bluuebunny/crossref_metadata_2025_split huggingface dataset:
Scorpion toxin inhibits the voltage‐gated proton channel using a Zn2+‐like long‐range conformational coupling mechanism
Authors: Tang Dongfang , Yang Yuqin , Xiao Zhen , Xu Jiahui , Yang Qiuchu , Dai Han , Liang Songping , Tang Cheng , Dong Hao , Liu Zhonghua 
Published: January 2020

Background and PurposeBlocking the voltage‐gated proton channel HV1 is a promising strategy for the treatment of diseases like ischaemia stroke and cancer. However, few HV1 channel antagonists have been reported. Here, we have identified a novel HV1 channel antagonist from scorpion venom and have elucidated its action mechanism.Experimental ApproachHV1 and NaV channels were heterologously expressed in mammalian cell lines and their currents recorded using whole‐cell patch clamp. Site‐directed mutagenesis was used to generate mutants. Toxins were recombinantly produced in Escherichia coli. AGAP/W38F‐HV1 interaction was modelled by molecular dynamics simulations.Key ResultsThe scorpion toxin AGAP (anti‐tumour analgesic peptide) potently inhibited HV1 currents. One AGAP mutant has reduced NaV channel activity but intact HV1 activity (AGAP/W38F). AGAP/W38F inhibited HV1 channel activation by trapping its S4 voltage sensor in a deactivated state and inhibited HV1 currents with less pH dependence than Zn2+. Mutation analysis showed that the binding pockets of AGAP/W38F and Zn2+ in HV1 channel partly overlapped (common sites are His140 and His193). The E153A mutation at the intracellular Coulombic network (ICN) in HV1 channel markedly reduced AGAP/W38F inhibition, as observed for Zn2+. Experimental data and MD simulations suggested that AGAP/W38F inhibited HV1 channel using a Zn2+‐like long‐range conformational coupling mechanism.Conclusion and ImplicationsOur results suggest that the Zn2+ binding pocket in HV1 channel might be a hotspot for modulators and valuable for designing HV1 channel ligands. Moreover, AGAP/W38F is a useful molecular probe to study HV1 channel and a lead compound for drug development.
Tetramethylpyrazine: A promising drug for the treatment of pulmonary hypertension
Authors: Chen Yuqin , Lu Wenju , Yang Kai , Duan Xin , Li Mengxi , Chen Xiuqing , Zhang Jie , Kuang Meidan , Liu Shiyun , Wu Xiongting , Zou Guofa , Liu Chunli , Hong Cheng , He Wenjun , Liao Jing , Hou Chi , Zhang Zhe , Zheng Qiuyu , Chen Jiyuan , Zhang Nuofu , Tang Haiyang , Vanderpool Rebecca R. , Desai Ankit A. , Rischard Franz , Black Stephen M. , Garcia Joe G.N. , Makino Ayako , Yuan Jason X.‐J. , Zhong Nanshan , Wang Jian 
Published: January 2020

Background and PurposeTetramethylpyrazine (TMP) was originally isolated from the traditional Chinese herb ligusticum and the fermented Japanese food natto and has since been synthesized. TMP has a long history of beneficial effects in the treatment of many cardiovascular diseases. Here we have evaluated the therapeutic effects of TMP on pulmonary hypertension (PH) in animal models and in patients with pulmonary arterial hypertension (PAH) or chronic thromboembolic pulmonary hypertension (CTEPH).Experimental ApproachThree well‐defined models of PH ‐chronic hypoxia (10% O2)‐induced PH (HPH), monocrotaline‐induced PH (MCT‐PH) and Sugen 5416/hypoxia‐induced PH (SuHx‐PH) ‐ were used in Sprague‐Dawley rats, and assessed by echocardiography, along with haemodynamic and histological techniques. Primary cultures of rat distal pulmonary arterial smooth muscle cells (PASMCs) were used to study intracellular calcium levels. Western blots and RT‐qPCR assays were also used. In the clinical cohort, patients with PAH or CTEPH were recruited. The effects of TMP were evaluated in all systems.Key ResultsTMP (100 mg·kg−1·day−1) prevented rats from developing experimental PH and ameliorated three models of established PH: HPH, MCT‐PH and SuHx‐PH. The therapeutic effects of TMP were accompanied by inhibition of intracellular calcium homeostasis in PASMCs. In a small cohort of patients with PAH or CTEPH, oral administration of TMP (100 mg, t.i.d. for 16 weeks) increased the 6‐min walk distance and improved the 1‐min heart rate recovery.Conclusion and ImplicationsOur results suggest that TMP is a novel and inexpensive medication for treatment of PH. Clinical trial is registered with www.chictr.org.cn (ChiCTR‐IPR‐14005379).
MicroRNA‐92b‐3p is a prognostic oncomiR that targets TSC1 in clear cell renal cell carcinoma
Authors: Wang Cong , Uemura Motohide , Tomiyama Eisuke , Matsushita Makoto , Koh Yoko , Nakano Kosuke , Hayashi Yujiro , Ishizuya Yu , Jingushi Kentaro , Kato Taigo , Hatano Koji , Kawashima Atsunari , Ujike Takeshi , Nagahara Akira , Fujita Kazutoshi , Imamura Ryoichi , Tsujikawa Kazutake , Nonomura Norio 
Published: January 2020

AbstractAlthough several studies have reported that microRNA (miR)‐92b‐3p is involved in various cellular processes related to carcinogenesis, its physiological role in clear cell renal cell carcinoma (ccRCC) remains unclear. To clarify the role of miR‐92b‐3p in ccRCC, we compared miR‐92b‐3p expression levels in ccRCC tissues and adjacent normal renal tissues. Significant upregulation of miR‐92b‐3p was observed in ccRCC tissues. Overexpression of miR‐92b‐3p using a miRNA mimic promoted proliferation, migration, and invasion activities of ACHN cells. Functional inhibition of miR‐92b‐3p by a hairpin miRNA inhibitor suppressed Caki‐2 cell growth and invasion activities in vitro. Mechanistically, it was found that miR‐92b‐3p directly targeted the TSC1 gene, a known upstream regulator of mTOR. Overexpression of miR‐92b‐3p decreased the protein expression of TSC1 and enhanced the downstream phosphorylation of p70S6 kinase, suggesting that the mTOR signaling pathway was activated by miR‐92b‐3p in RCC cells. Importantly, a multivariate Cox proportion hazard model, based on TNM staging and high levels of miR‐92b‐3p, revealed that miR‐92b‐3p expression (high vs. low hazard ratio, 2.86; 95% confidence interval, 1.20‐6.83; P = .018) was a significant prognostic factor for overall survival of ccRCC patients with surgical management. Taken together, miR‐92b‐3p was found to act as an oncomiR, promoting cell proliferation by downregulating TSC1 in ccRCC.
Reliability and Validity of an Adapted and Translated Version of the Mullen Scales of Early Learning (AT‐MSEL) in Rural Guatemala
Authors: Colbert Alison M. , Lamb Molly M. , Asturias Edwin J. , Muñoz Flor M. , Bauer Desirée , Arroyave Paola , Hernández Sara , Martínez Maria Alejandra , Paniagua‐Avila Alejandra , Olson Daniel , Calvimontes D. Mirella , Bolaños Guillermo A. , El Sahly Hana M. , Connery Amy K. 
Published: January 2020

AbstractBackgroundA growing literature base supports the use of tests developed in high‐income countries to assess children in low resource settings when carefully translated, adapted, and applied. Evaluation of psychometric properties of adapted and translated measures within populations is necessary. The current project sought to evaluate the reliability and validity of an adapted and translated version of the Mullen Scales of Early Learning (AT‐MSEL) in rural Guatelama.MethodsThe reliability and validity of the AT‐MSEL in rural Guatemala were analyzed for children ages 0–5 years.ResultsInterrater reliability coefficients (ICC = 0.99–1.0) and internal consistency (Cronbach's alpha = 0.91–0.93) were excellent for all subscales. General linear models utilizing paired data showed consistency between standard scores (p < 0.0001). Mean raw scores increased with chronological age, as expected. Across age groups, subscales were significantly, positively correlated with one another (p < 0.05 ‐ < 0.001) with one exception, visual reception and expressive language at the 0–10 month age range (p = 0.43).ConclusionsThe AT‐ MSEL showed strong psychometric properties in a sample of young children in rural Guatemala. Findings demonstrate that the AT‐MSEL can be used validly and reliably within this specific population of children. This work supports the concept that tests developed in high‐income countries can be used to assess children in low resource settings when carefully translated, adapted and applied.
Automatic speaker recognition from speech signal using bidirectional long‐short‐term memory recurrent neural network
Authors: Devi Kharibam Jilenkumari , Thongam Khelchandra 
Published: January 2020

AbstractSpeaker recognition is a major challenge in various languages for researchers. For programmed speaker recognition structure prepared by utilizing ordinary speech, shouting creates a confusion between the enlistment and test, henceforth minimizing the identification execution as extreme vocal exertion is required during shouting. Speaker recognition requires more time for classification of data, accuracy is optimized, and the low root‐mean‐square error rate is the major problem. The objective of this work is to develop an efficient system of speaker recognition. In this work, an improved method of Wiener filter algorithm is applied for better noise reduction. To obtain the essential feature vector values, Mel‐frequency cepstral coefficient feature extraction method is used on the noise‐removed signals. Furthermore, input samples are created by using these extracted features after the dimensions have been reduced using probabilistic principal component analysis. Finally, recurrent neural network‐bidirectional long‐short‐term memory is used for the classification to improve the prediction accuracy. For checking the effectiveness, the proposed work is compared with the existing methods based on accuracy, sensitivity, and error rate. The results obtained with the proposed method demonstrate an accuracy of 95.77%.
Subsidizing extinction?
Authors: Dempsey Jessica , Martin Tara G , Sumaila U. Rashid 
Published: January 2020

AbstractIn 2010 world governments agreed to eliminate, phase out or reform incentives that harm biodiversity by 2020. Yet few governments have even identified such incentives, never mind taking action on them. While some subsidies are well studied, such as in fisheries and fossil fuel production, there is an urgent need for the conservation community to study the potential effects a broader array of subsidies have on biodiversity. In addition, we need a better understanding of who benefits from these subsidies. We term this pursuit ‘subsidy accountability’, which is crucial but challenging work crossing disciplines and government ministries. It requires ecologists, forensic accountants, and policy wonks, calculating and forecasting the positive and negative effects of subsidies and their elimination on biodiversity and vulnerable human populations. The Intergovernmental Panel for Biodiversity and Ecosystem Services recently concluded that action on biodiversity loss requires transformative economic change; true action on subsidies is one step towards such change.
Biogeography and anthropogenic impact shape the success of invasive wasps on New Zealand's offshore islands
Authors: Schmack Julia M. , Schleuning Matthias , Ward Darren F. , Beggs Jacqueline R. 
Published: January 2020

AbstractAimThe theory of island biogeography predicts that the susceptibility of an island to invasion is determined by its isolation and size. However, many island ecosystems have been intensely modified by humans. Here, we investigated the biogeographic, biotic and anthropogenic drivers of invasive social wasps on 36 offshore islands.LocationIslands off the east coast of New Zealand's North Island.TaxaVespula germanica(Fabricius, 1793),Vespula vulgaris(Linnaeus, 1758) andPolistes chinensis antennalis(Fabricius, 1793), Polistes humilis(Fabricius, 1781).MethodsWe used GIS software for in situ randomization of plots on each island (36 islands, 409 plots) and conducted 5‐min wasp counts to estimate wasp abundance. Wasp abundance and canopy cover were recorded at each plot. Island isolation was measured using GIS software. Data on island size, human settlement and the presence of introduced rats (Rattusspp.) were collated from the literature and island managers. The number of boat docks per island was counted from satellite images. A generalized linear mixed‐effect model (GLMM) was fitted to identify drivers ofVespulaandPolistesabundance on offshore islands.ResultsThe abundance ofVespulawas negatively correlated with island isolation and canopy cover, yet positively correlated with island size.Vespulawere also more abundant on islands that have been settled by humans. The abundance ofPolisteswas negatively correlated with canopy cover. Finally, results did not support the notion that invasive wasps were associated with introduced rats on New Zealand's offshore islands.ConclusionsOur findings highlight the importance of biogeographic factors, such as island size and isolation, for species invasions, and suggest that intact forest cover could contribute to biotic resistance to invasive wasps in island ecosystems. Studies of invasive species should consider the joint effects of biogeographic, biotic and anthropogenic factors to best inform conservation management.
Assessing participation of children with acquired brain injury and cerebral palsy: a systematic review of measurement properties
Authors: Resch Christine , Van Kruijsbergen Mette , Ketelaar Marjolijn , Hurks Petra , Adair Brooke , Imms Christine , De Kloet Arend , Piskur Barbara , Van Heugten Caroline 
Published: January 2020

AimTo examine which instruments used to assess participation of children with acquired brain injury (ABI) or cerebral palsy (CP) align with attendance and/or involvement constructs of participation; and to systematically review measurement properties of these instruments in children with ABI or CP, to guide instrument selection.MethodFive databases were searched. Instruments that quantified ‘attendance’ and/or ‘involvement’ aspects of participation according to the family of participation‐related constructs were selected. Data on measurement properties were extracted and methodological quality of the studies assessed.ResultsThirty‐seven instruments were used to assess participation in children with ABI or CP. Of those, 12 measured attendance and/or involvement. The reliability, validity, and responsiveness of eight of these instruments were examined in 14 studies with children with ABI or CP. Sufficient measurement properties were reported for most of the measures, but no instrument had been assessed on all relevant properties. Moreover, most psychometric studies have marked methodological limitations.InterpretationInstruments to assess participation of children with ABI or CP should be selected carefully, as many available measures do not align with attendance and/or involvement. Evidence for measurement properties is limited, mainly caused by low methodological study quality. Future studies should follow recommended methodological guidelines.What this paper adds

Twelve instruments used to assess participation of children with acquired brain injury (ABI) or cerebral palsy (CP) aligned with attendance/involvement.

Seven instruments have some psychometric evidence supporting their use with children with CP.

For children with ABI, only the Child and Adolescent Scale of Participation has shown preliminary evidence of measurement properties.
Thinking ecologically about clinical education in dentistry
Authors: Perez Arnaldo , Green Jacqueline L. , Compton Sharon M. , Patterson Steven , Senior Anthea 
Published: January 2020

AbstractTraditional approaches to clinical education (CE) in dentistry have primarily focused on the needs and interests of students (student‐centred), patients (patient‐centred) or individuals receiving care (person‐centred). Research has shown that giving priority to the interests of one stakeholder (eg students) may negatively affect the interests of others (eg patients, instructors and administrators). In this commentary, we discuss some limitations of traditional approaches to CE and suggest an eco‐centred approach that assumes that the interests of all stakeholders must be considered when planning CE due to the interdependent relationships between stakeholders. A description of this new approach is provided, whilst research and innovation are encouraged to develop an ecologically informed system of CE.
Assessment of the immunocrit method to detect failure of passive immunity in newborn foals
Authors: Mortola Eduardo , Miceli Graciela , Alarcon Laura , Azcurra Mirian , Larsen Alejandra 
Published: January 2020

AbstractBackgroundIn newborn foals the absorption of colostrum immunoglobulins in the small intestine is maximal up to 8 hours after birth and then progressively decreases to become null after 24 hours post‐partum. Thus, equine practitioners need a simple, quick, inexpensive and reliable field test to identify foals affected by failure of passive transfer rather than an accurate method yielding quantitative results within the whole range of immunoglobulin concentrations.ObjectiveAs the validity of the immunocrit method to detect failure of passive transfer in foals had not been evaluated before, the objective of this study was to test the ability of this method to detect the concentration of immunoglobulins in a large number of foal serum samples.Study designAssay validation using samples collected for clinical purposes.MethodsThe immunocrit test, using a 40% ammonium sulphate solution, was used to measure the concentration of immunoglobulins in serum samples from 211 newborn Thoroughbred foals. The results were compared, by statistical analysis, with those of agarose gel electrophoresis, a reference quantitative method.ResultsThe values obtained by the immunocrit method were significantly correlated (R = .871;P < .001) with those measured by agarose gel electrophoresis. A cut‐off value of 8 g/L of serum immunoglobulins by agarose gel electrophoresis and its equivalent of 9.5% for the immunocrit test was indicative of failure of passive transfer. The sensitivity and specificity of the immunocrit method at this cut‐off point were 94% (95% CI, 90‐97.3) and 82% (95% CI, 72.13‐91.8) respectively.Main limitationsVariable times of sample extraction after colostrum suckling, over the study period.ConclusionsThe immunocrit test provides a quantitative, quick, inexpensive, reliable and objective method to detect failure of passive transfer of maternal immunity in newborn foals, which is easy to perform directly in horse farms, with minimum laboratory equipment.
Recovery quality following a single post‐anaesthetic dose of dexmedetomidine or romifidine in sevoflurane anaesthetised horses
Authors: Hector Rachel C. , Rezende Marlis L. , Mama Khursheed R. , Hess Ann M. 
Published: January 2020

AbstractBackgroundPost‐anaesthetic sedation is administered to horses to improve recovery quality from inhalant anaesthesia and reduce the risk of catastrophic injury. A single dose of dexmedetomidine for this purpose has not been evaluated clinically.ObjectivesTo determine whether dexmedetomidine improves recovery quality from sevoflurane anaesthesia compared to a previously studied dose of romifidine.Study designProspective, randomised, masked clinical trial.MethodsNinety‐nine, adult, client‐owned horses anaesthetised for elective procedures completed the trial. Anaesthetic protocol was standardised. Horses were randomly assigned to receive either dexmedetomidine 1 mcg/kg bwt (D) or romifidine 20 mcg/kg bwt (R) intravenously at their first spontaneous breath in recovery. Recoveries were reviewed and independently assigned subjective visual analogue scale (VAS) scores (0‐100 mm, worst to best) for overall quality and standing ataxia scores (1‐4, none to severe) by two anaesthesiologists blinded to treatment group. Objective anaesthesia and recovery data were also recorded. Comparisons were made using the Chi‐square, Wilcoxon rank sum, linear models or Welch‐Satterthwaite two‐samplet‐test (P ≤ .05). Predictors of VAS score were analysed independent of treatment group.ResultsThere were no significant differences between groups except end‐tidal sevoflurane (FE´Sevo) concentration and post‐induction extra ketamine dosing. Including FE´Sevo and additional ketamine in the analysis as covariates, VAS scores and time to standing were not significantly different between groups. Increased age, not receiving a nerve block, increased duration of hypotension, and having a nervous temperament were significant predictors of VAS score.Main limitationsNo universal recovery scale exists for inter‐study comparisons.ConclusionsAfter sevoflurane anaesthesia, sedation with dexmedetomidine or romifidine provides clinically similar recovery time and quality.
Meta‐analysis of global livestock urine‐derived nitrous oxide emissions from agricultural soils
Authors: López‐Aizpún Maria , Horrocks Claire A. , Charteris Alice F. , Marsden Karina A. , Ciganda Veronica S. , Evans Jess R. , Chadwick David R. , Cárdenas Laura M. 
Published: January 2020

AbstractNitrous oxide (N2O) is an air pollutant of major environmental concern, with agriculture representing 60% of anthropogenic global N2O emissions. Much of the N2O emissions from livestock production systems result from transformation of N deposited to soil within animal excreta. There exists a substantial body of literature on urine patch N2O dynamics, we aimed to identify key controlling factors influencing N2O emissions and to aid understanding of knowledge gaps to improve GHG reporting and prioritize future research. We conducted an extensive literature review and random effect meta‐analysis (using REML) of results to identify key relationships between multiple potential independent factors and global N2O emissions factors (EFs) from urine patches. Mean air temperature, soil pH and ruminant animal species (sheep or cow) were significant factors influencing the EFs reviewed. However, several factors that are known to influence N2O emissions, such as animal diet and urine composition, could not be considered due to the lack of reported data. The review highlighted a widespread tendency for inadequate metadata and uncertainty reporting in the published studies, as well as the limited geographical extent of investigations, which are more often conducted in temperate regions thus far. Therefore, here we give recommendations for factors that are likely to affect the EFs and should be included in all future studies, these include the following: soil pH and texture; experimental set‐up; direct measurement of soil moisture and temperature during the study period; amount and composition of urine applied; animal type and diet; N2O emissions with a measure of uncertainty; data from a control with zero‐N application and meteorological data.