Expression Of Mir-34a In T-cells Infected By Human T-lymphotropic Virus 1

Human T-lymphotropic virus 1 (HTLV-1) immortalizes T-cells and is the causative agent of adult T-cell leukemia/lymphoma (ATLL). HTLV-1 replication and transformation are governed by multiple interactions between viral regulatory proteins and host cell factors that remain to be fully elucidated. The present study investigated the impact of HTLV-1 infection on the expression of miR-34a, a microRNA whose expression is downregulated in many types of cancer. Results of RT-PCR assays showed that five out of six HTLV-1-positive cell lines expressed higher levels of miR-34a compared to normal PBMC or purified CD4+ T-cells. ATLL cell line ED, which did not express miR-34a, showed methylation of the miR-34a promoter. Newly infected PBMC and samples from 10 ATLL patients also showed a prominent increase in miR-34a expression compared to PBMC controls. The primary miR-34a transcript expressed in infected cell line C91PL contained binding motifs for NF-kappa B and p53. Pharmacological inhibition of NF-kappa B with Bay 11-7082 indicated that this pathway contributes to sustain miR-34a levels in infected cells. Treatment of infected cell lines with the p53 activator nutlin-3a resulted in a further increase in miR-34a levels, thus confirming it as a transcriptional target of p53. Nutlin-3a-treated cells showed downregulation of known miR-34a targets including the deacetylase SIRT1, which was accompanied by increased acetylation of p53, a substrate of SIRT1. Transfection of C91PL cells with a miR-34a mimic also led to downregulation of mRNA targets including SIRT1 as well as the pro-apoptotic factor BAX. Unlike nutlin-3a, the miR-34a mimic did not cause cell cycle arrest or reduce cell viability. On the other hand, sequestration of miR-34a with a sponge construct resulted in an increase in death of C91PL cells. These findings provide evidence for a functional role for miR-34a in fine-tuning the expression of target genes that influence the turnover of HTLV-1-infected cells

Conference highlights of the 15th international conference on human retrovirology: HTLV and related retroviruses, 4-8 june 2011, Leuven, Gembloux, Belgium

The June 2011 15th International Conference on Human Retrovirology: HTLV and Related Viruses marks approximately 30 years since the discovery of HTLV-1. As anticipated, a large number of abstracts were submitted and presented by scientists, new and old to the field of retrovirology, from all five continents. The aim of this review is to distribute the scientific highlights of the presentations as analysed and represented by experts in specific fields of epidemiology, clinical research, immunology, animal models, molecular and cellular biology, and virology

Shedding Light on Shadow IT: Definition, Related Concepts, and Consequences

The use of Information Technology (IT) without the approval and support of the IT department, called shadow IT, has challenged organizations to rethink ways to manage IT resources to cope with the use of unauthorized technologies within organizations. We review the literature on shadow IT to shed light on this phenomenon, discussing the conceptual definition and types, the related concepts, and its consequences. This study, then, is an effort to better understand the phenomenon based on the extant literature. We provide contributions by enhancing the emerging body of knowledge on shadow IT, as well as by suggesting research gaps to be addressed in future research in order to advance on the topic

Effects of Color Appeal, Perceived Risk and Culture on Users Decision in Presence of Warning Banner Message

Color is present in every aspect of human life, and color is driving our decisions. In the digital computer warning realm, in which a warning message is a communication mechanism, color represents an important design element, which aims at preventing the hazard and reducing negative outcomes from the user’s action. Interestingly, we are lacking the understanding of how color appeal influences behavioral intentions in culturally distinct countries when it comes to paying more attention to warning messages. We conducted a cross-cultural investigation by running an online experiment, followed by a survey of 258 participants from the United States and India. Supported by the color-in-context theory, we found that culture is an important dimension in the specific warning message context in which color appeal is a salient antecedent to behavioral intentions in culturally distinct countries. We derive several theoretical contributions and practitioners’ insights

Serum testosterone concentration in combat-related chronic posttraumatic stress disorder.

AIM: The primary aim of this study was to assess the testosterone levels of soldiers with posttraumatic stress disorder (PTSD), without considering their comorbid conditions, compared with the ones in the control group with combat experience. The secondary aim was to determine whether there was a difference in testosterone levels when the same group of soldiers with PTSD was divided according to their comorbid conditions into those with major depressive disorder (MDD) or alcohol dependence (ETOH) compared to the soldiers with PTSD with no comorbid conditions and the controls. METHODS: We analyzed serum testosterone in soldiers with PTSD without the division according to comorbid conditions (n = 66) in comparison to the controls (n = 34). We also analyzed testosterone in pure PTSD (n = 17), PTSD comorbid with MDD (n = 18), PTSD comorbid with ETOH (n = 31), and in the controls. RESULTS: Soldiers with PTSD, without considering comorbid conditions, did not show any difference in testosterone levels in comparison to the controls. However, when we divided the same PTSD sample based on comorbid conditions, pure PTSD showed significantly higher serum testosterone levels in comparison to PTSD comorbid with MDD, comorbid with ETOH, or controls. Also, there was no difference in testosterone levels between the PTSD groups with comorbid MDD, with comorbid ETOH, and the controls. ConcluSIONS: We did not find any differences in testosterone levels between the soldiers with PTSD without considering comorbid conditions and the controls. Considering comorbid conditions, soldiers with PTSD without comorbid conditions had higher testosterone levels compared to soldiers with PTSD with comorbid MDD or ETOH, or the controls

Targeting the cutaneous lymphocyte antigen (CLA) in inflammatory and neoplastic skin conditions

Introduction: The cutaneous lymphocyte antigen interacts with E-selectin on endothelial cells and is expressed on 15% of circulating T-cells. Skin-homing T-cells express the cutaneous lymphocyte antigen and play a role in local cutaneous immunity in inflammatory reactions and neoplastic conditions. Areas covered: Lymphocyte extravasation is the essential para-physiological mechanism enabling immune surveillance of tissues for tumors as well as effector cell recruitment to inflammatory sites. The authors focused on skin inflammatory disorders, on cutaneous lymphoproliferative disease, and on other skin malignancies. Expert opinion: Interfering with leukocyte extravasation has been regarded as an attractive strategy in skin disorders, in the past for inflammatory conditions and more recently for cutaneous T-cell lymphomas. Therapeutic blocking of skin-homing interactions has been attempted in psoriasis and atopic dermatitis and has been achieved in the treatment of cutaneous T-cell lymphomas. Cutaneous lymphocyte antigen is a potential molecular target for both systemic and skin-directed therapy for cutaneous T-cell lymphomas

Physical health management in psychiatric settings

Severe mental disorders have a chronic course associated with a high risk for co-morbid somatic illnesses and premature mortality, but despite this increased risk, general health care needs in this population are often neglected. Over recent years, several groups have developed screening and monitoring guidelines for metabolic and cardiovascular risk assessment in patients treated with antipsychotics. The psychiatrist needs to be aware of the potential metabolic side-effects of antipsychotic medication and to include them in the risk/benefit assessment when choosing a specific antipsychotic. He should also be responsible for the implementation of the necessary screening assessments and referral for treatment of any physical illness. Multidisciplinary assessment of psychiatric and medical conditions is needed. The somatic treatments offered to people with severe and enduring mental illness should be at par with general health care in the non-psychiatrically ill population. In our University Centre, a structured and elaborate screening and monitoring protocol was introduced in late 2003. This paper describes the practical aspects of this monitoring protocol and the results obtained 4 years after its implementation.status: publishe