Implications of direct-to-consumer whole-exome sequencing in South Africa

This editorial examines a number of vitally important ethical, legal and scientific concerns that have to be addressed to ensure proper and ethical implementation of direct-to-consumer whole-exome sequencing in South Africa. Individuals taking part in this endeavour must be fully informed of the positive and negative sequelae

T. gondii RP Promoters & Knockdown Reveal Molecular Pathways Associated with Proliferation and Cell-Cycle Arrest

Molecular pathways regulating rapid proliferation and persistence are fundamental for pathogens but are not elucidated fully in Toxoplasma gondii. Promoters of T. gondii ribosomal proteins (RPs) were analyzed by EMSAs and ChIP. One RP promoter domain, known to bind an Apetela 2, bound to nuclear extract proteins. Promoter domains appeared to associate with histone acetyl transferases. To study effects of a RP gene's regulation in T. gondii, mutant parasites (Δrps13) were engineered with integration of tetracycline repressor (TetR) response elements in a critical location in the rps13 promoter and transfection of a yellow fluorescent-tetracycline repressor (YFP-TetR). This permitted conditional knockdown of rps13 expression in a tightly regulated manner. Δrps13 parasites were studied in the presence (+ATc) or absence of anhydrotetracycline (-ATc) in culture. -ATc, transcription of the rps13 gene and expression of RPS13 protein were markedly diminished, with concomitant cessation of parasite replication. Study of Δrps13 expressing Myc-tagged RPL22, -ATc, showed RPL22 diminished but at a slower rate. Quantitation of RNA showed diminution of 18S RNA. Depletion of RPS13 caused arrest of parasites in the G1 cell cycle phase, thereby stopping parasite proliferation. Transcriptional differences ±ATc implicate molecules likely to function in regulation of these processes. In vitro, -ATc, Δrps13 persists for months and the proliferation phenotype can be rescued with ATc. In vivo, however, Δrps13 could only be rescued when ATc was given simultaneously and not at any time after 1 week, even when L-NAME and ATc were administered. Immunization with Δrps13 parasites protects mice completely against subsequent challenge with wildtype clonal Type 1 parasites, and robustly protects mice against wildtype clonal Type 2 parasites. Our results demonstrate that G1 arrest by ribosomal protein depletion is associated with persistence of T. gondii in a model system in vitro and immunization with Δrps13 protects mice against subsequent challenge with wildtype parasites

Anticipating ubiquitous computing: Logics to forecast technological futures

Visions of the future predict spaces apparently teaming with ever more novel and pervasive technologies. Significant amongst such forecasts is the notion of 'ubiquitous computing' (ubicomp), understood as an affordance or capacity tied (in)to people, places and things. This article stages an encounter between the futurity of ubicomp and recent debates in geography around anticipation. So, first, the future orientation in ubicomp research and development (R&D) is investigated as a mode of anticipation. 'Knowledges', and 'logics' of anticipation are subsequently, and second, discussed as the conceptual apparatus that constructs and perpetuates the 'proximate future' of ubicomp. This analysis connects recent discussion about 'anticipation' in social sciences research with the methods of ubicomp research, which fits with an emergent agenda around futurity in human geography. Third, the conceptual articulation of 'anticipatory logic' is applied to the analysis of empirical investigations of ubicomp R&D to identify the specific logics of anticipation at play. This article accordingly examines the logics of anticipation that both support and destabilise the certainty with which the future is imagined within ubicomp. In conclusion, the multiple ways of anticipating a future world and the ways in which they discipline understandings of futurity are framed as a politics of anticipation. © 2010 Elsevier Ltd

Homo sapiens in Arabia by 85,000 years ago.

Understanding the timing and character of the expansion of Homo sapiens out of Africa is critical for inferring the colonization and admixture processes that underpin global population history. It has been argued that dispersal out of Africa had an early phase, particularly ~130-90 thousand years ago (ka), that reached only the East Mediterranean Levant, and a later phase, ~60-50 ka, that extended across the diverse environments of Eurasia to Sahul. However, recent findings from East Asia and Sahul challenge this model. Here we show that H. sapiens was in the Arabian Peninsula before 85 ka. We describe the Al Wusta-1 (AW-1) intermediate phalanx from the site of Al Wusta in the Nefud desert, Saudi Arabia. AW-1 is the oldest directly dated fossil of our species outside Africa and the Levant. The palaeoenvironmental context of Al Wusta demonstrates that H. sapiens using Middle Palaeolithic stone tools dispersed into Arabia during a phase of increased precipitation driven by orbital forcing, in association with a primarily African fauna. A Bayesian model incorporating independent chronometric age estimates indicates a chronology for Al Wusta of ~95-86 ka, which we correlate with a humid episode in the later part of Marine Isotope Stage 5 known from various regional records. Al Wusta shows that early dispersals were more spatially and temporally extensive than previously thought. Early H. sapiens dispersals out of Africa were not limited to winter rainfall-fed Levantine Mediterranean woodlands immediately adjacent to Africa, but extended deep into the semi-arid grasslands of Arabia, facilitated by periods of enhanced monsoonal rainfall

Reading Redaction: Symptomatic Metadata, Erasure Poetry, and Mark Blacklock’s I’m Jack

In this article, through a reading of Mark Blacklock’s 2015 novel, I’m Jack, alongside the history of erasure poetry, I suggest that an apt literary-critical metaphor for reading redaction in contemporary literature comes from the term “metadata”. The article schematizes the ways in which redaction can work in literary contexts and points to the modalities through which supposedly blank surfaces are, in fact, textured depths that can be read

Redox balance influences differentiation status of neuroblastoma in the presence of all-trans retinoic acid

Neuroblastoma is the most common extra-cranial solid tumor in childhood; and patients in stage IV of the disease have a high propensity for tumor recurrence. Retinoid therapy has been utilized as a means to induce differentiation of tumor cells and to inhibit relapse. In this study, the expression of a common neuronal differentiation marker [neurofilament M (NF-M)] in human SK-N-SH neuroblastoma cells treated with 10 μM all-trans retinoic acid (ATRA) showed significantly increased expression in accordance with reduced cell number. This was accompanied by an increase in MitoSOX and DCFH2 oxidation that could be indicative of increased steady-state levels of reactive oxygen species (ROS) such as O2•− and H2O2, which correlated with increased levels of MnSOD activity and immuno-reactive protein. Furthermore PEG-catalase inhibited the DCFH2 oxidation signal to a greater extent in the ATRA-treated cells (relative to controls) at 96 h indicating that as the cells became more differentiated, steady-state levels of H2O2 increased in the absence of increases in peroxide-scavenging antioxidants (i.e., glutathione, glutathione peroxidase, and catalase). In addition, ATRA-induced stimulation of NF-M at 48 and 72 h was enhanced by decreasing SOD activity using siRNA directed at MnSOD. Finally, treatment with ATRA for 96 h in the presence of MnSOD siRNA or PEG-catalase inhibited ATRA induced increases in NF-M expression. These results provide strong support for the hypothesis that changes in steady-state levels of O2•− and H2O2 significantly contribute to the process of ATRA-induced differentiation in neuroblastoma, and suggest that retinoid therapy for neuroblastoma could potentially be enhanced by redox-based manipulations of superoxide metabolism to improve patient outcome

Confirmation of a late middle Pleistocene age for the Omo Kibish 1 cranium by direct uranium-series dating

While it is generally accepted that modern humans evolved in Africa, the specific physical evidence for that origin remains disputed. The modern-looking Omo 1 skeleton, discovered in the Kibish region of Ethiopia in 1967, was controversially dated at ?130 ka (thousands of years ago) by U-series dating on associated Mollusca, and it was not until 2005 that Ar–Ar dating on associated feldspar crystals in pumice clasts provided evidence for an even older age of ?195 ka. However, questions continue to be raised about the age and stratigraphic position of this crucial fossil specimen. Here we present direct U-series determinations on the Omo 1 cranium. In spite of significant methodological complications, which are discussed in detail, the results indicate that the human remains do not belong to a later intrusive burial and are the earliest representative of anatomically modern humans. Given the more archaic morphology shown by the apparently contemporaneous Omo 2 calvaria, we suggest that direct U-series dating is applied to this fossil as well, to confirm its age in relation to Omo 1