Molecular epidemiology of Kaposi sarcoma virus in Spain

Background: Since human herpesvirus 8 (HHV-8) infection may be underestimated and HHV-8 subtype circulation in Spain remains unknown, a molecular epidemiologic study is highly desirable. Objectives: This study aimed to analyse HHV-8 subtype diversity and their distribution in Spain. Study design: The study included 142 HHV-8 infected patients. A nested PCR was developed in order to permit Sanger sequencing of HHV-8 K1 ORF directly from clinical samples received at the CNM from 2013 to 2021. Phylogenetic characterization was performed. Results: Genotypes A and C comprised 55.6% and 42.3% of strains. Regarding subtypes, 25.4% of strains were C3, 19.7% were A3, 14.1% were A5, and C2, A1, A4, C1, A2, C7 were 11.3%, 11.3%, 8.5%, 4.2%, 2.1% and 1.4%, respectively. Subtype E1, E2 and B1 were found in only one patient each (0.7%). The Madrid region accounted for 52.1% of patients and showed a significantly different subtype distribution compared to the others (P = 0.018). Subtypes B1, E1, and E2 were observed to appear sporadically, although overall genotypes A and subtype C3 remained the most frequent and unwavering. Subtype A3 presented the highest diversity as displayed by the highest number of clusters in phylogenetic analysis. Non-significant differences in viral loads between genotypes were found, but significantly higher viral loads in subtype C2 compared to subtype C3 was found, while no significant subtype differences were observed between subtypes within genotype A. Infections with HHV-8 were detected in 94 (66.2%) patients without KS and compared to patients with KS non-significant differences in subtype distribution were found. Conclusions: Subtype prevalence and regional distribution followed a similar pattern compared to other western European countries. Our study is the first to report HHV-8 subtypes E1 and E2 circulating in Europe that might be reflective of migration of population from Caribbean countries. Our study suggests that infection by HHV-8 is underestimated, and wider screening should be recommended for risk groups.This work was supported by funds and a grant from Instituto de Salud Carlos III. Project code MPY 1372/2012 and MPY 434/2021. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.S

A Study of Carbon Features in Type Ia Supernova Spectra

One of the major differences between various explosion scenarios of Type Ia supernovae (SNe Ia) is the remaining amount of unburned (C+O) material and its velocity distribution within the expanding ejecta. While oxygen absorption features are not uncommon in the spectra of SNe Ia before maximum light, the presence of strong carbon absorption has been reported only in a minority of objects, typically during the pre-maximum phase. The reported low frequency of carbon detections may be due to low signal-to-noise data, low abundance of unburned material, line blending between C II 6580 and Si II 6355, ejecta temperature differences, asymmetrical distribution effects, or a combination of these. However, a survey of published pre-maximum spectra reveals that more SNe Ia than previously thought may exhibit C II 6580 absorption features and relics of line blending near 6300 Angstroms. Here we present new SN Ia observations where spectroscopic signatures of C II 6580 are detected, and investigate the presence of C II 6580 in the optical spectra of 19 SNe Ia using the parameterized spectrum synthesis code, SYNOW. Most of the objects in our sample that exhibit C II 6580 absorption features are of the low-velocity gradient subtype. Our study indicates that the morphology of carbon-rich regions is consistent with either a spherical distribution or a hemispheric asymmetry, supporting the recent idea that SN Ia diversity may be a result of off-center ignition coupled with observer line-of-sight effects.Comment: 10 papges, 9 figures, 3 table

Misidentification subtype of alzheimer's disease psychosis predicts a faster cognitive decline

The presence of psychosis is associated with more rapid decline in Alzheimer's disease (AD), but the impact of paranoid (persecutory delusions) and misidentification (misperceptions and/or hallucinations) subtypes of psychosis on the speed of decline in AD is still unclear. Here we analysed data on Alzheimer's Disease Neuroimaging Initiative (ADNI)2 participants with late mild cognitive impairment or AD and we described individual trajectories of Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-cog) scores using a semi-mechanistic, logistic model, with a mixed effects based approach, which accounted for drop-out, and adjusted for baseline Mini Mental State Examination scores. The covariate model included psychosis subtypes, age, gender, education, medications and Apo-e ε4 genotype. We found that ADAS-cog rate of increase was doubled in misidentification (βr,misid_subtype =0.63, p=0.031) and mixed (both subtypes) ((βr,mixed_subtype =0.70, p=0.003) compared to non-psychotic (or paranoid) subjects suggesting that the misidentification subtype may represent a distinct AD sub-phenotype associated with an accelerated pathological process. This article is protected by copyright. All rights reserved

Differences in the signaling pathways of α1A- and α1B-adrenoceptors are related to different endosomal targeting

Aims: To compare the constitutive and agonist-dependent endosomal trafficking of α1A- and α1B-adrenoceptors (ARs) and to establish if the internalization pattern determines the signaling pathways of each subtype. Methods: Using CypHer5 technology and VSV-G epitope tagged α1A- and α1B-ARs stably and transiently expressed in HEK 293 cells, we analyzed by confocal microscopy the constitutive and agonist-induced internalization of each subtype, and the temporal relationship between agonist induced internalization and the increase in intracellular calcium (determined by FLUO-3 flouorescence), or the phosphorylation of ERK1/2 and p38 MAP kinases (determined by Western blot). Results and Conclusions: Constitutive as well as agonist-induced trafficking of α1A and α1B ARs maintain two different endosomal pools of receptors: one located close to the plasma membrane and the other deeper into the cytosol. Each subtype exhibited specific characteristics of internalization and distribution between these pools that determines their signaling pathways: α1A-ARs, when located in the plasma membrane, signal through calcium and ERK1/2 pathways but, when translocated to deeper endosomes, through a mechanism sensitive to β-arrestin and concanavalin A, continue signaling through ERK1/2 and also activate the p38 pathway. α1B-ARs signal through calcium and ERK1/2 only when located in the membrane and the signals disappear after endocytosis and by disruption of the membrane lipid rafts by methyl-β-cyclodextrin

Impact of breast cancer subtypes on 3-year survival among adolescent and young adult women.

IntroductionYoung women have poorer survival after breast cancer than do older women. It is unclear whether this survival difference relates to the unique distribution of hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2)-defined molecular breast cancer subtypes among adolescent and young adult (AYA) women aged 15 to 39 years. The purpose of our study was to examine associations between breast cancer subtypes and short-term survival in AYA women, as well as to determine whether the distinct molecular subtype distribution among AYA women explains the unfavorable overall breast cancer survival statistics reported for AYA women compared with older women.MethodsData for 5,331 AYA breast cancers diagnosed between 2005 and 2009 were obtained from the California Cancer Registry. Survival by subtype (triple-negative; HR+/HER2-; HR+/HER2+; HR-/HER2+) and age-group (AYA versus 40- to 64-year-olds) was analyzed with Cox proportional hazards regression with follow-up through 2010.ResultsWith up to 6 years of follow-up and a mean survival time of 3.1 years (SD = 1.5 years), AYA women diagnosed with HR-/HER + and triple-negative breast cancer experienced a 1.6-fold and 2.7-fold increased risk of death, respectively, from all causes (HR-/HER + hazard ratio: 1.55; 95% confidence interval (CI): 1.10 to 2.18; triple-negative HR: 2.75; 95% CI, 2.06 to 3.66) and breast cancer (HR-/HER + hazard ratio: 1.63; 95% CI, 1.12 to 2.36; triple-negative hazard ratio: 2.71; 95% CI, 1.98 to 3.71) than AYA women with HR+/HER2- breast cancer. AYA women who resided in lower socioeconomic status neighborhoods, had public health insurance, and were of Black, compared with White, race/ethnicity experienced worse survival. This race/ethnicity association was attenuated somewhat after adjusting for breast cancer subtypes (hazard ratio, 1.33; 95% CI, 0.98 to 1.82). AYA women had similar all-cause and breast cancer-specific short-term survival as older women for all breast cancer subtypes and across all stages of disease.ConclusionsAmong AYA women with breast cancer, short-term survival varied by breast cancer subtypes, with the distribution of breast cancer subtypes explaining some of the poorer survival observed among Black, compared with White, AYA women. Future studies should consider whether distribution of breast cancer subtypes and other factors, including differential receipt of treatment regimens, influences long-term survival in young compared with older women

Characterization of Angiotensin Ii Receptor Subtypes in the Brain

The present studies explore binding, distribution, and function of angiotensin II (AII) receptors (AT\sb1 and AT\sb2) in the brain. The discovery that sulfhydryl reducing agents masked some but not all AII receptors in the brain prompts an evaluation of commonly used binding assay buffer constituents. EDTA enhances binding (40%) at both AT\sb1 and AT\sb2 nuclei, while bacitracin did not alter binding at either receptor subtype. Phenanthroline and BSA differentially altered binding at AT1 (220% of control) and AT\sb2 (118% of control) receptors. The results indicate that phenanthroline and BSA would be poor buffer constituents for studies comparing binding at AT\sb1 and AT\sb2 receptors. All receptors were mapped in normotensive and genetically hypertensive hamster brains and the subtype composition estimated for a number of brain nuclei and the pituitary. Binding in the hamster was similar to that previously observed in the rat brain with exceptions: (1) additional binding in the medial habenula and interpeduncular nuclei, (2) absence of binding in the inferior olive, suprachiasmatic nucleus, medial amygdala, piriform cortex, and subthalamic nucleus and (3) quantitative differences in the dorsomotor nucleus of the vagus, striatum, hippocampus and anterior pituitary. Unlike studies of the normotensive and spontaneously hypertensive rat, we found no significant differences in binding distribution, density or subtype composition when comparing normal and genetically hypertensive hamsters. Finally, the effects of brain angiotensin II (AII) on central catecholamine utilization were determined. We found no significant differences in norepinephrine, epinephrine or dopamine utilization in rat brain homogenates following intracerebroventricular injection of AII. Although there is evidence that AII alters catecholamine utilization in some brain nuclei, these alterations appear limited (anatomically and/or quantitatively) to a relatively small portion of the brain catecholaminergic system. The results indicate that the selection of buffer constituents is an important consideration for AII binding studies, that there are minor species differences in the distribution of AII receptors in the brain and that despite substantial functional and anatomical overlap, only a relatively small portion of the brain catecholaminergic system is modulated by angiotensin II

Automated identification of 2612 late-k and M dwarfs in the LAMOST commissioining data using the classification template fits

We develop a template-fit method to automatically identify and classify late-type K and M dwarfs in spectra from the LAMOST. A search of the commissioning data, acquired in 2009-2010, yields the identification of 2612 late-K and M dwarfs. The template fit method also provides spectral classification to half a subtype, classifies the stars along the dwarf-subdwarf metallicity sequence, and provides improved metallicity/gravity information on a finer scale. The automated search and classification is performed using a set of cool star templates assembled from the Sloan Digital Sky Survey spectroscopic database. We show that the stars can be efficiently classified despite shortcomings in the LAMOST commissioning data which include bright sky lines in the red. In particular we find that the absolute and relative strengths of the critical TiO and CaH molecular bands around 7000A are cleanly measured, which provides accurate spectral typing from late-K to mid-M, and makes it possible to estimate metallicities in a way that is more efficient and reliable than with the use of spectral indices or spectral-index based parameters such as zeta. Most of the cool dwarfs observed by LAMOST are found to be metal-rich dwarfs. We use a calibration of spectral type to absolute magnitude and estimate spectroscopic distances for all the stars; we also recover proper motions from the SUPERBLINK and PPMXL catalogs. Our analysis of the estimated transverse motions suggests a mean velocity and standard deviation for the UVW components of velocity to be: U=-9.8 km/s; V=-22.8 km/s; W=-7.9 km/s. The resulting values are general agreement with previous reported results, which yields confidence in our spectral classification and spectroscopic distance estimates, and illustrates the potential for using LAMOST spectra of K and M dwarfs for investigating the chemo-kinematics of the local Galactic disk and halo.Comment: 18 pages,16 figures,accepted for publication A