Miracle-dz/UniFAR-FTUs huggingface dataset:
A Calcium-Independent Activation of the Arabidopsis SOS2-Like Protein Kinase24 by Its Interacting SOS3-Like Calcium Binding Protein11[W][OPEN]

Calcium-independent protein kinase activity is important for inactivating Arabidopsis plasma membrane proton-translocating adenosine triphosphatase. The salt stress-induced SALT-OVERLY-SENSITIVE (SOS) pathway in Arabidopsis (Arabidopsis thaliana) involves the perception of a calcium signal by the SOS3 and SOS3-like CALCIUM-BINDING PROTEIN8 (SCaBP8) calcium sensors, which then interact with and activate the SOS2 protein kinase, forming a complex at the plasma membrane that activates the SOS1 Na+/H+ exchanger. It has recently been reported that phosphorylation of SCaBP proteins by SOS2-like protein kinases (PKSs) stabilizes the interaction between the two proteins as part of a regulatory mechanism that was thought to be common to all SCaBP and PKS proteins. Here, we report the calcium-independent activation of PKS24 by SCaBP1 and show that activation is dependent on interaction of PKS24 with the C-terminal tail of SCaBP1. However, unlike what has been found for other PKS-SCaBP pairs, multiple amino acids in SCaBP1 are phosphorylated by PKS24, and this phosphorylation is dependent on the interaction of the proteins through the PKS24 FISL motif and on the efficient activation of PKS24 by the C-terminal tail of SCaBP1. In addition, we show that Thr-211 and Thr-212, which are not common phosphorylation sites in the conserved PFPF motif found in most SCaBP proteins, are important for this activation. Finally, we also found that SCaBP1-regulated PKS24 kinase activity is important for inactivating the Arabidopsis plasma membrane proton-translocating adenosine triphosphatase. Together, these results suggest the existence of a novel SCaBP-PKS regulatory mechanism in plants.
Neutrophil Activation and Enhanced Release of Granule Products in HIV-TB Immune Reconstitution Inflammatory Syndrome

Background: Tuberculosis immune reconstitution inflammatory syndrome (TB-IRIS) remains incompletely understood. Neutrophils are implicated in tuberculosis pathology but detailed investigations in TB-IRIS are lacking. We sought to further explore the biology of TB-IRIS and, in particular, the role of neutrophils. Setting: Two observational, prospective cohort studies in HIV/TB coinfected patients starting antiretroviral therapy (ART), 1 to analyze gene expression and subsequently 1 to explore neutrophil biology. Methods: nCounter gene expression analysis was performed in patients with TB-IRIS (n = 17) versus antiretroviral-treated HIV/TB coinfected controls without IRIS (n = 17) in Kampala, Uganda. Flow cytometry was performed in patients with TB-IRIS (n = 18) and controls (n = 11) in Cape Town, South Africa to determine expression of neutrophil surface activation markers, intracellular cytokines, and human neutrophil peptides (HNPs). Plasma neutrophil elastase and HNP1-3 were quantified using enzyme-linked immunosorbent assay. Lymph node immunohistochemistry was performed on 3 further patients with TB-IRIS. Results: There was a significant increase in gene expression of S100A9 (P = 0.002), NLRP12 (P = 0.018), COX-1 (P = 0.025), and IL-10 (P = 0.045) 2 weeks after ART initiation in Ugandan patients with TB-IRIS versus controls, implicating neutrophil recruitment. Patients with IRIS in both cohorts demonstrated increases in blood neutrophil count, plasma HNP and elastase concentrations from ART initiation to week 2. CD62L (L-selectin) expression on neutrophils increased over 4 weeks in South African controls whereas patients with IRIS demonstrated the opposite. Intense staining for the neutrophil marker CD15 and IL-10 was seen in necrotic areas of the lymph nodes of the patients with TB-IRIS. Conclusions: Neutrophils in TB-IRIS are activated, recruited to sites of disease, and release granule contents, contributing to pathology.
Metabolic Acidosis and Malnutrition in Dialysis Patients

Acidosis is a classic uremic toxin that causes protein catabolism, mainly by selective breakdown of skeletal muscle protein. However, the importance of acidosis is often overlooked in dialysis patients. In the presence of acidosis, there is activation of the ubiquitin‐proteasome machinery as well as the branched‐chain keto acid dehydrogenase, resulting in catabolism of muscle protein. Acidosis acts synergistically with other catabolic factors, such as inflammatory cytokines and insulin resistance, in inducing protein catabolism. There is ample laboratory evidence showing that correction of acidosis prevents the up‐regulation of the ubiquitin‐proteasome machinery and reduces protein degradation. Randomized control trials further show that acidosis in dialysis patients can be treated successfully by a higher dialysate bicarbonate or lactate concentration, or by oral bicarbonate supplement. Correction of mild acidosis in dialysis patients is effective in improving nutritional status and reducing the duration of hospitalization.
Familial Waldenstrom’s macroglobulinemia and relation to immune defects, autoimmune diseases, and haematological malignancies – A population-based study from northern Sweden

Abstract Background: Waldenstrom’s macroglobulinemia (WM) is a rare lymphoprolipherative disorder with geographic and ethnic disparities in incidence. The cause of WM remains mostly unknown although a role for genetic, immune-related, and environmental factors has been suggested. Most cases of WM are sporadic although familial cases occur. Aim: This study estimated the incidence of WM in northern Sweden and identified and described patients with familial WM in this area. Patients and methods: The Swedish and Northern Lymphoma Registry, the Swedish Cancer Registry (1997–2011), and medical records were used to identify patients with WM in two counties (Norrbotten and Västerbotten) in northern Sweden and to calculate the overall age-adjusted incidence (2000–2012). We identified 12 families with a family history of WM, IgM monoclonal gammophathy (MGUS), and/or multiple myeloma (MM). Results: In Norrbotten and Västerbotten, the age-adjusted incidence of WM/LPL is 1.75 and 1.48 per 100 000 persons per year, respectively (2000–2012), rates that are higher than the overall incidence of WM/LPL in Sweden (1.05 per 100 000 persons per year; 2000–2012). Autoimmune diseases and other haematological malignancies in the medical history (their own or in relatives) were reported in 9/12 and 5/12 families, respectively. A high proportion of abnormal serum protein electrophoresis was found in the relatives; 12/56 (21%) had a MGUS and 13/56 (25%) showed abnormalities in the immunoglobulin levels (i.e. subnormal levels and poly/oligoclonality). Conclusion: The incidence of WM in Norrbotten and Västerbotten counties was higher than expected. We found a strong correlation between autoimmune/inflammatory diseases, other haematological malignancies, and familial WM and a high frequency of serum immunoglobulin abnormalities in the relatives of the WM patients, findings that strengthen the hypothesis that the aetiology of WM depends on both immune-related and genetic factors.
The study of local electrophysiology in macular diseases.

PURPOSES To observe the features and clinical utility values of local electroretinogram (LERG) and local visual evoked potentials (LVEP) in macular diseases. METHODS The spot stimuli were obtained by changing the shutters with different sizes of hole at the posterior of Ganzfeld ball. The recording electrode for LERG was made with the filament of platinum as blepharophthalmostat like. The LERG and LVEP were simultaneously recorded in macular diseases. RESULTS The exudative AMD, Stargardt's disease, central serous chorioretinopathy and idiopathic macular hole had seriously decreased amplitudes of LERG and higher abnormal rates, comparing with atrophic AMD and idiopathic preretinal membranes in the region of 2.5 degrees and 5 degrees at macula. The abnormal rates in these diseases were higher for LERG than for LVEP. CONCLUSION The LERG can objectively measure the variation of macular function in maculopathies. The sensitivities of LVEP are lower than those of LERG for macular diseases.
MRI vertebral corner inflammation followed by fat deposition is the strongest contributor to the development of new bone at the same vertebral corner: a multilevel longitudinal analysis in patients with ankylosing spondylitis

Objectives To study the sequential relationship between MRI vertebral corner inflammation (VCI), vertebral corner fat deposition (VCFD) and the development/growth of radiographic syndesmophytes at the same vertebral corner (VC). Methods Baseline, 24 and 102 weeks spinal MRIs were assessed for the presence/absence of VCI and VCFD. Anterior VCs of lateral radiographs of the cervical and lumbar spine (baseline and 102 weeks) were assessed for the development of new bone (syndesmophyte formation or syndesmophyte formation/growth combined). Data from 161 to 177 patients were analysed at the VC level using two-way and multilevel analyses adjusting for within-patient correlation and MRI reader (generalised estimating equations for binomial outcomes). Results The presence of VCI (adjusted (adj) OR 1.75 to 1.98) as well as the presence of VCFD (adjOR 1.60 to 2.32) at any time point (TP) were significantly associated with the development of new bone. The combination of VCI and VCFD at the same VC increased the strength of the association, both for the sequential or simultaneous presence of VCI and VCFD across the three TPs (adjOR 2.12 to 2.73), as well as for the development of new VCFD preceded by VCI at a previous TP (adjOR 2.12 to 3.01). The complete absence of both VCI and VCFD across the three TPs ‘protected’ against new bone formation (adjOR 0.45 to 0.62). However, 40–66% of new bone still developed in VCs without MRI inflammation or fat degeneration at any of the three TPs. Conclusions Both VCI and VCFD contribute to new bone formation in ankylosing spondylitis (AS), especially if VCI precedes VCFD. However, VCI, VCFD and this particular sequence of events only partially explain the development of new bone in AS.
On Activist Monetary Policy with Rational Expectations

The paper examines the case for activist monetary policy. It accepts the view that expectations are formed rationally, but not the implication of flexible price, equilibrium, rational expectations models, that monetary policy cannot and should not be used to affect real magnitudes. The paper starts by asking why the economy has not insulated itself from monetary disturbances through the adoption of indexing and other provisions that would effectively shorten contracts, and suggests that the costs of doing so must be substantial. These costs provide the rational for activist policy, whose aim should be to adjust for aggregate disturbances that the private sector has not made provision to handle. The arguments about activist policy then become those familiar from earlier discussions by Milton Friedman, concerning the long and variable lags with which policy operates, and the alleged propensity of the Fed to misbehave. It is argued that an activist policy that does not respond to minor disturbances, but does respond to actual and prospective major disturbances, would provide a stabilizing force for the economy.
Epigenetics and blood disorders

The last three decades of cancer research were guided by the hypothesis that cancer cells evolve due to the accumulation of many genetic aberrations over time. While this is still true for most solid cancers, it might be different in haemato‐malignant diseases, which are mostly characterized by chromosomal translocations that exhibit only few additional mutations. Some of the resulting fusion gene products functionally interfer with epigenetic mechanisms. Recent findings of mutated IDH1, IDH2, DNMT3A or TET2 in myelodysplastic syndrome/acute myeloid leukaemia patients underscore this notion, and point to the importance of epigenetic changes for developing tumour cells. This review aims (i) to give an overview about the different components of the epigenetic system, (ii) to describe the functions of different proteins or complexes that are involved in setting‐up the epigenetic layer, (iii) to highlight some recent findings, and (iv) to describe the failures and successes when using drugs that are targeting epigenetic components.
Outcomes of surgical repair of a single digital nerve in adults

Current standard management of a cut digital nerve is end-to-end microsurgical nerve coaptation where possible. A recent systematic review of adult digital nerve injuries that were either repaired or left unrepaired showed that the evidence for good nerve recovery or improved function following nerve repair is poor. In the 30 studies included, only 24% of repaired nerves regained sensory recovery close to or equivalent to estimated pre-injury levels. Neuroma rates were the same in those nerves repaired (4.6%) and those not repaired (5%). Questions under debate include proper assessment methods of outcomes, decision making for repair or no repair to different fingers or the thumb, levels of injury, age, and hand dominance. This review summarizes the major evidence available and debates the surgical dogma that surrounds this injury.
A Composite Element Binding the Vitamin D Receptor and the Retinoic X Receptor α Mediates the Transforming Growth Factor-β Inhibition of Decorin Gene Expression in Articular Chondrocytes*

Decorin, a small leucine-rich proteoglycan may play an important role in the attempt of cartilage repair initiated by chondrocytes in early stages of osteoarthritis, through its ability to bind collagen fibrils and growth factors such as transforming growth factor-β (TGF-β). We previously demonstrated that TGF-β decreased decorin mRNA steady state levels in articular chondrocytes (Demoor, M., Rédini, F., Boittin, M., and Pujol, J.-P. (1998)Biochim. Biophys. Acta 1398, 179–191). Here, we investigated the effect of TGF-β on decorin gene expression in both primary cultures of articular chondrocytes and chondrocytes dedifferentiated by serial passages. Transient transfection of cells with plasmid constructs of the decorin promoter linked to the luciferase reporter gene revealed transcriptional repression by TGF-β, in fully differentiated as well as dedifferentiated chondrocytes. Experiments with 5′-deleted constructs allowed characterization of a TGF-β-responsive element in the shortest construct (base pairs (bp) −155/+269). DNase I footprinting analysis delineated a negative TGF-β-responsive region between −140 and −111 bp in the decorin proximal promoter. Gel retardation assays demonstrated that TGF-β modulates decorin gene expression through transcription factors, the nature and mode of action of which depend on the differentiation state of the chondrocytes; two DNA-protein complexes were formed in the region −144/−127 bp with nuclear extracts from primary chondrocytes, whereas a higher mobility complex was observed in the −127/−111 bp region for dedifferentiated cells. Antibodies against vitamin D and retinoic acid receptors used in supershift experiments showed that these nuclear receptors are involved in the regulation of decorin gene expression in articular chondrocytes.
Is determination of matrix metalloproteinases and their tissue inhibitors serum concentrations useful in patients with gastroenteropancreatic and bronchopulmonary neuroendocrine neoplasms?

INTRODUCTION Gastroenteropancreatic (GEP) and bronchopulmonary (BP) neurendocrine neoplasms (NENs) are rare and slowly growing tumours. Matrix metalloproteinases (MMPs) degrade extracellular matrix and are responsible for invasion and metastasis. Tissue inhibitors of matrix metalloproteinases (TIMPs) affect the invasiveness of tumour cells and the formation of distant metastases. The aim of this study was to evaluate selected MMPs (MMP2 and MMP9) and their tissue inhibitors (TIMP1 and TIMP2) depending on the pTNM classification, grading, and the occurrence of metastases. MATERIAL AND METHODS The study group consisted of 86 patients with GEP NENs. The control group consisted of 31 healthy volunteers. Serum levels of TIMP1, TIMP2, MMP2 and MMP9 were determined by ELISA (R&D Systems) in all the study subjects. The statistical calculations were performed using MedCalc. RESULTS We observed significant differences in MMP2 and TIMP1 levels between the study group with NENs and the control group. TIMP1 levels were significantly higher in patients with high-grade NEN (NEC, neuroendocrine carcinoma) compared to patients with low-grade tumour (NET G1, neuroendocrine tumours G1) (p 〈 0.017). We also observed a significant correlation between TIMP1 levels and the presence of metastases in the group of patients with GEP NENs, and also higher TIMP1 levels than those in the patients without metastases (p 〈 0.05). We also found a higher likelihood of metastases in patients with GEP NENs with TIMP1 levels exceeding 206.4 ng/mL. CONCLUSIONS Patients with NENs secreted larger quantities of MMP2 and TIMP1. TIMP1 may be considered a marker of metastases in patients with GEP NENs.
Evidence for an Interaction of Halothane with the L-type Ca2+ Channel in Human Myocardium

Background:The present study was aimed at investigating the underlying mechanisms for the cardiac depressant effect of halothane. To test the hypothesis, whether there is an interaction of halothane with the L-type Ca2+ channels in human myocardium and whether this interaction has functional consequences for force generation In the human myocardium, effects of halothane were studied in human myocardial membranes and isolated cardiac preparations. Methods:The experiments were performed on isolated, electrically driven ventricular preparations (1 Hz, 37° C) and cardiac membranes with radioligand binding experiments using 3H-PN 200-110. Myocardium from human failing and nonfailing hearts was obtained at cardiac surgery. Results:Halothane produced a negative inotropic effect, which was similar in nonfailing and failing myocardium. Halothane shifted the concentration-response curve for the positive inotropic effect of the L-type Ca2+ channel agonist BayK 8644 to the right. The density of dihydropyridine receptors as judged from 3H-PN 200-110 radioligand binding experiments was similar in nonfailing and failing myocardium, whereas the density of β-adrenoceptors was reduced. Halothane concentration dependently reduced the binding of 3H-PN 200-110, an antagonist at the 1,4 dihydropyridine receptor site of the Ca2+ channel, to myocardial membranes. Furthermore, halothane produced a rightward shift of the competition curve of BayK 8644 for binding of 3H-PN 200-110 to cardiac membranes. Conclusions:In human ventricular myocardium, halothane exhibits an interaction with the L-type Ca2+ channel by interfering with its dihydropyridine binding sites. This may explain, at least in part, the observed negative inotropic effect of this agent and could hypothetically play a general role in its anesthetic effects.
The factors associated with community participation: Employment and education of people with disabilities in Turkey

Abstract Background: People with disabilities are facing not just health problems; they also experience restriction of participation due to various barriers. However, there is limited knowledge of which factors can be important to their community participation. Aim: This study investigated the factors that are associated with community participation of people with disabilities. Methods: A sample of 270 people with disabilities (aged range 18–55 years) recruited randomly through the “Turkish People with Disabilities Association”. This study, followed a survey design, took place in 15 cities in Turkey and a city of Turkish Republic of Northern Cyprus. Community Integration Questionnaire (CIQ), Functional Independence Measure, Measure of Quality of the Environment, Leisure Satisfaction Scale, State-Trait Anxiety Inventory, and Short-Form-12 were used. A stepwise multiple regression analysis was conducted to analyze the relationship of the dependent variable (CIQ) with the factors. Results: The results indicated that the community participation was importantly associated with employment and educational status, functional level, quality of life and satisfaction from leisure activities (p < 0.05). Wheelchair users’ participation level was lower than that of the other mobility groups (p < 0.05). Conclusions: The study provides a rich description of the multifaced nature of participation and its association with the factors such as employment, education, and leisure. Moreover, in terms of these factors and community participation, wheelchair users were the most disadvantaged group of people with disabilities at different mobility level.
Frequency of Intracranial Hemorrhage With Low-Dose Aspirin in Individuals Without Symptomatic Cardiovascular Disease: A Systematic Review and Meta-analysis.

Importance Use of low-dose aspirin for the primary prevention of cardiovascular events remains controversial because increased risk of bleeding may offset the overall benefit. Among major bleeding events, intracranial hemorrhage is associated with high mortality rates and functional dependency. Objective To assess the risk of intracranial hemorrhage associated with low-dose aspirin among individuals without symptomatic cardiovascular disease. Data Sources PubMed, Embase, the Cochrane Central Register of Controlled Trials, and ClinicalTrials.gov were searched from January 1966 to October 30, 2018. Study Selection Randomized clinical trials that compared low-dose aspirin (daily dose ≤100 mg) vs control and recorded the end points of intracranial hemorrhage separately for active treatment and control groups were included. Data Extraction and Synthesis A random-effect estimate was computed based on the Mantel-Haenszel method. Relative risk with 95% CI was used as a measure of aspirin vs control on risk of intracranial hemorrhage. Main Outcomes and Measures The main outcomes were any intracranial hemorrhage, intracerebral hemorrhage, subdural or extradural hemorrhage, and subarachnoid hemorrhage, for aspirin vs control. Results The search identified 13 randomized clinical trials of low-dose aspirin use for primary prevention, enrolling 134 446 patients. Pooling the results from the random-effects model showed that low-dose aspirin, compared with control, was associated with an increased risk of any intracranial bleeding (8 trials; relative risk, 1.37; 95% CI, 1.13-1.66; 2 additional intracranial hemorrhages in 1000 people), with potentially the greatest relative risk increase for subdural or extradural hemorrhage (4 trials; relative risk, 1.53; 95% CI, 1.08-2.18) and less for intracerebral hemorrhage and subarachnoid hemorrhage. Patient baseline features associated with heightened risk of intracerebral hemorrhage with low-dose aspirin, compared with control, were Asian race/ethnicity and low body mass index. Conclusions and Relevance Among people without symptomatic cardiovascular disease, use of low-dose aspirin was associated with an overall increased risk of intracranial hemorrhage, and heightened risk of intracerebral hemorrhage for those of Asian race/ethnicity or people with a low body mass index.