3,5-Dinitro­benzyl methane­sulfonate

The title compound, C8H8N2O7S, an inter­mediate in the synthesis of N,N-bis­(2-hydroxy­ethyl)-3,5-dinitro­aniline, exists as a discrete mol­ecule; the nitro groups are twisted with respect to the aromatic system [dihedral angles = 17.0 (1) and 26.3 (1)°]

N-[3-(tert-Butyl­dimethyl­siloxymeth­yl)-5-nitro­phen­yl]acetamide

The title compound, C15H24N2O4Si, was prepared by the reaction of (3-acetamido-5-nitro­benz­yl)methanol with tert-butyl­dimethyl­silyl chloride and is a key inter­mediate in the synthesis of novel nonsymmetrical DNA minor groove-binding agents. There are two independent mol­ecules in the structure, which differ primarily in the rotation about the C—O bond next to the Si atom. Two strong N—H⋯O hydrogen bonds align the mol­ecules into a wide ribbon extending approximately parallel to the b axis

Men at risk; a qualitative study on HIV risk, gender identity and violence among men who have sex with men who report high risk behavior in Kampala, Uganda.

In Uganda, men who have sex with men (MSM) are at high risk for HIV. Between May 2008 and February 2009 in Kampala, Uganda, we used respondent driven sampling (RDS) to recruit 295 MSM≥18 years who reported having had sex with another man in the preceding three months. The parent study conducted HIV and STI testing and collected demographic and HIV-related behavioral data through audio computer-assisted self-administered interviews. We conducted a nested qualitative sub-study with 16 men purposively sampled from among the survey participants based on responses to behavioral variables indicating higher risk for HIV infection. Sub-study participants were interviewed face-to-face. Domains of inquiry included sexual orientation, gender identity, condom use, stigma, discrimination, violence and health seeking behavior. Emergent themes included a description of sexual orientation/gender identity categories. All groups of men described conflicting feelings related to their sexual orientation and contextual issues that do not accept same-sex identities or behaviors and non-normative gender presentation. The emerging domains for facilitating condom use included: lack of trust in partner and fear of HIV infection. We discuss themes in the context of social and policy issues surrounding homosexuality and HIV prevention in Uganda that directly affect men\u27s lives, risk and health-promoting behaviors

N-{3-[Bis(2-hydroxy­ethyl)amino­meth­yl]-5-nitro­phen­yl}benzamide

The title compound, C18H21N3O5, was prepared by the reaction of 3-benzamido-5-nitro­benzyl methane­sulfonate with diethano­lamine and is an inter­mediate in the synthesis of DNA minor-groove-binding polybenzamide agents capable of being conjugated to additional biologically active species. The asymmetric unit contains two independent mol­ecules, which differ only in the orientations of the hydroxy­ethyl groups. In the crystal structure, inter­molecular N—H⋯O and O—H⋯O hydrogen bonds link mol­ecules into one-dimensional chains

Combining experiment and energy landscapes to explore anaerobic heme breakdown in multifunctional hemoproteins

To survive, many pathogens extract heme from their host organism and break down the porphyrin scaffold to sequester the Fe2+ ion via a heme oxygenase. Recent studies have revealed that certain pathogens can anaerobically degrade heme. Our own research has shown that one such pathway proceeds via NADH-dependent heme degradation, which has been identified in a family of hemoproteins from a range of bacteria. HemS, from Yersinia enterocolitica, is the main focus of this work, along with HmuS (Yersinia pestis), ChuS (Escherichia coli) and ShuS (Shigella dysenteriae). We combine experiments, Energy Landscape Theory, and a bioinformatic investigation to place these homologues within a wider phylogenetic context. A subset of these hemoproteins are known to bind certain DNA promoter regions, suggesting not only that they can catalytically degrade heme, but that they are also involved in transcriptional modulation responding to heme flux. Many of the bacterial species responsible for these hemoproteins (including those that produce HemS, ChuS and ShuS) are known to specifically target oxygen-depleted regions of the gastrointestinal tract. A deeper understanding of anaerobic heme breakdown processes exploited by these pathogens could therefore prove useful in the development of future strategies for disease prevention

Plant-expressed Hepatitis B core antigen virus-like particles: Characterization and investigation of their stability in simulated and pig gastro-intestinal fluids

Virus-like particles (VLPs) are potential oral vaccine candidates, as their highly compact structure may allow them to withstand the harsh conditions of the gastro-intestinal (GI) environment. Hepatitis B core antigen (HBcAg) is an immunogenic protein that assembles into 30 or 34 nm diameter VLPs. Here, the stabilities of both the HBcAg polypeptide itself and the three-dimensional structure of the VLPs upon exposure to in vitro and ex vivo simulated gastric and intestinal fluids were investigated. Plant-expressed HBcAg VLPs were efficiently purified by sucrose density gradient and characterized. The purified VLPs did not show major chemical or physical instability upon exposure to the low pH conditions typically found in the stomach; however, they completely agglomerated upon acidification and subsequent pH neutralization. The HBcAg polypeptide was highly digested upon exposure to pepsin in simulated gastric fluids. HBcAg appeared more stable in both simulated and ex vivo intestinal fluids, where despite a partial digestion of the HBcAg polypeptide, the VLPs maintained their most immunogenic epitopes and their particulate conformation. These results suggest that HBcAg VLPs are likely to be unstable in gastric fluids, yet if the gastric instability could be bypassed, they could maintain their particulate structure and immunogenicity in intestinal fluids

Local Population Structure and Patterns of Western Hemisphere Dispersal for Coccidioides spp., the Fungal Cause of Valley Fever.

UnlabelledCoccidioidomycosis (or valley fever) is a fungal disease with high morbidity and mortality that affects tens of thousands of people each year. This infection is caused by two sibling species, Coccidioides immitis and C. posadasii, which are endemic to specific arid locales throughout the Western Hemisphere, particularly the desert southwest of the United States. Recent epidemiological and population genetic data suggest that the geographic range of coccidioidomycosis is expanding, as new endemic clusters have been identified in the state of Washington, well outside the established endemic range. The genetic mechanisms and epidemiological consequences of this expansion are unknown and require better understanding of the population structure and evolutionary history of these pathogens. Here we performed multiple phylogenetic inference and population genomics analyses of 68 new and 18 previously published genomes. The results provide evidence of substantial population structure in C. posadasii and demonstrate the presence of distinct geographic clades in central and southern Arizona as well as dispersed populations in Texas, Mexico, South America, and Central America. Although a smaller number of C. immitis strains were included in the analyses, some evidence of phylogeographic structure was also detected in this species, which has been historically limited to California and Baja, Mexico. Bayesian analyses indicated that C. posadasii is the more ancient of the two species and that Arizona contains the most diverse subpopulations. We propose a southern Arizona-northern Mexico origin for C. posadasii and describe a pathway for dispersal and distribution out of this region.ImportanceCoccidioidomycosis, or valley fever, is caused by the pathogenic fungi Coccidioides posadasii and C. immitis The fungal species and disease are primarily found in the American desert southwest, with spotted distribution throughout the Western Hemisphere. Initial molecular studies suggested a likely anthropogenic movement of C. posadasii from North America to South America. Here we comparatively analyze eighty-six genomes of the two Coccidioides species and establish local and species-wide population structures to not only clarify the earlier dispersal hypothesis but also provide evidence of likely ancestral populations and patterns of dispersal for the known subpopulations of C. posadasii

Group 2: The Changing Structure of the New Zealand Work-Force

This discussion group focussed on questions surrounding the changing structure of the New Zealand work-force. The major questions in this field are to identify what it is they must decides and why it requires explanation. Trends must be identified and “forecasts” made of changes in the work-force, drawing attention to the range of policy “interventions’ they imply. This overall task involves examining changes in the demand for labour (the supply of jobs) and the supply of labour (the demand of jobs)

An experiment to assess the effects of diatom dissolution on oxygen isotope ratios

Rationale: Current studies which use the oxygen isotope composition from diatom silica (δ18Odiatom) as a palaeoclimate proxy assume that the δ18Odiatom value reflects the isotopic composition of the water in which the diatom formed. However, diatoms dissolve post mortem, preferentially losing less silicified structures in the water column and during/after burial into sediments. The impact of dissolution on δ18Odiatom values and potential misinterpretation of the palaeoclimate record are evaluated. Methods: Diatom frustules covering a range of ages (6 samples from the Miocene to the Holocene), environments and species were exposed to a weak alkaline solution for 48 days at two temperatures (20 °C and 4 °C), mimicking natural dissolution post mucilage removal. Following treatment, dissolution was assessed using scanning electron microscope images and a qualitative diatom dissolution index. The diatoms were subsequently analysed for their δ18O values using step-wise fluorination and isotope ratio mass spectrometry. Results: Variable levels of diatom dissolution were observed between the six samples; in all cases higher temperatures resulted in more frustule degradation. Dissolution was most evident in younger samples, probably as a result of the more porous nature of the silica. The degree of diatom dissolution does not directly equate to changes in the isotope ratios; the δ18Odiatom value was, however, lower after dissolution, but in only half the samples was this reduction outside the analytical error (2σ analytical error = 0.46‰). Conclusions: We have shown that dissolution can have a small negative impact on δ18Odiatom values, causing reductions of up to 0.59‰ beyond analytical error (0.46‰) at natural environmental temperatures. These findings need to be considered in palaeoenvironmental reconstructions using δ18Odiatom values, especially when interpreting variations in these values of <1‰