bluuebunny/crossref_metadata_2025_split huggingface dataset:
Genome sequencing of white-blotched river stingray (Potamotrygon leopoldi) provides novel clues for niche-adaptation and skeleton formation
Authors: Zhou Jingqi , Liu Ake , He Funan , Zhang Yunbin , Shen Libing , Yu Jun , Zhang Xiang 
Published: October 2021

AbstractThe white-blotched river stingray (Potamotrygon leopoldi) is a cartilaginous fish native to the Xingu River, a tributary of the Amazon River system. It possesses a lot of unique biological features such as disc-like body shape, bizarre color pattern and living in freshwater habitat while most stingrays and their close relatives are sea dwellers. As a member of the Potamotrygonidae family, P. leopoldi bears evolutionary signification in fish phylogeny, niche adaptation and skeleton formation. In this study, we present its draft genome of 4.11 Gb comprised of 16,227 contigs and 13,238 scaffolds, which has contig N50 of 3,937 kilobases and scaffold N50 of 5,675 kilobases in size. Our analysis shows that P. leopoldi is a slow-evolving fish, diverged from elephant shark about 96 million years ago. We find that two gene families related to immune system, immunoglobulin heavy constant delta genes, and T-cell receptor alpha/delta variable genes, stand out expanded in P. leopoldi only, suggesting robustness in response to freshwater pathogens in adapting novel environments. We also identified the Hox gene clusters in P. leopoldi and discovered that seven Hox genes shared by five representative fishes are missing in P. leopoldi. The RNA-seq data from P. leopoldi and other three fish species demonstrate that fishes have a more diversified tissue expression spectrum as compared to the corresponding mammalian data. Our functional studies suggest that the lack of genes encoding vitamin D-binding protein in cartilaginous (both P. leopoldi and Callorhinchus milii) fishes could partly explain the absence of hard bone in their endoskeleton. Overall, this genome resource provides new insights into the niche-adaptation, body plan and skeleton formation of P. leopoldi as well as the genome evolution in cartilaginous fish.
Expression and Neurotransmitter Association of the Synaptic Calcium Sensor Synaptotagmin in the Avian Auditory Brain Stem
Authors: MacLeod Katrina M. , Pandya Sangeeta 
Published: October 2021

AbstractIn the avian auditory brain stem, acoustic timing and intensity cues are processed in separate, parallel pathways via the two division of the cochlear nucleus, nucleus angularis (NA) and nucleus magnocellularis (NM). Differences in excitatory and inhibitory synaptic properties, such as release probability and short-term plasticity, contribute to differential processing of the auditory nerve inputs. We investigated the distribution of synaptotagmin, a putative calcium sensor for exocytosis, via immunohistochemistry and double immunofluorescence in the embryonic and hatchling chick brain stem (Gallus gallus). We found that the two major isoforms, synaptotagmin 1 (Syt1) and synaptotagmin 2 (Syt2), showed differential expression. In the NM, anti-Syt2 label was strong and resembled the endbulb terminals of the auditory nerve inputs, while anti-Syt1 label was weaker and more punctate. In NA, both isoforms were intensely expressed throughout the neuropil. A third isoform, synaptotagmin 7 (Syt7), was largely absent from the cochlear nuclei. In nucleus laminaris (NL, the target nucleus of NM), anti-Syt2 and anti-Syt7 strongly labeled the dendritic lamina. These patterns were established by embryonic day 18 and persisted to postnatal day 7. Double labeling immunofluorescence showed Syt1 and Syt2 were associated with Vesicular Glutamate Transporter 2 (VGluT2), but not Vesicular GABA Transporter (VGAT), suggesting these Syt isoforms were localized to excitatory, but not inhibitory, terminals. These results suggest that Syt2 is the major calcium binding protein underlying excitatory neurotransmission in the timing pathway comprising NM and NL, while Syt2 and Syt1 regulate excitatory transmission in the parallel intensity pathway via cochlear nucleus NA.
Molecular insights into phosphorylation-induced allosteric conformational changes in β2-adrenergic receptor
Authors: Madhu Midhun K. , Debroy Annesha , Murarka Rajesh K. 
Published: October 2021

AbstractThe large conformational flexibility of G protein-coupled receptors (GPCRs) has been a puzzle in structural and pharmacological studies for the past few decades. Apart from structural rearrangements induced by ligands, enzymatic phosphorylations by GPCR kinases (GRKs) at the carboxy-terminal tail (C-tail) of a GPCR also makes conformational alterations to the transmembrane helices and facilitates the binding of one of its transducer proteins named β-arrestin. Phosphorylation-induced conformational transition of the receptor that causes specific binding to β-arrestin but prevents the association of other transducers such as G proteins lacks atomistic understanding and is elusive to experimental studies. Using microseconds of all-atom conventional and Gaussian accelerated molecular dynamics (GaMD) simulations, we investigate the allosteric mechanism of phosphorylation induced-conformational changes in β2-adrenergic receptor, a well-characterized GPCR model system. Free energy profiles reveal that the phosphorylated receptor samples a new conformational state in addition to the canonical active state corroborating with recent nuclear magnetic resonance experimental findings. The new state has a smaller intracellular cavity that is likely to accommodate β-arrestin better than G protein. Using contact map and inter-residue interaction energy calculations, we found the phosphorylated C-tail adheres to the cytosolic surface of the transmembrane domain of the receptor. Transfer entropy calculations show that the C-tail residues drive the correlated motions of TM residues, and the allosteric signal is relayed via several residues at the cytosolic surface. Our results also illustrate how the redistribution of inter-residue nonbonding interaction couples with the allosteric communication from the phosphorylated C-tail to the transmembrane. Atomistic insight into phosphorylation-induced β-arrestin specific conformation is therapeutically important to design drugs with higher efficacy and fewer side effects. Our results therefore open novel opportunities to fine-tune β-arrestin bias in GPCR signaling.
Current and Lifetime Somatic Symptom Burden Among Transition-aged Autistic Young Adults
Authors: Williams Zachary J. , Gotham Katherine O. 
Published: October 2021

AbstractBackground and ObjectivesSomatic symptoms are the most common cause of outpatient medical visits in the general population, yet their presence and severity in individuals on the autism spectrum has rarely been studied. We sought to assess the prevalence, impact, and clinical correlates of fourteen commonly-reported somatic symptoms in a sample of transition-aged autistic young adults.MethodsA sample of 290 independent and cognitively able autistic young adults (aged 18–26 years; mean [SD]: 23.10 [2.38] years) was recruited from the Simons Foundation SPARK participant pool. A modified version of the Patient Health Questionnaire–15 was used to assess somatic symptom prevalence/impact, along with measures of depression, anxiety, autistic traits, and quality of life.ResultsSomatic symptom burden was much higher in autistic young adults than previously reported in the general population. The most commonly reported current symptoms were fatigue (72.8%), sleep problems (69.0%), and menstrual problems (61.4% of females). Moderate or severe symptom levels were reported by 53.9% of females and 18.75% of males in our cohort, with the odds of females of endorsing any given symptom being 2–4 times greater than males. Both individual symptoms and total symptom burden were related to higher levels of depression, anxiety, and autistic traits, along with lower quality of life.ConclusionDespite little research on this topic previously, somatic symptoms are highly prevalent in autistic young adults, particularly women. Future research is needed to investigate links between somatic symptoms, medical and psychiatric morbidity, and health care utilization in the autistic population.What’s Known on This SubjectSomatic symptoms are highly prevalent in the general population and account for a large proportion of health care costs. However, few studies have investigated the prevalence, impact, or correlates of these symptoms in individuals on the autism spectrum.What This Study AddsTo our knowledge, this is the first study to specifically assess current and lifetime somatic symptom burden, symptom onset patterns, and the clinical correlates of multisystem symptom distress in transition-aged young adults on the autism spectrum.
A Budding Yeast Model and Screen to Define the Functional Consequences of Oncogenic Histone Missense Mutations
Authors: Lemon Laramie D. , Kannan Sneha , Mo Kim Wai , Adams Miranda , Choi Haley G. , Gulka Alexander O. D. , Withers Elise S. , Nurelegne Hasset T. , Gomez Valeria , Ambrocio Reina E. , Tumminkatti Rhea , Lee Richard S. , Wan Morris , Fasken Milo B. , Spangle Jennifer M. , Corbett Anita H. 
Published: October 2021

ABSTRACTSomatic missense mutations in histone genes turn these essential proteins into oncohistones, which can drive oncogenesis. Understanding how missense mutations alter histone function is challenging in mammals as mutations occur in a single histone gene. For example, described oncohistone mutations predominantly occur in the histoneH3.3gene, despite the human genome encoding 15 H3 genes. To understand how oncogenic histone missense mutations alter histone function, we leveraged the budding yeast model, which contains only two H3 genes, to explore the functional consequences of oncohistones H3K36M, H3G34W, H3G34L, H3G34R, and H3G34V. Analysis of cells that express each of these variants as the sole copy of H3 reveals that H3K36 mutants show different drug sensitivities compared to H3G34 mutants. This finding suggests that changes to proximal amino acids in the H3 N-terminal tail alter distinct biological pathways. We exploited the caffeine sensitive growth of H3K36 mutant cells to perform a high copy suppressor screen. This screen identified genes linked to histone function and transcriptional regulation, including Esa1, a histone H4/H2A acetyltransferase; Tos4, a forkhead-associated domain-containing gene expression regulator; Pho92, an N6-methyladenosine RNA binding protein and Sgv1/Bur1, a cyclin-dependent kinase. We show that the Esa1 lysine acetyltransferase activity is critical for suppression of the caffeine sensitive growth of H3K36R mutant cells while the previously characterized binding interactions of Tos4 and Pho92 are not required for suppression. This screen identifies pathways that could be altered by oncohistone mutations and highlights the value of yeast genetics to identify pathways altered by such mutations.
Pyruvate dehydrogenase kinase supports macrophage NLRP3 inflammasome activation during acute inflammation
Authors: Meyers Allison K. , Wang Zhan , Han Wenzheng , Zhao Qingxia , Zabalawi Manal , Duan Likun , Liu Juan , Zhang Qianyi , Manne Rajesh K , Lorenzo Felipe , Quinn Matthew A. , Song Qianqian , Fan Daping , Lin Hui-Kuan , Furdui Cristina M. , Locasale Jason W. , McCall Charles E. , Zhu Xuewei 
Published: October 2021

SummaryActivating macrophage NLRP3 inflammasome can promote excessive inflammation, with severe cell and tissue damage and organ dysfunction. Here, we show that pharmacological or genetic inhibition of pyruvate dehydrogenase kinase (PDHK) significantly attenuates NLRP3 inflammasome activation in murine and human macrophages and septic mice by lowering caspase-1 cleavage and IL-1β secretion. Inhibiting PDHK reverses NLRP3 inflammasome-induced metabolic reprogramming, enhances autophagy, promotes mitochondrial fusion over fission, preserves cristae ultrastructure, and attenuates mitochondrial ROS production. The suppressive effect of PDHK inhibition on the NLRP3 inflammasome is independent of its canonical role as a pyruvate dehydrogenase regulator. We suggest that PDHK inhibition improves mitochondrial fitness by reversing NLRP3 inflammasome activation in acutely inflamed macrophages.
Compound Screening with Deep Learning for Neglected Diseases: Leishmaniasis
Authors: Smith Jonathan , Xu Hao , Li Xinran , Yang Laurence , Gutierrez Jahir M. 
Published: October 2021

AbstractDeep learning provides a tool for improving screening of candidates for drug re-purposing to treat neglected diseases. We show how a new pipeline can be developed to address the needs of repurposing for Leishmaniasis. In combination with traditional molecular docking techniques, this allows top candidates to be selected and analyzed, including for molecular descriptor similarity.
Pain is so close to pleasure: the same dopamine neurons can mediate approach and avoidance in Drosophila
Authors: Rohrsen Christian , Kumpf Aida , Semiz Kader , Aydin Ferruh , deBivort Benjamin , Brembs Björn 
Published: October 2021

AbstractIn mammals, dopamine is considered a central neuromodulator involved in all kinds of rewarding experiences (‘common currency’ hypothesis). In insects, the role of do-paminergic neurons in aversive stimuli was discovered before dopaminergic neurons were found to also be involved in processing appetitive stimuli. Here, we screened about 50 transgenic Drosophila lines, representing different subpopulations of dopa-minergic neurons for their ability to sustain approach or avoidance behavior, when activated optogenetically in four different operant self-stimulation paradigms. None of the lines sustain consistent behavioral valence in all experiments. Individual lines sustain approach in one experiment and avoidance in another. One line mediated strong avoidance early in the experiment and weak approach in later stages. The evidence presented here appears to contradict a ‘common currency’ dopamine function in flies. Instead, different dopaminergic neurons convey valence in a context-dependent and flexible manner, reflecting the genetic heterogeneity of the dopaminergic neuronal population.
Unpacking dialogic accounting: a systematic literature review and research agenda
Authors: Manetti Giacomo , Bellucci Marco , Oliva Stefania 
Published: October 2021

PurposeThis article aims to contribute to the critical accounting literature by reviewing how previous studies have addressed the topic of dialogic accounting (DA), examining the main themes investigated and discussing potential further developments of the DA research agenda.Design/methodology/approachThe present study builds on a systematic literature review of 186 research products indexed on Scopus, Web of Science and Google Scholar that were published between 2004 and 2019 in 55 accounting or non-accounting scientific journals and 14 books.FindingsFirst, a content analysis of each contribution informs a classification in terms of research design, methodology, geographical setting and sector of analysis. Second, a bibliometric analysis provides several visual representations of the network of research products included in our review using bibliographic coupling, cooccurrence and coauthorship analyses. Third, and most importantly, the main narrative review discusses the development of the research strand on DA from the seminal works that introduced the topic, through the core of critical contributions inspired by the struggle between democracy and agonism, to the most recent contributions, in which new topics emerge and innovative methodologies are applied to the study of DA.Originality/valueThe main contribution of this manuscript is twofold. In addition to providing a systematic, bibliometric and narrative review of the evolution of nearly two decades of literature on DA, the present study is intended to collect ideas for further research and to discuss how the advent of new technologies and the peculiarities of various institutional contexts can shape the future research agenda on this critical form of accounting.
Targeting millers to improve rice marketing in Uganda
Authors: Twine Edgar Edwin , Adur-Okello Stella Everline , Mujawamariya Gaudiose , Ndindeng Sali Atanga 
Published: October 2021

PurposeImproving milling quality is expected to improve the quality of domestic rice and hence the competitiveness of Uganda's rice industry. Therefore, this study aims to assess the determinants of four aspects of milling, namely, choice of milling technology, millers' perceptions of the importance of paddy quality attributes, milling return and milling capacity.Design/methodology/approachMultinomial logit, semi-nonparametric extended ordered probit, linear regression and additive nonparametric models are applied to cross-sectional data obtained from a sample of 196 rice millers.FindingsPhysical, economic, institutional, technological and sociodemographic factors are found to be important determinants of the four aspects of milling. Physical factors include the distance of the mill from major town and availability of storage space at the milling premises, while economic factors include milling charge and backward integration of miller into paddy production. Contracting and use of a single-pass mill are important institutional and technological factors, respectively, and miller's household size, age, gender and education are the key sociodemographic variables.Originality/valueThe study's originality lies in its scope, especially in terms of its breadth. Without compromising the needed analytical rigor, it focuses on four aspects of milling that are critical to improving the marketing of Uganda's rice. In doing so, it provides a holistic understanding of this segment of the value chain and offers specific recommendations for improving the marketing of Uganda's rice.
An evaluation of the quality characteristics of kefir fortified with olive (Olea europaea) leaf extract
Authors: Okur Özge Duygu 
Published: October 2021

PurposeThis study aims to produce a new type of healthy functional kefir by adding olive (Olea europaea) leaf extract and to determine its potential effect on the quality (physicochemical, sensory, phenolic contents and antioxidant properties) of kefir samples during storage at 4°C for 21 days.Design/methodology/approachFor this purpose, four kefir samples were produced by using olive leaf extract in different amounts (A: 0% (control), B: 0.1%, C: 0.15% and D: 0.35%). The physicochemical, sensory, phenolic contents and antioxidant properties of kefir samples were investigated during Days 1, 7, 14 and 21 of storage. The study was conducted to optimize the olive leaf extract addition level to obtain better-quality kefir functional food.FindingsFrom the results, it was determined that the addition of olive leaf extract affected the entire chemical components of the kefir samples (p < 0.05). It was found that the pH value decreased during storage. By contrast, it was observed that titration acidity values increased. The kefir sample with 0.35% olive leaf extract (D) had the highest total phenolic and antioxidant activity content (1,292.75 mg GAE/L and 10.20 mM TE, respectively) among the samples (p < 0.05). In the sensory analyses, the kefir sample with the highest score – in terms of sensory attributes – was the kefir sample containing 0.15% olive leaf extract (C).Originality/valueThus, it was concluded that kefir with added olive leaf extract could serve as a functional kefir of benefit to human health. When we looked at the enrichment studies on kefir as a functional product, no study has been found on the use of olive (Olea europaea) leaf extract, especially with kefir. In this sense, it is thought that the study will contribute to published literature.
Modelling, validation and parameter sensitivity of regenerative hydraulic-electric shock absorber
Authors: Zhang Min , Hu Cheng , Gao Jingwei , Zheng Peng 
Published: October 2021

PurposeSuspension is a significantly important component for automotive and railway vehicles. Regenerative hydraulic-electric shock absorbers (RHSA) have been proposed for the purpose of attenuating vibration of vehicle suspension, and also recover kinetic energy originated from vehicle vibration that is conventionally dissipated by hydraulic dampers. To advance the technology, the paper aims to present an RHSA system for heavy-duty and railway vehicles and create a dynamic modelling to discuss on the development process of RHSA model.Design/methodology/approachFirst, the development of RHSA dynamic model can be resolved into three stage models (an ideal one, a second one with an added accumulator and a third one that considers both accumulator and system losses) to comprehensively evaluate the RHSA's characterisation. Second, a prototype is fabricated for testing and the results meet desired agreements between simulation and measurement. Finally, the study of key parameters is carried out to investigate the influences of hydraulic-cylinder size, hydraulic-motor displacement and accumulator pre-charged pressure on the RHSA system.FindingsThe findings of sensitivity analysis indicate that the component design can satisfy the damping characteristics and power performance required for heavy-duty vehicle, freight wagon and typical passenger train. The results also show that reducing the losses is highly beneficial for saving suspension energy, improving system reliability and increasing power-conversion efficiency.Originality/valueThe paper presents a more detailed method for the development and analysis of a RHSA. Compared with the typical shock absorbers, RHSA can also recover the vibration energy dissipated by suspension.
ISM–ANP hybrid approach to prioritize the barriers in green lean Six Sigma implementation in construction sector
Authors: Thomas Dain , Khanduja Dinesh 
Published: October 2021

Purpose
The purpose of this paper is to prioritize and establish relationships among the barriers that affect green, lean and Six Sigma (GLSS) implementation in the Indian construction sector.

Design/methodology/approach
A hierarchal model consisting of several levels is generated by the interpretive structural modelling (ISM) methodology. For establishing the priority weights and the ranking of the barriers, the relationships among barriers from the model in ISM are used to provide an output from the analytic network process (ANP). The 12 vital barriers that affect implementation of GLSS adoption were shortlisted from literature and then finalized in consultation with experts belonging from both industry and academia.

Findings
Based on the ISM model “Lack of awareness for green products, Lack of top management commitment and involvement as well as Lack of funds along with an improper estimation” are at the highest level. Similar results were found while ranking the barriers through ISM–ANP integration.

Originality/value
This study identified and prioritized the barriers that affect GLSS implementation using ISM–ANP approach, such a study has not been attempted previously for the construction sector. The ISM model and ANP ranks are based on the inputs gathered from experts and academicians so as to ensure practical validity. This approach is assists decision-makers to focus on the key barriers priority basis and enables them to implement GLSS smoothly.