Hagandoherty1764

Molecular targets and neuromodulation advances have paved the way for a new generation of therapeutic agents in cluster headache. There are several other potential targets.

Molecular targets and neuromodulation advances have paved the way for a new generation of therapeutic agents in cluster headache. There are several other potential targets.Parkinson disease (PD) is a neurodegenerative disease characterized by selective loss of dopaminergic (DA) neurons in the midbrain. The regulatory role of a variety of microRNAs in PD has been confirmed, and our study is the first to demonstrate that miR-3473b is involved in the regulation of PD. In vitro, an miR-3473b inhibitor can inhibit the secretion of inflammatory factors (TNF-α and IL-1β) in moues microglia cell line (BV2) cells induced by lipopolysaccharide (LPS) and promote autophagy in BV2 cells. In vivo, miR-3473b antagomir can inhibit the activation of substantia nigra pars compacta (SNpc) microglia of C57BL/6 mice induced by 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) and promote autophagy. Deletion of TREM2, one of the most highly expressed receptors in microglia, leads to the occurrence and development of PD. ULK1 is a component of the Atg1 complex. Deletion of ULK1 aggravates the pathological reaction of PD. TREM2 and ULK1 are predicted potential targets of miR-3473b by Targetscan. Then, the results of our experiments indicate that transfection with a miR-3473b mimic can inhibit the expression of TREM2 and ULK1. Data from a double luciferase experiment indicate that the 3'-UTR of TREM2, but not ULK1, is the direct target of miR-3473b. Then we aim to investigate the regulation of TREM2 and ULK1 in PD. We found that the expression of p-ULK1 was significantly increased via up-regulation of TREM2. The increased expression of p-ULK1 can promote autophagy and inhibit the expression of inflammatory factors. The regulation of ULK1 by miR-3473b may be accomplished indirectly through TREM2. Thus, miR-3473b may regulate the secretion of proinflammatory mediators by targeting TREM2/ULK1 expression to regulate the role of autophagy in the pathogenesis of inflammation in Parkinson's disease, suggesting that mir-3473b may be a potential therapeutic target to regulate the inflammatory response in PD.Analysis of serum cytokine levels in Wiskott-Aldrich syndrome patients pre- and post- treatment reveals IL-18 as a stable and reliable marker of inflammation. Definitive stem cell treatment with good myeloid correction correlates with resolution of inflammation and reduction of circulating IL-18, highlighting the importance of actin cytoskeletal regulation of myeloid cells in control of inflammation.Herbivory has potential to modify vegetation responses to climatic changes. However, climate and herbivory also affect each other, and rarely work in isolation from other ecological factors, such as plant-plant competition. Thus, it is challenging to predict the extent to which herbivory can counteract, amplify, or interact with climate impacts on ecosystems. Here, we investigate how moose modify climatic responses of boreal trees by using experimental exclosures on two continents and modeling complex causal pathways including several climatic factors, multiple tree species, competition, tree height, time, food availability, and herbivore presence, density, and browsing intensity. click here We show that moose can counteract, that is, "cool down" positive temperature responses of trees, but that this effect varies between species depending on moose foraging preferences. Growth of preferred deciduous trees was strongly affected by moose, whereas growth of less preferred conifers was mostly driven by climate and tree height. In addition, moose changed temperature responses of rowan in Norway and balsam fir in Canada, by making fir more responsive to temperature but decreasing the strength of the temperature response of rowan. Snow protected trees from browsing, and therefore moose "cooling power" might increase should a warming climate result in decreased snow cover. Furthermore, we found evidence of indirect effects of moose via plant-plant competition By constraining growth of competing trees, moose can contribute positively to the growth of other trees. Our study shows that in boreal forests, herbivory cooling power is highly context dependent, and in order to understand its potential to prevent changes induced by warming climate, species differences, snow, competition, and climate effects on browsing need to be considered.Correspondence What do we lose when we can't go into the anatomy lab?Due to conflicting data from previous studies a new methodological approach to evaluate heel pad stiffness and soft tissue deformation has been developed. The purpose of this study was to compare heel pad (HP) stiffness in both limbs between males and females during a dynamic unloading and loading activity. Ten males and 10 females volunteered to perform three dynamic trials to unload and load the HP. The dynamic protocol consisted of three continuous phases foot flat (baseline phase), bilateral heel raise (unloading phase) and foot flat (loading phase) with each phase lasting two seconds. Six retroreflective markers (3 mm) were attached to the skin of the left and right heels using a customised marker set. Three-dimensional motion analysis cameras synchronised with force plates collected the kinematic and kinetic data throughout the trials. Three-way repeated measures ANOVA together with a Bonferroni post hoc test were applied to the stiffness and marker displacement datasets. On average, HP stiffness was higher in males than females during the loading and unloading phases. ANOVA results revealed no significant differences for the stiffness and displacement outputs with respect to sex, sidedness or phase interactions (p > .05) in the X, Y and Z directions. Irrespective of direction, there were significant differences in stiffness between the baseline and unloading conditions (p .116). Finally, females portrayed lower levels of mean HP stiffness whereas males had stiffer heels particularly in the vertical direction (Z) when the HP was both unloaded and loaded. High HP stiffness values and very small marker displacements could be valuable indicators for the risk of pathological foot conditions.Oil and natural gas prospecting requires precise pore characterisation of insulating rock samples, which involves severe charging problems in the state-of-art FIB-SEM tomography, such as overexposure, drift and distortion. For weak cemented samples with very poor conductivity, the conventional ways such as decreasing accelerating voltage or current as well as coating a thin layer of carbon or gold fail to eliminate all the detrimental effect, leading to image distortion in the form of lateral shift and longitudinal stretching. A new nanoprobe-assisted method is explored in FIB-SEM tomography to address this problem and improve image quality. To be specific, a metallic nanoprobe is induced and attached on the sample surface to create an express path for the export of excess electrons near the region of interest, which effectively removes distortion and drift when imaging. Two adjacent areas were characterised and reconstructed into 3D digital models by FIB-SEM tomography with nanoprobe-assisted method applied to one region only. The lateral shift creates zigzag feature for distorted region and the longitudinal stretching of undistorted object can reach 14%. Average pore size of distorted region is larger than that of the undistorted region, however considering the longitudinal stretching, the average pore size of distorted region can be corrected to the same level as the undistorted region. The systematic error caused by distortion for poorly conductive porous rock is hazardous for digital rock physics analysis. Therefore, the nanoprobe-assisted FIB-SEM tomography should be regarded as a one of the optional and feasible procedures in case decreasing accelerating voltage or current as well as coating a thin layer of conductive material does not work.Multiple sclerosis (MS) represents the most common demyelinating disease affecting the central nervous system (CNS) in adults as well as in children. Furthermore, in children, in addition to acquired diseases such as MS, genetically inherited diseases significantly contribute to the incidence of demyelinating disorders. Some genetic defects lead to sphingolipid alterations that are able to elicit neurological symptoms. Sphingolipids are essential for brain development, and their aberrant functionality may thus contribute to demyelinating diseases such as MS. In particular, sphingolipidoses caused by deficits of sphingolipid-metabolizing enzymes, are often associated with demyelination. Sphingolipids are not only structural molecules but also bioactive molecules involved in the regulation of cellular events such as development of the nervous system, myelination and maintenance of myelin stability. Changes in the sphingolipid metabolism deeply affect plasma membrane organization. Thus, changes in myelin sphingolipid composition might crucially contribute to the phenotype of diseases characterized by demyelinalization. Here, we review key features of several sphingolipids such as ceramide/dihydroceramide, sphingosine/dihydrosphingosine, glucosylceramide and, galactosylceramide which act in myelin formation during rat brain development and in human brain demyelination during the pathogenesis of MS, suggesting that this knowledge could be useful in identifying targets for possible therapies.

Atrial fibrillation (AF) and hypertension are independently associated with impaired autonomic function determined using heart rate variability (HRV). As these conditions frequently co-exist, we sought to determine whether AF would worsen HRV in hypertensive patients.

We studied HRV in AF (and hypertension) (n=61) and hypertension control group (n=33). The AF (and hypertension) group was subdivided into permanent AF (n=30) and paroxysmal AF (n=31) and re-studied. Time-domain, frequency-domain and nonlinear measures of HRV were determined. Permanent AF group (n=30) was followed up after 8weeks following optimisation of their heart rate and blood pressure (BP).

Time-domain and nonlinear indices of HRV were higher in AF (and hypertension) group compared to hypertensive controls (P≤.01). Time-domain and nonlinear indices of HRV were higher in permanent AF group compared to paroxysmal AF (P≤.001). Permanent AF was an independent predictor of HRV on multivariable analysis (P=.006). Optimisation of heart rate and BP had no significant impact on HRV in permanent AF.

AF, independent of hypertension, is characterised with marked HRV and is possibly related to vagal tone. HRV is higher in permanent AF compared to paroxysmal AF suggesting evident autonomic influence in the pathophysiology of permanent AF. Modulation of autonomic influence on cardiovascular system should be explored in future studies.

AF, independent of hypertension, is characterised with marked HRV and is possibly related to vagal tone. HRV is higher in permanent AF compared to paroxysmal AF suggesting evident autonomic influence in the pathophysiology of permanent AF. Modulation of autonomic influence on cardiovascular system should be explored in future studies.