No evidence for naturally occurring mutations resistant to HIV-1 reverse-transcriptase inhibitors among South African HIV-1 subtype C isolates

[No abstract available

Intra- and Inter-clade Cross-reactivity by HIV-1 Gag Specific T-Cells Reveals Exclusive and Commonly Targeted Regions: Implications for Current Vaccine Trials

The genetic diversity of HIV-1 across the globe is a major challenge for developing an HIV vaccine. To facilitate immunogen design, it is important to characterize clusters of commonly targeted T-cell epitopes across different HIV clades. To address this, we examined 39 HIV-1 clade C infected individuals for IFN-γ Gag-specific T-cell responses using five sets of overlapping peptides, two sets matching clade C vaccine candidates derived from strains from South Africa and China, and three peptide sets corresponding to consensus clades A, B, and D sequences. The magnitude and breadth of T-cell responses against the two clade C peptide sets did not differ, however clade C peptides were preferentially recognized compared to the other peptide sets. A total of 84 peptides were recognized, of which 19 were exclusively from clade C, 8 exclusively from clade B, one peptide each from A and D and 17 were commonly recognized by clade A, B, C and D. The entropy of the exclusively recognized peptides was significantly higher than that of commonly recognized peptides (p = 0.0128) and the median peptide processing scores were significantly higher for the peptide variants recognized versus those not recognized (p = 0.0001). Consistent with these results, the predicted Major Histocompatibility Complex Class I IC50 values were significantly lower for the recognized peptide variants compared to those not recognized in the ELISPOT assay (p<0.0001), suggesting that peptide variation between clades, resulting in lack of cross-clade recognition, has been shaped by host immune selection pressure. Overall, our study shows that clade C infected individuals recognize clade C peptides with greater frequency and higher magnitude than other clades, and that a selection of highly conserved epitope regions within Gag are commonly recognized and give rise to cross-clade reactivities

Hardness Evaluation of Porous Hydroxyapatite Coating

The extensive use of appropriate coatings to improve wear resistance, friction coefficient, electrical properties, corrosion resistance and biomedical application has stimulated a growing interest in their mechanical properties and especially hardness testing that is routinely used for coating evaluation. In this study Jönsson and Hogmark model is applied for the porous hydroxyapatite produced by plasma spraying on Ti6A14V substrate. Firstly, the effect of indentation load on hardness values of coating and substrate are studied. The modified Jönsson and Hogmark model is used to explain the composite hardness behavior and the effect of coating porosity

Nanocolloidal albumin-IRDye 800CW: a near-infrared fluorescent tracer with optimal retention in the sentinel lymph node

Purpose: At present, the only approved fluorescent tracer for clinical near-infrared fluorescence-guided sentinel node (SN) detection is indocyanine green (ICG), but the use of this tracer is limited due to its poor retention in the SN resulting in the detection of higher tier nodes. We describe the development and characterization of a next-generation fluorescent tracer, nanocolloidal albumin-IRDye 800CW that has optimal properties for clinical SN detection Methods: The fluorescent dye IRDye 800CW was covalently coupled to colloidal human serum albumin (HSA) particles present in the labelling kit Nanocoll in a manner compliant with current Good Manufacturing Practice. Characterization of nanocolloidal albumin-IRDye 800CW included determination of conjugation efficiency, purity, stability and particle size. Quantum yield was determined in serum and compared to that of ICG. For in vivo evaluation a lymphogenic metastatic tumour model in rabbits was used. Fluorescence imaging was performed directly after peritumoral injection of nanocolloidal albumin-IRDye 800CW or the reference ICG/HSA (i.e. ICG mixed with HSA), and was repeated after 24 h, after which fluorescent lymph nodes were excised. Results: Conjugation of IRDye 800CW to nanocolloidal albumin was always about 50% efficient and resulted in a stable and pure product without affecting the particle size of the nanocolloidal albumin. The quantum yield of nanocolloidal albumin-IRDye 800CW was similar to that of ICG. In vivo evaluation revealed noninvasive detection of the SN within 5 min of injection of either nanocolloidal albumin-IRDye 800CW or ICG/HSA. No decrease in the fluorescence signal from SN was observed 24 h after injection of the nanocolloidal albumin-IRDye 800CW, while a strong decrease or complete disappearance of the fluorescence signal was seen 24 h after injection of ICG/HSA. Fluorescence-guided SN biopsy was very easy. Conclusion: Nanocolloidal albumin-IRDye 800CW is a promising fluorescent tracer with optimal kinetic features for SN detection. © The Author(s) 2012

Timing Constraints of In Vivo Gag Mutations during Primary HIV-1 Subtype C Infection

Background: Aiming to answer the broad question “When does mutation occur?” this study examined the time of appearance, dominance, and completeness of in vivo Gag mutations in primary HIV-1 subtype C infection. Methods: A primary HIV-1C infection cohort comprised of 8 acutely and 34 recently infected subjects were followed frequently up to 500 days post-seroconversion (p/s). Gag mutations were analyzed by employing single-genome amplification and direct sequencing. Gag mutations were determined in relation to the estimated time of seroconversion. Time of appearance, dominance, and completeness was compared for different types of in vivo Gag mutations. Results: Reverse mutations to the wild type appeared at a median (IQR) of 62 (44;139) days p/s, while escape mutations from the wild type appeared at 234 (169;326) days p/s (p&lt;0.001). Within the subset of mutations that became dominant, reverse and escape mutations appeared at 54 (30;78) days p/s and 104 (47;198) days p/s, respectively (p&lt;0.001). Among the mutations that reached completeness, reverse and escape mutations appeared at 54 (30;78) days p/s and 90 (44;196) days p/s, respectively (p = 0.006). Time of dominance for reverse mutations to and escape mutations from the wild type was 58 (44;105) days p/s and 219 (90;326) days p/s, respectively (p&lt;0.001). Time of completeness for reverse and escape mutations was 152 (100;176) days p/s and 243 (101;370) days p/s, respectively (p = 0.001). Fitting a Cox proportional hazards model with frailties confirmed a significantly earlier time of appearance (hazard ratio (HR): 2.6; 95% CI: 2.3–3.0), dominance (4.8 (3.4–6.8)), and completeness (3.6 (2.3–5.5)) of reverse mutations to the wild type Gag than escape mutations from the wild type. Some complex mutational pathways in Gag included sequential series of reversions and escapes. Conclusions: The study identified the timing of different types of in vivo Gag mutations in primary HIV-1 subtype C infection in relation to the estimated time of seroconversion. Overall, the in vivo reverse mutations to the wild type occurred significantly earlier than escape mutations from the wild type. This shorter time to incidence of reverse mutations remained in the subsets of in vivo Gag mutations that reached dominance or completeness

Hypertonicity counteracts MCL 1 and renders BCL XL a synthetic lethal target in head and neck cancer

Head and neck squamous cell carcinoma (HNSCC) is an aggressive and difficult‐to‐treat cancer entity. Current therapies ultimately aim to activate the mitochondria‐controlled (intrinsic) apoptosis pathway, but complex alterations in intracellular signaling cascades and the extracellular microenvironment hamper treatment response. On the one hand, proteins of the BCL‐2 family set the threshold for cell death induction and prevent accidental cellular suicide. On the other hand, controlling a cell's readiness to die also determines whether malignant cells are sensitive or resistant to anticancer treatments. Here, we show that HNSCC cells upregulate the proapoptotic BH3‐only protein NOXA in response to hyperosmotic stress. Induction of NOXA is sufficient to counteract the antiapoptotic properties of MCL‐1 and switches HNSCC cells from dual BCL‐XL/MCL‐1 protection to exclusive BCL‐XL addiction. Hypertonicity‐induced functional loss of MCL‐1 renders BCL‐XL a synthetically lethal target in HNSCC, and inhibition of BCL‐XL efficiently kills HNSCC cells that poorly respond to conventional therapies. We identify hypertonicity‐induced upregulation of NOXA as link between osmotic pressure in the tumor environment and mitochondrial priming, which could perspectively be exploited to boost efficacy of anticancer drugs

A REVISION of the SOUTH AFRICAN SPECIES OF HYPERICUM

No abstract availabl

The Ahlmannryggen group, the viddalen formation and the associated igneous rocks in the viddalen area, western droning Maud land, Antarctica

Nunataks within an area of approximately 3 400 km2 between latitudes 71°50' and 72°35' south and longitudes 1°30' and 4°00' west were mapped geologically by the 12th South African National Antarctic Expedition during the summer of 1971-72. The area is underlain mainly by subhorizontal arenaceous and argillaceous sediments, extensively intruded by thick mafic sills and dykes of Precambrian age. An isolated succession comprising agglomerate, tuff and lava flows with intercalated sediments in its upper part is exposed in the east and south. A new lithostratigraphic subdivision is proposed, based on detailed investigation of field relationships combined with subsequent petrological studies and radiometric age determinations. The oldest rocks in the area belong to the Pyramiden Formation which consists mostly of feldspathic graywacke and siltstone. Correlates of this formation were discovered at Kjolrabbane, Babordsranten and at Nashornet and Viddalskollen. At the latter locality the sequence is subdivided into a Lower Member, 140 m thick, deposited under low-energy, deep-water conditions, and an Upper Member, 250 m thick, which was deposited in shallower water under higher energy conditions .. The overlying Grunehogna Formation has the widest distribution of all sedimentary formations in the area and consists of alternating persistent beds of light-coloured arenite and dark-coloured argillite. This succession is conformably overlain by the H6gfonna Formation which is subdivided into a lower, Borgmassivet Member, consisting of feldspathic quartzite, shale and jasper-bearing conglomerate, and an upper, Jekselen Member which consists of calcareous, jasperbearing arenaceous sediments. All the formations mentioned above are assigned to the Ahlmannryggen Group. It is suggested that the Raudberget Formation, which is not exposed in the area investigated, is also included in this Group. The volcanic-sedimentary succession at Tindeklypa and Istind is believed to overlie the Hogfonna Formation conformably and is collectively called the Viddalen Formation. It is subdivided into two conformable members: a lower, Tindeklypa Member, some 500 m thick, which consists of agglomerate with subordinate tuff and andesitic lava flows, and an upper, Istind Member, 340 m thick, consisting of alternating feldspathic quartzite, agglomerate, tuff and lava flows. (ii) A continuous upward gradation from plutonic through hypabyssal to volcanic rock (near-surface intrusions) was detected in the 1 700 My mafic sill (Krylen Intrusions) at Jekselen. The lava flows in the Viddalen Formation are believed to be the volcanic equivalent of the Krylen Intrusions. Two samples of Krylen Intrusions from Jekselen and Istind were submitted for 40 Ar/39 Ar wholerock age determinations. Ages of 1 339 ±. 55 My and 603 ±.. 12 My respectively were computed, both being minimum ages resulting from complete overprinting by metamorphism. The majority of the large mafic intrusions in the area are believed to have an age of around 1 000 My and are called Ytstenut Intrusions. Minor felsic intrusions are also included under this heading as they were found to represent only local remobilised differentiation products formed by the reaction between the mafic intrusions and the sediments. Two samples of Ytstenut Intrusions from Grunehogna and Ytstenut were submitted for 40 Ar/39 Ar whole-rock age determinations. Minimum ages of 83 2 .±. 2 and 924 .± 4 My respectively were obtained; the latter age was regarded by the analysts as being close to the real date of intrusion. The youngest rocks in the area are represented by minor dolerite dykes of Jurassic age and are called Post-Ytstenut Intrusions.Dissertation (MSc)--University of Pretoria, 1976.GeologyMScUnrestricte

THE GENUS <i>ELYONURUS</i> Humb. and Bonpl. IN SOUTH AFRICA.

No abstract availabl

A new species of <i>Phaeoramularia</i> (Fungi Imperfecti: Dematiaceae) from South Africa

A dematiaceous Hyphomycete isolated fro n wheat and oat straw, as well as lucerne seed in South Africa, is described as Phaeoramularia kellermaniana Marasas & Bred ill, sp. nov. The relationships ofP. kellermaniana to  Cladosporium resinae (Lindau) de Vries and other species of Phaeoramularia are discussed