Full-energy-peak efficiencies of three gamma-ray detectors.

Two sodium iodide scintillators and a lithium-drifted germanium detector are used in the analysis by gamma-ray spectrometry of gaseous fission products obtained in sweep-capsule fission product release experiments. A description is given of the measurements of full-energy-peak efficiencies of the three detectors for the source geometries used in counting the fission product samples. Experimental efficiencies are compared with calculated efficiencies for one of the sodium iodide detectors. Measurements made of the resolutions obtained with each detector are also noted

Widespread sex differences in gene expression and splicing in the adult human brain

There is strong evidence to show that men and women differ in terms of neurodevelopment, neurochemistry and susceptibility to neurodegenerative and neuropsychiatric disease. The molecular basis of these differences remains unclear. Progress in this field has been hampered by the lack of genome-wide information on sex differences in gene expression and in particular splicing in the human brain. Here we address this issue by using post-mortem adult human brain and spinal cord samples originating from 137 neuropathologically confirmed control individuals to study whole-genome gene expression and splicing in 12 CNS regions. We show that sex differences in gene expression and splicing are widespread in adult human brain, being detectable in all major brain regions and involving 2.5% of all expressed genes. We give examples of genes where sex-biased expression is both disease-relevant and likely to have functional consequences, and provide evidence suggesting that sex biases in expression may reflect sex-biased gene regulatory structures

Expression and Localization of Mitochondrial Ferritin mRNA in Alzheimer's Disease Cerebral Cortex

Mitochondrial ferritin (MtF) has been identified as a novel ferritin encoded by an intron-lacking gene with specific mitochondrial localization located on chromosome 5q23.1. MtF has been associated with neurodegenerative disorders such as Friedreich ataxia and restless leg syndrome. However, little information is available about MtF in Alzheimer's disease (AD). In this study, therefore, we investigated the expression and localization of MtF messenger RNA (mRNA) in the cerebral cortex of AD and control cases using real-time polymerase chain reaction (PCR) as well as in situ hybridization histochemistry. We also examined protein expression using western-blot assay. In addition, we used in vitro methods to further explore the effect of oxidative stress and β-amyloid peptide (Aβ) on MtF expression. To do this we examined MtF mRNA and protein expression changes in the human neuroblastoma cell line, IMR-32, after treatment with Aβ, H2O2, or both. The neuroprotective effect of MtF on oxidative stress induced by H2O2 was measured by MTT assay. The in situ hybridization studies revealed that MtF mRNA was detected mainly in neurons to a lesser degree in glial cells in the cerebral cortex. The staining intensity and the number of positive cells were increased in the cerebral cortex of AD patients. Real-time PCR and western-blot confirmed that MtF expression levels in the cerebral cortex were significantly higher in AD cases than that in control cases at both the mRNA and the protein level. Cell culture experiments demonstrated that the expression of both MtF mRNA and protein were increased by treatment with H2O2 or a combination of Aβ and H2O2, but not with Aβ alone. Finally, MtF expression showed a significant neuroprotective effect against H2O2-induced oxidative stress (p<0.05). The present study suggests that MtF is involved in the pathology of AD and may play a neuroprotective role against oxidative stress

The Sun Health Research Institute Brain Donation Program: Description and Eexperience, 1987–2007

The Brain Donation Program at Sun Health Research Institute has been in continual operation since 1987, with over 1000 brains banked. The population studied primarily resides in the retirement communities of northwest metropolitan Phoenix, Arizona. The Institute is affiliated with Sun Health, a nonprofit community-owned and operated health care provider. Subjects are enrolled prospectively to allow standardized clinical assessments during life. Funding comes primarily from competitive grants. The Program has made short postmortem brain retrieval a priority, with a 2.75-h median postmortem interval for the entire collection. This maximizes the utility of the resource for molecular studies; frozen tissue from approximately 82% of all cases is suitable for RNA studies. Studies performed in-house have shown that, even with very short postmortem intervals, increasing delays in brain retrieval adversely affect RNA integrity and that cerebrospinal fluid pH increases with postmortem interval but does not predict tissue viability

Development and evaluation of a cultural competency training curriculum

BACKGROUND: Increasing the cultural competence of physicians and other health care providers has been suggested as one mechanism for reducing health disparities by improving the quality of care across racial/ethnic groups. While cultural competency training for physicians is increasingly promoted, relatively few studies evaluating the impact of training have been published. METHODS: We recruited 53 primary care physicians at 4 diverse practice sites and enrolled 429 of their patients with diabetes and/or hypertension. Patients completed a baseline survey which included a measure of physician culturally competent behaviors. Cultural competency training was then provided to physicians at 2 of the sites. At all 4 sites, physicians received feedback in the form of their aggregated cultural competency scores compared to the aggregated scores from other physicians in the practice. The primary outcome at 6 months was change in the Patient-Reported Physician Cultural Competence (PRPCC) score; secondary outcomes were changes in patient trust, satisfaction, weight, systolic blood pressure, and glycosylated hemoglobin. Multiple analysis of variance was used to control for differences patient characteristics and baseline levels of the outcome measure between groups. RESULTS: Patients had a mean of 2.8 + 2.2 visits to the study physician during the study period. Changes in all outcomes were similar in the "Training + Feedback" group compared to the "Feedback Only" group (PRPCC: 3.7 vs.1.8; trust: -0.7 vs. -0.2 ; satisfaction: 1.9 vs. 2.5; weight: -2.5 lbs vs. -0.7 lbs; systolic blood pressure: 1.7 mm Hg vs. 0.1 mm Hg; glycosylated hemoglobin 0.02% vs. 0.07%; p = NS for all). CONCLUSION: The lack of measurable impact of physician training on patient-reported and disease-specific outcomes in the current has several possible explanations, including the relatively limited nature of the intervention. We hope that the current study will help provide a basis for future studies, using more intensive interventions with different provider groups

Linkage between fitness of yeast cells and adenylate kinase catalysis

Enzymes have evolved with highly specific values of their catalytic parameters kcat and KM. This poses fundamental biological questions about the selection pressures responsible for evolutionary tuning of these parameters. Here we are address these questions for the enzyme adenylate kinase (Adk) in eukaryotic yeast cells. A plasmid shuffling system was developed to allow quantification of relative fitness (calculated from growth rates) of yeast in response to perturbations of Adk activity introduced through mutations. Biophysical characterization verified that all variants studied were properly folded and that the mutations did not cause any substantial differences to thermal stability. We found that cytosolic Adk is essential for yeast viability in our strain background and that viability could not be restored with a catalytically dead, although properly folded Adk variant. There exist a massive overcapacity of Adk catalytic activity and only 12% of the wild type kcat is required for optimal growth at the stress condition 20°C. In summary, the approach developed here has provided new insights into the evolutionary tuning of kcat for Adk in a eukaryotic organism. The developed methodology may also become useful for uncovering new aspects of active site dynamics and also in enzyme design since a large library of enzyme variants can be screened rapidly by identifying viable colonies

Cellular injury and neuroinflammation in children with chronic intractable epilepsy

<p>Abstract</p> <p>Objective</p> <p>To elucidate the presence and potential involvement of brain inflammation and cell death in neurological morbidity and intractable seizures in childhood epilepsy, we quantified cell death, astrocyte proliferation, microglial activation and cytokine release in brain tissue from patients who underwent epilepsy surgery.</p> <p>Methods</p> <p>Cortical tissue was collected from thirteen patients with intractable epilepsy due to focal cortical dysplasia (6), encephalomalacia (5), Rasmussen's encephalitis (1) or mesial temporal lobe epilepsy (1). Sections were processed for immunohistochemistry using markers for neuron, astrocyte, microglia or cellular injury. Cytokine assay was performed on frozen cortices. Controls were autopsy brains from eight patients without history of neurological diseases.</p> <p>Results</p> <p>Marked activation of microglia and astrocytes and diffuse cell death were observed in epileptogenic tissue. Numerous fibrillary astrocytes and their processes covered the entire cortex and converged on to blood vessels, neurons and microglia. An overwhelming number of neurons and astrocytes showed DNA fragmentation and its magnitude significantly correlated with seizure frequency. Majority of our patients with abundant cell death in the cortex have mental retardation. IL-1beta, IL-8, IL-12p70 and MIP-1beta were significantly increased in the epileptogenic cortex; IL-6 and MCP-1 were significantly higher in patients with family history of epilepsy.</p> <p>Conclusions</p> <p>Our results suggest that active neuroinflammation and marked cellular injury occur in pediatric epilepsy and may play a common pathogenic role or consequences in childhood epilepsy of diverse etiologies. Our findings support the concept that immunomodulation targeting activated microglia and astrocytes may be a novel therapeutic strategy to reduce neurological morbidity and prevent intractable epilepsy.</p

Male Mating Tactics in Captive Rhesus Macaques (Macaca mulatta): The Influence of Dominance, Markets, and Relationship Quality

Male mating success in a multimale–multifemale group can depend on several variables: body condition, dominance, coalitions, “friendship,” or an exchange of services for mating access. Exchange patterns may also be determined by market effects or social relationships. We studied the mating tactics of males in a captive, multimale–multifemale group of rhesus macaques and the resulting patterns of mating and paternity to determine the influence of dominance rank, mating markets, and relationship quality on their mating tactics. Male rank was positively related to the total number of copulations and the number of mating partners, but did not explain male mating distribution completely. Moreover, male fertilization success was not related to male rank. Males did not exchange grooming for mating access on the same day and neither the supply nor the rank (as a proxy for quality) of receptive females affected the amount of male grooming, suggesting that market effects did not explain male mating access. However, there was a positive correlation between long-term grooming patterns of both males and females and mating access, indicating that social relationships were important for male mating access. Paternity data revealed that these social relationships were also important for male reproductive success. We conclude that both male rank and male–female “friendship” determined male mating access in these rhesus macaques, but that “friendship” was more important in determining paternity, emphasizing the importance of intersex social bonds in male mating success in multimale primate societies

A comprehensive screening of copy number variability in dementia with Lewy bodies

The role of genetic variability in dementia with Lewy bodies (DLB) is now indisputable; however, data regarding copy number variation (CNV) in this disease has been lacking. Here, we used whole-genome genotyping of 1454 DLB cases and 1525 controls to assess copy number variability. We used 2 algorithms to confidently detect CNVs, performed a case-control association analysis, screened for candidate CNVs previously associated with DLB-related diseases, and performed a candidate gene approach to fully explore the data. We identified 5 CNV regions with a significant genome-wide association to DLB; 2 of these were only present in cases and absent from publicly available databases: one of the regions overlapped LAPTM4B, a known lysosomal protein, whereas the other overlapped the NME1 locus and SPAG9. We also identified DLB cases presenting rare CNVs in genes previously associated with DLB or related neurodegenerative diseases, such as SNCA, APP, and MAPT. To our knowledge, this is the first study reporting genome-wide CNVs in a large DLB cohort. These results provide preliminary evidence for the contribution of CNVs in DLB risk.info:eu-repo/semantics/publishedVersio