Zobrazení zdroje stránky Lodbergcarr3710

CD4+ T regulatory cells (Tregs) are a group of T lymphocytes that maintain self-tolerance and protect the host from inflammation-induced tissue damage. An interacting network of cytokines and transcription factors influence the origin, differentiation, and function of the Tregs in primary and secondary lymphoid organs. However, following antigenic stimulation, it can also be induced at the sites of infection. Immune cell resident microbial pathogens, such as Leishmania, employ varieties of mechanisms to promote the suppressive functions of Tregs for protective evasion from the host immune system. This establishes a state of immune unresponsiveness in the host, exacerbating the disease in Leishmania infection. Elimination of Leishmania pathogens is accomplished with a strong pro-inflammatory response accompanied by the release of host protective cytokines such as Interleukin-2 (IL-2), Interferon-gamma (IFN-γ), and Tumor necrosis factor-alpha (TNF-α), which functions through suppression of Tregs or making the effector cells recalcitrant to Treg mediated suppression. Nevertheless, during chronic infection, the persistence of unwarranted pro-inflammatory cytokines can trigger self-tissue damage. Tregs limit the consequence of chronic inflammation to restrict self-harm suggesting its mutually opposing role in host protection. Furthermore, Tregs function to prevent complete parasite clearance to provide long-term immunity to re-infection. This review summarizes the roles of pro-inflammatory and anti-inflammatory cytokines involved in the homing, activation, differentiation, and suppression of Tregs in the course of Leishmania infection. We also suggest cytokines that can be modulated as potential therapeutic targets to treat Leishmania infection.Responses to developmental and environmental cues depend on precise spatiotemporal control of gene transcription. Enhancers, which comprise DNA elements bound by regulatory proteins, can activate target genes in response to these external signals. Recent studies have shown that enhancers are transcribed to produce enhancer RNAs (eRNAs). Do eRNAs play a functional role in activating gene expression or are they non-functional byproducts of nearby transcription machinery? The unstable nature of eRNAs and over-reliance on knockdown approaches have made elucidating the possible functions of eRNAs challenging. We focus here on studies using cloned eRNAs to study their function as transcripts, revealing roles for eRNAs in enhancer-promoter looping, recruiting transcriptional machinery, and facilitating RNA polymerase pause-release to regulate gene expression.Histone methylation is central to the regulation of eukaryotic transcription. Here, we review how the histone methylation system itself is regulated. There is substantial evidence that mammalian histone methyltransferases and demethylases are phosphorylated and regulated by upstream signalling pathways. Functional studies of specific phosphosites are revealing which kinases and pathways signal to the histone methylation system and are discovering the diverse effects of phosphorylation on enzyme function. Nevertheless, the majority of phosphosites have no known kinase or function and our understanding of how histone methylation is regulated is fragmentary. Improved approaches are needed to establish and study the key regulatory phosphorylation sites on histone methyltransferases and demethylases, to avoid focus on constitutive sites which may have little regulatory purpose.<br /><br /> Rhythmic body rocking movements may occur in prefrontal epileptic seizures. Here, we compare quantified time-evolving frequency of stereotyped rocking with signal analysis of intracerebral electroencephalographic data.<br /><br /> In a single patient, prefrontal seizures with rhythmic anteroposterior body rocking recorded on stereoelectroencephalography (SEEG) were analyzed using fast Fourier transform, time-frequency decomposition and phase amplitude coupling, with regards to quantified video data. Comparison was made with seizures without rocking in the same patient, as well as resting state data.<br /><br /> Rocking movements in the delta (∼1 Hz) range began a few seconds after SEEG onset of low voltage fast discharge. During rocking movements (1) presence of a peak of delta band activity was visible in bipolar montage, with maximal power in epileptogenic zone and corresponding to mean rocking frequency; (2) correlation, using phase amplitude coupling, was shown between the phase of this delta activity and high-gamma power in the epileptogenic zone and the anterior cingulate region.<br /><br /> Here, delta range rhythmic body rocking was associated with cortical delta oscillatory activity and phase-coupled high-gamma energy. These results suggest a neural signature during expression of motor semiology incorporating both temporal features associated with rhythmic movements and spatial features of seizure discharge.<br /><br />Here, delta range rhythmic body rocking was associated with cortical delta oscillatory activity and phase-coupled high-gamma energy. These results suggest a neural signature during expression of motor semiology incorporating both temporal features associated with rhythmic movements and spatial features of seizure discharge.<br /><br /> Risk markers for breast cancer include earlier onset of menarche (age at menarche [AAM]) and peak height velocity (PHV). Insulin-like growth factor-1 (IGF-1) is associated with pubertal milestones, as well as cancer risk. This study examined the relationships between pubertal milestones associated with breast cancer risk and hormone changes in puberty.<br /><br /> This is a longitudinal study of pubertal maturation in 183 girls, recruited at ages 6-7, followed up between 2004 and 2018. Measures included age at onset of puberty, and adult height attained; PHV; AAM; adult height, and serum IGF-1, and estrone-to-androstenedione (EA) ratio.<br /><br /> PHV was greatest in early, and least in late maturing girls; length of the pubertal growth spurt was longest in early, and shortest in late maturing girls. Earlier AAM was related to greater PHV. IGF-1 concentrations tracked significantly during puberty; higher IGF-1 was related to earlier age of PHV, earlier AAM, greater PHV, and taller adult height. Greater EA ratio was associated with earlier AAM.<br /><br /> Factors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility.<br /><br />Factors driving the association of earlier menarche and pubertal growth with breast cancer risk may be explained through a unifying concept relating higher IGF-1 concentrations, greater lifelong estrogen exposure, and longer pubertal growth period, with an expanded pubertal window of susceptibility..Myotonic dystrophy type 2 (DM2) lacks validated patients´ reported outcomes (PROs). This represents a limit for monitoring disease progression and perceived efficacy of symptomatic treatments. Our aim was to investigate whether PROs for activities of daily living designed for other neuromuscular diseases could be used in DM2. Sixty-six DM2 patients completed the following PROs DM1-Activ-c, Rasch-built Pompe-specific activity (R-PAct) scale, McGill-pain questionnaire, fatigue and daytime sleepiness scale and Beck depression inventory (BDI-II). Clinical data and motor outcome measures (6-minutes walking test - 6MWT, manual muscle testing, quick motor function test and myotonia behavior scale) were collected as well. Patients underwent one visit at baseline and one after 10 months. Ceiling/flooring effects, criterion validity and discriminant validity were calculated. DM1-activ-c and R-PAct showed acceptable ceiling effects despite being built for myotonic dystrophy type 1 and Pompe disease, respectively. The difficulty hierarchy of the single items was better preserved in R-PAct than in DM1-Activ-c. Both tests showed excellent criterion validity highly correlating with 6MWT, quick motor function test, myalgia and disease duration. They could partially discriminate patients with different disability grades. These results suggest that DM1-Activ-c, slightly better than R-PAct, might be adopted for monitoring activities of daily living also in DM2, at least until disease-specific PROs will be available.Coronavirus Disease 2019 (COVID-19) is a dangerous global threat that has no clinically approved treatment yet. Bioinformatics represent an outstanding approach to reveal key immunogenic regions in viral proteins. Here, five severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural proteins (NSPs) (NSP7, NSP8, NSP9, NSP12, and NSP13) were screened to identify potential human leukocyte antigen (HLA) binding peptides. These peptides showed robust viral antigenicity, immunogenicity, and a marked interaction with HLA alleles. Interestingly, several peptides showed affinity by HLA class I (HLA-I) alleles that commonly activates to natural killer (NK) cells. Notably, HLA biding peptides are conserved among SARS-CoV-2, severe acute respiratory syndrome coronavirus (SARS-CoV), and Middle Eastern respiratory syndrome coronavirus (MERS-CoV). Interestingly, HLA-I and HLA class II (HLA-II) binding peptides induced humoral and cell-mediated responses after in silico vaccination. These results may open further in vitro and in vivo investigations to develop novel therapeutic strategies against coronaviral infections.<br /><br /> To develop a 16-fold accelerated real-time, free-breathing cine cardiovascular magnetic resonance (CMR) pulse sequence with compressed sensing reconstruction and test whether it is capable of producing clinically acceptable summed visual scores (SVS) and accurate left ventricular ejection fraction (LVEF) in patients with a cardiac implantable electronic device (CIED).<br /><br /> A 16-fold accelerated real-time cine CMR pulse sequence was developed using gradient echo readout, Cartesian k-space sampling, and compressed sensing. [https://www.selleckchem.com/products/eidd-1931.html selleck chemicals llc] We scanned 13 CIED patients (mean age = 59 years; 9/4 males/females) using clinical standard, breath-hold cine and real-time, free-breathing cine. Two clinical readers performed a visual assessment of image quality in four categories (conspicuity of endocardial wall at end diastole, temporal fidelity of wall motion, any artifact level on the heart, noise) using a five-point Likert scale (1 worst; 3 clinically acceptable; 5 best). SVS was calculated as the sum of 4 individual scores, where 12 was defined as clinical acceptable. The Wilcoxon signed-rank test was performed to compare SVS, and the Bland-Altman analysis was conducted to evaluate the agreement of LVEF.<br /><br /> Median scan time was 3.7 times shorter for real-time (3.5 heartbeats per slice) than clinical standard (13 heartbeats per slice, excluding nonscanning time between successive breath-hold acquisitions). Median SVS was not significantly different between clinical standard (15.0) and real-time (14.5). The mean difference in LVEF was -2% (4.7% of mean), and the limits of agreement was 5.8% (13.5% of mean).<br /><br /> This study demonstrates that the proposed real-time cine method produces clinically acceptable SVS and relatively accurate LVEF in CIED patients.<br /><br />This study demonstrates that the proposed real-time cine method produces clinically acceptable SVS and relatively accurate LVEF in CIED patients.