bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chasing coevolutionary signals in intrinsically disordered proteins complexes
Authors: Iserte Javier A. , Lazar Tamas , Tosatto Silvio C. E. , Tompa Peter , Marino-Buslje Cristina 
Published: October 2020

AbstractIntrinsically disordered proteins/regions (IDPs/IDRs) are crucial components of the cell, they are highly abundant and participate ubiquitously in a wide range of biological functions, such as regulatory processes and cell signaling. Many of their important functions rely on protein interactions, by which they trigger or modulate different pathways. Sequence covariation, a powerful tool for protein contact prediction, has been applied successfully to predict protein structure and to identify protein–protein interactions mostly of globular proteins. IDPs/IDRs also mediate a plethora of protein–protein interactions, highlighting the importance of addressing sequence covariation-based inter-protein contact prediction of this class of proteins. Despite their importance, a systematic approach to analyze the covariation phenomena of intrinsically disordered proteins and their complexes is still missing. Here we carry out a comprehensive critical assessment of coevolution-based contact prediction in IDP/IDR complexes and detail the challenges and possible limitations that emerge from their analysis. We found that the coevolutionary signal is faint in most of the complexes of disordered proteins but positively correlates with the interface size and binding affinity between partners. In addition, we discuss the state-of-art methodology by biological interpretation of the results, formulate evaluation guidelines and suggest future directions of development to the field.
Technical considerations when designing a gene expression panel for renal transplant diagnosis
Authors: Toulza F. , Dominy K. , Cook T. , Galliford J. , Beadle J. , McLean A. , Roufosse C. 
Published: October 2020

AbstractGene expression analysis is emerging as a new diagnostic tool in transplant pathology, in particular for the diagnosis of antibody-mediated rejection. Diagnostic gene expression panels are defined on the basis of their pathophysiological relevance, but also need to be tested for their robustness across different preservatives and analysis platforms. The aim of this study is the investigate the effect of tissue sampling and preservation on candidate genes included in a renal transplant diagnostic panel. Using the NanoString platform, we compared the expression of 219 genes in 51 samples, split for formalin-fixation and paraffin-embedding (FFPE) and RNAlater preservation (RNAlater). We found that overall, gene expression significantly correlated between FFPE and RNAlater samples. However, at the individual gene level, 46 of the 219 genes did not correlate across the 51 matched FFPE and RNAlater samples. Comparing gene expression results using NanoString and qRT-PCR for 18 genes in the same pool of RNA (RNAlater), we found a significant correlation in 17/18 genes. Our study indicates that, in samples from the same routine diagnostic renal transplant biopsy procedure split for FFPE and RNAlater, 21% of 219 genes of potential biological significance do not correlate in expression. Whether this is due to fixatives or tissue sampling, selection of gene panels for routine diagnosis should take this information into consideration.
Potent inhibition of tumour cell proliferation and immunoregulatory function by mitochondria-targeted atovaquone
Authors: Cheng Gang , Hardy Micael , Topchyan Paytsar , Zander Ryan , Volberding Peter , Cui Weiguo , Kalyanaraman Balaraman 
Published: October 2020

AbstractThe FDA-approved prophylactic antimalarial drug atovaquone (ATO) recently was repurposed as an antitumor drug. Studies show that ATO exerts a profound antiproliferative effect in several cancer cells, including breast, ovarian, and glioma. Analogous to the mechanism of action proposed in parasites, ATO inhibits mitochondrial complex III and cell respiration. To enhance the chemotherapeutic efficacy and oxidative phosphorylation inhibition, we developed a mitochondria-targeted triphenylphosphonium-conjugated ATO with varying alkyl side chains (Mito4-ATO, Mito10-ATO, Mito12-ATO, and Mito16-ATO). Results show, for the first time, that triphenylphosphonium-conjugated ATO potently enhanced the antiproliferative effect of ATO in cancer cells and, depending upon the alkyl chain length, the molecular target of inhibition changes from mitochondrial complex III to complex I. Mito4-ATO and Mito10-ATO inhibit both pyruvate/malate-dependent complex I and duroquinol-dependent complex III-induced oxygen consumption whereas Mito12-ATO and Mito16-ATO inhibit only complex I-induced oxygen consumption. Mitochondrial target shifting may have immunoregulatory implications.
Perception of vibrotactile distance on the back
Authors: Plaisier Myrthe A. , Sap Lotte I. N. , Kappers Astrid M. L. 
Published: October 2020

AbstractVibrotactile displays worn on the back can be used as sensory substitution device. Often vibrotactile stimulation is chosen because vibration motors are easy to incorporate and relatively cheap. When designing such displays knowledge about vibrotactile perception on the back is crucial. In the current study we investigated distance perception. Biases in distance perception can explain spatial distortions that occur when, for instance, tracing a shape using vibration. We investigated the effect of orientation (horizontal vs vertical), the effect of positioning with respect to the spine and the effect of switching vibration motors on sequentially versus simultaneously. Our study includes four conditions. The condition which had a horizontal orientation with both vibration motors switching on sequentially on the same side of the spine was chosen is the baseline condition. The other three conditions were compared to this baseline condition. We found that distances felt longer in the vertical direction than in the horizontal direction. Furthermore, distances were perceived to be longer when vibration motors were distributed on both sides of the spine compared to when they were on the same side. Finally, distances felt shorter when vibration motors were switched on simultaneously compared to sequentially. In the simultaneous case a distance of 4 cm was not clearly perceived differently than a distance of 12 cm. When designing vibrotactile displays these anisotropies in perceived distance need to be taken into account because otherwise the intended shape will not match the perceived shape. Also, dynamically presented distances are more clearly perceived than static distances. This finding supports recommendations made in previous studies that dynamic patterns are easier to perceive than static patterns.
Identification of drivers of breast cancer invasion by secretome analysis: insight into CTGF signaling
Authors: Hellinger Johanna W. , Schömel Franziska , Buse Judith V. , Lenz Christof , Bauerschmitz Gerd , Emons Günter , Gründker Carsten 
Published: October 2020

AbstractAn altered consistency of tumor microenvironment facilitates the progression of the tumor towards metastasis. Here we combine data from secretome and proteome analysis using mass spectrometry with microarray data from mesenchymal transformed breast cancer cells (MCF-7-EMT) to elucidate the drivers of epithelial-mesenchymal transition (EMT) and cell invasion. Suppression of connective tissue growth factor (CTGF) reduced invasion in 2D and 3D invasion assays and expression of transforming growth factor-beta-induced protein ig-h3 (TGFBI), Zinc finger E-box-binding homeobox 1 (ZEB1) and lysyl oxidase (LOX), while the adhesion of cell-extracellular matrix (ECM) in mesenchymal transformed breast cancer cells is increased. In contrast, an enhanced expression of CTGF leads to an increased 3D invasion, expression of fibronectin 1 (FN1), secreted protein acidic and cysteine rich (SPARC) and CD44 and a reduced cell ECM adhesion. Gonadotropin-releasing hormone (GnRH) agonist Triptorelin reduces CTGF expression in a Ras homolog family member A (RhoA)-dependent manner. Our results suggest that CTGF drives breast cancer cell invasion in vitro and therefore could be an attractive therapeutic target for drug development to prevent the spread of breast cancer.
High plasma salivary α-amylase, but not high AMY1 copy number, associated with low obesity rate in Qatari adults: cross-sectional study
Authors: Al-Akl Neyla , Thompson Richard I. , Arredouani Abdelilah 
Published: October 2020

AbstractThe relationship between salivary α-amylase activity (psAAa) or AMY1 copy number and the risk of obesity remains controversial. We aimed to assess this relationship in a cohort from Qatar, where obesity affects 43% of adults. The relationship was investigated cross-sectionally in 923 Qatari adults from the Qatar biobank cohort. AMY1 CN was estimated form whole genome sequencing data. The associations with obesity prevalence were assessed by linear and logistic regressions. We found no difference in AMY1 CN between obese and normal-weight individuals. However, the psAAa was significantly lower in obese individuals. Significant inverse correlations were found between adiposity markers and psAAa in both sexes, but were marginally stronger in men. A significant effect of high psAAa, but not AMY1 CN, on reduced obesity rates was identified in men (OR per psAAa unit 0.957 [95% CI 0.937–0.977], p < 0.001, with psAAa ranging between 5 to 66 U/L). A significantly higher prevalence of obesity was observed in the lowest quartile of psAAa in men (75% (Q1) vs. 36% (Q4), p < 0.001) and women (74% (Q1) vs 56% (Q4), p = 0.009). Our findings suggest that high psAAa, but not AMY1 CN, has a potential positive benefit against obesity in the Qatari population.
Cold weather increases the risk of scrotal torsion events: results of an ecological study of acute scrotal pain in Scotland over 25 years
Authors: Molokwu Chidi N. , Ndoumbe Judith K. , Goodman Chris M. 
Published: October 2020

AbstractThe role of ambient temperature in the aetiology of acute scrotal pain (ASP) remains uncertain. The most common causes of ASP are torsion of the testis (TT) or its appendages (TA) and epidymo-orchitis (EO). We undertook an ecological study of ASP in Scotland to determine whether a seasonal variation could be observed. Episode reports for TT, TA and EO in Scotland over 25 years were collated monthly. Statistical analyses were performed to determine whether changes in ambient temperature during the year could explain variations in monthly frequency. 7882 episodes of TT and TA (Group A), and 25,973 episodes of EO (Group B) were reported. There was significant variance in the frequency of Group A (p < 0.0001) and B (p = 0.0031) episodes by month, higher frequency of Group A episodes in the colder half of the year (p < 0.0001), and an inverse correlation between the frequency of Group A episodes and ambient temperature (Spearman r = − 0.8757, 95% CI − 0.9661 to − 0.5941, p = 0.0004). Ambient temperature is likely to be playing a role in the aetiology of TT and TA in Scotland but not EO. Further study is warranted to explain underlying mechanisms.
Pharmacologic profiling of patient-derived xenograft models of primary treatment-naïve triple-negative breast cancer
Authors: Powell Reid T. , Redwood Abena , Liu Xuan , Guo Lei , Cai Shirong , Zhou Xinhui , Tu Yizheng , Zhang Xiaomei , Qi Yuan , Jiang Yan , Echeverria Gloria , Feng Ningping , Ma XiaoYan , Giuliani Virginia , Marszalek Joseph R. , Heffernan Timothy P. , Vellano Christopher P. , White Jason B. , Stephan Clifford , Davies Peter J. , Moulder Stacy , Symmans W. Fraser , Chang Jeffrey T. , Piwnica-Worms Helen 
Published: October 2020

AbstractTriple-negative breast cancer (TNBC) accounts for 15–20% of breast cancer cases in the United States, lacks targeted therapeutic options, and is associated with a 40–80% risk of recurrence. Thus, identifying actionable targets in treatment-naïve and chemoresistant TNBC is a critical unmet medical need. To address this need, we performed high-throughput drug viability screens on human tumor cells isolated from 16 patient-derived xenograft models of treatment-naïve primary TNBC. The models span a range of TNBC subtypes and exhibit a diverse set of putative driver mutations, thus providing a unique patient-derived, molecularly annotated pharmacologic resource that is reflective of TNBC. We identified therapeutically actionable targets including kinesin spindle protein (KSP). The KSP inhibitor targets the mitotic spindle through mechanisms independent of microtubule stability and showed efficacy in models that were resistant to microtubule inhibitors used as part of the current standard of care for TNBC. We also observed subtype selectivity of Prima-1Met, which showed higher levels of efficacy in the mesenchymal subtype. Coupling pharmacologic data with genomic and transcriptomic information, we showed that Prima-1Met activity was independent of its canonical target, mutant p53, and was better associated with glutathione metabolism, providing an alternate molecularly defined biomarker for this drug.
Direct measurement of the thermoelectric properties of electrochemically deposited Bi2Te3 thin films
Authors: Recatala-Gomez Jose , Kumar Pawan , Suwardi Ady , Abutaha Anas , Nandhakumar Iris , Hippalgaonkar Kedar 
Published: October 2020

AbstractThe best known thermoelectric material for near room temperature heat-to-electricity conversion is bismuth telluride. Amongst the possible fabrication techniques, electrodeposition has attracted attention due to its simplicity and low cost. However, the measurement of the thermoelectric properties of electrodeposited films is challenging because of the conducting seed layer underneath the film. Here, we develop a method to directly measure the thermoelectric properties of electrodeposited bismuth telluride thin films, grown on indium tin oxide. Using this technique, the temperature dependent thermoelectric properties (Seebeck coefficient and electrical conductivity) of electrodeposited thin films have been measured down to 100 K. A parallel resistor model is employed to discern the signal of the film from the signal of the seed layer and the data are carefully analysed and contextualized with literature. Our analysis demonstrates that the thermoelectric properties of electrodeposited films can be accurately evaluated without inflicting any damage to the films.
Multi-strain volatile profiling of pathogenic and commensal cutaneous bacteria
Authors: Fitzgerald Shane , Duffy Emer , Holland Linda , Morrin Aoife 
Published: October 2020

AbstractThe detection of volatile organic compounds (VOC) emitted by pathogenic bacteria has been proposed as a potential non-invasive approach for characterising various infectious diseases as well as wound infections. Studying microbial VOC profiles in vitro allows the mechanisms governing VOC production and the cellular origin of VOCs to be deduced. However, inter-study comparisons of microbial VOC data remains a challenge due to the variation in instrumental and growth parameters across studies. In this work, multiple strains of pathogenic and commensal cutaneous bacteria were analysed using headspace solid phase micro-extraction coupled with gas chromatography–mass spectrometry. A kinetic study was also carried out to assess the relationship between bacterial VOC profiles and the growth phase of cells. Comprehensive bacterial VOC profiles were successfully discriminated at the species-level, while strain-level variation was only observed in specific species and to a small degree. Temporal emission kinetics showed that the emission of particular compound groups were proportional to the respective growth phase for individual S. aureus and P. aeruginosa samples. Standardised experimental workflows are needed to improve comparability across studies and ultimately elevate the field of microbial VOC profiling. Our results build on and support previous literature and demonstrate that comprehensive discriminative results can be achieved using simple experimental and data analysis workflows.
Superior survival in right-sided versus left-sided colon signet ring cell carcinoma
Authors: Zhao Zhuang , Wang Dun-wei , Yan Na , Pan Shu , Li Zhi-wen 
Published: October 2020

AbstractThis study aimed to explore the association of tumor sidedness with the prognosis of patients with colon signet ring cell carcinoma (SRCC). Eligible patients were retrieved from the Surveillance, Epidemiology, and End Results database between 2004 and 2015. Cancer-specific survival (CSS) and overall survival (OS) were compared between patients with left-sided colon SRCC and those with right-sided lesions. A total of 2660 patients were included, among them, 1983 (74.5%) had right-sided colon SRCC. Compared to patients with left-sided colon SRCC, those who had the right-sided colon SRCC showed higher proportion of white race, female, aged ≥ 65 years, receiving total colectomy and ≥ 4 regional lymph node dissection; while had lower proportion of advanced AJCC stage. Besides, right-sided patients exhibited superior 5-year CSS (32.74% vs. 25.89%, P = 0.001) and OS (27.38% vs. 23.02%, P = 0.024) rates compared with left-sided ones. Multivariate analysis revealed that tumor sidedness was an independent prognostic factor. To be specific, patients with right-sided colon SRCC showed better CSS (HR: 0.873; 95% CI 0.777–0.981; P = 0.023) and OS (HR: 0.838; 95% CI 0.753–0.965; P = 0.002). Moreover, subgroup analysis demonstrated superior CSS and OS for right-sided patients in most subgroups. Tumor sidedness was an independent prognostic indicator for colon SRCC. Besides, patients with right-sided colon SRCC have superior prognosis than those with left-sided lesions.
Value of liver iron concentration in healthy volunteers assessed by MRI
Authors: Obrzut Marzanna , Atamaniuk Vitaliy , Glaser Kevin J. , Chen Jun , Ehman Richard L. , Obrzut Bogdan , Cholewa Marian , Gutkowski Krzysztof 
Published: October 2020

AbstractIron overload is a relatively common clinical condition resulting from disorders such as hereditary hemochromatosis, thalassemia, sickle cell disease, and myelodysplasia that can lead to progressive fibrosis and eventually cirrhosis of the liver. Therefore, it is essential to recognize the disease process at the earliest stage. Liver biopsy is the reference test for the assessment of liver fibrosis. It also allows for quantifying liver iron concentration (LIC) in patients. However, this is an invasive method with significant limitations and possible risks. Magnetic resonance imaging (MRI) and evaluation of the R2* relaxation rate can be an alternative to biopsy for assessing LIC. However, it causes a need for accurate R2* data corresponding to standard value for further comparison with examined patients. This study aimed to assess the normative values of liver R2* in healthy individuals. A total of 100 volunteers that met established criteria were enrolled in the study: 36 (36%) men and 64 (64%) women. The mean age was 22.9 years (range 20 to 32 years). R2* was estimated by an MRI exam with a 1.5 T clinical magnetic resonance scanner. Images for measuring the LIC and liver fat concentration were obtained using the IDEAL-IQ technique for liver imaging. The Mean (SD) liver R2* was 28.34 (2.25) s−1 (95% CI, 27.78–28.90, range 23.67–33.00 s−1) in females, 29.57 (3.20) s−1 (95% CI, 28.49–30.66, range 23.93–37.77 s−1) in males, and 28.72 (2.69) s−1 (range 23.67–37.77 s−1) in the whole group. R2* value in this particular population with a high proportion of young women did not exceed 38 s−1. In the absence of fibrosis or steatosis, liver stiffness and fat fraction did not show any relationship with R2*.
Mass distribution of magnetized quark-nugget dark matter and comparison with requirements and observations
Authors: VanDevender J. Pace , Shoemaker Ian M. , Sloan T. , VanDevender Aaron P. , Ulmen Benjamin A. 
Published: October 2020

AbstractQuark nuggets are a candidate for dark matter consistent with the Standard Model. Previous models of quark nuggets have investigated properties arising from their being composed of strange, up, and down quarks and have not included any effects caused by their self-magnetic field. However, Tatsumi found that the core of a magnetar star may be a quark nugget in a ferromagnetic state with core magnetic field Bsurface = 1012±1 T. We apply Tatsumi’s result to quark-nugget dark-matter and report results on aggregation of magnetized quark nuggets (MQNs) after formation from the quark-gluon plasma until expansion of the universe freezes out the mass distribution to ~ 10−24 kg to ~ 1014 kg. Aggregation overcomes weak-interaction decay. Computed mass distributions show MQNs are consistent with requirements for dark matter and indicate that geologic detectors (craters in peat bogs) and space-based detectors (satellites measuring radio-frequency emissions after passage through normal matter) should be able to detect MQN dark matter. Null and positive observations narrow the range of a key parameter Bo ~ Bsurface to 1 × 1011 T < Bo ≤ 3 × 1012 T.
Individual dietary specialization reduces intraspecific competition, rather than feeding activity, in black amur bream (Megalobrama terminalis)
Authors: Xia Yuguo , Li Yuefei , Zhu Shuli , Li Jie , Li Shanghao , Li Xinhui 
Published: October 2020

AbstractIndividual specialization and high plasticity in feeding activity are common in natural populations. However, the role of these two in intraspecific competition is unclear. In this study, the rhythm of feeding activity, dietary composition, niche width, niche overlap, and individual specialization was explored in four different size groups of black amur bream (Megalobrama terminalis), using microscopic identification of foregut contents and stable isotope analysis (δ13C and δ15N) of dorsal muscle. Both methods observed ontogenetic shifts in dietary preference and individual specializations, and revealed that the total niche width of large individuals was greater than small individuals. Mixed linear models indicated that feeding activity was significantly influenced by time (p < 0.0001), and no significant changes among size groups was evident (p = 0.244). Niche overlaps revealed that there was intensive diet competition between different size groups of black amur bream. Individual specialization in small juveniles was likely to be stronger than sub-adult and adult groups. Pearson’s correlation analysis revealed that the individual specialization was positively correlated with mean diet similarity within a group. The results indicated that intraspecific competition is reduced mainly by individual dietary specialization, rather than shift in feeding activity.