bluuebunny/crossref_metadata_2025_split huggingface dataset:
Restoring colistin sensitivity in colistin-resistant E. coli: Combinatorial use of MarR inhibitor with efflux pump inhibitor
Authors: Sundaramoorthy Niranjana Sri , Suresh Pavithira , Selva Ganesan Subramaniapillai , GaneshPrasad ArunKumar , Nagarajan Saisubramanian 
Published: December 2019

AbstractAntibiotics like colistin are the last resort to deal with infections by carbapenem-resistant Enterobacteriaceae (CREB). Resistance to colistin severely restricts therapeutic options. To tackle this dire situation, urgent measures to restore colistin sensitivity are needed. In this study, whole-genome sequencing of colistin-resistant E. coli strain was performed and the genome analysis revealed that the strain belonged to the sequence type ST405. Multiple mutations were observed in genes implicated in colistin resistance, especially those related to the L-Ara-4-N pathway but mgrB was unmutated and mcr1-9 genes were missing. MarR inhibitor salicylate was used to re-sensitize this strain to colistin, which increased the negative charge on the cell surface especially in colistin resistant E. coli (U3790 strain) and thereby facilitated a decrease in colistin MIC by 8 fold. It is indeed well known that MarR inhibition by salicylate triggers the expression of AcrAB efflux pumps through MarA. So, in order to fully restore colistin sensitivity, a potent efflux pump inhibitor (BC1), identified earlier by this group was employed. The combination of colistin with both salicylate and BC1 caused a remarkable 6 log reduction in cell counts of U3790 in time-kill assay. Infection of muscle tissue of zebrafish with U3790 followed by various treatments showed that the combination of colistin + salicylate + BC1 was highly effective in reducing bioburden in infected muscle tissue by 4 log fold. Thus, our study shows that a combination of MarR inhibitor to enhance colistin binding and efflux pump inhibitor to reduce colistin extrusion was highly effective in restoring colistin sensitivity in colistin-resistant clinical isolate of E. coli in vitro and in vivo.
Effects of cold exposure revealed by global transcriptomic analysis in ferret peripheral blood mononuclear cells
Authors: Reynés Bàrbara , van Schothorst Evert M. , Keijer Jaap , Palou Andreu , Oliver Paula 
Published: December 2019

AbstractAnimal studies, mostly performed in rodents, show the beneficial anti-obesity effects of cold studies. This is due to thermogenic activation of brown adipose tissue (BAT), a tissue also recently discovered in adult humans. Studies in humans, however, are hampered by the accessibility of most tissues. In contrast, peripheral blood mononuclear cells (PBMC) are accessible and share the expression profile of different sets of genes with other tissues, including those that reflect metabolic responses. Ferrets are an animal model physiologically closer to humans than rodents. Here, we investigated the effects on ferrets of one-week acclimation to 4 °C by analysing the PBMC transcriptome. Cold exposure deeply affected PBMC gene expression, producing a widespread down-regulation of genes involved in different biological pathways (cell cycle, gene expression regulation/protein synthesis, immune response, signal transduction, and genes related to extracellular matrix/cytoskeleton), while thermogenic and glycogenolysis-related processes were increased. Results obtained in PBMC reflected those of adipose tissue, but hardly those of the liver. Our study, using ferret as a model, reinforce PBMC usefulness as sentinel biological material for cold-exposure studies in order to deepen our understanding of the general and specific pathways affected by cold acclimation. This is relevant for future development of therapies to be used clinically.
Place of death trends among patients with dementia in Japan: a population-based observational study
Authors: Koyama Toshihiro , Sasaki Misato , Hagiya Hideharu , Zamami Yoshito , Funahashi Tomoko , Ohshima Ayako , Tatebe Yasuhisa , Mikami Naoko , Shinomiya Kazuaki , Kitamura Yoshihisa , Sendo Toshiaki , Hinotsu Shiro , Kano Mitsunobu R. 
Published: December 2019

AbstractDementia is a major public health concern in ageing societies. Although the population of Japan is among the most aged worldwide, long-term trends in the place of death (PoD) among patients with dementia is unknown. In this Japanese nationwide observational study, we analysed trends in PoD using the data of patients with dementia who were aged ≥65 years and died during 1999–2016. Trends in the crude death rates and PoD frequencies were analysed using the Joinpoint regression model. Changes in these trends were assessed using the Joinpoint regression analysis in which significant change points, the annual percentage change (APC) and average APCs (AAPC) in hospitals, homes, or nursing homes were estimated. During 1999–2016, the number of deaths among patients with dementia increased from 3,235 to 23,757 (total: 182,000). A trend analysis revealed increased mortality rates, with an AAPC of 8.2% among men and 9.3% among women. Most patients with dementia died in the hospital, although the prevalence of hospital deaths decreased (AAPC: -1.0%). Moreover, the prevalence of nursing home deaths increased (AAPC: 5.6%), whereas the prevalence of home deaths decreased (AAPC: -5.8%). These findings support a reconsideration of the end-of-life care provided to patients with dementia.
Genetic risk score for risk prediction of diabetic nephropathy in Han Chinese type 2 diabetes patients
Authors: Liao Li-Na , Li Tsai-Chung , Li Chia-Ing , Liu Chiu-Shong , Lin Wen-Yuan , Lin Chih-Hsueh , Yang Chuan-Wei , Chen Ching-Chu , Chang Chiz-Tzung , Yang Ya-Fei , Liu Yao-Lung , Kuo Huey-Liang , Tsai Fuu-Jen , Lin Cheng-Chieh 
Published: December 2019

AbstractWe evaluated whether genetic information could offer improvement on risk prediction of diabetic nephropathy (DN) while adding susceptibility variants into a risk prediction model with conventional risk factors in Han Chinese type 2 diabetes patients. A total of 995 (including 246 DN cases) and 519 (including 179 DN cases) type 2 diabetes patients were included in derivation and validation sets, respectively. A genetic risk score (GRS) was constructed with DN susceptibility variants based on findings of our previous genome-wide association study. In derivation set, areas under the receiver operating characteristics (AUROC) curve (95% CI) for model with clinical risk factors only, model with GRS only, and model with clinical risk factors and GRS were 0.75 (0.72–0.78), 0.64 (0.60–0.68), and 0.78 (0.75–0.81), respectively. In external validation sample, AUROC for model combining conventional risk factors and GRS was 0.70 (0.65–0.74). Additionally, the net reclassification improvement was 9.98% (P = 0.001) when the GRS was added to the prediction model of a set of clinical risk factors. This prediction model enabled us to confirm the importance of GRS combined with clinical factors in predicting the risk of DN and enhanced identification of high-risk individuals for appropriate management of DN for intervention.
The neurocognitive gains of diagnostic reasoning training using simulated interactive veterinary cases
Authors: Nassar Maaly 
Published: December 2019

AbstractThe present longitudinal study ascertained training-associated transformations in the neural underpinnings of diagnostic reasoning, using a simulation game named “Equine Virtual Farm” (EVF). Twenty participants underwent structural, EVF/task-based and resting-state MRI and diffusion tensor imaging (DTI) before and after completing their training on diagnosing simulated veterinary cases. Comparing playing veterinarian versus seeing a colorful image across training sessions revealed the transition of brain activity from scientific creativity regions pre-training (left middle frontal and temporal gyrus) to insight problem-solving regions post-training (right cerebellum, middle cingulate and medial superior gyrus and left postcentral gyrus). Further, applying linear mixed-effects modelling on graph centrality metrics revealed the central roles of the creative semantic (inferior frontal, middle frontal and angular gyrus and parahippocampus) and reward systems (orbital gyrus, nucleus accumbens and putamen) in driving pre-training diagnostic reasoning; whereas, regions implicated in inductive reasoning (superior temporal and medial postcentral gyrus and parahippocampus) were the main post-training hubs. Lastly, resting-state and DTI analysis revealed post-training effects within the occipitotemporal semantic processing region. Altogether, these results suggest that simulation-based training transforms diagnostic reasoning in novices from regions implicated in creative semantic processing to regions implicated in improvised rule-based problem-solving.
Biological Carbon Recovery from Sugar Refinery Washing Water into Microalgal DHA: Medium Optimization and Stress Induction
Authors: Moon Myounghoon , Park Won-Kun , Suh William I. , Chang Yong Keun , Lee Bongsoo 
Published: December 2019

AbstractSugar refinery washing water (SRWW) contains abundant levels of carbon sources and lower levels of contaminants than other types of wastewater, which makes it ideal for heterotrophic cultivation of microalgae. Here, carbon sources in SRWW were utilized for conversion into the form of value-added docosahexaenoic acid (DHA) usingAurantiochytriumsp. KRS101. Since SRWW is not a defined medium, serial optimizations were performed to maximize the biomass, lipid, and DHA yields by adjusting the nutrient (carbon, nitrogen, and phosphorus) concentrations as well as the application of salt stress. Optimum growth performance was achieved with 30% dilution of SRWW containing a total organic carbon of 95,488 mg L−1. Increasing the nutrient level in the medium by supplementation of 9 g L−1KH2PO4and 20 g L−1yeast extract further improved the biomass yield by an additional 14%, albeit at the expense of a decrease in the lipid content. Maximum biomass, lipid, and DHA yields (22.9, 6.33, and 2.03 g L−1, respectively) were achieved when 35 g L−1sea salt was applied on a stationary phase for osmotic stress. These results demonstrate the potential of carbon-rich sugar refinery washing water for DHA production usingAurantiochytriumsp. KRS101 and proper cultivation strategy.
Evaluation of mitochondria in oocytes following γ-irradiation
Authors: Wang Qiaochu , Stringer Jessica M. , Liu Jun , Hutt Karla J. 
Published: December 2019

AbstractStandard cytotoxic cancer treatments, such as radiation, can damage and deplete the supply of oocytes stored within the ovary, which predisposes females to infertility and premature menopause later in life. The mechanisms by which radiation induces oocyte damage have not been completely elucidated. The objective of this study was to determine if γ-irradiation changes mitochondrial characteristics in oocytes, possibly contributing to a reduction in oocyte number and quality. Immature oocytes were collected from postnatal day (PN) 9–11 C57Bl6 mice 3, 6 and 24 hours after 0.1 Gy γ-irradiation to monitor acute mitochondrial changes. Oocytes were classified as small (>20 µm) or growing (40–60 µm). Mitochondrial membrane potential was lost in 20% and 44% of small oocytes (~20 µm) at 3 and 6 hours after γ-irradiation, respectively, consistent with the induction of apoptosis. However, mitochondrial mass, distribution and membrane potential in the surviving small oocytes were similar to the non-irradiated controls at both time points. At 24 hours after γ-irradiation, all mitochondrial parameters analysed within immature oocytes were similar to untreated controls. Mitochondrial parameters within growing oocytes were also similar to untreated controls. When mice were superovulated more than 3 weeks after γ-irradiation, there was a significant reduction in the number of mature oocytes harvested compared to controls (Control 18 ± 1 vs 0.1 Gy 4 ± 1, n = 6/16 mice, p < 0.05). There was a slight reduction in mitochondrial mass in mature oocytes after γ-irradiation, though mitochondrial localization, mtDNA copy number and ATP levels were similar between groups. In summary, this study shows that γ-irradiation of pre-pubertal mice is associated with loss of mitochondrial membrane potential in a significant proportion of small immature oocytes and a reduction in the number of mature oocytes harvested from adult mice. Furthermore, these results suggest that immature oocytes that survive γ-irradiation and develop through to ovulation contain mitochondria with normal characteristics. Whether the oocytes that survive radiation and eventually undergo meiosis can support fertility remains to be determined.
Impact of spaceflight on the murine thymus and mitigation by exposure to artificial gravity during spaceflight
Authors: Horie Kenta , Kato Tamotsu , Kudo Takashi , Sasanuma Hiroki , Miyauchi Maki , Akiyama Nobuko , Miyao Takahisa , Seki Takao , Ishikawa Tatsuya , Takakura Yuki , Shirakawa Masaki , Shiba Dai , Hamada Michito , Jeon Hyojung , Yoshida Nobuaki , Inoue Jun-ichiro , Muratani Masafumi , Takahashi Satoru , Ohno Hiroshi , Akiyama Taishin 
Published: December 2019

AbstractThe environment experienced during spaceflight may impact the immune system and the thymus appears to undergo atrophy during spaceflight. However, molecular aspects of this thymic atrophy remain to be elucidated. In this study, we analysed the thymi of mice on board the international space station (ISS) for approximately 1 month. Thymic size was significantly reduced after spaceflight. Notably, exposure of mice to 1 × gusing centrifugation cages in the ISS significantly mitigated the reduction in thymic size. Although spaceflight caused thymic atrophy, the global thymic structure was not largely changed. However, RNA sequencing analysis of the thymus showed significantly reduced expression of cell cycle-regulating genes in two independent spaceflight samples. These reductions were partially countered by 1 × gexposure during the space flights. Thus, our data suggest that spaceflight leads to reduced proliferation of thymic cells, thereby reducing the size of the thymus, and exposure to 1 × gmight alleviate the impairment of thymus homeostasis induced by spaceflight.
Genomic and functional gene studies suggest a key role of beta-carotene oxygenase 1 like (bco1l) gene in salmon flesh color
Authors: Helgeland Hanna , Sodeland Marte , Zoric Nina , Torgersen Jacob Seilø , Grammes Fabian , von Lintig Johannes , Moen Thomas , Kjøglum Sissel , Lien Sigbjørn , Våge Dag Inge 
Published: December 2019

AbstractRed coloration of muscle tissue (flesh) is a unique trait in several salmonid genera, including Atlantic salmon. The color results from dietary carotenoids deposited in the flesh, whereas the color intensity is affected both by diet and genetic components. Herein we report on a genome-wide association study (GWAS) to identify genetic variation underlying this trait. Two SNPs on ssa26 showed strong associations to the flesh color in salmon. Two genes known to be involved in carotenoid metabolism were located in this QTL- region: beta-carotene oxygenase 1 (bco1) and beta-carotene oxygenase 1 like (bco1l). To determine whether flesh color variation is caused by one, or both, of these genes, functional studies were carried out including mRNA and protein expression in fish with red and pale flesh color. The catalytic abilities of these two genes were also tested with different carotenoids. Our results suggest bco1l to be the most likely gene to explain the flesh color variation observed in this population.
Post-comatose patients with minimal consciousness tend to preserve reading comprehension skills but neglect syntax and spelling
Authors: Kwiatkowska Agnieszka , Lech Michał , Odya Piotr , Czyżewski Andrzej 
Published: December 2019

AbstractModern eye tracking technology provides a means for communication with patients suffering from disorders of consciousness (DoC) or remaining in locked-in-state. However, being able to use an eye tracker for controlling text-based contents by such patients requires preserved reading ability in the first place. To our knowledge, this aspect, although of great social importance, so far has seemed to be neglected. In the paper, we presented the possibility of using an eye-tracking technology for assessing reading comprehension skills in post-comatose patients with minimal consciousness. We prepared various syllable-, word- and sentence-based tasks, controlled by gaze, used for assessing the reading comprehension skills. The obtained results showed that people with minimal consciousness preserved the reading comprehension skills, in most cases to a high extent, but had difficulties with recognizing errors in the written text. The ability to maintain attention during performing the tasks was in statistically significant correlation with motivation, and that one was in a statistically significant correlation with the reading ability. The results indicate that post-comatose patients with minimal consciousness can read words and sentences, hence some useful hints may be provided for the development of gaze tracking-based human-computer interfaces for these people.
Spatio-temporal expression and distribution of collagen VI during zebrafish development
Authors: Tonelotto Valentina , Trapani Valeria , Bretaud Sandrine , Heumüller Stefanie Elisabeth , Wagener Raimund , Ruggiero Florence , Bonaldo Paolo 
Published: December 2019

AbstractCollagen VI (ColVI) is an extracellular matrix (ECM) protein involved in a range of physiological and pathological conditions. Zebrafish (Danio rerio) is a powerful model organism for studying vertebrate development and for in vivo analysis of tissue patterning. Here, we performed a thorough characterization of ColVI gene and protein expression in zebrafish during development and adult life. Bioinformatics analyses confirmed that zebrafish genome contains single genes encoding for α1(VI), α2(VI) and α3(VI) ColVI chains and duplicated genes encoding for α4(VI) chains. At 1 day post-fertilization (dpf) ColVI transcripts are expressed in myotomes, pectoral fin buds and developing epidermis, while from 2 dpf abundant transcript levels are present in myosepta, pectoral fins, axial vasculature, gut and craniofacial cartilage elements. Using newly generated polyclonal antibodies against zebrafish α1(VI) protein, we found that ColVI deposition in adult fish delineates distinct domains in the ECM of several organs, including cartilage, eye, skin, spleen and skeletal muscle. Altogether, these data provide the first detailed characterization of ColVI expression and ECM deposition in zebrafish, thus paving the way for further functional studies in this species.
A genetic toolkit for the analysis of metabolic changes in Drosophila provides new insights into metabolic responses to stress and malignant transformation
Authors: Gándara L. , Durrieu L. , Behrensen C. , Wappner P. 
Published: December 2019

AbstractRegulation of the energetic metabolism occurs fundamentally at the cellular level, so analytical strategies must aim to attain single cell resolution to fully embrace its inherent complexity. We have developed methods to utilize a toolset of metabolic FRET sensors for assessing lactate, pyruvate and 2-oxoglutarate levels of Drosophila tissues in vivo by imaging techniques. We show here how the energetic metabolism is altered by hypoxia: While some larval tissues respond to low oxygen levels by executing a metabolic switch towards lactic fermentation, the fat body and salivary glands do not alter their energetic metabolism. Analysis of tumor metabolism revealed that depending on the genetic background, some tumors undergo a lactogenic switch typical of the Warburg effect, while other tumors do not. This toolset allows for developmental and physiologic studies in genetically manipulated Drosophila individuals in vivo.
Detection and genotyping of CMV and HPV in tumors and fallopian tubes from epithelial ovarian cancer patients
Authors: Paradowska Edyta , Jabłońska Agnieszka , Studzińska Mirosława , Wilczyński Miłosz , Wilczyński Jacek R. 
Published: December 2019

AbstractViral and bacterial infections are detected in epithelial ovarian cancer (EOC) tissues. Since the fallopian tubes are often affected by pelvic inflammatory disease (PID) and the majority of serous EOCs appear to originate from dysplastic lesions in the distal tube, it is relevant to consider the potential role that infectious agents may play in ovarian carcinogenesis. We sought to analyze the prevalence of human papillomavirus (HPV) and cytomegalovirus (CMV) in EOC tissue and fallopian tube specimens obtained at tumor resection. Ovarian cancer and fallopian tube tissue samples obtained from patients with EOC were analyzed by both qualitative and quantitative PCR to detect and quantify viral DNA. The presence of CMV and HPV DNA was detected in 70% and 74% cancerous ovarian tissues, respectively, and was significantly higher in EOC than in benign tumor cases (P ≤ 0.01). CMV or HPV infection was observed also in the fallopian tube samples. Infection with HPV16 was determined in 70% of EOC cases. Almost two thirds of EOC patients demonstrated coinfection with CMV and HPV in the pathological samples. The results revealed that the presence of CMV and HPV in EOC samples is common. CMV and HPV infections can be potential risks for EOC development.
Phenoxyethyl Piperidine/Morpholine Derivatives as PAS and CAS Inhibitors of Cholinesterases: Insights for Future Drug Design
Authors: Pourshojaei Yaghoub , Abiri Ardavan , Eskandari Khalil , Haghighijoo Zahra , Edraki Najmeh , Asadipour Ali 
Published: December 2019

AbstractAcetylcholinesterase (AChE) catalyzes the conversion of Aβ peptide to its aggregated form and the peripheral anionic site (PAS) of AChE is mainly involved in this phenomenon. Also catalytic active site (CAS) of donepezil stimulates the break-down of acetylcholine (ACh) and depletion of ACh in cholinergic synapses are well established in brains of patients with AD. In this study, a set of compounds bearing phenoxyethyl amines were synthesized and their inhibitory activity toward electric eel AChE (eeAChE) and equine butyrylcholinesterase (eqBuChE) were evaluated. Molecular dynamics (MD) was employed to record the binding interactions of best compounds against human cholinesterases (hAChE and hBuChE) as well as donepezil as reference drug. In vitro results revealed that compound 5c is capable of inhibiting eeAChE activity at IC50 of 0.50 µM while no inhibitory activity was found for eqBuChE for up to 100 µM concentrations. Compound 5c, also due to its facile synthesis, small structure and high selectivity for eeAChE would be very interesting candidate in forthcoming studies. The main interacting parts of compound 5c and compound 7c (most potent eeAChE and eqBuChE inhibitors respectively) with receptors which confer selectivity for AChE and BuChE inhibition were identified, discussed, and compared with donepezil’s interactions. Also during MD simulation it was discovered for the first time that binding of substrates like donepezil to dual CAS and PAS or solely CAS region might have a suppressive impact on 4-α-helical bundles near the tryptophan amphiphilic tetramerization (WAT) domain of AChE and residues which are far away from AChE active site. The results proposed that residues involved in donepezil interactions (Trp86 and Phe295) which are located in CAS and mid-gorge are the mediator of conformational changes in whole protein structure.