bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multidrug therapy with terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India: Results of a randomized pragmatic trial
Authors: Singh Sanjay , Jha Bandana , Shukla Prakriti , Anchan Vinayak N 
Published: August 2019

AbstractBackgroundTreatment responsiveness of tinea has decreased considerably in recent past in India. We tested effectiveness of oral terbinafine daily plus fluconazole weekly (TFw) and terbinafine daily plus fluconazole daily (TFd) versus oral terbinafine daily (T) in tinea corporis, tinea cruris and tinea faciei in a pragmatic randomized open trial.MethodsOne hundred and seventeen microscopy confirmed patients were allocated to T (6 mg/kg/day), TFw (terbinafine 6 mg/kg/day+fluconazole 12 mg/kg once weekly), or TFd (terbinafine 6 mg/kg/day+fluconazole 6 mg/kg/day) groups by concealed randomization and treated for 8 weeks or cure. Each group included 39 patients.ResultsAt 4 weeks, 9 (23.1%), 8 (20.5%) and 14 (35.9%) patients were cured in T, TFw and TFd groups, respectively (P=0.279). At 8 weeks, number of patients cured was as follows: T 13 (33.3%), TFw 18 (46.2%) and TFd 25 (64.1%). TFd was more effective than T (P=0.012), other comparisons were not significantly different. However, effect size as calculated by number needed to treat (NNT) (versus terbinafine) was 8 for TFw and 4 for TFd. Relapse rates one month after cure were similar in all groups (P=0.664).ConclusionsIn view of cure rates and NNT, terbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India.One Sentence SummaryTerbinafine plus daily fluconazole is more effective than terbinafine alone or terbinafine plus weekly fluconazole in current epidemic of altered dermatophytosis in India.
Characterization of the gut microbiota in the Anjak (Schizocypris altidorsalis), a native fish species of Iran
Authors: Ghanbari Mahdi , Jami Mansooreh , Shahraki Hadi , Domig Konrad J. 
Published: August 2019

AbstractThe antiquity, diversity and dietary variations among fish species present an exceptional opportunity for understanding the variety and nature of symbioses in vertebrate gut microbial communities. In this study for the first time the composition of the gut bacterial communities in the anjak was surveyed by 16S rRNA gene 454-pyrosequencing. Anjak (Schizocypris altidorsalis), is a native benthopelagic and commercially important fish species in Hamun Lake and Hirmand River system in Sistan basin, Iran. Thirteen 16S rRNA PCR libraries were generated, representing 13 samples of Anjak gut microbiota. After quality filtering, a total of 137 978 read pairs remained from the V3–V6 16S rRNA gene regions, each measuring 680 bp, and were assigned to bacterial OTU’s at a minimum sequence homology of 97%, resulted in total 608 OTUs. The results provided evidence of the presence of a very diverse microbial community present in this fish. The majority of sequences belonged to members of the Firmicutes; however, members of the Proteobacteria, Tenericutes, Bacteroidetes and Cyanobacteria were also well represented in the anjak gut microbiota. The most abundant classes recorded in the samples were uncultured CK-1C4-19 class of Tenericutes, Flavobacteriia, α-Proteobacteria, Erysipelotrichi, Synechococcophycideae, γ-Proteobacteria, and Clostridia. The presence of many different types of bacteria in the anjak is not unexpected since it has been shown that eukaryotes with a detritivorous and planktivorous diet have a higher microbial diversity compared to omnivorous and herbivorous fish species. Many of these microbes might be of high physiological relevance for snow trout and may play key roles in the functioning of a healthy gut in this fish.
Exploring the microbial diversity in oil-contaminated mangrove sediments using 16S rRNA metagenomics
Authors: Ghanbari Mahdi , Jami Mansooreh , Moghadam Mohsen Shahriari , Domig Konrad J. 
Published: August 2019

AbstractWith an area of 390 hectares, the mangrove forests of Nayband Bay are the widest mangrove communities above 27 degrees latitude in the Persian Gulf. They are the last dense, extensive structures of these ecosystems found in the north-west Indian Ocean. Growing industrial activities near the Nayband Bay and the consequent marine pollution has resulted in damage and threatened different marine habitats in recent years. To date, a comprehensive description of the microbial life in the mangrove ecosystem that has been exposed to oil contamination is lacking. This information could significantly contribute to a better overview of the function and resilience of the ecosystem. This work represents a first effort to better understand the Nayband Bay mangrove microbiology by applying 16S rRNA metagenomics. A total of 65,408 readings from the V3–V4 16S rRNA gene regions were obtained from 24 sediment samples, each measuring 440 bp. Most sequences belonged to members of the Proteobacteria phylum (mainly γ-Proteobacteria); however, members of the Bacteroidetes phylum (mainly Flavobacteriia) were also well represented in the samples. We discovered that the community of this ecosystem strongly exhibit typical structures of oil-contaminated marine environments. This is likely due to the growing industrial activity in the area and its consequent marine polluting effects. The use of practicable and applicable bioremediation protocols for habitat restoration in this valuable area is needed.
Does meiotic drive alter male mate preference?
Authors: Finnegan Sam Ronan , Nitsche Leslie , Mondani Matteo , Camus M. Florencia , Fowler Kevin , Pomiankowski Andrew 
Published: August 2019

AbstractMale mate preferences have been demonstrated across a range of species, including the Malaysian stalk-eyed fly,Teleopsis dalmanni. This species is subject to SR, an X-linked male meiotic driver, that causes the dysfunction of Y-sperm and the production all female broods. SR is associated with a low frequency inversion spanning most of the X chromosome that causes reduced organismal fitness. While there has been work considering female avoidance of meiotic drive males, the mating decisions of drive-bearing males have not been considered previously. As drive males are of lower genetic quality they may be less able to bear the cost of choice or may experience weaker selection for its maintenance if they are avoided by females. We investigated preference of drive males using binary choice trials. We confirmed that males prefer to mate with large females (indicative of greater fecundity) but found no evidence that the strength of male mate preference differs between drive and standard males. This suggests that the cost of choice does not restrict male reference among drive males. In a further experiment, we found that large eyespan males showed strong preference whereas small eyespan males showed no preference. This is likely to weaken mate preference in drive males, as on average they have reduced eyespan compared to standard males. In this respect, drive males are subject to and exert weak sexual selection.Lay summaryWe studied male mate preference in stalk-eyed flies. This species suffers from meiotic drive, a selfish genetic element that causes a reduction in sperm production and organismal fitness. We predicted that males with meiotic drive would show weak mate preference. Males preferred to mate with large females, but there was no difference in the strength of preference between drive and non-drive males. Males with larger eyespan showed stronger mate preference. Meiotic drive males usually have reduced eyespan so on average they exert weaker sexual selection on females, but this is mediated by eyespan, not genotypeper se.
Base-resolution models of transcription factor binding reveal soft motif syntax
Authors: Avsec Žiga , Weilert Melanie , Shrikumar Avanti , Krueger Sabrina , Alexandari Amr , Dalal Khyati , Fropf Robin , McAnany Charles , Gagneur Julien , Kundaje Anshul , Zeitlinger Julia 
Published: August 2019

SummaryThe arrangement of transcription factor (TF) binding motifs (syntax) is an important part of the cis-regulatory code, yet remains elusive. We introduce a deep learning model, BPNet, that uses DNA sequence to predict base-resolution ChIP-nexus binding profiles of pluripotency TFs. We develop interpretation tools to learn predictive motif representations and identify soft syntax rules for cooperative TF binding interactions. Strikingly, Nanog preferentially binds with helical periodicity, and TFs often cooperate in a directional manner, which we validate using CRISPR-induced point mutations. Our model represents a powerful general approach to uncover the motifs and syntax of cis-regulatory sequences in genomics data.HighlightsThe neural network BPNet accurately predicts TF binding data at base-resolution.Model interpretation discovers TF motifs and TF interactions dependent on soft syntax.Motifs for Nanog and partners are preferentially spaced at ∼10.5 bp periodicity.Directional cooperativity is validated: Sox2 enhances Nanog binding, but not vice versa.
Ancestral hybridisation facilitated species diversification in the Lake Malawi cichlid fish adaptive radiation
Authors: Svardal Hannes , Quah Fu Xiang , Malinsky Milan , Ngatunga Benjamin P , Miska Eric A , Salzburger Walter , Genner Martin J , Turner George F , Durbin Richard 
Published: August 2019

AbstractThe adaptive radiation of cichlid fishes in East Afrian Lake Malawi encompasses over 500 species that are believed to have evolved within the last 800 thousand years from a common founder population. It has been proposed that hybridisation between ancestral lineages can provide the genetic raw material to fuel such exceptionally high diversification rates, and evidence for this has recently been presented for the Lake Victoria Region cichlid superflock. Here we report that Lake Malawi cichlid genomes also show evidence of hybridisation between two lineages that split 3-4 million years ago, today represented by Lake Victoria cichlids and the riverine Astatotilapia sp. ‘ruaha blue’. The two ancestries in Malawi cichlid genomes are present in large blocks of several kilobases, but there is little variation in this pattern between Malawi cichlid species, suggesting that the large-scale mosaic structure of the genomes was largely established prior to the radiation. Nevertheless, tens of thousands of polymorphic variants apparently derived from the hybridisation are interspersed in the genomes. These loci show a striking excess of differentiation across ecological subgroups in the Lake Malawi cichlid assemblage, and parental alleles sort differentially into benthic and pelagic Malawi cichlid lineages, consistent with strong differential selection on these loci during species divergence. Furthermore, these loci are enriched for genes involved in immune response and vision, including opsin genes previously identified as important for speciation. Our results reinforce the role of ancestral hybridisation in explosive diversification by demonstrating its significance in one of the largest recent vertebrate adaptive radiations.
Pod and seed trait QTL identification to assist breeding for peanut market preferences
Authors: Chavarro Carolina , Chu Ye , Holbrook Corley , Isleib Thomas , Bertioli David , Hovav Ran , Butts Christopher , Lamb Marshall , Sorensen Ronald , Jackson Scott A. , Ozias-Akins Peggy 
Published: August 2019

ABSTRACTAlthough seed and pod traits are important for peanut breeding, little is known about the inheritance of these traits. A recombinant inbred line (RIL) population of 156 lines from a cross of Tifrunner x NC 3033 was genotyped with the Axiom_Arachis1 SNP array and SSRs to generate a genetic map composed of 1524 markers in 29 linkage groups (LG). The genetic positions of markers were compared with their physical positions on the peanut genome to confirm the validity of the linkage map and explorethe distribution of recombination and potential chromosomal rearrangements. These traits were phenotyped over three consecutive years for the purpose of developing trait-associated markers for breeding. Forty-nine QTL were identified in 14 LG for seed size index, kernel percentage, seed weight, pod weight, single-kernel, double-kernel, pod area and pod density. Twenty QTL demonstrated phenotypic variance explained (PVE) greater than 10% and eight more than 20%. Of note, seven of the eight major QTL for pod area, pod weight and seed weight (PVE >20% variance) were attributed to NC 3033 and located in a single linkage group, LG B06_1. In contrast, the most consistent QTL for kernel percentage were located on A07/B07 and derived from Tifrunner.
Heart Rate n-Variability (HRnV) and Its Application to Risk Stratification of Chest Pain Patients in the Emergency Department
Authors: Liu Nan , Guo Dagang , Koh Zhi Xiong , Ho Andrew Fu Wah , Xie Feng , Tagami Takashi , Sakamoto Jeffrey Tadashi , Pek Pin Pin , Chakraborty Bibhas , Lim Swee Han , Tan Jack Wei Chieh , Ong Marcus Eng Hock 
Published: August 2019

AbstractBackgroundChest pain is one of the most common complaints among patients presenting to the emergency department (ED). Causes of chest pain can be benign or life threatening, making accurate risk stratification a critical issue in the ED. In addition to the use of established clinical scores, prior studies have attempted to create predictive models with heart rate variability (HRV). In this study, we proposed heart rate n-variability (HRnV), an alternative representation of beat-to-beat variation in electrocardiogram (ECG) and investigated its association with major adverse cardiac events (MACE) for ED patients with chest pain.MethodsWe conducted a retrospective analysis of data collected from the ED of a tertiary hospital in Singapore between September 2010 and July 2015. Patients >20 years old who presented to the ED with chief complaint of chest pain were conveniently recruited. Five to six-minute single-lead ECGs, demographics, medical history, troponin, and other required variables were collected. We developed the HRnV-Calc software to calculate HRnV parameters. The primary outcome was 30-day MACE, which included all-cause death, acute myocardial infarction, and revascularization. Univariable and multivariable logistic regression analyses were conducted to investigate the association between individual risk factors and the outcome. Receiver operating characteristic (ROC) analysis was performed to compare the HRnV model (based on leave-one-out cross-validation) against other clinical scores in predicting 30-day MACE.ResultsA total of 795 patients were included in the analysis, of which 247 (31%) had MACE within 30 days. The MACE group was older and had a higher proportion of male patients. Twenty-one conventional HRV and 115 HRnV parameters were calculated. In univariable analysis, eleven HRV parameters and 48 HRnV parameters were significantly associated with 30-day MACE. The multivariable stepwise logistic regression identified 16 predictors that were strongly associated with the MACE outcome; these predictors consisted of one HRV, seven HRnV parameters, troponin, ST segment changes, and several other factors. The HRnV model outperformed several clinical scores in the ROC analysis.ConclusionsThe novel HRnV representation demonstrated its value of augmenting HRV and traditional risk factors in designing a robust risk stratification tool for patients with chest pain at the ED.
Two forms of Opa1 cooperate to complete fusion of the mitochondrial inner-membrane
Authors: Ge Yifan , Shi Xiaojun , Boopathy Sivakumar , McDonald Julie , Smith Adam W. , Chao Luke H. 
Published: August 2019

AbstractMitochondrial membrane dynamics is a cellular rheostat that relates metabolic function and organelle morphology. Using an in vitro reconstitution system, we describe a mechanism for how mitochondrial inner-membrane fusion is regulated by the ratio of two forms of Opa1. We found that the long-form of Opa1 (l-Opa1) is sufficient for membrane docking, hemifusion and low levels of content release. However, stoichiometric levels of the processed, short form of Opa1 (s-Opa1) work together with l-Opa1 to mediate efficient and fast membrane pore opening. Additionally, we found that excess levels of s-Opa1 inhibit fusion activity, as seen under conditions of altered proteostasis. These observations describe a mechanism for gating membrane fusion.
Mitochondrial protein interaction landscape of SS-31
Authors: Chavez Juan D. , Tang Xiaoting , Campbell Matthew D. , Reyes Gustavo , Kramer Philip A. , Stuppard Rudy , Keller Andrew , Marcinek David J. , Bruce James E. 
Published: August 2019

AbstractMitochondrial dysfunction underlies the etiology of a broad spectrum of diseases including heart disease, cancer, neurodegenerative diseases, and the general aging process. Therapeutics that restore healthy mitochondrial function hold promise for treatment of these conditions. The synthetic tetrapeptide, elamipretide (SS-31), improves mitochondrial function, but mechanistic details of its pharmacological effects are unknown. Reportedly, SS-31 primarily interacts with the phospholipid cardiolipin in the inner mitochondrial membrane. Here we utilize chemical cross-linking with mass spectrometry to identify protein interactors of SS-31 in mitochondria. The SS-31-interacting proteins, all known cardiolipin binders, fall into two groups, those involved in ATP production through the oxidative phosphorylation pathway and those involved in 2-oxoglutarate metabolic processes. Residues cross-linked with SS-31 reveal binding regions that in many cases, are proximal to cardiolipin-protein interacting regions. These results offer the first glimpse of the protein interaction landscape of SS-31 and provide new mechanistic insight relevant to SS-31 mitochondrial therapy.Significance StatementSS-31 is a synthetic peptide that improves mitochondrial function and is currently undergoing clinical trials for treatments of heart failure, primary mitochondrial myopathy, and other mitochondrial diseases. SS-31 interacts with cardiolipin which is abundant in the inner mitochondrial membrane, but mechanistic details of its pharmacological effects are unknown. Here we apply a novel chemical cross-linking/mass spectrometry method to provide the first direct evidence for specific interactions between SS-31 and mitochondrial proteins. The identified SS-31 interactors are functional components in ATP production and 2-oxoglutarate metabolism and signaling, consistent with improved mitochondrial function resultant from SS-31 treatment. These results offer the first glimpse of the protein interaction landscape of SS-31 and provide new mechanistic insight relevant to SS-31 mitochondrial therapy.
Sirolimus plus nintedanib treats vascular pathology in HHT mouse models
Authors: Ruiz Santiago , Zhao Haitian , Chandakkar Pallavi , Papoin Julien , Choi Hyunwoo , Nomura-Kitabayashi Aya , Patel Radhika , Gillen Matthew , Diao Li , Chatterjee Prodyot K. , He Mingzhu , Al-Abed Yousef , Wang Ping , Metz Christine N. , Oh S. Paul , Blanc Lionel , Campagne Fabien , Marambaud Philippe 
Published: August 2019

ABSTRACTHereditary hemorrhagic telangiectasia (HHT), a genetic bleeding disorder leading to systemic arteriovenous malformations (AVMs), is caused by loss-of-function mutations in the ALK1-ENG-Smad1/5/8 pathway. Evidence suggests that HHT pathogenesis strongly relies on overactivated PI3K-Akt-mTOR and VEGFR2 pathways in endothelial cells (ECs). In the BMP9/10-immunoblocked (BMP9/10ib) neonatal mouse model of HHT, we report here that the mTOR inhibitor, sirolimus, and the receptor tyrosine-kinase inhibitor, nintedanib, could synergistically fully block, but also reversed, retinal AVMs to avert retinal bleeding and anemia. Sirolimus plus nintedanib prevented vascular pathology in the oral mucosa, lungs, and liver of the BMP9/10ib mice, as well as significantly reduced gastrointestinal bleeding and anemia in inducible ALK1-deficient adult mice. Mechanistically, in vivo in BMP9/10ib mouse ECs, sirolimus and nintedanib blocked the overactivation of mTOR and VEGFR2, respectively. Furthermore, we found that sirolimus activated ALK2-mediated Smad1/5/8 signaling in primary ECs—including in HHT patient blood outgrowth ECs—and partially rescued Smad1/5/8 activity in vivo in BMP9/10ib mouse ECs. These data demonstrate that the combined correction of endothelial Smad1/5/8, mTOR, and VEGFR2 pathways opposes HHT pathogenesis. Repurposing of sirolimus plus nintedanib might provide therapeutic benefit in HHT patients.
Leptin promotes expression of EMT-related transcription factors and invasion in a Src and FAK-dependent pathway in MCF10A mammary epithelial cells
Authors: Olea-Flores Monserrat , Zuñiga-Eulogio Miriam , Tacuba-Saavedra Arvey , Bueno-Salgado Magdalena , Sánchez-Carvajal Andrea , Vargas-Santiago Yovani , Mendoza-Catalán Miguel A. , Salazar Eduardo Pérez , García-Hernández Alejandra , Padilla-Benavides Teresita , Navarro-Tito Napoleón 
Published: August 2019

AbstractLeptin is one of the main adipokines secreted in breast tissue, and has been associated with epithelial-mesenchymal transition (EMT) and tumor progression in breast cancer. Leptin promotes EMT, cell migration and invasion in epithelial breast cells, leading to tumor progression. However, the molecular mechanism that underlies these events is not fully understood; however, the activation of different signaling pathways appears to be essential. In this sense, the effect of leptin on the activation of kinases like Src and FAK, which regulate signaling pathways that activate the EMT program, has not been completely described. Therefore, we investigated the involvement of these kinases using anin vitromodel for leptin-induced EMT process in the non-tumorigenic MCF10A cell line. To this end, MCF10A cells were stimulated with leptin, and Src and FAK activation was assessed. Specific events occurring during EMT were also evaluated in the presence or absence of the kinases’s chemical inhibitors PP2 and PF-573228. For instance, we tested the expression and subcellular localization of the EMT-related transcription factors Twist and □-catenin, by western blot and immunofluorescence. We also evaluated the secretion and activation of matrix metalloproteases (MMP-2 and MMP-9) by gelatin zymography. Invasiveness properties of leptin-stimulated cells were determined by invadopodia formation assays, and by the transwell chamber method. Our results showed that leptin promotes EMT through Src and FAK activation, which leads to the secretion and activation of MMP-2 and MMP-9, invadopodia formation and cell invasion in MCF10A cells. In conclusion, our data suggest that leptin promotes an increase in the expression levels of Twist and □-catenin, the secretion of MMP-2, MMP-9, the invadopodia formation and invasion in MCF10A cells in a Src and FAK-dependent manner.