Mitochondria as a Potential Antifungal Target for Isocyanide Compounds

The discovery of antibiotics and antifungals greatly impacted medicine and human health, allowing the effective treatment of infections that were previously deadly. However, due to routine and sometimes excessive usage of these compounds, the development of antimicrobial resistance has created a need for new antibiotic and antifungal compounds. Isocyanide compounds have been shown to have antibacterial, antifungal, and anti-cancer properties, but very little is known about their biochemical effects. Our research aims to understand the mechanism of action of isocyanide compounds. We have conducted a genetic screen of a Saccharomyces gene-deletion (“knockout”) collection on media containing an easily synthesized model isocyanide compound, para-nitrophenyl isocyanide (p-NPIC). This allowed us to identify genes which, when deleted, render the mutant strains resistant or hypersensitive to the compound. Based on our genetic screen for hypersensitive mutants, we hypothesize that the isocyanides impact mitochondrial function, specifically altering the function of the Cu++-containing respiratory complex, Cytochrome C Oxidase (Complex IV). Our findings provide new information on the mechanism(s) of action of this class of antimicrobials and will help guide the development of new molecules based on lead-compounds such as p-NPIC

Cultivar-Dependent Expression of a Maize Lipoxygenase Responsive to Seed Infesting Fungi

Maize kernels are highly susceptible to Aspergillus spp. infection and aflatoxin (AF) contamination. Fatty acid signaling molecules appear to mediate the plant–fungal interaction by affecting the growth, development, and AF production of the fungus. In particular, fatty acid derivatives of the plant lipoxygenase (LOX) pathway are implicated in the Aspergillus spp.-seed interaction. The 9(S)-hydroperoxide derivative of linoleic acid promotes transcription of AF genes, whereas the 13(S)-hydroperoxide derivative decreases AF gene expression and production; both are sporulation factors. Our goal was to identify LOX genes responsive to Aspergillus spp. colonization and determine their specificities, 9(S)- or 13(S)-. Screening maize LOX expressed sequence tags (ESTs) identified one clone, cssap 92, which is highly expressed in Aspergillus spp.-infected seed susceptible to AF contamination and repressed in lines with resistance to AF contamination. The accumulation of cssap 92 transcript was similar during Fusarium spp. infection. The cDNA clone has 94% identity to the previously described L2 LOX gene from maize. Product-specificity analysis of the CSSAP 92 protein shows that it preferentially adds oxygen to carbon 9 of linoleic acid. Because 9(S)-hydroperoxy linoleic acid has been implicated as an aflatoxin-signaling molecule, it is possible that cssap 92 could be used as a biomarker that is indicative of AF resistance in maize lines

Cultivar-Dependent Expression of a Maize Lipoxygenase Responsive to Seed Infesting Fungi

Maize kernels are highly susceptible to Aspergillus spp. infection and aflatoxin (AF) contamination. Fatty acid signaling molecules appear to mediate the plant–fungal interaction by affecting the growth, development, and AF production of the fungus. In particular, fatty acid derivatives of the plant lipoxygenase (LOX) pathway are implicated in the Aspergillus spp.-seed interaction. The 9(S)-hydroperoxide derivative of linoleic acid promotes transcription of AF genes, whereas the 13(S)-hydroperoxide derivative decreases AF gene expression and production; both are sporulation factors. Our goal was to identify LOX genes responsive to Aspergillus spp. colonization and determine their specificities, 9(S)- or 13(S)-. Screening maize LOX expressed sequence tags (ESTs) identified one clone, cssap 92, which is highly expressed in Aspergillus spp.-infected seed susceptible to AF contamination and repressed in lines with resistance to AF contamination. The accumulation of cssap 92 transcript was similar during Fusarium spp. infection. The cDNA clone has 94% identity to the previously described L2 LOX gene from maize. Product-specificity analysis of the CSSAP 92 protein shows that it preferentially adds oxygen to carbon 9 of linoleic acid. Because 9(S)-hydroperoxy linoleic acid has been implicated as an aflatoxin-signaling molecule, it is possible that cssap 92 could be used as a biomarker that is indicative of AF resistance in maize lines

Data report : hypoxia in the James River, 1992

As part of the hypoxia program of the Virginia Chesapeake Bay Initiatives, the Department of Physical Sciences of the Virginia Institute of Marine Science (VIMS) conducted a series of measurements around the mouth of the James River estuary. The measurements were made in the summer of 1992. Two types of measurements were conducted: measurements at moored stations and measurements by slackwater surveys. The former collected data for investigation of dissolved oxygen (DO) variation, and associated physical parameters, in an intratidal time scale, as well as for studying the vertical distributions of the measured parameters. The latter collected data for spatial distributions of DO, temperature, and salinity, and for investigation of temporal variation over the summer. This data report describes the field measurements and provides graphical presentation of the data. The numerical values of the data are archived and stored on magnetic tapes, which may be retrieved through the VIMS computer system

Aphid Thermal Tolerance Is Governed by a Point Mutation in Bacterial Symbionts

Symbiosis is a ubiquitous phenomenon generating biological complexity, affecting adaptation, and expanding ecological capabilities. However, symbionts, which can be subject to genetic limitations such as clonality and genomic degradation, also impose constraints on hosts. A model of obligate symbiosis is that between aphids and the bacterium Buchnera aphidicola, which supplies essential nutrients. We report a mutation in Buchnera of the aphid Acyrthosiphon pisum that recurs in laboratory lines and occurs in field populations. This single nucleotide deletion affects a homopolymeric run within the heat-shock transcriptional promoter for ibpA, encoding a small heat-shock protein. This Buchnera mutation virtually eliminates the transcriptional response of ibpA to heat stress and lowers its expression even at cool or moderate temperatures. Furthermore, this symbiont mutation dramatically affects host fitness in a manner dependent on thermal environment. Following a short heat exposure as juveniles, aphids bearing short-allele symbionts produced few or no progeny and contained almost no Buchnera, in contrast to aphids bearing symbionts without the deletion. Conversely, under constant cool conditions, aphids containing symbionts with the short allele reproduced earlier and maintained higher reproductive rates. The short allele has appreciable frequencies in field populations (up to 20%), further supporting the view that lowering of ibpA expression improves host fitness under some conditions. This recurring Buchnera mutation governs thermal tolerance of aphid hosts. Other cases in which symbiont microevolution has a major effect on host ecological tolerance are likely to be widespread because of the high mutation rates of symbiotic bacteria and their crucial roles in host metabolism and development

Mitochondria as a Potential Antifungal Target for Isocyanide Compounds

The discovery of antibiotics and antifungals greatly impacted medicine and human health, allowing the effective treatment of infections that were previously deadly. However, due to routine and sometimes excessive usage of these compounds, the development of antimicrobial resistance has created a need for new antibiotic and antifungal compounds. Isocyanide compounds have been shown to have antibacterial, antifungal, and anti-cancer properties, but very little is known about their biochemical effects. Our research aims to understand the mechanism of action of isocyanide compounds. We have conducted a genetic screen of a Saccharomyces gene-deletion (“knockout”) collection on media containing an easily synthesized model isocyanide compound, para-nitrophenyl isocyanide (p-NPIC). This allowed us to identify genes which, when deleted, render the mutant strains resistant or hypersensitive to the compound. Based on our genetic screen for hypersensitive mutants, we hypothesize that the isocyanides impact mitochondrial function, specifically altering the function of the Cu++-containing respiratory complex, Cytochrome C Oxidase (Complex IV). Our findings provide new information on the mechanism(s) of action of this class of antimicrobials and will help guide the development of new molecules based on lead-compounds such as p-NPIC

The Spitzer Warm Mission Science Prospects

After exhaustion of its cryogen, the Spitzer Space telescope will still have a fully functioning two-channel mid-IR camera that will have sensitivities better than any other ground or space-based telescopes until the launch of JWST. This document provides a description of the expected capabilities of Spitzer during its warm mission phase, and provides brief descriptions of several possible very large science programs that could be conducted. This information is intended to serve as input to a wide ranging discussion of the warm mission science, leading up to the Warm Mission Workshop in June 2007

Patient and Provider Perspectives on How Trust Influences Maternal Vaccine Acceptance Among Pregnant Women in Kenya

Background Pregnant women and newborns are at high risk for infectious diseases. Altered immunity status during pregnancy and challenges fully vaccinating newborns contribute to this medical reality. Maternal immunization is a strategy to protect pregnant women and their newborns. This study aimed to find out how patient-provider relationships affect maternal vaccine uptake, particularly in the context of a lower middle- income country where limited research in this area exists. Methods We conducted semi-structured, in-depth narrative interviews of both providers and pregnant women from four sites in Kenya: Siaya, Nairobi, Mombasa, and Marsabit. Interviews were conducted in either English or one of the local regional languages. Results We found that patient trust in health care providers (HCPs) is integral to vaccine acceptance among pregnant women in Kenya. The HCP-patient relationship is a fiduciary one, whereby the patients’ trusts is primarily rooted in the provider’s social position as a person who is highly educated in matters of health. Furthermore, patient health education and provider attitudes are crucial for reinstating and fostering that trust, especially in cases where trust was impeded by rumors, community myths and misperceptions, and religious and cultural factors. Conclusion Patient trust in providers is a strong facilitator contributing to vaccine acceptance among pregnant women in Kenya. To maintain and increase immunization trust, providers have a critical role in cultivating a positive environment that allows for favorable interactions and patient health education. This includes educating providers on maternal immunizations and enhancing knowledge of effective risk communication tactics in clinical encounters

A genome-wide association study identifies a susceptibility locus for biliary atresia on 2p16.1 within the gene EFEMP1

Biliary atresia (BA) is a rare pediatric cholangiopathy characterized by fibrosclerosing obliteration of the extrahepatic bile ducts, leading to cholestasis, fibrosis, cirrhosis, and eventual liver failure. The etiology of BA remains unknown, although environmental, inflammatory, infectious, and genetic risk factors have been proposed. We performed a genome-wide association study (GWAS) in a European-American cohort of 343 isolated BA patients and 1716 controls to identify genetic loci associated with BA. A second GWAS was performed in an independent European-American cohort of 156 patients with BA and other extrahepatic anomalies and 212 controls to confirm the identified candidate BA-associated SNPs. Meta-analysis revealed three genome-wide significant BA-associated SNPs on 2p16.1 (rs10865291, rs6761893, and rs727878; P < 5 ×10-8), located within the fifth intron of the EFEMP1 gene, which encodes a secreted extracellular protein implicated in extracellular matrix remodeling, cell proliferation, and organogenesis. RNA expression analysis showed an increase in EFEMP1 transcripts from human liver specimens isolated from patients with either BA or other cholestatic diseases when compared to normal control liver samples. Immunohistochemistry demonstrated that EFEMP1 is expressed in cholangiocytes and vascular smooth muscle cells in liver specimens from patients with BA and other cholestatic diseases, but it is absent from cholangiocytes in normal control liver samples. Efemp1 transcripts had higher expression in cholangiocytes and portal fibroblasts as compared with other cell types in normal rat liver. The identification of a novel BA-associated locus, and implication of EFEMP1 as a new BA candidate susceptibility gene, could provide new insights to understanding the mechanisms underlying this severe pediatric disorder

Predictors of financial capacity performance in older adults using the Financial Competence Assessment Inventory

Background