Distinguishing G_2-manifolds

In this survey, we describe invariants that can be used to distinguish connected components of the moduli space of holonomy G_2 metrics on a closed 7-manifold, or to distinguish G_2-manifolds that are homeomorphic but not diffeomorphic. We also describe the twisted connected sum and extra-twisted connected sum constructions used to realise G_2-manifolds for which the above invariants differ.Comment: 22 pages, 5 figures. To appear in a forthcoming volume of the Fields Institute Communications, entitled "Lectures and Surveys on G2 manifolds and related topics

Effect of bio-engineering on size, shape, composition and rigidity of bacterial microcompartments

Bacterial microcompartments (BMCs) are proteinaceous organelles that are found in a broad range of bacteria and are composed of an outer shell that encases an enzyme cargo representing a specific metabolic process. The outer shell is made from a number of different proteins that form hexameric and pentameric tiles, which interact to allow the formation of a polyhedral edifice. We have previously shown that the Citrobacter freundii BMC associated with 1,2-propanediol utilization can be transferred into Escherichia coli to generate a recombinant BMC and that empty BMCs can be formed from just the shell proteins alone. Herein, a detailed structural and proteomic characterization of the wild type BMC is compared to the recombinant BMC and a number of empty BMC variants by 2D-gel electrophoresis, mass spectrometry, transmission electron microscopy (TEM) and atomic force microscopy (AFM). Specifically, it is shown that the wild type BMC and the recombinant BMC are similar in terms of composition, size, shape and mechanical properties, whereas the empty BMC variants are shown to be smaller, hollow and less malleable

Regulation of mammary gland branching morphogenesis by the extracellular matrix and its remodeling enzymes.

A considerable body of research indicates that mammary gland branching morphogenesis is dependent, in part, on the extracellular matrix (ECM), ECM-receptors, such as integrins and other ECM receptors, and ECM-degrading enzymes, including matrix metalloproteinases (MMPs) and their inhibitors, tissue inhibitors of metalloproteinases (TIMPs). There is some evidence that these ECM cues affect one or more of the following processes: cell survival, polarity, proliferation, differentiation, adhesion, and migration. Both three-dimensional culture models and genetic manipulations of the mouse mammary gland have been used to study the signaling pathways that affect these processes. However, the precise mechanisms of ECM-directed mammary morphogenesis are not well understood. Mammary morphogenesis involves epithelial 'invasion' of adipose tissue, a process akin to invasion by breast cancer cells, although the former is a highly regulated developmental process. How these morphogenic pathways are integrated in the normal gland and how they become dysregulated and subverted in the progression of breast cancer also remain largely unanswered questions

T-Analyst: a program for efficient analysis of protein conformational changes by torsion angles

T-Analyst is a user-friendly computer program for analyzing trajectories from molecular modeling. Instead of using Cartesian coordinates for protein conformational analysis, T-Analyst is based on internal bond-angle-torsion coordinates in which internal torsion angle movements, such as side-chain rotations, can be easily detected. The program computes entropy and automatically detects and corrects angle periodicity to produce accurate rotameric states of dihedrals. It also clusters multiple conformations and detects dihedral rotations that contribute hinge-like motions. Correlated motions between selected dihedrals can also be observed from the correlation map. T-Analyst focuses on showing changes in protein flexibility between different states and selecting representative protein conformations for molecular docking studies. The program is provided with instructions and full source code in Perl

Comparative analysis of carboxysome shell proteins

Carboxysomes are metabolic modules for CO2 fixation that are found in all cyanobacteria and some chemoautotrophic bacteria. They comprise a semi-permeable proteinaceous shell that encapsulates ribulose-1,5-bisphosphate carboxylase/oxygenase (RuBisCO) and carbonic anhydrase. Structural studies are revealing the integral role of the shell protein paralogs to carboxysome form and function. The shell proteins are composed of two domain classes: those with the bacterial microcompartment (BMC; Pfam00936) domain, which oligomerize to form (pseudo)hexamers, and those with the CcmL/EutN (Pfam03319) domain which form pentamers in carboxysomes. These two shell protein types are proposed to be the basis for the carboxysome’s icosahedral geometry. The shell proteins are also thought to allow the flux of metabolites across the shell through the presence of the small pore formed by their hexameric/pentameric symmetry axes. In this review, we describe bioinformatic and structural analyses that highlight the important primary, tertiary, and quaternary structural features of these conserved shell subunits. In the future, further understanding of these molecular building blocks may provide the basis for enhancing CO2 fixation in other organisms or creating novel biological nanostructures

Internal and external forcing of multidecadal Atlantic climate variability over the past 1,200 years

The North Atlantic experiences climate variability on multidecadal scales, which is sometimes referred to as Atlantic multidecadal variability. However, the relative contributions of external forcing such as changes in solar irradiance or volcanic activity and internal dynamics to these variations are unclear. Here we provide evidence for persistent summer Atlantic multidecadal variability from AD 800 to 2010 using a network of annually resolved terrestrial proxy records from the circum-North Atlantic region. We find that large volcanic eruptions and solar irradiance minima induce cool phases of Atlantic multidecadal variability and collectively explain about 30% of the variance in the reconstruction on timescales greater than 30 years. We are then able to isolate the internally generated component of Atlantic multidecadal variability, which we define as the Atlantic multidecadal oscillation. We find that the Atlantic multidecadal oscillation is the largest contributor to Atlantic multidecadal variability over the past 1,200 years. We also identify coherence between the Atlantic multidecadal oscillation and Northern Hemisphere temperature variations, leading us to conclude that the apparent link between Atlantic multidecadal variability and regional to hemispheric climate does not arise solely from a common response to external drivers, and may instead reflect dynamic processes

Effect of protocatechuic acid on insulin responsiveness and inflammation in visceral adipose tissue from obese individuals: possible role for PTP1B

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Increased masticatory activity and quality of life in elderly persons with dementia-a longitudinal matched cluster randomized single-blind multicenter intervention study.

Background: Worldwide, millions of people are suffering from dementia and this number is rising. An index of quality of life (QoL) can describe the impact a disease or treatment has on a person's wellbeing. QoL comprises many variables, including physical health and function, and mental health and function. QoL is related to masticatory ability and physical activity. Animal studies show that disruption of mastication due to loss of teeth or a soft diet leads to memory loss and learning problems. Since these are common complaints in dementia, it is hypothesized that improvement of masticatory function and normalization of diet consistency can increase QoL in elderly persons suffering from dementia. Therefore, the goal of the present study is to examine whether an increase in masticatory activity, achieved by increased food consistency and enhancement of masticatory function through improved oral health care has a positive effect on QoL, including cognition, mood, activities of daily living (ADL), and circadian rhythm in elderly persons with dementia.Methods and design: The described study is a prospective longitudinal matched cluster randomized single-blind multicenter study. Participants are elderly persons living in the Netherlands, suffering from dementia and receiving psychogeriatric care. An intervention group will receive improved oral health care and a diet of increased consistency. A control group receives care as usual. Participants will be assessed four times; outcome variables besides QoL are cognition, mood, independence, rest-activity rhythm, blood pressure, and masticatory function.Discussion: This research protocol investigates the effect of an intervention executed by daily caregivers. The intervention will increase masticatory activity, which is achieved by three different actions, (providing oral health care, increasing food consistency, or a combination of both). There is a certain amount of variety in the nature of the interventions due to local differences in nursing homes. This might be a scientific weakness in the study design; however, a practical implementation of any findings will be subject to the same factors, making this study design clinically relevant.Trial registration: NTR1561. © 2013 Weijenberg et al.; licensee BioMed Central Ltd

Fine-Scale Phylogeographic Structure of Borrelia lusitaniae Revealed by Multilocus Sequence Typing

Borrelia lusitaniae is an Old World species of the Lyme borreliosis (LB) group of tick-borne spirochetes and prevails mainly in countries around the Mediterranean Basin. Lizards of the family Lacertidae have been identified as reservoir hosts of B. lusitaniae. These reptiles are highly structured geographically, indicating limited migration. In order to examine whether host geographic structure shapes the evolution and epidemiology of B. lusitaniae, we analyzed the phylogeographic population structure of this tick-borne bacterium using a recently developed multilocus sequence typing (MLST) scheme based on chromosomal housekeeping genes. A total of 2,099 questing nymphal and adult Ixodes ricinus ticks were collected in two climatically different regions of Portugal, being ∼130 km apart. All ticks were screened for spirochetes by direct PCR. Attempts to isolate strains yielded 16 cultures of B. lusitaniae in total. Uncontaminated cultures as well as infected ticks were included in this study. The results using MLST show that the regional B. lusitaniae populations constitute genetically distinct populations. In contrast, no clear phylogeographic signals were detected in sequences of the commonly used molecular markers ospA and ospC. The pronounced population structure of B. lusitaniae over a short geographic distance as captured by MLST of the housekeeping genes suggests that the migration rates of B. lusitaniae are rather low, most likely because the distribution of mediterranean lizard populations is highly parapatric. The study underlines the importance of vertebrate hosts in the geographic spread of tick-borne microparasites

Dimensional and hierarchical models of depression using the Beck Depression Inventory-II in an Arab college student sample

Abstract Background An understanding of depressive symptomatology from the perspective of confirmatory factor analysis (CFA) could facilitate valid and interpretable comparisons across cultures. The objectives of the study were: (i) using the responses of a sample of Arab college students to the Beck Depression Inventory (BDI-II) in CFA, to compare the "goodness of fit" indices of the original dimensional three-and two-factor first-order models, and their modifications, with the corresponding hierarchical models (i.e., higher - order and bifactor models); (ii) to assess the psychometric characteristics of the BDI-II, including convergent/discriminant validity with the Hopkins Symptom Checklist (HSCL-25). Method Participants (N = 624) were Kuwaiti national college students, who completed the questionnaires in class. CFA was done by AMOS, version 16. Eleven models were compared using eight "fit" indices. Results In CFA, all the models met most "fit" criteria. While the higher-order model did not provide improved fit over the dimensional first - order factor models, the bifactor model (BFM) had the best fit indices (CMNI/DF = 1.73; GFI = 0.96; RMSEA = 0.034). All regression weights of the dimensional models were significantly different from zero (P Conclusion The broadly adequate fit of the various models indicates that they have some merit and implies that the relationship between the domains of depression probably contains hierarchical and dimensional elements. The bifactor model is emerging as the best way to account for the clinical heterogeneity of depression. The psychometric characteristics of the BDI-II lend support to our CFA results.</p