Do Life Style Factors And Socioeconomic Variables Explain Why Black Women Have A Remarkably Higher Body Mass Index (BMI) Than White Women In The United States? Findings From The 2010 National Health Interview Survey

Objective: There are marked inequalities in body mass index (BMI), overweight, and obesity across ethnic groups. We sought to examine the extent to which lifestyle factors and socioeconomic variables explain the higher BMI in Black women compared to White women in the United States. Methods: We used data from the 2010 National Health Interview Survey (NHIS) and limited the sample to non-Hispanic Black and non-Hispanic White women (n = 9,491). We employed normal regression and compared the association of race with BMI before and after adjusting for lifestyle factors (diet, physical activity, smoking, and drinking) and socioeconomic variables (education, ratio of income to poverty threshold, occupation, and home ownership). Data analysis was performed in 2012. Results: The difference between the BMI of Black and White women decreased from 2.91 to 2.17 Kg/m2 (i.e. a decrease of 27.2%) after adjusting for lifestyle factors and socioeconomic variables. Multivariate results also showed that higher consumption of fruit/vegetables and beans, lower consumption of red meat and sugar sweetened beverages, physical activity, smoking, regular drinking, and higher socioeconomic status were associated with lower BMI. Conclusions: Lifestyle factors and socioeconomic variables explain about a quarter of the BMI inequality between Black and White women. Thus, interventions that promote healthy eating and physical activity among Blacks as well as social policies that ameliorate socioeconomic inequalities between races might be able to reduce the current BMI inequality between Black and White women

Preliminary X-ray crystallographic analysis of B-carbonic anhydrase psCA3 from Pseudomonas aeruginosa

Pseudomonas aeruginosa is a Gram-negative bacterium that causes life-threatening infections in susceptible individuals and is resistant to most clinically available antimicrobials. Genomic and proteomic studies have identified three genes, pa0102, pa2053 and pa4676, in P. aeruginosa PAO1 encoding three functional [beta]-carbonic anhydrases ([beta]-CAs): psCA1, psCA2 and psCA3, respectively. These [beta]-CAs could serve as novel antimicrobial drug targets for this pathogen. X-ray crystallographic structural studies have been initiated to characterize the structure and function of these proteins. This communication describes the production of two crystal forms (A and B) of [beta]-CA psCA3. Form A diffracted to a resolution of 2.9 A; it belonged to space group P212121, with unit-cell parameters a = 81.9, b = 84.9, c = 124.2 A, and had a calculated Matthews coefficient of 2.23 A3 Da-1 assuming four molecules in the crystallographic asymmetric unit. Form B diffracted to a resolution of 3.0 A; it belonged to space group P21212, with unit-cell parameters a = 69.9, b = 77.7, c = 88.5 A, and had a calculated Matthews coefficient of 2.48 A3 Da-1 assuming two molecules in the crystallographic asymmetric unit. Preliminary molecular-replacement solutions have been determined with the PHENIX AutoMR wizard and refinement of both crystal forms is currently in progress.Peer reviewedMicrobiology and Molecular Genetic

Mapping Selective Inhibition of the Cancer-Related Carbonic Anhydrase IX Using Structure-Activity Relationships of Glucosyl-Based Sulfamates

Inhibition of human carbonic anhydrase IX (hCA IX) has shown to be therapeutically advantageous for treating many types of highly aggressive cancers. However, designing selective inhibitors for hCA IX has been difficult due to its high structural homology and sequence similarity with off-target hCAs. Recently, the use of glucosyl sulfamate inhibitors has shown promise as selective inhibitors for hCA IX. In this study, we present five X-ray crystal structures, determined to a resolution of 1.7 Å or better, of both hCA II (a ubiquitous CA) and an engineered hCA IX-mimic in complex with selected glucosyl sulfamates and structurally rationalize mechanisms for hCA IX selectivity. Results from this study have allowed us, for the first time, to empirically “map” key interactions of the hCA IX active site in order to establish parameters needed to design novel hCA IX selective inhibitors.No Full Tex

Septin 9 isoform expression, localization and epigenetic changes during human and mouse breast cancer progression

International audienceABSTRACT: INTRODUCTION: Altered expression of Septin 9 (SEPT9), a septin coding for multiple isoform variants, has been observed in several carcinomas including colorectal, head and neck, ovarian and breast, compared to normal tissue. Mechanisms regulating its expression during tumor initiation and progression in vivo and the oncogenic function of its different isoforms remain elusive. METHODS: Using an integrative approach, we investigated SEPT9 at the genetic, epigenetic, mRNA, and protein levels in breast cancer. We analyzed a panel of breast cancer cell lines, human primary tumors and corresponding tumor-free areas, normal breast from reduction mammoplasty patients, as well as primary mammary gland adenocarcinomas derived from the Polyoma Virus Middle T antigen mouse model (PyMT). MCF7 clones expressing individual GFP-tagged SEPT9 isoforms were used to determine their respective intracellular distribution and affect on cell migration. RESULTS: An overall increase in gene amplification and altered expression of SEPT9 was observed during breast tumorigenesis. We identified an intragenic alternative promoter whose methylation regulates SEPT9_v3 expression. Transfection of specific GFP-SEPT9 isoforms in MCF7 cells indicates that these isoforms exhibit differential localization and affect migration rates. Additionally, the loss of an uncharacterized SEPT9 nucleolar localization is observed during tumorigenesis. CONCLUSIONS: In this study we found conserved in vivo changes of SEPT9 gene amplification and overexpression during human and mouse breast tumorigenesis. We show that DNA methylation is a prominent mechanism responsible for regulating differential SEPT9 isoform expression and that breast tumor samples exhibit distinctive SEPT9 intracellular localization. Together, these findings support the significance of SEPT9 as a promising tool in breast cancer detection and further emphasize the importance of analyzing and targeting SEPT9 isoform specific expression and function

Probing the Surface of Human Carbonic Anhydrase for Clues towards the Design of Isoform Specific Inhibitors

The alpha carbonic anhydrases (α-CAs) are a group of structurally related zinc metalloenzymes that catalyze the reversible hydration of CO2 to HCO3-. Humans have 15 different α-CAs with numerous physiological roles and expression patterns. Of these, 12 are catalytically active, and abnormal expression and activities are linked with various diseases, including glaucoma and cancer. Hence there is a need for CA isoform specific inhibitors to avoid off-target CA inhibition, but due to the high amino acid conservation of the active site and surrounding regions between each enzyme, this has proven difficult. However, residues towards the exit of the active site are variable and can be exploited to design isoform selective inhibitors. Here we discuss and characterize this region of “selective drug targetability” and how these observations can be utilized to develop isoform selective CA inhibitors

Rapid crystallization of glycine using metal-assisted and microwave-accelerated evaporative crystallization: the effect of engineered surfaces and sample volume

Metal-Assisted and Microwave-Accelerated Evaporative Crystallization (MA-MAEC), is a new approach to crystallization of drug compounds, amino acids, DNA and proteins. In this work, we report our additional findings on the effect of engineered surfaces and sample volume on the rapid crystallization of glycine. With the use of hydrophilic functionalized surfaces and the MA-MAEC technique, glycine crystals ~1 mm in size were grown in 35 seconds with 100% selectivity for the α-form.The use of moderately hydrophobic surfaces resulted in the growth of glycine crystals only at room temperature. An increase in volume of initial glycine solution (5-100 μL) resulted in an increase in crystal size without a significant increase in total crystallization time. Raman spectroscopy and powder X-ray diffraction results demonstrated that the glycine crystals grown on engineered surfaces were structurally identical to those grown using conventional evaporative crystallization

Rapid and Sensitive Colorimetric ELISA Using Silver Nanoparticles, Microwaves and Split Ring Resonator Structures

We report a new approach to colorimetric Enzyme-Linked Immunosorbent Assay (ELISA) that reduces the total assay time to < 2 min and the lower-detection-limit by 100-fold based on absorbance readout. The new approach combines the use of silver nanoparticles, microwaves and split ring resonators (SRR). The SRR structure is comprised of a square frame of copper thin film (30 µm thick, 1 mm wide, overall length of ~9.4 mm on each side) with a single split on one side, which was deposited onto a circuit board (2×2 cm(2)). A single micro-cuvette (10 µl volume capacity) was placed in the split of the SRR structures. Theoretical simulations predict that electric fields are focused in and above the micro-cuvette without the accumulation of electrical charge that breaks down the copper film. Subsequently, the walls and the bottom of the micro-cuvette were coated with silver nanoparticles using a modified Tollen’s reaction scheme. The silver nanoparticles served as a mediator for the creation of thermal gradient between the bioassay medium and the silver surface, where the bioassay is constructed. Upon exposure to low power microwave heating, the bioassay medium in the micro-cuvette was rapidly and uniformly heated by the focused electric fields. In addition, the creation of thermal gradient resulted in the rapid assembly of the proteins on the surface of silver nanoparticles without denaturing the proteins. The proof-of-principle of the new approach to ELISA was demonstrated for the detection of a model protein (biotinylated-bovine serum albumin, b-BSA). In this regard, the detection of b-BSA with bulk concentrations (1 µM to 1 pM) was carried out on commercially available 96-well high throughput screening (HTS) plates and silver nanoparticle-deposited SRR structures at room temperature and with microwave heating, respectively. While the room temperature bioassay (without microwave heating) took 70 min to complete, the identical bioassay took < 2 min to complete using the SRR structures (with microwave heating). A lower detection limit of 0.01 nM for b-BSA (100-fold lower than room temperature ELISA) was observed using the SRR structures

Ultrafast and sensitive bioassay using split ring resonator structures and microwave heating

In this paper, we have reported that split ring resonators (SRRs) structures can be used for bioassay applications in order to further improve the assay time and sensitivity. The proof-of-principle demonstration of the ultrafast bioassays was accomplished by using a model biotin-avidin bioassay. While the identical room temperature bioassay (without microwave heating) took 70 min to complete, the identical bioassay took less than 2 min to complete by using SRR structures (with microwave heating). A lower detection limit of 0.01 nM for biotinylated-bovine serum albumin (100-fold lower than the room temperature bioassay) was observed by using SRR structures