Characterization of a Novel Fusion Protein from IpaB and IpaD of Shigella spp. and Its Potential as a Pan-Shigella Vaccine

Shigellosis is an important disease in the developing world, where about 90 million people become infected with Shigella spp. each year. We previously demonstrated that the type three secretion apparatus (T3SA) proteins IpaB and IpaD are protective antigens in the mouse lethal pulmonary model. In order to simplify vaccine formulation and process development, we have evaluated a vaccine design that incorporates both of these previously tested Shigella antigens into a single polypeptide chain. To determine if this fusion protein (DB fusion) retains the antigenic and protective capacities of IpaB and IpaD, we immunized mice with the DB fusion and compared the immune response to that elicited by the IpaB/IpaD combination vaccine. Purification of the DB fusion required coexpression with IpgC, the IpaB chaperone, and after purification it maintained the highly α-helical characteristics of IpaB and IpaD. The DB fusion also induced comparable immune responses and retained the ability to protect mice against Shigella flexneri and S. sonnei in the lethal pulmonary challenge. It also offered limited protection against S. dysenteriae challenge. Our results show the feasibility of generating a protective Shigella vaccine comprised of the DB fusion

Transformative intersectionality: moving business towards a critical praxis

Drawing on intersectionality’s historical feminist roots of critical praxis and recent re-radicalization of the theory, this paper urges for an expansion of the concept of intersectionality in business and marketing-related studies. To extend the transformative potential of intersectionality theory, we call for scholars and practitioners to move beyond the study of intersecting identity markers (e.g., gender, race, class) to include assessments of power structures and intersectional oppressions. We propose the transformative intersectional framework (TIF) to help scholars and practitioners to explore sources of oppressions more deeply and broadly. We illustrate the analytical capability of the TIF by examining a much lauded business-to-business service that seeks social justice and change—diversity training programs. Using the TIF, we identify the inherent and (in)visible complexities of injustices with which organizations must grapple. We close by demonstrating how the TIF can enrich practice and propose recommendations for action

Specific nuclear envelope transmembrane proteins can promote the location of chromosomes to and from the nuclear periphery

BACKGROUND: Different cell types have distinctive patterns of chromosome positioning in the nucleus. Although ectopic affinity-tethering of specific loci can be used to relocate chromosomes to the nuclear periphery, endogenous nuclear envelope proteins that control such a mechanism in mammalian cells have yet to be widely identified. RESULTS: To search for such proteins twenty three nuclear envelope transmembrane proteins were screened for their ability to promote peripheral localization of human chromosomes in HT1080 fibroblasts. Five of these proteins had strong effects on chromosome 5, but individual proteins affected different subsets of chromosomes. The repositioning effects were reversible and the proteins with effects all exhibited highly tissue-restricted patterns of expression. Depletion of two nuclear envelope transmembrane proteins that were preferentially expressed in liver each reduced the normal peripheral positioning of chromosome 5 in liver cells. CONCLUSIONS: The discovery of nuclear envelope transmembrane proteins that can modulate chromosome position and have restricted patterns of expression may enable dissection of the functional relevance of tissue-specific patterns of radial chromosome positioning.Publisher PDFPeer reviewe

Integration of prevention and control measures for female genital schistosomiasis, HIV and cervical cancer

Female genital schistosomiasis as a result of chronic infection with Schistosoma haematobium (commonly known as bilharzia) continues to be largely ignored by national and global health policy-makers. International attention for large-scale action against the disease focuses on whether it is a risk factor for the transmission of human immunodeficiency virus (HIV). Yet female genital schistosomiasis itself is linked to pain, bleeding and sub- or infertility, leading to social stigma, and is a common issue for women in schistosomiasis-endemic areas in sub-Saharan Africa. The disease should therefore be recognized as another component of a comprehensive health and human rights agenda for women and girls in Africa, alongside HIV and cervical cancer. Each of these three diseases has a targeted and proven preventive intervention: antiretroviral therapy and pre-exposure prophylaxis for HIV; human papilloma virus vaccine for cervical cancer; and praziquantel treatment for female genital schistosomiasis. We discuss how female genital schistosomiasis control can be integrated with HIV and cervical cancer care. Such a programme will be part of a broader framework of sexual and reproductive health and rights, women’s empowerment and social justice in Africa. Integrated approaches that join up multiple public health programmes have the potential to expand or create opportunities to reach more girls and women throughout their life course. We outline a pragmatic operational research agenda that has the potential to optimize joint implementation of a package of measures responding to the specific needs of girls and wome

‘Inspired and assisted’, or ‘berated and destroyed’? Research leadership, management and performativity in troubled times

Research leadership in Australian universities takes place against a backdrop of policy reforms concerned with measurement and comparison of institutional research performance. In particular, the Excellence in Research in Australian initiative undertaken by the Australian Research Council sets out to evaluate research quality in Australian universities, using a combination of expert review process, and assessment of performance against &lsquo;quality indicators&rsquo;. Benchmarking exercises of this sort continue to shape institutional policy and practice, with inevitable effects on the ways in which research leadership, mentoring and practice are played out within university faculties and departments. In an exploratory study that interviewed 32 Australian academics in universities in four Australian states, we asked participants, occupying formal or informal research leadership roles, to comment on their perceptions of research leadership as envisioned and enacted in their particular workplaces. We found a pervasive concern amongst participants that coalesced around binaries characterized in metaphoric terms of &lsquo;carrots and whips&rsquo;. Research leadership was seen by many as managerial in nature, and as such, largely tethered to instrumentalist notions of productivity and performativity, while research cultures were seen as languishing under the demoralizing weight of reward and punishment systems. Here, we consider what is at stake for the future of the academic workforce under such conditions, arguing that new models of visionary research leadership are urgently needed in the &lsquo;troubled times&rsquo; of techno-bureaucratic university reforms.<br /

Rietveld refinement of Sr5(AsO4)3Cl from high-resolution synchrotron data

The apatite-type compound, penta­strontium tris­[arsenate(V)] chloride, Sr5(AsO4)3Cl, has been synthesized by ion exchange at high temperature from a synthetic sample of mimetite [Pb5(AsO4)3Cl] with SrCO3 as a by-product. The results of the Rietveld refinement, based on high resolution synchrotron X-ray powder diffraction data, show that the title compound crystallizes in the same structure as other halogenoapatites with general formula A 5(YO4)3 X (A = divalent cation, Y = penta­valent cation, and X = F, Cl or Br) in the space group P63/m. The structure consists of isolated tetra­hedral AsO4 3− anions (the As atom and two O atoms have m symmetry), separated by two crystallographically independent Sr2+ cations that are located on mirror planes and threefold rotation axes, respectively. One Sr atom is coordinated by nine O atoms and the other by six. The chloride anions (site symmetry ) are at the 2a sites and are located in the channels of the structure

PADI4 genotype is not associated with rheumatoid arthritis in a large UK Caucasian population

BACKGROUND: Polymorphisms of the peptidylarginine deiminase type 4 (PADI4) gene confer susceptibility to rheumatoid arthritis (RA) in East Asian people. However, studies in European populations have produced conflicting results. This study explored the association of the PADI4 genotype with RA in a large UK Caucasian population. METHODS: The PADI4_94 (rs2240340) single nucleotide polymorphism (SNP) was directly genotyped in a cohort of unrelated UK Caucasian patients with RA (n=3732) and population controls (n=3039). Imputed data from the Wellcome Trust Case Control Consortium (WTCCC) was used to investigate the association of PADI4_94 with RA in an independent group of RA cases (n=1859) and controls (n=10 599). A further 56 SNPs spanning the PADI4 gene were investigated for association with RA using data from the WTCCC study. RESULTS: The PADI4_94 genotype was not associated with RA in either the present cohort or the WTCCC cohort. Combined analysis of all the cases of RA (n=5591) and controls (n=13 638) gave an overall OR of 1.01 (95% CI 0.96 to 1.05, p=0.72). No association with anti-CCP antibodies and no interaction with either shared epitope or PTPN22 was detected. No evidence for association with RA was identified for any of the PADI4 SNPs investigated. Meta-analysis of previously published studies and our data confirmed no significant association between the PADI4_94 genotype and RA in people of European descent (OR 1.06, 95% CI 0.99 to 1.13, p=0.12). CONCLUSION: In the largest study performed to date, the PADI4 genotype was not a significant risk factor for RA in people of European ancestry, in contrast to Asian populations