bluuebunny/crossref_metadata_2025_split huggingface dataset:
Chemometric approach to find relationships between physiological elements and elements causing toxic effects in herb roots by ICP-MS
Authors: Sajnóg Adam , Koko Elwira , Kayzer Dariusz , Barałkiewicz Danuta 
Published: October 2021

AbstractIn this paper 13 elements, both physiological and causing toxic effects, were determined by inductively coupled plasma mass spectrometry in roots of 26 species of herbs used in Traditional Chinese Medicine. The herbs were purchased from online shop in two batches 1 year apart to verify the variability of elemental content in time. The multivariate statistical methods—multiple regression, canonical variates and interaction effect analysis—were applied to interpret the data and to show the relationships between elements and two batches of herb roots. The maximum permissible concentration of Cd (0.3 mg kg−1) was exceeded in 7 herb roots which makes 13% of all specimens. The multiple regression analysis revealed the significant relationships between elements: Mg with Sr; V with Pb, As and Ba; Mn with Pb; Fe with As and Ba; Co with Ni and Sr, Cu with Pb, Cd and As; Zn with Pb, Cd, As and Ba. The canonical variates analysis showed that the statistical inference should not be based solely on the type of herb or number of batch because of the underlying interaction effects between those two variables that may be a source of variability of the content of determined elements.
Altered protein O-GlcNAcylation in placentas from mothers with diabetes causes aberrant endocytosis in placental trophoblast cells
Authors: Palin Victoria , Russell Matthew , Graham Robert , Aplin John D. , Westwood Melissa 
Published: October 2021

AbstractWomen with pre-existing diabetes have an increased risk of poor pregnancy outcomes, including disordered fetal growth, caused by changes to placental function. Here we investigate the possibility that the hexosamine biosynthetic pathway, which utilises cellular nutrients to regulate protein function via post-translationally modification with O-linked N-acetylglucosamine (GlcNAc), mediates the placental response to the maternal metabolic milieu. Mass spectrometry analysis revealed that the placental O-GlcNAcome is altered in women with type 1 (n = 6) or type 2 (n = 6) diabetes T2D (≥ twofold change in abundance in 162 and 165 GlcNAcylated proteins respectively compared to BMI-matched controls n = 11). Ingenuity pathway analysis indicated changes to clathrin-mediated endocytosis (CME) and CME-associated proteins, clathrin, Transferrin (TF), TF receptor and multiple Rabs, were identified as O-GlcNAcylation targets. Stimulating protein O-GlcNAcylation using glucosamine (2.5 mM) increased the rate of TF endocytosis by human placental cells (p = 0.02) and explants (p = 0.04). Differential GlcNAcylation of CME proteins suggests altered transfer of cargo by placentas of women with pre-gestational diabetes, which may contribute to alterations in fetal growth. The human placental O-GlcNAcome provides a resource to aid further investigation of molecular mechanisms governing placental nutrient sensing.
Recreational water exposure and waterborne infections in a prospective salivary antibody study at a Lake Michigan beach
Authors: Egorov Andrey I. , Converse Reagan , Griffin Shannon M. , Bonasso Russell , Wickersham Lindsay , Klein Elizabeth , Kobylanski Jason , Ritter Rebecca , Styles Jennifer N. , Ward Honorine , Sams Elizabeth , Hudgens Edward , Dufour Alfred , Wade Timothy J. 
Published: October 2021

AbstractIn a prospective observational study, seroconversion to a specific pathogen can serve as a marker of an incident infection, whether or not that infection is symptomatic or clinically diagnosed. While self-reported symptoms can be affected by reporting bias, seroconversion is likely to be free of this bias as it is based on objective measurements of antibody response. Non-invasive salivary antibody tests can be used instead of serum tests to detect seroconversions in prospective studies. In the present study, individuals and families were recruited at a Lake Michigan beach in Wisconsin in August 2011. Data on recreational water exposure and baseline saliva samples (S1) were collected at recruitment. Follow-up data on gastrointestinal symptoms were collected via a telephone interview approximately 10 days post-recruitment. Follow-up saliva samples were self-collected approximately 2 weeks (S2) and 30–40 days post-recruitment (S3) and mailed to the study laboratory. Samples were analyzed for immunoglobulin (Ig) G responses to recombinant antigens of three noroviruses and Cryptosporidium, as well as protein purification tags as internal controls, using an in-house multiplex suspension immunoassay on the Luminex platform. Responses were defined as ratios of antibody reactivities with a target protein and its purification tag. Seroconversions were defined as at least four-fold and three-fold increases in responses in S2 and S3 samples compared to S1, respectively. In addition, an S2 response had to be above the upper 90% one-sided prediction limit of a corresponding spline function of age. Among 872 study participants, there were seven (0.8%) individuals with seroconversions, including six individuals with seroconversions to noroviruses and two to Cryptosporidium (one individual seroconverted to both pathogens). Among 176 (20%) individuals who reported swallowing lake water, there were six (3.4%) seroconversions compared to one (0.14%) seroconversion among the remaining 696 individuals: the crude and age-standardized risk differences per 1000 beachgoers were 32.7 (95% confidence limits 5.7; 59.6) and 94.8 (4.6; 276), respectively. The age-adjusted odds ratio of seroconversion in those who swallowed water vs. all others was 49.5 (4.5; 549), p = 0.001. Individuals with a norovirus seroconversion were more likely to experience vomiting symptoms within 4 days of the index beach visit than non-converters with an odds ratio of 34 (3.4, 350), p = 0.003. This study contributed further evidence that recreational water exposure is associated with symptomatic and asymptomatic waterborne infections, and that salivary antibody assays can be used in epidemiological surveys of norovirus and Cryptosporidium infections.
siRNA delivery using intelligent chitosan-capped mesoporous silica nanoparticles for overcoming multidrug resistance in malignant carcinoma cells
Authors: Heidari Razieh , Khosravian Pegah , Mirzaei Seyed Abbas , Elahian Fatemeh 
Published: October 2021

AbstractAlthough siRNA is a promising technology for cancer gene therapy, effective cytoplasmic delivery has remained a significant challenge. In this paper, a potent siRNA transfer system with active targeting moieties toward cancer cells and a high loading capacity is introduced to inhibit drug resistance. Mesoporous silica nanoparticles are of great potential for developing targeted gene delivery. Amino-modified MSNs (NH2-MSNs) were synthesized using a modified sol–gel method and characterized by FTIR, BET, TEM, SEM, X-ray diffraction, DLS, and 1H-NMR. MDR1-siRNA was loaded within NH2-MSNs, and the resulting negative surface was capped by functionalized chitosan as a protective layer. Targeting moieties such as TAT and folate were anchored to chitosan via PEG-spacers. The loading capacity of siRNA and the protective effect of chitosan for siRNA were determined by gel retardation assay. MTT assay, flow cytometry, real-time PCR, and western blot were performed to study the cytotoxicity, cellular uptake assay, targeting evaluation, and MDR1 knockdown efficiency. The synthesized NH2-MSNs had a particle size of ≈ 100 nm and pore size of ≈ 5 nm. siRNA was loaded into NH2-MSNs with a high loading capacity of 20% w/w. Chitosan coating on the surface of siRNA-NH2-MSNs significantly improved the siRNA protection against enzyme activity compared to naked siRNA-NH2-MSNs. MSNs and modified MSNs did not exhibit significant cytotoxicity at therapeutic concentrations in the EPG85.257-RDB and HeLa-RDB lines. The folate-conjugated nanoparticles showed a cellular uptake of around two times higher in folate receptor-rich HeLa-RDB than EPG85.257-RDB cells. The chitosan-coated siRNA-NH2-MSNs produced decreased MDR1 transcript and protein levels in HeLa-RDB by 0.20 and 0.48-fold, respectively. The results demonstrated that functionalized chitosan-coated siRNA-MSNs could be a promising carrier for targeted cancer therapy. Folate-targeted nanoparticles were specifically harvested by folate receptor-rich HeLa-RDB and produced a chemosensitized phenotype of the multidrug-resistant cancer cells.
Podocyte-specific Crb2 knockout mice develop focal segmental glomerulosclerosis
Authors: Tanoue Akiko , Katayama Kan , Ito Yugo , Joh Kensuke , Toda Masaaki , Yasuma Taro , D’Alessandro-Gabazza Corina N. , Kawachi Hiroshi , Yan Kunimasa , Ito Masaaki , Gabazza Esteban C. , Tryggvason Karl , Dohi Kaoru 
Published: October 2021

AbstractCrb2 is a cell polarity-related type I transmembrane protein expressed in the apical membrane of podocytes. Knockdown of crb2 causes glomerular permeability defects in zebrafish, and its complete knockout causes embryonic lethality in mice. There are also reports of Crb2 mutations in patients with steroid-resistant nephrotic syndrome, although the precise mechanism is unclear. The present study demonstrated that podocyte-specific Crb2 knockout mice develop massive albuminuria and microhematuria 2-month after birth and focal segmental glomerulosclerosis and tubulointerstitial fibrosis with hemosiderin-laden macrophages at 6-month of age. Transmission and scanning electron microscopic studies demonstrated injury and foot process effacement of podocytes in 6-month aged podocyte-specific Crb2 knockout mice. The number of glomerular Wt1-positive cells and the expressions of Nphs2, Podxl, and Nphs1 were reduced in podocyte-specific Crb2 knockout mice compared to negative control mice. Human podocytes lacking CRB2 had significantly decreased F-actin positive area and were more susceptible to apoptosis than their wild-type counterparts. Overall, this study's results suggest that the specific deprivation of Crb2 in podocytes induces altered actin cytoskeleton reorganization associated with dysfunction and accelerated apoptosis of podocytes that ultimately cause focal segmental glomerulosclerosis.
Experimental characterization of bending effects for solid and hollow dielectric waveguides at V-band
Authors: Vu Thanh-Luan , Barlerin Stéphane , Stricot Yves , Sauleau Ronan , Ettorre Mauro , González-Ovejero David 
Published: October 2021

AbstractMm-wave dielectric waveguides are a promising and low-cost technology for the transmission of ultra-high data rates. Besides the attenuation (losses) and group delay, the bending loss of the dielectric waveguides is also one of the key parameters to establish the capacity and energy efficiency of such wired links, when deployed in realistic scenarios. In this context, we report the experimental characterizations of bending effects for various solid and hollow commercially available dielectric waveguides at V-band (50–75 GHz). A wide-band transition has been designed to carry out the measurements using a Vector Network Analyzer (VNA) and extension modules. The measured results are in very good agreement with full-wave simulations. Our experimental results show an average bending loss of 1.46 dB over the entire V-band for the fundamental $${HE}_{11}^{y}$$

HE

11

y

mode of a PTFE solid dielectric waveguide (core diameter of 3.06 mm) with a 90° bending angle and 25 mm radius of curvature. This value rises up to 2.88 dB (or 3.25 dB) when bending radius is changed to 15 mm (or bending angle grows up to 140°). The measurements also show that the measured bending losses increase significantly for hollow dielectric waveguides, in particular when the inner to outer diameter ratio gets larger.
Arginine metabolism and nitric oxide turnover in the ZSF1 animal model for heart failure with preserved ejection fraction
Authors: Büttner Petra , Werner Sarah , Baskal Svetlana , Tsikas Dimitrios , Adams Volker , Lurz Philipp , Besler Christian , Knauth Sarah , Bahls Martin , Schwedhelm Edzard , Thiele Holger 
Published: October 2021

AbstractEndothelial dysfunction and altered nitric oxide (NO) metabolism are considered causal factors in heart failure with preserved ejection fraction (HFpEF). NO synthase activity depends on the availability of arginine and its derivatives. Thus, we analyzed arginine, associated metabolites, arginine-metabolizing enzymes and NO turnover in 20-week-old female healthy lean (L-ZSF1) and obese ZSF1 rats (O-ZSF1) with HFpEF. Serum, urine and lysates of liver, kidney and heart were analyzed. There were significantly lower lysine (− 28%), arginine (− 31%), homoarginine (− 72%) and nitrite (− 32%) levels in serum of O-ZSF1 rats. Ornithine (+ 60%) and citrulline (+ 20%) levels were higher. Similar results were found in the heart. Expression of arginine consuming enzymes in liver and kidney was unchanged. Instead, we observed a 5.8-fold higher arginase 1 expression, presumably of granulocyte origin, in serum and > fourfold increased cardiac macrophage invasion in O-ZSF1. We conclude that inflammatory cells in blood and heart consume arginine and probably homoarginine via arginase 1 and inducible NO synthase and release ornithine and citrulline. In combination with evidence for decreased NO turnover in O-ZSF1 rats, we assume lower arginine bioavailability to endothelial NO synthase.
Scaling up DNA digital data storage by efficiently predicting DNA hybridisation using deep learning
Authors: Buterez David 
Published: October 2021

AbstractDeoxyribonucleic acid (DNA) has shown great promise in enabling computational applications, most notably in the fields of DNA digital data storage and DNA computing. Information is encoded as DNA strands, which will naturally bind in solution, thus enabling search and pattern-matching capabilities. Being able to control and predict the process of DNA hybridisation is crucial for the ambitious future of Hybrid Molecular-Electronic Computing. Current tools are, however, limited in terms of throughput and applicability to large-scale problems. We present the first comprehensive study of machine learning methods applied to the task of predicting DNA hybridisation. For this purpose, we introduce an in silico-generated hybridisation dataset of over 2.5 million data points, enabling the use of deep learning. Depending on hardware, we achieve a reduction in inference time ranging from one to over two orders of magnitude compared to the state-of-the-art, while retaining high fidelity. We then discuss the integration of our methods in modern, scalable workflows.
Deep post-GWAS analysis identifies potential risk genes and risk variants for Alzheimer’s disease, providing new insights into its disease mechanisms
Authors: Wang Zhen , Zhang Quanwei , Lin Jhih-Rong , Jabalameli M. Reza , Mitra Joydeep , Nguyen Nha , Zhang Zhengdong D. 
Published: October 2021

AbstractAlzheimer’s disease (AD) is a genetically complex, multifactorial neurodegenerative disease. It affects more than 45 million people worldwide and currently remains untreatable. Although genome-wide association studies (GWAS) have identified many AD-associated common variants, only about 25 genes are currently known to affect the risk of developing AD, despite its highly polygenic nature. Moreover, the risk variants underlying GWAS AD-association signals remain unknown. Here, we describe a deep post-GWAS analysis of AD-associated variants, using an integrated computational framework for predicting both disease genes and their risk variants. We identified 342 putative AD risk genes in 203 risk regions spanning 502 AD-associated common variants. 246 AD risk genes have not been identified as AD risk genes by previous GWAS collected in GWAS catalogs, and 115 of 342 AD risk genes are outside the risk regions, likely under the regulation of transcriptional regulatory elements contained therein. Even more significantly, for 109 AD risk genes, we predicted 150 risk variants, of both coding and regulatory (in promoters or enhancers) types, and 85 (57%) of them are supported by functional annotation. In-depth functional analyses showed that AD risk genes were overrepresented in AD-related pathways or GO terms—e.g., the complement and coagulation cascade and phosphorylation and activation of immune response—and their expression was relatively enriched in microglia, endothelia, and pericytes of the human brain. We found nine AD risk genes—e.g., IL1RAP, PMAIP1, LAMTOR4—as predictors for the prognosis of AD survival and genes such as ARL6IP5 with altered network connectivity between AD patients and normal individuals involved in AD progression. Our findings open new strategies for developing therapeutics targeting AD risk genes or risk variants to influence AD pathogenesis.
Hierarchical genetic structure and implications for conservation of the world’s largest salmonid, Hucho taimen
Authors: Galland Lanie M. , Simmons James B. , Jahner Joshua P. , Luzuriaga-Neira Agusto R. , Sloat Matthew R. , Chandra Sudeep , Hogan Zeb , Jensen Olaf P. , Parchman Thomas L. 
Published: October 2021

AbstractPopulation genetic analyses can evaluate how evolutionary processes shape diversity and inform conservation and management of imperiled species. Taimen (Hucho taimen), the world’s largest freshwater salmonid, is threatened, endangered, or extirpated across much of its range due to anthropogenic activity including overfishing and habitat degradation. We generated genetic data using high throughput sequencing of reduced representation libraries for taimen from multiple drainages in Mongolia and Russia. Nucleotide diversity estimates were within the range documented in other salmonids, suggesting moderate diversity despite widespread population declines. Similar to other recent studies, our analyses revealed pronounced differentiation among the Arctic (Selenge) and Pacific (Amur and Tugur) drainages, suggesting historical isolation among these systems. However, we found evidence for finer-scale structure within the Pacific drainages, including unexpected differentiation between tributaries and the mainstem of the Tugur River. Differentiation across the Amur and Tugur basins together with coalescent-based demographic modeling suggests the ancestors of Tugur tributary taimen likely diverged in the eastern Amur basin, prior to eventual colonization of the Tugur basin. Our results suggest the potential for differentiation of taimen at different geographic scales, and suggest more thorough geographic and genomic sampling may be needed to inform conservation and management of this iconic salmonid.
Relationship between chronic kidney disease and sarcopenia
Authors: Yu Ming-Dian , Zhang Hui-Zhen , Zhang Yu , Yang Sheng-Ping , Lin Miao , Zhang Yan-Min , Wu Jia-Bin , Hong Fu-Yuan , Chen Wen-Xin 
Published: October 2021

AbstractFew studies have investigated the relationship between sarcopenia and mild to moderate renal decline. This study aimed to investigate the relationship between chronic kidney disease (CKD) and sarcopenia. In total, 123 patients hospitalized with CKD and 57 healthy volunteers who underwent physical examination during the same period (control group) were analyzed. Body compositions were measured by dual-energy X-ray absorptiometry, and the relative appendicular skeletal muscle index (RASMI) was calculated. Muscular strength was evaluated using hydraulic hand dynamometer. Walking speed within 6 m was measured for muscular function assessment. Single-photon emission computed tomography was performed to measure the glomerular filtration rate of CKD patients, who were then divided into CKD1 (55 patients in CKD stages 1 and 2) and CKD2 (68 patients in CKD stages 3–5). RASMI showed a downward trend with CKD progression (P = 0.001). Multivariate logistic regression analysis showed that age and CKD progression were independent risk factors for sarcopenia. The morbidity of sarcopenia was significantly greater in CKD patients than in healthy volunteers, and the degree of muscle loss was closely related to CKD progression.
Drug repurposing improves disease targeting 11-fold and can be augmented by network module targeting, applied to COVID-19
Authors: Rivero-García Inés , Castresana-Aguirre Miguel , Guglielmo Luca , Guala Dimitri , Sonnhammer Erik L. L. 
Published: October 2021

AbstractThis analysis presents a systematic evaluation of the extent of therapeutic opportunities that can be obtained from drug repurposing by connecting drug targets with disease genes. When using FDA-approved indications as a reference level we found that drug repurposing can offer an average of an 11-fold increase in disease coverage, with the maximum number of diseases covered per drug being increased from 134 to 167 after extending the drug targets with their high confidence first neighbors. Additionally, by network analysis to connect drugs to disease modules we found that drugs on average target 4 disease modules, yet the similarity between disease modules targeted by the same drug is generally low and the maximum number of disease modules targeted per drug increases from 158 to 229 when drug targets are neighbor-extended. Moreover, our results highlight that drug repurposing is more dependent on target proteins being shared between diseases than on polypharmacological properties of drugs. We apply our drug repurposing and network module analysis to COVID-19 and show that Fostamatinib is the drug with the highest module coverage.
Two-photon interferences of weak coherent lights
Authors: Kim Heonoh , Kwon Osung , Moon Han Seb 
Published: October 2021

AbstractMultiphoton interference is an important phenomenon in modern quantum mechanics and experimental quantum optics, and it is fundamental for the development of quantum information science and technologies. Over the last three decades, several theoretical and experimental studies have been performed to understand the essential principles underlying such interference and to explore potential applications. Recently, the two-photon interference (TPI) of phase-randomized weak coherent states has played a key role in the realization of long-distance quantum communication based on the use of classical light sources. In this context, we investigated TPI experiments with weak coherent pulses at the single-photon level and quantitatively analyzed the results in terms of the single- and coincidence-counting rates and one- and two-photon interference-fringe shapes. We experimentally examined the Hong–Ou–Mandel-type TPI of phase-randomized weak coherent pulses to compare the TPI effect with that of correlated photons. Further experiments were also performed with two temporally- and spatially separated weak coherent pulses. Although the observed interference results, including the results of visibility and fringe shape, can be suitably explained by classical intensity correlation, the physics underlying the TPI effect needs to be interpreted as the interference between the two-photon states at the single-photon level within the utilized interferometer. The results of this study can provide a more comprehensive understanding of the TPI of coherent light at the single-photon level.