Expression of podocalyxin separates the hematopoietic and vascular potentials of mouse embryonic stem cell-derived mesoderm.

In the mouse embryo and differentiating embryonic stem cells, the hematopoietic, endothelial, and cardiomyocyte lineages are derived from Flk1+ mesodermal progenitors. Here, we report that surface expression of Podocalyxin (Podxl), a member of the CD34 family of sialomucins, can be used to subdivide the Flk1+ cells in differentiating embryoid bodies at day 4.75 into populations that develop into distinct mesodermal lineages. Definitive hematopoietic potential was restricted to the Flk1+Podxl+ population, while the Flk1-negative Podxl+ population displayed only primitive erythroid potential. The Flk1+Podxl-negative population contained endothelial cells and cardiomyocyte potential. Podxl expression distinguishes Flk1+ mesoderm populations in mouse embryos at days 7.5, 8.5, and 9.5 and is a marker of progenitor stage primitive erythroblasts. These findings identify Podxl as a useful tool for separating distinct mesodermal lineages.

Neuroimaging signatures of frailty: A population-based study in community-dwelling older adults (the Atahualpa Project).

AIMS: Frailty is a geriatric state of physical vulnerability that might be associated with cognitive decline in the absence of a concurrent neurodegenerative disorder. This assumes that neuroimaging studies are normal, but such examinations have rarely been considered for a frailty work-up. The present study identifies neuroimaging signatures in older adults interviewed with the Edmonton Frail Scale (EFS). METHODS: Community-dwellers aged ≥60 years enrolled in the Atahualpa Project were invited to undergo brain magnetic resonance imaging. Using generalized regression models, we evaluated the association between frailty and diffuse cortical and subcortical brain damage, after adjusting for relevant confounders. Multivariate models estimated the interaction of age in the association between frailty and these neuroimaging signatures. RESULTS: Out of 298 participants (mean age 70 ± 8 years, 57% women), 151 (51%) had moderate-to-severe cortical atrophy and 74 (25%) had moderate-to-severe white matter hyperintensities of presumed vascular origin. Mean EFS scores were 5 ± 3 points, with 140 (47%) individuals classified as robust, 65 (22%) as pre-frail and 93 (31%) as frail. Multivariate models showed a significant association between cortical atrophy with the continuous (P = 0.002) and the categorized (P = 0.008) EFS score. The relationship between white matter hyperintensities and the EFS was marginal. According to interaction models, prefrail or frail individuals aged ≥67 years presented more prominent neuroimaging signatures of diffuse cortical or subcortical damage than their robust counterparts. CONCLUSIONS: Neuroimaging signatures of frailty are mainly related to age. This reinforces the importance of early frailty detection to reduce its catastrophic consequences. Geriatr Gerontol Int 2017; 17: 270-276.

Reliability of Two Ankle-Brachial Index Methods to Predict Silent Lacunar Infarcts: A Population-Based Study in Stroke-Free Older Adults (the Atahualpa Project).

Individuals with an abnormal ankle-brachial index (ABI) are four times more likely to have a silent lacunar infarct (SLI), but reliability of ABI in predicting the presence of these lesions has not been estimated yet. We compared two methods of calculating ABI to assess their reliability in predicting SLIs. Stroke-free Atahualpa residents aged ≥ 60 years underwent MRI of the brain and ABI determinations. Persons with ABI ≥ 1.4 were excluded. Using receiver operator characteristic curve analysis, we calculated the reliability of the traditional as well as an alternative ABI method to identify individuals with SLI. The traditional ABI uses the higher systolic pressure of either the dorsalis pedis or the posterior tibial arteries as the numerator, whereas the alternative ABI uses the lower pressure. Of the 247 participants, 38 (15%) had traditional and 95 (38%) had alternative ABIs ≤ 0.9. Twenty-one individuals had SLI. Traditional and alternative ABIs ≤ 0.9 identified 9 and 13 individuals with SLI, respectively. The traditional ABI had sensitivity of 42.9% (22.6-65.6%) and specificity of 87.2% (81.9-91.1%). The alternative ABI had sensitivity of 61.9% (38.6-81%) and specificity of 63.7% (57-69.9%). The area under the curve for the predictive value of SLI was 0.65 (0.54-0.76) for the traditional and 0.63 (0.52-0.74) for the alternative ABI ≤ 0.9. The ABI is moderately reliable for identifying candidates for MRI screening in studies assessing the burden of SLI in older adults. The traditional ABI seems to be more suitable for this purpose.

The Effect of Age in the Association between Frailty and Poor Sleep Quality: A Population-Based Study in Community-Dwellers (The Atahualpa Project).

PURPOSE: To assess the effect of age in the association between poor sleep quality and frailty status. DESIGN AND SETTING: Population-based, cross-sectional study conducted in Atahualpa, a rural village located in coastal Ecuador. METHODS: Out of 351 Atahualpa residents aged ≥ 60 years, 311 (89%) were interviewed with the Pittsburgh Sleep Quality Index (PSQI) and the Edmonton Frail Scale (EFS). The independent association between PSQI and EFS scores was evaluated by the use of a generalized linear model adjusted for relevant confounders. A contour plot with Shepard interpolation was constructed to assess the effect of age in this association. RESULTS: Mean score in the PSQI was 5 ± 2 points, with 34% individuals classified as poor sleepers. Mean score in the EFS was 5 ± 3 points, with 46% individuals classified as robust, 23% as prefrail, and 31% as frail. In the fully adjusted model, higher scores in the PSQI were significantly associated with higher scores in the EFS (ß 0.23; 95% CI 0.11-0.35; P < .0001). Several clusters depicted the strong effect of age in the association between PSQI and EFS scores. Older individuals were more likely to have high scores in the EFS and the PSQI, and younger individuals had low EFS scores and were good sleepers. Clusters of younger individuals who were poor sleepers and had high EFS scores accounted for the independent association between PSQI and EFS scores. CONCLUSIONS: This study shows the strong effect of age in the association between poor sleep quality and frailty status.

Rapid evolution of in vivo-selected sequences and structures replacing 20% of a subviral RNA.

The 356 nt noncoding satellite RNA C (satC) of Turnip crinkle virus (TCV) is composed of 5' sequences from a second TCV satRNA (satD) and 3' sequences derived from TCV. SHAPE structure mapping revealed that 76 nt in the poorly-characterized satD-derived region form an extended hairpin (H2). Pools of satC in which H2 was replaced with 76, 38, or 19 random nt were co-inoculated with TCV helper virus onto plants and satC fitness assessed using in vivo functional selection (SELEX). The most functional progeny satCs, including one as fit as wild-type, contained a 38-39 nt H2 region that adopted a hairpin structure and exhibited an increased ratio of dimeric to monomeric molecules. Some progeny of satC with H2 deleted featured a duplication of 38 nt, partially rebuilding the deletion. Therefore, H2 can be replaced by a 38-39 nt hairpin, sufficient for overall structural stability of the 5' end of satC.