A Review of Some Aspects of L-Forms and Gonococci

Systemic manifestations of gonococcal disease, such as arthritis, are often sterile on the usual culture methods used to grow gonococci. Allergic mechanisms have been invoked to explain this but with little evidence to support the concept. With the report by Holmes et al., that L-forms of gonococci were isolated from joint fluid of a patient with gonococcal arthritis, we decided to investigate the possible role of L-forms in gonococcal disease

Expansion of the Parkinson disease-associated SNCA-Rep1 allele upregulates human alpha-synuclein in transgenic mouse brain.

Alpha-synuclein (SNCA) gene has been implicated in the development of rare forms of familial Parkinson disease (PD). Recently, it was shown that an increase in SNCA copy numbers leads to elevated levels of wild-type SNCA-mRNA and protein and is sufficient to cause early-onset, familial PD. A critical question concerning the molecular pathogenesis of PD is what contributory role, if any, is played by the SNCA gene in sporadic PD. The expansion of SNCA-Rep1, an upstream, polymorphic microsatellite of the SNCA gene, is associated with elevated risk for sporadic PD. However, whether SNCA-Rep1 is the causal variant and the underlying mechanism with which its effect is mediated by remained elusive. We report here the effects of three distinct SNCA-Rep1 variants in the brains of 72 mice transgenic for the entire human SNCA locus. Human SNCA-mRNA and protein levels were increased 1.7- and 1.25-fold, respectively, in homozygotes for the expanded, PD risk-conferring allele compared with homozygotes for the shorter, protective allele. When adjusting for the total SNCA-protein concentration (endogenous mouse and transgenic human) expressed in each brain, the expanded risk allele contributed 2.6-fold more to the SNCA steady-state than the shorter allele. Furthermore, targeted deletion of Rep1 resulted in the lowest human SNCA-mRNA and protein concentrations in murine brain. In contrast, the Rep1 effect was not observed in blood lysates from the same mice. These results demonstrate that Rep1 regulates human SNCA expression by enhancing its transcription in the adult nervous system and suggest that homozygosity for the expanded Rep1 allele may mimic locus multiplication, thereby elevating PD risk

Endophytic Beauveria bassiana increases galling of ‘Rutgers’ tomato roots with Meloidogyne incognita

Beauveria bassiana is endophytic in many plant species and has been shown to protect host plants against insect pests and plant pathogens. However, less is known about its activity against plant-parasitic nematodes. In vitro and plant assays were conducted to determine the effect of B. bassiana 11-98 (Bb) on Meloidogyne incognita (root-knot nematode; RKN). Beauveria bassiana was confirmed as an endophyte in ‘Rutgers’ tomato and colonization patterns of Bb in ‘Rutgers’ (highly susceptible to RKN) were compared with those in ‘Mountain Spring’ (less susceptible to RKN). In greenhouse tests with ‘Rutgers’ at 30 and 60 days after treatment (DAT) with RKN and Bb, there were few differences in plant growth variables among treatments in repeated trials. However, RKN root galling and egg count/root system were enhanced in plants treated with Bb at 60 DAT. In an in vitro assay with egg masses from greenhouse tests, the percentages of hatched eggs, and mobile and immobile nematodes did not differ significantly for RKN and RKN+Bb treatments. The presence of viable Bb from roots was confirmed by collecting egg suspensions from root galls and plating them on selective medium. Colonies of Bb were verified on agar medium, but no parasitism of RKN eggs was observed. Research is needed to investigate factors responsible for increased galling by RKN in the presence of endophytic Bb in ‘Rutgers’ tomato

‘It Takes Two Hands to Clap’: How Gaddi Shepherds in the Indian Himalayas Negotiate Access to Grazing

This article examines the effects of state intervention on the workings of informal institutions that coordinate the communal use and management of natural resources. Specifically it focuses on the case of the nomadic Gaddi shepherds and official attempts to regulate their access to grazing pastures in the Indian Himalayas. It is often predicted that the increased presence of the modern state critically undermines locally appropriate and community-based resource management arrangements. Drawing on the work of Pauline Peters and Francis Cleaver, I identify key instances of socially embedded ‘common’ management institutions and explain the evolution of these arrangements through dynamic interactions between individuals, communities and the agents of the state. Through describing the ‘living space’ of Gaddi shepherds across the annual cycle of nomadic migration with their flocks I explore the ways in which they have been able to creatively reinterpret external interventions, and suggest how contemporary arrangements for accessing pasture at different moments of the annual cycle involve complex combinations of the formal and the informal, the ‘traditional’ and the ‘modern’

Phase I Safety and Immunogenicity Evaluation of MVA-CMDR, a Multigenic, Recombinant Modified Vaccinia Ankara-HIV-1 Vaccine Candidate

We conducted a Phase I randomized, dose-escalation, route-comparison trial of MVA-CMDR, a candidate HIV-1 vaccine based on a recombinant modified vaccinia Ankara viral vector expressing HIV-1 genes env/gag/pol. The HIV sequences were derived from circulating recombinant form CRF01_AE, which predominates in Thailand. The objective was to evaluate safety and immunogenicity of MVA-CMDR in human volunteers in the US and Thailand.MVA-CMDR or placebo was administered intra-muscularly (IM; 10(7) or 10(8) pfu) or intradermally (ID; 10(6) or 10(7) pfu) at months 0, 1 and 3, to 48 healthy volunteers at low risk for HIV-1 infection. Twelve volunteers in each dosage group were randomized to receive MVA-CMDR or placebo (10∶2). Volunteers were actively monitored for local and systemic reactogenicity and adverse events post vaccination. Cellular immunogenicity was assessed by a validated IFNγ Elispot assay, an intracellular cytokine staining assay, lymphocyte proliferation and a (51)Cr-release assay. Humoral immunogenicity was assessed by ADCC for gp120 and binding antibody ELISAs for gp120 and p24. MVA-CMDR was safe and well tolerated with no vaccine related serious adverse events. Cell-mediated immune responses were: (i) moderate in magnitude (median IFNγ Elispot of 78 SFC/10(6) PBMC at 10(8) pfu IM), but high in response rate (70% (51)Cr-release positive; 90% Elispot positive; 100% ICS positive, at 10(8) pfu IM); (ii) predominantly HIV Env-specific CD4(+) T cells, with a high proliferative capacity and durable for at least 6 months (100% LPA response rate by the IM route); (iv) dose- and route-dependent with 10(8) pfu IM being the most immunogenic treatment. Binding antibodies against gp120 and p24 were detectable in all vaccination groups with ADCC capacity detectable at the highest dose (40% positive at 10(8) pfu IM).MVA-CMDR delivered both intramuscularly and intradermally was safe, well-tolerated and elicited durable cell-mediated and humoral immune responses.ClinicalTrials.gov NCT00376090

Role of Coronin 1B in PDGF-Induced Migration of Vascular Smooth Muscle Cells

The type I subclass of Coronins, a family of actin binding proteins, regulates various actin dependent cellular processes including migration. However, the existence and role of coronins in vascular smooth muscle cell (VSMC) migration has yet to be determined