Primary aldosteronism (PA) is one of the most frequent forms of secondary hypertension, associated with atherosclerosis and higher risk of cardiovascular events. Platelets play a key role in the ...atherosclerotic process. The aim of the study was to evaluate the platelet activation by measuring serum levels of soluble CD40L (sCD40L) and P-selectin (sP-selectin) in consecutive PA patients subgroup: aldosterone-secreting adrenal adenoma (APA) and bilateral adrenal hyperplasia (IHA), matched with essential hypertensive (EH) patients. The subgroup of APA patients was revaluated 6-months after unilateral adrenalectomy. In all PA group, we measured higher serum levels of both sP-selectin (14.29±9.33 pg/ml) and sCD40L (9.53±4.2 ng/ml) compared to EH patients (9.39±5.3 pg/ml and 3.54±0.94 ng/ml, respectively; p<0.001). After removal of APA, PA patients showed significant reduction of blood pressure (BP) values, plasma aldosterone (PAC) levels and ARR-ratio, associated with a significant reduction of sP-selectin (16.74±8.9 pg/ml vs. 8.1±3.8 pg/ml; p<0.01) and sCD40L (8.6±1 ng/ml vs. 5.24±0.94 ng/ml; p<0.001). In PA patients, we found a significant correlation between sP-selectin and sCD40L with PAC (r=0.52, p<0.01; r=0.50, p<0.01, respectively); this correlation was stronger in APA patients (r=0.54; p<0.01 r=0.63; p<0.01, respectively). Our results showed that PA is related to platelet activation, expressed as higher plasma values of sCD40L and sP-selectin values. Surgical treatment and consequent normalization of aldosterone secretion was associated with significant reduction of sCD40L and sP-selectin values in APA patients.
We present a three-dimensional density model of coronal prominence cavities, and a morphological fit that has been tightly constrained by a uniquely well-observed cavity. Observations were obtained ...as part of an International Heliophysical Year campaign by instruments from a variety of space- and ground-based observatories, spanning wavelengths from radio to soft X-ray to integrated white light. From these data it is clear that the prominence cavity is the limb manifestation of a longitudinally extended polar-crown filament channel, and that the cavity is a region of low density relative to the surrounding corona. As a first step toward quantifying density and temperature from campaign spectroscopic data, we establish the three-dimensional morphology of the cavity. This is critical for taking line-of-sight projection effects into account, since cavities are not localized in the plane of the sky and the corona is optically thin. We have augmented a global coronal streamer model to include a tunnel-like cavity with elliptical cross-section and a Gaussian variation of height along the tunnel length. We have developed a semi-automated routine that fits ellipses to cross-sections of the cavity as it rotates past the solar limb, and have applied it to Extreme Ultraviolet Imager observations from the two Solar Terrestrial Relations Observatory spacecraft. This defines the morphological parameters of our model, from which we reproduce forward-modeled cavity observables. We find that cavity morphology and orientation, in combination with the viewpoints of the observing spacecraft, explain the observed variation in cavity visibility for the east versus west limbs.
The nonsense-mediated mRNA decay (NMD) pathway serves an important role in gene expression by targeting aberrant mRNAs that have acquired premature termination codons (PTCs) as well as a subset of ...normally processed endogenous mRNAs. One determinant for the targeting of mRNAs by NMD is the occurrence of translation termination distal to the poly(A) tail. Yet, a large subset of naturally occurring mRNAs contain long 3' UTRs, many of which, according to global studies, are insensitive to NMD. This raises the possibility that such mRNAs have evolved mechanisms for NMD evasion. Here, we analyzed a set of human long 3' UTR mRNAs and found that many are indeed resistant to NMD. By dissecting the 3' UTR of one such mRNA, TRAM1 mRNA, we identified a cis element located within the first 200 nt that inhibits NMD when positioned in downstream proximity of the translation termination codon and is sufficient for repressing NMD of a heterologous reporter mRNA. Investigation of other NMD-evading long 3' UTR mRNAs revealed a subset that, similar to TRAM1 mRNA, contains NMD-inhibiting cis elements in the first 200 nt. A smaller subset of long 3' UTR mRNAs evades NMD by a different mechanism that appears to be independent of a termination-proximal cis element. Our study suggests that different mechanisms have evolved to ensure NMD evasion of human mRNAs with long 3' UTRs.
Naturally occurring sympathetic neuron death is the result of two apoptotic signaling events: one normally suppressed by NGF/TrkA survival signals, and a second activated by the p75 neurotrophin ...receptor. Here we demonstrate that the p53 tumor suppressor protein, likely as induced by the MEKK-JNK pathway, is an essential component of both of these apoptotic signaling cascades. In cultured neonatal sympathetic neurons, p53 protein levels are elevated in response to both NGF withdrawal and p75NTR activation. NGF withdrawal also results in elevation of a known p53 target, the apoptotic protein Bax. Functional ablation of p53 using the adenovirus E1B55K protein inhibits neuronal apoptosis as induced by either NGF withdrawal or p75 activation. Direct stimulation of the MEKK-JNK pathway using activated MEKK1 has similar effects; p53 and Bax are increased and the subsequent neuronal apoptosis can be rescued by E1B55K. Expression of p53 in sympathetic neurons indicates that p53 functions downstream of JNK and upstream of Bax. Finally, when p53 levels are reduced or absent in p53+/- or p53-/- mice, naturally occurring sympathetic neuron death is inhibited. Thus, p53 is an essential common component of two receptor-mediated signal transduction cascades that converge on the MEKK-JNK pathway to regulate the developmental death of sympathetic neurons.
We show that the well-known "Waldmeier effect," or anticorrelation between the peak in sunspot number of a cycle and the time from minimum to reach that peak, is not present in sunspot area data ...averaged in the same way. With a 13-rotation Gaussian running average applied to both sunspot number and sunspot area, we find the correlation between cycle rise time and cycle peak is r = -0.71 for sunspot number and r = 10 super(-4) for sunspot area. Hathaway et al. previously showed that the Waldmeier effect is much weaker (r = -0.34) in sunspot group number. Thus the Waldmeier effect may be specific to only Wolf sunspot number.
In this report, we provide evidence that NGF and BDNF have functionally antagonistic actions on sympathetic neuron growth and target innervation, with NGF acting via TrkA to promote growth and BDNF ...via p75NTR to inhibit growth. Specifically, in cultured sympathetic neurons that themselves synthesize BDNF, exogenous BDNF inhibits and function-blocking BDNF antibodies enhance process outgrowth. Both exogenous and autocrine BDNF mediate this effect via p75NTR because (1) BDNF does not inhibit growth of neurons lacking p75NTR, (2) function-blocking p75NTR antibodies enhance NGF-mediated growth, and (3) p75NTR-/- sympathetic neurons grow more robustly in response to NGF than do their wild-type counterparts. To determine the physiological relevance of this functional antagonism, we examined the pineal gland, a well defined sympathetic target organ. BDNF is present in the pineal gland during target innervation, and incoming sympathetic axons are p75NTR positive. Moreover, the pineal glands of BDNF+/- and BDNF-/- mice are hyperinnervated with sympathetic fibers, and tyrosine hydroxylase (TH) levels are elevated. Increased tyrosine hydroxylase is also observed in the BDNF+/- carotid artery, another sympathetic neuron target. Thus, BDNF, made by sympathetic neurons and/or their target organs, acts via p75NTR to antagonize NGF-mediated growth and target innervation, suggesting that sympathetic target innervation is determined by the balance of positively and negatively acting neurotrophins present in developing and potentially mature targets.
Purpose
The diagnostic, therapeutic and health-care management protocol (Protocollo Gestionale Diagnostico-Terapeutico-Assistenziale, PDTA) by the Association of the Italian Endocrine Surgery Units ...(U.E.C. CLUB) aims to help treat the patient in a topical, rational way that can be shared by health-care professionals.
Methods
This fourth consensus conference involved: a selected group of experts in the preliminary phase; all members, via e-mail, in the elaboration phase; all the participants of the XI National Congress of the U.E.C. CLUB held in Naples in the final phase. The following were examined: diagnostic pathway and clinical evaluation; mode of admission and waiting time; therapeutic pathway (patient preparation for surgery, surgical treatment, postoperative management, management of major complications); hospital discharge and patient information; outpatient care and follow-up.
Results
A clear and concise style was adopted to illustrate the reasons and scientific rationales behind behaviors and to provide health-care professionals with a guide as complete as possible on who, when, how and why to act. The protocol is meant to help the surgeon to treat the patient in a topical, rational way that can be shared by health-care professionals, but without influencing in any way the physician–patient relationship, which is based on trust and clinical judgment in each individual case.
Conclusions
The PDTA in thyroid surgery approved by the fourth consensus conference (June 2015) is the official PDTA of U.E.C. CLUB.
We examine the relative intensity of sunspot umbrae during the period from 1986 to 2012 using photometric images from the San Fernando Observatory. We confirm the presence of a relationship between ...the mean umbral core intensity and the mean sunspot area, as found in previous studies, and do not find a notable change in this relationship between cycles 22 and 23. We looked for a possible time variation in the sunspot umbral contrast during the 27 yr covering cycles 22, 23, and the rise of cycle 24, and we did not find a significant change. These findings do not indicate that sunspots have become less dark during cycles 23 and 24.
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