Multidate MESMA for monitoring vegetation growth forms in southern California shrublands

Identifying habitats that should be protected from further disturbance or conversion and isolating high-risk areas is a focus of community habitat plans in southern California shrublands. Larger wildfires are occurring at shorter intervals in recent decades, contributing to degradation and conversion of shrubland vegetation. Multitemporal remote-sensing approaches can bridge the gap between vegetation mapping and field sampling in habitats where frequent quantification and mapping of vegetation growth forms over large extents is required. The objective of this study is to examine the reliability and stability of a multiple endmember spectral mixture analysis (MESMA) approach with moderate spatial resolution imagery for monitoring changes in growth form fractional cover in shrubland habitats. Estimates from visual interpretation of high spatial resolution image were used as reference data for validating MESMA-derived maps and as basis for providing complementary monitoring protocols that may be accurate and cost-effective across multiple scales. Growth form proportions modelled in burned and unburned management areas compare well with expected fractional cover in mature and regenerating shrublands. In the management areas recovering from fire, herbaceous cover fraction exceeded 0.40 for all three study dates, suggesting that large portions of those management areas may already be invaded. From 2008 to 2011 overall herbaceous cover fraction in shrubland area increased by 2%. Herbaceous cover fraction was modelled with an overall mean absolute error (MAE) of 0.08, a smaller percentage than the percentage of herbaceous cover change recorded in areas recovering from fire (increase in herbaceous cover fraction from 0.09 to 0.13). This MESMA approach would be effective for quantifying changes in fractional cover that exceed 0.10, providing a way to delineate and quantify herbaceous invasions and expansions following disturbance or succession.     

Hydroxypyridinethione Inhibitors of Human Insulin-Degrading Enzyme

Insulin-degrading enzyme (IDE) is a human mononuclear Zn²⁺-dependent metalloenzyme that is widely regarded as the primary peptidase responsible for insulin degradation. Despite its name, IDE is also critically involved in the hydrolysis of several other disparate peptide hormones, including glucagon, amylin, and the amyloid β-protein. As such, the study of IDE inhibition is highly relevant to deciphering the role of IDE in conditions such as type-2 diabetes mellitus and Alzheimer disease. There have been few reported IDE inhibitors, and of these, inhibitors that directly target the active-site Zn²⁺ ion have yet to be fully explored. In an effort to discover new, zinc-targeting inhibitors of IDE, a library of ∼350 metal-binding pharmacophores was screened against IDE, resulting in the identification of 1-hydroxypyridine-2-thione (1,2-HOPTO) as an effective Zn²⁺-binding scaffold. Screening a focused library of HOPTO compounds identified 3-sulfonamide derivatives of 1,2-HOPTO as inhibitors of IDE (K_i values of ∼50 μM). Further structure-activity relationship studies yielded several thiophene-sulfonamide HOPTO derivatives with good, broad-spectrum activity against IDE that have the potential to be useful pharmacological tools for future studies of IDE.     

Improving the Compostability of Natural Fiber-Reinforced Thermoset Composites with a Tertiary Oil Phase

Although fiberglass-reinforced composites play important roles in many industrial applications, the non-biodegradability of the fibers poses some environmental concerns. In this study, bamboo, cotton and hemp are used as natural reinforcing fibers for polyester and epoxy composites. A tertiary oil phase is also added to the matrix and its effect on material biodegradability is characterized. Results show that material biodegradability is increased up to 100% under controlled composting conditions with oil addition. Polyester biodegrades more effectively than epoxy under both macroscopic and microscopic mechanisms. Mechanical strengths of the polyester composites are also found to correlate strongly with material biodegradability.     

Network behavior of thermosetting polyimide/multiwalled carbon nanotube composites

In previous published research, network formation has been used to understand morphology and properties in polymer nanocomposites containing carbon nanotubes (CNTs) through measurements of rheological and electrical percolation thresholds, largely in thermoplastic matrices. In this research, these tools are explored as a means to understand network transport mechanisms and changes in CNT dispersion during curing in a thermosetting matrix. Specifically, rheological and electrical measurements were performed on the uncured nanocomposites, and electrical measurements were performed on the cured nanocomposites. The resulting data were applied to a percolation model. The results showed that the uncured resin played a limited role in mediating rheological transport and that little CNT aggregation occurred during curing. The results of this initial work suggest that such a combination of techniques is applicable to understanding dispersion changes resulting from curing and provides complementary insight to that provided by electron microscopy imaging of the same phenomenon.     

Recombination signal sequence binding protein Jkappa is constitutively bound to the NF-kappaB site of the interleukin-6 promoter and acts as a negative regulatory factor

Analysis by electrophoretic mobility shift assays (EMSA) of the different proteins associated with the kappaB sequence of the interleukin-6 (IL-6) promoter (IL6-kappaB) allowed us to detect a specific complex formed with the recombination signal sequence binding protein Jkappa (RBP-Jkappa). Single-base exchanges within the oligonucleotide sequence defined the critical base pairs involved in the interaction between RBP-Jkappa and the IL6-kappaB motif. Binding analysis suggests that the amount of RBP-Jkappa protein present in the nucleus is severalfold higher than the total amount of inducible NF-kappaB complexes but that the latter bind DNA with a 10-fold-higher affinity. A reporter gene study was performed to determine the functional implication of this binding; we found that the constitutive occupancy of the IL6-kappaB site by the RBP-Jkappa protein was responsible for the low basal levels of IL-6 promoter activity in L929sA fibrosarcoma cells and that RBP-Jkappa partially blocked access of NF-kappaB complexes to the IL-6 promoter. We propose that such a mechanism could be involved in the constitutive repression of the IL-6 gene under normal physiological conditions.     

Validity and cost-effectiveness of antisperm antibody testing before in vitro fertilization

OBJECTIVE: To determine the usefulness of and cost-effectiveness of antisperm antibody testing in the prediction of poor fertilization rates in couples undergoing IVF. DESIGN: Retrospective cohort study. SETTING: A hospital-based reproductive endocrinology and infertility practice. PATIENT(S): Male partners of 251 couples undergoing IVF between 1992 and 1997. MAIN OUTCOME MEASURE(S): Fertilization rates in couples undergoing conventional IVF. RESULT(S): One hundred nineteen couples were evaluated for antisperm antibodies; fertilization rates were similar in those couples whose husbands were and were not tested (64% versus 68%). Antisperm antibodies were detected in 16 men. Four (25%) of the 16 couples whose husbands had antisperm antibodies fertilized < or = 50% of oocytes, compared with 31 (30%) of the 103 couples whose husbands did not have these antibodies. Overall, 21 couples (8.4%) experienced complete fertilization failure. In a program that included antisperm antibody testing for selected couples and intracytoplasmic sperm injection (ICSI) for those who tested positive, it would cost $11,735 to prevent a fertilization failure (assuming ICSI were 100% effective), whereas it would cost $9,250 to perform ICSI in a second IVF cycle for those who initially failed. CONCLUSION(S): In this practice setting, antisperm antibody testing has low sensitivity in predicting low or no fertilization and does not appear to be cost-effective when selectively ordered as part of an IVF workup.     

Development of new cancer chemoprevention agents: role of pharmacokinetic/pharmacodynamic and intermediate endpoint biomarker monitoring

Dimerization is a prerequisite for many growth factors in their receptor activation leading to cellular response. FGF-1 and FGF-2, members of the Fibroblast Growth Factor (FGF) family, were shown to form non-covalent dimers and oligomers in vitro. Using the two-hybrid system as an in vivo binding assay we show here that of three representative members of the FGF family, only FGF-2 is able to homodimerize. Moreover the FGF-2 isoforms could heterodimerize. Two single-point mutants (T121F and W123R), defective in their dimerization capability, were isolated through random mutagenesis and were used to study the role of FGF-2 dimerization with regard to its biological activity. Remarkably, these mutant proteins were still able to induce cell differentiation, but were strongly affected in their capacity to promote cell proliferation. This study thus highlights the uncoupling between proliferation and differentiation FGF-2 signaling pathways and the crucial role of FGF-2 dimerization in the mitogenic activity of this factor.     

An efficient strategy for detection of known and new mutations of the CYP2D6 gene using single strand conformation polymorphism analysis

To detect mutations in the cytochrome P450 CYP2D6 gene (CYP2D6), we developed a strategy based on single-strand conformation polymorphism (SSCP) analysis of the gene amplified by polymerase chain reaction (PCR). The efficiency of the method was evaluated by analysing DNA samples from extensive metabolizers (EM) and poor metabolizers (PM) of debrisoquine. Haplotypes, alleles and mutations of CYP2D6 had previously been characterized in each individual using PCR assays, Xba I restriction fragment length polymorphism (RFLP) and sequencing. PCR-SSCP results were in complete agreement with those obtained using established methods. All previously characterized mutations were associated with particular shifts in the electrophoretic mobility of DNA fragments allowing their identification. We further tested the efficiency of PCR-SSCP for detecting new CYP2D6 mutations. DNA from a PM subject presumed to carry an unknown non-functional mutant allele of CYP2D6 was amplified and bands with aberrant migration patterns were observed on SSCP gels. Sequence analysis of the corresponding DNA fragments revealed the causative mutations. In this way, a novel non-functional allele of the gene, carrying three previously reported mutations and a new mutation in the third exon which results in a premature termination codon, was characterized. Finally, CYP2D6 SSCP analysis was performed on DNA amplified with fluorescent primers and an automated DNA sequencer was used for SSCP analysis of products. We conclude that the PCR-SSCP approach is a powerful method of identifying simultaneously known and new mutations of the CYP2D6 gene.     

Validity of the MMPI-2 Depression content scale with psychiatric inpatients

The concurrent and construct validity of the MMPI-2 Depression content scale was examined for a group of 62 psychiatric inpatients. Correlation coefficients with other measures of depression, hopelessness, low self-esteem, and suicide ideation ranged from .58 to .66 and were statistically significant. Also, the Depression content scale successfully differentiated patients according to psychiatric diagnosis (depressed versus nondepressed) and assessed suicide risk (at risk versus not at risk). Thus, the concurrent and construct validities of the scale were supported.     

Purification and Use of Glycomacropeptide for Nutritional Management of Phenylketonuria

ABSTRACT:  Individuals with phenylketonuria (PKU) cannot metabolize phenylalanine (Phe) and must adhere to a low-Phe diet in which most dietary protein is provided by a Phe-free amino acid formula. Glycomacropeptide (GMP) is the only naturally occurring protein that does not contain Phe, and is of interest as a source of protein for dietary management of PKU. However, commercially available GMP contains too much Phe from residual whey proteins and does not contain adequate levels of all the indispensable amino acids to provide a nutritionally complete protein. The aim of this study was to increase purity of GMP and develop a mass balance calculation for indispensable amino acid supplementation of GMP foods. Cation exchange chromatography, ultrafiltration/diafiltration, and lyophilization were used at the pilot plant scale to decrease Phe. Enough purified GMP (5 kg) was manufactured to provide 15 PKU subjects with a 4-d diet in which the majority of protein was from GMP foods. A mass balance was used to supplement GMP foods so that all indispensable amino acids met or exceeded the daily recommended intake. GMP foods were tested in a human clinical trial as a replacement for the traditional amino acid formula. Nutritionally complete GMP foods created with high purity GMP provide individuals with PKU with more options to manage PKU, which may lead to improved compliance and quality of life.