Miracle-dz/UniFAR-FTUs huggingface dataset:
Apicomplexan C-Mannosyltransferases Modify Thrombospondin Type I-containing Adhesins of the TRAP Family

In many metazoan species, an unusual type of protein glycosylation, called C-mannosylation, occurs on adhesive thrombospondin type 1 repeats (TSRs) and type I cytokine receptors. This modification has been shown to be catalyzed by the Caenorhabditis elegans DPY-19 protein and orthologues of the encoding gene were found in the genome of apicomplexan parasites. Lately, the micronemal adhesin thrombospondin-related anonymous protein (TRAP) was shown to be C-hexosylated in Plasmodium falciparum sporozoites. Here, we demonstrate that also the micronemal protein MIC2 secreted by Toxoplasma gondii tachyzoites is C-hexosylated. When expressed in a mammalian cell line deficient in C-mannosylation, P. falciparum and T. gondii Dpy19 homologs were able to modify TSR domains of the micronemal adhesins TRAP/MIC2 family involved in parasite motility and invasion. In vitro, the apicomplexan enzymes can transfer mannose to a WXXWXXC peptide but, in contrast to C. elegans or mammalian C-mannosyltransferases, are inactive on a short WXXW peptide. Since TSR domains are commonly found in apicomplexan surface proteins, C-mannosylation may be a common modification in this phylum.
Abnormal intrinsic brain functional network dynamics in Parkinson’s disease

Parkinson’s disease is a neurodegenerative disorder characterized by nigrostriatal dopamine depletion. Previous studies measuring spontaneous brain activity using resting state functional magnetic resonance imaging have reported abnormal changes in broadly distributed whole-brain networks. Although resting state functional connectivity, estimating temporal correlations between brain regions, is measured with the assumption that intrinsic fluctuations throughout the scan are stable, dynamic changes of functional connectivity have recently been suggested to reflect aspects of functional capacity of neural systems, and thus may serve as biomarkers of disease. The present work is the first study to investigate the dynamic functional connectivity in patients with Parkinson’s disease, with a focus on the temporal properties of functional connectivity states as well as the variability of network topological organization using resting state functional magnetic resonance imaging. Thirty-one Parkinson’s disease patients and 23 healthy controls were studied using group spatial independent component analysis, a sliding windows approach, and graph-theory methods. The dynamic functional connectivity analyses suggested two discrete connectivity configurations: a more frequent, sparsely connected within-network state (State I) and a less frequent, more strongly interconnected between-network state (State II). In patients with Parkinson’s disease, the occurrence of the sparsely connected State I dropped by 12.62%, while the expression of the more strongly interconnected State II increased by the same amount. This was consistent with the altered temporal properties of the dynamic functional connectivity characterized by a shortening of the dwell time of State I and by a proportional increase of the dwell time pattern in State II. These changes are suggestive of a reduction in functional segregation among networks and are correlated with the clinical severity of Parkinson’s disease symptoms. Additionally, there was a higher variability in the network global efficiency, suggesting an abnormal global integration of the brain networks. The altered functional segregation and abnormal global integration in brain networks confirmed the vulnerability of functional connectivity networks in Parkinson’s disease.
Registration Accuracy of CT/MRI Fusion for Localisation of Deep Brain Stimulation Electrode Position: An Imaging Study and Systematic Review

Background: Postoperative imaging is essential for verifying electrode location in patients undergoing deep brain stimulation (DBS). MRI offers better visualisation of brain targets, but concerns about adverse events have limited its use. Preoperative stereotactic MRI fused with a postoperative stereotactic CT, demonstrating the electrode position, is now widely used. Objectives: The aims of this study were to: (1) evaluate the accuracy of image registration using Neuroinspire, and (2) undertake a systematic review of the literature on CT/MRI fusion techniques to ascertain the accuracy of other software packages. Methods: Twenty patients who underwent bilateral subthalamic nucleus DBS for Parkinson's disease were selected. The postoperative CT was registered and fused with the preoperative MRI using Neuroinspire. The position of each electrode tip was determined in stereotactic coordinates both in the (unfused) postoperative CT and the fused CT/MRI. The difference in tip position was used to evaluate the registration accuracy. Results: The mean error ± SD of CT/MRI fusion using Neuroinspire was 0.25 ± 0.15, 0.33 ± 0.26 and 0.46 ± 0.55 mm in lateral, anteroposterior and vertical axes. A systematic review suggested that CT/MRI registration with Neuroinspire is more accurate than that achieved with other tested CT/MRI fusion algorithms. Conclusion: CT/MRI fusion for localisation of electrode placement offers an accurate, reliable and safe modality for assessing electrode location.
Explorative Randomized Phase II Clinical Study of the Efficacy and Safety of Finafloxacin versus Ciprofloxacin for Treatment of Complicated Urinary Tract Infections

ABSTRACT The broad-spectrum C-8-cyano-fluoroquinolone finafloxacin displays enhanced activity under acidic conditions. This phase II clinical study compared the efficacies and safeties of finafloxacin and ciprofloxacin in patients with complicated urinary tract infection and/or pyelonephritis. A 5-day regimen with 800 mg finafloxacin once a day (q.d.) (FINA05) had results similar to those of a 10-day regimen with 800 mg finafloxacin q.d. (FINA10). Combined microbiological and clinical responses at the test-of-cure (TOC) visit were 70% for FINA05, 68% for FINA10, and 57% for a 10-day ciprofloxacin regimen (CIPRO10) in 193 patients (64 for FINA05, 68 for FINA10, and 61 for CIPRO10) of the microbiological intent-to-treat (mITT) population. Additionally, the clinical effects of ciprofloxacin on patients with an acidic urine pH (80% of patients) were reduced, whereas the effects of finafloxacin were unchanged. Finafloxacin was safe and well tolerated. Overall, 43.4% of the patients in the FINA05 group, 42.7% in the FINA10 group, and 54.2% in the CIPRO10 group experienced mostly mild and treatment-emergent but unrelated adverse events. A short-course regimen of 5 days of finafloxacin resulted in high eradication and improved clinical outcome rates compared to those for treatment with ciprofloxacin for 10 days. In contrast to those of ciprofloxacin, the clinical effects of finafloxacin were not reduced by acidic urine pH. Hospitalized adults were randomized 1:1:1 to finafloxacin treatment (800 mg q.d.) for either 5 or 10 days or to ciprofloxacin treatment (400 mg/500 mg b.i.d.) for 10 days with an optional switch from intravenous (i.v.) to oral administration at day 3. The primary endpoint was the combined microbiological and clinical response at the TOC visit in the microbiological intent-to-treat population. (This study has been registered at ClinicalTrials.gov under identifier NCT01928433.)
A closed-loop ΣΔ modulator for micromechanical capacitive sensors

: This paper describes a CMOS fully-differential switched-capacitor (SC) single-loop Sigma-Delta (ΣΔ) modulator specialized for highly precise micromechanical capacitive sensors. This design adopts a single-loop, fourth-order, one-bit quantization architecture with feedforward paths for lower nonlinearities and power consumption. Systematic optimization is used to avoid deterioration in conversion accuracy caused by capacitor mismatch. Chopper-stabilization and double-sampling techniques are also employed to enhance performances in noise depression. Manufactured in a standard 0.35 μm CMOS process, the ASIC occupies an area of 5.32 mm 2 including 25 pads. This modulator achieves a signal-to-noise ratio (SNR) of 105.2 dB and dynamic range (DR) of 113.7 dB. The whole chip consumes 12.6 mW from a 5V supply.
Dexamethasone inhibits lung epithelial cell apoptosis induced by IFN-γ and Fas.

Lung epithelium plays a central role in modulation of the inflammatory response and in lung repair. Airway epithelial cells are targets in asthma, viral infection, acute lung injury, and fibrotic lung disease. Activated T lymphocytes release cytokines such as interferon-γ (IFN-γ) that can cooperate with apoptotic signaling pathways such as the Fas-APO-1 pathway to induce apoptosis of damaged epithelial cells. We report that IFN-γ alone and in combination with activation of the Fas pathway induced apoptosis in A549 lung epithelial cells. Interestingly, the corticosteroid dexamethasone was the most potent inhibitor of IFN-γ- and IFN-γ plus anti-Fas-induced apoptosis. IFN-γ induced expression of an effector of apoptosis, the cysteine protease interleukin-1β-converting enzyme, in A549 cells. Dexamethasone, in contrast, induced expression of an inhibitor of apoptosis, human inhibitor of apoptosis (hIAP-1), also known as cIAP2. We suggest that the inhibition of epithelial cell apoptosis by corticosteroids may be one mechanism by which they suppress the inflammatory response.
Characterization of Enterotoxigenic Bacillus cereus sensu lato and Staphylococcus aureus Isolates and Associated Enterotoxin Production Dynamics in Milk or Meat-Based Broth

Bacillus cereus sensu lato species, as well as Staphylococcus aureus, are important pathogenic bacteria which can cause foodborne illness through the production of enterotoxins. This study characterised enterotoxin genes of these species and examined growth and enterotoxin production dynamics of isolates when grown in milk or meat-based broth. All B. cereus s. l. isolates harboured nheA, hblA and entFM toxin genes, with lower prevalence of bceT and hlyII. When grown at 16 °C, toxin production by individual B. cereus s. l. isolates varied depending on the food matrix; toxin was detected at cell densities below 5 log10(CFU/mL). At 16 °C no staphylococcal enterotoxin C (SEC) production was detected by S. aureus isolates, although low levels of SED production was noted. At 30 °C all S. aureus isolates produced detectable enterotoxin in the simulated meat matrix, whereas SEC production was significantly reduced in milk. Relative to B. cereus s. l. toxin production, S. aureus typically required reaching higher cell numbers to produce detectable levels of enterotoxin. Phylogenetic analysis of the sec and sel genes suggested population evolution which correlated with animal host adaptation, with subgroups of bovine isolates or caprine/ovine isolates noted, which were distinct from human isolates. Taken together, this study highlights the marked differences in the production of enterotoxins both associated with different growth matrices themselves, but also in the behaviour of individual strains when exposed to different food matrices.
Insulin-like growth factor-binding protein-5 (IGFBP-5) stimulates phosphorylation of the IGFBP-5 receptor.

The finding that insulin-like growth factor (IGF)-binding protein-5 (IGFBP-5) binding to mouse osteoblasts was capable of being downregulated by IGFBP-5 suggested that the 420-kDa membrane protein, which interacted with IGFBP-5, may be a signaling receptor (Andress, D. L. J. Biol. Chem. 270: 28289-28296, 1995). In the current study, a carboxy-terminal IGFBP-5 peptide, IGFBP-5-(201-218), which was found to competitively inhibit125I-IGFBP-5 binding and to specifically bind to osteoblast monolayers, was used to affinity-purify the 420-kDa membrane protein. Coincubation of the affinity-purified membrane protein with [32P]ATP resulted in autophosphorylation at serine residues. Serine phosphorylation of the 420-kDa protein was enhanced by intact IGFBP-5, IGFBP-5-(1-169), and IGFBP-5-(201-218). When the IGFBP-5 receptor was incubated with dephosphorylated casein in the presence of [32P]ATP, casein became phosphorylated on serine residues. These data indicate that IGFBP-5 stimulates the phosphorylation of the IGFBP-5 receptor and suggest that serine/threonine kinase activation may be important in mediating some of the IGF-independent effects of IGFBP-5.
Clinical characteristics and outcomes of HIV-associated immune complex kidney disease.

BACKGROUND The pathogenesis and natural history of HIV-associated immune complex kidney disease (HIVICK) is not well understood. Key questions remain unanswered, including the role of HIV infection and replication in disease development and the efficacy of antiretroviral therapy (ART) in the prevention and treatment of disease. METHODS In this multicentre study, we describe the renal pathology of HIVICK and compare the clinical characteristics of patients with HIVICK with those with IgA nephropathy and HIV-associated nephropathy (HIVAN). Poisson regression models were used to identify risk factors for each of these pathologies. RESULTS Between 1998 and 2012, 65 patients were diagnosed with HIVICK, 27 with IgA nephropathy and 70 with HIVAN. Black ethnicity and HIV RNA were associated with HIVICK, receipt of ART with IgA nephropathy and black ethnicity and CD4 cell count with HIVAN. HIVICK was associated with lower rates of progression to end-stage kidney disease compared with HIVAN and IgA nephropathy (P < 0.0001). Patients with HIVICK who initiated ART and achieved suppression of HIV RNA experienced improvements in estimated glomerular filtration rate and proteinuria. CONCLUSIONS These findings suggest a pathogenic role for HIV replication in the development of HIVICK and that ART may improve kidney function in patients who have detectable HIV RNA at the time of HIVICK diagnosis. Our data also suggest that IgA nephropathy should be viewed as a separate entity and not included in the HIVICK spectrum.
Assessing the Appropriateness of Oral Anticoagulation for Atrial Fibrillation in Advanced Frailty: Use of Stroke and Bleeding Risk-Prediction Models.

BACKGROUND Atrial fibrillation (AF) is common among frail older adults. Oral anticoagulation (OAC) is particularly challenging for these due to overlapping stroke and bleeding risk factor profiles. OBJECTIVE To compare the utility of stroke and haemorrhage risk-prediction instruments in the treatment of AF among frail older adults. DESIGN Cross-sectional study. SETTINGS AND PARTICIPANTS Frail residents in four nursing homes with a Clinical Frailty Scale score ≥5 (median 7±0). MEASUREMENTS The prevalence of AF was assessed by ECG and chart review. Stroke (CHADS2 and CHA2DS2-VASc) and bleeding (HASBLED and HEMORR2HAGES) risk-prediction scores were then applied. A validated, risk-based, colour-coded decision support tool, incorporating these instruments, was then used to create a risk matrix and assess the appropriateness of OAC. RESULTS In total, 225 patients were included. The distribution of CFS scores was similar irrespective of AF status. In all, 86/225 (38%) had any history of AF. Of these, only 15/86 (17%) were prescribed OAC. All those in AF scored ≥2 on the CHA2DS2-VASc. One-third also scored high-risk of bleeding using HAS-BLED or HEMORR2HAGES. Risk-prediction scores were similar between those with 'known' (documented) and occult (only on ECG) AF. The colour-coded decision tree suggested that OAC would be recommended for the majority in AF when HAS-BLED (60/86, 70%) was used as the bleeding risk-prediction instrument. Despite this, only 12/60 (20%) were anticoagulated. When HEMORR2HAGES was incorporated instead, one patient was advised OAC, the remainder no treatment (57%) or an antiplatelet (42%). DISCUSSION Stroke risk was high and bleeding risk levels comparatively low, suggesting that the balance of risk may favor OAC for AF in this cohort of patients with advanced frailty. Despite this and the high prevalence of AF, OAC prescription rates were low. The decision-support tool used showed mixed results, depending on the bleeding-risk score incorporated, suggesting that while useful, they should not replace clinical judgement.
Tracking of fruit and vegetable consumption from adolescence into adulthood and its longitudinal association with overweight

The objective of the present study was to assess to what extent fruit and vegetable intakes track over a 24-year time period and to assess longitudinal associations between fruit and vegetable intakes and (change in) BMI and sum of skinfolds. Dietary intake and anthropometrics were repeatedly assessed for 168 men and women between the ages of 12 and 36 years. Linear general estimating equations analyses were applied (1) to estimate tracking coefficients, (2) to estimate predictability for meeting the national recommendation for fruit and vegetable intake and for being in the highest quartile for fruit and vegetable intake, and (3) to estimate the association between fruit and vegetable intake and BMI and sum of skinfolds. We found that tracking coefficients were 0·33 (P < 0·001) for fruit intake and 0·27 (P < 0·001) for vegetable intake. Mean fruit intake decreased over a 24-year period. For fruit intake, predictability was higher in men than in women (OR 6·02 (P < 0·001) and 2·33 (P = 0·001) for meeting the recommendation for men and women respectively). After adjustment, fruit intake was not associated with BMI, but being in the lowest quartile of fruit intake was significantly associated with a lower sum of skinfolds. Women in the lowest quartiles of vegetable intake had significantly higher BMI and sum of skinfolds and also greater positive changes in these parameters. In conclusion, tracking and predictability for fruit and vegetable intake appear to be low to moderate, which might indicate that fruit and vegetable promotion should be started at an early age and continued into adulthood. Despite the fact that we only observed beneficial weight-maintaining effects of vegetable intake in women, promoting vegetables is important for both sexes because of other positive properties of vegetables. No evidence was found for promoting fruit intake as a means of weight maintenance.
Threatened or Threatening? How Ideology Shapes Asylum Seekers’ Immigration Policy Attitudes in Israel and Australia

Can different political ideologies explain policy preferences regarding asylum seekers? We focus on attitudes regarding governmental policy towards out-group members and suggest that perceptions of threat help to shape these policy attitudes. Study 1 compared public opinion regarding asylum policy in Israel (N = 137) and Australia (N = 138), two countries with restrictive asylum policies and who host a large number of asylum seekers; Study 2, a longitudinal study, was conducted during two different time periods in Israel—before and during the Gaza conflict. Results of both studies showed that threat perceptions of out-group members drive the relationship between conservative political ideologies and support for exclusionary asylum policies among citizens. Perceptions of threat held by members of the host country (the in-group) towards asylum seekers (the out-group) may influence policy formation. The effect of these out-groups threats needs to be critically weighed when considering Israeli and Australian policies towards asylum seekers.
Y Box-Binding Protein 1 Promotes Epithelial-Mesenchymal Transition, Invasion, and Metastasis of Cervical Cancer via Enhancing the Expressions of Snail

Objective Y box-binding protein 1 (YB-1) is a potent oncogenic protein. How it regulates Snail in most tumors including cervical cancer is unknown. This article is to study if YB-1 plays a role in cervical cancer via regulating the expression of Snail. Methods Immunohistochemical staining of YB-1, Snail, and E-cadherin (E-cad) was performed on tissue specimens including 35 cases of chronic cervicitis (as a control), 35 cases of cervical intraepithelial neoplasm (CIN) I, 35 cases of CIN II/III, 28 cases of unmetastatic cervical squamous cell carcinoma, and 19 cases of metastatic cervical squamous cell carcinoma. RNA interference technique was used to knock down YB-1, E6, and Snail genes. Quantitative polymerase chain reaction, western blot, and transwell experiment were used to detect RNA, protein, and cell invasion of cervical cancer cell lines Hela and C33A, respectively. Results First, YB-1 knockdown significantly reduced messenger RNA (mRNA) and protein levels of Snail, followed by the increased mRNA and protein levels of E-cad and the decreased invasive ability in both Hela (human papillomavirus [HPV] 18+) and C33A (HPV−) cell lines. Second, YB-1 and Snail protein were correlatively expressed in the group order of metastatic cervical squamous cell carcinoma > unmetastatic cervical squamous cell carcinoma > CINs > cervicitis, with the inverse expression mode of E-cad in the group order, P value less than 0.01, between any 2 groups. Finally, HPV18 E6 knockdown reduced the mRNA and protein levels of YB-1 and Snail in Hela cells. Conclusions The results firstly reported that YB-1 whose mRNA expression is regulated by HPV18 E6 promotes epithelial-mesenchymal transition and progression of cervical cancer via enhancing the expressions of Snail, which indicated that YB-1/Snail/epithelial-mesenchymal transition axis could have a potential use in the diagnosis and therapy of cervical cancer metastasis as a cancer marker and molecular target.
Localization of cyclooxygenase-2 and regulation of its mRNA expression in gastric ulcers in rats.

It has been reported that cyclooxygenase-2 (COX-2) may play a crucial role in gastric ulcer healing. We examined the localization of COX-2 and the regulation of COX-2 mRNA expression in acetic acid ulcers in rats. PGE2 production was elevated in ulcerated tissue but not in intact tissue. COX-2 mRNA expression was induced in only the ulcerated tissue, and COX-2 protein was found in fibroblasts, monocytes/macrophages, and granulocytes. A selective COX-2 inhibitor inhibited increased PGE2 production by the ulcerated tissue. Interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and transforming growth factor-β1 (TGF-β1) mRNAs were also expressed only in the ulcerated tissue. In a culture of isolated ulcer base, blockade of IL-1β and TNF-α reduced COX-2 mRNA expression and PGE2 production. In contrast, COX-2 mRNA expression and PGE2 production were promoted by prevention of TGF-β1 action. These results indicate that COX-2 protein is highly localized in the base of gastric ulcers in rats and that COX-2 mRNA expression might be regulated positively by IL-1β and TNF-α and negatively by TGF-β1.
RECQL4 Regulates p53 Function In Vivo During Skeletogenesis

RECQ DNA helicases play critical roles in maintaining genomic stability, but their role in development has been less well studied. Rothmund‐Thomson syndrome, RAPADILINO, and Baller‐Gerold syndrome are rare genetic disorders caused by mutations in the RECQL4 gene. These patients have significant skeletal developmental abnormalities including radial ray, limb and craniofacial defects. To investigate the role of Recql4 in the developing skeletal system, we generated Recql4 conditional knockout mice targeting the skeletal lineage. Inactivation of Recql4 using the Prx1‐Cre transgene led to limb abnormalities and craniosynostosis mimicking the major bone findings in human RECQL4 patients. These Prx1‐Cre+;Recql4fl/fl mice as well as Col2a1‐Cre+;Recql4fl/fl mice exhibited growth plate defects and an increased p53 response in affected tissues. Inactivation of Trp53 in these Recql4 mutants resulted in genetic rescue of the skeletal phenotypes, indicating an in vivo interaction between Recql4 and Trp53, and p53 activation as an underlying mechanism for the developmental bone abnormalities in RECQL4 disorders. Our findings show that RECQL4 is critical for skeletal development by modulating p53 activity in vivo. © 2015 American Society for Bone and Mineral Research