Early role of vascular dysregulation on late-onset Alzheimer's disease based on multifactorial data-driven analysis

Multifactorial mechanisms underlying late-onset Alzheimer’s disease (LOAD) are poorly characterized from an integrative perspective. Here spatiotemporal alterations in brain amyloid-β deposition, metabolism, vascular, functional activity at rest, structural properties, cognitive integrity and peripheral proteins levels are characterized in relation to LOAD progression. We analyse over 7,700 brain images and tens of plasma and cerebrospinal fluid biomarkers from the Alzheimer’s Disease Neuroimaging Initiative (ADNI). Through a multifactorial data-driven analysis, we obtain dynamic LOAD–abnormality indices for all biomarkers, and a tentative temporal ordering of disease progression. Imaging results suggest that intra-brain vascular dysregulation is an early pathological event during disease development. Cognitive decline is noticeable from initial LOAD stages, suggesting early memory deficit associated with the primary disease factors. High abnormality levels are also observed for specific proteins associated with the vascular system’s integrity. Although still subjected to the sensitivity of the algorithms and biomarkers employed, our results might contribute to the development of preventive therapeutic interventions

The effect of acute exercise on cognitive performance in children with and without ADHD

AbstractBackgroundAttention deficit hyperactivity disorder (ADHD) is a common childhood disorder that affects approximately 11% of children in the United States. Research supports that a single session of exercise benefits cognitive performance by children, and a limited number of studies have demonstrated that these effects can also be realized by children with ADHD. The purpose of this study was to examine the effect of acute exercise on cognitive performance by children with and without ADHD.MethodsChildren with and without ADHD were asked to perform cognitive tasks on 2 days following treatment conditions that were assigned in a random, counterbalanced order. The treatment conditions consisted of a 30-min control condition on 1 day and a moderate intensity exercise condition on the other day.ResultsExercise significantly benefited performance on all three conditions of the Stroop Task, but did not significantly affect performance on the Tower of London or the Trail Making Test.Conclusionchildren with and without ADHD realize benefits in speed of processing and inhibitory control in response to a session of acute exercise, but do not experience benefits in planning or set shifting

Four distinct trajectories of tau deposition identified in Alzheimer's disease

Alzheimer’s disease (AD) is characterized by the spread of tau pathology throughout the cerebral cortex. This spreading pattern was thought to be fairly consistent across individuals, although recent work has demonstrated substantial variability in the population with AD. Using tau-positron emission tomography scans from 1,612 individuals, we identified 4 distinct spatiotemporal trajectories of tau pathology, ranging in prevalence from 18 to 33%. We replicated previously described limbic-predominant and medial temporal lobe-sparing patterns, while also discovering posterior and lateral temporal patterns resembling atypical clinical variants of AD. These ‘subtypes’ were stable during longitudinal follow-up and were replicated in a separate sample using a different radiotracer. The subtypes presented with distinct demographic and cognitive profiles and differing longitudinal outcomes. Additionally, network diffusion models implied that pathology originates and spreads through distinct corticolimbic networks in the different subtypes. Together, our results suggest that variation in tau pathology is common and systematic, perhaps warranting a re-examination of the notion of ‘typical AD’ and a revisiting of tau pathological staging

miRNA in situ hybridization in circulating tumor cells - MishCTC

irculating tumor cells (CTCs) must be phenotypically and genetically characterized before they can be utilized in clinical applications. Here, we present the first protocol for the detection of miRNAs in CTCs using in situ hybridization (ISH) combined with immunomagnetic selection based on cytokeratin (CK) expression and immunocytochemistry. Locked-Nucleic Acid (LNA) probes associated with an enzyme-labeled fluorescence (ELF) signal amplification approach were used to detect miRNA-21 in CTCs. This protocol was optimized using both epithelial tumor (MDA-MB468) and epithelial non-tumor (MCF-10A) cell lines, and miRNA-21 was selected as the target miRNA because of its known role as an onco-miRNA. Hematopoietic cells do not express miRNA-21; thus, miRNA-21 is an ideal marker for detecting CTCs. Peripheral blood samples were taken from 25 cancer patients and these samples were analyzed using our developed protocol. Of the 25 samples, 11 contained CTCs. For all 11 CTC-positive samples, the isolated CTCs expressed both CK and miRNA-21. Finally, the protocol was applied to monitor miRNA-21 expression in epithelial to mesenchymal transition (EMT)-induced MCF-7 cells, an epithelial tumor cell line. CK expression was lost in these cells, whereas miRNA-21 was still expressed, suggesting that miRNA-21 might be a good marker for detecting CTCs with an EMT phenotype.JJDM thanks the Spanish Ministerio de Economía y Competitividad for a Ramón y Cajal Fellowship (Grant CTQ2012-34778). This research was partially supported by Marie Curie Career Integration Grants within the 7th European Community Framework Program (FP7-PEOPLE-2011-CIG-Project Number 294142 to RMSM and FP7-PEOPLE-2012-CIG-Project Number 322276 toJJDM). Thisresearch wasalso partially supported by Consejeria de Salud de la Junta de Andalucı ́ a (PI0294-2012)

Time-resolved thermal lens measurements of the thermo-optical properties of glasses at low temperature down to 20 K

In this work the time resolved thermal lens spectrometry was applied to measure the absolute values of the thermo-optical properties of low silica calcium aluminosilicate and soda lime glasses at low temperatures, in the range between 20 and 300 K. The thermal relaxation calorimetry was used as a complementary technique to determine the specific heat. The results showed a marked decrease of the thermal diffusivity with the temperature rise, with a dependence similar to that of the mean free path (similar to T-1) in the interval between 20 and 70 K, while in the range between 70 and 300 K the dependence was T-(0.33 +/- 0.02). The marked variation of the temperature coefficient of the optical path length change with the temperature rise was attributed to the increase in the coefficient of the electronic polarizability. The results also showed that for the aluminosilicate glass the excess in the specific heat correlated to the so-called boson peak occurred at about 17 K, higher than that of soda lime, which occurs at about 12 K. In conclusion, our results showed the ability of the time resolved thermal lens to determine the thermo-optical properties of glasses at low temperatures, bringing possibilities for experiments in a wide range of optical materials.712

The evolution of diabetic chronic complications after pancreas transplantation

Pancreas transplantation is an invasive procedure that can restore and maintain normoglycemic level very successfully and for a prolonged period in DM1 patients. The procedure elevates the morbimortality rates in the first few months following the surgery if compared to kidney transplants with living donors, but it offers a better quality of life to patients

Disentangling the effects of sex, life history and genetic background in Atlantic salmon: growth, heart and liver under common garden conditions

Livestock domestication has long been a part of agriculture, estimated to have first occurred approximately 10 000 years ago. Despite the plethora of traits studied, there is little understanding of the possible impacts domestication has had on internal organs, which are key determinants of survival. Moreover, the genetic basis of observed associated changes in artificial environments is still puzzling. Here we examine impacts of captivity on two organs in Atlantic salmon (Salar salar) that have been domesticated for approximately 50 years: heart and liver, in addition to growth. We studied multiple families of wild, domesticated, F1 and F2 hybrid, and backcrossed strains of S. salar in replicated common garden tanks during the freshwater and marine stages of development. Heart and liver weight were investigated, along with heart morphology metrics examined in just the wild, domesticated and F1 hybrid strains (heart height and width). Growth was positively linked with the proportion of the domesticated strain, and recombination in F2 hybrids (and the potential disruption of co-adapted gene complexes) did not influence growth. Despite the influence of domestication on growth, we found no evidence for domestication-driven divergence in heart or liver morphology. However, sexual dimorphism was detected in heart morphology, and after controlling for body size, females exhibited significantly larger heart weight and heart width when compared with males. Wild females also had an increased heart height when compared with wild males, and this was not observed in any other strain. Females sampled in saltwater showed significantly larger heart height with rounder hearts, than saltwater males. Collectively, these results demonstrate an additive basis of growth and, despite a strong influence of domestication on growth, no clear evidence of changes in heart or liver morphology associated with domestication was identifie

New highlights on stroma–epithelial interactions in breast cancer

Although the stroma in which carcinomas arise has been previously regarded as a bystander to the clonal expansion and acquisition of malignant characteristics of tumor cells, it is now generally acknowledged that stromal changes are required for the establishment of cancer. In the present article, we discuss three recent publications that highlight the complex role the stroma has during the development of cancer and the potential for targeting the stroma by therapeutic approaches