Miracle-dz/UniFAR-FTUs huggingface dataset:
Analysis of Cellular Factors That Mediate Nuclear Export of RNAs Bearing the Mason-Pfizer Monkey Virus Constitutive Transport Element

ABSTRACT There is now convincing evidence that the human Tap protein plays a critical role in mediating the nuclear export of mRNAs that contain the Mason-Pfizer monkey virus constitutive transport element (CTE) and significant evidence that Tap also participates in global poly(A)+ RNA export. Previously, we had mapped carboxy-terminal sequences in Tap that serve as an essential nucleocytoplasmic shuttling domain, while others had defined an overlapping Tap sequence that can bind to the FG repeat domains of certain nucleoporins. Here, we demonstrate that these two biological activities are functionally correlated. Specifically, mutations in Tap that block nucleoporin binding also block both nucleocytoplasmic shuttling and the Tap-dependent nuclear export of CTE-containing RNAs. In contrast, mutations that do not inhibit nucleoporin binding also fail to affect Tap shuttling. Together, these data indicate that Tap belongs to a novel class of RNA export factors that can target bound RNA molecules directly to the nuclear pore without the assistance of an importin β-like cofactor. In addition to nucleoporins, Tap has also been proposed to interact with a cellular cofactor termed p15. Although we were able to confirm that Tap can indeed bind p15 specifically both in vivo and in vitro, a mutation in Tap that blocked p15 binding only modestly inhibited CTE-dependent nuclear RNA export. However, p15 did significantly enhance the affinity of Tap for the CTE in vitro and readily formed a ternary complex with Tap on the CTE. This result suggests that p15 may play a significant role in the recruitment of the Tap nuclear export factor to target RNA molecules in vivo.
Dimension Reduction of Optical Remote Sensing Images via Minimum Change Rate Deviation Method

This paper introduces a new dimension reduction (DR) method, called minimum change rate deviation (MCRD), which is applicable to the DR of remote sensing images. As the main shortcoming of the well-known principal component analysis (PCA) method is that it does not consider the spatial relation among image points, our proposed approach takes into account the spatial relation among neighboring image pixels while preserving all useful properties of PCA. These include uncorrelatedness property in resulted components and the decrease of error with the increasing of the number of selected components. Our proposed method can be considered as a generalization of PCA and, under certain conditions, reduces to it. The proposed MCRD method employs linear spatial operators to consider the spatiality of images. The superiority of MCRD over conventional PCA is demonstrated both mathematically and experimentally. It is shown that MCRD, with an acceptable speed, outperforms PCA in retaining the required information for classification purposes. Moreover, as the locally linear embedding (LLE) method also employs the spatial relations in its DR process, the performances of MCRD and LLE are compared, and the superiority of the proposed method in both classification accuracy and computational cost is shown.
Physiological Non-equivalence of the Two Isoforms of Angiotensin-converting Enzyme*

The structurally related somatic and germinal isoforms of angiotensin-converting enzyme (ACE) contain the same catalytic active center and are encoded by the same gene, whose disruption causes renal atrophy, hypotension, and male sterility. The reason for the evolutionary conservation of both isozymes is an enigma, because, in vitro, they have very similar enzymatic properties. Despite the common enzymatic properties, discrete expression of both isoforms is maintained in alternate cell types. We have previously shown that sperm-specific expression of transgenic germinal ACE in Ace −/− male mice restores fertility without curing their other abnormalities (Ramaraj, P., Kessler, S. P., Colmenares, C. & Sen, G. C. (1998)J. Clin. Invest. 102, 371–378). In this report we tested the biological equivalence of somatic ACE and germinal ACE utilizing an in vivo isozymic substitution approach. Here we report that restoration of male fertility was not achieved by the transgenic expression of enzymatically active, somatic ACE in the sperm of Ace −/− mice. Therefore, the requisite physiological functions of the two tissue-specific isozymes of ACE are not interchangeable.
The air pollutant sodium sulfite enhances mite crude extract-stimulated detachment of A549 airway epithelium cells.

BACKGROUND AND PURPOSE It has been previously reported that the pollutant sodium sulfite (Na2SO3) can activate airway epithelial cells; however, there is as yet no evidence of any direct relationship between house dust mite allergen exposure and Na2SO3 with regards to the pathogenesis of airway allergy. This study investigated the effect of sulfite on mite-stimulated human airway epithelial cells. METHODS The A549 human lung epithelial cell line was used as an in vitro model. Cells were treated with 10 microg/mL mite crude extract for 8 h and/or Na2SO3 (0, 10, 100, 500, 1000 and 5000 microM) for 16 h, and cell adhesion and dissociation on a cell culture plastic surface were quantitated with a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide colorimetric assay. Changes in cell adhesion were also analyzed by monitoring the expression of the cell surface of adhesion molecules integrin alpha2 (CD49b) and integrin alpha6 (CD49f) using flow cytometry. RESULTS A549 cells treated with either mite crude extract only or Na2SO3 only did not show a significant increase in dissociation from the cell culture plastic surface. However, when cells were pretreated with mite extract for 8 h, followed by 16-h incubation with various concentrations of Na2SO3, cell dissociation was enhanced in a dose-dependent manner. A dose-dependent decrease of CD49b and CD49f expression was also seen in cells treated with Na2SO3 only and in mite-pretreated cells. Mite treatment decreased CD49b expression, and a cumulative effect was seen in cells further treated with Na2SO3. CONCLUSION Significant dissociation of airway epithelial cells with Na2SO3 stimulation only occurred in cells pretreated with mite extract. Mite pretreatment enhanced Na2SO3-induced CD49f down-regulation; Na2SO3 and/or mite extract down-regulated CD49b expression of A549 cells. These findings indicate that a synergistic effect of mite extract and sulfite can severely disrupt the airway bronchial epithelial barrier.
DOC concentrations across a depth-dependent light gradient on a Caribbean coral reef

Photosynthates released by benthic primary producers (BPP), such as reef algae and scleractinian corals, fuel the dissolved organic carbon (DOC) production on tropical coral reefs. DOC concentrations near BPP have repeatedly been observed to be elevated compared to those in the surrounding water column. As the DOC release of BPP increases with increasing light availability, elevated DOC concentrations near them will, in part, also depend on light availability. Consequently, DOC concentrations are likely to be higher on the shallow, well-lit reef terrace than in deeper sections on the fore reef slope. We measured in situ DOC concentrations and light intensity in close proximity to the reef alga Dictyota sp. and the scleractinian coral Orbicella faveolata along a depth-dependent light gradient from 5 to 20 m depth and compared these to background concentrations in the water column. At 10 m (intermediate light), DOC concentrations near Dictyota sp. were elevated by 15 µmol C L−1 compared to background concentrations in the water column, but not at 5 and 20 m (high and low light, respectively), or near O. faveolata at any of the tested depths. DOC concentrations did not differ between depths and thereby light environments for any of the tested water types. However, water type and depth appear to jointly affect in situ DOC concentrations across the tested depth-dependent light gradient. Corroborative ex situ measurements of excitation pressure on photosystem II suggest that photoinhibition in Dictyota sp. is likely to occur at light intensities that are commonly present on Curaçaoan coral reefs under high light levels at 5 m depth during midday. Photoinhibition may have thereby reduced the DOC release of Dictyota sp. and DOC concentrations in its close proximity. Our results indicate that the occurrence of elevated DOC concentrations did not follow a natural light gradient across depth. Instead, a combination of multiple factors, such as water type, light availability (including the restriction by photoinhibition), and water movement are proposed to interactively determine the DOC concentrations in the close vicinity of BPP.
Bone mineral density in patients with psoriatic arthritis: data from the Nord-Trøndelag Health Study 3

Background The risk of osteoporosis in patients with psoriatic arthritis (PsA) remains unclear. The aim of this study was to compare bone mineral density (BMD) measured by dual-energy X-ray absorptiometry (DXA) in patients with PsA and controls. Patients and methods Patients with PsA and controls were recruited from the Nord-Trøndelag Health Study (HUNT) 3. Results Patients with PsA (n=69) and controls (n=11 703) were comparable in terms of age (56.8 vs 55.3 years, p=0.32), gender distribution (females 65.2% vs 64.3%, p=0.87) and postmenopausal status (75.6% vs 62.8%, p=0.08). Body mass index (BMI) was higher in patients with PsA compared with controls (28.5 vs 27.2 kg/m2, p=0.01). After adjusting for potential confounding factors (including BMI), BMD was higher in patients with PsA compared with controls at lumbar spine 1–4 (1.213 vs 1.147 g/cm2, p=0.003) and femoral neck (0.960 vs 0.926 g/cm2, p=0.02), but not at total hip (1.013 vs 0.982 g/cm2, p=0.11). Controls had significantly higher odds of having osteopenia or osteoporosis based on measurements of BMD in both the femoral neck (p=0.001), total hip (p=0.033) and lumbar spine (p=0.033). Conclusion Our population-based data showed comparable BMD in patients with PsA and controls. This supports that the PsA population is not at increased risk of osteoporosis.
The Promises and Pitfalls of Factor Timing

The potential to dynamically allocate across factors, or factor timing, has been an area of academic and practitioner research for decades. In this article, the authors revisit the promises of factor timing, documenting the historical linkages between equity factor performance and different groupings of predictors: sentiment, valuation, trend, economic conditions, and financial conditions. The authors highlight that different predictors are more relevant for certain horizons, so the horizon is critical in factor timing. They also argue there are significant pitfalls with factor timing as well. The difficulty of timing factors has been well documented, given the uncertainty of exogenous elements affecting their behavior and the complexity of the underlying relationships. Most importantly, the underlying causal links are time varying. In addition, these relationships are observed with the benefit of hindsight and thus suffer from the age-old problem of data mining. Despite these caveats, the authors believe that at the margin it is possible to time certain elements that can add value and improve outcomes.
Inhibition of α-SMA by the Ectodomain of FGFR2c Attenuates Lung Fibrosis

The soluble ectodomain of fibroblast growth factor receptor-IIIc (sFGFR2c) is able to bind to fibroblast growth factor (FGF) ligands and block the activation of the FGF-signaling pathway. In this study, sFGFR2c inhibited lung fibrosis dramatically in vitro and in vivo. The upregulation of α-smooth muscle actin (α-SMA) in fibroblasts by transforming growth factor-β1 (TGF-β1) is an important step in the process of lung fibrosis, in which FGF-2, released by TGF-β1, is involved. sFGFR2c inhibited α-SMA induction by TGF-β1 via both the extracellular signal-regulated kinase 1/2 (ERK1/2) and Smad3 pathways in primary mouse lung fibroblasts and the proliferation of mouse lung fibroblasts. In a mouse model of bleomycin (BLM)-induced lung fibrosis, mice were treated with sFGFR2c from d 3 or d 10 to 31 after BLM administration. Then we used hematoxylin and eosin staining, Masson staining and immunohistochemical staining to evaluate the inhibitory effects of sFGFR2c on lung fibrosis. The treatment with sFGFR2c resulted in significant attenuation of the lung fibrosis score and collagen deposition. The expression levels of α-SMA, p-FGFRs, p-ERK1/2 and p-Smad3 in the lungs of sFGFR2c-treated mice were markedly lower. sFGFR2c may have potential for the treatment of lung fibrosis as an FGF-2 antagonist.
Information needs of cancer patients in west Scotland: cross sectional survey of patients' views

Abstract Objective: To assess the needs of patients with cancer for information about their condition. Design: Cross sectional survey of patients' views by means of semistructured interview with questionnaire. Setting: A regional cancer centre and two university hospitals in west Scotland. Subjects: 250 (93%) of 269 cancer patients invited to participate in study who were selected by age, sex, socioeconomic status, and tumour site to be representative of cancer patients in west Scotland. Main outcome measures: Patients' need to know whether they had cancer, the medical name of their illness, progress through treatment, how treatment works, side effects, chances of cure, and treatment options. Results: 79% (95% confidence interval 73% to 84%) of patients wanted as much information as possible, and 96% (93% to 98%) had a need or an absolute need to know if they had cancer. Most patients also wanted to know the chance of cure (91% (87% to 94%)) and about side effects of treatment (94% (90% to 97%)). When the replies were cross tabulated with patients' age, sex, deprivation score, and type of treatment there was a linear trend for patients from more affluent areas to want more information and those from deprived areas to want less. There was a strong preference for diagnosis of cancer to be given by a hospital doctor (60% (53% to 66%). Conclusion: Almost all patients wanted to know their diagnosis, and most wanted to know about prognosis, treatment options, and side effects. Key messages We interviewed 250 patients with cancer to find out what information they wanted Almost all the patients wanted to know their diagnosis, and most also wanted to know the chance of cure and the side effects of their treatment Younger patients, women, and those receiving radical treatment in particular wanted to know more about treatment options The overwhelming preference was for the diagnosis of cancer to be given by a hospital doctor
Clustering-based spot segmentation of cDNA microarray images

Microarrays are utilized as that they provide useful information about thousands of gene expressions simultaneously. In this study segmentation step of microarray image processing has been implemented. Clustering-based methods, fuzzy c-means and k-means, have been applied for the segmentation step that separates the spots from the background. The experiments show that fuzzy c-means have segmented spots of the microarray image more accurately than the k-means.
Positive airway pressure and electrical stimulation methods for obstructive sleep apnea treatment: a patent review (2005 – 2014)

Introduction: Obstructive sleep apnea–hypopnea syndrome (OSAHS) is a major health problem with significant negative effects on the health and quality of life. Continuous positive airway pressure (CPAP) is currently the primary treatment option and it is considered the most effective therapy for OSAHS. Nevertheless, comfort issues due to improper fit to patient’s changing needs and breathing gas leakage limit the patient’s adherence to treatment. Areas covered: The present patent review describes recent innovations in the treatment of OSAHS related to optimization of the positive pressure delivered to the patient, methods and systems for continuous self-adjusting pressure during inspiration and expiration phases, and techniques for electrical stimulation of nerves and muscles responsible for the airway patency. Expert opinion: In the last few years, CPAP-related inventions have mainly focused on obtaining an optimal self-adjusting pressure according to patient’s needs. Despite intensive research carried out, treatment compliance is still a major issue. Hypoglossal electrical nerve stimulation could be an effective secondary treatment option when CPAP primary therapy fails. Several patents have been granted focused on selective stimulation techniques and parameter optimization of the stimulating pulse waveform. Nevertheless, there remain important issues to address, like effectiveness and adverse events due to improper stimulation.
Acylated Cholesteryl Galactosides Are Specific Antigens of Borrelia Causing Lyme Disease and Frequently Induce Antibodies in Late Stages of Disease

Borrelia burgdorferi sensu lato is the causative agent of Lyme disease (LD), an infectious disease occurring in North America, Europe, and Asia in different clinical stages. B. burgdorferi sensu lato encompasses at least 12 species, with B. burgdorferi sensu stricto, B. garinii, and B. afzelii being of highest clinical importance. Immunologic testing for LD as well as recent vaccination strategies exclusively refer to proteinaceous antigens. However, B. burgdorferi sensu stricto exhibits glycolipid antigens, including 6-O-acylated cholesteryl β-d-galactopyranoside (ACGal), and first the data indicated that this compound may act as an immunogen. Here we investigated whether B. garinii and B. afzelii also possess this antigen, and whether antibodies directed against these compounds are abundant among patients suffering from different stages of LD. Gas-liquid chromatography/mass spectroscopy and NMR spectroscopy showed that both B. garinii and B. afzelii exhibit ACGal in high quantities. In contrast, B. hermsii causing relapsing fever features 6-O-acylated cholesteryl β-d-glucopyranoside (ACGlc). Sera derived from patients diagnosed for LD contained antibodies against ACGal, with 80% of patients suffering from late stage disease exhibiting this feature. Antibodies reacted with ACGal from all three B. burgdorferi species tested, but not with ACGlc from B. hermsii. These data show that ACGal is present in all clinically important B. burgdorferi species, and that specific antibodies against this compound are frequently found during LD. ACGal may thus be an interesting tool for improving diagnostics as well as for novel vaccination strategies.
Neurosteroid dehydroepiandrosterone exerts anti‐apoptotic effects by membrane‐mediated, integrated genomic and non‐genomic pro‐survival signaling pathways

Dehydroepiandrosterone (DHEA) protects neural crest‐derived PC12 cells from serum deprivation‐induced apoptosis via G protein‐associated specific plasma membrane‐binding sites (mDBS). Here, we studied the signaling pathways involved in the pro‐survival effects of DHEA‐mediated activation of the mDBS binding sites. Membrane impermeable DHEA‐bovine serum albumin (BSA) conjugate induced an acute phosphorylation of the prosurvival kinases Src, protein kinase A (PKA), MEK1/2/ERK1/2, and PI3K/Akt in serum deprived PC12 cells in parallel to an elevation of intracellular cAMP. The physiological significance of these findings was further assessed in a series of experiments using several selective pro‐survival kinase inhibitors. Our combined findings suggest that the following sequence of events may take place following activation of mDBS binding sites: DHEA‐BSA induces an acute but transient sequential phosphorylation of the pro‐survival kinases Src/PKCa/b/MEK1/2/ERK1/2 which, in their turn, activate transcription factors cAMP responsive element binding protein and nuclear factor kappa B which induce the expression of the anti‐apoptotic Bcl‐2 genes. In parallel, DHEA‐BSA increases intracellular cAMP, and the subsequent phosphorylation of PKA kinase and of cAMP responsive element binding protein. Finally, DHEA‐BSA induces phosphorylation of PI3K/Akt kinases which, subsequently, lead to phosphorylation/deactivation of the pro‐apoptotic Bad. Our findings suggest that the neurosteroid DHEA affects neural crest‐derived cell survival by multiple pro‐survival signaling pathways comprising an integrated system of non‐genomic and genomic mechanisms.
Adalimumab for treating rheumatoid arthritis.

OBJECTIVE To assess the efficacy and safety of adalimumab in the treatment of rheumatoid arthritis (RA). METHODS A Cochrane systematic review was performed. The literature search, selection and assessment of the methodological quality of the studies, and the data extraction were performed according to the standard methodology of the Cochrane reviews. Outcome measures included American College of Rheumatology (ACR) and European League Against Rheumatism responses, Disease Activity Score 28 and components of the ACR response, and radiographic and safety data. Weighted mean difference and relative risk were used for reporting continuous and dichotomous data, respectively. Number needed to treat (NNT) or to harm (NNH) were estimated when appropriate. When significant heterogeneity was not found, data were pooled. RESULTS Six studies with 2,390 patients were included in this review. With adalimumab 40 mg every other week (eow) + methotrexate versus placebo + methotrexate, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 52 weeks were 35%, 32%, and 19% with NNT of 2.9, 3.1, and 5.3, respectively. At 52 weeks, adalimumab 40 mg eow and 20 mg every week (ew) significantly slowed the radiological progression. With adalimumab 40 mg eow versus placebo, the absolute risk differences to achieve an ACR20, ACR50, and ACR70 response at 24/26 weeks were 23.64%, 15.31%, and 12.22% with NNT of 5.0, 7.0, and 9.0, respectively. In most of the analyzed studies and comparisons, there were no significant differences in safety outcomes between adalimumab and control groups. CONCLUSION On the basis of studies reviewed here, adalimumab is efficacious in the treatment of RA. No serious adverse effects occurred.
Suicide-related behaviours in schizophrenia in China: a comprehensive meta-analysis

Aims. Suicide-related behaviours are common in schizophrenia and are significantly associated with premature death. The objective of this meta-analysis study was to estimate the pooled prevalence of suicide-related behaviours in schizophrenia patients in China. Methods. The relevant literature was searched systematically via the relevant electronic databases (PubMed, Embase, PsycINFO, Chinese National Knowledge Infrastructure, Wanfang Databases and Chinese Biological Medical Literature Database) from their inception until 14 September 2016. Only original studies that reported the prevalence of suicide-related behaviours including suicidal ideation (SI), suicide plan, suicide attempt (SA) and completed suicide were selected. Results. Nineteen articles met the inclusion criteria and were analysed. The pooled lifetime prevalence of SI and SA were 25.8% (95% CI 14.7–41.1%) and 14.6% (95% CI 9.1–22.8%), respectively. The 1-month prevalence of SI was 22.0% (95% CI 18.2–26.4%). Subgroup analyses of lifetime SI and SA showed that gender, sample size, survey year, study location and source of patients have no significant mediating effects on the results. Conclusions. Suicide-related behaviours are common in Chinese schizophrenia patients. Due to the high mortality risk, regular screening and effective suicide prevention programmes are warranted.