Immune recognition. A new receptor for beta-glucans.

The carbohydrate polymers known as beta-1,3-d-glucans exert potent effects on the immune system - stimulating antitumour and antimicrobial activity, for example - by binding to receptors on macrophages and other white blood cells and activating them. Although beta-glucans are known to bind to receptors, such as complement receptor 3 (ref. 1), there is evidence that another beta-glucan receptor is present on macrophages. Here we identify this unknown receptor as dectin-1 (ref. 2), a finding that provides new insights into the innate immune recognition of beta-glucans.     

Annealing-induced interfacial toughening using a molecular nanolayer

Self-assembled molecular nanolayers (MNLs) composed of short organic chains and terminated with desired functional groups are attractive for modifying surface properties for a variety of applications. For example, organosilane MNLs are used as lubricants, in nanolithography, for corrosion protection and in the crystallization of biominerals. Recent work has explored uses of MNLs at thin-film interfaces, both as active components in molecular devices, and as passive layers, inhibiting interfacial diffusion, promoting adhesion and toughening brittle nanoporous structures. The relatively low stability of MNLs on surfaces at temperatures above 350-400 degrees C (refs 12, 13), as a result of desorption or degradation, limits the use of surface MNLs in high-temperature applications. Here we harness MNLs at thin-film interfaces at temperatures higher than the MNL desorption temperature to fortify copper-dielectric interfaces relevant to wiring in micro- and nano-electronic devices. Annealing Cu/MNL/SiO2 structures at 400-700 degrees C results in interfaces that are five times tougher than pristine Cu/SiO2 structures, yielding values exceeding approximately 20 J m(-2). Previously, similarly high toughness values have only been obtained using micrometre-thick interfacial layers. Electron spectroscopy of fracture surfaces and density functional theory modelling of molecular stretching and fracture show that toughening arises from thermally activated interfacial siloxane bridging that enables the MNL to be strongly linked to both the adjacent layers at the interface, and suppresses MNL desorption. We anticipate that our findings will open up opportunities for molecular-level tailoring of a variety of interfacial properties, at processing temperatures higher than previously envisaged, for applications where microlayers are not a viable option-such as in nanodevices or in thermally resistant molecular-inorganic hybrid devices.     

Functional specificity of local synaptic connections in neocortical networks

Neuronal connectivity is fundamental to information processing in the brain. Therefore, understanding the mechanisms of sensory processing requires uncovering how connection patterns between neurons relate to their function. On a coarse scale, long-range projections can preferentially link cortical regions with similar responses to sensory stimuli. But on the local scale, where dendrites and axons overlap substantially, the functional specificity of connections remains unknown. Here we determine synaptic connectivity between nearby layer 2/3 pyramidal neurons in vitro, the response properties of which were first characterized in mouse visual cortex in vivo. We found that connection probability was related to the similarity of visually driven neuronal activity. Neurons with the same preference for oriented stimuli connected at twice the rate of neurons with orthogonal orientation preferences. Neurons responding similarly to naturalistic stimuli formed connections at much higher rates than those with uncorrelated responses. Bidirectional synaptic connections were found more frequently between neuronal pairs with strongly correlated visual responses. Our results reveal the degree of functional specificity of local synaptic connections in the visual cortex, and point to the existence of fine-scale subnetworks dedicated to processing related sensory information.     

Mechanisms regulating immune surveillance of cellular stress in cancer

The purpose of this review is to explore immune-mediated mechanisms of stress surveillance in cancer, with particular emphasis on the idea that all cancers have classical hallmarks (Hanahan and Weinberg in Cell 100:57–70, 67; Cell 144:646–674, 68) that could be interrelated. We postulate that hallmarks of cancer associated with cellular stress pathways (Luo et al. in Cell 136:823–837, 101) including oxidative stress, proteotoxic stress, mitotic stress, DNA damage, and metabolic stress could define and modulate the inflammatory component of cancer. As such, the overarching goal of this review is to define the types of cellular stress that cancer cells undergo, and then to explore mechanisms by which immune cells recognize, respond to, and are affected by each stress response.     

Bridging the molecular and biological functions of the oxysterol-binding protein family

Oxysterol-binding protein (OSBP) and OSBP-related proteins (ORPs) constitute a large eukaryotic gene family that transports and regulates the metabolism of sterols and phospholipids. The original classification of the family based on oxysterol-binding activity belies the complex dual lipid-binding specificity of the conserved OSBP homology domain (OHD). Additional protein- and membrane-interacting modules mediate the targeting of select OSBP/ORPs to membrane contact sites between organelles, thus positioning the OHD between opposing membranes for lipid transfer and metabolic regulation. This unique subcellular location, coupled with diverse ligand preferences and tissue distribution, has identified OSBP/ORPs as key arbiters of membrane composition and function. Here, we will review how molecular models of OSBP/ORP-mediated intracellular lipid transport and regulation at membrane contact sites relate to their emerging roles in cellular and organismal functions.     

Robust model rankings of forecasting performance

This paper investigates robust model rankings in out‐of‐sample, short‐horizon forecasting. We provide strong evidence that rolling window averaging consistently produces robust model rankings while improving the forecasting performance of both individual models and model averaging. The rolling window averaging outperforms the (ex post) “optimal” window forecasts in more than 50% of the times across all rolling windows.     

Cryptic and non-cryptic diversity in New Guinea ground snakes of the genus Stegonotus Duméril,Bibron and Duméril, 1854: a description of four new species (Squamata: Colubridae)

ABSTRACT

The island of New Guinea has been identified as biologically megadiverse but many taxa are still poorly known. This is especially the case for many of the island’s snakes, which by their very nature can be difficult to collect and study. Here we examine the phylogenetic and phylogeographic structure of a poorly studied snake genus, Stegonotus, focusing on the species of New Guinea; until now, Stegonotus has never been examined using modern phylogenetic methods. Using molecular data from 49 individuals representing eight of the ten described species, and including all New Guinea taxa, we estimate a multilocus phylogeny and examine population structure to help identify undescribed taxa. We use morphological data from the corresponding museum vouchered specimens (where available) and also examine additional specimens for taxa not included in the molecular data set to determine morphological differences among putative taxa. We find molecular evidence for four new species of Stegonotus, both morphologically obvious and cryptic, and describe them herein. The recognition of these four species indicates that Stegonotus diversity has been previously underestimated and also suggests that there are likely additional undescribed taxa within the genus. These four taxa increase the number of described species by 40% and further confirm New Guinea as the centre of diversity for the genus.

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