Chimaeric HIV-1 subtype C Gag molecules with large in-frame C-terminal polypeptide fusions form virus-like particles

HIV-1 Pr55 Gag virus-like particles (VLPs) are strong immunogens with potential as candidate HIV vaccines. VLP immunogenicity can be broadened by making chimaeric Gag molecules: however, VLPs incorporating polypeptides longer than 200 aa fused in frame with Gag have not yet been reported. We constructed a range of gag-derived genes encoding in-frame C-terminal fusions of myristoylation-competent native Pr55Gag and p6-truncated Gag (Pr50Gag) to test the effects of polypeptide length and sequence on VLP formation and morphology, in an insect cell expression system. Fused sequences included a modified reverse transcriptase-Tat-Nef fusion polypeptide (RTTN, 778 aa), and truncated versions of RTTN ranging from 113 aa to 450 aa. Baculovirus-expressed chimaeric proteins were examined by western blot and electron microscopy. All chimaeras formed VLPs which could be purified by sucrose gradient centrifugation. VLP diameter increased with protein MW, from ∼100 nm for Pr55Gag to ∼250 nm for GagRTTN. The presence or absence of the Gag p6 region did not obviously affect VLP formation or appearance. GagRT chimaeric particles were successfully used in mice to boost T-cell responses to Gag and RT that were elicited by a DNA vaccine encoding a GagRTTN polypeptide, indicating the potential of such chimaeras to be used as candidate HIV vaccines. © 2008 Elsevier B.V. All rights reserved.

An investigation into the use of human papillomavirus type 16 virus-like particles as a delivery vector system for foreign proteins: N- and C-terminal fusion of GFP to the L1 and L2 capsid proteins

Development of vaccine strategies against human papillomavirus (HPV), which causes cervical cancer, is a priority. We investigated the use of virus-like particles (VLPs) of the most prevalent type, HPV-16, as carriers of foreign proteins. Green fluorescent protein (GFP) was fused to the N or C terminus of both L1 and L2, with L2 chimeras being co-expressed with native L1. Purified chimaeric VLPs were comparable in size (∼55 nm) to native HPV VLPs. Conformation-specific monoclonal antibodies (Mabs) bound to the VLPs, thereby indicating that they possibly retain their antigenicity. In addition, all of the VLPs encapsidated DNA in the range of 6-8 kb. © 2007 Springer-Verlag.

DRD2/ANKK1 Taq1A (rs 1800497 C>T) genotypes are associated with susceptibility to second generation antipsychotic-induced akathisia

Rationale Although the advent of atypical, second-generation antipsychotics (SGAs) has resulted in reduced likelihood of akathisia, this adverse effect remains a problem. Extrapyramidal adverse effects are associated with increased drug occupancy of dopamine 2 receptors (DRD2). The A1 allele of the DRD2/ANKK1,rs1800497, is associated with decreased striatal DRD2 density. Objectives The aim of this study was to identify whether the A1(T) allele of the DRD2/ANKK1 was associated with akathisia (measured with the Barnes Akathisia Rating Scale) in a clinical sample of 234 patients treated with antipsychotics. Results Definite akathisia (a score≥ 2 for the global clinical assessment of akathisia) was significantly less common in subjects prescribed SGAs (16.8 %) than those prescribed FGAs (47.6%), p<0.0001. Overall, 24.1% of A1+ (A1A2/A1A1) patients treated with SGAs had akathisia compared to 10.8% of A1- (A2A2) patients. A1+ (A1A2/A1A1) patients administered SGAs also had higher global clinical assessment of akathisia scores than A1- subjects (p=0.01). SGAs maintained their advantage over FGAs regarding akathisia even in A1+ patients treated with SGAs. Conclusions These results strongly suggest that A1+ variants of the DRD2/ANKK1 Taq1A allele confer risk for akathisia in patients treated with SGAs and may explain inconsistencies across prior studies comparing FGAs and SGAs.

RcppArmadillo : accelerating R with high-performance C++ linear algebra

The R statistical environment and language has demonstrated particular strengths for interactive development of statistical algorithms, as well as data modelling and visualisation. Its current implementation has an interpreter at its core which may result in a performance penalty in comparison to directly executing user algorithms in the native machine code of the host CPU. In contrast, the C++ language has no built-in visualisation capabilities, handling of linear algebra or even basic statistical algorithms; however, user programs are converted to high-performance machine code, ahead of execution. A new method avoids possible speed penalties in R by using the Rcpp extension package in conjunction with the Armadillo C++ matrix library. In addition to the inherent performance advantages of compiled code, Armadillo provides an easy-to-use template-based meta-programming framework, allowing the automatic pooling of several linear algebra operations into one, which in turn can lead to further speedups. With the aid of Rcpp and Armadillo, conversion of linear algebra centered algorithms from R to C++ becomes straightforward. The algorithms retains the overall structure as well as readability, all while maintaining a bidirectional link with the host R environment. Empirical timing comparisons of R and C++ implementations of a Kalman filtering algorithm indicate a speedup of several orders of magnitude.

Analytical Solution of a Walters’ Liquid B Flow Over a Linear Stretching Sheet in a Porous Medium

This chapter represents the analytical solution of two-dimensional linear stretching sheet problem involving a non-Newtonian liquid and suction by (a) invoking the boundary layer approximation and (b) using this result to solve the stretching sheet problem without using boundary layer approximation. The basic boundary layer equations for momentum, which are non-linear partial differential equations, are converted into non-linear ordinary differential equations by means of similarity transformation. The results reveal a new analytical procedure for solving the boundary layer equations arising in a linear stretching sheet problem involving a non-Newtonian liquid (Walters’ liquid B). The present study throws light on the analytical solution of a class of boundary layer equations arising in the stretching sheet problem.

Enhancing photoactivity of TiO2(B)/anatase core-shell nanofibers by selectively doping cerium ions into the TiO2(B) Core

Cerium ions (Ce3+) can beselectively doped into the TiO2(B) core of TiO2(B)/anatase core–shell nanofibers by means of a simple one-pot hydrothermal treatment of a starting material of hydrogen trititanate (H2Ti3O7) nanofibers. These Ce3+ ions (≈0.202 nm) are located on the (110) lattice planes of the TiO2(B) core in tunnels (width≈0.297 nm). The introduction of Ce3+ ions reduces the defects of the TiO2(B) core by inhibiting the faster growth of (110) lattice planes. More importantly, the redox potential of the Ce3+/Ce4+ couple (E0(Ce3+/Ce4+)=1.715 V versus the normal hydrogen electrode) is more negative than the valence band of TiO2(B). Therefore, once the Ce3+-doped nanofibers are irradiated by UV light, the doped Ce3+ ions in close vicinity to the interface between the TiO2(B) core and anatase nanoshell can efficiently trap the photogenerated holes. This facilitates the migration of holes from the anatase shell and leaves more photogenerated electrons in the anatase nanoshell, which results in a highly efficient separation of photogenerated charges in the anatase nanoshell. Hence, this enhanced charge-separation mechanism accelerates dye degradation and alcohol oxidation processes. The one-pot treatment doping strategy is also used to selectively dope other metal ions with variable oxidation states such as Co2+/3+ and Cu+/2+ ions. The doping substantially improves the photocatalytic activity of the mixed-phase nanofibers. In contrast, the doping of ions with an invariable oxidation state, such as Zn2+, Ca2+, or Mg2+, does not enhance the photoactivity of the mixed-phase nanofibers as the ions could not trap the photogenerated holes.

Vibrational spectroscopy of the borate mineral henmilite Ca2Cu[B(OH)4]2(OH)4

Henmilite is a triclinic mineral with the crystal structure consisting of isolated B(OH)4 tetrahedra, planar Cu(OH)4 groups and Ca(OH)3 polyhedra. The structure can also be viewed as having dimers of Ca polyhedra connected to each other through 2B(OH) tetrahedra to form chains parallel to the C axis. The structure of the mineral has been assessed by the combination of Raman and infrared spectra. Raman bands at 902, 922, 951, and 984 cm−1 and infrared bands at 912, 955 and 998 cm−1 are assigned to stretching vibrations of tetragonal boron. The Raman band at 758 cm−1 is assigned to the symmetric stretching mode of tetrahedral boron. The series of bands in the 400–600 cm−1 region are due to the out-of-plane bending modes of tetrahedral boron. Two very sharp Raman bands are observed at 3559 and 3609 cm−1. Two infrared bands are found at 3558 and 3607 cm−1. These bands are assigned to the OH stretching vibrations of the OH units in henmilite. A series of Raman bands are observed at 3195, 3269, 3328, 3396, 3424 and 3501 cm−1 are assigned to water stretching modes. Infrared spectroscopy also identified water and OH units in the henmilite structure. It is proposed that water is involved in the structure of henmilite. Hydrogen bond distances based upon the OH stretching vibrations using a Libowitzky equation were calculated. The number and variation of water hydrogen bond distances are important for the stability off the mineral.

A revision of Calyptochloa C.E.Hubb. (Poaceae), with two new species and a new subspecies

Thompson, E.J. & Simon, B.K. (2012). A revision of Calyptochloa C.E.Hubb. (Poaceae), with two new species and a new subspecies. Austrobaileya 8(4): 634–652. Two new species of Calyptochloa C.E.Hubb. (Calyptochloa cylindrosperma E.J.Thomps. & B.K.Simon and C. johnsoniana E.J.Thomps. & B.K.Simon) endemic to central Queensland, and a new subspecies of Calyptochloa gracillima C.E.Hubb. (C. gracillima subsp. ipsviciensis E.J.Thomps. & B.K.Simon) endemic to southeast Queensland are described and illustrated.

Reply to William B. Grant

THE UVI working group acknowledges the contribution of Vitamin D to bone health as stated in our paper. However, we concluded that an optimal level of Vitamin D for humans has not yet been established with any certainty...

The feral horse foot. Part B : radiographic, gross visual and histopathological parameters of foot health in 100 Australian feral horses

Background It has been proposed that the feral horse foot is a benchmark model for foot health in horses. However, the foot health of feral horses has not been formally investigated. Objectives To investigate the foot health of Australian feral horses and determine if foot health is affected by environmental factors, such as substrate properties and distance travelled. Methods Twenty adult feral horses from five populations (n = 100) were investigated. Populations were selected on the basis of substrate hardness and the amount of travel typical for the population. Feet were radiographed and photographed, and digital images were surveyed by two experienced assessors blinded to each other's assessment and to the population origin. Lamellar samples from 15 feet from three populations were investigated histologically for evidence of laminitis. Results There was a total of 377 gross foot abnormalities identified in 100 left forefeet. There were no abnormalities detected in three of the feet surveyed. Each population had a comparable prevalence of foot abnormalities, although the type and severity of abnormality varied among populations. Of the three populations surveyed by histopathology, the prevalence of chronic laminitis ranged between 40% and 93%. Conclusions Foot health appeared to be affected by the environment inhabited by the horses. The observed chronic laminitis may be attributable to either nutritional or traumatic causes. Given the overwhelming evidence of suboptimal foot health, it may not be appropriate for the feral horse foot to be the benchmark model for equine foot health.

Hepatitis C : a socio-cultural perspective on the effects of a new virus on a community’s health

Since the emergence of diagnostic medical tests in Australia in 1990, hepatitis C (HCV) has been shown to account for over 90 percent of all non-A non-B hepatitis, revealing it to be a widespread and major public health problem. The diagnosis of HCV involves a diverse range of issues for affected persons, introducing identity and lifestyle changes, which are commonly articulated through psychological concepts. In this article we argue that it is important to examine the broader social and cultural contexts that contribute to the experiences of persons affected by HCV. The thematic analysis of qualitative data from six individuals diagnosed with HCV is included to exemplify some of the processes that are involved in the changing identity of a person following a positive diagnosis. The theoretical framework for the interpretation of these processes is interpretive interactionism. In this research, we are attempting to extend the understanding of the effects of HCV diagnoses beyond internal, psychological processes by examining how these diagnoses transform some of the processes of self-formation and expression. The participants’ experiences indicate that there are at least four dimensions of self that were significant to their changing sense of self: relationship of self to others; the emotional self; self-stories and identity; and self-scrutiny and relationships. We conclude that a socio-cultural perspective contributes to the explanation of the transition period following a HCV-positive diagnosis and the redefinition of self towards a HCV status.

First-principle studies of electronic structure and C-doping effect in boron nitride nanoribbon

Structural and electronic properties have been studied for Boron Nitride nanoribbons (BNNR) with both zigzag and armchair shaped edge (Z-BNNR and A-BNNR) by first-principle spin-polarized total energy calculations. We found that the energy band gap of Z-BNNR is indirect and decreases monotonically with the increasing ribbon width, whereas direct energy band gap oscillation was observed for A-BNNRs. Additionally, C-substitution at either single boron or nitrogen atom site in BNNRs could induce spontaneous magnetization. Our results could be potentially useful to design magnetic nano-devices based on BNNRs.

Hepatitis C, mental health and equity of access to antiviral therapy : a systematic narrative review

Introduction Access to hepatitis C (hereafter HCV) antiviral therapy has commonly excluded populations with mental health and substance use disorders because they were considered as having contraindications to treatment, particularly due to the neuropsychiatric effects of interferon that can occur in some patients. In this review we examined access to HCV interferon antiviral therapy by populations with mental health and substance use problems to identify the evidence and reasons for exclusion. Methods We searched the following major electronic databases for relevant articles: PsycINFO, Medline, CINAHL, Scopus, Google Scholar. The inclusion criteria comprised studies of adults aged 18 years and older, peer-reviewed articles, date range of (2002--2012) to include articles since the introduction of pegylated interferon with ribarvirin, and English language. The exclusion criteria included articles about HCV populations with medical co-morbidities, such as hepatitis B (hereafter HBV) and human immunodeficiency virus (hereafter HIV), because the clinical treatment, pathways and psychosocial morbidity differ from populations with only HCV. We identified 182 articles, and of these 13 met the eligibility criteria. Using an approach of systematic narrative review we identified major themes in the literature. Results Three main themes were identified including: (1) pre-treatment and preparation for antiviral therapy, (2) adherence and treatment completion, and (3) clinical outcomes. Each of these themes was critically discussed in terms of access by patients with mental health and substance use co-morbidities demonstrating that current research evidence clearly demonstrates that people with HCV, mental health and substance use co-morbidities have similar clinical outcomes to those without these co-morbidities. Conclusions While research evidence is largely supportive of increased access to interferon by people with HCV, mental health and substance use co-morbidities, there is substantial further work required to translate evidence into clinical practice. Further to this, we conclude that a reconsideration of the appropriateness of the tertiary health service model of care for interferon management is required and exploration of the potential for increased HCV care in primary health care settings.

A phase II study of mitomycin C and oral etoposide for advanced adenocarcinoma of the upper gastrointestinal tract

Background: Mitomycin C and etoposide have both demonstrated activity against gastric carcinoma. Etoposide is a topoisomerase II inhibitor with evidence for phase-specific and schedule-dependent activity. Patients and method. Twenty-eight consecutive patients with advanced upper gastrointestinal adenocarcinoma were treated with intravenous (i.v.) bolus mitomycin C 6 mg/m2 on day 1 every 21 days to a maximum of four courses. Oral etoposide capsules 50 mg b.i.d. (or 35 mg b.i.d. liquid) were administered days 1 to 10 extending to 14 days in subsequent courses if absolute neutrophil count >1.5 x 109/l on day 14 of first course, for up to six courses. Results: Twenty-six patients were assessed for response of whom 12 had measurable disease and 14 evaluable disease. Four patients had a documented response (one complete remission, three partial remissions) with an objective response rate of 15% (95% confidence interval (95% CI) 4%-35%). Eight patients had stable disease and 14 progressive disease. The median survival was six months. The schedule was well tolerated with no treatment-related deaths. Nine patients experienced leucopenia (seven grade II and two grade III). Nausea and vomiting (eight grade II, one grade III), fatigue (eight grade II, two grade III) and anaemia (seven grade II, two grade III) were the predominant toxicities. Conclusion: This out-patient schedule is well tolerated and shows modest activity in the treatment of advanced upper gastrointestinal adenocarcinoma. Further studies using protracted schedules of etoposide both orally and as infusional treatment should be developed.

bcl-2 and c-erbB-2 proteins are involved in the regulation of VEGF and of thymidine phosphorylase angiogenic activity in non-small-cell lung cancer

Tumour angiogenesis has been recently recognised as one of the most important prognostic factors in lung cancer. Although a variety of angiogenic factors have been identified, the angiogenesis process remains poorly understood. Bcl-2, c-erbB-2 and p53 are well-known oncogenes involved in non- small-cell lung cancer pathogenesis. A direct correlation of thymidine phosphorylase (TP) and of vascular endothelial growth factor (VEGF) with intratumoural angiogenesis has been reported. In the present study we investigated the possible regulatory role if bcl-2, c-erB-2 proteins in angiogenesis and in VEGF and TP expression in non-small-cell lung cancer. Two hundred sixteen specimens from T1,2-NO, 1 staged patients treated with surgery alone were immunohistochemically examined. Bcl-2 and c-erbB-2 were significantly inversely related to each other (P = 0.04) and both were inversely associated with microvessel density (P < 0.02). High TP and VEGF reactivity was statistically related to loss of bcl-2 expression (P < 0.01). A significant co-expression of c-erbB-2 with TP was noted (P = 0.01). However, TP expression was related to high angiogenesis only in cases with absence of c-erB-2 expression (P < 0.0001). c-erbB-2 expression in poorly vascularised tumours was linked with poor outcome (P = 0.03). The present study provides strong evidence that the bcl-2 gene has a suppressive function over genes involved in both angiogenesis (VEGF and TP) and cell migration (c- erbB-2) in NSCLC. TP and c-erbB-2 proteins are significantly, and often simultaneously, expressed in bcl-2 negative cases. However, expression of the c-erbB-2 abolishes the TP-related angiogenic activity. Whether this is a result of a direct activity of the c-erbB-2 protein or a consequence of a c- erbB-2-related immune response remains to be further investigated.