Miracle-dz/UniFAR-FTUs huggingface dataset:
The CpxQ sRNA Negatively Regulates Skp To Prevent Mistargeting of β-Barrel Outer Membrane Proteins into the Cytoplasmic Membrane

ABSTRACT The promoter most strongly induced upon activation of the Cpx two-component envelope stress response is the cpxP promoter. The 3′ untranscribed region (UTR) of the cpxP transcript is shown to produce a small RNA (sRNA), CpxQ. We investigated the role of CpxQ in combating envelope stress. Remarkably, the two effectors specified by the transcript are deployed to combat distinct stresses in different cellular compartments. CpxP acts in both a regulatory negative-feedback loop and as an effector that combats periplasmic protein misfolding. We find that CpxQ combats toxicity at the inner membrane (IM) by downregulating the synthesis of the periplasmic chaperone Skp. Our data indicate that this regulation prevents Skp from inserting β-barrel outer membrane proteins (OMPs) into the IM, a lethal event that likely collapses the proton motive force. Our findings suggest that Skp can fold and directly insert OMPs into a lipid bilayer in vivo without the aid of the Bam complex. IMPORTANCE Skp is a well-characterized periplasmic chaperone that binds unfolded OMPs. Surprisingly, we find that Skp can catalyze the folding and mistargeting of OMPs into the inner membrane without the aid of the other cellular proteins that normally assemble OMPs. Several OMPs function as diffusion pores. Accordingly, their mistargeting is lethal because it depolarizes the inner membrane. We show that the most highly expressed transcript of the Cpx stress response produces an sRNA from the 3′ UTR, CpxQ, which combats this potential toxicity by downregulating Skp production. Defects in OMP assembly trigger the σE response to upregulate factors, including Skp, that promote OMP folding. The Cpx response downregulates σE. Our findings reveal that this heretofore puzzling hierarchy exists to protect the inner membrane. Skp is a well-characterized periplasmic chaperone that binds unfolded OMPs. Surprisingly, we find that Skp can catalyze the folding and mistargeting of OMPs into the inner membrane without the aid of the other cellular proteins that normally assemble OMPs. Several OMPs function as diffusion pores. Accordingly, their mistargeting is lethal because it depolarizes the inner membrane. We show that the most highly expressed transcript of the Cpx stress response produces an sRNA from the 3′ UTR, CpxQ, which combats this potential toxicity by downregulating Skp production. Defects in OMP assembly trigger the σE response to upregulate factors, including Skp, that promote OMP folding. The Cpx response downregulates σE. Our findings reveal that this heretofore puzzling hierarchy exists to protect the inner membrane.
Characteristics and distribution of M cells in arterially perfused canine left ventricular wedge preparations.

BACKGROUND Much of the characterization of the M cell to date has been accomplished using isolated tissues and cells. This study uses an arterially perfused wedge preparation to examine the characteristics and distribution of M cells within the anterior wall of the canine left ventricle under more physiological conditions. METHODS AND RESULTS Floating microelectrodes were used to record transmembrane action potentials simultaneously from epicardial, M region, and endocardial or subendocardial Purkinje sites in isolated arterially perfused canine left ventricular wedge preparations. A transmural ECG was recorded concurrently. M cells with the longest action potentials were found in the deep subendocardium in wedge preparations isolated from the anterior wall of the left ventricle. Fairly smooth transitions in action potential duration (APD) were observed except in the region between epicardium and deep subepicardium. Tissue resistivity increased 2.8-fold in this region and much more modestly in the deep subendocardium. Dispersion of APD90 across the left ventricular wall averaged 51+/-19 and 64+/-25 ms at basic cycle lengths of 1000 and 2000 ms, respectively, whereas transmural dispersion of repolarization time was smaller (34+/-18 and 45+/-25 ms), owing to the endocardial to epicardial activation sequence. CONCLUSIONS We conclude that the qualitative differences between the 3 ventricular cell types previously described in isolated tissues and cells are maintained in intact canine left ventricular wall preparations in which the myocardial cells are electrically well coupled. As anticipated, differences in APD are quantitatively smaller because of electrotonic interactions among the 3 cell types. Our data indicate that transmural dispersion of repolarization is the result of intrinsic differences in APD of cells spanning the ventricular wall as well as a heterogeneous distribution of tissue resistivity across the wall.
High Magnetic Loss Mg–Cu Ferrites for Ultrahigh Frequency EMI Suppression Applications

Mg<sub>1-x</sub>Cu<sub>x</sub>Fe<sub>2</sub>O<sub>4</sub> ferrites for electromagnetic interference suppression were systematically investigated in crystallographic structure, morphologies, and magnetic and dielectric spectra over a frequency range of 10-1000 MHz. Findings indicated that the Mg<sub>1-x</sub>Cu<sub>x</sub>Fe<sub>2</sub>O<sub>4</sub> ferrites with x= 0-0.6 showed a single-phase cubic spinel structure, but the sample structure with x = 0.8 transforms into a tetragonal phase. Moreover, the substitution of Cu was shown to lower the sintering temperature and enhance densification of the ferrites, resulting in increased saturation magnetization (67%) and decreased coercivity (88%). More importantly, the complex permeability and permittivity of Mg-Cu ferrites could be tailored with Cu content, leading to an enhanced magnetic loss and permeability. The magnetic loss tangent of the Mg<sub>0.4</sub>Cu<sub>0.6</sub>Fe<sub>2</sub>O<sub>4</sub> ferrite sintered at 1150°C was significantly increased by 56% at f > 300 MHz.
Back pain in lower and upper secondary school pupils living in urban areas of Poland. The case of Poznań.

BACKGROUND To determine the lifetime prevalence and characteristics of non-specific back pain (low back pain, upper back pain) and neck pain in adolescents living in urban areas of Poland. We also studied the impact of back/neck pain on adolescents' daily activity as well as the association of back pain with computer use, watching TV, physical work, and physical activity. MATERIAL AND METHODS. A school-based questionnaire survey of back pain and physical activity, computer use, watching TV and functional disorders was distributed among 1475 randomly selected adolescents aged 13 to 20 years attending lower and upper secondary schools in Poznań, Poland. RESULTS A total of 986 (67%) teenagers reported having experienced one or more episodes of back/neck pain in their lives. Low back pain was the most common presentation. Back/neck pain symptoms appeared mostly between the 14th and 16th year of life. The daily activities mostly impaired by back/neck pain were physical activity, learning/concentration and lifting objects. No significant differences were found in computer use and physical activity between adolescents with and without a history of back/neck pain. Pain-free teenagers watched TV significantly longer. Boys with back/neck pain performed physical work more frequently than pain-free boys. CONCLUSIONS 1. Compared to adolescents and adults in other European countries, the lifetime prevalence of back/neck pain in Polish adolescents living in urban areas is similar. 2. The findings support the hypothesis that physical activity, computer use and watching TV cannot be regarded as risk factors for back/neck pain. 3. Back/neck pain may have a negative influence on the daily activities of adolescents. Nevertheless, this impact is probably temporary and adolescents seem to develop strategies for coping with pain in order to participate normally in daily activities. More detailed studies of these coping strategies are recommended.
Opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia

Summary Adrenal insufficiency is a rare cause of hypercalcaemia and should be considered when more common causes such as primary hyperparathyroidism and malignancy are excluded. Opioid therapy as a cause of adrenal insufficiency is a possibly under-recognised endocrinopathy with potentially life-threatening adverse effects. We report on a case of opioid-induced secondary adrenal insufficiency presenting as hypercalcaemia. The patient was a 25-year-old man who developed hypercalcaemia during the recovery stage after a period of critical illness. Systematic investigation of his hypercalcaemia found it to be due to secondary adrenal insufficiency, developing as a consequence of methadone opioid analgesia. Treatment with i.v. saline and subsequent glucocorticoid replacement led to resolution of the hypercalcaemia. The hypoadrenalism resolved when opioids were subsequently weaned and ceased. These two interacting endocrinopathies of opioid-induced adrenal insufficiency and consequent hypercalcaemia highlight the importance of maintaining awareness of the potentially serious adverse clinical outcomes which can occur as a result of opioids, particularly considering that symptoms of hypoadrenalism can overlap with those of concomitant illness. Treatment with hydration and glucocorticoid replacement is effective in promptly resolving the hypercalcaemia due to hypoadrenalism. Hypoadrenalism due to prescribed and recreational opioids may be more common than is currently recognised. Learning points Opioid therapy can cause clinically significant secondary adrenal insufficiency, and this may be more common than is currently recognised. Adrenal insufficiency is reversible after discontinuation of the opioid therapy. Hypercalcaemia can occur as a consequence of adrenal insufficiency, and may be the presenting feature. Treatment of hypercalcaemia due to adrenal insufficiency involves i.v. saline and glucocorticoid replacement.
Protocol: Effect of intravitreal bevacizumab (avastin) in the treatment of macular edema: A systematic review of randomized controlled trials

Cystoid macular edema (CME) is a relatively common painless condition usually accompanied by blurred vision. The prevalence of CME varied from 5% to 47% depending on cause of pathology. There are several treatments available for ME including intravitreal use of bevacizumab that has been used in different doses in few studies. However, there is still scarcity of data available on the use of bevacizumab for the treatment of ME. A systematic review is needed to provide a foundational base to discuss and synthesize the available information on the effectiveness and safety of intravitreal bevacizumab in macular edema, so that recommendations and policies can be built regarding controversial use of bevacizumab in macular edema. We have planned to perform a systematic review with an objective to compare the effects of a single injection of 1.25 mg intravitreal bevacizumab (avastin) in the improvement of visual acuity, macular edema, and thickness with other interventions/controls for the treatment of macular edema at 3 and 6 months interval using randomized controlled trials. This is only a protocol of the review and we will be conducting a full length review, addressing the issue in future.
Quantification of glutathione in the human brain by MR spectroscopy at 3 Tesla: Comparison of PRESS and MEGA‐PRESS

Glutathione (GSH) is an important intracellular antioxidant in the brain. A number of studies report its measurement by localized 1H spectroscopy using PRESS and STEAM. This study evaluates the reliability and accuracy of GSH measurements from PRESS at 3 Tesla (T) and compares the results to those obtained with MEGA‐PRESS.
Situational and Dispositional Determinants of Intentional Deceiving

Does opportunity make the thief or are people dispositionally prone to deceive? The interaction between personality and the circumstances surrounding deception is crucial to understand what promotes dishonesty in our society. Due to its inherent spontaneity and sociality, deceptive behaviour may be hardly reproducible in experimental settings. We developed a novel paradigm in the form of an interactive game where participants can choose whether to lie to another person in situations of loss vs. gain, and of no-reputation-risk vs. reputation-risk linked to the disclosure of their deceptive behaviour to others. Thus, our ecological paradigm allowed subjects to spontaneously decide when to lie and face the challenge of deceiving others. In the case of loss, participants lied to reverse the outcome in their favour. Deception was lower in the reputation-risk condition where personality traits concerning social interactions also played an important role. The results suggest that deception is definitely promoted by unfavourable events, and that maintaining one's own reputation encourages honesty, particularly in socially inclined individuals.
An Enzyme-Linked Immunosorbent Assay with the Recombinant Merozoite Protein as Antigen for Detection of Antibodies to Eimeria necatrix

Abstract A cDNA library was constructed with Eimeria necatrix merozoite mRNA and immunologically screened by chicken sera against this parasite. One of the positive clones containing an insert of 879 nucleotides, pNP19, showed similarity to part of a published gene expressed in E. tenella merozoite by the homology search system. The inserted DNA was subcloned into baculovirus, and a 35-kD protein was expressed, purified, and used for the antigen in enzyme-linked immunosorbent assay (ELISA). Antibodies from the chickens vaccinated with the E. necatrix attenuated strain, Nn-P125, were detected from 14 days after vaccination by ELISA. The mean absorbance increased rapidly to a peak around 21 days after vaccination; thereafter, it began to decline. Even though some of the vaccinated chickens showed very low levels of antibody response to the recombinant protein 56 days after vaccination, they were protected against challenge with virulent strain of E. necatrix. The mean absorbances in sera from both vaccinated and nonvaccinated chickens highly increased 14 days after challenge. On the other hand, the antibody was not detected in ELISA when chickens were exposed to other Eimeria species such as E. tenella, E. acervulina, and E. maxima. These results demonstrate that this recombinant protein is suitable for detecting the specific antibody in chickens infected with both attenuated and virulent strains of E. necatrix.
Prepsychotic phase of schizophrenia and related disorders: recent progress and future opportunities

Background Clinical and research focus has recently shifted from established psychotic disorders to first-episode psychosis and the prepsychotic phase of illness. Aims To describe the principles, progress and dilemmas associated with the prospective detection, engagement and treatment of young people at risk of developing a psychotic disorder. Method Strategies to identify young people at heightened risk of a psychotic disorder are described. Preventive interventions and results of their evaluation are provided. Results Well-validated criteria for identifying young people at heightened risk of psychosis have been developed, evidence of the efficacy of various psychological and pharmacological interventions in preventing progression has accumulated and progress towards the identification of clinical and neurobiological predictors of transition to acute psychosis has been made. Conclusions The detection, monitoring and treatment of young people in the prepsychotic phase is a growth area in psychiatry. The ethical considerations about treatment options, treatment of minors and provision of information about risk status must be treated with sensitivity if the potential benefit to many young people and their families is to be realised.
Micro-preparation of wooden samples to study the distribution of natural glue systems in wood

Wood properties at macroscopic scale depend on its structure at microscopic scale. Currently, there are few data concerning the microscopic-macroscopic relationship, and this is why here is detailed and developed a method of wood slicing with a thickness of 3 microns, in order to visually observe the microstructure and in some cases its interactions with adhesives (when present), and establish possible links with the mechanical properties of a given specie. This method implementation is based on an already existing method. The sample is soaked in a resin via the succession of dehydration steps, then cured by heating in the oven. According to various tests, the resin used by the University of Freiburg proved to be the best, whereas at the level of the blade used for the samples slicing, the use of a diamond blade with a preslicing using a metallic blade of profile D, proved to be the most conclusive regarding the quality and fineness of slicing, as well as less wear on the diamond blade. Indeed, cuts of 3 microns can be obtained, thus allowing excellent microscopic observation, which can be applied for an accurate study of the microstructure in different projects.
Chemotactic Chemokines Are Important in the Pathogenesis of Irritable Bowel Syndrome

Irritable bowel syndrome (IBS) is one of the most frequently diagnosed disorders, affecting about 20% of the general population in Western countries. This syndrome poses an enormous socio-economic burden, impairs the quality of life substantially, and increases healthcare costs. IBS can be classified as either idiopathic (ID-IBS) with unknown etiology or post-infectious (PI-IBS), which develops after a bout of acute diarrhea or gastroenteritis. Little is known about the immunopathogenesis of these two forms of IBS. We evaluated various biomarkers in clinical samples of ID-IBS and PI-IBS patients with the goal to test the hypothesis that the immunologic presentations of these forms of IBS are similar, despite their apparent different etiologic origins. Sera and stool samples from PI-IBS, ID-IBS, and healthy volunteers were analyzed for relative amounts of 36 different biomarkers using the Proteome Profiler Human Cytokine Array Panel A Kit and quantitative ELISA. Our results demonstrated significantly high levels of chemotactic chemokines monocytes chemotactic protein-1 (CCL2) [p-value = 0.003], macrophage inflammatory protein-1β (CCL4) [p-value = 0.010], and CXCL16 (p-value 0.001) in the sera and stools of both ID-IBS and PI-IBS patients. Furthermore, pro-inflammatory cytokines (IFN-γ, IL-1β, and TNF-α) were significantly higher in IBS patients. Anti-inflammatory cytokines (IL-10, IL-4, and IL-13) were variable except IL-10, which was significantly higher in the healthy volunteers than the IBS patients. Remarkably, the amounts and expression pattern of these biomarkers were not significantly different between ID-IBS and PI-IBS. Thus, ID-IBS and PI-IBS present similar immunologic and clinical phenotypes, in spite of their different etiologic origins.
Role of Plant-Specific N-Terminal Domain of Maize CK2β1 Subunit in CK2β Functions and Holoenzyme Regulation

Protein kinase CK2 is a highly pleiotropic Ser/Thr kinase ubiquituous in eukaryotic organisms. CK2 is organized as a heterotetrameric enzyme composed of two types of subunits: the catalytic (CK2α) and the regulatory (CK2β). The CK2β subunits enhance the stability, activity and specificity of the holoenzyme, but they can also perform functions independently of the CK2 tetramer. CK2β regulatory subunits in plants differ from their animal or yeast counterparts, since they present an additional specific N-terminal extension of about 90 aminoacids that shares no homology with any previously characterized functional domain. Sequence analysis of the N-terminal domain of land plant CK2β subunit sequences reveals its arrangement through short, conserved motifs, some of them including CK2 autophosphorylation sites. By using maize CK2β1 and a deleted version (ΔNCK2β1) lacking the N-terminal domain, we have demonstrated that CK2β1 is autophosphorylated within the N-terminal domain. Moreover, the holoenzyme composed with CK2α1/ΔNCK2β1 is able to phosphorylate different substrates more efficiently than CK2α1/CK2β1 or CK2α alone. Transient overexpression of CK2β1 and ΔNCK2β1 fused to GFP in different plant systems show that the presence of N-terminal domain enhances aggregation in nuclear speckles and stabilizes the protein against proteasome degradation. Finally, bimolecular fluorescence complementation (BiFC) assays show the nuclear and cytoplasmic location of the plant CK2 holoenzyme, in contrast to the individual CK2α/β subunits mainly observed in the nucleus. All together, our results support the hypothesis that the plant-specific N-terminal domain of CK2β subunits is involved in the down-regulation of the CK2 holoenzyme activity and in the stabilization of CK2β1 protein. In summary, the whole amount of data shown in this work suggests that this domain was acquired by plants for regulatory purposes.
Glucose Kinetics in the Collagen-Induced Arthritis Model: An All-in-One Model to Assess Both Efficacy and Metabolic Side Effects of Glucocorticoids

Prednisolone and other glucocorticoids (GCs) are potent anti-inflammatory drugs, but chronic use is hampered by metabolic side effects. Therefore, there is an urgent medical need for improved GCs that are as effective as classical GCs but have a better safety profile. A well-established model to assess anti-inflammatory efficacy is the chronic collagen-induced arthritis (CIA) model in mice, a model with features resembling rheumatoid arthritis. Models to quantify undesired effects of glucocorticoids on glucose kinetics are less well-established. Recently, we have described a model to quantify basal blood glucose kinetics using stably-labeled glucose. In the present study, we have integrated this blood glucose kinetic model in the CIA model to enable quantification of both efficacy and adverse effects in one animal model. Arthritis scores were decreased after treatment with prednisolone, confirming the anti-inflammatory properties of GCs. Both inflammation and prednisolone induced insulin resistance as insulin secretion was strongly increased whereas blood glucose concentrations and hepatic glucose production were only slightly decreased. This insulin resistance did not directly resulted in hyperglycemia, indicating a highly adaptive compensatory mechanism in these mice. In conclusion, this ‘all-in-one’ model allows for studying effects of (novel) GC compounds on the development of arthritis and glucose kinetics in a single animal. This integrative model provides a valuable tool for investigating (drug-induced) metabolic dysregulation in an inflammatory setting.
A Method of Images for the Evaluation of Electrostatic Fields in Systems of Closely Spaced Conducting Cylinders

A long-standing area of materials science research has been the study of electrostatic, magnetic, and elastic fields in composites with densely packed inclusions whose material properties differ markedly from that of the background. While powerful tools exist for dilute suspensions, accurate calculations in the close-to-touching case have been carried out largely by asymptotic methods and only for simple geometries such as regular arrays of cylinders or spheres. In this paper, we develop a hybrid numerical method for the evaluation of electrostatic fields in composites consisting of arbitrary dispersions of cylinders. Our approach is based on an integral equation formulation of the governing interface problem combined with a new method of images. High accuracy is achieved using only a small number of degrees of freedom for each inclusion.