bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sociability strongly affects the behavioural responses of wild guanacos to drones
Authors: Schroeder Natalia M. , Panebianco Antonella 
Published: October 2021

AbstractDrones are being increasingly used in research and recreation but without an adequate assessment of their potential impacts on wildlife. Particularly, the effect of sociability on behavioural responses to drone-associated disturbance remains largely unknown. Using an ungulate with complex social behaviour, we (1) assessed how social aggregation and offspring presence, along with flight plan characteristics, influence the probability of behavioural reaction and the flight distance of wild guanacos (Lama guanicoe) to the drone's approach, and (2) estimated reaction thresholds and flight heights that minimise disturbance. Sociability significantly affected behavioural responses. Large groups showed higher reaction probability and greater flight distances than smaller groups and solitary individuals, regardless of the presence of offspring. This suggests greater detection abilities in large groups, but we cannot rule out the influence of other features inherent to each social unit (e.g., territoriality) that might be working simultaneously. Low flight heights increased the probability of reaction, although the effect of drone speed was less clear. Reaction thresholds ranged from 154 m (solitary individuals) to 344 m (mixed groups), revealing that the responsiveness of this guanaco population to the drone is the most dramatic reported so far for a wild species.
Proteomic analysis of peritoneal fluid identified COMP and TGFBI as new candidate biomarkers for endometriosis
Authors: Janša V. , Klančič T. , Pušić M. , Klein M. , Vrtačnik Bokal E. , Ban Frangež H. , Rižner T. Lanišnik 
Published: October 2021

AbstractEndometriosis is a common non-malignant gynecological disease that significantly compromises fertility and quality of life of the majority of patients. The gold standard for diagnosis is visual inspection of the pelvic organs by surgical laparoscopy and there are no biomarkers that would allow non-invasive diagnosis. The pathogenesis of endometriosis is not completely understood, thus analysis of peritoneal fluid might contribute in this respect. Our prospective case–control study included 58 patients undergoing laparoscopy due to infertility, 32 patients with peritoneal endometriosis (cases) and 26 patients with unexplained primary infertility (controls). Discovery proteomics using antibody microarrays that covered 1360 proteins identified 16 proteins with different levels in casesversusthe control patients. The validation using an ELISA approach confirmed significant differences in the levels of cartilage oligomeric matrix protein (COMP) and transforming growth factor-β-induced protein ig-h3 (TGFBI) and nonsignificant differences in angiotensinogen (AGT). A classification model based on a linear support vector machine revealed AUC of > 0.83, sensitivity of 0.81 and specificity of 1.00. Differentially expressed proteins represent candidates for diagnostic and prognostic biomarkers or drug targets. Our findings have brought new knowledge that will be helpful in the understanding of the pathophysiology of endometriosis and warrant further studies in blood samples.
Bioinformatic identification of genomic instability-associated lncRNAs signatures for improving the clinical outcome of cervical cancer by a prognostic model
Authors: Zhang Jian , Ding Nan , He Yongxing , Tao Chengbin , Liang Zhongzhen , Xin Wenhu , Zhang Qianyun , Wang Fang 
Published: October 2021

AbstractThe research is executed to analyze the connection between genomic instability-associated long non-coding RNAs (lncRNAs) and the prognosis of cervical cancer patients. We set a prognostic model up and explored different risk groups' features. The clinical datasets and gene expression profiles of 307 patients have been downloaded from The Cancer Genome Atlas database. We established a prognostic model that combined somatic mutation profiles and lncRNA expression profiles in a tumor genome and identified 35 genomic instability-associated lncRNAs in cervical cancer as a case study. We then stratified patients into low-risk and high-risk groups and were further checked in multiple independent patient cohorts. Patients were separated into two sets: the testing set and the training set. The prognostic model was built using three genomic instability-associated lncRNAs (AC107464.2, MIR100HG, and AP001527.2). Patients in the training set were divided into the high-risk group with shorter overall survival and the low-risk group with longer overall survival (p < 0.001); in the meantime, similar comparable results were found in the testing set (p = 0.046), whole set (p < 0.001). There are also significant differences in patients with histological grades, FIGO stages, and different ages (p < 0.05). The prognostic model focused on genomic instability-associated lncRNAs could predict the prognosis of cervical cancer patients, paving the way for further research into the function and resource of lncRNAs, as well as a key approach to customizing individual care decision-making.
Preclinical pharmacology of glucosylceramide synthase inhibitor venglustat in a GBA-related synucleinopathy model
Authors: Viel Catherine , Clarke Jennifer , Kayatekin Can , Richards Amy M. , Chiang Ming Sum R. , Park Hyejung , Wang Bing , Shihabuddin Lamya S. , Sardi S. Pablo 
Published: October 2021

AbstractMutations in GBA, the gene encoding the lysosomal enzyme glucocerebrosidase (GCase), represent the greatest genetic risk factor for developing synucleinopathies including Parkinson’s disease (PD). Additionally, PD patients harboring a mutant GBA allele present with an earlier disease onset and an accelerated disease progression of both motor and non-motor symptoms. Preclinical studies in mouse models of synucleinopathy suggest that modulation of the sphingolipid metabolism pathway via inhibition of glucosylceramide synthase (GCS) using a CNS-penetrant small molecule may be a potential treatment for synucleinopathies. Here, we aim to alleviate the lipid storage burden by inhibiting the de novo synthesis of the primary glycosphingolipid substrate of GCase, glucosylceramide (GlcCer). We have previously shown that systemic GCS inhibition reduced GlcCer and glucosylsphingosine (GlcSph) accumulation, slowed α-synuclein buildup in the hippocampus, and improved cognitive deficits. Here, we studied the efficacy of a brain-penetrant clinical candidate GCS inhibitor, venglustat, in mouse models of GBA-related synucleinopathy, including a heterozygous Gba mouse model which more closely replicates the typical GBA-PD patient genotype. Collectively, these data support the rationale for modulation of GCase-related sphingolipid metabolism as a therapeutic strategy for treating GBA-related synucleinopathies.
A cold seep triggered by a hot ridge subduction
Authors: Villar-Muñoz Lucía , Kinoshita Masataka , Bento Joaquim P. , Vargas-Cordero Ivan , Contreras-Reyes Eduardo , Tinivella Umberta , Giustiniani Michela , Abe Natsue , Anma Ryo , Orihashi Yuji , Iwamori Hikaru , Nishikawa Tomoaki , Veloso Eugenio Andres , Haraguchi Satoru 
Published: October 2021

AbstractThe Chile Triple Junction, where the hot active spreading centre of the Chile Rise system subducts beneath the South American plate, offers a unique opportunity to understand the influence of the anomalous thermal regime on an otherwise cold continental margin. Integrated analysis of various geophysical and geological datasets, such as bathymetry, heat flow measured directly by thermal probes and calculated from gas hydrate distribution limits, thermal conductivities, and piston cores, have improved the knowledge about the hydrogeological system. In addition, rock dredging has evidenced the volcanism associated with ridge subduction. Here, we argue that the localized high heat flow over the toe of the accretionary prism results from fluid advection promoted by pressure-driven discharge (i.e., dewatering/discharge caused by horizontal compression of accreted sediments) as reported previously. However, by computing the new heat flow values with legacy data in the study area, we raise the assumption that these anomalous heat flow values are also promoted by the eastern flank of the currently subducting Chile Rise. Part of the rift axis is located just below the toe of the wedge, where active deformation and vigorous fluid advection are most intense, enhanced by the proximity of the young volcanic chain. Our results provide valuable information to current and future studies related to hydrothermal circulation, seismicity, volcanism, gas hydrate stability, and fluid venting in this natural laboratory.
Gestational diabetes triggers postpartum cardiac hypertrophy via activation of calcineurin/NFAT signaling
Authors: Verma Nirmal , Srodulski Sarah , Velmurugan Sathya , Hoskins Amanda , Pandey Vivek K. , Despa Florin , Despa Sanda 
Published: October 2021

AbstractPopulation-based studies identified an association between a prior pregnancy complicated by gestational diabetes mellitus (GDM) and cardiac hypertrophy and dysfunction later in life. It is however unclear whether GDM initiates this phenotype and what are the underlying mechanisms. We addressed these questions by using female rats that express human amylin (HIP rats) as a GDM model and their wild-type (WT) littermates as the normal pregnancy model. Pregnant and two months postpartum HIP females had increased left-ventricular mass and wall thickness compared to non-pregnant HIP females, which indicates the presence of concentric hypertrophy. These parameters were unchanged in WT females during both pregnancy and postpartum periods. Hypertrophic Ca2+-dependent calcineurin/NFAT signaling was stimulated two months after giving birth in HIP females but not in the WT. In contrast, the CaMKII/HDAC hypertrophy pathway was active immediately after giving birth and returned to the baseline by two months postpartum in both WT and HIP females. Myocytes from two months postpartum HIP females exhibited slower Ca2+ transient relaxation and higher diastolic Ca2+ levels, which may explain calcineurin activation. No such effects occurred in the WT. These results suggest that a GDM-complicated pregnancy accelerates the development of pathological cardiac remodeling likely through activation of calcineurin/NFAT signaling.
Nkx3-1 and Fech genes might be switch genes involved in pituitary non-functioning adenoma invasiveness
Authors: Khayer Nasibeh , Jalessi Maryam , Jahanbakhshi Amin , Tabib khooei Alireza , Mirzaie Mehdi 
Published: October 2021

AbstractNon-functioning pituitary adenomas (NFPAs) are typical pituitary macroadenomas in adults associated with increased mortality and morbidity. Although pituitary adenomas are commonly considered slow-growing benign brain tumors, numerous of them possess an invasive nature. Such tumors destroy sella turcica and invade the adjacent tissues such as the cavernous sinus and sphenoid sinus. In these cases, the most critical obstacle for complete surgical removal is the high risk of damaging adjacent vital structures. Therefore, the development of novel therapeutic strategies for either early diagnosis through biomarkers or medical therapies to reduce the recurrence rate of NFPAs is imperative. Identification of gene interactions has paved the way for decoding complex molecular mechanisms, including disease-related pathways, and identifying the most momentous genes involved in a specific disease. Currently, our knowledge of the invasion of the pituitary adenoma at the molecular level is not sufficient. The current study aimed to identify critical biomarkers and biological pathways associated with invasiveness in the NFPAs using a three-way interaction model for the first time. In the current study, the Liquid association method was applied to capture the statistically significant triplets involved in NFPAs invasiveness. Subsequently, Random Forest analysis was applied to select the most important switch genes. Finally, gene set enrichment (GSE) and gene regulatory network (GRN) analyses were applied to trace the biological relevance of the statistically significant triplets. The results of this study suggest that “mRNA processing” and “spindle organization” biological processes are important in NFAPs invasiveness. Specifically, our results suggestNkx3-1 and Fechas two switch genes in NFAPs invasiveness that may be potential biomarkers or target genes in this pathology.
Experimental analysis of control technology and deformation failure mechanism of inclined coal seam roadway using non-contact DIC technique
Authors: Xiong Xianyu , Dai Jun , Ouyang Yibo , Shen Pan 
Published: October 2021

AbstractThe deformation and failure forms of inclined coal seam roadway under the joint action of dip angle and various geological conditions are complex, and there is a lack of targeted support measures, which brings great problems to the stability control of roadway surrounding rock. In order to safely and economically mine inclined coal seams, taking the engineering geology of Shitanjing No. 2 mining area as the background, and the physical similarity model of right-angle trapezoidal roadway in inclined coal seam, in which the non-contact digital image correlation (DIC) technology and the stress sensor is employed to provide full-field displacement and stress measurements. The deformation control technology of the roadway surrounding rock was proposed, verified by numerical simulation and applied to engineering practice. The research results show that the stress and deformation failure of surrounding rock in low sidewall of roadway are greater than those in high sidewall, showing asymmetric characteristics, and the maximum stress concentration coefficients of roadway sidewall, roof and floor are 4.1, 3.4 and 2.8, respectively. A concept of roadway "cyclic failure" mechanism is proposed that is, the cyclic interaction of the two sidewalls, the sharp angles and roof aggravated the failure of roadway, resulting in the overall instability of roadway. The roadway sidewall is serious rib spalling, the roof is asymmetric "Beret" type caving arch failure, and the floor is slightly bulging. On this basis, the principle of roadway deformation control is revealed and asymmetric support design is adopted, and the deformation of roadway is controlled, which support scheme is effective.
A glutamate synthase mutant of Bradyrhizobium sp. strain ORS285 is unable to induce nodules on Nod factor-independent Aeschynomene species
Authors: Nouwen Nico , Chaintreuil Clémence , Fardoux Joel , Giraud Eric 
Published: October 2021

AbstractThe Bradyrhizobium sp. strain ORS285 is able to establish a nitrogen-fixing symbiosis with both Nod factor (NF) dependent and NF-independent Aeschynomene species. Here, we have studied the growth characteristics and symbiotic interaction of a glutamate synthase (GOGAT; gltD::Tn5) mutant of Bradyrhizobium ORS285. We show that the ORS285 gltD::Tn5 mutant is unable to use ammonium, nitrate and many amino acids as nitrogen source for growth and is unable to fix nitrogen under free-living conditions. Moreover, on several nitrogen sources, the growth rate of the gltB::Tn5 mutant was faster and/or the production of the carotenoid spirilloxanthin was much higher as compared to the wild-type strain. The absence of GOGAT activity has a drastic impact on the symbiotic interaction with NF-independent Aeschynomene species. With these species, inoculation with the ORS285 gltD::Tn5 mutant does not result in the formation of nodules. In contrast, the ORS285 gltD::Tn5 mutant is capable to induce nodules on NF-dependent Aeschynomene species, but these nodules were ineffective for nitrogen fixation. Interestingly, in NF-dependent and NF-independent Aeschynomene species inoculation with the ORS285 gltD::Tn5 mutant results in browning of the plant tissue at the site of the infection suggesting that the mutant bacteria induce plant defence responses.
Identification of ecological networks and nodes in Fujian province based on green and blue corridors
Authors: Zhou Qingqing , van den Bosch Cecil C. Konijnendijk , Chen Jingru , Zhang Wenbing , Dong Jianwen 
Published: October 2021

AbstractChina's Green Space System Planning (GSSP) research has gradually expanded from central urban areas to municipal and provincial scales in recent years. Besides, the research on the role of green space in the water environment has also attracted much attention. However, the study of green corridors usually ignored hydrological data, which widespread absence especially in the large area scale. And the scale of green corridor construction mainly focused on central urban areas. This paper took China's Fujian province as an example. Based on the DEM elevation data, the article identified blue corridors without hydrological data. In addition, the green corridors were determined based on the land use data. According to the green corridors and blue corridors protection, we identified the ecological networks and nodes by the network analysis method. The results showed that the blue corridors identified by DEM data were consistent with the hydrological status quo. The regional status of the identified ecological networks and nodes were basically in line with their characteristics, proving the value of the planning methods. Finally, based on the identification results, suggestions for Fujian's ecological networks and nodes are put forward.
Morphological differences in the calcaneus among extant great apes investigated by three-dimensional geometric morphometrics
Authors: Nozaki Shuhei , Amano Hideki , Oishi Motoharu , Ogihara Naomichi 
Published: October 2021

AbstractInvestigating the morphological differences of the calcaneus in humans and great apes is crucial for reconstructing locomotor repertories of fossil hominins. However, morphological variations in the calcaneus of the great apes (chimpanzees, gorillas, and orangutans) have not been sufficiently studied. This study aims to clarify variations in calcaneal morphology among great apes based on three-dimensional geometric morphometrics. A total of 556 landmarks and semilandmarks were placed on the calcaneal surface to calculate the principal components of shape variations among specimens. Clear interspecific differences in calcaneal morphology were extracted, corresponding to the degree of arboreality of the three species. The most arboreal orangutans possessed comparatively more slender calcaneal tuberosity and deeper pivot region of the cuboid articular surface than chimpanzees and gorillas. However, the most terrestrial gorillas exhibited longer lever arm of the triceps surae muscle, larger peroneal trochlea, more concave plantar surface, more inverted calcaneal tuberosity, more everted cuboid articular surface, and more prominent plantar process than the orangutans and chimpanzees. These interspecific differences possibly reflect the functional adaptation of the calcaneus to locomotor behavior in great apes. Such information might be useful for inferring foot functions and reconstructing the locomotion of fossil hominoids and hominids.
Induction of inverted morphology in brain organoids by vertical-mixing bioreactors
Authors: Suong Dang Ngoc Anh , Imamura Keiko , Inoue Ikuyo , Kabai Ryotaro , Sakamoto Satoko , Okumura Tatsuya , Kato Yoshikazu , Kondo Takayuki , Yada Yuichiro , Klein William L. , Watanabe Akira , Inoue Haruhisa 
Published: October 2021

AbstractOrganoid technology provides an opportunity to generate brain-like structures by recapitulating developmental steps in the manner of self-organization. Here we examined the vertical-mixing effect on brain organoid structures using bioreactors and established inverted brain organoids. The organoids generated by vertical mixing showed neurons that migrated from the outer periphery to the inner core of organoids, in contrast to orbital mixing. Computational analysis of flow dynamics clarified that, by comparison with orbital mixing, vertical mixing maintained the high turbulent energy around organoids, and continuously kept inter-organoid distances by dispersing and adding uniform rheological force on organoids. To uncover the mechanisms of the inverted structure, we investigated the direction of primary cilia, a cellular mechanosensor. Primary cilia of neural progenitors by vertical mixing were aligned in a multidirectional manner, and those by orbital mixing in a bidirectional manner. Single-cell RNA sequencing revealed that neurons of inverted brain organoids presented a GABAergic character of the ventral forebrain. These results suggest that controlling fluid dynamics by biomechanical engineering can direct stem cell differentiation of brain organoids, and that inverted brain organoids will be applicable for studying human brain development and disorders in the future.
Activation of the adipocyte CREB/CRTC pathway in obesity
Authors: Yoon Young-Sil , Liu Weiyi , Van de Velde Sam , Matsumura Shigenobu , Wiater Ezra , Huang Ling , Montminy Marc 
Published: October 2021

AbstractObesity is a major risk factor for the development of type II diabetes. Increases in adipose tissue mass trigger insulin resistance via the release of pro-inflammatory cytokines from adipocytes and macrophages. CREB and the CRTC coactivators have been found to promote insulin resistance in obesity, although the mechanism is unclear. Here we show that high fat diet feeding activates the CREB/CRTC pathway in adipocytes by decreasing the expression of SIK2, a Ser/Thr kinase that phosphorylates and inhibits CRTCs. SIK2 levels are regulated by the adipogenic factor C/EBPα, whose expression is reduced in obesity. Exposure to PPARγ agonist rescues C/EBPα expression and restores SIK2 levels. CRTC2/3 promote insulin resistance via induction of the chemokines CXCL1/2. Knockout of CRTC2/3 in adipocytes reduces CXCL1/2 expression and improves insulin sensitivity. As administration of CXCL1/2 reverses salutary effects of CRTC2/3 depletion, our results demonstrate the importance of the CREB/CRTC pathway in modulating adipose tissue function.
AdRoit is an accurate and robust method to infer complex transcriptome composition
Authors: Yang Tao , Alessandri-Haber Nicole , Fury Wen , Schaner Michael , Breese Robert , LaCroix-Fralish Michael , Kim Jinrang , Adler Christina , Macdonald Lynn E. , Atwal Gurinder S. , Bai Yu 
Published: October 2021

AbstractBulk RNA sequencing provides the opportunity to understand biology at the whole transcriptome level without the prohibitive cost of single cell profiling. Advances in spatial transcriptomics enable to dissect tissue organization and function by genome-wide gene expressions. However, the readout of both technologies is the overall gene expression across potentially many cell types without directly providing the information of cell type constitution. Although several in-silico approaches have been proposed to deconvolute RNA-Seq data composed of multiple cell types, many suffer a deterioration of performance in complex tissues. Here we present AdRoit, an accurate and robust method to infer the cell composition from transcriptome data of mixed cell types. AdRoit uses gene expression profiles obtained from single cell RNA sequencing as a reference. It employs an adaptive learning approach to alleviate the sequencing technique difference between the single cell and the bulk (or spatial) transcriptome data, enhancing cross-platform readout comparability. Our systematic benchmarking and applications, which include deconvoluting complex mixtures that encompass 30 cell types, demonstrate its preferable sensitivity and specificity compared to many existing methods as well as its utilities. In addition, AdRoit is computationally efficient and runs orders of magnitude faster than most methods.