bluuebunny/crossref_metadata_2025_split huggingface dataset:
G392E neuroserpin causing the dementia FENIB is secreted from cells but is not synaptotoxic
Authors: Ingwersen Thies , Linnenberg Christian , D’Acunto Emanuela , Temori Shabnam , Paolucci Irene , Wasilewski David , Mohammadi Behnam , Kirchmair Johannes , Glen Robert C. , Miranda Elena , Glatzel Markus , Galliciotti Giovanna 
Published: April 2021

AbstractFamilial encephalopathy with neuroserpin inclusion bodies (FENIB) is a progressive neurodegenerative disease caused by point mutations in the gene for neuroserpin, a serine protease inhibitor of the nervous system. Different mutations are known that are responsible for mutant neuroserpin polymerization and accumulation as inclusion bodies in many cortical and subcortical neurons, thereby leading to cell death, dementia and epilepsy. Many efforts have been undertaken to elucidate the molecular pathways responsible for neuronal death. Most investigations have concentrated on analysis of intracellular mechanisms such as endoplasmic reticulum (ER) stress, ER-associated protein degradation (ERAD) and oxidative stress. We have generated a HEK-293 cell model of FENIB by overexpressing G392E-mutant neuroserpin and in this study we examine trafficking and toxicity of this polymerogenic variant. We observed that a small fraction of mutant neuroserpin is secreted via the ER-to-Golgi pathway, and that this release can be pharmacologically regulated. Overexpression of the mutant form of neuroserpin did not stimulate cell death in the HEK-293 cell model. Finally, when treating primary hippocampal neurons with G392E neuroserpin polymers, we did not detect cytotoxicity or synaptotoxicity. Altogether, we report here that a polymerogenic mutant form of neuroserpin is secreted from cells but is not toxic in the extracellular milieu.
Spatial and temporal pattern of wildfires in California from 2000 to 2019
Authors: Li Shu , Banerjee Tirtha 
Published: April 2021

AbstractThe environmental pollution, property losses and casualties caused by wildfires in California are getting worse by the year. To minimize the interference of wildfires on economic and social development, and formulate targeted mitigation strategies, it is imperative to understand the scale and extent of previous wildfire occurrences. In this study, we first investigated the temporal distributions of past wildfires in California divided by size and causes and analyzed the changes observed in the past two decades against the last century. The trend of wildfires in different time scales (yearly and monthly), as well as the distribution of wildfires across different spatial scales (administrative units, climate divisions in California from 2000 to 2019) were also studied. Furthermore, to extract the significant variables on the risk of wildfire occurrence, multivariate analyses of environmental and human-related variables with wildfire densities were carried out. The results show that the wildfire density distribution of the burned area in California conforms to the characteristics of the Pareto distribution. Over the past two decades, the frequency of small (< 500 acres), human-caused wildfires has increased most rapidly, and they are widely distributed in central and western California. The wildfire season has lengthened and the peak months have been advanced from August to July. In terms of the variables related to the risk of wildfire occurrence, the temperature, vapor pressure deficit, grass cover, and the distance to roads are crucial. This study reveals the relationship between environmental and social background conditions and the spatial-temporal distribution of wildfires, which can provide a reference for wildfire management, the formulation of future targeted wildfire emergency plans, and the planning of future land use in California.
Sex difference in the weighting of expected uncertainty under chronic stress
Authors: Lei Huijie , Mochizuki Yasuhiro , Chen Chong , Hagiwara Kosuke , Hirotsu Masako , Matsubara Toshio , Nakagawa Shin 
Published: April 2021

AbstractThe neurobiological literature implicates chronic stress induced decision-making deficits as a major contributor to depression and anxiety. Given that females are twice as likely to suffer from these disorders, we hypothesized the existence of sex difference in the effects of chronic stress on decision-making. Here employing a decision-making paradigm that relies on reinforcement learning of probabilistic predictive relationships, we show female volunteers with a high level of perceived stress in the past month are more likely to make suboptimal choices than males. Computational characterizations of this sex difference suggest that while under high stress, females and males differ in their weighting but not learning of the expected uncertainty in the predictive relationships. These findings provide a mechanistic account of the sex difference in decision-making under chronic stress and may have important implications for the epidemiology of sex difference in depression and anxiety.
Genetic variant rs10251977 (G>A) in EGFR-AS1 modulates the expression of EGFR isoforms A and D
Authors: Dhamodharan Shankar , Rose Mathew Maria , Chakkarappan Sundaram Reddy , Umadharshini Karuppiah Vijayamuthuramalingam , Arulmurugan Ramalingam , Subbiah Shanmugam , Inoue Ituro , Munirajan Arasambattu Kannan 
Published: April 2021

AbstractTyrosine kinase inhibitor is an effective chemo-therapeutic drug against tumors with deregulated EGFR pathway. Recently, a genetic variant rs10251977 (G>A) in exon 20 of EGFR reported to act as a prognostic marker for HNSCC. Genotyping of this polymorphism in oral cancer patients showed a similar frequency in cases and controls. EGFR-AS1 expressed significantly high level in tumors and EGFR-A isoform expression showed significant positive correlation (r = 0.6464, p < 0.0001) with reference to EGFR-AS1 expression levels, consistent with larger TCGA HNSCC tumor dataset. Our bioinformatic analysis showed enrichment of alternative splicing marks H3K36me3 and presence of intronic polyA sites spanning around exon 15a and 15b of EGFR facilitates skipping of exon 15b, thereby promoting the splicing of EGFR-A isoform. In addition, high level expression of PTBP1 and its binding site in EGFR and EGFR-AS1 enhances the expression of EGFR-A isoform (r = 0.7404, p < 0.0001) suggesting that EGFR-AS1 expression modulates the EGFR-A and D isoforms through alternative splicing. In addition, this polymorphism creates a binding site for miR-891b in EGFR-AS1 and may negatively regulate the EGFR-A. Collectively, our results suggested the presence of genetic variant in EGFR-AS1 modulates the expression of EGFR-D and A isoforms.
The plasminogen protein is associated with high myopia as revealed by the iTRAQ-based proteomic analysis of the aqueous humor
Authors: Wen Kai , Shao Xianfeng , Li Yahong , Li Yaoling , Li Yongtao , Wang Qing , Su Ruihong , Zhang Lujie , Cai Yang , Sun Jing , Zhang Yan 
Published: April 2021

AbstractTo explore the pathogenesis of high myopia (HM) using quantitative proteomics. The aqueous humor of patients with simple nuclear cataract and nuclear cataract complicated with HM (hereinafter referred to as “C” and “HM” groups, respectively) were collected. The isobaric tags for relative and absolute quantitation (iTRAQ)-based liquid chromatography–tandem mass spectrometry (LC–MS/MS) proteomics approach was employed to explore differentially expressed proteins (DEPs). Bioinformatics was used to interpret the proteomic results. Furthermore, the plasminogen (PLG) protein was confirmed by enzyme-linked immunosorbent assay (ELISA) as the candidate biomarker for HM through a receiver operating characteristic curve analysis. The study showed 32 upregulated and 26 downregulated proteins. The gene ontology analysis demonstrated that 58 DEPs corresponded to 325 biological processes, 33 cell components, and 45 molecular functional annotations. The Kyoto Encyclopedia of Genes and Genomes analysis showed that the upregulated DEPs were highly enriched in the coagulation and complement cascades, consistent with the gene set enrichment analysis. Our data suggested that some DEPs might be hallmarks of the development of HM. ELISA confirmed that the PLG expression levels were significantly upregulated in HM. This was a new study investigating alterations in protein levels and affected pathways in HM using iTRAQ-based quantitative proteomics. Our study provided a comprehensive dataset on overall protein changes and shed light on its potential molecular mechanism in human HM.
A high-resolution assessment of climate change impact on water footprints of cereal production in India
Authors: Mali Santosh S. , Shirsath Paresh B. , Islam Adlul 
Published: April 2021

AbstractWater footprint (WF), a comprehensive indicator of water resources appropriation, has evolved as an efficient tool to improve the management and sustainability of water resources. This study quantifies the blue and green WF of major cereals crops in India using high resolution soil and climatic datasets. A comprehensive modelling framework, consisting of Evapotranspiration based Irrigation Requirement (ETIR) tool, was developed for WF assessment. For assessing climate change impact on WF, multi-model ensemble climate change scenarios were generated using the hybrid-delta ensemble method for RCP4.5 and RCP6.0 and future period of 2030s and 2050s. The total WF of the cereal crops are projected to change in the range of − 3.2 to 6.3% under different RCPs in future periods. Although, the national level green and blue WF is projected to change marginally, distinct trends were observed for Kharif (rainy season—June to September) and rabi (winter season—October to February) crops. The blue WF of paddy is likely to decrease by 9.6%, while for wheat it may increase by 4.4% under RCP4.5 during 2050s. The green WF of rabi crops viz. wheat and maize is likely to increase in the range of 20.0 to 24.1% and 9.9 to 16.2%, respectively. This study provides insights into the influences of climate change on future water footprints of crop production and puts forth regional strategies for future water resource management. In view of future variability in the WFs, a water footprint-based optimization for relocation of crop cultivation areas with the aim of minimising the blue water use would be possible management alternative.
Expression of CCL2/CCR2 signaling proteins in breast carcinoma cells is associated with invasive progression
Authors: Fang Wei Bin , Sofia Acevedo Diana , Smart Curtis , Zinda Brandon , Alissa Nadia , Warren Kyle , Fraga Garth , Huang Li-Ching , Shyr Yu , Li Wei , Xie Lu , Staggs Vincent , Hong Yan , Behbod Fariba , Cheng Nikki 
Published: April 2021

AbstractDuctal carcinoma in situ (DCIS) is the most common type of pre-invasive breast cancer diagnosed in women. Because the majority of DCIS cases are unlikely to progress to invasive breast cancer, many women are over-treated for DCIS. By understanding the molecular basis of early stage breast cancer progression, we may identify better prognostic factors and design treatments tailored specifically to the predicted outcome of DCIS. Chemokines are small soluble molecules with complex roles in inflammation and cancer progression. Previously, we demonstrated that CCL2/CCR2 chemokine signaling in breast cancer cell lines regulated growth and invasion through p42/44MAPK and SMAD3 dependent mechanisms. Here, we sought to determine the clinical and functional relevance of CCL2/CCR2 signaling proteins to DCIS progression. Through immunostaining analysis of DCIS and IDC tissues, we show that expression of CCL2, CCR2, phospho-SMAD3 and phospho-p42/44MAPK correlate with IDC. Using PDX models and an immortalized hDCIS.01 breast epithelial cell line, we show that breast epithelial cells with high CCR2 and high CCL2 levels form invasive breast lesions that express phospho-SMAD3 and phospho-p42/44MAPK. These studies demonstrate that increased CCL2/CCR2 signaling in breast tissues is associated with DCIS progression, and could be a signature to predict the likelihood of DCIS progression to IDC.
Support vector regression-based QSAR models for prediction of antioxidant activity of phenolic compounds
Authors: Shi Ying 
Published: April 2021

AbstractThe Support vector regression (SVR) was used to investigate quantitative structure–activity relationships (QSAR) of 75 phenolic compounds with Trolox-equivalent antioxidant capacity (TEAC). Geometric structures were optimized at the EF level of the MOPAC software program. Using Pearson correlation coefficient analysis, four molecular descriptors [n(OH), Cosmo Area (CA), Core-Core Repulsion (CCR) and Final Heat of Formation (FHF)] were selected as independent variables. The QSAR model was developed from the training set consisting of 57 compounds and then used the leave-one-out cross-validation (LOOCV) correlation coefficient to evaluate the prediction ability of the QSAR model. Used Artificial neural network (ANN) and multiple linear regression (MLR) for comparing. The RMSE (root mean square error) values of LOOCV in SVR, ANN and MLR models were 0.44, 0.46 and 0.54. The RMSE values of prediction of external 18 compounds were 0.41, 0.39 and 0.54 for SVR, ANN and MLR models, respectively. The obtained result indicated that the SVR models exhibited excellent predicting performance and competent for predicting the TEAC of phenolic compounds.
Quantitative real-time analysis of the efflux by the MacAB-TolC tripartite efflux pump clarifies the role of ATP hydrolysis within mechanotransmission mechanism
Authors: Souabni Hager , Batista dos Santos William , Cece Quentin , Catoire Laurent J. , Puvanendran Dhenesh , Bavro Vassiliy N. , Picard Martin 
Published: April 2021

AbstractTripartite efflux pumps built around ATP-binding cassette (ABC) transporters are membrane protein machineries that perform vectorial export of a large variety of drugs and virulence factors from Gram negative bacteria, using ATP-hydrolysis as energy source. Determining the number of ATP molecules consumed per transport cycle is essential to understanding the efficiency of substrate transport. Using a reconstituted pump in a membrane mimic environment, we show that MacAB-TolC from Escherichia coli couples substrate transport to ATP-hydrolysis with high efficiency. Contrary to the predictions of the currently prevailing “molecular bellows” model of MacB-operation, which assigns the power stroke to the ATP-binding by the nucleotide binding domains of the transporter, by utilizing a novel assay, we report clear synchronization of the substrate transfer with ATP-hydrolysis, suggesting that at least some of the power stroke for the substrate efflux is provided by ATP-hydrolysis. Our findings narrow down the window for energy consumption step that results in substrate transition into the TolC-channel, expanding the current understanding of the efflux cycle of the MacB-based tripartite assemblies. Based on that we propose a modified model of the MacB cycle within the context of tripartite complex assembly.
The pleiotropic effects of antithrombotic drugs in the metabolic–cardiovascular–neurodegenerative disease continuum: impact beyond reduced clotting
Authors: Alaaeddine Rana A. , AlZaim Ibrahim , Hammoud Safaa H. , Arakji Aya , Eid Ali H. , Abd-Elrahman Khaled S. , El-Yazbi Ahmed F. 
Published: April 2021

Abstract
Antithrombotic drugs are widely used for primary and secondary prevention, as well as treatment of many cardiovascular disorders. Over the past few decades, major advances in the pharmacology of these agents have been made with the introduction of new drug classes as novel therapeutic options. Accumulating evidence indicates that the beneficial outcomes of some of these antithrombotic agents are not solely related to their ability to reduce thrombosis. Here, we review the evidence supporting established and potential pleiotropic effects of four novel classes of antithrombotic drugs, adenosine diphosphate (ADP) P2Y12-receptor antagonists, Glycoprotein IIb/IIIa receptor Inhibitors, and Direct Oral Anticoagulants (DOACs), which include Direct Factor Xa (FXa) and Direct Thrombin Inhibitors. Specifically, we discuss the molecular evidence supporting such pleiotropic effects in the context of cardiovascular disease (CVD) including endothelial dysfunction (ED), atherosclerosis, cardiac injury, stroke, and arrhythmia. Importantly, we highlight the role of DOACs in mitigating metabolic dysfunction-associated cardiovascular derangements. We also postulate that DOACs modulate perivascular adipose tissue inflammation and thus, may reverse cardiovascular dysfunction early in the course of the metabolic syndrome. In this regard, we argue that some antithrombotic agents can reverse the neurovascular damage in Alzheimer’s and Parkinson’s brain and following traumatic brain injury (TBI). Overall, we attempt to provide an up-to-date comprehensive review of the less-recognized, beneficial molecular aspects of antithrombotic therapy beyond reduced thrombus formation. We also make a solid argument for the need of further mechanistic analysis of the pleiotropic effects of antithrombotic drugs in the future.
Halomonasas a chassis
Authors: Ye Jian-Wen , Chen Guo-Qiang 
Published: April 2021

AbstractWith the rapid development of systems and synthetic biology, the non-model bacteria, Halomonas spp., have been developed recently to become a cost-competitive platform for producing a variety of products including polyesters, chemicals and proteins owing to their contamination resistance and ability of high cell density growth at alkaline pH and high salt concentration. These salt-loving microbes can partially solve the challenges of current industrial biotechnology (CIB) which requires high energy-consuming sterilization to prevent contamination as CIB is based on traditional chassis, typically, Escherichia coli, Bacillus subtilis, Pseudomonas putida and Corynebacterium glutamicum. The advantages and current status of Halomonas spp. including their molecular biology and metabolic engineering approaches as well as their applications are reviewed here. Moreover, a systematic strain engineering streamline, including product-based host development, genetic parts mining, static and dynamic optimization of modularized pathways and bioprocess-inspired cell engineering are summarized. All of these developments result in the term called next-generation industrial biotechnology (NGIB). Increasing efforts are made to develop their versatile cell factories powered by synthetic biology to demonstrate a new biomanufacturing strategy under open and continuous processes with significant cost-reduction on process complexity, energy, substrates and fresh water consumption.
The Neural Circuitry Underlying the “Rhythm Effect” in Stuttering
Authors: Frankford Saul A. , Heller Murray Elizabeth S. , Masapollo Matthew , Cai Shanqing , Tourville Jason A. , Nieto-Castañón Alfonso , Guenther Frank H. 
Published: April 2021

PurposeStuttering is characterized by intermittent speech disfluencies, which are dramatically reduced when speakers synchronize their speech with a steady beat. The goal of this study was to characterize the neural underpinnings of this phenomenon using functional magnetic resonance imaging.MethodData were collected from 16 adults who stutter and 17 adults who do not stutter while they read sentences aloud either in a normal, self-paced fashion or paced by the beat of a series of isochronous tones (“rhythmic”). Task activation and task-based functional connectivity analyses were carried out to compare neural responses between speaking conditions and groups after controlling for speaking rate.ResultsAdults who stutter produced fewer disfluent trials in the rhythmic condition than in the normal condition. Adults who stutter did not have any significant changes in activation between the rhythmic condition and the normal condition, but when groups were collapsed, participants had greater activation in the rhythmic condition in regions associated with speech sequencing, sensory feedback control, and timing perception. Adults who stutter also demonstrated increased functional connectivity among cerebellar regions during rhythmic speech as compared to normal speech and decreased connectivity between the left inferior cerebellum and the left prefrontal cortex.ConclusionsModulation of connectivity in the cerebellum and prefrontal cortex during rhythmic speech suggests that this fluency-inducing technique activates a compensatory timing system in the cerebellum and potentially modulates top-down motor control and attentional systems. These findings corroborate previous work associating the cerebellum with fluency in adults who stutter and indicate that the cerebellum may be targeted to enhance future therapeutic interventions.Supplemental Materialhttps://doi.org/10.23641/asha.14417681
Generational Differences in Work Ethic Among Speech-Language Pathologists
Authors: McCullough Helga M. , Gaugler Trent 
Published: April 2021

Purpose
To date, there is limited available research with a specific focus on the potential differences in work ethic among speech-language pathologists from different social generations. The purpose of this study was to provide a better understanding of the work ethic profile of three generations of speech-language pathologists and, in particular, of any differences in work ethic profiles among the three generations.

Method
This study used a quantitative, nonexperimental, cross-sectional design to better understand work ethic among the three generations of speech-language pathologists through the use of an online survey containing the Multidimensional Work Ethic Profile–Short Form.

Results
The 814 surveys analyzed indicated that the three distinct generations of speech-language pathologists exhibited differences in four out of the seven dimensions of work ethic.

Conclusions
Through this study, the authors developed a work ethic profile for each of the three generations of speech-language pathologists licensed in the Commonwealth of Pennsylvania. While there were some similarities in the dimensions of work ethic among the three generational cohorts, statistically significant differences were discovered in the dimensions of Morality/Ethics, Leisure, Centrality of Work, and Wasted Time. Understanding differences in work ethic could be beneficial to employers, administrators, and supervisors for recruitment and retention purposes as well as to speech-language pathologists who work with colleagues of different generational cohorts.