Steroid hormone receptors in the developing brain

Sex differences exist in the behavioral patterns of adult vertebrate species. Many of these behavioral differences arise as a, result of the developmental imprinting of sex specific patterns in the anatomical, biochemical and molecular substrates of the brain. It is well established that steroid hormones play an important role during critical periods of development to organize the brain to a male or female specific pattern. In order to demonstrate that these hormones can act directly on brain tissue, ligand specific receptors for estrogen and androgen have been demonstrated in the developing brain, using a variety of techniques. Each class of steroid hormone receptor exhibits a unique distribution in the brain. Furthermore, each receptor undergoes a unique and tissue specific ontogenetic pattern of expression. A careful examination of the distribution and ontogeny of expression allows one to formulate specific hypotheses regarding the role of each of these receptors in the development and maturation of the brain.Biomedical Reviews 1997; 7: 51-66

Effect of Duplicate Isolates of Methicillin-Susceptible and Methicillin-Resistant Staphylococcus aureus on Antibiogram Data

This is the published version, also available here: http://www.dx.doi.org/10.1128/JCM.41.10.4611-4616.2003

Enhancement of PCA-based fault detection system through utilising dissimilarity matrix for continuous-based process

This research is about enhancement of PCA-based fault detection system through utilizing dissimilarity matrix. Nowadays, the chemical process industry is highly based on the non-linear relationships between measured variables. However, the conventional PCA-based MSPC is no longer effective because it only valid for the linear relationships between measured variables. Due in order to solve this problem, the technique of dissimilarity matrix is used in multivariate statistical process control as alternative technique which models the non-linear process and can improve the process monitoring performance. The conventional PCA system was run and the dissimilarity system was developed and lastly the monitoring performance in each technique were compared and analysed to achieve aims of this research. This research is to be done by using Matlab software. The findings of this study are illustrated in the form of Hotelling’s T2 and Squared Prediction Errors (SPE) monitoring statistics to be analysed. As a conclusion, the dissimilarity system is comparable to the conventional method. Thus can be the other alternative ways in the process monitoring performance. Finally, it is recommended to use data from other chemical processing systems for more concrete justification of the new technique

Gender-specific effects of HIV protease inhibitors on body mass in mice

Protease inhibitors, as part of highly active anti-retroviral therapy (HAART), have significantly increased the lifespan of human immunodeficiency virus (HIV) infected patients. Several deleterious side effects including dyslipidemia and lipodystrophy, however, have been observed with HAART. Women are at a higher risk of developing adipose tissue alterations and these alterations have different characteristics as compared to men. We have previously demonstrated that in mice the HIV protease inhibitor, ritonavir, caused a reduction in weight gain in females, but had no effect on male mice. In the present study, we examined the potential causes of this difference in weight gain. Low-density lipoprotein receptor (LDL-R) null mice or wild-type C57BL/6 mice, were administered 15 mug/ml ritonavir or vehicle (0.01% ethanol) in the drinking water for 6 weeks. The percent of total body weight gained during the treatment period was measured and confirmed that female LDL-R gained significantly less weight with ritonavir treatment than males. In wild type mice, however, there was no effect of ritonavir treatment in either sex. Despite the weight loss in LDL-R null mice, ritonavir increased food intake, but no difference was observed in gonadal fat weight. Serum leptin levels were significantly lower in females. Ritonavir further suppressed leptin levels in (p \u3c 0.05). Ritonavir did not alter serum adiponectin levels in either gender. To determine the source of these differences, female mice were ovariectomized remove the gonadal sex hormones. Ovariectomy prevented the weight loss induced by ritonavir (p \u3c 0.05). Furthermore, leptin levels were no longer suppressed by ritonavir (p \u3c 0.05). This study demonstrates that gonadal factors in females influence the hormonal control of weight gain changes induced by HIV protease inhibitors in an environment of elevated cholesterol

The Effects of Perinatal Oxycodone Exposure on Behavioral Outcome in a Rodent Model

Opiate addiction is now a major public health problem. Perinatal insults and exposure to opiates such as morphine in utero are well known to affect development of the hypothalamic–pituitary–adrenal axis of the offspring adversely and are associated with a higher risk of developing neurobehavioral problems. Oxycodone is now one of the most frequently abused pain killers during pregnancy; however, limited data are available regarding whether and how perinatal oxycodone exposure (POE) alters neurobehavioral outcomes of the offspring. We demonstrated that exposure to 0.5 mg/kg/day oxycodone in utero was associated with hyperactivity in adult rats in an open field. No significant effects of POE were detected on isolation-induced ultrasonic vocalizations in the early postnatal period or on learning and memory in the water maze in adult offspring. Our findings are consistent with hyperactivity problems identified in children exposed to opiates in utero

Considerations for Studying Sex as a Biological Variable in Spinal Cord Injury

In response to NIH initiatives to investigate sex as a biological variable in preclinical animal studies, researchers have increased their focus on male and female differences in neurotrauma. Inclusion of both sexes when modeling neurotrauma is leading to the identification of novel areas for therapeutic and scientific exploitation. Here, we review the organizational and activational effects of sex hormones on recovery from injury and how these changes impact the long-term health of spinal cord injury (SCI) patients. When determining how sex affects SCI it remains imperative to expand outcomes beyond locomotor recovery and consider other complications plaguing the quality of life of patients with SCI. Interestingly, the SCI field predominately utilizes female rodents for basic science research which contrasts most other male-biased research fields. We discuss the unique caveats this creates to the translatability of preclinical research in the SCI field. We also review current clinical and preclinical data examining sex as biological variable in SCI. Further, we report how technical considerations such as housing, size, care management, and age, confound the interpretation of sex-specific effects in animal studies of SCI. We have uncovered novel findings regarding how age differentially affects mortality and injury-induced anemia in males and females after SCI, and further identified estrus cycle dysfunction in mice after injury. Emerging concepts underlying sexually dimorphic responses to therapy are also discussed. Through a combination of literature review and primary research observations we present a practical guide for considering and incorporating sex as biological variable in preclinical neurotrauma studies

Real-Time Feedback of Air Quality in Children’s Bedrooms Reduces Exposure to Secondhand Smoke

Introduction:Secondhand smoke (SHS) exposure creates health risks for nonsmokers and is especially detrimental to children. This study evaluated whether immediate feedback in response to poor indoor air quality in children’s bedrooms can reduce the potential for SHS exposure, as measured by adherence to a World Health Organization (WHO) indoor air standard.Methods:Homes that contained children and an adult who regularly smoked inside (n=298) had an air particle monitor installed in the child’s bedroom. These devices measured the concentration of particulate matter (PM2.5) for approximately three months and, for half of the participants, immediately provided aversive feedback in response to elevated PM2.5. Hierarchical linear models were fit to the data to assess whether the intervention increased the probability that: 1) a given day was below the WHO guideline for daily exposure, and 2) a household established and maintained a smoke-free home (SFH), operationalized as achieving 30 consecutive days below the WHO guideline. The intervention’s impact was calculated as groupby- time effects.Results:The likelihood that a child’s bedroom met the WHO indoor air quality standard on a given day increased such that the baseline versus post-baseline odds ratio (OR) of maintaining indoor PM2.5 levels below the WHO guideline was 2.38 times larger for participants who received the intervention. Similarly, the baseline versus post-baseline OR associated with achieving an SFH was 3.49 times larger for participants in the intervention group.Conclusions:The real-time intervention successfully drove clinically meaningful changes in smoking behavior that mitigated indoor PM2.5 levels in children’s bedrooms and thereby reduced SHS exposure. These results demonstrate the effectiveness of targeting sensitive microenvironments by giving caregivers actionable information about children’s SHS risks. Future extensions should examine additional microenvironments and focus on identifying the potential for SHS exposure before it occurs

VCAM-1/α4β1 Integrin Interaction is Crucial for Prompt Recruitment of Immune T Cells into the Brain During the Early Stage of Reactivation of Chronic Infection with \u3cem\u3eToxoplasma gondii\u3c/em\u3e to Prevent Toxoplasmic Encephalitis

Reactivation of chronic infection with Toxoplasma gondii can cause life-threatening toxoplasmic encephalitis in immunocompromised individuals. We examined the role of VCAM-1/α4β1 integrin interaction in T cell recruitment to prevent reactivation of the infection in the brain. SCID mice were infected and treated with sulfadiazine to establish a chronic infection. VCAM-1 and ICAM-1 were the endothelial adhesion molecules detected on cerebral vessels of the infected SCID and wild-type animals. Immune T cells from infected wild-type mice were treated with anti-α4 integrin or control antibodies and transferred into infected SCID or nude mice, and the animals received the same antibody every other day. Three days later, sulfadiazine was discontinued to initiate reactivation of infection. Expression of mRNAs for CD3δ, CD4, CD8β, gamma interferon (IFN-γ), and inducible nitric oxide synthase (NOS2) (an effector molecule to inhibit T. gondii growth) and the numbers of CD4+ and CD8+ T cells in the brain were significantly less in mice treated with anti-α4 integrin antibody than in those treated with control antibody at 3 days after sulfadiazine discontinuation. At 6 days after sulfadiazine discontinuation, cerebral tachyzoite-specific SAG1 mRNA levels and numbers of inflammatory foci associated with tachyzoites were markedly greater in anti-α4 integrin antibody-treated than in control antibody-treated animals, even though IFN-γ and NOS2 mRNA levels were higher in the former than in the latter. These results indicate that VCAM-1/α4β1 integrin interaction is crucial for prompt recruitment of immune T cells and induction of IFN-γ-mediated protective immune responses during the early stage of reactivation of chronic T. gondii infection to control tachyzoite growth

HDL-Associated Estradiol Stimulates Endothelial NO Synthase and Vasodilation in an SR-BI–Dependent Manner

Cardiovascular diseases remain the leading cause of death in the United States. Two factors associated with a decreased risk of developing cardiovascular disease are elevated HDL levels and sex — specifically, a decreased risk is found in premenopausal women. HDL and estrogen stimulate eNOS and the production of nitric oxide, which has numerous protective effects in the vascular system including vasodilation, antiadhesion, and anti-inflammatory effects. We tested the hypothesis that HDL binds to its receptor, scavenger receptor class B type I (SR-BI), and delivers estrogen to eNOS, thereby stimulating the enzyme. HDL isolated from women stimulated eNOS, whereas HDL isolated from men had minimal activity. Studies with ovariectomized and ovariectomized/estrogen replacement mouse models demonstrated that HDL-associated estradiol stimulation of eNOS is SR-BI dependent. Furthermore, female HDL, but not male HDL, promoted the relaxation of muscle strips isolated from C57BL/6 mice but not SR-BI null mice. Finally, HDL isolated from premenopausal women or postmenopausal women receiving estradiol replacement therapy stimulated eNOS, whereas HDL isolated from postmenopausal women did not stimulate eNOS. We conclude that HDL-associated estrodial is capable of the stimulating eNOS. These studies establish a new paradigm for examining the cardiovascular effects of HDL and estrogen

High-Resolution Modeling of the Dust and Water Cycles with the NASA Ames Mars Global Climate Model

NASAs Mars Climate Modeling Center at Ames Research Center is currently undergoing an exciting period of growth in personnel, modeling capabilities, and science productivity. We are transitioning from our legacy Arakawa C-grid finite-difference dynamical core to the NOAA/GFDL cubed-sphere finite-volume dynamical core for simulating the climate of Mars in a global framework. This highly parallelized core is scalable and flexible, which allows for significant improvements in the horizontal and vertical resolutions of our simulations. We have implemented the Ames water ice cloud microphysics package described in Haberle et al. (2018) into this new dynamical core. We will present high-resolution simulations of the dust and water cycles that show that sub-degree horizontal resolution improves the agreement between the vertical distribution of dust and water ice and observations. In particular, both water ice clouds and dust are transported to higher altitudes due to stronger topographic circulations at high resolution. Preliminary results suggest that high-resolution global modeling is needed to properly capture critical features of the dust and water cycles, and thus the current Mars climate