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Contains fulltext : 299836.pdf (Publisher’s version ) (Open Access), BACKGROUND AND OBJECTIVES: The existing literature highlights the importance of reading books in middle-to-older adulthood for cognitive functioning; very few studies, however, have examined the importance of childhood cognitive resources for cognitive outcomes later in life. RESEARCH DESIGN AND METHODS: Using data from 11 countries included in the Survey of Health, Ageing, and Retirement in Europe (SHARE) data set (N = 32,783), multistate survival models (MSMs) were fit to examine the importance of access to reading material in childhood on transitions through cognitive status categories (no cognitive impairment and impaired cognitive functioning) and death. Additionally, using the transition probabilities estimated by the MSMs, we estimated the remaining years of life without cognitive impairment and total longevity. All models were fit individually in each country, as well as within the pooled SHARE sample. RESULTS: Adjusting for age, sex, education, and childhood socioeconomic status, the overall pooled estimate indicated that access to more books at age 10 was associated with a decreased risk of developing cognitive impairment (adjusted hazard ratio = 0.79, confidence interval: 0.76-0.82). Access to childhood books was not associated with risk of transitioning from normal cognitive functioning to death, or from cognitive impairment to death. Total longevity was similar between participants reporting high (+1 standard deviation [SD]) and low (-1 SD) number of books in the childhood home; however, individuals with more access to childhood books lived a greater proportion of this time without cognitive impairment. DISCUSSION AND IMPLICATIONS: Findings suggest that access to cognitive resources in childhood is protective for cognitive aging processes in older adulthood.

Chlorite (C)-corrensite (Co)-smectite (S) seriesminerals occur as vein constituents in the two epithermal ore veins, the Chuetsu and Shuetsu veins of the Todoroki Au-Ag deposit. The characteristics of the C-Co-S seriesminerals indicate that the clays may be products of direct precipitation from hydrothermal fluids and subsequent mineralogical transformations during and/or after vein formation. The minerals from the Chuetsu vein are characterized by 'monomineralic' corrensite showing an extensive distribution throughout the vein, and trioctahedral smectite occurring locally. The Shuetsu vein minerals are characterized by C-Co series minerals which can be divided into three different types: a I type including discrete chlorite with minor amounts of S layers, a II type comprising interstratified C/Co and discrete chlorite, and a III type characterized by segregation structures of C and Co layers. The C-Co series minerals show slightly different spatial distributions in the Shuetsu vein. Different epithermal environments during the vein formations and possible kinetic effects may have played a role in the formation and conversion of Co-C series at the Shuetsu vein and S-Co series at the Chuetsu vein.

Chlorite (C)-corrensite (Co)-smectite (S) seriesminerals occur as vein constituents in the two epithermal ore veins, the Chuetsu and Shuetsu veins of the Todoroki Au-Ag deposit. The characteristics of the C-Co-S seriesminerals indicate that the clays may be products of direct precipitation from hydrothermal fluids and subsequent mineralogical transformations during and/or after vein formation. The minerals from the Chuetsu vein are characterized by 'monomineralic' corrensite showing an extensive distribution throughout the vein, and trioctahedral smectite occurring locally. The Shuetsu vein minerals are characterized by C-Co series minerals which can be divided into three different types: a I type including discrete chlorite with minor amounts of S layers, a II type comprising interstratified C/Co and discrete chlorite, and a III type characterized by segregation structures of C and Co layers. The C-Co series minerals show slightly different spatial distributions in the Shuetsu vein. Different epithermal environments during the vein formations and possible kinetic effects may have played a role in the formation and conversion of Co-C series at the Shuetsu vein and S-Co series at the Chuetsu vein.

The marked biogeographic difference between western (Malay Peninsula and Sumatra) and eastern (Borneo) Sundaland is surprising given the long time that these areas have formed a single landmass. A dispersal barrier in the form of a dry savanna corridor during glacial maxima has been proposed to explain this disparity. However, the short duration of these dry savanna conditions make it an unlikely sole cause for the biogeographic pattern. An additional explanation might be related to the coarse sandy soils of central Sundaland. To test these two nonexclusive hypotheses, we performed a floristic cluster analysis based on 111 tree inventories from Peninsular Malaysia, Sumatra, and Borneo. We then identified the indicator genera for clusters that crossed the central Sundaland biogeographic boundary and those that did not cross and tested whether drought and coarse-soil tolerance of the indicator genera differed between them. We found 11 terminal floristic clusters, 10 occurring in Borneo, 5 in Sumatra, and 3 in Peninsular Malaysia. Indicator taxa of clusters that occurred across Sundaland had significantly higher coarse-soil tolerance than did those from clusters that occurred east or west of central Sundaland. For drought tolerance, no such pattern was detected. These results strongly suggest that exposed sandy sea-bed soils acted as a dispersal barrier in central Sundaland. However, we could not confirm the presence of a savanna corridor. This finding makes it clear that proposed biogeographic explanations for plant and animal distributions within Sundaland, including possible migration routes for early humans, need to be reevaluated.

The Sox9 transcription factor plays an essential role in promoting chondrogenesis and regulating expression of chondrocyte extracellular-matrix genes. To identify genes that interact with Sox9 in promoting chondrocyte differentiation, we screened a cDNA library generated from the murine chondrogenic ATDC5 cell line to identify activators of the collagen, type II, alpha 1 (Col2a1) promoter. Here we have shown that paraspeckle regulatory protein 54-kDa nuclear RNA-binding protein (p54nrb) is an essential link between Sox9-regulated transcription and maturation of Sox9-target gene mRNA. We found that p54nrb physically interacted with Sox9 and enhanced Sox9-dependent transcriptional activation of the Col2a1 promoter. In ATDC5 cells, p54nrb colocalized with Sox9 protein in nuclear paraspeckle bodies, and knockdown of p54nrb suppressed Sox9-dependent Col2a1 expression and promoter activity. We generated a p54nrb mutant construct lacking RNA recognition motifs, and overexpression of mutant p54nrb in ATDC5 cells markedly altered the appearance of paraspeckle bodies and inhibited the maturation of Col2a1 mRNA. The mutant p54nrb inhibited chondrocyte differentiation of mesenchymal cells and mouse metatarsal explants. Furthermore, transgenic mice expressing the mutant p54nrb in the chondrocyte lineage exhibited dwarfism associated with impairment of chondrogenesis. These data suggest that p54nrb plays an important role in the regulation of Sox9 function and the formation of paraspeckle bodies during chondrogenesis.

In this paper we extend HOTL (Hypotheses and Observations Testing Logic) to provide a formal framework to test timed systems. The main idea underlying HOTL is to infer whether a set of observations (i.e., results of test applications) allows to claim that the IUT conforms to the specification if a specific set of hypotheses is assumed. In this paper we adapt HOTL to cope with the inclusion of time issues. In addition, we show the soundness and completeness of the new framework, that we call THOTL, with respect to a general notion of timed conformance.

Cell biology

c-src deletion in mice leads to osteopetrosis as a result of reduced bone resorption due to an alteration of the osteoclast. We report that deletion/reduction of Src expression enhances osteoblast differentiation and bone formation, contributing to the increase in bone mass. Bone histomorphometry showed that bone formation was increased in Src null compared with wild-type mice. In vitro, alkaline phosphatase (ALP) activity and nodule mineralization were increased in primary calvarial cells and in SV40-immortalized osteoblasts from Src(-/-) relative to Src(+/+) mice. Src-antisense oligodeoxynucleotides (AS-src) reduced Src levels by approximately 60% and caused a similar increase in ALP activity and nodule mineralization in primary osteoblasts in vitro. Reduction in cell proliferation was observed in primary and immortalized Src(-/-) osteoblasts and in normal osteoblasts incubated with the AS-src. Semiquantitative reverse transcriptase-PCR revealed upregulation of ALP, Osf2/Cbfa1 transcription factor, PTH/PTHrP receptor, osteocalcin, and pro-alpha 2(I) collagen in Src-deficient osteoblasts. The expression of the bone matrix protein osteopontin remained unchanged. Based on these results, we conclude that the reduction of Src expression not only inhibits bone resorption, but also stimulates osteoblast differentiation and bone formation, suggesting that the osteogenic cells may contribute to the development of the osteopetrotic phenotype in Src-deficient mice.