bluuebunny/crossref_metadata_2025_split huggingface dataset:
Addiction to protein kinase Cɩ due to PRKCI gene amplification can be exploited for an aptamer-based targeted therapy in ovarian cancer
Authors: Rehmani Hina , Li Yue , Li Tao , Padia Ravi , Calbay Ozlem , Jin Lingtao , Chen Huijun , Huang Shuang 
Published: August 2020

AbstractPRKCI, the gene for protein kinase Cι (PKCι), is frequently amplified in ovarian cancer and recent studies have shown that PKCι participates in ovary tumorigenesis. However, it is unknown whether PKCι is differentially involved in the growth/survival between PRKCI-amplified and non-amplified ovarian cancer cells. In this study, we analyzed ovarian cancer patient dataset and revealed that PRKCI is the only PKC family member significantly amplified in ovarian cancer and PRKCI amplification is associated with higher PKCι expression. Using a panel of ovarian cancer cell lines, we found that abundance of PKCι is generally associated with PRKCI amplification. Interestingly, silencing PKCι led to apoptosis in PRKCI-amplified ovarian cancer cells but not in those without PRKCI amplification, thus indicating an oncogenic addiction to PKCɩ in PRKCI-amplified cells. Since small-molecule inhibitors characterized to selectively block atypical PKCs did not offer selectivity nor sensitivity in PRKCI-amplified ovarian cancer cells and were even cytotoxic to non-cancerous ovary surface or fallopian tube epithelial cells, we designed an EpCAM aptamer-PKCι siRNA chimera (EpCAM-siPKCι aptamer). EpCAM-siPKCι aptamer not only effectively induced apoptosis of PRKCI-amplified ovarian cancer cells but also greatly deterred intraperitoneal tumor development in xenograft mouse model. This study has demonstrated a precision medicine-based strategy to target a subset of ovarian cancer that contains PRKCI amplification and shown that the EpCAM aptamer-delivered PKCι siRNA may be used to suppress such tumors.
Polygenic background modifies penetrance of monogenic variants for tier 1 genomic conditions
Authors: Fahed Akl C. , Wang Minxian , Homburger Julian R. , Patel Aniruddh P. , Bick Alexander G. , Neben Cynthia L. , Lai Carmen , Brockman Deanna , Philippakis Anthony , Ellinor Patrick T. , Cassa Christopher A. , Lebo Matthew , Ng Kenney , Lander Eric S. , Zhou Alicia Y. , Kathiresan Sekar , Khera Amit V. 
Published: August 2020

AbstractGenetic variation can predispose to disease both through (i) monogenic risk variants that disrupt a physiologic pathway with large effect on disease and (ii) polygenic risk that involves many variants of small effect in different pathways. Few studies have explored the interplay between monogenic and polygenic risk. Here, we study 80,928 individuals to examine whether polygenic background can modify penetrance of disease in tier 1 genomic conditions — familial hypercholesterolemia, hereditary breast and ovarian cancer, and Lynch syndrome. Among carriers of a monogenic risk variant, we estimate substantial gradients in disease risk based on polygenic background — the probability of disease by age 75 years ranged from 17% to 78% for coronary artery disease, 13% to 76% for breast cancer, and 11% to 80% for colon cancer. We propose that accounting for polygenic background is likely to increase accuracy of risk estimation for individuals who inherit a monogenic risk variant.
An atlas of O-linked glycosylation on peptide hormones reveals diverse biological roles
Authors: Madsen Thomas D. , Hansen Lasse H. , Hintze John , Ye Zilu , Jebari Shifa , Andersen Daniel B. , Joshi Hiren J. , Ju Tongzhong , Goetze Jens P. , Martin Cesar , Rosenkilde Mette M. , Holst Jens J. , Kuhre Rune E. , Goth Christoffer K. , Vakhrushev Sergey Y. , Schjoldager Katrine T. 
Published: August 2020

AbstractPeptide hormones and neuropeptides encompass a large class of bioactive peptides that regulate physiological processes like anxiety, blood glucose, appetite, inflammation and blood pressure. Here, we execute a focused discovery strategy to provide an extensive map of O-glycans on peptide hormones. We find that almost one third of the 279 classified peptide hormones carry O-glycans. Many of the identified O-glycosites are conserved and are predicted to serve roles in proprotein processing, receptor interaction, biodistribution and biostability. We demonstrate that O-glycans positioned within the receptor binding motifs of members of the neuropeptide Y and glucagon families modulate receptor activation properties and substantially extend peptide half-lives. Our study highlights the importance of O-glycosylation in the biology of peptide hormones, and our map of O-glycosites in this large class of biomolecules serves as a discovery platform for an important class of molecules with potential opportunities for drug designs.
Photo-acoustic dual-frequency comb spectroscopy
Authors: Wildi Thibault , Voumard Thibault , Brasch Victor , Yilmaz Gürkan , Herr Tobias 
Published: August 2020

AbstractPhoto-acoustic spectroscopy (PAS) is one of the most sensitive non-destructive analysis techniques for gases, fluids and solids. It can operate background-free at any wavelength and is applicable to microscopic and even non-transparent samples. Extension of PAS to broadband wavelength coverage is a powerful tool, though challenging to implement without sacrifice of wavelength resolution and acquisition speed. Here we show that dual-frequency comb spectroscopy (DCS) and its potential for unmatched precision, speed and wavelength coverage can be combined with the advantages of photo-acoustic detection. Acoustic wave interferograms are generated in the sample by dual-comb absorption and detected by a microphone. As an example, weak gas absorption features are precisely and rapidly sampled; long-term coherent averaging further increases the sensitivity. This novel approach of dual-frequency comb photo-acoustic spectroscopy (DCPAS) generates unprecedented opportunities for rapid and sensitive multi-species molecular analysis across all wavelengths of light.
Large cation ethylammonium incorporated perovskite for efficient and spectra stable blue light-emitting diodes
Authors: Chu Zema , Zhao Yang , Ma Fei , Zhang Cai-Xin , Deng Huixiong , Gao Feng , Ye Qiufeng , Meng Junhua , Yin Zhigang , Zhang Xingwang , You Jingbi 
Published: August 2020

AbstractPerovskite light-emitting diodes (PeLEDs) have showed significant progress in recent years; the external quantum efficiency (EQE) of electroluminescence in green and red regions has exceeded 20%, but the efficiency in blue lags far behind. Here, a large cation CH3CH2NH2+ is added in PEA2(CsPbBr3)2PbBr4 perovskite to decrease the Pb–Br orbit coupling and increase the bandgap for blue emission. X-ray diffraction and nuclear magnetic resonance results confirmed that the EA has successfully replaced Cs+ cations to form PEA2(Cs1-xEAxPbBr3)2PbBr4. This method modulates the photoluminescence from the green region (508 nm) into blue (466 nm), and over 70% photoluminescence quantum yield in blue is obtained. In addition, the emission spectra is stable under light and thermal stress. With configuration of PeLEDs with 60% EABr, as high as 12.1% EQE of sky-blue electroluminescence located at 488 nm has been demonstrated, which will pave the way for the full color display for the PeLEDs.
Magnetic field detection limits for ultraclean graphene Hall sensors
Authors: Schaefer Brian T. , Wang Lei , Jarjour Alexander , Watanabe Kenji , Taniguchi Takashi , McEuen Paul L. , Nowack Katja C. 
Published: August 2020

AbstractSolid-state magnetic field sensors are important for applications in commercial electronics and fundamental materials research. Most magnetic field sensors function in a limited range of temperature and magnetic field, but Hall sensors in principle operate over a broad range of these conditions. Here, we evaluate ultraclean graphene as a material platform for high-performance Hall sensors. We fabricate micrometer-scale devices from graphene encapsulated with hexagonal boron nitride and few-layer graphite. We optimize the magnetic field detection limit under different conditions. At 1 kHz for a 1 μm device, we estimate a detection limit of 700 nT Hz−1/2 at room temperature, 80 nT Hz−1/2 at 4.2 K, and 3 μT Hz−1/2 in 3 T background field at 4.2 K. Our devices perform similarly to the best Hall sensors reported in the literature at room temperature, outperform other Hall sensors at 4.2 K, and demonstrate high performance in a few-Tesla magnetic field at which the sensors exhibit the quantum Hall effect.
Evidence that the TRPV1 S1-S4 membrane domain contributes to thermosensing
Authors: Kim Minjoo , Sisco Nicholas J. , Hilton Jacob K. , Montano Camila M. , Castro Manuel A. , Cherry Brian R. , Levitus Marcia , Van Horn Wade D. 
Published: August 2020

AbstractSensing and responding to temperature is crucial in biology. The TRPV1 ion channel is a well-studied heat-sensing receptor that is also activated by vanilloid compounds, including capsaicin. Despite significant interest, the molecular underpinnings of thermosensing have remained elusive. The TRPV1 S1-S4 membrane domain couples chemical ligand binding to the pore domain during channel gating. Here we show that the S1-S4 domain also significantly contributes to thermosensing and couples to heat-activated gating. Evaluation of the isolated human TRPV1 S1-S4 domain by solution NMR, far-UV CD, and intrinsic fluorescence shows that this domain undergoes a non-denaturing temperature-dependent transition with a high thermosensitivity. Further NMR characterization of the temperature-dependent conformational changes suggests the contribution of the S1-S4 domain to thermosensing shares features with known coupling mechanisms between this domain with ligand and pH activation. Taken together, this study shows that the TRPV1 S1-S4 domain contributes to TRPV1 temperature-dependent activation.
Effects of a herbal formulation, KGC3P, and its individual component, nepetin, on coal fly dust-induced airway inflammation
Authors: Saba Evelyn , Lee Young-sil , Yang Won-Kyung , Lee Yuan Yee , Kim MinKi , Woo Su-Min , Kim KilSoo , Kwon Young-Sam , Kim Tae-Hwan , Kwak Dongmi , Park Yang-Chun , Shin Han Jae , Han Chang Kyun , Oh Jae-Wook , Lee Young Cheol , Kang Hyung-Sik , Rhee Man Hee , Kim Seung-Hyung 
Published: August 2020

AbstractCoal fly dust (CFD)-induced asthma model is used as an ambient particulate matter model of serious pulmonary damage. We aimed to evaluate the effects of a combination of ginseng and Salvia plebeia R. Br extract (KGC-03-PS; KG3P) and its individual components (hispidulin, nepetin and rosmarinic acid) in a CFD-induced mouse model of airway inflammation (asthma). We also evaluated signal transduction by KG3P and its individual components in the alveolar macrophage cell line, MH-S cells. In vitro, KG3P and its individual components inhibited nitric oxide production and expression of pro-inflammatory mediators and cytokines (iNOS, COX-2, IL-1β, IL-6 and TNF-α) through the NF-κB and MAPK pathways in coal fly ash (CFA)-induced inflammation in MH-S cells. Moreover, in the CFD-induced asthma model in mice, KG3P and its predominant individual component, nepetin, inhibited Asymmetric Dimethyl arginine (ADMA) and Symmetric Dimethyl arginine (SDMA) in serum, and decreased the histopathologic score in the lungs. A significant reduction in the neutrophils and immune cells in BALF and lung tissue was demonstrated, with significant reduction in the expression of the pro-inflammatory cytokines. Finally, IRAK-1 localization was also potently inhibited by KG3P and nepetin. Thus, KG3P extract can be considered as a potent candidate for amelioration of airway inflammation.
Innovative low-cost biosorption process of Cr6+ by Pseudomonas alcaliphila NEWG-2
Authors: El-Naggar Noura El-Ahmady , El-khateeb Ayman Y. , Ghoniem Abeer Abdulkhalek , El-Hersh Mohammed S. , Saber WesamEldin I. A. 
Published: August 2020

AbstractChromium is one of the heavy metal pollutants that causing risky health issues when discharged into the aquatic ecosystems. The current investigation focused on the bioremoval of Cr6+ depending on the bacterial sorption process by using Pseudomonas sp. NEWG-2 which was identified on the basis of morphological, cultural characteristics, 16S rRNA sequencing and phylogenetic analysis as Pseudomonas alcaliphila strain NEWG-2. It is clear from the FCCD experiments that the bacterium can grow normally and remove 96.60% of 200 mg/l of Cr6+ using yeast extract (5.6 g/l), glucose (4.9 g/l), pH (7) for 48 h incubation period. SEM and EDS analyses proved that the Cr6+ was biosorbed by P. alcaliphila NEWG-2. FTIR spectra indicated that the phenolic, carbonyl ester, acetyl, carboxylate, alkanes and carbonyl were the main groups involved in the chromium biosorption. Of the equilibrium isotherms models, the Langmuir model was more obedient, with a maximum uptake (qmax) of 10 mg/g (bacterial-alginate beads), than the Freundlich one. The findings reveal the efficiency of P. alcaliphila NEWG-2 in Cr6+ biosorption, with feasibility in the treatment of chromium-contaminated water as a green-technology tool. Interestingly, to the best of our knowledge, this is the first report on Cr6+ biosorption process by P. alcaliphila.
Homozygous deletions implicate non-coding epigenetic marks in Autism spectrum disorder
Authors: Schmitz-Abe Klaus , Sanchez-Schmitz Guzman , Doan Ryan N. , Hill R. Sean , Chahrour Maria H. , Mehta Bhaven K. , Servattalab Sarah , Ataman Bulent , Lam Anh-Thu N. , Morrow Eric M. , Greenberg Michael E. , Yu Timothy W. , Walsh Christopher A. , Markianos Kyriacos 
Published: August 2020

AbstractMore than 98% of the human genome is made up of non-coding DNA, but techniques to ascertain its contribution to human disease have lagged far behind our understanding of protein coding variations. Autism spectrum disorder (ASD) has been mostly associated with coding variations via de novo single nucleotide variants (SNVs), recessive/homozygous SNVs, or de novo copy number variants (CNVs); however, most ASD cases continue to lack a genetic diagnosis. We analyzed 187 consanguineous ASD families for biallelic CNVs. Recessive deletions were significantly enriched in affected individuals relative to their unaffected siblings (17% versus 4%,p < 0.001). Only a small subset of biallelic deletions were predicted to result in coding exon disruption. In contrast, biallelic deletions in individuals with ASD were enriched for overlap with regulatory regions, with 23/28 CNVs disrupting histone peaks in ENCODE (p < 0.009). Overlap with regulatory regions was further demonstrated by comparisons to the 127-epigenome dataset released by the Roadmap Epigenomics project, with enrichment for enhancers found in primary brain tissue and neuronal progenitor cells. Our results suggest a novel noncoding mechanism of ASD, describe a powerful method to identify important noncoding regions in the human genome, and emphasize the potential significance of gene activation and regulation in cognitive and social function.
Recombinant Plasmodium vivax circumsporozoite surface protein allelic variants: antibody recognition by individuals from three communities in the Brazilian Amazon
Authors: Soares Isabela Ferreira , López-Camacho César , Rodrigues-da-Silva Rodrigo Nunes , da Silva Matos Ada , de Oliveira Baptista Barbara , Totino Paulo Renato Rivas , de Souza Rodrigo Medeiros , Harrison Kate , Gimenez Alba Marina , de Freitas Elisângela Oliveira , Kim Young Chan , Oliveira-Ferreira Joseli , Daniel-Ribeiro Cláudio Tadeu , Reyes-Sandoval Arturo , Pratt-Riccio Lilian Rose , Lima-Junior Josué da Costa 
Published: August 2020

AbstractCircumsporozoite protein (CSP) variants of P. vivax, besides having variations in the protein repetitive portion, can differ from each other in aspects such as geographical distribution, intensity of transmission, vectorial competence and immune response. Such aspects must be considered to P. vivax vaccine development. Therefore, we evaluated the immunogenicity of novel recombinant proteins corresponding to each of the three P. vivax allelic variants (VK210, VK247 and P. vivax-like) and of the C-terminal region (shared by all PvCSP variants) in naturally malaria-exposed populations of Brazilian Amazon. Our results demonstrated that PvCSP-VK210 was the major target of humoral immune response in studied population, presenting higher frequency and magnitude of IgG response. The IgG subclass profile showed a prevalence of cytophilic antibodies (IgG1 and IgG3), that seem to have an essential role in protective immune response. Differently of PvCSP allelic variants, antibodies elicited against C-terminal region of protein did not correlate with epidemiological parameters, bringing additional evidence that humoral response against this protein region is not essential to protective immunity. Taken together, these findings increase the knowledge on serological response to distinct PvCSP allelic variants and may contribute to the development of a global and effective P. vivax vaccine.
Machine learning-based automated classification of headache disorders using patient-reported questionnaires
Authors: Kwon Junmo , Lee Hyebin , Cho Soohyun , Chung Chin-Sang , Lee Mi Ji , Park Hyunjin 
Published: August 2020

AbstractClassification of headache disorders is dependent on a subjective self-report from patients and its interpretation by physicians. We aimed to apply objective data-driven machine learning approaches to analyze patient-reported symptoms and test the feasibility of the automated classification of headache disorders. The self-report data of 2162 patients were analyzed. Headache disorders were merged into five major entities. The patients were divided into training (n = 1286) and test (n = 876) cohorts. We trained a stacked classifier model with four layers of XGBoost classifiers. The first layer classified between migraine and others, the second layer classified between tension-type headache (TTH) and others, and the third layer classified between trigeminal autonomic cephalalgia (TAC) and others, and the fourth layer classified between epicranial and thunderclap headaches. Each layer selected different features from the self-reports by using least absolute shrinkage and selection operator. In the test cohort, our stacked classifier obtained accuracy of 81%, sensitivity of 88%, 69%, 65%, 53%, and 51%, and specificity of 95%, 55%, 46%, 48%, and 51% for migraine, TTH, TAC, epicranial headache, and thunderclap headaches, respectively. We showed that a machine-learning based approach is applicable in analyzing patient-reported questionnaires. Our result could serve as a baseline for future studies in headache research.
RhCMV serostatus and vaccine adjuvant impact immunogenicity of RhCMV/SIV vaccines
Authors: Chang W. L. William , Deere Jesse D. , Kieu Hung T. , Castillo Luis D. , Machmach Kawthar , Shen Xiaoying , Tomaras Georgia D. , Shacklett Barbara L. , Barry Peter A. , Hartigan-O’Connor Dennis J. , Sparger Ellen E. 
Published: August 2020

AbstractRhesus cytomegalovirus (RhCMV) strain 68-1-vectored simian immunodeficiency virus (RhCMV/SIV) vaccines are associated with complete clearance of pathogenic SIV challenge virus, non-canonical major histocompatibility complex restriction, and absent antibody responses in recipients previously infected with wild-type RhCMV. This report presents the first investigation of RhCMV/SIV vaccines in RhCMV-seronegative macaques lacking anti-vector immunity. Fifty percent of rhesus macaques (RM) vaccinated with a combined RhCMV-Gag, -Env, and -Retanef (RTN) vaccine controlled pathogenic SIV challenge despite high peak viremia. However, kinetics of viral load control by vaccinated RM were considerably delayed compared to previous reports. Impact of a TLR5 agonist (flagellin; FliC) on vaccine efficacy and immunogenicity was also examined. An altered vaccine regimen containing an SIV Gag-FliC fusion antigen instead of Gag was significantly less immunogenic and resulted in reduced protection. Notably, RhCMV-Gag and RhCMV-Env vaccines elicited anti-Gag and anti-Env antibodies in RhCMV-seronegative RM, an unexpected contrast to vaccination of RhCMV-seropositive RM. These findings confirm that RhCMV-vectored SIV vaccines significantly protect against SIV pathogenesis. However, pre-existing vector immunity and a pro-inflammatory vaccine adjuvant may influence RhCMV/SIV vaccine immunogenicity and efficacy. Future investigation of the impact of pre-existing anti-vector immune responses on protective immunity conferred by this vaccine platform is warranted.
Three-component D–A hybrid heterostructures with enhanced photochromic, photomodulated luminescence and selective anion-sensing properties
Authors: Li Meng-Hua , Lv Shu-Li , You Ming-Hua , Lin Mei-Jin 
Published: August 2020

Three novel three-component hybrid heterostructures with inorganic [CoIII(CN)6]3− anions as electron donors and viologen tectons as electron acceptors exhibit combined properties of photochromism, photomodulated luminescence and anion sensing.
Identification of key gene modules and genes in colorectal cancer by co-expression analysis weighted gene co-expression network analysis
Authors: Wang Peng , Zheng Huaixin , Zhang Jiayu , Wang Yashu , Liu Pingping , Xuan Xiaoyan , Li Qianru , Du Ying 
Published: August 2020

Abstract
Colorectal cancer (CRC) has been one of the most common malignancies worldwide, which tends to get worse for the growth and aging of the population and westernized lifestyle. However, there is no effective treatment due to the complexity of its etiology. Hence, the pathogenic mechanisms remain to be clearly defined. In the present study, we adopted an advanced analytical method—Weighted Gene Co-expression Network Analysis (WGCNA) to identify the key gene modules and hub genes associated with CRC. In total, five gene co-expression modules were highly associated with CRC, of which, one gene module correlated with CRC significantly positive (R = 0.88). Functional enrichment analysis of genes in primary gene module found metabolic pathways, which might be a potentially important pathway involved in CRC. Further, we identified and verified some hub genes positively correlated with CRC by using Cytoscape software and UALCAN databases, including PAICS, ATR, AASDHPPT, DDX18, NUP107 and TOMM6. The present study discovered key gene modules and hub genes associated with CRC, which provide references to understand the pathogenesis of CRC and may be novel candidate target genes of CRC.
Experimentelle Forschung an der Klinik und Poliklinik für Dermatologie und Venerologie
Authors: Boeckmann L. , Bernhardt T. , Schäfer M. , Semmler M. L. , Glatzel A. , Martens M. C. , Ulrich M. , Thiem A. , Tietze J. , Jung O. , Panzer R. , Fischer T. , Emmert S. 
Published: August 2020

ZusammenfassungSeit Antritt von Prof. Dr. med. Steffen Emmert als Ordinarius der Klinik und Poliklinik für Dermatologie und Venerologie im Jahr 2015 konnte das dermatologische Forschungslabor sukzessive aufgebaut und erweitert werden. Im Einklang mit dem onkologischen Schwerpunkt der Universitätsmedizin Rostock sowie dem von der Landesregierung forcierten „Gesundheitsland Mecklenburg-Vorpommern“ wird grundlagenorientierten und translationalen Projekten nachgegangen. Das vorwiegend drittmittelfinanzierte und stetig wachsende Forschungsteam bearbeitet diverse Fragestellungen in den Bereichen der Dermato-Onkologie, Plasmamedizin und seltenen Hauterkrankungen. Inzwischen auf einem soliden Fundament stehend, befindet sich der Forschungsbereich weiterhin in einem dynamischen Entwicklungsprozess. Nicht nur personell, sondern auch thematisch und methodisch wird er derzeit durch die Integration weiterer Arbeitsgruppen unter der Leitung von Ärzten aus der Klinik ergänzt und ausgebaut. Diverse Kollaborationen an der Universitätsmedizin Rostock und im Land zeugen von einem freundlichen, unterstützenden und kollegialen Umfeld, das die Integration am Standort befördert hat.