Comparison of HTLV-associated myelopathy (HAM) in HIV-positive and HIV-negative patients at a tertiary South African hospital

Background. HTLV-1 associated myelopathy (HAM), or tropical spastic paraparesis, is caused by a retrovirus, the human T-cell lymphotropic virus (HTLV). Although patients with HAM and HIV infection have been described, to our knowledge no direct comparison has been made between patients who are HIV positive and suffering from HAM (HHAM) v. those who are HIV negative and suffering from HAM.Aim. We aimed to compare clinical and radiological findings in HIV-positive and -negative patients with HAM.Methods. Adult patients who presented to the Neurology Unit at the Steve Biko Academic Hospital from May 2005 to June 2012 with a progressive myelopathy and HTLV seropositivity were retrospectively identified and their clinical and radiological data were collected and reviewed.Results. 21 patients with HAM were identified, of whom 9 were HIV-positive and 11 HIV-negative. One patient, whose HIV status had not been established, was not included in the study. Although the trend did not reach statistical significance, co-infected patients tended to present at an earlier age (HHAM 6/9 (66%) <40 years old; HAM 2/11 (18%) <40 years old) and presented to hospital earlier (HHAM 6/9 (66%) < 3 years symptomatic; HAM 7/11 (63%) > 3 years symptomatic). Cord atrophy occurred in 7/8 dually infected patients and 8/10 HIV-negative patients.Conclusion. Although the study is limited by the small number of patients, co-infected patients tended to have a younger age of onset and to present to hospital sooner, and thoracic cord atrophy was very common

TOR1A mutation-related isolated childhood-onset generalised dystonia in South Africa

Background. Childhood-onset generalised dystonia is commonly caused by TOR1A mutations and is known to respond well to pallidal deep-brain stimulation (DBS) surgery. The incidence and prevalence of monogenic dystonia in individuals from Africa and specifically of African ancestry are unknown, and no local cases of TOR1A mutation dystonia are found in the literature.Objectives. To describe our experience with the outcome of TOR1A mutation-positive patients with isolated generalised dystonia (IGD) of childhood onset who were treated with pallidal DBS.Methods. All patients with TOR1A mutations from Steve Biko Academic Hospital and the Pretoria Neurology Institute in Pretoria, South Africa (SA), who underwent DBS for IGD of childhood onset were identified. We conducted a retrospective analysis of their demographics, clinical presentation and time to generalisation, genetic status and family history, and response to DBS treatment of the internal segment of the globus pallidus (GPi), utilising pre- and post-surgical scores of the United Dystonia Rating Scale (UDRS).Results. Three patients, all of black African ancestry, were identified. The median age at onset was 12 years and the median time to surgery from dystonia generalisation was 3 years. Two children presented with cervical-onset dystonia. Two patients were related, representing the only two with a positive family history. All three patients had a positive outcome after surgery, with improvement of 67 - 90% on the UDRS recorded at last follow-up.Conclusions. TOR1A mutations are found in SA patients of black African ancestry, with age of onset and generalisation comparable to those described in international studies. However, onset with cervical dystonia was more common than previously reported. Response to GPi DBS was excellent in all patients.

Soil communities: who responds and how quickly to a change in agricultural system?

The use of conservation and sustainable practices could restore the abundance and richness of soil organisms in agroecosystems. Fitting in this context, this study aimed to highlight whether and how different soil living communities reacted to the conversion from an integrated to an organic orchard. The metataxonomic approach for fungi and bacteria and the determination of biological forms of diatoms and microarthropods were applied. Soil analyses were carried out in order to evaluate the effect of soil chemical features on four major soil living communities. Our results showed that the different taxa reacted with different speeds to the management changes. Fungi responded quickly to the changes, suggesting that modification in agricultural practices had a greater impact on fungal communities. Bacteria and microarthropods were more affected by abiotic parameters and less by the management. The diatom composition seemed to be affected by seasonality but the highest H’ (Shannon index) value was measured in the organic system. Fungi, but also diatoms, seemed to be promising for monitoring changes in the soil since they were sensitive to both the soil features and the anthropic impact. Our study showed that soil biodiversity could be affected by the conversion to sustainable management practices from the early years of an orchard onwards. Therefore, better ecological orchard management may strengthen soil sustainability and resilience in historically agricultural region

Soil communities: Who responds and how quickly to a change in agricultural system?

The use of conservation and sustainable practices could restore the abundance and richness of soil organisms in agroecosystems. Fitting in this context, this study aimed to highlight whether and how different soil living communities reacted to the conversion from an integrated to an organic orchard. The metataxonomic approach for fungi and bacteria and the determination of biological forms of diatoms and microarthropods were applied. Soil analyses were carried out in order to evaluate the effect of soil chemical features on four major soil living communities. Our results showed that the different taxa reacted with different speeds to the management changes. Fungi responded quickly to the changes, suggesting that modification in agricultural practices had a greater impact on fungal communities. Bacteria and microarthropods were more affected by abiotic parameters and less by the management. The diatom composition seemed to be affected by seasonality but the highest H’ (Shannon index) value was measured in the organic system. Fungi, but also diatoms, seemed to be promising for monitoring changes in the soil since they were sensitive to both the soil features and the anthropic impact. Our study showed that soil biodiversity could be affected by the conversion to sustainable management practices from the early years of an orchard onwards. Therefore, better ecological orchard management may strengthen soil sustainability and resilience in historically agricultural regions

Rrp1b, a New Candidate Susceptibility Gene for Breast Cancer Progression and Metastasis

A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b), was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM) genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis

Measurement of the branching ratios of the Z0 into heavy quarks

We measure the hadronic branching ratios of the Z0 boson into heavy quarks: Rb=Gamma(Z0->bb)/Gamma(Z0->hadrons) and Rc=Gamma(Z0->cc/Gamma(Z0->hadrons) using a multi-tag technique. The measurement was performed using about 400,000 hadronic Z0 events recorded in the SLD experiment at SLAC between 1996 and 1998. The small and stable SLC beam spot and the CCD-based vertex detector were used to reconstruct bottom and charm hadron decay vertices with high efficiency and purity, which enables us to measure most efficiencies from data. We obtain, Rb=0.21604 +- 0.00098(stat.) +- 0.00073(syst.) -+ 0.00012(Rc) and, Rc= 0.1744 +- 0.0031(stat.) +- 0.0020(syst.) -+ 0.0006(Rb)Comment: 37 pages, 8 figures, to be submitted to Phys. Rev. D version 2: changed title to ratios, used common D production fractions for Rb and Rc and corrected Zgamma interference. Identical to PRD submissio

Evading innate immunity in nonviral mRNA delivery : don't shoot the messenger

In de field of non-viral gene therapy, in vitro transcribed (IVT) mRNA has emerged as a promising tool for the delivery of genetic information. Over the past few years it has become widely known the introduction of IVT mRNA into mammalian cells elicits an innate immune response which has favored mRNA use towards immunotherapeutic vaccination strategies. However, for non-immunotherapy related applications this intrinsic immune-stimulatory activity directly interferes with the aimed therapeutic outcome, as it can seriously compromise the expression of the desired protein. This review presents an overview of the immune-related obstacles that limit mRNA advance for non-immunotherapy related applications

Direct Measurements of A_b and A_c using Vertex/Kaon Charge Tags at SLD

Exploiting the manipulation of the SLC electron-beam polarization, we present precise direct measurements of the parity violation parameters A_c and A_b in the Z boson - c quark and Z boson - b quark coupling. Quark/antiquark discrimination is accomplished via a unique algorithm that takes advantage of the precise SLD CCD vertex detector, employing the net charge of displaced vertices as well as the charge of kaons that emanate from those vertices. From the 1996-98 sample of 400,000 Z decays, produced with an average beam polarization of 73.4%, we find A_c = 0.673 +/- 0.029 (stat.) +/- 0.023 (syst.) and A_b = 0.919 +/- 0.018 (stat.) +/- 0.017 (syst.).Comment: 11 pages, 2 figures, 2 tables, to be submitted to Physical Review Letters; version 2 reflects changes suggested by the refere