis of benzoxazinoids in rye (Secale cerealeL.) – where does the story begin?
Authors: Rakoczy-Trojanowska Monika , Różańska Elżbieta , Święcicka Magdalena , Burza Wojciech , Bakera Beata , Kowalczyk Mariusz , Łotocka Barbara , Szabała Bartosz 
Published: March 2021

AbstractAccording to current opinion, the first step of benzoxazinoids (BXs) synthesis, that is, the conversion of indole-3-glycerol phosphate to indole, occurs exclusively in the photosynthesising parts of plants. However, the results of our previous work and some other studies suggest that this process may also occur in the roots. In this study, we provide evidence that the first step of BXs synthesis does indeed occur in the roots of rye seedlings. We detectedScBx1transcripts, BX1 enzyme, and six BXs (2-hydroxy-1,4-benzoxazin-3-one, 2,4-dihydroxy-1,4-benzoxazin-3-one, (2R)-2-O-β-d-glucopyranosyl-4-hydroxy-(2H)-1,4-benzoxazin-3(4H)-one glucoside, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-one glucoside, and 6-methoxy-2-benzoxazolinone) in the roots developed from seeds deprived of the coleoptile at 2 days after sowing (i.e., roots without contact with aerial parts). In roots regeneratedin vitro, bothScBx1transcripts and BX1 enzyme were detected at a low but still measurable levels. Thus, BXs are able to be synthesised in both the roots and above-ground parts of rye plants.HighlightThe first step benzoxazinoids synthesis occurs in both the above-ground parts and roots of rye plants. Benzoxazinoids can be synthesisedde novoin roots, independently of plants’ photosynthesising parts.
Non-academic employment and matching satisfaction among PhD graduates with high intersectoral mobility potential
Authors: Alfano Vincenzo , Gaeta Giuseppe , Pinto Mauro 
Published: March 2021

PurposeThis paper contributes to the empirical analysis of PhD holders' transition into the non-academic labor market (i.e. their intersectoral mobility). The research focuses on doctoral graduates specialized in a field of study supposed to have notable non-academic applications, namely Industrial and Information Engineering. We inspect whether these doctoral graduates experience lower satisfaction with PhD knowledge use on the job when they work outside universities and non-public research centers.Design/methodology/approachWe use cross-sectional survey data collected by the Italian National Institute of Statistics in 2014. Ordinary least squares and ordered logit analyses provide baseline results; furthermore, we apply a multinomial endogenous treatment model to control for potential bias arising from self-selection into employment sectors.FindingsWe find evidence that for PhD holders Industrial and Information Engineering being employed in the industrial and services sector implies lower satisfaction with the use of doctoral knowledge than that reported by their counterparts working in universities or public research centers.Originality/valueThese results complement and extend previous evidence about PhD holders' career outcomes by focusing on the intersectoral mobility issue and on a specific group of doctoral graduates whose intersectoral mobility potential is expected to be high. Our findings call for policies that might trigger a better alignment between doctoral education and non-academic jobs.
Evaluating the quality of reported outcomes for microsurgical TESE in men with non‐obstructive azoospermia: A methodological analysis
Authors: Ernandez John , Berk Brittany , Han Tracy , Abou Ghayda Ramy , Kathrins Martin 
Published: March 2021

AbstractBackgroundPublications of microsurgical testicular sperm extraction (mTESE) techniques and outcomes are heterogeneous, which may limit creation of best surgical practices.ObjectiveTo study the quality and heterogeneity of published mTESE outcomes via a methodological analysis.Materials/MethodsA systematic methodological analysis of all published literature on the use of mTESE in men with non‐obstructive azoospermia from 1999 to the July 2020 was performed. PubMed and MEDLINE searches were performed using the search terms “microdissection TESE OR microsurgical TESE.” Publications were evaluated on their reporting of pre‐operative factors, intraoperative techniques, surgical and clinical outcomes, and adverse events.ResultsFifty‐five studies met inclusion criteria. Surgical technique and sperm retrieval rates were the most reported criteria. Reporting on the presence of an embryologist intraoperatively was observed in approximately 30% of articles, while other procedural details including method of sperm quantification, quantity retrieved, and number of cryopreserved vials were observed in fewer than 10% of articles. Clinical outcomes, including pregnancy rates and live birth rates, were reported in fewer than 40% of the articles. Fetal outcomes including fetal and neonatal anomalies were rarely reported. Fetal growth restriction, preterm delivery, small or large for gestational age, and NICU admissions were never reported.ConclusionThere are inconsistencies in reporting quality of mTESE outcomes, specifically a lack of information on the quantity and quality of sperm retrieved, the role of embryology intraoperatively, and clinical outcomes, such as live birth rate and fetal anomalies. These gaps may guide development of standardized reporting guidelines to better assess and compare clinical outcomes across institutions and maintain focus on couples‐centric fertility outcomes in future mTESE studies.