Precuneus contributes to attentive control of finger movement

AIM: To examine whether precuneus subserves the attentive control of finger movement or whether it mediates the movement preparation and motor inhibition. METHODS: In the Preparation Stage, subjects were shown with a 5-number string in which each number stood for a key-pressing response, the number strings included a complex pattern (eg, 4-1-4-2-3), or a simple one (eg, 2-2-2-2-2), or a null one (ie, x-x-x-x-x). In the Execution Stage, five reaction signs were presented one by one and subjects were required to press the corresponding key to each sign sequentially (eg, in the 4-1-4-2-3 preparation example, subjects press key 4 to the first sign, press key 1 to the second sign, key 4 to the third sign and so on). For the null preparation pattern, five numbers, rather than the reaction signs, were shown at the same pace as in the other two conditions and subjects were to press the corresponding keys. RESULTS: Left medial frontal gyrus (BA 6) and precentral gyrus (BA 6) were involved in both of the Preparation Stage and the Execution Stage, whereas left precuneus (BA 7) was activated only in the Execution Stage. CONCLUSION: Precuneus mediates the attentive control of finger movement, but not the movement preparation or motor inhibition.AIM: To examine whether precuneus subserves the attentive control of finger movement or whether it mediates the movement preparation and motor inhibition. METHODS: In the Preparation Stage, subjects were shown with a 5-number string in which each number stood for a key-pressing response, the number strings included a complex pattern (eg, 4-1-4-2-3), or a simple one (eg, 2-2-2-2-2), or a null one (ie, x-x-x-x-x). In the Execution. Stage, five reaction signs were presented one by one and subjects were required to press the corresponding key to each sign sequentially (eg, in the 4-1-4-2-3 preparation example, subjects press key 4 to the first sign, press key 1 to the second sign, key 4 to the third sign and so on). For the null preparation pattern, five numbers, rather than the reaction signs, were shown at the same pace as in the other two conditions and subjects were to press the corresponding keys. RESULTS: Left medial frontal gyrus (BA 6) and precentral gyrus (BA 6) were involved in both of the Preparation Stage and the Execution Stage, whereas left precuneus (BA 7) was activated only in the Execution Stage. CONCLUSION: Precuneus mediates the attentive control of finger movement, but not the movement preparation or motor inhibition

Myocardial Autophagy after Severe Burn in Rats

Autophagy plays a major role in myocardial ischemia and hypoxia injury. The present study investigated the effects of autophagy on cardiac dysfunction in rats after severe burn.Protein expression of the autophagy markers LC3 and Beclin 1 were determined at 0, 1, 3, 6, and 12 h post-burn in Sprague Dawley rats subjected to 30% total body surface area 3rd degree burns. Autophagic, apoptotic, and oncotic cell death were evaluated in the myocardium at each time point by immunofluorescence. Changes of cardiac function were measured in a Langendorff model of isolated heart at 6 h post-burn, and the autophagic response was measured following activation by Rapamycin and inhibition by 3-methyladenine (3-MA). The angiotensin converting enzyme inhibitor enalaprilat, the angiotensin receptor I blocker losartan, and the reactive oxygen species inhibitor diphenylene iodonium (DPI) were also applied to the ex vivo heart model to examine the roles of these factors in post-burn cardiac function.Autophagic cell death was first observed in the myocardium at 3 h post-burn, occurring in 0.008 ± 0.001% of total cardiomyocytes, and continued to increase to a level of 0.022 ± 0.005% by 12 h post-burn. No autophagic cell death was observed in control hearts. Compared with apoptosis, autophagic cell death occurred earlier and in larger quantities. Rapamycin enhanced autophagy and decreased cardiac function in isolated hearts 6 h post-burn, while 3-MA exerted the opposite response. Enalaprilat, losartan, and DPI all inhibited autophagy and enhanced heart function.Myocardial autophagy is enhanced in severe burns and autophagic cell death occurred early at 3 h post-burn, which may contribute to post-burn cardiac dysfunction. Angiotensin II and reactive oxygen species may play important roles in this process by regulating cell signaling transduction

Total syntheses of shizukaols A and E

Shizukaols possess a common heptacyclic framework containing more than ten contiguousstereocenters and potential biological activities. Here we report that the total syntheses ofshizukaols A (1)and E(2), two lindenane-type dimers from the Chloranthaceae family, areachieved via a modified biomimetic Diels–Alder reaction. The common crucial biomimetic diene23and ethylene species (6,17) are obtained through either a highlyZ-selective olefination ofα-siloxy ketone with ynolate anions or an intramolecular Horner–Wadsworth–Emmons olefinationfrom commercially available Wieland–Miescher ketone (7). This synthetic approach here opensup practical avenues for the total syntheses of the intriguing Chloranthaceae family members, aswell as the understanding of their relevant biological action in natur

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe