Large temperature drop across the Eocene-Oligocene transition in central North America

The Eocene-Oligocene transition towards a cool climate (approximately 33.5 million years ago) was one of the most pronounced climate events during the Cenozoic era. The marine record of this transition has been extensively studied. However, significantly less research has focused on continental climate change at the time, yielding partly inconsistent results on the magnitude and timing of the changes. Here we use a combination of in vivo stable isotope compositions of fossil tooth enamel with diagenetic stable isotope compositions of fossil bone to derive a high-resolution (about 40,000 years) continental temperature record for the Eocene-Oligocene transition. We find a large drop in mean annual temperature of 8.2 +/- 3.1 degrees C over about 400,000 years, the possibility of a small increase in temperature seasonality, and no resolvable change in aridity across the transition. The large change in mean annual temperature, exceeding changes in sea surface temperatures at comparable latitudes and possibly delayed in time with respect to marine changes by up to 400,000 years, explains the faunal turnover for gastropods, amphibians and reptiles, whereas most mammals in the region were unaffected. Our results are in agreement with modelling studies that attribute the climate cooling at the Eocene-Oligocene transition to a significant drop in atmospheric carbon dioxide concentrations.     

PLA2G6, encoding a phospholipase A2, is mutated in neurodegenerative disorders with high brain iron

Neurodegenerative disorders with high brain iron include Parkinson disease, Alzheimer disease and several childhood genetic disorders categorized as neuroaxonal dystrophies. We mapped a locus for infantile neuroaxonal dystrophy (INAD) and neurodegeneration with brain iron accumulation (NBIA) to chromosome 22q12-q13 and identified mutations in PLA2G6, encoding a calcium-independent group VI phospholipase A2, in NBIA, INAD and the related Karak syndrome. This discovery implicates phospholipases in the pathogenesis of neurodegenerative disorders with iron dyshomeostasis.     

热和声：两种不同声能流，可否作统一的数学处理？

设计每栋建筑的目的在于蔽护人类，使之与外界有所隔离．此外界不仅指气候条件，同时也指人类自身产生的某些现象（如噪声），尽管人类并不喜欢它．适当的建筑设计的基础是这些构成法则的知识，它使人们得以预见热和噪声是如何透过住宅墙体以及有多少数量的热和噪声透过墙体渗入居住空间．这些法则源自两个不同但区别不大的方程．它们都是用来解决相同的物理现象（即散射）的、文中结果表明有可能发展出一种单一的理论来处理这两种物理现象，可从研究频率这一有效反映弹性介质中的物质对压力渡的固有反应的初始差别来着手分析．     

Single-molecule fluorescence reveals sequence-specific misfolding in multidomain proteins

A large range of debilitating medical conditions is linked to protein misfolding, which may compete with productive folding particularly in proteins containing multiple domains. Seventy-five per cent of the eukaryotic proteome consists of multidomain proteins, yet it is not understood how interdomain misfolding is avoided. It has been proposed that maintaining low sequence identity between covalently linked domains is a mechanism to avoid misfolding. Here we use single-molecule F?rster resonance energy transfer to detect and quantify rare misfolding events in tandem immunoglobulin domains from the I band of titin under native conditions. About 5.5 per cent of molecules with identical domains misfold during refolding in vitro and form an unexpectedly stable state with an unfolding half-time of several days. Tandem arrays of immunoglobulin-like domains in humans show significantly lower sequence identity between neighbouring domains than between non-adjacent domains. In particular, the sequence identity of neighbouring domains has been found to be preferentially below 40 per cent. We observe no misfolding for a tandem of naturally neighbouring domains with low sequence identity (24 per cent), whereas misfolding occurs between domains that are 42 per cent identical. Coarse-grained molecular simulations predict the formation of domain-swapped structures that are in excellent agreement with the observed transfer efficiency of the misfolded species. We infer that the interactions underlying misfolding are very specific and result in a sequence-specific domain-swapping mechanism. Diversifying the sequence between neighbouring domains seems to be a successful evolutionary strategy to avoid misfolding in multidomain proteins.     

PML targeting eradicates quiescent leukaemia-initiating cells

The existence of a small population of 'cancer-initiating cells' responsible for tumour maintenance has been firmly demonstrated in leukaemia. This concept is currently being tested in solid tumours. Leukaemia-initiating cells, particularly those that are in a quiescent state, are thought to be resistant to chemotherapy and targeted therapies, resulting in disease relapse. Chronic myeloid leukaemia is a paradigmatic haematopoietic stem cell disease in which the leukaemia-initiating-cell pool is not eradicated by current therapy, leading to disease relapse on drug discontinuation. Here we define the critical role of the promyelocytic leukaemia protein (PML) tumour suppressor in haematopoietic stem cell maintenance, and present a new therapeutic approach for targeting quiescent leukaemia-initiating cells and possibly cancer-initiating cells by pharmacological inhibition of PML.     

Suppression of star formation in early-type galaxies by feedback from supermassive black holes

Detailed high-resolution observations of the innermost regions of nearby galaxies have revealed the presence of supermassive black holes. These black holes may interact with their host galaxies by means of 'feedback' in the form of energy and material jets; this feedback affects the evolution of the host and gives rise to observed relations between the black hole and the host. Here we report observations of the ultraviolet emissions of massive early-type galaxies. We derive an empirical relation for a critical black-hole mass (as a function of velocity dispersion) above which the outflows from these black holes suppress star formation in their hosts by heating and expelling all available cold gas. Supermassive black holes are negligible in mass compared to their hosts but nevertheless seem to play a critical role in the star formation history of galaxies.