bluuebunny/crossref_metadata_2025_split huggingface dataset:
A genome-wide scan for candidate lethal variants in Thoroughbred horses
Authors: Todd Evelyn T. , Thomson Peter C. , Hamilton Natasha A. , Ang Rachel A. , Lindgren Gabriella , Viklund Åsa , Eriksson Susanne , Mikko Sofia , Strand Eric , Velie Brandon D. 
Published: August 2020

AbstractDomestic animal populations are often characterised by high rates of inbreeding and low effective population sizes due to selective breeding practices. These practices can result in otherwise rare recessive deleterious alleles drifting to high frequencies, resulting in reduced fertility rates. This study aimed to identify potential recessive lethal haplotypes in the Thoroughbred horse breed, a closed population that has been selectively bred for racing performance. In this study, we identified a haplotype in the LY49B gene that shows strong evidence of being homozygous lethal, despite having high frequencies of heterozygotes in Thoroughbreds and other domestic horse breeds. Variant analysis of whole-genome sequence data identified two SNPs in the 3′UTR of the LY49B gene that may result in loss of function. Analysis of transcriptomic data from equine embryonic tissue revealed that LY49B is expressed in the trophoblast during placentation stage of development. These findings suggest that LY49B may have an essential, but as yet unknown function in the implantation stage of equine development. Further investigation of this region may allow for the development of a genetic test to improve fertility rates in horse populations. Identification of other lethal variants could assist in improving natural levels of fertility in horse populations.
Topical application of Chlorin e6-PVP (Ce6-PVP) for improved endoscopic detection of neoplastic lesions in a murine colitis-associated cancer model
Authors: Ganzleben Ingo , Hohmann Martin , Grünberg Alexander , Gonzales-Menezes Jean , Vieth Michael , Liebing Eva , Günther Claudia , Thonn Veronika , Beß Daniel , Becker Christoph , Schmidt Michael , Neurath Markus F. , Waldner Maximilian J. 
Published: August 2020

AbstractScreening colonoscopy is crucial in reducing the mortality of colorectal cancer. However, detecting adenomas against the backdrop of an inflamed mucosa (e.g. in ulcerative colitis) remains exceedingly difficult. Therefore, we aimed to improve neoplastic lesion detection by employing a fluorescence-based endoscopic approach. We used the well-established murine AOM/DSS model to induce inflammation-driven carcinogenesis in the colon. In our diagnostic approach, we evaluated Chlorin e6 polyvinylpyrrolidone (Ce6-PVP)-based fluorescence endoscopy in comparison to standard white-light endoscopy. A specialized pathologist then analyzed the histology of the detected lesions. Complementary in vitro studies were performed using human cell lines and a murine organoid system. Ce6-PVP-based fluorescence endoscopy had an improved detection rate of 100% (8/8) in detecting high-grade dysplasias and carcinomas over white-light detection alone with 75% (6/8). Trade-off for this superior detection rate was an increased rate of false positive lesions with an increase in the false discovery rate from 45% for white-light endoscopy to 81% for fluorescence endoscopy. We demonstrate in a proof-of-concept study that Ce6-PVP-based fluorescence endoscopy is a highly sensitive red flag technology to identify biopsy-worthy lesions in the colon.
Identification of differentially expressed genes profiles in a combined mouse model of Parkinsonism and colitis
Authors: Gil-Martinez A. L. , Cuenca-Bermejo L. , Gonzalez-Cuello A. M. , Sanchez-Rodrigo C. , Parrado A. , Vyas S. , Fernandez-Villalba E. , Herrero M. T. 
Published: August 2020

AbstractDifferent cellular mechanisms have been described as being potentially involved in the progression of neurodegeneration in Parkinson’s disease, although their role is still unclear. The present study aimed to identify in detail, through differentially expressed genes analysis by bioinformatics approaches, the molecular mechanisms triggered after a systemic insult in parkinsonian mice. To address this objective, we combined a dextran sodium sulfate (DSS)-induced ulcerative colitis experimental mice model with an acute 1-methyl-4-phenyl-1,2,3,6-tetradropyridine (MPTP) intoxication. The animals were divided into four experimental groups based on the different treatments: (i) control, (ii) DSS, (iii) MPTP and (iv) MPTP + DSS. The data obtained by microarray and functional enrichment analysis point out the implication of different molecular mechanisms depending on the experimental condition. We see, in the striatum of animals intoxicated only with DSS, dysfunction processes related to the blood. On the other hand, oxidative stress processes are more prominent at the MPTP intoxicated mice. Finally, differentially expressed genes within the MPTP + DSS show functional enrichment in inflammation and programmed cell death. Interestingly, we identify a significant synergistic negative effect of both toxins since the expression of differentially expressed genes (DEGs) related to balanced cellular homeostasis was not enough to prevent processes associated with cell death. This work provides detailed insights into the involvement of systemic inflammation, triggered after an insult in the colon, in the progression of the degeneration in Parkinsonism. In this way, we will be able to identify promising therapeutic targets that prevent the contribution of inflammatory processes in the progression of Parkinson’s disease.
Nutritional value and safety of animal feed supplemented with Talaromyces verruculosus-treated cocoa pod husks
Authors: Oduro-Mensah Daniel , Ocloo Augustine , Nortey Thomas , Antwi Stephen , Okine Laud K. , Adamafio Naa A. 
Published: August 2020

AbstractTheobromine exerts deleterious effects on animal physiology. Removal of theobromine from the millions of metric tons of cocoa pod husks (CPH) discarded annually could allow for the production of cheap, CPH-based animal feed. The aim of this study was to evaluate safety and nutritional value of bio-detheobrominated CPH in Sprague–Dawley rats. Theobromine was removed from CPH by treatment with an isolate of Talaromyces verruculosus (TvTD). Substituted feeds containing CPH were formulated by replacing 30% or 50% of the maize content of regular rat feed with TvTD-treated or inactivated TvTD-treated CPH. Feeding groups included control groups without or with theobromine administration. Effects of the feed formulations on water and feed intake, weight gain, blood biochemistry and organ-specific toxicity were assessed. Rats ingesting theobromine in inactivated TvTD-treated CPH-based diet or by oral gavage variably exhibited marked deleterious effects, mainly evident in body weight, thymus wet weight and tissue histology. In contrast, substitution with TvTD-treated CPH caused significant increase in body weight. Substitution at 30% did not cause mortality or organ-specific toxicity with reference to the testes, kidneys, spleen or liver, unlike substitution at 50%. The data demonstrate that detheobrominated CPH may safely replace up to 30% of maize in animal feed formulations.
IL-17F induces inflammation, dysfunction and cell death in mouse islets
Authors: Catterall Tara , Fynch Stacey , Kay Thomas W. H. , Thomas Helen E. , Sutherland Andrew P. R. 
Published: August 2020

AbstractType 17 immune responses, typified by the production of the cytokines IL-17A and IL-17F, have been implicated in the development of type 1 diabetes in animal models and human patients, however the underlying pathogenic mechanisms have not been clearly elucidated. While previous studies show that IL-17A enhances inflammatory gene expression and cell death in mouse β-cells and human islets, the function of IL-17F in pancreatic β-cells is completely untested to date. Here we show that IL-17F exhibits potent pathogenic effects in mouse β-cell lines and islets. IL-17F signals via the IL-17RA and -RC subunits in β-cells and in combination with other inflammatory cytokines induces expression of chemokine transcripts, suppresses the expression of β-cell identity genes and impairs glucose stimulated insulin secretion. Further IL-17F induces cell death in primary mouse islets. This occurs via Jnk, p38 and NF-κB dependent induction of Nos2 and is completely ablated in the presence of an inducible nitric oxide synthase (iNOS) inhibitor. Together these data indicate that IL-17F possesses similar pathogenic activities to IL-17A in mouse β-cell lines and islets and is likely to be a type 17 associated pathogenic factor in type 1 diabetes.
High spatially sensitive quantitative phase imaging assisted with deep neural network for classification of human spermatozoa under stressed condition
Authors: Butola Ankit , Popova Daria , Prasad Dilip K. , Ahmad Azeem , Habib Anowarul , Tinguely Jean Claude , Basnet Purusotam , Acharya Ganesh , Senthilkumaran Paramasivam , Mehta Dalip Singh , Ahluwalia Balpreet Singh 
Published: August 2020

AbstractSperm cell motility and morphology observed under the bright field microscopy are the only criteria for selecting a particular sperm cell during Intracytoplasmic Sperm Injection (ICSI) procedure of Assisted Reproductive Technology (ART). Several factors such as oxidative stress, cryopreservation, heat, smoking and alcohol consumption, are negatively associated with the quality of sperm cell and fertilization potential due to the changing of subcellular structures and functions which are overlooked. However, bright field imaging contrast is insufficient to distinguish tiniest morphological cell features that might influence the fertilizing ability of sperm cell. We developed a partially spatially coherent digital holographic microscope (PSC-DHM) for quantitative phase imaging (QPI) in order to distinguish normal sperm cells from sperm cells under different stress conditions such as cryopreservation, exposure to hydrogen peroxide and ethanol. Phase maps of total 10,163 sperm cells (2,400 control cells, 2,750 spermatozoa after cryopreservation, 2,515 and 2,498 cells under hydrogen peroxide and ethanol respectively) are reconstructed using the data acquired from the PSC-DHM system. Total of seven feedforward deep neural networks (DNN) are employed for the classification of the phase maps for normal and stress affected sperm cells. When validated against the test dataset, the DNN provided an average sensitivity, specificity and accuracy of 85.5%, 94.7% and 85.6%, respectively. The current QPI + DNN framework is applicable for further improving ICSI procedure and the diagnostic efficiency for the classification of semen quality in regard to their fertilization potential and other biomedical applications in general.
Reduced Mrp2 surface availability as PI3Kγ-mediated hepatocytic dysfunction reflecting a hallmark of cholestasis in sepsis
Authors: Beer Anne J. , Hertz David , Seemann Eric , Beretta Martina , Westermann Martin , Bauer Reinhard , Bauer Michael , Kessels Michael M. , Qualmann Britta 
Published: August 2020

AbstractSepsis-associated liver dysfunction manifesting as cholestasis is common during multiple organ failure. Three hepatocytic dysfunctions are considered as major hallmarks of cholestasis in sepsis: impairments of microvilli covering canalicular membranes, disruptions of tight junctions sealing bile-collecting canaliculae and disruptions of Mrp2-mediated hepatobiliary transport. PI3Kγ loss-of-function was suggested as beneficial in early sepsis. Yet, the PI3Kγ-regulated cellular processes in hepatocytes remained largely unclear. We analysed all three sepsis hallmarks for responsiveness to massive PI3K/Akt signalling and PI3Kγ loss-of-function, respectively. Surprisingly, neither microvilli nor tight junctions were strongly modulated, as shown by electron microscopical studies of mouse liver samples. Instead, quantitative electron microscopy proved that solely Mrp2 surface availability, i.e. the third hallmark, responded strongly to PI3K/Akt signalling. Mrp2 plasma membrane levels were massively reduced upon PI3K/Akt signalling. Importantly, Mrp2 levels at the plasma membrane of PI3Kγ KO hepatocytes remained unaffected upon PI3K/Akt signalling stimulation. The effect explicitly relied on PI3Kγ’s enzymatic ability, as shown by PI3Kγ kinase-dead mice. Keeping the surface availability of the biliary transporter Mrp2 therefore is a cell biological process that may underlie the observation that PI3Kγ loss-of-function protects from hepatic excretory dysfunction during early sepsis and Mrp2 should thus take center stage in pharmacological interventions.
Unravelling molecular interactions in uracil clusters by XPS measurements assisted by ab initio and tight-binding simulations
Authors: Mattioli Giuseppe , Avaldi Lorenzo , Bolognesi Paola , Bozek John D. , Castrovilli Mattea C. , Chiarinelli Jacopo , Domaracka Alicja , Indrajith Suvasthika , Maclot Sylvain , Milosavljević Aleksandar R. , Nicolafrancesco Chiara , Nicolas Christophe , Rousseau Patrick 
Published: August 2020

AbstractThe C, N and O 1s XPS spectra of uracil clusters in the gas phase have been measured. A new bottom-up approach, which relies on computational simulations starting from the crystallographic structure of uracil, has been adopted to interpret the measured spectra. This approach sheds light on the different molecular interactions (H-bond, π-stacking, dispersion interactions) at work in the cluster and provides a good understanding of the observed XPS chemical shifts with respect to the isolated molecule in terms of intramolecular and intermolecular screening occurring after the core–hole ionization. The proposed bottom-up approach, reasonably expensive in terms of computational resources, has been validated by finite-temperature molecular dynamics simulations of clusters composed of up to fifty molecules.
The perception threshold of the panda illusion, a particular form of 2D pulse-width-modulated halftone, correlates with visual acuity
Authors: Straßer Torsten , Kurtenbach Anne , Langrová Hana , Kuehlewein Laura , Zrenner Eberhart 
Published: August 2020

AbstractTo call attention to the danger of extinction of the panda bear, the Lithuanian artist Ilja Klemencov created the artwork “They can disappear”. The illustration is composed of black-and-white zigzagged lines, which form the famous panda logo of the World Wild Fund For Nature (WWF) when seen from a distance. If one is too close to the artwork, it is difficult to spot the bear, however, if one steps back or takes off one’s glasses the panda suddenly appears. This led us to ask if the ability to see the panda is related to the visual acuity of the observer and if therefore, the panda illusion can be used to assess the spatial resolution of the eye. Here we present the results of the comparison between visual acuity determined using the Landolt C and that predicted from the panda illusion in 23 healthy volunteers with artificially reduced visual acuity. Furthermore, we demonstrate that the panda illusion is based on a 2D pulse-width modulation, explain its technical history, and provide the equations required to create the illusion. Finally, we explain why the illusion indeed can be used to predict visual acuity and discuss the neural causes of its perception with best-corrected visual acuity.
Human antimicrobial peptide, LL-37, induces non-inheritable reduced susceptibility to vancomycin in Staphylococcus aureus
Authors: Friberg Cathrine , Haaber Jakob Krause , Vestergaard Martin , Fait Anaëlle , Perrot Veronique , Levin Bruce R. , Ingmer Hanne 
Published: August 2020

AbstractAntimicrobial peptides (AMPs) are central components of the innate immune system providing protection against pathogens. Yet, serum and tissue concentrations vary between individuals and with disease conditions. We demonstrate that the human AMP LL-37 lowers the susceptibility to vancomycin in the community-associated methicillin-resistant S. aureus (CA-MRSA) strain FPR3757 (USA300). Vancomycin is used to treat serious MRSA infections, but treatment failures occur despite MRSA strains being tested susceptible according to standard susceptibility methods. Exposure to physiologically relevant concentrations of LL-37 increased the minimum inhibitory concentration (MIC) of S. aureus towards vancomycin by 75%, and resulted in shortened lag-phase and increased colony formation at sub-inhibitory concentrations of vancomycin. Computer simulations using a mathematical antibiotic treatment model indicated that a small increase in MIC might decrease the efficacy of vancomycin in clearing a S. aureus infection. This prediction was supported in a Galleria mellonella infection model, where exposure of S. aureus to LL-37 abolished the antimicrobial effect of vancomycin. Thus, physiological relevant concentrations of LL-37 reduce susceptibility to vancomycin, indicating that tissue and host specific variations in LL-37 concentrations may influence vancomycin susceptibility in vivo.
Prognostic value of neutrophil-to-lymphocyte ratio in human epidermal growth factor receptor 2-negative breast cancer patients who received neoadjuvant chemotherapy
Authors: Bae Soong June , Cha Yoon Jin , Yoon Changik , Kim Dooreh , Lee Janghee , Park Soeun , Cha Chihwan , Kim Jee Ye , Ahn Sung Gwe , Park Hyung Seok , Park Seho , Kim Seung Il , Jeong Joon 
Published: August 2020

AbstractWe aimed to investigate the correlation between neutrophil-to-lymphocyte ratio (NLR) and pathologic complete response (pCR) and survival outcomes in human epidermal growth factor receptor 2 (HER2)-negative breast cancer patients who received neoadjuvant chemotherapy. The baseline NLR was evaluated in non-metastatic, HER2-negative breast cancer patients who received neoadjuvant chemotherapy. Baseline NLR was calculated as absolute neutrophil per lymphocyte count from pre-treatment blood samples. Any value ≥ 2.74 was considered to be a high NLR. In the 1,097 patients studied, 272 (24.4%) had high NLR and 825 (75.6%) had low NLR. The high NLR was an independent factor for pCR (OR 0.595; 95% CIs 0.398–0.890; P = 0.011). Furthermore, high NLR was a significant independent parameter affecting DFS (HR 2.298; 95% CIs 1.691–3.124; P < 0.001) and OS (HR 1.905; 95% CIs 1.167–3.108; P = 0.010). Regardless of the baseline NLR, survival outcomes were excellent in patients who achieved pCR, but high NLR was associated with worse survival for patients with residual invasive disease. Our study showed that NLR was predictive for treatment response and a prognostic factor in patients with HER2-negative breast cancer who received neoadjuvant chemotherapy. Moreover, we identified that high NLR was associated with poor survival outcomes in patients who did not achieve pCR.
A preliminary study of the concentration of metallic elements in the blood of patients with multiple sclerosis as measured by ICP-MS
Authors: de Oliveira Marcela , Gianeti Thiago Marcelo Ribeiro , da Rocha Fernando Coronetti Gomes , Lisboa-Filho Paulo Noronha , Piacenti-Silva Marina 
Published: August 2020

AbstractIt is estimated that multiple sclerosis (MS) affects 35,000 Brazilians and 2.5 million individuals worldwide. Many studies have suggested a possible role of metallic elements in the etiology of MS, but their concentration in the blood of MS patients is nonetheless little investigated in Brazil. In this work, these elements were studied through Inductively Coupled Plasma Mass Spectrometry (ICP-MS), whose analysis provides a tool to quantify the concentrations of metal elements in the blood samples of individuals with neurodegenerative disorders. This study aimed to compare the concentration of metallic elements in blood samples from patients with MS and healthy individuals. Blood was collected from 30 patients with multiple sclerosis and compared with the control group. Blood samples were digested in closed vessels using a microwave and ICP-MS was used to determine the concentrations of 12 metallic elements (Ba, Be, Ca, Co, Cr, Cu, Fe, Mg, Mo, Ni, Pb and Zn). In MS patients, we observed a reduction in the concentrations of beryllium, copper, chromium, cobalt, nickel, magnesium and iron. The mean concentration of lead in blood was significantly elevated in the MS group. However, no difference was observed in the concentrations of Mo, Ba, Ca and Zn in blood samples from MS patients and the control group. According to our data, there is a possible role for the concentrations of 8 of the 12 evaluated metallic elements in multiple sclerosis. Abnormalities in transition metals levels in biological matrices have been reported in several neurological diseases.
Reduction of focal sweating by lipid nanoparticle-delivered myricetin
Authors: Ban Choongjin , Park Joon-Bum , Cho Sora , Kim Hye Rin , Kim Yong Joon , Choi Young Jin , Chung Woo-Jae , Kweon Dae-Hyuk 
Published: August 2020

AbstractMyricetin—a flavonoid capable of inhibiting the SNARE complex formation in neurons—reduces focal sweating after skin-application when delivers as encapsulated in lipid nanoparticles (M-LNPs). The stability of M-LNP enables efficient delivery of myricetin to sudomotor nerves located underneath sweat glands through transappendageal pathways while free myricetin just remained on the skin. Furthermore, release of myricetin from M-LNP is accelerated through lipase-/esterase-induced lipolysis in the skin-appendages, enabling uptake of myricetin by the surrounding cells. The amount of sweat is reduced by 55% after application of M-LNP (0.8 mg kg−1) on the mouse footpad. This is comparable to that of subcutaneously injected anticholinergic agents [0.25 mg kg−1 glycopyrrolate; 0.8 U kg−1 botulinum neurotoxin-A-type (BoNT/A)]. M-LNP neither shows a distal effect after skin-application nor induced cellular/ocular toxicity. In conclusion, M-LNP is an efficient skin-applicable antiperspirant. SNARE-inhibitory small molecules with suitable delivery systems have the potential to replace many BoNT/A interventions for which self-applications are preferred.
Single-nucleotide polymorphism rs4664308 in PLA2R1 gene is associated with the risk of idiopathic membranous nephropathy: a meta-analysis
Authors: Yoshikawa Masahiro , Asaba Kensuke 
Published: August 2020

AbstractAlthough many studies investigated the associations between single-nucleotide polymorphisms (SNPs) in the M-type phospholipase A2 receptor-1 (PLA2R1) gene and susceptibility to idiopathic membranous nephropathy (IMN), some showed inconsistent results. Here, we conducted a meta-analysis examining the associations between PLA2R1 SNPs and IMN susceptibility after systematic searches in the PubMed and Web of Science databases. Our meta-analysis for rs4664308 A>G including 2,542 IMN patients and 4,396 controls in seven studies showed a significant association between the G allele and a lower risk of IMN, as determined using an allelic model (odds ratio, 0.45; 95% confidence interval [0.41–0.50]), an additive model (for GG vs. AA: 0.26; [0.21–0.33]; for AG vs. AA: 0.40; [0.36–0.45]), a dominant model (0.37; [0.34–0.42]) and a recessive model (0.38; [0.31–0.48]). Our meta-analysis also suggested associations between rs3828323, rs35771982, rs3749117 and rs3749119 and IMN susceptibility although high heterogeneities and/or publication biases were observed. We did not study in our meta-analysis, but other studies indicated that high-risk genotype combinations of rs2187668 in the human leucocyte antigen-DQ a-chain 1 gene and rs4664308 in the PLA2R1 gene had even stronger associations and could affect the formation of anti-PLA2R1 antibodies, suggesting these SNPs could be novel therapeutic targets.