bluuebunny/crossref_metadata_2025_split huggingface dataset:
Polarity signaling ensures epidermal homeostasis by coupling cellular mechanics and genomic integrity
Authors: Dias Gomes Martim , Letzian Soriba , Saynisch Michael , Iden Sandra 
Published: July 2019

AbstractEpithelial homeostasis requires balanced progenitor cell proliferation and differentiation, whereas disrupting this equilibrium fosters degeneration or cancer. Here we studied how cell polarity signaling orchestrates epidermal self-renewal and differentiation. Using genetic ablation, quantitative imaging, mechanochemical reconstitution and atomic force microscopy, we find that mammalian Par3 couples genome integrity and epidermal fate through shaping keratinocyte mechanics, rather than mitotic spindle orientation. Par3 inactivation impairs RhoA activity, actomyosin contractility and viscoelasticity, eliciting mitotic failures that trigger aneuploidy, mitosis-dependent DNA damage responses, p53 stabilization and premature differentiation. Importantly, reconstituting myosin activity is sufficient to restore mitotic fidelity, genome integrity, and balanced differentiation and stratification. Collectively, this study deciphers a mechanical signaling network in which Par3 acts upstream of Rho/actomyosin contractility to promote intrinsic force generation, thereby maintaining mitotic accuracy and cellular fitness at the genomic level. Disturbing this network may compromise not only epidermal homeostasis but potentially also that of other self-renewing epithelia.
Differential mechanisms of action of the trace amines octopamine, synephrine and tyramine on the porcine coronary and mesenteric artery
Authors: Koh Andy Hsien Wei , Chess-Williams Russ , Lohning Anna Elizabeth 
Published: July 2019

AbstractTrace amines such as p-tyramine, p-octopamine and p-synephrine are found in low concentrations in animals and plants. Consumption of pre-workout supplements containing these plant-derived amines has been associated with cardiovascular side effects. The aim of this study was to determine the mechanisms of action of these trace amines on porcine isolated coronary and mesenteric arteries. Noradrenaline caused contraction of mesenteric arteries and relaxation of coronary arteries. In both tissues, all three trace amines induced contractions with similar potencies and responses were unaffected by the β-adrenoceptor antagonist propranolol (1 µM), the nitric oxide synthase inhibitor L-NNA (100 µM), or the TAAR-1 antagonist, EPPTB (100 nM). However, the contractile responses of mesenteric arteries, but not coronary arteries, were significantly reduced by depletion of endogenous noradrenaline. Mesenteric responses to all three amines were abolished in the presence of prazosin (1 µM) whereas residual contractile responses remained in the coronary artery which were inhibited by a high concentration (100 µM) of EPPTB. The results suggest complex responses of the coronary artery to the trace amines, with activity at α1-adrenoceptors and potentially TAARs other than TAAR-1. In contrast the actions of the amines on the mesenteric artery appeared to involve indirect sympathomimetic actions and direct actions on α1-adrenoceptors.
Prognostic Significance of Metabolic Parameters and Textural Features on 18F-FDG PET/CT in Invasive Ductal Carcinoma of Breast
Authors: Chang Chin-Chuan , Chen Chao-Jung , Hsu Wen-Ling , Chang Shu-Min , Huang Ying-Fong , Tyan Yu-Chang 
Published: July 2019

AbstractTo investigate the prognostic significance of metabolic parameters and texture analysis on 18F-fluorodeoxyglucose positron emission tomography/computed tomography (FDG PET/CT) in patients with breast invasive ductal carcinoma (IDC), from August 2005 to May 2015, IDC patients who had undergone pre-treatment FDG PET/CT were enrolled. The metabolic parameters, including maximal standardized uptake value of breast tumor (SUVbt) and ipsilateral axillary lymph node (SUVln), metabolic tumor volume (MTVbt) and total lesion glycolysis (TLGbt) of breast tumor, whole-body MTV (MTVwb) and whole-body TLG (TLGwb) were recorded. Nine textural features of tumor (four co-occurrence matrices and five SUV-based statistics) were measured. The prognostic significance of above parameters and clinical factors was assessed by univariate and multivariate analyses. Thirty-five patients were enrolled. Patients with low and high MTVwb had 5-year progression-free survival (PFS) of 81.0 and 14.3% (p < 0.0001). The 5-year overall survival for low and high MTVwb was 88.5% and 43.6% (p = 0.0005). Multivariate analyses showed MTVwb was an independent prognostic factor for PFS (HR: 8.29, 95% CI: 2.17–31.64, p = 0.0020). The SUV, TLG and textural features were not independently predictive. Elevated MTVwb was an independent predictor for shorter PFS in patients with breast IDC.
Screening older adults for amnestic mild cognitive impairment and early-stage Alzheimer’s disease using upper-extremity dual-tasking
Authors: Toosizadeh Nima , Ehsani Hossein , Wendel Christopher , Zamrini Edward , Connor Kathy O’ , Mohler Jane 
Published: July 2019

AbstractThe purpose of the current study was to develop an objective tool based on dual-task performance for screening early-stage Alzheimer’s disease (AD) and mild cognitive impairment (MCI of the Alzheimer’s type). Dual-task involved a simultaneous execution of a sensor-based upper-extremity function (UEF) motor task (normal or rapid speed) and a cognitive task of counting numbers backward (by ones or threes). Motor function speed and variability were recorded and compared between cognitive groups using ANOVAs, adjusted for age, gender, and body mass index. Cognitive indexes were developed using multivariable ordinal logistic models to predict the cognitive status using UEF parameters. Ninety-one participants were recruited; 35 cognitive normal (CN, age = 83.8 ± 6.9), 34 MCI (age = 83.9 ± 6.6), and 22 AD (age = 84.1 ± 6.1). Flexion number and sensor-based motion variability parameters, within the normal pace elbow flexion, showed significant between-group differences (maximum effect size of 1.10 for CN versus MCI and 1.39 for CN versus AD, p < 0.0001). Using these parameters, the cognitive status (both MCI and AD) was predicted with a receiver operating characteristic area under curve of 0.83 (sensitivity = 0.82 and specificity = 0.72). Findings suggest that measures of motor function speed and accuracy within a more practical upper-extremity test (instead of walking) may provide enough complexity for cognitive impairment assessment.
The influence of dilute aluminum and molybdenum on stacking fault and twin formation in FeNiCoCr-based high entropy alloys based on density functional theory
Authors: Yu Peijun , Zhuang Yu , Chou Jyh-Pin , Wei Jie , Lo Yu-Chieh , Hu Alice 
Published: July 2019

AbstractStacking faults, as defects of disordered crystallographic planes, are one of the most important slipping mechanisms in the commonly seen lattice, face-centered cubic (FCC). Such defects can initiate twinning which strengthens mechanical properties, e.g. twinning-induced plasticity (TWIP), of high entropy alloys (HEAs) at cryogenic temperatures. In this work, by using density functional theory (DFT), the twinning initiated from stacking faults is discussed with regard to two different solute elements, Al and Mo, in the FeNiCoCr HEAs. Our results show that adding aluminum (Al) has noticeable enhancement of twinnability while molybdenum (Mo) only induces more stacking faults in the FeNiCoCr-based HEAs.
Taxonomy of Arabian Temnothorax Mayr (Formicidae: Myrmicinae) with description of a new species enhanced by x-ray microtomography
Authors: Sharaf Mostafa R. , Aldawood Abdulrahman S. , Economo Evan P. , Wachkoo Aijaz Ahmad , Hita Garcia Francisco 
Published: July 2019

AbstractTemnothorax elmenshawyisp. n., a new ant species from the Asir Mountains of the southwestern region of the Kingdom of Saudi Arabia, is described based on the worker caste. The new species is a member of theT. exilisspecies group and is distinguished from the other species included in this group by the impressed metanotal groove, the short, acute and broadly-based propodeal spines, the finely punctate posterior half of cephalic surface, and absence of a median clypeal carina. Despite extensive collecting by the authors at the type locality, only two specimens are available for description, suggesting that this species may be rare and likely endemic to the Asir Mountains. The species description is complemented by still images of volume renderings of a 3D model and a 3D rotation video of the holotype based on x-ray microtomography (micro-CT), allowing remote in-depth examination of the specimen. The virtual micro-CT data is provided as cybertype dataset and freely available onlinehttps://doi.org/10.5061/dryad.4gg39k6, as well as 3D surface model (Sketchfab.com, https://skfb.ly/6HYRz). An updated identification key to the Arabian species is presented.
Transformation of normal cells by aberrant activation of YAP via cMyc with TEAD
Authors: Nishimoto Masazumi , Uranishi Kousuke , Asaka Masamitsu N. , Suzuki Ayumu , Mizuno Yosuke , Hirasaki Masataka , Okuda Akihiko 
Published: July 2019

AbstractYAP (also known as YAP1 or YAP65) is a transcriptional coactivator that interacts with a number of transcription factors including RUNX and TEAD and plays a pivotal role in controlling cell growth. YAP is classified as a proto-oncogene. However, the mechanism by which activated YAP induces cancerous changes is not well known. Here we demonstrate that overexpression of YAP in NIH3T3 cells was sufficient for inducing tumorigenic transformation of cells. Mechanistically, YAP exerts its function in cooperation with the TEAD transcription factor. Our data also show that cMYC is a critical factor that acts downstream of the YAP/TEAD complex. Furthermore, we also found that aberrant activation of YAP is sufficient to drive tumorigenic transformation of non-immortalized mouse embryonic fibroblasts. Together our data indicate that YAP can be categorized as a new type of proto-oncogene distinct from typical oncogenes, such as H-RAS, whose expression in non-immortalized cells is tightly linked to senescence.
Roux-Y Gastric Bypass and Sleeve Gastrectomy directly change gut microbiota composition independent of surgery type
Authors: Paganelli Fernanda L. , Luyer Misha , Hazelbag C. Marijn , Uh Hae-Won , Rogers Malbert R. C. , Adriaans Danielle , Berbers Roos-Marijn , Hendrickx Antoni P. A. , Viveen Marco C. , Groot James A. , Bonten Marc J. M. , Fluit Ad C. , Willems Rob J. L. , Leavis Helen L. 
Published: July 2019

AbstractBariatric surgery in morbid obesity, either through sleeve gastrectomy (SG) or Roux-Y gastric bypass (RYGB), leads to sustainable weight loss, improvement of metabolic disorders and changes in intestinal microbiota. Yet, the relationship between changes in gut microbiota, weight loss and surgical procedure remains incompletely understood. We determined temporal changes in microbiota composition in 45 obese patients undergoing crash diet followed by SG (n = 22) or RYGB (n = 23). Intestinal microbiota composition was determined before intervention (baseline, S1), 2 weeks after crash diet (S2), and 1 week (S3), 3 months (S4) and 6 months (S5) after surgery. Relative to S1, the microbial diversity index declined at S2 and S3 (p < 0.05), and gradually returned to baseline levels at S5. Rikenellaceae relative abundance increased and Ruminococcaceae and Streptococcaceae abundance decreased at S2 (p < 0.05). At S3, Bifidobacteriaceae abundance decreased, whereas those of Streptococcaceae and Enterobacteriaceae increased (p < 0.05). Increased weight loss between S3-S5 was not associated with major changes in microbiota composition. No significant differences appeared between both surgical procedures. In conclusion, undergoing a crash diet and bariatric surgery were associated with an immediate but temporary decline in microbial diversity, with immediate and permanent changes in microbiota composition, independent of surgery type.
Preparation of Monoacylglycerol Derivatives from Indonesian Edible Oil and Their Antimicrobial Assay against Staphylococcus aureus and Escherichia coli
Authors: Jumina Jumina , Lavendi Wenggi , Singgih Tubagus , Triono Sugeng , Steven Kurniawan Yehezkiel , Koketsu Mamoru 
Published: July 2019

AbstractIn the present work, linoleic acid and oleic acid were isolated from Indonesian corn oil and palm oil and they were used to prepare monoacylglycerol derivatives as the antibacterial agent. Indonesian corn oil contains 57.74% linoleic acid, 19.88% palmitic acid, 11.84% oleic acid and 3.02% stearic acid. While Indonesian palm oil contains 44.72% oleic acid, 39.28% palmitic acid, 4.56% stearic acid and 1.54% myristic acid. The oleic acid was purified by using Urea Inclusion Complex (UIC) method and its purity was significantly increased from 44.72% to 94.71%. Meanwhile, with the UIC method, the purity of ethyl linoleate was increased from 57.74% to 72.14%. 1-Monolinolein and 2-monoolein compounds were synthesized via two-step process from the isolated linoleic acid and oleic acid, respectively. The preliminary antibacterial assay shows that the 1-monolinolein did not give any antibacterial activity against Staphylococcus aureus and Escherichia coli, while 2-monoolein showed weak antibacterial activity against Staphylococcus aureus.
Establishment of a Murine Pro-acinar Cell Line to Characterize Roles for FGF2 and α3β1 Integrins in Regulating Pro-acinar Characteristics
Authors: Thiemann Renée F. , Nelson Deirdre A. , Michael DiPersio C. , Larsen Melinda , LaFlamme Susan E. 
Published: July 2019

AbstractRadiation therapy for head and neck cancers results in permanent damage to the saliva producing acinar compartment of the salivary gland. To date, a pure pro-acinar cell line to study underlying mechanisms of acinar cell differentiation in culture has not been described. Here, we report the establishment of a pro-acinar (mSG-PAC1) and ductal (mSG-DUC1) cell line, from the murine submandibular salivary gland (SMG), which recapitulate developmental milestones in differentiation. mSG-DUC1 cells express the ductal markers, keratin-7 and keratin-19, and form lumenized spheroids. mSG-PAC1 cells express the pro-acinar markers SOX10 and aquaporin-5. Using the mSG-PAC1 cell line, we demonstrate that FGF2 regulates specific steps during acinar cell maturation. FGF2 up-regulates aquaporin-5 and the expression of the α3 and α6 subunits of the α3β1 and α6β1 integrins that are known to promote SMG morphogenesis and differentiation. mSG-DUC1 and mSG-PAC1 cells were derived from genetically modified mice, homozygous for floxed alleles of the integrin α3 subunit. Similar to SMGs from α3-null mice, deletion of α3 alleles in mSG-PAC1 cells results in the up-regulation of E-cadherin and the down-regulation of CDC42. Our data indicate that mSG-DUC1 and mSG-PAC1 cells will serve as important tools to gain mechanistic insight into salivary gland morphogenesis and differentiation.
Predictability of US West Coast Ocean Temperatures is not solely due to ENSO
Authors: Capotondi Antonietta , Sardeshmukh Prashant D. , Di Lorenzo Emanuele , Subramanian Aneesh C. , Miller Arthur J. 
Published: July 2019

AbstractThe causes of the extreme and persistent warming in the Northeast Pacific from the winter of 2013/14 to that of 2014/15 are still not fully understood. While global warming may have contributed, natural influences may also have played a role. El Niño events are often implicated in anomalously warm conditions along the US West Coast (USWC). However, the tropical Pacific sea surface temperature (SST) anomalies were generally weak during 2014, calling into question their role in the USWC warming. In this study, we identify tropical Pacific “sensitivity patterns” that optimally force USWC warming at a later time. We find that such sensitivity patterns do not coincide with the mature SST anomaly patterns usually associated with ENSO, but instead include elements associated with ENSO SST precursors and SST anomalies in the central/western equatorial Pacific. El Niño events that produce large USWC warming, irrespective of their magnitude, do project on the sensitivity pattern and are characterized by a distinct evolution of the North Pacific atmospheric and oceanic fields. However, even weak tropical SST anomalies in the right location, and not necessarily associated with ENSO, can significantly influence USWC conditions and enhance their predictability.
Protein phosphatases regulate growth, development, cellulases and secondary metabolism in Trichoderma reesei
Authors: Rodriguez-Iglesias Aroa , Schmoll Monika 
Published: July 2019

AbstractTrichoderma reeseirepresents one of the most prolific producers of plant cell wall degrading enzymes. Recent research showed broad regulation by phosphorylation inT. reesei, including important transcription factors involved in cellulase regulation. To evaluate factors crucial for changes in these phosphorylation events, we studied non-essential protein phosphatases (PPs) ofT. reesei. Viable deletion strains were tested for growth on different carbon sources, osmotic and oxidative stress response, asexual and sexual development, cellulase and protease production as well as secondary metabolism. Six PPs were found to be positive or negative regulators for cellulase production. A correlation of the effects of PPs on protease activities and cellulase activities was not detected. Hierarchical clustering of regulation patterns and phenotypes of deletion indicated functional specialization within PP classes and common as well as variable effects. Our results confirmed the central role of catalytic and regulatory subunits of PP2A which regulates several aspects of cell growth and metabolism. Moreover we show that the additional homologue of PPH5 inTrichodermaspp., PPH5-2 assumes distinct functions in metabolism, development and stress response, different from PPH5. The influence of PPs on both cellulase gene expression and secondary metabolite production support an interrelationship in the underlying regulation mechanisms.
Atlantic origin of asynchronous European interdecadal hydroclimate variability
Authors: Zanchettin Davide , Toniazzo Thomas , Taricco Carla , Rubinetti Sara , Rubino Angelo , Tartaglione Nazario 
Published: July 2019

AbstractDischarge time series of major large-catchment European rivers are known to display significant decadal and interdecadal fluctuations. However, the hydroclimate variability causing such fluctuations remains poorly understood, particularly due to a lack of a spatio-temporal integrated assessment. Here, we demonstrate for the first time that European hydroclimate variability is dominated by a meridional delayed oscillation characterized by a lag of approximately 5 years in interdecadal discharge fluctuations of continental (northern) European rivers with respect to those of Euro-Mediterranean (southern) rivers. We demonstrate a connection of this coherent signal with the large-scale atmospheric circulation over the North Atlantic, and suggest a hitherto unexplored multiannual atmosphere-ocean mechanism in the subpolar North Atlantic at its root.
High prevalence of the MLH1 V384D germline mutation in patients with HER2-positive luminal B breast cancer
Authors: Lee Seung Eun , Lee Hye Seung , Kim Kyoung-Yeon , Park Jung-Hoon , Roh Hanseong , Park Ha Young , Kim Wan-Seop 
Published: July 2019

AbstractHER2-positive luminal B breast cancer (BC), a subset of the luminal B subtype, is ER-positive and HER2-positive BC which is approximately 10% of all BC. However, HER2-positive luminal B BC has received less attention and is less represented in previous molecular analyses than other subtypes. Hence, it is important to elucidate the molecular biology of HER2-positive luminal B BC to stratify patients in a way that allows them to receive their respective optimal treatment. We performed molecular profiling using targeted next-generation sequencing on 94 HER2-positive luminal B BC to identify its molecular characteristics. A total of 134 somatic nonsynonymous mutations, including 131 nonsynonymous single nucleotide variants and three coding insertions/deletions were identified in 30 genes of 75 samples. PIK3CA was most frequently mutated (38/94, 40.4%), followed by TP53 (31/94, 33.0%), and others were detected at lower frequencies. Recurrent germline mutations of MLH1 V384D were found in 13.8% (13/94), with a significantly high TP53 mutations rate. The frequency of MLH1 V384D germline mutation in individuals with HER2-positive luminal B BC was significantly higher than that observed in the controls. All 13 cases were classified as microsatellite stable tumors. Tumor mutation burdens (TMB) were not significantly different between MLH1 V384D carrier and wild type. The concordant results of microsatellite instability (MSI) and TMB suggest that the haploinsufficiency of MLH1 plays a role as a tumor predisposition factor rather than a direct oncogenic driver. Our study identified, for the first time, that MLH1 V384D germline variant is frequently detected in HER2-positive luminal B BC. MLH1 V384D germline variant may not only contribute to gastrointestinal cancer predisposition but may also contribute to BC in East Asians.
Migration rather than proliferation transcriptomic signatures are strongly associated with breast cancer patient survival
Authors: Nair Nishanth Ulhas , Das Avinash , Rogkoti Vasiliki-Maria , Fokkelman Michiel , Marcotte Richard , de Jong Chiaro G. , Koedoot Esmee , Lee Joo Sang , Meilijson Isaac , Hannenhalli Sridhar , Neel Benjamin G. , de Water Bob van , Le Dévédec Sylvia E. , Ruppin Eytan 
Published: July 2019

AbstractThe efficacy of prospective cancer treatments is routinely estimated by in vitro cell-line proliferation screens. However, it is unclear whether tumor aggressiveness and patient survival are influenced more by the proliferative or the migratory properties of cancer cells. To address this question, we experimentally measured proliferation and migration phenotypes across more than 40 breast cancer cell-lines. Based on the latter, we built and validated individual predictors of breast cancer proliferation and migration levels from the cells’ transcriptomics. We then apply these predictors to estimate the proliferation and migration levels of more than 1000 TCGA breast cancer tumors. Reassuringly, both estimates increase with tumor’s aggressiveness, as qualified by its stage, grade, and subtype. However, predicted tumor migration levels are significantly more strongly associated with patient survival than the proliferation levels. We confirmed these findings by conducting siRNA knock-down experiments on the highly migratory MDA-MB-231 cell lines and deriving gene knock-down based proliferation and migration signatures. We show that cytoskeletal drugs might be more beneficial in patients with high predicted migration levels. Taken together, these results testify to the importance of migration levels in determining patient survival.