Developmental Changes in the Structure and Composition of the Postsynaptic Density

The development of the brain and its underlying circuitry is dependent on the formation of trillions of chemical synapses, which are highly specialized contacts that regulate the flow of information from one neuron to the next. It is through these synaptic connections that neurons wire together into networks capable of performing specific tasks, and activity-dependent changes in their structural and physiological state is one way that the brain is thought to adapt and store information. At the ultrastructural level, developmental and activity-dependent changes in the size and shape of dendritic spines have been well documented, and it is widely believed that structural changes in spines are a hallmark sign of synapse maturation and alteration of synaptic physiology. While changes in spine structure have been studied extensively, changes in one of its most prominent components, the postsynaptic density (PSD), have largely evaded observation. The PSD is a protein-rich organelle on the cytoplasmic side of the postsynaptic membrane, where it sits in direct opposition to the presynaptic terminal. The PSD functions both to cluster neurotransmitter receptors at the cell surface as well as organize the intracellular signaling molecules responsible for transducing extracellular signals to the postsynaptic cell. Much is known about the chemical composition of the PSD, but the structural arrangement of its molecular components is not well documented. Adding to the difficulty of understanding such a complex mass of protein machinery is the fact that its protein composition is known to change in response to synaptic activity, meaning that its structure is plastic and no two PSDs are identical. Here, immuno-gold labeling and electron tomography of PSDs isolated throughout development was used to track changes in both the structure and molecular composition of the PSD. State-of-the-art cryo-electron tomography was used to study the fine structure of the PSD during development, and provides an unprecedented glimpse into its molecular architecture in an un-fixed, unstained and hydrated state. Through this analysis, large structural and compositional changes are apparent and suggest a model by which the PSD is first assembled as a mesh-like lattice of proteins that function as support for the later recruitment of various PSD components. Spatial analysis of the recruitment of proteins into the PSD demonstrated that its assembly has an underlying order.

THE EFFECTS OF CURCUMIN ON BODY COMPOSITION OF PATIENTS WITH ADVANCED PANCREATIC CANCER

Cachexia is very common among patients with advanced pancreatic cancer and is a marker of poor prognosis. Weight loss in cachexia is due to both adipose and muscle compartments, and sarcopenia (severe muscle depletion) is associated with worse outcomes. Curcumin has shown a myriad of biological effects, including anti-cancer and anti-inflammatory. The ability of curcumin to attenuate cachexia and muscle loss has been tested in animal models, with conflicting results so far. The hypothesis of this study was that patients with advanced pancreatic cancer treated with curcumin for two months have less fat and muscle loss as compared to matched controls not treated with this compound. A matched 1:2 case-control retrospective study was conducted with 22 patients with pancreatic cancer who were treated with curcumin on a previous protocol and 44 untreated controls with the same diagnosis matched by age, gender, time from advanced cancer, body mass index, and number of prior therapies. Data was collected regarding oncologic treatment, medication use, weights, heights, and survival. Body composition was determined by computerized tomography analyses at two timepoints separated by 60±20 days. For treated patients, the first image was at the beginning of treatment and for controls it was determined by the matching time from advanced cancer. The evolution of body composition over time was quantitatively analyzed comparing both groups. All patients lost weight both due to fat and muscle losses, and patients treated with curcumin presented greater losses both in lean adipose body mass. Use of medications, chemotherapy, age, time from advanced cancer, baseline albumin, performance status, and number of prior therapies were not independently correlated with changes in body composition variables. Patients treated with curcumin had borderline shorter survival when compared with untreated patients. Sarcopenic treated patients had significantly shorter survival than non-sarcopenic counterparts, and sarcopenia status was not associated with survival among the controls. Treated patients with shorter survival showed a tendency to lose more lean and especially fat body mass as compared to untreated patients, maybe suggesting an effect of curcumin on shifting weight loss towards the end of life by impacting its mechanisms.

A QUANTITATIVE INVESTIGATION OF SOURCE AND ELEMENTAL COMPOSITION OF INDOOR AND OUTDOOR FINE PARTICULATE AIR POLLUTION IN HOUSTON (TEXAS)

An investigation was undertaken to determine the chemical characterization of inhalable particulate matter in the Houston area, with special emphasis on source identification and apportionment of outdoor and indoor atmospheric aerosols using multivariate statistical analyses.^ Fine (<2.5 (mu)m) particle aerosol samples were collected by means of dichotomous samplers at two fixed site (Clear Lake and Sunnyside) ambient monitoring stations and one mobile monitoring van in the Houston area during June-October 1981 as part of the Houston Asthma Study. The mobile van allowed particulate sampling to take place both inside and outside of twelve homes.^ The samples collected for 12-h sampling on a 7 AM-7 PM and 7 PM-7 AM (CDT) schedule were analyzed for mass, trace elements, and two anions. Mass was determined gravimetrically. An energy-dispersive X-ray fluorescence (XRF) spectrometer was used for determination of elemental composition. Ion chromatography (IC) was used to determine sulfate and nitrate.^ Average chemical compositions of fine aerosol at each site were presented. Sulfate was found to be the largest single component in the fine fraction mass, comprising approximately 30% of the fine mass outdoors and 12% indoors, respectively.^ Principal components analysis (PCA) was applied to identify sources of aerosols and to assess the role of meteorological factors on the variation in particulate samples. The results suggested that meteorological parameters were not associated with sources of aerosol samples collected at these Houston sites.^ Source factor contributions to fine mass were calculated using a combination of PCA and stepwise multivariate regression analysis. It was found that much of the total fine mass was apparently contributed by sulfate-related aerosols. The average contributions to the fine mass coming from the sulfate-related aerosols were 56% of the Houston outdoor ambient fine particulate matter and 26% of the indoor fine particulate matter.^ Characterization of indoor aerosol in residential environments was compared with the results for outdoor aerosols. It was suggested that much of the indoor aerosol may be due to outdoor sources, but there may be important contributions from common indoor sources in the home environment such as smoking and gas cooking. ^

The effects of ethnicity and ethnic composition of schools on physical activity and nutrition behaviors of 8th and 11th graders in Texas

With rates of obesity and overweight continuing to increase in the US, the attention of public health researchers has focused on nutrition and physical activity behaviors. However, attempts to explain the disparate rates of obesity and overweight between whites and Hispanics have often proven inadequate. Indeed, the nebulous term ‘ethnicity’ provides little important detail in addressing potential biological, behavioral, and environmental factors that may affect rates of obesity and overweight. In response to this, the present research seeks to test the explanatory powers of ethnicity by situating the nutrition and physical activity behaviors of whites and Hispanic into their broader social contexts. It is hypothesized that a student's gender and grade level, as well as the socioeconomic status and ethnic composition of their school, will have more predictive power for these behaviors than will self-reported ethnicity. ^ Analyses revealed that while ethnicity did not seem to impact nutrition behaviors among the wealthier schools and those with fewer Hispanics, ethnicity was relevant in explaining these behaviors in the poorest tertile of schools and those with the highest number of Hispanics. With respect to physical activity behaviors, the results were mixed. The variables representing regular physical activity, participation in extracurricular physical activities, and performance of strengthening and toning exercises were more likely to be determined by SES and ethnic composition than ethnicity, especially among 8th grade males. However, school sports team and physical education participation continued to vary by ethnicity, even after controlling for SES and ethnic composition of schools. In conclusion then, it is important to understand the intersecting demographic and social variables that define and surround the individual in order to understand nutrition and physical activity behaviors and thus overweight and obesity.^