Brain Weight and Life-Span in Primate Species

In haplorhine primates (tarsiers, monkeys, apes, and humans), there is a significant correlation between brain weight and maximum life-span when the effect of body size is removed. There is also a significant correlation in haplorhine primates between brain weight and female age at first reproduction. For strepsirhine primates (lorises and lemurs), there are no significant correlations between brain weight and either life-span or female reproductive age when the effect of body size is removed. This lack of correlation in strepsirhine primates may be related to the fact that these primates are nocturnal and/or natives of the island of Madagascar, both of which conditions may reduce competition for resources and predation pressure. These findings suggest that in haplorhine primates the genetic systems controlling brain growth are linked to the systems governing the life cycle so that species with longer cycles have larger brains. When the effect of body weight is removed, leaf-eating haplorhines have significantly smaller brains and shorter lives than haplorhines with other diets. Harem-living haplorhines also have significantly smaller brains and shorter life-spans than troop-living haplorhines when the effect of body weight is removed. We also sought to test the rate-of-living hypothesis by determining whether primates with basal metabolic rates that are higher than would be expected for their body size have shorter maximum life-spans than would be expected for their body size. Metabolic rate is not correlated with life-span or female age at first reproduction when the effect of body size is removed

p58IPK Is an Endogenous Neuroprotectant for Retinal Ganglion Cells

p58IPK is an endoplasmic reticulum (ER)-resident chaperone playing a critical role in facilitating protein folding and protein homeostasis. Previously, we have demonstrated that p58IPK is expressed broadly in retinal neurons including retinal ganglion cells (RGCs) and loss of p58IPK results in age-related RGC degeneration. In the present study, we investigate the role of p58IPK in neuroprotection by in vitro and in vivo studies using primary RGC culture and two well-established disease-relevant RGC injury models: retinal ischemia/reperfusion (I/R) and microbead-induced ocular hypertension. Our results demonstrate that in both in vivo models, p58IPK −/− mice exhibit significantly increased RGC loss compared to wild type (WT) mice. In vitro, p58IPK-deficient RGCs show reduced viability and are more susceptible to cell death induced by the ER stress inducer tunicamycin (TM). Overexpression of p58IPK by adeno-associated virus (AAV) significantly diminishes TM-induced cell death in both WT and p58IPK −/− RGCs. Interestingly, we find that loss of p58IPK leads to reduced mRNA expression, but not the protein level, of mesencephalic astrocyte-derived neurotrophic factor (MANF), a neurotrophic factor that resides in the ER. Treatment with recombinant MANF protein protects R28 retinal neural cells and mouse retinal explants from TM-induced cell death. Taken together, our study suggests that p58IPK functions as an endogenous neuroprotectant for RGCs. The mechanisms underlying p58IPK’s neuroprotective action and the potential interactions between p58IPK and MANF warrant future investigation

Opioid growth factor modulates angiogenesis

AbstractObjective: Induced angiogenesis has recently been attempted as a therapeutic modality in patients with occlusive arterial atherosclerotic disease. We investigated the possible role of endogenous opioids in the modulation of angiogenesis. Methods: Chick chorioallantoic membrane was used as an in vivo model to study angiogenesis. Fertilized chick eggs were incubated for 3 days, explanted, and incubated for an additional 2 days. Three-millimeter methylcellulose disks were placed on the surface of the chorioallantoic membrane; each disk contained opioid growth factor ([Met5]-enkephalin; 5 μg), the short-acting opioid receptor antagonist naloxone (5 μg), opioid growth factor and naloxone together (5 μg of each), the long-acting opioid antagonist naltrexone (5 μg), or distilled water (control). A second series of experiments was performed with distilled water, the angiogenic inhibitor retinoic acid (1 μg), and vascular endothelial growth factor (1 μg) to further evaluate our model. The developing vasculature was imaged 2 days later with a digital camera and exported to a computer for image analysis. Total number of blood vessels, total vessel length, and mean vessel length were measured within a 100-mm2 region surrounding each applied disk. Immunocytochemical analysis was performed with antibodies directed against opioid growth factor and its receptor (OGFr). Results: Opioid growth factor had a significant inhibitory effect on angiogenesis, both the number of blood vessels and the total vessel length being decreased (by 35% and 20%, respectively) in comparison with control levels (P <.005). The simultaneous addition of naloxone and opioid growth factor had no effect on blood vessel growth, nor did naloxone alone. Chorioallantoic membranes exposed to naltrexone displayed increases of 51% and 24% in blood vessel number and length, respectively, in comparison with control specimens (P <.005). These results indicate that the opioid growth factor effects are receptor mediated and tonically active. Immunocytochemistry demonstrated the presence of both opioid growth factor and OGFr within the endothelial cells and mesenchymal cells of the developing chorioallantoic membrane vessel wall. Retinoic acid significantly reduced the number and the total length of blood vessels, whereas vascular endothelial growth factor increased both the number and the length of blood vessels in comparison with the controls (P <.0001). The magnitude of opioid growth factor's effects were comparable to those seen with retinoic acid, whereas inhibition of opioid growth factor with naltrexone induced an increase in total vessel length comparable to that for vascular endothelial growth factor. Conclusions: These results demonstrate for the first time that endogenous opioids modulate in vivo angiogenesis. Opioid growth factor is a tonically active peptide that has a receptor-mediated action in regulating angiogenesis in developing endothelial and mesenchymal vascular cells. (J Vasc Surg 2000;32:364-73.

A Descriptive, Multiyear Examination of Positive Behavior Support

A major goal of positive behavior support (PBS) is to produce broad-based, long-term improvements in adaptive behavior; however, the empirical base, at present, is mainly composed of relatively short-term studies carried out in circumscribed contexts. Therefore, a need exists for reliable data that can inform the field regarding the comprehensive lifestyle effects of PBS implementation in natural community contexts over extended periods of time. The current investigation was conducted to provide a descriptive analysis of PBS with diverse participants and broad measurement strategies over multiple years. Using extensive data portfolios for 21 participants, we employed rating scales to quantify changes in key variables from baseline through 2 years of intervention. The data revealed variable levels of intervention integrity, generalized reductions in problem behavior with occasional relapses, and encouraging enhancements across six domains of quality of life. This study represents an initial attempt to understand the processes and outcomes of behavioral support by documenting behavioral patterns across full days, entire years, and all environments. We discuss the need to consider new conceptual and methodological frameworks for further study of efficacious and sustainable behavior support

Influence of HLA-DR and -DQ alleles on autoantibody recognition of distinct epitopes within the juxtamembrane domain of the IA-2 autoantigen in type 1 diabetes

Aims/hypothesis: Insulinoma-associated protein 2 (IA-2) is a major target of autoimmunity in type 1 diabetes. When first detected, IA-2-autoantibodies commonly bind epitopes in the juxtamembrane (JM) domain of IA-2 and antibody responses subsequently spread to the tyrosine phosphatase domain. Definition of structures of epitopes in the JM domain, and genetic requirements for autoimmunity to these epitopes, is important for our understanding of initiation and progression of autoimmunity. The aims of this study were to investigate the contribution of individual amino acids in the IA-2 JM domain to antibody binding to these epitopes and the role of HLA genotypes in determining epitope specificity. Methods: Regions of the JM domain recognised by autoantibodies were identified by peptide competition and inhibitory effects of alanine substitutions of residues within the JM region. Antibody binding was determined by radioligand binding assays using sera from patients genotyped for HLA-DRB1 and -DQB1 alleles. Results: Patients were categorised into two distinct groups of JM antibody reactivity according to peptide inhibition. Inhibition by substitutions of individual amino acids within the JM domain differed between patients, indicating heterogeneity in epitope recognition. Cluster analysis defined six groups of residues having similar inhibitory effects on antibody binding, with three clusters showing differences in patients affected or unaffected by peptide. One cluster demonstrated significant differences in antibody binding between HLA-DRB1*04 and HLA-DRB1*07 patients and within DRB1*04 individuals; antibody recognition of a second cluster depended on expression of HLA-DQB1*0302. Conclusions/interpretation: The results identify amino acids contributing to distinct epitopes on IA-2, with both HLA-DR and HLA-DQ alleles influencing epitope specificity

Understanding the decomposition reaction mechanism of chrysanthemic acid: a computational study

<p>Abstract</p> <p>Background</p> <p>Chrysanthemic acid (<b>CHA</b>) is a major product from the photodecomposition of pyrethrin which is an important class of pesticide compounds.</p> <p>In the following paper, Hybrid density functional theory (DFT) calculations of the potential energy surface (PES) for three possible channels decomposition of chrysanthemic acid <b>(</b>cis-trans isomerization, rearrangement and fragmentation) have been carried at the B3LYP/6-311+G** level of theory. DFT was employed to optimize the geometry parameters of the reactants, transition states, intermediates and products based on detailed potential energy surfaces (PES).</p> <p>Results</p> <p>Our results suggest that all three pathways of <b>CHA </b>are endothermic. DFT calculations revealed that the activation barriers for cis-trans isomerization are low, leading to a thermodynamically favorable process than other two pathways. We also investigated the solvent effect on the PES using the polarizable continuum model (PCM). In addition, time-dependent density functional theory (TDDFT) calculations showed that these reactions occur in the ground state rather than in an excited state.</p> <p>Conclusion</p> <p>The rearrangement process seems to be more favorable than the decomposition of <b>CHA </b>to carbene formation. The solvent effect calculations indicated no changes in the shape of the PES with three continua (water, ethanol and cyclohexane), although the solvents tend to stabilize all of the species.</p

Working memory filtering continues to develop into late adolescence

While most measures of working memory (WM) performance have been shown to plateau by mid-adolescence and developmental changes in fronto-parietal regions supporting WM encoding and maintenance have been well characterized, little is known about developmental variation in WM filtering. We investigated the possibility that the neural underpinnings of filtering in WM reach maturity later in life than WM function without filtering. Using a cued WM filtering task (McNab and Klingberg, 2008), we investigated neural activity during WM filtering in a sample of 64 adults and adolescents. Regardless of age, increases in WM activity with load were concentrated in the expected fronto-parietal network. For adults, but not adolescents, recruitment of the basal ganglia during presentation of a filtering cue was associated with neural and behavioral indices of successful filtering, suggesting that WM filtering and related basal ganglia function may still be maturing throughout adolescence and into adulthood