Miracle-dz/UniFAR-FTUs huggingface dataset:
Detection of phospholipase activity of Candida albicans and non albicans isolated from women of reproductive age with vulvovaginal candidiasis in rural area

Background: Vulvovaginal candidiasis (VVC) is most common accounting for 17 to 39% of symptomatic women. Both Candida albicans and non albicans Candida species are involved in VVC. Amongst various virulence factors proposed for Candida, extracellular phospholipases is one of the virulence factor implicated in its pathogenicity. With this background the present study was carried out to find the prevalence of different Candida species and to detect phospholipase producing strains isolated from symptomatic women with VVC. Materials and Methods: At least two vaginal swabs from 156 women of reproductive age with abnormal vaginal discharge were collected. Direct microscopy and Gram′s stained smear examined for presence of budding yeast and pseudo mycelia followed by isolation and identification of Candida species. Extracellular phospholipase activity was studied by inoculating all isolates on Sabouraud′s dextrose egg yolk agar (SDA) medium. Results: Of the 156 women with curdy white discharge alone or in combination with other signs, 59 (37.82%) women showed laboratory evidence of VVC. A total of 31 (52.54%) women had curdy white discharge followed by 12 (20.33%) with other signs and symptoms. C. albicans (62.59%) and non albicans Candida (37.28%) in a ratio of 1.68:1 were isolated. Of the 37 strains of C. albians 30 (81.08%) showed the enzyme activity. Seventeen (56.66%) strains showed higher Pz value of < 0.70 (++++). Conclusion: Although there may be typical clinical presentation of Candidiasis. all the patients did not show laboratory evidence of infection. Pregnancy was found to be major risk factor for development of VVC. C. albicans was prevalent species but non albicans species were also frequently isolated. Extracellular phospholipase activity was seen in C. albicans and not in non albicans Candida isolates.
Do the Time-Warp : Continuous Alignment of Gene Expression Time-Series Data

Recent advances in DNA microarray technologies are enabling researchers to measure the expression levels of thousands of genes simultaneously, with time-series data offering particularly rich opportunities for understanding dynamic biological processes. Unfortunately, DNA microarray data is plagued by quality issues including noise and missing data points. Expression time-series data introduce additional complications, including sampling rate differences between experiments and variations in the timing of biological processes. In this thesis, a probabilistic framework is presented for making gene expression timeseries data from different experiments directly comparable. This method addresses the issues of DNA microarray data noise, missing values, different sampling rates between experiments, and variability in the timing of biological processes. Gene expression time-series data are represented as a set of continuous spline curves (piecewise polynomials) using a linear mixedeffects model, a statistical method that allows for a fixed or group effect as well as a random or individual effect. The model constrains a gene's expression curve to be generally similar to those of co-expressed genes, while still allowing for gene specific variations. A continuous alignment algorithm is then introduced in which a search is performed for a function that transforms the time-scale of one gene expression process into that of another, while minimizing a measure of error between expression profiles in the two processes. Three applications are then presented of the continuous representation/alignment algorithm to DNA microarray expression data, which yield biologically meaningful results. First, it is shown that the linear mixed-effects spline model can effectively predict missing data values, achieving lower error for cases of one or two consecutive missing values than the best method previously reported in the literature. Second, it is demonstrated that the alignment algorithm can produce stable low-error alignments, allowing data from three different yeast cell cycle experiments (with period and phase differences) to be combined. Finally, it is shown that the alignment algorithm can be used to identify genes that behave differently in normal versus genetically modified cells. Thesis Supervisor: David K. Gifford Title: Professor of Electrical Engineering and Computer Science
HSV-1 ICP0: An E3 Ubiquitin Ligase That Counteracts Host Intrinsic and Innate Immunity

The herpes simplex virus type 1 (HSV-1) encoded E3 ubiquitin ligase, infected cell protein 0 (ICP0), is required for efficient lytic viral replication and regulates the switch between the lytic and latent states of HSV-1. As an E3 ubiquitin ligase, ICP0 directs the proteasomal degradation of several cellular targets, allowing the virus to counteract different cellular intrinsic and innate immune responses. In this review, we will focus on how ICP0’s E3 ubiquitin ligase activity inactivates the host intrinsic defenses, such as nuclear domain 10 (ND10), SUMO, and the DNA damage response to HSV-1 infection. In addition, we will examine ICP0’s capacity to impair the activation of interferon (innate) regulatory mediators that include IFI16 (IFN γ-inducible protein 16), MyD88 (myeloid differentiation factor 88), and Mal (MyD88 adaptor-like protein). We will also consider how ICP0 allows HSV-1 to evade activation of the NF-κB (nuclear factor kappa B) inflammatory signaling pathway. Finally, ICP0’s paradoxical relationship with USP7 (ubiquitin specific protease 7) and its roles in intrinsic and innate immune responses to HSV-1 infection will be discussed.
From ear to uncertainty: vestibular contributions to cognitive function

In addition to the deficits in the vestibulo-ocular and vestibulo-spinal reflexes that occur following vestibular dysfunction, there is substantial evidence that vestibular loss also causes cognitive disorders, some of which may be due to the reflexive deficits and some of which are related to the role that ascending vestibular pathways to the limbic system and neocortex play in spatial orientation. In this review we summarize the evidence that vestibular loss causes cognitive disorders, especially spatial memory deficits, in animals and humans and critically evaluate the evidence that these deficits are not due to hearing loss, problems with motor control, oscillopsia or anxiety and depression. We review the evidence that vestibular lesions affect head direction and place cells as well as the emerging evidence that artificial activation of the vestibular system, using galvanic vestibular stimulation (GVS), can modulate cognitive function.
Rapid Differential Diagnosis between Extrapulmonary Tuberculosis and Focal Complications of Brucellosis Using a Multiplex Real-Time PCR Assay

Background Arduous to differ clinically, extrapulmonary tuberculosis and focal complications of brucellosis remain important causes of morbidity and mortality in many countries. We developed and applied a multiplex real-time PCR assay (M RT-PCR) for the simultaneous detection of Mycobacterium tuberculosis complex and Brucella spp. Methodology Conventional microbiological techniques and M RT-PCR for M. tuberculosis complex and Brucella spp were performed on 45 clinical specimens from patients with focal complications of brucellosis or extrapulmonary tuberculosis and 26 control samples. Fragments of 207 bp and 164 bp from the conserved region of the genes coding for an immunogenic membrane protein of 31 kDa of B. abortus (BCSP31) and the intergenic region SenX3-RegX3 were used for the identification of Brucella and M. tuberculosis complex, respectively. Conclusions The detection limit of the M RT-PCR was 2 genomes per reaction for both pathogens and the intra- and inter-assay coefficients of variation were 0.44% and 0.93% for Brucella and 0.58% and 1.12% for Mycobacterium. M RT-PCR correctly identified 42 of the 45 samples from patients with tuberculosis or brucellosis and was negative in all the controls. Thus, the overall sensitivity, specificity, PPV and NPV values of the M RT PCR assay were 93.3%, 100%, 100% and 89.7%, respectively, with an accuracy of 95.8% (95% CI, 91.1%–100%). Since M RT-PCR is highly reproducible and more rapid and sensitive than conventional microbiological tests, this technique could be a promising and practical approach for the differential diagnosis between extrapulmonary tuberculosis and focal complications of brucellosis.
Endothelial Senescence Contributes to Heart Failure With Preserved Ejection Fraction in an Aging Mouse Model

Background— Because of global aging, the prevalence of heart failure with preserved ejection fraction (HFpEF) continues to rise. Although HFpEF pathophysiology remains incompletely understood, endothelial inflammation is stated to play a central role. Cellular senescence is a process of cellular growth arrest linked with aging and inflammation. We used mice with accelerated aging to investigate the role of cellular senescence in HFpEF development. Methods and Results— Senescence-accelerated mice (SAM, n=18) and control mice with normal senescence (n=15) were fed normal chow or a high-fat, high-salt diet (WD). Vascular and cardiac function was assessed at 8, 16, and 24 weeks of age. At 24 weeks, both SAM on WD (SAM-WD) and SAM on regular diet displayed endothelial dysfunction, as evidenced by impaired acetylcholine-induced relaxation of aortic segments and reduced basal nitric oxide. At week 24, SAM-WD had developed HFpEF, characterized by diastolic dysfunction, left ventricular hypertrophy, left atrial dilatation, and interstitial fibrosis. Also, exercise capacity was reduced and lung weight increased. Cardiovascular inflammation and senescence were assessed by immunohistochemical and immunofluorescence staining of hearts and aortas. SAM-WD showed increased endothelial inflammation (intercellular adhesion molecule 1 expression) and increased endothelial senescence (acetyl-p53/CD31 costaining). The latter correlated with diastolic function and intercellular adhesion molecule 1 expression. Conclusions— SAM develop endothelial dysfunction. Adding a high-salt, high-fat diet accelerates endothelial senescence and instigates endothelial inflammation. This coincides with hemodynamic and structural changes typical of HFpEF. Targeting endothelial senescence could be a new therapeutic avenue in HFpEF.
Chlamydia pneumoniae and asthma

BACKGROUND This study was designed to test the association of Chlamydia pneumoniae infection with asthma in a multiracial population, after adjustments for several potential confounding variables. METHODS Antibodies to C pneumoniaewere measured by microimmunofluorescence in 123 patients with acute asthma, 1518 control subjects admitted to the same hospital with various non-cardiovascular, non-pulmonary disorders, and 46 patients with severe chronic asthma, including some with “brittle” asthma. Acute infection or reinfection was defined by titres of IgG of ⩾512 or IgM ⩾8 or a fourfold rise in IgG, and previous infection by IgG 64–256 or IgA ⩾8. Logistic regression was used to control for likely confounders, including ethnic origin, age, sex, smoking habit, steroid medication, diabetes mellitus and social deprivation, on antibody levels. RESULTS Antibody titres consistent with acuteC pneumoniae infection were found in 5.7% of patients with acute asthma and 5.7% of control patients, while 14.6% of patients with acute asthma and 12.7% of control patients had titres suggesting previous infection. These two groups did not differ significantly. However, titres suggesting previous infection were found in 34.8% of patients with severe chronic asthma: the difference between this group and the control group was statistically significant with an adjusted odds ratio of 3.99 (95% confidence interval 1.60 to 9.97). CONCLUSIONS These data raise important questions about the previously demonstrated association of C pneumoniae infection with asthma, and suggest that future studies of this association should give particular attention to the presence or absence of a history of severe chronic asthma.
Using bio-manipulation to optimise nutrient management within intensive farm systems

The research project aims to enhance organic nutrient management in livestock farms using microbial and enzyme inoculations, with a particular focus on the phosphorus biogeochemical cycle. In order to do this the first approach consists of characterising the chemical and biological properties of farm slurries as a baseline to evaluate possible amendments of the intrinsic properties of the slurry. Consequently, it is pivotal to consider properties such as plant nutrients, i.e., phosphorus, nitrogen and potassium, as well as the microbial community within the slurry. Likewise, attention needs to be paid to soil chemical and biological properties, e.g. pH, salinity and organic matter, as well as to the variety of organisms inhabiting the soil, in order to determine the impact of inoculation on phosphorus cycling and nutrient availability for plant use. Furthermore, it is important to know how soil and its productivity may be influenced by the addition of the inoculated slurry. Of particular interest are also the soil properties which have an effect on plant growth. The pH of soil and, notably, nutrient availability and retention capacity are some of the features on which to direct the research in order to assess the quality of soil and, as a result, the production of a grass crop in livestock farms. The characterisation of these properties will be performed using a variety of approaches, beginning with analysis at laboratory- and mesocosm-scales and progressing to a fieldwork approach in order to evaluate the results directly in a farm system.
Interest of genotyping and phenotyping of drug-metabolizing enzymes for the interpretation of biological monitoring of exposure to styrene.

In the field of occupational and/or environmental toxicology, the measurement of specific metabolites in urine may serve to assess exposure to the parent compounds (biological monitoring of exposure). Styrene is one of the chemicals for which biological monitoring programs have been validated and implemented in environmental and occupational medicine. However, inter-individual differences in the urinary excretion exist both for the main end-products (mandelic acid and phenylglyoxylic acid) and for its specific mercapturic acids (phenylhydroxyethylmercapturic acids, PHEMA). This limits to a certain extent the use of these metabolites for an accurate assessment of styrene exposure. In a group of 26 volunteers selected with relevant genotypes, and exposed to styrene vapours (50 mg/m3, 8 h) in an inhalation chamber, we evaluated whether genotyping or phenotyping relevant drug-metabolizing enzymes (CYP2E1, EPHX1, GSTM1, GSTT1 and GSTP1) may help to explain the observed inter-individual variability in the urinary metabolite excretion. Peripheral blood lymphocytes were used for genotyping and as reporter cells for the phenotyping of CYP2E1 and EPHX1. The GSTM1 genotype was clearly the most significant parameter explaining the variance in urinary PHEMA excretion (6-fold lower in GSTM1 null subjects; P < 0.0001) so that systematic GSTM1 genotyping should be recommended routinely for a correct interpretation of PHEMA urinary levels. Variant alleles CYP2E1*6 (7632T>A) and His113EPHX1 were associated with a significant reduction of, respectively, the expression (P = 0.047) and activity (P = 0.022) of the enzyme in peripheral blood lymphocytes. In combination with GSTM1 genotyping, the phenotyping approach also contributed to improve the interpretation of urinary results, as illustrated by the combined effect of CYP2E1 expression and GSTM1 allelic status that explained 77% of the variance in PHEMA excretion and allows the recommendation of mercapturates as specific and reliable biomarkers of exposure to styrene.
ATP-Induced Ca2+ Release in Cochlear Outer Hair Cells: Localization of an Inositol Triphosphate-Gated Ca2+ Store to the Base of the Sensory Hair Bundle

We used a high-performance fluorescence imaging system to visualize rapid changes in intracellular free Ca2+concentration ([Ca2+]i) evoked by focal applications of extracellular ATP to the hair bundle of outer hair cells (OHCs): the sensory–motor receptors of the cochlea. Simultaneous recordings of the whole-cell current and Calcium Green-1 fluorescence showed a two-component increase in [Ca2+]i. After an initial entry of Ca2+ through the apical membrane, a second and larger, inositol triphosphate (InsP3)-gated, [Ca2+]i surge occurred at the base of the hair bundle. Electron microscopy of this intracellular Ca2+ release site showed that it coincides with the localization of a unique system of endoplasmic reticulum (ER) membranes and mitochondria known as Hensen’s body. Using confocal immunofluorescence microscopy, we showed that InsP3receptors share this location. Consistent with a Ca2+-mobilizing second messenger system linked to ATP-P2 receptors, we also determined that an isoform of G-proteins is present in the stereocilia. Voltage-driven cell shape changes and nonlinear capacitance were monitored before and after ATP application, showing that the ATP-evoked [Ca2+]irise did not interfere with the OHC electromotility mechanism. This second messenger signaling mechanism bypasses the Ca2+-clearance power of the stereocilia and transiently elevates [Ca2+]i at the base of the hair bundle, where it can potentially modulate the action of unconventional myosin isozymes involved in maintaining the hair bundle integrity and potentially influence mechanotransduction.
Orchiectomy Attenuates Kidney Fibrosis after Ureteral Obstruction by Reduction of Oxidative Stress in Mice

Background/Aims: Men are generally more prone to chronic kidney disease and progression to end-stage renal disease than women. However, the underlying mechanisms remain unclear. In this study, we investigated the role of reactive oxygen species and testosterone in the progression of renal fibrosis in mice with unilateral ureteral obstruction (UUO). Methods: Mice were subjected to either orchiectomy or sham operation 14 days before either UUO or sham surgery. Harvesting of the kidney was performed 7 days after the UUO surgery to measure the production of reactive oxygen species and expression of antioxidants such as catalase, copper-zinc superoxide dismutase, and manganese superoxide dismutase, as well as fibrosis markers including α-smooth muscle actin (α-SMA) and collagen. Results: UUO resulted in increased expression of α-SMA and collagen deposition in the kidneys of both female and male mice. These increases were significantly greater in males than females. Orchiectomy significantly reduced increases in α-SMA expression and collagen deposition when compared with intact male. UUO increased the production of hydrogen peroxide and lipid peroxidation along with the decreases in expression of manganese superoxide dismutase, copper-zinc superoxide dismutase, and catalase. These changes induced by UUO were significantly attenuated by orchiectomy. Conclusion: Males are more susceptible to UUO-induced kidney fibrosis compared with females, and the higher susceptibility of males is obviated by orchiectomy along with reduction in oxidative stress.
Force and Acceleration Corridors from Lateral Head Impact

This study was conducted to provide force and acceleration corridors at different velocities describing the dynamic biomechanics of the lateral region of the human head. Temporo-parietal impact tests were conducted using specimens from ten unembalmed post-mortem human subjects. The specimens were isolated at the occipital condyle level, and pre-test x-ray and computed tomography images were obtained. They were prepared with multiple triaxial accelerometers and subjected to increasing velocities (up to 7.7 m/s) using free-fall techniques by impacting onto a force plate from which forces were recorded. A 40-durometer padding (50-mm thickness) material covering the force plate served as the impacting boundary condition. Computed tomography images obtained following the final impact test were used to identify pathology. Four specimens sustained skull fractures. Peak force, displacement, acceleration, energy, and head injury criterion variables were used to describe the dynamic biomechanics. Force and acceleration responses obtained from this experimental study along with other data will be of value in validating finite element models. The study underscored the need to enhance the sample size to derive probability-based human tolerance to side impacts.
Clinical significance of parathyroid intervention on CKD-MBD management

Recently published ‘Guidelines for the management of secondary hyperparathyroidism in chronic dialysis patients’ by the Japanese Society for Dialysis Therapy advocate that percutaneous ethanol injection into enlarged glands, which has been considered as the only alternative to parathyroidectomy (PTx), should be indicated in patients with a single enlarged parathyroid gland (estimated volume >500 mm3, or estimated major axis >10 mm), and that PTx should be recommended in patients with multiple enlarged glands. Cinacalcet cannot achieve optimal control of chronic kidney disease–mineral bone disorder in all patients, and parathyroid intervention will be required in a considerable number of patients with refractory secondary hyperparathyroidism.
Major human epididymis‐specific gene product, HE3, is the first representative of a novel gene family

Differential screening of a human epididymal cDNA library led to the isolation and characterization of a major epididymis‐specific cDNA clone family, referred to as HE3. More detailed sequence and PCR analysis identified two different but homologous gene transcripts, HE3α and HE3β. The former represents an mRNA of ca. 1 kb, encoding a putative small secretory polypeptide of 14903 MW. The HE3β transcript was only found as incomplete 3′ fragments. Analysis of human genomic DNA by Southern blotting suggested the presence in the human genome of at least three independent HE3‐related genes. Isolation of genomic clones for the HE3α gene showed this to contain a single intron of 1.4 kb in the 5′ noncoding region. Although genomic clones corresponding to HE3β could not be found, a third highly homologous gene, HE3γ, was identified as a potential pseudogene. Neither nucleotide nor encoded amino acid sequences of the HE3 gene family are related to any other known sequence in the central databases, and thus represents a novel human gene family, with at least three nonallelic members. Northern hybridization analysis showed that HE3 gene products are specifically expressed in the human epididymis, and not in any other tissue examined. Furthermore, except for the pig, no other nonprimate species has been identified to express homologous sequences in the epididymis. RNase protection assays showed that both the HE3α and HE3β, but not the HE3γ genes, are expressed in the human epididymis. © 1994 Wiley‐Liss, Inc.
Automatic Generation of Student Report Cards

The Learning Analytics Report Card (LARC) is a pilot system which takes time-series data from a student’s course-related activity in a Virtual Learning Environment and generates automatic textual summaries in real time. Students are able to generate reports as often as they like, and to choose which aspects of their behaviour are included in each report. As well as rating a student’s scores against set standards, the generated texts make comparisons with the individual student’s previous behaviour from the same course, and with the average scores of their student cohort. In addition, we carry out sentiment analysis on the student’s forum posts, and generate a sum-mary using quantiﬁers. We report some student reactions to initial trials of the system.