Structure of the TPR Domain of AIP: Lack of Client Protein Interaction with the C-Terminal alpha-7 Helix of the TPR Domain of AIP Is Sufficient for Pituitary Adenoma Predisposition

PMCID: PMC3534021This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited

Neuroinflammation, Mast Cells, and Glia: Dangerous Liaisons

The perspective of neuroinflammation as an epiphenomenon following neuron damage is being replaced by the awareness of glia and their importance in neural functions and disorders. Systemic inflammation generates signals that communicate with the brain and leads to changes in metabolism and behavior, with microglia assuming a pro-inflammatory phenotype. Identification of potential peripheral-to-central cellular links is thus a critical step in designing effective therapeutics. Mast cells may fulfill such a role. These resident immune cells are found close to and within peripheral nerves and in brain parenchyma/meninges, where they exercise a key role in orchestrating the inflammatory process from initiation through chronic activation. Mast cells and glia engage in crosstalk that contributes to accelerate disease progression; such interactions become exaggerated with aging and increased cell sensitivity to stress. Emerging evidence for oligodendrocytes, independent of myelin and support of axonal integrity, points to their having strong immune functions, innate immune receptor expression, and production/response to chemokines and cytokines that modulate immune responses in the central nervous system while engaging in crosstalk with microglia and astrocytes. In this review, we summarize the findings related to our understanding of the biology and cellular signaling mechanisms of neuroinflammation, with emphasis on mast cell-glia interactions

Lighting and perceptual cues: Effects on gait measures of older adults at high and low risk for falls

<p>Abstract</p> <p>Background</p> <p>The visual system plays an important role in maintaining balance. As a person ages, gait becomes slower and stride becomes shorter, especially in dimly lighted environments. Falls risk has been associated with reduced speed and increased gait variability.</p> <p>Methods</p> <p>Twenty-four older adults (half identified at risk for falls) experienced three lighting conditions: pathway illuminated by 1) general ceiling-mounted fixtures, 2) conventional plug-in night lights and 3) plug-in night lights supplemented by laser lines outlining the pathway. Gait measures were collected using the GAITRite^©walkway system.</p> <p>Results</p> <p>Participants performed best under the general ceiling-mounted light system and worst under the night light alone. The pathway plus night lights increased gait velocity and reduced step length variability compared to the night lights alone in those at greater risk of falling.</p> <p>Conclusions</p> <p>Practically, when navigating in more challenging environments, such as in low-level ambient illumination, the addition of perceptual cues that define the horizontal walking plane can potentially reduce falls risks in older adults.</p

Parent-of-origin-specific allelic associations among 106 genomic loci for age at menarche.

Age at menarche is a marker of timing of puberty in females. It varies widely between individuals, is a heritable trait and is associated with risks for obesity, type 2 diabetes, cardiovascular disease, breast cancer and all-cause mortality. Studies of rare human disorders of puberty and animal models point to a complex hypothalamic-pituitary-hormonal regulation, but the mechanisms that determine pubertal timing and underlie its links to disease risk remain unclear. Here, using genome-wide and custom-genotyping arrays in up to 182,416 women of European descent from 57 studies, we found robust evidence (P < 5 × 10(-8)) for 123 signals at 106 genomic loci associated with age at menarche. Many loci were associated with other pubertal traits in both sexes, and there was substantial overlap with genes implicated in body mass index and various diseases, including rare disorders of puberty. Menarche signals were enriched in imprinted regions, with three loci (DLK1-WDR25, MKRN3-MAGEL2 and KCNK9) demonstrating parent-of-origin-specific associations concordant with known parental expression patterns. Pathway analyses implicated nuclear hormone receptors, particularly retinoic acid and γ-aminobutyric acid-B2 receptor signalling, among novel mechanisms that regulate pubertal timing in humans. Our findings suggest a genetic architecture involving at least hundreds of common variants in the coordinated timing of the pubertal transition

New genetic loci implicated in fasting glucose homeostasis and their impact on type 2 diabetes risk.

Levels of circulating glucose are tightly regulated. To identify new loci influencing glycemic traits, we performed meta-analyses of 21 genome-wide association studies informative for fasting glucose, fasting insulin and indices of beta-cell function (HOMA-B) and insulin resistance (HOMA-IR) in up to 46,186 nondiabetic participants. Follow-up of 25 loci in up to 76,558 additional subjects identified 16 loci associated with fasting glucose and HOMA-B and two loci associated with fasting insulin and HOMA-IR. These include nine loci newly associated with fasting glucose (in or near ADCY5, MADD, ADRA2A, CRY2, FADS1, GLIS3, SLC2A2, PROX1 and C2CD4B) and one influencing fasting insulin and HOMA-IR (near IGF1). We also demonstrated association of ADCY5, PROX1, GCK, GCKR and DGKB-TMEM195 with type 2 diabetes. Within these loci, likely biological candidate genes influence signal transduction, cell proliferation, development, glucose-sensing and circadian regulation. Our results demonstrate that genetic studies of glycemic traits can identify type 2 diabetes risk loci, as well as loci containing gene variants that are associated with a modest elevation in glucose levels but are not associated with overt diabetes

Psychological correlates of self-reported functional limitation in patients with ankylosing spondylitis

Abstract Introduction Functional status is an integral component of health-related quality of life in patients with ankylosing spondylitis (AS). The purpose of this study was to investigate the role of psychological variables in self-reported functional limitation in patients with AS, while controlling for demographic and medical variables. Methods 294 AS patients meeting modified New York Criteria completed psychological measures evaluating depression, resilience, active and passive coping, internality and helplessness at the baseline visit. Demographic, clinical, and radiologic data were also collected. Univariate and multivariate analyses were completed to determine the strength of correlation of psychological variables with functional limitation, as measured by the Bath AS Functional Index (BASFI). Results In the multivariate regression analysis, the psychological variables contributed significantly to the variance in BASFI scores, adding an additional 24% to the overall R-square beyond that accounted by demographic and medical variables (R-square 32%), resulting in a final R-square of 56%. Specifically, arthritis helplessness, depression and passive coping beside age, ESR and the Bath AS Radiograph Index accounted for a significant portion of the variance in BASFI scores in the final model. Conclusions Arthritis helplessness, depression, and passive coping accounted for significant variability in self-reported functional limitation beyond demographic and clinical variables in patients with AS. Psychological health should be examined and accounted for when assessing functional status in the AS patients

Controlled Radical Polymerization of Vinyl Acetate Mediated by a Bis(imino)pyridine Vanadium Complex

Source type: Prin

Can we predict Λ\Lambda for the Non-SUSY sector of the Landscape ?

We propose a new selection criteria for predicting the most probable wavefunction of the universe that propagates on the string landscape background, by studying its dynamics from a quantum cosmology view. Previously we applied this proposal to the $SUSY$ sector of the landscape. In this work the dynamic selection criterion is applied to the investigation of the non-$SUSY$ sector.In the absence of detailed information about its structure, it is assumed that this sector has a stochastic distribution of vacua energies.The calculation of a distribution probability for the cosmological constants $\Lambda_{eff}$, obtained from the density of states $\rho$, indicates that the most probable wavefunction is peaked around universes with zero $\Lambda_{eff}$. In contrast to the {\it extended wavefunction} solutions found for the $SUSY$ sector with $N$-vacua and peaked around $\Lambda_{eff}\simeq \frac{1}{N^2}$, wavefunctions residing on the non-$SUSY$ sector exhibit {\it Anderson localization}.Although minisuperspace is a limited approach it presently provides a dynamical quantum selection rule for the most probable vacua solution from the landscape.Comment: 6 pages, 1 figur