bluuebunny/crossref_metadata_2025_split huggingface dataset:
Dual-probe molecular MRI for the in vivo characterization of atherosclerosis in a mouse model: Simultaneous assessment of plaque inflammation and extracellular-matrix remodeling
Authors: Reimann Carolin , Brangsch Julia , Kaufmann Jan O. , Adams Lisa C. , Onthank David C. , Thöne-Reineke Christa , Robinson Simon P. , Hamm Bernd , Botnar Rene M. , Makowski Marcus R. 
Published: September 2019

AbstractMolecular MRI is a promising in-vivo modality to detect and quantify morphological and molecular vessel-wall changes in atherosclerosis. The combination of different molecular biomarkers may improve the risk stratification of patients. This study aimed to investigate the feasibility of simultaneous visualization and quantification of plaque-burden and inflammatory activity by dual-probe molecular MRI in a mouse-model of progressive atherosclerosis and in response-to-therapy. Homozygous apolipoprotein E knockout mice (ApoE−/−) were fed a high-fat-diet (HFD) for up to four-months prior to MRI of the brachiocephalic-artery. To assess response-to-therapy, a statin was administered for the same duration. MR imaging was performed before and after administration of an elastin-specific gadolinium-based and a macrophage-specific iron-oxide-based probe. Following in-vivo MRI, samples were analyzed using histology, immunohistochemistry, inductively-coupled-mass-spectrometry and laser-inductively-coupled-mass-spectrometry. In atherosclerotic-plaques, intraplaque expression of elastic-fibers and inflammatory activity were not directly linked. While the elastin-specific probe demonstrated the highest accumulation in advanced atherosclerotic-plaques after four-months of HFD, the iron-oxide-based probe showed highest accumulation in early atherosclerotic-plaques after two-months of HFD. In-vivo measurements for the elastin and iron-oxide-probe were in good agreement with ex-vivo histopathology (Elastica-van-Giesson stain: y = 298.2 + 5.8, R2 = 0.83, p < 0.05; Perls‘ Prussian-blue-stain: y = 834.1 + 0.67, R2 = 0.88, p < 0.05). Contrast-to-noise-ratio (CNR) measurements of the elastin probe were in good agreement with ICP-MS (y = 0.11x-11.3, R² = 0.73, p < 0.05). Late stage atherosclerotic-plaques displayed the strongest increase in both CNR and gadolinium concentration (p < 0.05). The gadolinium probe did not affect the visualization of the iron-oxide-probe and vice versa. This study demonstrates the feasibility of simultaneous assessment of plaque-burden and inflammatory activity by dual-probe molecular MRI of progressive atherosclerosis. The in-vivo detection and quantification of different MR biomarkers in a single scan could be useful to improve characterization of atherosclerotic-lesions.
Association study identified biologically relevant receptor genes with synergistic functions in celiac disease
Authors: Banerjee Pratibha , Bhagavatula Sandilya , Sood Ajit , Midha Vandana , Thelma B. K. , Senapati Sabyasachi 
Published: September 2019

AbstractReceptors are essential mediators of cellular physiology, which facilitate molecular and cellular cross-talk with the environment. Nearly 20% of the all known celiac disease (CD) genes are receptors by function. We hypothesized that novel biologically relevant susceptibility receptor genes act in synergy in CD pathogenesis. We attempted to identify novel receptor genes in CD by re-analyzing published Illumina Immunochip dense genotype data for a north Indian and a European (Dutch) cohort. North Indian dataset was screened for 269 known receptor genes. Association statistics for SNPs were considered with minor allele frequency >15% and association P ≤ 0.005 to attend desired study power. Identified markers were tested for cross-ethnic replication in a European CD dataset. Markers were analyzed in-silico to explain their functional significance in CD. Six novel SNPs from MOG (rs29231, p = 1.21e-11), GABBR1 (rs3025643, p = 1.60e-7), OR2H2 (rs1233388, p = 0.0002), ABCF1 (rs9262119, p = 0.0005), ADRA1A (rs10102024, p = 0.003), and ACVR2A (rs7560426, p = 0.004) were identified in north Indians, of which three genes namely, GABBR1 (rs3025643, p = 5.38e-8), OR2H2 (rs1233388, p = 3.29e-5) and ABCF1 (rs9262119, p = 0.0002) were replicated in Dutch. Tissue specific functional annotation, potential epigenetic regulation, co-expression, protein-protein interaction and pathway enrichment analyses indicated differential expression and synergistic function of key genes that could alter cellular homeostasis, ubiquitination mediated phagosome pathway and cellular protein processing to contribute for CD. At present multiple therapeutic compounds/drugs are available targeting GABBR1 and ADRA1A, which could be tested for their effectiveness against CD in controlled drug trials.
Conservation and novelty in the microRNA genomic landscape of hyperdiverse cichlid fishes
Authors: Xiong Peiwen , Schneider Ralf F. , Hulsey C. Darrin , Meyer Axel , Franchini Paolo 
Published: September 2019

AbstractMicroRNAs (miRNAs) play crucial roles in the post-transcriptional control of messenger RNA (mRNA). These miRNA-mRNA regulatory networks are present in nearly all organisms and contribute to development, phenotypic divergence, and speciation. To examine the miRNA landscape of cichlid fishes, one of the most species-rich families of vertebrates, we profiled the expression of both miRNA and mRNA in a diverse set of cichlid lineages. Among these, we found that conserved miRNAs differ from recently arisen miRNAs (i.e. lineage specific) in average expression levels, number of target sites, sequence variability, and physical clustering patterns in the genome. Furthermore, conserved miRNA target sites tend to be enriched at the 5′ end of protein-coding gene 3′ UTRs. Consistent with the presumed regulatory role of miRNAs, we detected more negative correlations between the expression of miRNA-mRNA functional pairs than in random pairings. Finally, we provide evidence that novel miRNA targets sites are enriched in genes involved in protein synthesis pathways. Our results show how conserved and evolutionarily novel miRNAs differ in their contribution to the genomic landscape and highlight their particular evolutionary roles in the adaptive diversification of cichlids.
DeNeRD: high-throughput detection of neurons for brain-wide analysis with deep learning
Authors: Iqbal Asim , Sheikh Asfandyar , Karayannis Theofanis 
Published: September 2019

AbstractMapping the structure of the mammalian brain at cellular resolution is a challenging task and one that requires capturing key anatomical features at the appropriate level of analysis. Although neuroscientific methods have managed to provide significant insights at the micro and macro level, in order to obtain a whole-brain analysis at a cellular resolution requires a meso-scopic approach. A number of methods can be currently used to detect and count cells, with, nevertheless, significant limitations when analyzing data of high complexity. To overcome some of these constraints, we introduce a fully automated Artificial Intelligence (AI)-based method for whole-brain image processing to Detect Neurons in different brain Regions during Development (DeNeRD). We demonstrate a high performance of our deep neural network in detecting neurons labeled with different genetic markers in a range of imaging planes and imaging modalities.
Gene co-expression network analysis reveals key potential gene modules in utero-vaginal junction associated with duration of fertility trait of breeder hens
Authors: Gu Lantao , Jing Ruoxi , Gong Yanzhang , Yu Mei , Elokil Abdelmotaleb , Li Shijun 
Published: September 2019

AbstractThe number of days (DN) when hens lay fertile eggs as well as the number of fertile eggs (FN) were produced after a single artificial insemination (AI), including the two duration of fertility (DF) traits. Indeed, they are the key production performance that associates with the production cost of hatching egg when its determination the interval between successive artificial inseminations. However, the relevant genes response for regulating the DF has not been uncovered yet. Therefore, we performed a weighted gene co-expression network analysis (WGCNA) to investigate the insight into co-expression gene modules on DF process in hens. The total mRNA was extracted from the utero-vaginal junction (UVJ, with the sperm storage function in hen’s oviduct which is the biological basis for DF) of 20 hens with several levels of DF traits, and performed transcriptome sequences of mRNA. As a result, three co-expression gene modules were identified to be highly correlated with DF traits. Moreover, the expression changes of top 5 hub genes in each module with DF traits were further confirmed in other 20 hens by RT-PCR. These findings highlighted the co-expression modules and their affiliated genes as playing important roles in the regulation of DF traits.
GRK2 promotes growth of medulloblastoma cells and protects them from chemotherapy-induced apoptosis
Authors: Pathania Anup S. , Ren Xiuhai , Mahdi Min Y. , Shackleford Gregory M. , Erdreich-Epstein Anat 
Published: September 2019

AbstractG-protein coupled receptor kinase 2 (GRK2; ADRBK1, BARK1) is most known as a regulator of G-protein coupled receptors. However, GRK2 also has other functions. Medulloblastomas are the most common malignant brain cancers in children. GRK2 has not been implicated in medulloblastoma biology. Here we report that GRK2 knockdown slowed cell growth, diminished proliferation, and enhanced cisplatin- and etoposide-induced apoptosis in medulloblastoma cell lines UW228-2 and Daoy. Reciprocally, GRK2 overexpression attenuated apoptosis induced by these chemotherapy drugs. Cisplatin and etoposide increased phosphorylation of AKT (S473) and GRK2 knockdown mitigated this increase. Cisplatin and etoposide attenuated ERK phosphorylation, but GRK2 knockdown did not alter this effect. Wildtype GRK2 reversed the increase in cisplatin- and etoposide-induced apoptosis caused by GRK2 knockdown. GRK2-K220R (kinase dead) and GRK2-S670A (unphosphorylated, constitutively active) conferred protection from cisplatin that was similar to wildtype GRK2, suggesting that this protection may be mediated though a kinase-independent activity of GRK2. These data demonstrate that GRK2 contributes to proliferation and survival of these medulloblastoma cell lines and to their protection from cisplatin- and etoposide-induced apoptosis.
Percutaneous stereotactic image-guided microwave ablation for malignant liver lesions
Authors: Perrodin Stéphanie , Lachenmayer Anja , Maurer Martin , Kim-Fuchs Corina , Candinas Daniel , Banz Vanessa 
Published: September 2019

AbstractThermal ablation has proven beneficial for hepatocellular carcinoma and possibly for colorectal liver metastases, but data is lacking for other liver metastases. Computer-assisted navigation can increase ablation efficacy and broaden its indications. We present our experience with percutaneous stereotactic image-guided microwave ablation (SMWA) for non-colorectal liver metastases (NCRLM), in form of a retrospective study including all SMWA for NCRLM from 2015 to 2017. Indication for SMWA was determined at a multidisciplinary tumorboard. End-points include recurrence, overall and liver-specific disease progression and complications. Twenty-three patients underwent 25 interventions for 40 lesions, including 17 neuroendocrine tumor, nine breast cancer, four sarcoma, two non-small cell lung cancer, three duodenal adenocarcinoma, one esophageal adenocarcinoma, one pancreatic adenocarcinoma, one ampullary carcinoma, one prostate carcinoma, and one renal cell carcinoma metastases. Median follow-up was 15 months (2–32). Incomplete ablation rate was 2.5% (1/40), local recurrence rate 10% (4/40). Three patients (12%) had minor complications. Overall disease progression was 73.9% (17/23), median disease-free survival 7 months (0–26) and overall survival 18 months (2–39). SIMWA is feasible, safe and minimally invasive for NCRLM in selected patients. While it might offer an alternative to resection or palliative strategies, the oncological benefit needs to be evaluated in a larger patient cohort.
Spatial distribution of core monomers in acrylamide-based core-shell microgels with linear swelling behaviour
Authors: Cors Marian , Wrede Oliver , Wiehemeier Lars , Feoktystov Artem , Cousin Fabrice , Hellweg Thomas , Oberdisse Julian 
Published: September 2019

AbstractThe peculiar linear temperature-dependent swelling of core-shell microgels has been conjectured to be linked to the core-shell architecture combining materials of different transition temperatures. Here the structure of pNIPMAM-core and pNNPAM-shell microgels in water is studied as a function of temperature using small-angle neutron scattering with selective deuteration. Photon correlation spectroscopy is used to scrutinize the swelling behaviour of the colloidal particles and reveals linear swelling. Moreover, these experiments are also employed to check the influence of deuteration on swelling. Using a form-free multi-shell reverse Monte Carlo approach, the small-angle scattering data are converted into radial monomer density profiles. The comparison of ‘core-only’ particles consisting of identical cores to fully hydrogenated core-shell microgels, and finally to H-core/D-shell architectures unambiguously shows that core and shell monomers display gradient profiles with strong interpenetration, leading to cores embedded in shells which are bigger than their isolated ‘core-only’ precursor particles. This surprising result is further generalized to different core cross-linker contents, for temperature ranges encompassing both transitions. Our analysis demonstrates that the internal structure of pNIPMAM-core and pNNPAM-shell microgels is heterogeneous and strongly interpenetrated, presumably allowing only progressive core swelling at temperatures intermediate to both transition temperatures, thus promoting linear swelling behaviour.
Establishment of an Experimental Intracerebral Haemorrhage Model for Mass Effect Research using a Thermo-sensitive Hydrogel
Authors: Gong Yuhua , Gong Yuping , Hou Zongkun , Guo Tingwang , Deng Jia , Hao Shilei , Wang Bochu 
Published: September 2019

AbstractThe mechanical response of brain tissue closely relates to cerebral blood flow and brain diseases. During intracerebral haemorrhage (ICH), a mass effect occurs during the initial bleeding and results in significant tissue deformation. However, fewer studies have focused on the brain damage mechanisms and treatment approaches associated with mass effects compared to the secondary brain injuries after ICH, which may be a result of the absence of acceptable animal models mimicking a mass effect. Thus, a thermo-sensitive poly (N-isopropylacrylamide) (PNIPAM) hydrogel was synthesized and injected into the rat brain to establish an ICH model for mass effect research. The PNIPAM hydrogel or autologous blood was injected to establish an ICH animal model, and the space-occupying volumes, brain tissue elasticity, brain oedema, neuronal cell death, iron deposition and behavioural recovery were evaluated. The lower critical solution temperature of PNIPAM hydrogel was 32 °C, and the PNIPAM hydrogel had a rough surface with similar topography and pore structure to a blood clot. Furthermore, the ICH model animals who received an injection of PNIPAM and blood produced similar lesion volumes, elasticity changes and mechanically activated ion channel piezo-2 upregulation in brain tissue. Meanwhile, slight iron deposition, neuronal cell death and brain oedema were observed in the PNIPAM hydrogel model compared to the blood model. In addition, the PNIPAM hydrogel showed good biocompatibility and stability in vivo via subcutaneous implantation. Our findings show that PNIPAM hydrogel cerebral infusion can form a mass effect similar to haematoma and minimize the interference of blood, and the establishment of a mass effect ICH model is beneficial for understanding the mechanism of primary brain injury and the role of mass effects in secondary brain damage after ICH.
Comparison of the microbial composition of African fermented foods using amplicon sequencing
Authors: Diaz Maria , Kellingray Lee , Akinyemi Nwanneka , Adefiranye Oyetayo Olaoluwa , Olaonipekun Arinola B. , Bayili Geoffroy Romaric , Ibezim Jekwu , du Plessis Adriana Salomina , Houngbédji Marcel , Kamya Deus , Mukisa Ivan Muzira , Mulaw Guesh , Manthi Josiah Samuel , Onyango Chienjo William , Atter Amy , Agbemafle Evans , Annan Theophilus , Bernice Ackah Nina , Buys Elna M. , Joseph Hounhouigan D. , Muyanja Charles , Nakavuma Jesca , Odeny Damaris Achieng , Sawadogo-Lingani Hagretou , Tesfaye Tefera Anteneh , Amoa-Awua Wisdom , Obodai Mary , Mayer Melinda J. , Oguntoyinbo Folarin A. , Narbad Arjan 
Published: September 2019

AbstractFermented foods play a major role in the diet of people in Africa, where a wide variety of raw materials are fermented. Understanding the microbial populations of these products would help in the design of specific starter cultures to produce standardized and safer foods. In this study, the bacterial diversity of African fermented foods produced from several raw materials (cereals, milk, cassava, honey, palm sap, and locust beans) under different conditions (household, small commercial producers or laboratory) in 8 African countries was analysed by 16S rRNA gene amplicon sequencing during the Workshop “Analysis of the Microbiomes of Naturally Fermented Foods Training Course”. Results show that lactobacilli were less abundant in fermentations performed under laboratory conditions compared to artisanal or commercial fermentations. Excluding the samples produced under laboratory conditions, lactobacilli is one of the dominant groups in all the remaining samples. Genera within the order Lactobacillales dominated dairy, cereal and cassava fermentations. Genera within the order Lactobacillales, and genera Zymomonas and Bacillus were predominant in alcoholic beverages, whereas Bacillus and Lactobacillus were the dominant genera in the locust bean sample. The genus Zymomonas was reported for the first time in dairy, cereal, cassava and locust bean fermentations.
Transcriptional regulator ArcA mediates expression of oligopeptide transport systems both directly and indirectly in Shewanella oneidensis
Authors: Liang Huihui , Mao Yinting , Sun Yijuan , Gao Haichun 
Published: September 2019

AbstractIn γ-proteobacterial species, such asEscherichia coli, the Arc (anoxic redox control) two-component system plays a major role in mediating the metabolic transition from aerobiosis to anaerobiosis, and thus is crucial for anaerobic growth but dispensable for aerobic growth. InShewanella oneidensis, a bacterium renowned for respiratory versatility, Arc (SoArc) primarily affects aerobic growth. To date, how this occurs has remained largely unknown although the growth defect resulting from the loss of DNA-binding response regulatorSoArcA is tryptone-dependent. In this study, we demonstrated that the growth defect is in part linked to utilization of oligopeptides and di-tripeptides, and peptide uptake but not peptide degradation is significantly affected by theSoArcA loss. A systematic characterization of major small peptide uptake systems manifests that ABC peptide transporter Sap and four proton-dependent oligopeptide transporters (POTs) are responsible for transport of oligopeptides and di-tripeptides respectively. Among them, Sap and DtpA (one of POTs) are responsive to theSoarcAmutation but onlydtpAis under the direct control ofSoArcA. We further showed that both Sap and DtpA, when overproduced, improve growth of theSoarcAmutant. While the data firmly establish a link between transport of oligopeptides and di-tripeptides and theSoarcAmutation, other yet-unidentified factors are implicated in the growth defect resulting from theSoArcA loss.
The characteristics of drug information inquiries in an Ethiopian university hospital: A two-year observational study
Authors: Tefera Yonas Getaye , Gebresillassie Begashaw Melaku , Ayele Asnakew Achaw , Belay Yared Belete , Emiru Yohannes Kelifa 
Published: September 2019

AbstractThe types of drug-related information request from patients and health professionals, the extent of inquiry and capability of existing drug information centers are seldom studied in Ethiopia. This study aimed to identify the types and potential areas of drug information inquiry at the Drug Information Center (DIC) of Gondar University specialized Hospital (GUSH), Ethiopia. An observational study was employed. The drug information query was collected by distributing the drug information queries in different hospital units through two batches of graduating undergraduate pharmacy students. Descriptive statistics used to describe, characterize and classify drug related queries. Binary logistic regression test was employed to identify predictor variables to type of drug information query. A total of 781 drug related queries were collected and 697 were included in the final analysis. Near to half (45.3%) of queries comes from the pharmacists followed by general practitioners (11.3%) and nurses (10.2%). Slightly greater than half of the queries (51.9%) were focused on therapeutic information. 39.6% of drug related queries related to infectious disease case scenarios, followed by cardiovascular cases in 21.3% of queries. More than half of (53.9%) and nearly one in five (19.4%) of the queries took 5 to 30 minutes and 30 minutes to 1 hour of literature searching to answer, respectively. Pharmacists (with odds ratio of 2.474(95% CI (1.373-4.458)) and patients (with odds ratio of 4.121(1.403–12.105)) ask patient-specific questions in their drug related queries higher than other group of health professionals. Pharmacists are the primary drug information users and frequent drug related information inquirers at the DIC. Most of the queries targeted therapeutic indications, adverse drug events, infectious or cardiovascular disease related requests. This is imperative that drug information services can assist the growing role of pharmacists in addressing the patient specific drug related needs.
MicroRNA-27a/b-3p and PPARG regulate SCAMP3 through a feed- forward loop during adipogenesis
Authors: Kulyté Agné , Kwok Kelvin Ho Man , de Hoon Michiel , Carninci Piero , Hayashizaki Yoshihide , Arner Peter , Arner Erik 
Published: September 2019

AbstractMicroRNAs (miRNA) modulate gene expression through feed-back and forward loops. Previous studies identified miRNAs that regulate transcription factors, including Peroxisome Proliferator Activated Receptor Gamma (PPARG), in adipocytes, but whether they influence adipogenesis via such regulatory loops remain elusive. Here we predicted and validated a novel feed-forward loop regulating adipogenesis and involved miR-27a/b-3p, PPARG and Secretory Carrier Membrane Protein 3 (SCAMP3). In this loop, expression of both PPARG and SCAMP3 was independently suppressed by miR-27a/b-3p overexpression. Knockdown of PPARG downregulated SCAMP3 expression at the late phase of adipogenesis, whereas reduction of SCAMP3 mRNA levels increased PPARG expression at early phase in differentiation. The latter was accompanied with upregulation of adipocyte-enriched genes, including ADIPOQ and FABP4, suggesting an anti-adipogenic role for SCAMP3. PPARG and SCAMP3 exhibited opposite behaviors regarding correlations with clinical phenotypes, including body mass index, body fat mass, adipocyte size, lipolytic and lipogenic capacity, and secretion of pro-inflammatory cytokines. While adipose PPARG expression was associated with more favorable metabolic phenotypes, SCAMP3 expression was linked to increased fat mass and insulin resistance. Together, we identified a feed-forward loop through which miR-27a/b-3p, PPARG and SCAMP3 cooperatively fine tune the regulation of adipogenesis, which potentially may impact whole body metabolism.