8 research outputs found
Determinants of Collaborative Leadership: Civic Engagement, Gender or Organizational Norms?
This analysis attempts to unravel competing explanations of collaborative leadership styles of state legislative committee chairs. Specifically, the paper considers the influence of community or volunteer experience, gender, and institutional variables. The data show that women chairs are more likely than their male peers to cite as valuable the leadership skills and experiences that they gain through community and volunteer experience. Compared to their male colleagues, women committee chairs on average also report a greater reliance on collaborative strategies in the management of their committees. Prior community or volunteer experience has little or no direct effect on collaborative styles. In contrast, institutional factors have a much stronger and countervailing influence. Legislative professionalization produces a strong negative effect on collaborative style. Results suggest that conformity to institutional norms may be a more compelling influence than prior community experience. The analysis also points to the gendered nature of organizational leadership with men's and women's styles showing different associations to style depending on the number and power of women in a legislature.Yeshttps://us.sagepub.com/en-us/nam/manuscript-submission-guideline
Arundifungin, a novel antifungal compound produced by fungi: biological activity and taxonomy of the producing organisms
Echinocandins, the lipopeptide class of glucan synthase inhibitors, are an alternative to ergosterol-synthesis inhibitors to treat candidiasis and aspergillosis. Their oral absorption, however, is low and they can only be used parenterally. During a natural product screening program for novel types of glucan synthesis inhibitors with improved bioavailability, a fungal extract was found that inhibited the growth of both a wild-type Saccharomyces cerevisiae strain and the null mutant of the FKS1 gene (fks1::HIS). The mutant strain was more sensitive to growth inhibition, suggesting that the fungal extract could contain an inhibitor of glucan synthesis. A novel acidic steroid, named arundifungin, was purified from a fungal extract obtained from a liquid culture of Arthrinium arundinis collected in Costa Rica. Arundifungin caused the same pattern of hallmark morphological alterations in Aspergillus fumigatus hyphae as echinocandins, further supporting the idea that arundifungin belongs to a new class of glucan synthesis inhibitors. Moreover, its antifungal spectrum was comparable to those of echinocandins and papulacandins, preferentially inhibiting the growth of Candida and Aspergillus strains, with very poor activity against Cryptococcus. Arundifungin was also detected in nine other fungal isolates which were ecologically and taxonomically unrelated, as assessed by sequencing of the ITS1 region. Further, it was also found in two more Arthrinium spp from tropical and temperate regions, in five psychrotolerant conspecific isolates collected on Macquarie Island South Pacific) and belonging to the Leotiales, and in two endophytes collected in central Spain a sterile fungus belonging to the Leotiales and an undetermined coelomycete)
Antifungal Spectrum, In Vivo Efficacy, and Structure–Activity Relationship of Ilicicolin H
Ilicicolin H is a polyketidenonribosomal peptide
synthase
(NRPS)natural product isolated from <i>Gliocadium roseum</i>, which exhibits potent and broad spectrum antifungal activity, with
sub-μg/mL MICs against <i>Candida</i> spp., <i>Aspergillus fumigatus</i>, and <i>Cryptococcus</i> spp. It showed a novel mode of action, potent inhibition (IC<sub>50</sub> = 2–3 ng/mL) of the mitochondrial cytochrome bc1
reductase, and over 1000-fold selectivity relative to rat liver cytochrome
bc1 reductase. Ilicicolin H exhibited in vivo efficacy in murine models
of <i>Candida albicans</i> and <i>Cryptococcus neoformans</i> infections, but efficacy may have been limited by high plasma protein
binding. Systematic structural modification of ilicicolin H was undertaken
to understand the structural requirement for the antifungal activity.
The details of the biological activity of ilicicolin H and structural
modification of some of the key parts of the molecule and resulting
activity of the derivatives are discussed. These data suggest that
the β-keto group is critical for the antifungal activity
A Novel Staphylococcus aureus Vaccine: Iron Surface Determinant B Induces Rapid Antibody Responses in Rhesus Macaques and Specific Increased Survival in a Murine S. aureus Sepsis Model
Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the rate of resistance to clinically relevant antibiotics, such as methicillin, is increasing; furthermore, there has been an increase in the number of methicillin-resistant S. aureus community-acquired infections. Effective treatment and prevention strategies are urgently needed. We investigated the potential of the S. aureus surface protein iron surface determinant B (IsdB) as a prophylactic vaccine against S. aureus infection. IsdB is an iron-sequestering protein that is conserved in diverse S. aureus clinical isolates, both methicillin resistant and methicillin sensitive, and it is expressed on the surface of all isolates tested. The vaccine was highly immunogenic in mice when it was formulated with amorphous aluminum hydroxyphosphate sulfate adjuvant, and the resulting antibody responses were associated with reproducible and significant protection in animal models of infection. The specificity of the protective immune responses in mice was demonstrated by using an S. aureus strain deficient for IsdB and HarA, a protein with a high level of identity to IsdB. We also demonstrated that IsdB is highly immunogenic in rhesus macaques, inducing a more-than-fivefold increase in antibody titers after a single immunization. Based on the data presented here, IsdB has excellent prospects for use as a vaccine against S. aureus disease in humans