cyclophilin D (cypD) is a peptidyl-prolyl isomerase expressed in the nucleus and transported into the mitochondria where it is best associated with the regulation of the mitochondrial permeability transition pore (Mptp). there are, however, other possible roles of cypD in the mitochondria which may or may not be linked with the Mptp. Alpha synuclein (αSyn) is shown here to interact directly with cypD via its acidic proline-rich c-terminus region and binding at the putative ligand binding pocket of cypD. the study shows that cypD binding with soluble αSyn prevents its aggregation. furthermore, the addition of cypD to preformed αSyn fibrils leads to the disassembly of these fibrils. Enzymaticallycompromised mutants of cypD show reduced abilities to dissociate αSyn aggregates, suggesting that fibril disassembly is linked to the increased rate of peptidyl-prolyl isomerisation catalysed by CypD. protein aggregation in the mitochondria is increasingly seen as the cause of neurodegeneration. However, protein aggregation is a reversible process but disaggregation requires help from other proteins such as isomerases and chaperones. the results here demonstrate a possible mechanism by which cypD achieves this and suggest that disaggregation could be one of the many functions of this protein. Cyclophilin D (CypD) is a mitochondrial peptidyl-prolyl isomerase that has been implicated to be involved in the mechanisms of many diseases, although it is best known as a regulator for the opening of the mitochondria permeability transition pore (MPTP). These conclusions were drawn from outcomes observed in in vivo studies involving the use of the potent inhibitor, cyclosporine A (CsA), and ppif gene knockdown mice 1,2. In a recent study, genetic ablation of CypD resulted in a delayed onset of Parkinson's Disease (PD) and extended lifespan of PD mice 3. Co-immunoprecipitation experiments in the same study show very weak direct interactions between CypD and αSyn 3. The connection between CypD and PD has not been clearly established, with the exception that mitochondrial dysfunction is a hallmark of PD 4. PD is characterised by the formation of Lewy bodies, which are protein aggregates containing the protein alpha-synuclein (αSyn) and selective degeneration of dopaminergic neurons in the substantia nigra brain region 5,6. Genome-wide analyses place mutations in SNCA, the gene encoding αSyn, as the top risk factor for those developing sporadic forms of the disease 7,8. αSyn redistributes from the cytoplasm to the outer and inner mitochondrial membrane with increased accumulation in PD 9,10. There is a correlation between αSyn entry into the mitochondria, reduced mitochondrial membrane potential (∆Ψ m) and mitochondria dysfunction, implicating the involvement of the MPTP 11,12. These effects of αSyn can be rescued by the addition of CsA, a CypD inhibitor, although this could be through the role of CypD as a regulator of the MPTP rather than as a result of direct interaction between αSyn and CypD 13. Proteins currently known to dissociate...

Research of young people shows a lack of understanding of the term grooming in online communications and that internet risks are taken because internet literacy is poor for this group. However, limited research has investigated the perceptions of young adults in this context. The aim of this study was to understand young adults’ perceptions of risk, their internet behaviors, and understanding of the grooming concept. Furthermore, to understand the types of risk behaviors young people engage in online, whether they perceive these behaviors as risky, and what implications this has for vulnerability to negative experiences. An examination of internet communication perceptions and the grooming concept focused on 10 young males and females aged between 18 and 23 years. Semi-structured interviews were conducted at open access youth organizations in the North West of England, UK, and the duration of each interview was approximately 30 min. The data were transcribed and analyzed using thematic analysis. Emergent themes were (a) grooming as a concept, (b) virtual lives, and (c) perception of risk. The findings concur there is limited understanding of the term grooming but that explanations may not be simply confined to literacy. Risks being taken online were not always perceived as risky. Recommendations include the need for a more nuanced definition of the term grooming and that more information is available to children and caregivers. Further work should focus on younger participants’ perceptions of grooming to address wider issues, together with a focus on risk taking behaviors among other vulnerable groups.

The prevalence of infection with herpes simplex virus (HSV) continues to increase largely due to the inability of current antiviral agents to eradicate latent infection. This article reviews strategies to slow the transmission of HSV infection, most importantly through the development of vaccines, as well as established and emerging choices for treatment of primary and recurrent genital herpes, herpes labialis, infections in immunocompromised hosts, and acyclovir-resistant infections. The role of chronic suppressive therapy in the management of genital herpes as well as its potential impact on transmission rates will also be discussed.Herpes simplex virus (HSV) is a widespread pathogen in the United States, with more than 100 million U.S. citizens having serologic evidence of HSV-1 infection and 40-60 million, nearly one-fifth of the adolescent and adult population, infected with HSV-2 (1,2). The prevalence of HSV-2, the major cause of genital herpes, has increased 30% since the late 1970s (2). The fact that most of those infected with HSV are asymptomatic and yet may still be subclinically shedding virus further complicates efforts to slow the spread of transmission (3). Therefore proper management of herpetic infections requires that the clinician be able to effectively diagnose those with HSV infection, to educate them regarding means of spread and symptoms indicative of infection, and to adequately treat infections which are identified in order to alleviate patient symptoms and slow the transmission of the virus. We review options for preventing infection, treating primary infections, and treating recurrent infections in order to accomplish these goals.

No abstract