Biophysical Modulations of Functional Connectivity

Resting-state low frequency oscillations have been detected in many functional magnetic resonance imaging (MRI) studies and appear to be synchronized between functionally related areas. Converging evidence from MRI and other imaging modalities suggest that this activity has an intrinsic neuronal origin. Multiple consistent networks have been found in large populations, and have been shown to be stable over time. Further, these patterns of functional connectivity have been shown to be altered in healthy controls under various physiological challenges. This review will present the biophysical characterization of functional connectivity, and examine the effects of physical state manipulations (such as anesthesia, fatigue, and aging) in healthy controls.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/90432/1/brain-2E2011-2E0039.pd

Mutations in Membrin/GOSR2 Reveal Stringent Secretory Pathway Demands of Dendritic Growth and Synaptic Integrity.

Mutations in the Golgi SNARE (SNAP [soluble NSF attachment protein] receptor) protein Membrin (encoded by the GOSR2 gene) cause progressive myoclonus epilepsy (PME). Membrin is a ubiquitous and essential protein mediating ER-to-Golgi membrane fusion. Thus, it is unclear how mutations in Membrin result in a disorder restricted to the nervous system. Here, we use a multi-layered strategy to elucidate the consequences of Membrin mutations from protein to neuron. We show that the pathogenic mutations cause partial reductions in SNARE-mediated membrane fusion. Importantly, these alterations were sufficient to profoundly impair dendritic growth in Drosophila models of GOSR2-PME. Furthermore, we show that Membrin mutations cause fragmentation of the presynaptic cytoskeleton coupled with transsynaptic instability and hyperactive neurotransmission. Our study highlights how dendritic growth is vulnerable even to subtle secretory pathway deficits, uncovers a role for Membrin in synaptic function, and provides a comprehensive explanatory basis for genotype-phenotype relationships in GOSR2-PME

Preliminary Evidence for the Cross-Cultural Utility of the Type D Personality Construct in the Ukraine

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Clinical trials update of the European Organization for Research and Treatment of Cancer Breast Cancer Group

The present clinical trial update consists of a review of two of eight current studies (the 10981-22023 AMAROS trial and the 10994 p53 trial) of the European Organization for Research and Treatment of Cancer Breast Cancer Group, as well as a preview of the MIND-ACT trial. The AMAROS trial is designed to prove equivalent local/regional control for patients with proven axillary lymph node metastasis by sentinel node biopsy if treated with axillary radiotherapy instead of axillary lymph node dissection, with reduced morbidity. The p53 trial started to assess the potential predictive value of p53 using a functional assay in yeast in patients with locally advanced/inflammatory or large operable breast cancer prospectively randomised to a taxane regimen versus a nontaxane regimen

Modelling chemistry in the nocturnal boundary layer above tropical rainforest and a generalised effective nocturnal ozone deposition velocity for sub-ppbv NOx conditions

Measurements of atmospheric composition have been made over a remote rainforest landscape. A box model has previously been demonstrated to model the observed daytime chemistry well. However the box model is unable to explain the nocturnal measurements of relatively high [NO] and [O3], but relatively low observed [NO2]. It is shown that a one-dimensional (1-D) column model with simple O3 -NOx chemistry and a simple representation of vertical transport is able to explain the observed nocturnal concentrations and predict the likely vertical profiles of these species in the nocturnal boundary layer (NBL). Concentrations of tracers carried over from the end of the night can affect the atmospheric chemistry of the following day. To ascertain the anomaly introduced by using the box model to represent the NBL, vertically-averaged NBL concentrations at the end of the night are compared between the 1-D model and the box model. It is found that, under low to medium [NOx] conditions (NOx <1 ppbv), a simple parametrisation can be used to modify the box model deposition velocity of ozone, in order to achieve good agreement between the box and 1-D models for these end-of-night concentrations of NOx and O3. This parametrisation would could also be used in global climate-chemistry models with limited vertical resolution near the surface. Box-model results for the following day differ significantly if this effective nocturnal deposition velocity for ozone is implemented; for instance, there is a 9% increase in the following day’s peak ozone concentration. However under medium to high [NOx] conditions (NOx > 1 ppbv), the effect on the chemistry due to the vertical distribution of the species means no box model can adequately represent chemistry in the NBL without modifying reaction rate constants

Holography of AdS vacuum bubbles

We consider the fate of AdS vacua connected by tunneling events. A precise holographic dual of thin-walled Coleman--de Luccia bounces is proposed in terms of Fubini instantons in an unstable CFT. This proposal is backed by several qualitative and quantitative checks, including the precise calculation of the instanton action appearing in evaluating the decay rate. Big crunches manifest themselves as time dependent processes which reach the boundary of field space in a finite time. The infinite energy difference involved is identified on the boundary and highlights the ill-defined nature of the bulk setup. We propose a qualitative scenario in which the crunch is resolved by stabilizing the CFT, so that all attempts at crunching always end up shielded from the boundary by the formation of black hole horizons. In all these well defined bulk processes the configurations have the same asymptotics and are finite energy excitations.Comment: version submitted to journal. Note added referring to previous work on holographic instantons

Using palaeoenvironmental DNA to reconstruct past environments: progress and prospects

Palaeoenvironmental DNA (PalEnDNA) is defined as ancient DNA (aDNA) originating from disseminated genetic material within palaeoenvironmental samples. Sources of PalEnDNA include marine and lake sediments, peat, loess, till, ice, permafrost, palaeosols, coprolites, preserved gut contents, dental calculus, tephras, and soils as well as deposits in caves/rockshelters and at archaeological sites. PalEnDNA analysis provides a relatively new tool for Quaternary and archaeological sciences and its applications have included palaeoenvironmental and palaeodietary reconstructions, testing hypotheses regarding megafaunal extinctions, human–environment interactions, taxonomic studies and studies of DNA damage. Because PalEnDNA samples comprise markedly different materials, and represent wide-ranging depositional and taphonomic contexts, various issues must be addressed to achieve robust, reproducible findings. Such issues include climatic and temporal limitations, the biological origin and state (free versus bound) of PalEnDNA, stratigraphic reliability, sterile sampling, ability to distinguish modern from aDNA signals, DNA damage and PCR amplification, DNA extraction methods, and taxonomic resolution. In this review, we provide a non-specialist introduction to the use of PalEnDNA for Quaternary and archaeological researchers, assess attributes and limitations of this palaeoenvironmental tool, and discuss future prospects of using PalEnDNA to reconstruct past environments

Interferon regulatory factor 8-deficiency determines massive neutrophil recruitment but T cell defect in fast growing granulomas during tuberculosis

Following Mycobacterium tuberculosis (Mtb) infection, immune cell recruitment in lungs is pivotal in establishing protective immunity through granuloma formation and neogenesis of lymphoid structures (LS). Interferon regulatory factor-8 (IRF-8) plays an important role in host defense against Mtb, although the mechanisms driving anti-mycobacterial immunity remain unclear. In this study, IRF-8 deficient mice (IRF-8−/−) were aerogenously infected with a low-dose Mtb Erdman virulent strain and the course of infection was compared with that induced in wild-type (WT-B6) counterparts. Tuberculosis (TB) progression was examined in both groups using pathological, microbiological and immunological parameters. Following Mtb exposure, the bacterial load in lungs and spleens progressed comparably in the two groups for two weeks, after which IRF-8−/− mice developed a fatal acute TB whereas in WT-B6 the disease reached a chronic stage. In lungs of IRF-8−/−, uncontrolled growth of pulmonary granulomas and impaired development of LS were observed, associated with unbalanced homeostatic chemokines, progressive loss of infiltrating T lymphocytes and massive prevalence of neutrophils at late infection stages. Our data define IRF-8 as an essential factor for the maintenance of proper immune cell recruitment in granulomas and LS required to restrain Mtb infection. Moreover, IRF-8−/− mice, relying on a common human and mouse genetic mutation linked to susceptibility/severity of mycobacterial diseases, represent a valuable model of acute TB for comparative studies with chronically-infected congenic WT-B6 for dissecting protective and pathological immune reactions