Miracle-dz/UniFAR-FTUs huggingface dataset:
Molecular biology of rat cytomegalovirus : genome-wide transcriptional program and molecular mimicry

Rat cytomegalovirus (RCMV) is a β-herpesvirus with a 230-kbp genome containing over 167 open reading frames (ORFs). RCMV gene expression is tightly regulated in cultured cells, occurring in three distinct kinetic classes (immediate early, early and late). However, the extent of viral gene expression in vivo and its relationship to the in vitro expression is unknown. In this study, we used RCMV-specific DNA microarrays to investigate the viral transcriptional profiles in cultured, RCMV-infected endothelial cells, fibroblasts and aortic smooth muscle cells, and to compare these profiles to those found in tissues from RCMV-infected rat heart transplant recipients. In cultured cells, RCMV expresses approximately 95% of the known viral ORFs with few differences between cell types. By contrast, in vivo viral gene expression in tissues from rat heart allograft recipients is highly restricted. In the tissues studied, a total of 80 viral genes expressing levels twice above background (5-10,000 copies per 2 μg of total RNA) were detected. In each tissue type there were a number of genes expressed exclusively in that tissue. Although viral mRNA and genomic DNA levels were lower in the spleen compared to submandibular glands, the number of individual viral genes expressed was higher in the spleen (61 vs. 40). This finding suggests that the number of viral genes expressed is specific to a given tissue and is not dependent upon viral load or viral mRNA levels. Our results demonstrate that the profiles as well as the amplitude of viral gene expression are tissue-specific and are dramatically different compared to those in infected cultured cells, indicating that RCMV gene expression in vitro does not reflect viral gene expression in vivo.
Evolution of Escherichia coli to 42 °C and Subsequent Genetic Engineering Reveals Adaptive Mechanisms and Novel Mutations

Adaptive laboratory evolution (ALE) has emerged as a valuable method by which to investigate microbial adaptation to a desired environment. Here, we performed ALE to 42 °C of ten parallel populations of Escherichia coli K-12 MG1655 grown in glucose minimal media. Tightly controlled experimental conditions allowed selection based on exponential-phase growth rate, yielding strains that uniformly converged toward a similar phenotype along distinct genetic paths. Adapted strains possessed as few as 6 and as many as 55 mutations, and of the 144 genes that mutated in total, 14 arose independently across two or more strains. This mutational recurrence pointed to the key genetic targets underlying the evolved fitness increase. Genome engineering was used to introduce the novel ALE-acquired alleles in random combinations into the ancestral strain, and competition between these engineered strains reaffirmed the impact of the key mutations on the growth rate at 42 °C. Interestingly, most of the identified key gene targets differed significantly from those found in similar temperature adaptation studies, highlighting the sensitivity of genetic evolution to experimental conditions and ancestral genotype. Additionally, transcriptomic analysis of the ancestral and evolved strains revealed a general trend for restoration of the global expression state back toward preheat stressed levels. This restorative effect was previously documented following evolution to metabolic perturbations, and thus may represent a general feature of ALE experiments. The widespread evolved expression shifts were enabled by a comparatively scant number of regulatory mutations, providing a net fitness benefit but causing suboptimal expression levels for certain genes, such as those governing flagellar formation, which then became targets for additional ameliorating mutations. Overall, the results of this study provide insight into the adaptation process and yield lessons important for the future implementation of ALE as a tool for scientific research and engineering.
Twisting tongues to test for conflict-monitoring in speech production

A number of recent studies have hypothesized that monitoring in speech production may occur via domain-general mechanisms responsible for the detection of response conflict. Outside of language, two ERP components have consistently been elicited in conflict-inducing tasks (e.g., the flanker task): the stimulus-locked N2 on correct trials, and the response-locked error-related negativity (ERN). The present investigation used these electrophysiological markers to test whether a common response conflict monitor is responsible for monitoring in speech and non-speech tasks. Electroencephalography (EEG) was recorded while participants performed a tongue twister (TT) task and a manual version of the flanker task. In the TT task, people rapidly read sequences of four nonwords arranged in TT and non-TT patterns three times. In the flanker task, people responded with a left/right button press to a center-facing arrow, and conflict was manipulated by the congruency of the flanking arrows. Behavioral results showed typical effects of both tasks, with increased error rates and slower speech onset times for TT relative to non-TT trials and for incongruent relative to congruent flanker trials. In the flanker task, stimulus-locked EEG analyses replicated previous results, with a larger N2 for incongruent relative to congruent trials, and a response-locked ERN. In the TT task, stimulus-locked analyses revealed broad, frontally-distributed differences beginning around 50 ms and lasting until just before speech initiation, with TT trials more negative than non-TT trials; response-locked analyses revealed an ERN. Correlation across these measures showed some correlations within a task, but little evidence of systematic cross-task correlation. Although the present results do not speak against conflict signals from the production system serving as cues to self-monitoring, they are not consistent with signatures of response conflict being mediated by a single, domain-general conflict monitor.
Visual Scanning Training for Neglect after Stroke with and without a Computerized Lane Tracking Dual Task

Neglect patients typically fail to explore the contralesional half-space. During visual scanning training, these patients learn to consciously pay attention to contralesional target stimuli. It has been suggested that combining scanning training with methods addressing non-spatial attention might enhance training results. In the present study, a dual task training component was added to a visual scanning training (i.e., Training di Scanning Visuospaziale – TSVS; Pizzamiglio et al., 1990). Twenty-nine subacute right hemisphere stroke patients were semi-randomly assigned to an experimental (N = 14) or a control group (N = 15). Patients received 30 training sessions during 6 weeks. TSVS consisted of four standardized tasks (digit detection, reading/copying, copying drawings, and figure description). Moreover, a driving simulator task was integrated in the training procedure. Control patients practiced a single lane tracking task for 2 days a week during 6 weeks. The experimental group was administered the same training schedule, but in weeks 4–6 of the training, the TSVS digit detection task was combined with lane tracking on the same projection screen, so as to create a dual task (computerized visual reaction time task designed for training). Various neglect tests and driving simulator tasks were administered before and after training. No significant group and interaction effects were found that might reflect additional positive effects of dual task training. Significant improvements after training were observed in both groups taken together on most assessment tasks. Ameliorations were generally not correlated to post-onset time, but spontaneous recovery, test–retest variability, and learning effects could not be ruled out completely, since these were not controlled for. Future research might focus on increasing the amount of dual task training, the implementation of progressive difficulty levels in driving simulator tasks, and further exploration of relationships between dual task training and daily functioning.
Metagenomic approaches to microbial source tracking

xix Chapter One Introduction . 1 1.1 Microbial source tracking . 1 1.1.1 Faecal indicator bacteria . 3 1.1.2 Library-dependent methods . 3 1.1.2.1 Phenotypic methods . 4 1.1.2.2 Genotypic methods . 5 1.1. 3 Library-independent methods . 5 1.1. 3.1 PCR-based methods . 7 1.1. 3.1.1 Host-specific markers . 7 1.1. 3.1.2 Bacteroidales as targets . 9 1.1. 3.2 Alternative methods . 10 1.1. 3.2.1 Alternative gene markers . 10 1.1. 3.2.2 Virus targets . 10 1.1. 3.2. 3 Eukaryotic markers . 11 1.1. 3.2. 4 Chemical methods . 11 1.1. 3.2. 5 Microarrays . 12 1.1. 4 16S ribosomal RNA gene . 12 1.2 DNA Sequencing . 13 Table of
The genome sequence of Salmonella enterica serovar Choleraesuis, a highly invasive and resistant zoonotic pathogen

Salmonella enterica serovar Choleraesuis (S.Choleraesuis), a highly invasive serovar among non-typhoidal Salmonella, usually causes sepsis or extra-intestinal focal infections in humans. S.Choleraesuis infections have now become particularly difficult to treat because of the emergence of resistance to multiple antimicrobial agents. The 4.7 Mb genome sequence of a multidrug-resistant S.Choleraesuis strain SC-B67 was determined. Genome wide comparison of three sequenced Salmonella genomes revealed that more deletion events occurred in S.Choleraesuis SC-B67 and S.Typhi CT18 relative to S.Typhimurium LT2. S.Choleraesuis has 151 pseudogenes, which, among the three Salmonella genomes, include the highest percentage of pseudogenes arising from the genes involved in bacterial chemotaxis signal-transduction pathways. Mutations in these genes may increase smooth swimming of the bacteria, potentially allowing more effective interactions with and invasion of host cells to occur. A key regulatory gene of TetR/AcrR family, acrR, was inactivated through the introduction of an internal stop codon resulting in overexpression of AcrAB that appears to be associated with cipro-floxacin resistance. While lateral gene transfer providing basic functions to allow niche expansion in the host and environment is maintained during the evolution of different serovars of Salmonella, genes providing little overall selective benefit may be lost rapidly. Our findings suggest that the formation of pseudogenes may provide a simple evolutionary pathway that complements gene acquisition to enhance virulence and antimicrobial resistance in S.Choleraesuis.
EVALUATION OF PREVALENCE OF DIABETIC FOOT ULCER AND ITS RELATED FACTORS IN DIABETIC PATIENTS ADMITTED TO KHATAM-OL-ANBIA HOSPITAL IN SHOUSHTAR DURING 2015-2016: A RETROSPECTIVE STUDY

International Journal of Ecosystems and Ecology Science (IJEES) Volume 8, issue 3, 2018 https://doi.org/10.31407/ijees https://doi.org/10.31407/ijees83 _____________________________________________________________________________________________ 14 Vol. 8 (3): 545-552 (2018) EVALUATION OF PREVALENCE OF DIABETIC FOOT ULCER AND ITS RELATED FACTORS IN DIABETIC PATIENTS ADMITTED TO KHATAM-OL-ANBIA HOSPITAL IN SHOUSHTAR DURING 2015-2016: A RETROSPECTIVE STUDY Mostafa Madmoli, Fatemeh Rostami, Nastaran Mirsami Yazdi, Ahmad Mosavi, Shahram Baraz Emergency Medical Technician, Dezful University of Medical Sciences, Dezful, Iran; Bushehr University of Medical Sciences, Bushehr, Iran; Dezful University of Medical Sciences, Dezful, Iran; Nursing Care Research Center in Chronic Diseases, School of Nursing and Midwifery, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran; *Corresponding author Fatemeh Rostami, email: fa.rostami@bpums.ac. ir; Received May, 2018; Accepted May, 2018; Published June, 2018; doi: https://doi.org/10.31407/ijees8314 UOI license: http://u-o-i.org/1.01/ijees/54099599
Chest

A newborn baby was admitt ed for respiratory distress, soon after a Caesarian section performed for acute polyhydramnios in the third trimester. The baby had not cried aft er birth and, at admission, was moaning, cyanosed, drowsy, limp, and not responding to stimuli; APGAR scores were 4/10, 8/10, and 7/10. The baby showed nasal ß aring and sternal and substernal retraction. All neonatal reß exes were absent and there was hypotonia of all the muscles. The baby was put under an oxygen hood, but then required mechanical ventilation. Neuro USG showed no hemorrhage in the germinal matrix or the ventricle. Chest radiographs revealed normal lungs on day 1 [Figure 1] but showed a collapsed left lung on day 2 [Figure 2].
Haematological, Biochemical and Therapeutic Aspects of Parturient Haemoglobinuria in Buffaloes

A total of thirty buffaloes suffering from parturient haemoglobinuria were selected from district Chakwal during December 2010 - January 2011. Sixty apparently healthy buffaloes of similar description were also selected from the same areas as controls. Blood samples collected with and without anticoagulant (EDTA) were analyzed for various haematological and biochemical parameters. Significantly (P 0.05) differences were recorded in mean corpuscular haemoglobin concentration, platelet distribution width, serum glucose, cholesterol and copper concentrations between haemoglobinuric and healthy buffaloes. These thirty haemoglobinuric buffaloes were divided into three groups for clinical trial to compare and assess the recovery rates of three different treatment packages. Highest recovery rate (100%) was recorded for combined therapy of sodium acid phosphate and blood transfusion The recovery rates for combination of sodium acid phosphate with tranexamic acid and tranexamic acid with Novacoc forte injection were 70% and 50%, respectively.
The NHGRI GWAS Catalog, a curated resource of SNP-trait associations

The National Human Genome Research Institute (NHGRI) Catalog of Published Genome-Wide Association Studies (GWAS) Catalog provides a publicly available manually curated collection of published GWAS assaying at least 100 000 single-nucleotide polymorphisms (SNPs) and all SNP-trait associations with P <1 × 10−5. The Catalog includes 1751 curated publications of 11 912 SNPs. In addition to the SNP-trait association data, the Catalog also publishes a quarterly diagram of all SNP-trait associations mapped to the SNPs’ chromosomal locations. The Catalog can be accessed via a tabular web interface, via a dynamic visualization on the human karyotype, as a downloadable tab-delimited file and as an OWL knowledge base. This article presents a number of recent improvements to the Catalog, including novel ways for users to interact with the Catalog and changes to the curation infrastructure.
Drug screening linked to molecular profiling identifies novel dependencies in patient-derived primary cultures of paediatric high grade glioma and DIPG

Paediatric high grade glioma and diffuse midline glioma (including DIPG) are comprised of multiple biological and clinical subgroups, the majority of which urgently require novel therapies. Patient-derived in vitro primary cell cultures represent potentially useful tools for mechanistic and preclinical investigation based upon their retention of key features of tumour subgroups under experimental conditions amenable to high-throughput approaches. We present 17 novel primary cultures derived from patients in London, Dublin and Belfast, and together with cultures established or shared from Barcelona, Brisbane, Rome and Stanford, assembled a panel of 52 models under 2D (laminin matrix) and/or 3D (neurospheres) conditions, fully credentialed by phenotypic and molecular comparison to the original tumour sample (methylation BeadArray, panel/exome sequencing, RNAseq). In screening a subset of these against a panel of ~400 approved chemotherapeutics and small molecules, we identified specific dependencies associated with tumour subgroups and/or specific molecular markers. These included MYCN-amplified cells and ATM/DNA-PK inhibitors, and DIPGs with PPM1D activating truncating mutations and inhibitors of MDM2 or PARP1. Specific mutations in PDGFRA were found to confer sensitivity to a range of RTK inhibitors, though not all such mutations conferred sensitivity to targeted agents. Notably, dual PDGFRA/FGFR and downstream pathway MEK inhibitors showed profound effects against both PDGFRA-sensitising mutant and FGFR1-dependent non-brainstem pHGG and DIPG. In total, 85% cells were found to have at least one drug screening hit in short term assays linked to the underlying biology of the patient’s tumour, providing a rational approach for individualised clinical translation.
Einstellungen zur Allgemeinmedizin: eine vergleichende querschnittliche Befragung von Medizinstudierenden des 1. und 5. Studienjahres

Objective: Positive attitudes towards General Practice can be understood as a prerequisite for becoming a General Practitioner (GP) and for colCarsten Kruschinski Birgitt Wiese laboration with GPs later on. This study aimed to assess attitudes of medical students at the beginning and the end of medical school. Eva Hummers-Pradier 3 Methods: A total of 160 1 year students at Hannover Medical School were surveyed. Their attitudes were compared to those of 287 5 year 1 Hannover Medical School, Institute of General Practice, Hannover, Germany students. Descriptive, biand multivariate analyses were performed to investigate influences of year of study and gender. Results: Year of study and gender both were associated with the attitudes towards General Practice. The interest in General Practice and 2 Hannover Medical School, Institute of Biometry, Hannover, Germany patient-orientation (communication, care of older patients with chronic diseases) was higher in 1 year students compared to more advanced 3 University Medicine Göttingen, Department of students. Female students valued such requirements more than male students, the differences in attitudes between the years of study being more pronounced in male students. General Practice/Family Medicine, Göttingen, Germany Conclusion: Despite some limitations caused by the cross-sectional design, the attitudes towards General Practice competencies changed to their disadvantage during medical school. This suggests a formative influence of the strategies used in medical education. Educational strategies, however, could be used to bring about a change of attitudes in the other direction.
Keloids and Hypertrophic Scars: Update and Future Directions

Summary: The development of cutaneous pathological scars, namely, hypertrophic scars (HSs) and keloids, involves complex pathways, and the exact mechanisms by which they are initiated, evolved, and regulated remain to be fully elucidated. The generally held concepts that keloids and HSs represent “aberrant wound healing” or that they are “characterized by hyalinized collagen bundles” have done little to promote their accurate clinicopathological classification or to stimulate research into the specific causes of these scars and effective preventative therapies. To overcome this barrier, we review here the most recent findings regarding the pathology and pathogenesis of keloids and HSs. The aberrations of HSs and keloids in terms of the inflammation, proliferation, and remodeling phases of the wound healing process are described. In particular, the significant roles that the extracellular matrix and the epidermal and dermal layers of skin play in scar pathogenesis are examined. Finally, the current hypotheses of pathological scar etiology that should be tested by basic and clinical investigators are detailed. Therapies that have been found to be effective are described, including several that evolved directly from the aforementioned etiology hypotheses. A better understanding of pathological scar etiology and manifestations will improve the clinical and histopathological classification and treatment of these important lesions.
Genome-Wide Assessment of the Association of Rare and Common Copy Number Variations to Testicular Germ Cell Cancer

Testicular germ cell cancer (TGCC) is one of the most heritable forms of cancer. Previous genome-wide association studies have focused on single nucleotide polymorphisms, largely ignoring the influence of copy number variants (CNVs). Here we present a genome-wide study of CNV on a cohort of 212 cases and 437 controls from Denmark, which was genotyped at ∼1.8 million markers, half of which were non-polymorphic copy number markers. No association of common variants were found, whereas analysis of rare variants (present in less than 1% of the samples) initially indicated a single gene with significantly higher accumulation of rare CNVs in cases as compared to controls, at the gene PTPN1 (P = 3.8 × 10−2, 0.9% of cases and 0% of controls). However, the CNV could not be verified by qPCR in the affected samples. Further, the CNV calling of the array-data was validated by sequencing of the GSTM1 gene, which showed that the CNV frequency was in complete agreement between the two platforms. This study therefore disconfirms the hypothesis that there exists a single CNV locus with a major effect size that predisposes to TGCC. Genome-wide pathway association analysis indicated a weak association of rare CNVs related to cell migration (false-discovery rate = 0.021, 1.8% of cases and 1.1% of controls). Dysregulation during migration of primordial germ cells has previously been suspected to be a part of TGCC development and this set of multiple rare variants may thereby have a minor contribution to an increased susceptibility of TGCCs.
Predicted Functions of MdmX in Fine-Tuning the Response of p53 to DNA Damage

Tumor suppressor protein p53 is regulated by two structurally homologous proteins, Mdm2 and MdmX. In contrast to Mdm2, MdmX lacks ubiquitin ligase activity. Although the essential interactions of MdmX are known, it is not clear how they function to regulate p53. The regulation of tumor suppressor p53 by Mdm2 and MdmX in response to DNA damage was investigated by mathematical modeling of a simplified network. The simplified network model was derived from a detailed molecular interaction map (MIM) that exhibited four coherent DNA damage response pathways. The results suggest that MdmX may amplify or stabilize DNA damage-induced p53 responses via non-enzymatic interactions. Transient effects of MdmX are mediated by reservoirs of p53∶MdmX and Mdm2∶MdmX heterodimers, with MdmX buffering the concentrations of p53 and/or Mdm2. A survey of kinetic parameter space disclosed regions of switch-like behavior stemming from such reservoir-based transients. During an early response to DNA damage, MdmX positively or negatively regulated p53 activity, depending on the level of Mdm2; this led to amplification of p53 activity and switch-like response. During a late response to DNA damage, MdmX could dampen oscillations of p53 activity. A possible role of MdmX may be to dampen such oscillations that otherwise could produce erratic cell behavior. Our study suggests how MdmX may participate in the response of p53 to DNA damage either by increasing dependency of p53 on Mdm2 or by dampening oscillations of p53 activity and presents a model for experimental investigation.