bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dispersal ability predicts spatial genetic structure in native mammals persisting across an urbanization gradient
Authors: Richardson Jonathan L. , Michaelides Sozos , Combs Matthew , Djan Mihajla , Bisch Lianne , Barrett Kerry , Silveira Georgianna , Butler Justin , Aye Than Thar , Munshi‐South Jason , DiMatteo Michael , Brown Charles , McGreevy Thomas J. 
Published: September 2020

AbstractAs the rate of urbanization continues to increase globally, a growing body of research is emerging that investigates how urbanization shapes the movement—and consequent gene flow—of species in cities. Of particular interest are native species that persist in cities, either as small relict populations or as larger populations of synanthropic species that thrive alongside humans in new urban environments. In this study, we used genomic sequence data (SNPs) and spatially explicit individual‐based analyses to directly compare the genetic structure and patterns of gene flow in two small mammals with different dispersal abilities that occupy the same urbanized landscape to evaluate how mobility impacts genetic connectivity. We collected 215 white‐footed mice (Peromyscus leucopus) and 380 big brown bats (Eptesicus fuscus) across an urban‐to‐rural gradient within the Providence, Rhode Island (U.S.A.) metropolitan area (population =1,600,000 people). We found that mice and bats exhibit clear differences in their spatial genetic structure that are consistent with their dispersal abilities, with urbanization having a stronger effect on Peromyscus mice. There were sharp breaks in the genetic structure of mice within the Providence urban core, as well as reduced rates of migration and an increase in inbreeding with more urbanization. In contrast, bats showed very weak genetic structuring across the entire study area, suggesting a near‐panmictic gene pool likely due to the ability to disperse by flight. Genetic diversity remained stable for both species across the study region. Mice also exhibited a stronger reduction in gene flow between island and mainland populations than bats. This study represents one of the first to directly compare multiple species within the same urban‐to‐rural landscape gradient, an important gap to fill for urban ecology and evolution. Moreover, here we document the impacts of dispersal capacity on connectivity for native species that have persisted as the urban landscape matrix expands.
Evidence for a dominant‐negative mechanism in HARS1‐mediated peripheral neuropathy
Authors: Meyer‐Schuman Rebecca , Antonellis Anthony 
Published: September 2020

The pathogenic mechanism of neuropathy‐associated aminoacyl‐tRNA synthetase (ARS) gene variants is poorly defined. Mullen et al. generate new models of pathogenic, dominant HARS1 mutations and show that they increase eIF2α phosphorylation and decrease protein translation in neurons. These results are consistent with a dominant‐negative mechanism of ARS‐mediated peripheral neuropathy.Comment on: https://doi.org/10.1111/febs.15449
Disciplined discourses: The logic of appropriateness in discourses on organizational gender equality policies
Authors: Amstutz Nathalie , Nussbaumer Melanie , Vöhringer Hanna 
Published: September 2020

AbstractOrganizational gender equality policies must address critical issues in organizations, as well as challenge hierarchies and the unequal distribution of power and resources. At the same time, they are reliant on acceptance by organizations when developing an official course of action. On the basis of a neo‐institutional perspective, this study investigates how gender equality discourses are disciplined so that they fit organizational expectations by maintaining the rationality myth of the organization. The empirical analysis of four Swiss organizations demonstrates that, although they intend to reduce gender inequalities, their gender equality policies are shaped by a logic of appropriateness that leads to a continuous reproduction of heteronormativity within gender equality policies. This study thus contributes to the understanding of how the logic of appropriateness protects the heteronormative matrix in organizations by disciplining gender equality discourses.
Optimizing the management of patients with haemophilia A and inhibitors in the era of emicizumab: Recommendations from a German expert panel
Authors: Escuriola‐Ettingshausen Carmen , Auerswald Günter , Königs Christoph , Kurnik Karin , Scholz Ute , Klamroth Robert , Oldenburg Johannes 
Published: September 2020

AbstractStandard treatment of haemophilia A is based on replacing the missing coagulation factor VIII (FVIII) to treat and prevent bleeding episodes. The most challenging complication of FVIII therapy is the development of neutralizing antibodies (inhibitors) that can render treatment ineffective. Eradication of the inhibitor through immune tolerance induction (ITI) remains the most effective strategy for managing these patients. Bypassing agents can be used to help restore haemostasis in inhibitor patients. Several novel agents have recently been developed, such as the FVIII mimetic agent emicizumab, which has been effective in reducing the annualized bleeding rate in haemophilia A patients with inhibitors. When coadministered with repetitive high doses of activated prothrombin complex concentrate (ie >100 U/kg/d for ≥24 hours), emicizumab was associated with thrombotic microangiopathy and thrombosis events. As a consequence the United Kingdom Haemophilia Centres Doctors' Organisation (UKHCDO) issued the first guidance on the treatment of bleeding episodes in patients receiving emicizumab. To build on and extend this work, a panel of German haemophilia specialists met to discuss the UK guidance, review current evidence and provide additional guidance for German healthcare professionals on how to optimize the management of patients with haemophilia A receiving emicizumab. Recommendations are provided on the use of bypassing and other agents to manage breakthrough bleeding, ITI in the emicizumab era, haemostatic support during surgery and issues relating to laboratory monitoring.
Neuroimmune crosstalk and evolving pharmacotherapies in neurodegenerative diseases
Authors: Baidya Falguni , Bohra Mariya , Datta Aishika , Sarmah Deepaneeta , Shah Birva , Jagtap Priya , Raut Swapnil , Sarkar Ankan , Singh Upasna , Kalia Kiran , Borah Anupom , Wang Xin , Dave Kunjan R. , Yavagal Dileep R. , Bhattacharya Pallab 
Published: September 2020

SummaryNeurodegeneration is characterized by gradual onset and limited availability of specific biomarkers. Apart from various aetiologies such as infection, trauma, genetic mutation, the interaction between the immune system and CNS is widely associated with neuronal damage in neurodegenerative diseases. The immune system plays a distinct role in disease progression and cellular homeostasis. It induces cellular and humoral responses, and enables tissue repair, cellular healing and clearance of cellular detritus. Aberrant and chronic activation of the immune system can damage healthy neurons. The pro‐inflammatory mediators secreted by chief innate immune components, the complement system, microglia and inflammasome can augment cytotoxicity. Furthermore, these inflammatory mediators accelerate microglial activation resulting in progressive neuronal loss. Various animal studies have been carried out to unravel the complex pathology and ascertain biomarkers for these harmful diseases, but have had limited success. The present review will provide a thorough understanding of microglial activation, complement system and inflammasome generation, which lead the healthy brain towards neurodegeneration. In addition to this, possible targets of immune components to confer a strategic treatment regime for the alleviation of neuronal damage are also summarized.
Localization and distribution of nitric oxide synthase and other neuronal markers in the podia of Holothuria arguinensis
Authors: Marquet Nathalie , Canário Adelino V. M. , Power Deborah M. 
Published: September 2020

AbstractThe organization of the nervous system of the holothurian podia—the tentacles, papillae, and tube feet—is still poorly understood, which limits the development of functional studies. Knowledge of nitric oxide (NO) signaling in sea cucumbers is nonexistent, although it is known to play an important role in many essential biological functions, including neurotransmission, throughout the animal kingdom. The objective of this study was to characterize the holothurian podia in Holothuria arguinensis. To this end, we used classical histology, nitric oxide synthase (NOS) distribution, using NADPH‐diaphorase histochemistry and NOS immunostaining, and neuronal immunohistochemistry. Our results revealed an abundant distribution of NO in the nervous components of the holothurian podia, suggesting an important role for NO as a neuronal messenger in these structures. Nitrergic fibers were intensely labeled in the longitudinal nerve and the nerve plexus surrounding the stem, but were more weakly labeled in the mesothelium. NOS was also found in scattered cell bodies and abundant fibers in the podia terminal end (i.e., the discs in tentacles and tube feet, and the pointed conical structures in the papillae), with evident neuronal projections to the bud surface, especially in the tentacles. The podia terminal end was the most specialized area and was characterized by a specific nervous arrangement, consisting of a distinct nerve plate, rich in cells and fibers containing potential sensory cells staining positively for neuronal markers, which makes this the most likely candidate to be a chemosensory region and an important candidate for future exploration.
Maackiain dampens osteoclastogenesis via attenuating RANKL‐stimulated NF‐κB signalling pathway and NFATc1 activity
Authors: Liu Yuhao , Zeng Weizai , Ma Chao , Wang Ziyi , Wang Chao , Li Shaobin , He Wei , Zhang Qingwen , Xu Jiake , Zhou Chi 
Published: September 2020

AbstractOsteolytic diseases are typified by over‐enhanced formation and resorbing function of osteoclasts and have a major impact on human health. Inhibition of osteoclastic differentiation and function is a key strategy for clinical therapy of osteolytic conditions. Maackiain is a natural compound extracted from Sophora flavescens, which has been applied to anti‐allergic and anti‐tumour treatments. The present results showed that Maackiain could restrain receptor activator of nuclear factor‐κB ligand (RANKL)‐stimulated osteoclast formation and hydroxyapatite resorption dose‐dependently, and interrupt the structures of F‐actin belts in the mature osteoclasts. It also repressed the expressions of osteoclast‐specific genes and proteins. Furthermore, Maackiain could inhibit RANKL‐stimulated NF‐κB and calcium signalling pathways, and dampen Nuclear factor of activated T cell cytoplasmic 1 activity, protein expression and translocation into the nucleus. These results revealed that Maackiain may have a potential therapeutic effect on osteoclast‐related disorders.
Empagliflozin reduces the senescence of cardiac stromal cells and improves cardiac function in a murine model of diabetes
Authors: Madonna Rosalinda , Doria Vanessa , Minnucci Ilaria , Pucci Angela , Pierdomenico Donato Sante , De Caterina Raffaele 
Published: September 2020

AbstractThe sodium‐glucose cotransporter 2 (SGLT2) inhibitor empagliflozin reduces heart failure in diabetes, but underlying mechanisms remain elusive. We hypothesized that empagliflozin could counteract the senescence of cardiac stromal cells (CSC), the action of which limits cardiac damage and cardiac fibrosis in diabetic‐like conditions in vitro and in vivo. CSC were isolated from murine heart biopsies (n = 5) through cardiosphere (CSp) formation and incubated for 3 or 48 hours with 5.5 mmol/L normal glucose (NG), high glucose (12‐5 and 30.5 mmol/L, HG) or a hyperosmolar control of mannitol (HM) in the presence or absence of empagliflozin 100 nmol/L. The senescent CSC status was verified by β‐gal staining and expression of the pro‐survival marker Akt (pAkt) and the pro‐inflammatory marker p38 (p‐P38). The cardiac effects of empagliflozin were also studied in vivo by echocardiography and by histology in a murine model of streptozotocin (STZ)‐induced diabetes. Compared to NG, incubations with HG and HM significantly reduced the number of CSps, increased the β‐gal‐positive CSC and P‐p38, while decreasing pAkt, all reversed by empagliflozin (P < .01). Empagliflozin also reversed cardiac dysfunction, cardiac fibrosis and cell senescence in mice with (STZ)‐induced diabetes (P < .01). Empagliflozin counteracts the pro‐senescence effect of HG and of hyperosmolar stress on CSC, and improves cardiac function via decreasing cardiac fibrosis and senescence in diabetic mice, possibly through SGLT2 off‐target effects. These effects may explain empagliflozin unexpected benefits on cardiac function in diabetic patients.
Identification and validation of critical alternative splicing events and splicing factors in gastric cancer progression
Authors: Feng Haoran , Jin Zhijian , Liu Kun , Peng Yi , Jiang Songyao , Wang Changgang , Hu Jiele , Shen Xiaoyun , Qiu Weihua , Cheng Xi , Zhao Ren 
Published: September 2020

AbstractGene expression and alternative splicing (AS) interact in complex ways to regulate biological process which is associated with cancer development. Here, by integrated analysis of gene expression and AS events, we aimed to identify the hub AS events and splicing factors relevant in gastric cancer development (GC). RNA‐seq data, clinical data and AS events of 348 GC samples were obtained from the TCGA and TCGASpliceSeq databases. Cox univariable and multivariable analyses, KEGG and GO pathway analyses were performed to identify hub AS events and splicing factor/spliceosome genes, which were further validated in 53 GCs. By bioinformatics methods, we found that gene AS event‐ and gene expression‐mediated GC progression shared the same mechanisms, such as PI3K/AKT pathway, but the involved genes were different. Though expression of 17 hub AS events were confirmed in 53 GC tissues, only 10 AS events in seven genes were identified as critical candidates related to GC progression, notably the AS events (Exon Skip) in CLSTN1 and SEC16A. Expression of these AS events in GC correlated with activation of the PI3K/AKT pathway. Genes with AS events associated with clinical parameters and prognosis were different from the genes whose mRNA levels were related to clinical parameters and prognosis. Besides, we further revealed that QKI and NOVA1 were the crucial splicing factors regulating expression of AS events in GC, but not spliceosome genes. Our integrated analysis revealed hub AS events in GC development, which might be the potential therapeutic targets for GC.
Transdisciplinary Generalism: Naming the epistemology and philosophy of the generalist
Authors: Lynch Johanna M. , Dowrick Christopher , Meredith Pamela , McGregor Sue L. T. , van Driel Mieke 
Published: September 2020

AbstractBackgroundTransdisciplinary research and generalist practice both face the task of integrating and discerning the value of knowledge across disciplinary and sectoral knowledge cultures. Transdisciplinarity and generalism also both offer philosophical and practical insights into the epistemology, ontology, axiology, and logic of seeing the ‘whole’. Although generalism is a skill that can be used in many settings from industry to education, the focus of this paper is the literature of the primary care setting (i.e., general practice or family medicine). Generalist philosophy and practice in the family medicine setting highly values whole person care that uses integrative and interpretive wisdom to include both biomedical and biographical forms of knowledge. Generalist researchers are often caught between reductionist (positivist) biomedical measures and social science (post‐positivist) constructivist theories of knowing. Neither of these approaches, even when juxtaposed in mixed‐methods research, approximate the complexity of the generalist clinical encounter. A theoretically robust research methodology is needed that acknowledges the complexity of interpreting these ways of knowing in research and clinical practice.MethodsA conceptual review of literature to define the alignment between (a) the philosophy and practice of generalism in primary care and (b) both the practical (Zurich) and philosophical or methodological (Nicolescuian) schools of transdisciplinarity.ResultsThe alignment between generalism and transdisciplinarity included their broad scope, relational process, complex knowledge management, humble attitude to knowing, and real‐world outcome focus.ConclusionThe concurrence between these approaches to knowing is offered here as Transdisciplinary Generalism – a coherent epistemology for both primary care researchers and generalist clinicians to understand, enact, and research their own sophisticated craft of managing diverse forms of knowledge.
Rheological modeling and activation energy of Persian grape molasses
Authors: Tavakolipour Hamid , Mokhtarian Mohsen , Kalbasi‐Ashtari Ahmad 
Published: September 2020

AbstractStudy the rheological behavior, modeling and activation energy (Ea) of Persian grape molasses (PGM) at different conditions. The shear rate and shear stress of PGM were measured at 25, 45, and 65°C and Brix concentrations (BC) of 35, 50, and 76%. Next different statistical parameters and Sigma plot software were used to test the obtained data on six different rheological models. Then the Ea and consistency coefficient of PGM were calculated at different BC using exponential and power equations. PGM exhibited a shear‐thickening behavior (n > 1) at BC's of 35–76% between 25 and 65°C. It showed the best fitness (R2 = 1.00) with power law (Ostwald–de‐Waele) model. The exponential relationship for computing Ea had higher R2 (0.937) than those in power law relationship (0.876). When the BC in PGM increased from 35 to 50% and then from 50 to 76% both at 25°C, the Ea raised ~10 and >100%. Exponential relationships were more trustable to calculate the effects of BC on consistency coefficient and Ea of PGM than power law equations. There is a high potential to raise the empirical Ea by increasing the BC of PGM to 76% at low temperature and retard its degradation process significantly.Practical ApplicationsPersian grape molasses (PGM) has high content of glucose and fructose, mineral, organic acid and bioactive compounds. The PGM with good nutritional components can be substituted instead of sugar in different food, and its rheological parameters will enhance the organoleptic (texture, color and flavor) properties of resulting products, considerably. On the other hand, rheological values of PGM will help us to solve numerous engineering calculations involved with this product when is produced in an industrial scale. Additionally, identifying rheological properties will help us to select and control processing equipment (such as mixing, dispersing, refining, spinning, concentration, and packaging), predict energy requirements, and evaluate sensory assessment of this product properly. Additionally, calculation of empirical activation energy could assist us to evaluate the degradation process of PGM and possibly predict its storage time at different brix concentrations and storage temperatures.
Changes in access to educational and healthcare services for individuals with intellectual and developmental disabilities during COVID‐19 restrictions
Authors: Jeste S. , Hyde C. , Distefano C. , Halladay A. , Ray S. , Porath M. , Wilson R. B. , Thurm A. 
Published: September 2020

AbstractBackgroundCOVID‐19 restrictions have significantly limited access to in‐person educational and healthcare services for all, including individuals with intellectual and developmental disabilities (IDDs). The objectives of this online survey that included both national and international families were to capture changes in access to healthcare and educational services for individuals with IDDs that occurred shortly after restrictions were initiated and to survey families on resources that could improve services for these individuals.MethodsThis was an online survey for caregivers of individuals with (1) a genetic diagnosis and (2) a neurodevelopmental diagnosis, including developmental delay, intellectual disability, autism spectrum disorder or epilepsy. The survey assessed (1) demographics, (2) changes in access to educational and healthcare services and (3) available and preferred resources to help families navigate the changes in service allocation.ResultsOf the 818 responses (669 within the USA and 149 outside of the USA), most families reported a loss of at least some educational or healthcare services. Seventy‐four per cent of parents reported that their child lost access to at least one therapy or education service, and 36% of respondents lost access to a healthcare provider. Only 56% reported that their child received at least some continued services through tele‐education. Those that needed to access healthcare providers did so primarily through telemedicine. Telehealth (both tele‐education and telemedicine) was reported to be helpful when available, and caregivers most often endorsed a need for an augmentation of these remote delivery services, such as 1:1 videoconference sessions, as well as increased access to 1:1 aides in the home.ConclusionsCOVID‐19 restrictions have greatly affected access to services for individuals with syndromic IDDs. Telehealth may provide opportunities for delivery of care and education in a sustainable way, not only as restrictions endure but also after they have been lifted.
Three‐dimensional neuron–astrocyte construction on matrigel enhances establishment of functional voltage‐gated sodium channels
Authors: Karahuseyinoglu Sercin , Sekerdag Emine , Aria Mohammad Mohammadi , Cetin Tas Yagmur , Nizamoglu Sedat , Solaroglu Ihsan , Gürsoy‐Özdemir Yasemin 
Published: September 2020

AbstractThis study aimed to investigate and compare cell growth manners and functional differences of primary cortical neurons cultured on either poly‐d‐lysine (PDL) and or Matrigel, to delineate the role of extracellular matrix on providing resemblance to in vivo cellular interactions in nervous tissue. Primary cortical neurons, obtained from embryonic day 15 mice pups, seeded either on PDL‐ or Matrigel‐coated culture ware were investigated by DIC/bright field and fluorescence/confocal microscopy for their morphology, 2D and 3D structure, and distribution patterns. Patch clamp, western blot, and RT‐PCR studies were performed to investigate neuronal firing thresholds and sodium channel subtypes Nav1.2 and Nav1.6 expression. Cortical neurons cultured on PDL coating possessed a 2D structure composed of a few numbers of branched and tortuous neurites that contacted with each other in one to one manner, however, neurons on Matrigel coating showed a more complicated dimensional network that depicted tight, linear axonal bundles forming a 3D interacted neuron–astrocyte construction. This difference in growth patterns also showed a significant alteration in neuronal firing threshold which was recorded between 80 < Iinj > 120 pA on PDL and 2 < Iinj > 160 pA on Matrigel. Neurons grown up on Matrigel showed increased levels of sodium channel protein expression of Nav1.2 and Nav1.6 compared to neurons on PDL. These results have demonstrated that a 3D interacted neuron–astrocyte construction on Matrigel enhances the development of Nav1.2 and Nav1.6 in vitro and decreases neuronal firing threshold by 40 times compared to conventional PDL, resembling in vivo neuronal networks and hence would be a better in vitro model of adult neurons.
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