Imaging local genetic influences on cortical folding

Recent progress in deciphering mechanisms of human brain cortical folding leave unexplained whether spatially patterned genetic influences contribute to this folding. High-resolution in vivo brain MRI can be used to estimate genetic correlations (covariability due to shared genetic factors) in interregional cortical thickness, and biomechanical studies predict an influence of cortical thickness on folding patterns. However, progress has been hampered because shared genetic influences related to folding patterns likely operate at a scale that is much more local (cm) than that addressed in prior imaging studies. Here, we develop methodological approaches to examine local genetic influences on cortical thickness and apply these methods to two large, independent samples. We find that such influences are markedly heterogeneous in strength, and in some cortical areas are notably stronger in specific orientations relative to gyri or sulci. The overall, phenotypic local correlation has a significant basis in shared genetic factors and is highly symmetric between left and right cortical hemispheres. Furthermore, the degree of local cortical folding relates systematically with the strength of local correlations, which tends to be higher in gyral crests and lower in sulcal fundi. The relationship between folding and local correlations is stronger in primary sensorimotor areas and weaker in association areas such as prefrontal cortex, consistent with reduced genetic constraints on the structural topology of association cortex. Collectively, our results suggest that patterned genetic influences on cortical thickness, measurable at the scale of in vivo MRI, may be a causal factor in the development of cortical folding

Overexpression of LCMR1 is significantly associated with clinical stage in human NSCLC

<p>Abstract</p> <p>Background</p> <p>Lung cancer is one of the most common human cancers and the leading cause of cancer death worldwide. The identification of lung cancer associated genes is essential for lung cancer diagnosis and treatment.</p> <p>Methods</p> <p>Differential Display-PCR technique was used to achieve the novel cDNA, which were then verified by real-time PCR. Northern blot was utilized to observe the expression of LCMR1 in different human tissues. 84 cases human NSCLC tissues and normal counterparts were analyzed for the expression of LCMR1 by immunohistochemistry.</p> <p>Results</p> <p>A novel 778-bp cDNA fragment from human large cell lung carcinoma cell lines 95C and 95D was obtained, and named <it>LCMR1 </it>(Lung Cancer Metastasis Related protein 1). LCMR1 was differentially expressed in different human tissues. LCMR1 was strongly overexpressed in NSCLC and its expression was significantly associated with clinical stage.</p> <p>Conclusion</p> <p>Our data indicated that <it>LCMR1</it>, strongly overexpressed in NSCLC, might have applications in the clinical diagnosis and treatment of lung cancer.</p

A global multiproxy database for temperature reconstructions of the Common Era

Reproducible climate reconstructions of the Common Era (1 CE to present) are key to placing industrial-era warming into the context of natural climatic variability. Here we present a community-sourced database of temperature- sensitive proxy records from the PAGES2k initiative. The database gathers 692 records from 648 locations, including all continental regions and major ocean basins. The records are from trees, ice, sediment, corals, speleothems, documentary evidence, and other archives. They range in length from 50 to 2000 years, with a median of 547 years, while temporal resolution ranges from biweekly to centennial. Nearly half of the proxy time series are significantly correlated with HadCRUT4.2 surface temperature over the period 1850–2014. Global temperature composites show a remarkable degree of coherence between high- and low-resolution archives, with broadly similar patterns across archive types, terrestrial versus marine locations, and screening criteria. The database is suited to investigations of global and regional temperature variability over the Common Era, and is shared in the Linked Paleo Data (LiPD) format, including serializations in Matlab, R and Python

European summer temperatures since Roman times

The spatial context is critical when assessing present-day climate anomalies, attributing them to potential forcings and making statements regarding frequency and severity in the long-term perspective. Recent initiatives have expanded the number of high-quality proxy-records and developed new reconstruction methods. These advances allow more rigorous regional past temperature reconstructions and the possibility of evaluating climate models on policy-relevant, spatio-temporal scales. We provide a new proxy-based, annually-resolved, spatial reconstruction of the European summer temperature fields back to 755 CE based on a Bayesian hierarchical modelling (BHM), together with estimates of the European mean temperature variation since 138 BCE based on Composite-plus-Scaling. Our reconstructions compare well with independent instrumental and proxy-based temperature estimates, but suggest a larger amplitude in summer temperature variability than previously reported. Temperature differences between the medieval period, the recent period and Little Ice Age are larger in reconstructions than simulations. This may indicate either inflated variability of the reconstructions, a lack of sensitivity to external forcing on sub-hemispheric scales in the climate models and/or an underestimation of internal variability on centennial and longer time scales including the representation of internal feedback mechanisms

Lineage-specific dynamic and pre-established enhancer–promoter contacts cooperate in terminal differentiation

Chromosome conformation is an important feature of metazoan gene regulation; however, enhancer–promoter contact remodeling during cellular differentiation remains poorly understood. To address this, genome-wide promoter capture Hi-C (CHi-C) was performed during epidermal differentiation. Two classes of enhancer–promoter contacts associated with differentiation-induced genes were identified. The first class ('gained') increased in contact strength during differentiation in concert with enhancer acquisition of the H3K27ac activation mark. The second class ('stable') were pre-established in undifferentiated cells, with enhancers constitutively marked by H3K27ac. The stable class was associated with the canonical conformation regulator cohesin, whereas the gained class was not, implying distinct mechanisms of contact formation and regulation. Analysis of stable enhancers identified a new, essential role for a constitutively expressed, lineage-restricted ETS-family transcription factor, EHF, in epidermal differentiation. Furthermore, neither class of contacts was observed in pluripotent cells, suggesting that lineage-specific chromatin structure is established in tissue progenitor cells and is further remodeled in terminal differentiation

Is time-variant information stickiness state-dependent?

This paper estimates information stickiness with regard to inflation expectations in the United States and the Eurozone for the 1981/06–2015/12 and 1998/Q4–2015/Q2 periods, respectively, and further investigates whether such information stickiness is state- dependent. Based on a bootstrap sub-sample rolling-window estimation, we find that information stickiness varies over time, which contradicts the strict time dependency implied under sticky-information theory. We provide evidence that information stickiness depends on inflation volatility, which indicates that information stickiness is state-dependent and that it has a time trend. Using a threshold model, we estimate structural changes in the state- dependence and time-trend of information stickiness. The results show that information stickiness has been more dependent on inflation volatility and has had a higher time-trend in both regions following the 2008 financial crisis.info:eu-repo/semantics/publishedVersio