Miracle-dz/UniFAR-FTUs huggingface dataset:
Protein kinase C regulates bombesin-induced rapid VEGF secretion in neuroblastoma cells.

BACKGROUND Intracellular signaling responsible for gastrin-releasing peptide (GRP) receptor-mediated neovascularization is not clearly understood. We sought to determine the cellular mechanisms involved in the GRP receptor regulation of vascular endothelial growth factor (VEGF) release in neuroblastoma cells. MATERIALS AND METHODS BE(2)-C cells were treated with bombesin (BBS), the amphibian equivalent of GRP, Phorbol myristate acetate (PMA) a PKC agonist, or GF109293X (GFX), and analyses were performed for VEGF secretion, phosphorylated protein kinase B (AKT), extracellular signal-regulated kinases (ERK) and protein kinase D (PKD) expression. RESULTS BBS rapidly increased VEGF secretion at 30 min. Pre-treatment with PMA alone produced similar results; this effect was synergistic with the addition of GRP. Conversely, GFX blocked PMA-stimulated increase in VEGF secretion. Immunofluorescent staining for VEGF correlated to BBS, PMA and GFX. CONCLUSION PKC is critically responsible for rapid VEGF secretion by GRP receptor signaling in neuroblastoma cells. Inhibition of VEGF significantly reduced GRP-mediated cell proliferation, suggesting its crucial role in neuroblastoma tumorigenesis.
Designing, prototype making and evaluating a mechanical aid device for patient transfer between bed and stretcher

Introduction. The present study aimed at designing, prototype making and evaluating a new assistive device to improve patient transfer conditions. Methods. A new aid device for patient transfer was designed and its prototype was made. Comfort and perceived physical exertion of users and stability and applicability of the device were examined. The test subjects included 37 healthcare workers from a hospital with patient transfer experience. The data collection tools consisted of visual analog scales (VAS) and Borg’s rating physical effort scale. The rapid entire body assessment (REBA) method was applied to evaluate working posture. Results. The results showed that in 70% of the wards, patient transfer was performed manually more than five times per shift. While using the newly designed device, the mean (SD) of the users’ comfort, and the clients’ comfort and safety, was measured as 8.59 (0.87), 8.46 (0.92) and 8.67 (0.71), respectively, as reported by VAS. The results revealed a significant reduction in the users’ rating of perceived exertion (p < 0.001). Additionally, the REBA score was lower in mechanical transfer. Conclusion. The new assistive device increased the users’ and the clients’ comfort, reduced the users’ physical exertion and improved working postures.
Glycoprotein G of Herpes Simplex Virus 2 as a Novel Vaccine Antigen for Immunity to Genital and Neurological Disease

ABSTRACT The envelope glycoproteins of herpes simplex virus 1 (HSV-1) and HSV-2, with the exception of glycoprotein G, elicit cross-reactive B- and T-cell responses. Human vaccine trials, using the cross-reactive glycoproteins B and D, have shown no protection against genital HSV-2 infection or disease. In this study, the mature form of glycoprotein G (mgG-2) of HSV-2 was used for immunization of mice, either alone or in combination with adjuvant CpG, followed by an intravaginal challenge with a lethal dose of a fully virulent HSV-2 strain. Mice immunized with mgG-2 plus CpG showed low disease scores and a significantly higher survival rate (73%) than mice immunized with mgG-2 alone (20%) or controls (0%). Accordingly, limited numbers of infectious HSV-2 particles were detected in the spinal cord of mice immunized with mgG-2 plus CpG. The observed protection was associated with a gamma interferon (IFN-γ) response by splenic CD4+ T cells upon antigen restimulation in vitro and in vaginal washes 1 day postinfection. The majority of sera collected from mice immunized with mgG-2 plus CpG showed macrophage-mediated antibody-dependent cellular cytotoxicity and antibody-dependent complement-mediated cytolysis, while no neutralization activity was observed. In conclusion, we have shown that immunization with the type-specific mgG-2 protein in combination with CpG could elicit protective immunity against an otherwise lethal vaginal HSV-2 challenge. The mgG-2 protein may therefore constitute a promising HSV-2 vaccine antigen to be considered for future human trials.
Paradoxical Role of Ascorbic Acid and Riboflavin in Solutions of Total Parenteral Nutrition: Implication in Photoinduced Peroxide Generation

In the presence of light, a multivitamin preparation is the main source of peroxides in solutions of total parenteral nutrition (TPN). This preparation contains two photosensitive products, 5′-phosphate flavin mononucleotide(FMN) and polysorbates (PS), as well as electron donors such as ascorbate(AH). We hypothesized that the admixture of FMN or PS with electron donors generates peroxides in TPN and alters the quality of nutrients. Using xylenol orange, peroxide concentrations were measured in solutions containing AH, FMN, and/or PS in water, a dextrose solution, an amino acid preparation, and a lipid emulsion. Thiol functions were evaluated by reduction of 5,5-dithiobis(2-nitrobenzoic acid) in the amino acid preparation. After 24-h light exposure, dextrose solutions with admixtures of AH + FMN or AH + FMN + PS generated peroxides at concentrations similar to those observed in a 1% multivitamin solution, and over three times higher than those observed with FMN, PS, or AH alone. However, in the presence of amino acids, FMN alone induced a generation of peroxides comparable to that observed with FMN + AH. In the lipid emulsion, peroxides increased over 3-fold in the presence of FMN or FMN + AH. The addition of catalase suggested that lipid peroxides and H2O2 were produced, and the loss of thiol function suggested that an oxidation of amino acids occurred. When exposed to light, FMN induces reactions with amino acids, polyunsaturated fatty acids, and even AH, altering the quality of nutrients. Paradoxically, AH without FMN has a protective effect on peroxide generation in TPN.
Substrate Trapping Proteomics Reveals Targets of the βTrCP2/FBXW11 Ubiquitin Ligase

ABSTRACT Defining the full complement of substrates for each ubiquitin ligase remains an important challenge. Improvements in mass spectrometry instrumentation and computation and in protein biochemistry methods have resulted in several new methods for ubiquitin ligase substrate identification. Here we used the parallel adapter capture (PAC) proteomics approach to study βTrCP2/FBXW11, a substrate adaptor for the SKP1–CUL1–F-box (SCF) E3 ubiquitin ligase complex. The processivity of the ubiquitylation reaction necessitates transient physical interactions between FBXW11 and its substrates, thus making biochemical purification of FBXW11-bound substrates difficult. Using the PAC-based approach, we inhibited the proteasome to “trap” ubiquitylated substrates on the SCFFBXW11 E3 complex. Comparative mass spectrometry analysis of immunopurified FBXW11 protein complexes before and after proteasome inhibition revealed 21 known and 23 putatively novel substrates. In focused studies, we found that SCFFBXW11 bound, polyubiquitylated, and destabilized RAPGEF2, a guanine nucleotide exchange factor that activates the small GTPase RAP1. High RAPGEF2 protein levels promoted cell-cell fusion and, consequently, multinucleation. Surprisingly, this occurred independently of the guanine nucleotide exchange factor (GEF) catalytic activity and of the presence of RAP1. Our data establish new functions for RAPGEF2 that may contribute to aneuploidy in cancer. More broadly, this report supports the continued use of substrate trapping proteomics to comprehensively define targets for E3 ubiquitin ligases. All proteomic data are available via ProteomeXchange with identifier PXD001062.
Blood pressure and other determinants of new-onset atrial fibrillation in patients at high cardiovascular risk in the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease studie

Background: Evidence on new-onset atrial fibrillation in high-risk vascular patients without heart failure is limited. New-onset atrial fibrillation was a prespecified secondary objective of the Ongoing Telmisartan Alone and in Combination With Ramipril Global Endpoint Trial (ONTARGET)/Telmisartan Randomized AssessmeNt Study in ACE iNtolerant subjects with cardiovascular Disease (TRANSCEND) studies. Methods: We studied 30 424 ONTARGET/TRANSCEND patients (mean age ± SD, 66.4 ± 7.0) with vascular disease or complicated diabetes who were in sinus rhythm at entry. A copy of ECG was sent to central office every time new atrial fibrillation was detected by investigators. Results: During a median follow-up period of 4.7 years, new atrial fibrillation occurred in 2092 patients (15.1 per 1000 patient-years). Risk of atrial fibrillation increased with age, SBP and pulse pressure, left ventricular hypertrophy, BMI, serum creatinine and history of hypertension, coronary artery disease and cerebrovascular disease (all P < 0.01). After adjustment for BMI and other variables, atrial fibrillation risk increased with hip circumference. History of hypertension was associated with a 34% higher risk of new atrial fibrillation. New atrial fibrillation portended an increased risk of congestive heart failure [hazard ratio 2.89, 95% confidence interval (CI) 2.45–3.40, P < 0.01] and cardiovascular death (hazard ratio 1.22, 95% CI 1.05–1.41, P < 0.01). Risk of stroke was unaffected (hazard ratio 1.14, 95% CI 0.93–1.40), whereas that of myocardial infarction was reduced (hazard ratio 0.64, 95% CI 0.50–0.82). Patients with new atrial fibrillation were more likely to receive vitamin K antagonists (P < 0.01), statins (P < 0.05) and &bgr;-blockers (P < 0.01) than those in sinus rhythm. Conclusion: New atrial fibrillation is common in high-risk vascular patients and is associated with several risk factors including history of hypertension. Hip circumference was the strongest anthropometric predictor. Despite extensive use of modern therapies, new atrial fibrillation carries a high risk of congestive heart failure and death over a relatively short term.
Influence of hydraulic retention time on partial nitrification of continuous-flow aerobic granular-sludge reactor

This study investigated the effects of hydraulic retention time (HRT) at 12 h, 7.2 h and 2.4 h on partial nitrification efficiency of continuous-flow aerobic granular reactors (CFAGRs) with mature aerobic granules (500±20 mg l−1). At HRT 12 h and 7.2 h, the removal efficiency of both ammonia–nitrogen (NH 4+−N) and nitrite accumulation rate were exceeding 90%. At HRT 2.4 h, NH 4+−N removal efficiency was reduced but most of the conversion efficiency to nitrite was only slightly reduced. At HRT<2.4 h, washout of aerobic granules occurred. In all tests conducted herein, the chemical oxygen demand removal efficiencies exceeded 90%. The clone library results noted the presence of ammonia-oxidizing bacteria belonged to β -Proteobacteria subclass, including 94% of Nitrosomonas europaea and 6% of Nitrosomonas sp. The polymerase chain reaction and denaturing gradient gel electrophoresis results suggested that Alpha proteobacterium, Pseudoxanthomonas mexicana strain, Sphaerotilus natans and Uncultured gamma proteobacterium were responsible for the aerobic granular stability and processing performance. The present CFAGR successfully implemented continuous partial nitrification using aerobic granules at low HRT.
Novel Industrial Wireless Sensor Networks for Machine Condition Monitoring and Fault Diagnosis

This paper proposes a novel industrial wireless sensor network (IWSN) for industrial machine condition monitoring and fault diagnosis. In this paper, the induction motor is taken as an example of monitored industrial equipment due to its wide use in industrial processes. Motor stator current and vibration signals are measured for further processing and analysis. On-sensor node feature extraction and on-sensor fault diagnosis using neural networks are then investigated to address the tension between the higher system requirements of IWSNs and the resource-constrained characteristics of sensor nodes. A two-step classifier fusion approach using Dempster-Shafer theory is also explored to increase diagnosis result quality. Four motor operating conditions-normal without load, normal with load, loose feet, and mass imbalance-are monitored to evaluate the proposed system. Experimental results show that, compared with raw data transmission, on-sensor fault diagnosis could reduce payload transmission data by 99%, decrease node energy consumption by 97%, and prolong node lifetime from 106 to 150 h, an increase of 43%. The final fault diagnosis results using the proposed classifier fusion approach give a result certainty of at least 97.5%. To leverage the advantages of on-sensor fault diagnosis, another system operating mode is explored, which only transmits the fault diagnosis result when a fault happens or at a fixed interval. For this mode, the node lifetime reaches 73 days if sensor nodes transmit diagnosis results once per hour.
Interference control commonalities in patients with schizophrenia, bipolar disorder, and borderline personality disorder

ABSTRACT Background: Whereas deficits in executive functioning have been widely reported in schizophrenia and, somewhat less, in bipolar disorder, few studies have addressed this issue in people diagnosed with borderline personality disorder. Importantly, no studies to date have compared the ability to cope with interfering information in all three groups of patients. Impairment in executive control has been associated with reduced daily functioning. Method: The sample included 20 patients diagnosed with schizophrenia, 19 with bipolar disorder, 20 with borderline personality disorder, and 19 demographically matched healthy volunteers. Participants were administered two different experimental tasks to assess the ability to exert control over interference arisen from semantic memory or from distracting perceptual information. Results: The three groups of patients showed similar impairment in solving interference from semantic memory compared to controls. However, no psychiatric group showed impairment in controlling interference from distracting perceptual information relative to controls. Conclusions: Our study shows, for the first time, that schizophrenia, bipolar disorder, and borderline personality disorder entail a common impairment in exerting control over interference arisen from memory but intact control over perceptual interference. These findings reinforce the idea that similar cognitive functioning may underlie severe mental disorders sharing poor global functioning but with different patterns of symptomatology.
A pseudoknot ribozyme structure is active in vivo and required for hepatitis delta virus RNA replication

The ribozymes of hepatitis delta virus (HDV) have so far been studied primarily in vitro. Several structural models for HDV ribozymes based on truncated HDV RNA fragments, which are different from the hammerhead or the hairpin/paperclip ribozyme model proposed for plant viroid or virusoid RNAs, have been proposed. Whether these structures actually exist in vivo and whether ribozymes actually function in the HDV replication cycle have not been demonstrated. We have now developed an in vivo ribozyme self-cleavage assay capable of detecting self-cleavage of dimer or trimer HDV RNA in vivo. By site-directed mutagenesis and compensatory mutations to disrupt and restore potential base pairing in the ribozyme domain of the full-length HDV RNA according to the various structural models, a close correlation between the detected in vivo and the predicted in vitro ribozyme activities of various mutant RNAs was demonstrated. These results suggest that the proposed in vitro ribozyme structure likely exists and functions during the HDV replication cycle in vivo. Furthermore, the pseudoknot model most likely represents the structure responsible for the ribozyme activity in vivo. All of the mutants that had lost the ribozyme activity could not replicate, indicating that the ribozyme activities are indeed required for HDV RNA replication. However, some of the compensatory mutants which have restored both the cleavage and ligation activities could not replicate, suggesting that the ribozyme domains are also involved in other unidentified functions or in the formation of an alternative structure that is required for HDV RNA replication. This study thus established that the ribozyme has important biological functions in the HDV life cycle.
Cadherin-13 Deficiency Increases Dorsal Raphe 5-HT Neuron Density and Prefrontal Cortex Innervation in the Mouse Brain

Background: During early prenatal stages of brain development, serotonin (5-HT)-specific neurons migrate through somal translocation to form the raphe nuclei and subsequently begin to project to their target regions. The rostral cluster of cells, comprising the median and dorsal raphe (DR), innervates anterior regions of the brain, including the prefrontal cortex. Differential analysis of the mouse 5-HT system transcriptome identified enrichment of cell adhesion molecules in 5-HT neurons of the DR. One of these molecules, cadherin-13 (Cdh13) has been shown to play a role in cell migration, axon pathfinding, and synaptogenesis. This study aimed to investigate the contribution of Cdh13 to the development of the murine brain 5-HT system. Methods: For detection of Cdh13 and components of the 5-HT system at different embryonic developmental stages of the mouse brain, we employed immunofluorescence protocols and imaging techniques, including epifluorescence, confocal and structured illumination microscopy. The consequence of CDH13 loss-of-function mutations on brain 5-HT system development was explored in a mouse model of Cdh13 deficiency. Results: Our data show that in murine embryonic brain Cdh13 is strongly expressed on 5-HT specific neurons of the DR and in radial glial cells (RGCs), which are critically involved in regulation of neuronal migration. We observed that 5-HT neurons are intertwined with these RGCs, suggesting that these neurons undergo RGC-guided migration. Cdh13 is present at points of intersection between these two cell types. Compared to wildtype controls, Cdh13-deficient mice display increased cell densities in the DR at embryonic stages E13.5, E17.5, and adulthood, and higher serotonergic innervation of the prefrontal cortex at E17.5. Conclusion: Our findings provide evidence for a role of CDH13 in the development of the serotonergic system in early embryonic stages. Specifically, we indicate that Cdh13 deficiency affects the cell density of the developing DR and the posterior innervation of the prefrontal cortex (PFC), and therefore might be involved in the migration, axonal outgrowth and terminal target finding of DR 5-HT neurons. Dysregulation of CDH13 expression may thus contribute to alterations in this system of neurotransmission, impacting cognitive function, which is frequently impaired in neurodevelopmental disorders including attention-deficit/hyperactivity and autism spectrum disorders.
Mutations of MLC1 (KIAA0027), encoding a putative membrane protein, cause megalencephalic leukoencephalopathy with subcortical cysts.

Megalencephalic leukoencephalopathy with subcortical cysts (MLC) is an autosomal recessive disorder characterized by macrocephaly, deterioration of motor functions with ataxia, and spasticity, eventuating in mental decline. The brain appears swollen on magnetic resonance imaging, with diffuse white-matter abnormalities and the invariable presence of subcortical cysts. MLC was recently localized on chromosome 22q(tel). We have narrowed down the critical region by linkage analysis of 11 informative families with MLC to a region of approximately 250 kb, containing four known genes. One family with two patients who were siblings did not display linkage between the MLC phenotype and any of the analyzed microsatellite markers on chromosome 22q(tel), suggesting genetic heterogeneity and the existence of at least a second MLC locus. The maximum two-point LOD score for the 11 families was 6.6 at recombination fraction . 02. Twelve different mutations in seven informative and six uninformative families were found in one of the candidate genes, KIAA0027, which we renamed "MLC1. " The gene encodes a putative membrane protein with eight predicted transmembrane domains. The patients of one family were compound heterozygotes for mutations that both introduced stop codons. The mutations further included frameshifts, splice-acceptor mutations, a putative splice-donor mutation, and amino acid substitutions of residues in predicted transmembrane domains. These data provide strong evidence that mutations of MLC1 cause the disease.
Vestibular Migraine

Abstract Vestibular migraine presents with attacks of spontaneous or positional vertigo, head motion-induced vertigo, and visual vertigo lasting 5 minutes to 3 days. The recent classification of vestibular migraine, jointly proposed by the Bárány Society and the International Headache Society, allows identification of vestibular migraine and probable vestibular migraine based on explicit criteria. The diagnosis is based on symptom type, severity and duration, a history of migraine, temporal association of migraine symptoms with vertigo attacks, and exclusion of other causes. Because headache is often absent during acute attacks, other migraine features such as photophobia or auras have to be specifically inquired about. During acute attacks, one may find central spontaneous or positional nystagmus, and less commonly, unilateral vestibular hypofunction. In the symptom-free interval, vestibular testing adds little to the diagnosis as findings are mostly minor and nonspecific. The pathophysiology of vestibular migraine is unknown, but several mechanisms link the trigeminal system, which is activated during migraine attacks, and the vestibular system. Treatment includes antiemetics for severe acute attacks, pharmacological migraine prophylaxis, and lifestyle changes.
Testing differences: the implementation of Western HIV testing norms in sub-Saharan Africa

This paper examines the implementation of Western HIV testing norms – counselling, consent and confidentiality (‘3Cs’) – in Malawi, a high prevalence, rural African setting. It considers the differential perspectives of three categories of stakeholders: proponents, implementers and intended beneficiaries. The proponents are members of the ‘Counseling and Testing Establishment’. For them, the 3Cs are human rights imports that are worth defending formally, but not always worth prioritising in practice. The implementers are HIV Counsellors. For them, knowledge of the 3Cs as Western biomedical jargon distinguishes them from villagers, but places them in situations where the ethics of testing conflict with their moral concerns for those whom they were trained to help, thus they adapt them in practice. And the intended beneficiaries, the rural Malawians whose rights are meant to be protected by the 3Cs, perceive the norms as protecting themselves as individuals, but as harming rather than benefitting their communities. The case study of Malawi illustrates a tension between Western, individual rights-oriented public health norms and local concerns for the health and wellbeing of the imagined communities that they are meant to benefit.