The influence of a peer-based HIV prevention intervention on conversation about HIV prevention among injection drug users in Baltimore, Maryland

Background STEP into Action assessed the effectiveness of a peer-based HIV prevention intervention on the reduction in risk behaviors among injection drug users (IDUs) in Baltimore. This analysis examined the effect of the peer-based intervention on (i) the change in frequency of conversation about HIV prevention topics over time among IDUs, (ii) sustainability of the change in frequency of the conversation, and (iii) which topics IDUs were more likely to discuss at the end of the follow-up period. Methods Of 227 Index participants 114 were randomized into intervention and 113 into control group. Participants were 18 years of age or older and self-reported injecting drugs in the 6 months prior to enrollment in the trial. Data were collected prospectively at 6, 12, and 18 months. The outcome of interest was the frequency of conversation among IDUs about different HIV prevention topics. Results Retention of the participants in the study exceeded 80% for each of the 3 visits. The odds of talking ‘at least a few times a week’ compared to ‘never’ about HIV testing (odds ratio (OR) = 1.86; 95% confidence interval (CI) = 0.87 - 3.95), HIV transmission (OR = 3.22; 95% CI = 1.39 - 7.46), needle cleaning (OR = 4.35; 95% CI = 1.88 - 10.07), needle sharing (OR = 4.35; 95% CI = 1.80 - 10.54), and condom use (OR = 2.25; 95% CI = 1.05 - 4.84) were higher in the intervention group compared to the control group at 6 months. At 18 months odds ratios that remained statistically significant were only for conversation about the danger of needle sharing (odds ratio (OR) = 3.21; 95% CI = 1.45 - 7.14) and condom use (OR = 2.81; 95% CI = 1.28 - 6.17). Conclusions This study demonstrated that the intervention had a positive influence on the conversation about HIV prevention among IDUs, but the sustainability of the high frequency of conversation past 6 months remained a challenge for most of the conversation topics. Thus, the findings suggest that interventions should be designed to constantly reinforce positive behavior among IDUs

Paleolinguistics brings more light on the earliest history of the traditional Eurasian pulse crops

Traditional pulse crops such as pea, lentil, field bean, bitter vetch, chickpea and common vetch originate from Middle East, Mediterranean and Central Asia^1^. They were a part of human diets in hunter-gatherers communities^2^ and are one of the most ancient cultivated crops^3,4^. Europe has always been rich in languages^5^, with individual families still preserving common vocabularies related to agriculture^6,7^. The evidence on the early pulse history witnessed by the attested roots in diverse Eurasian proto-languages remains insufficiently clarified and its potential for supporting archaeobotanical findings is still non-assessed. Here we show that the paleolinguistic research may contribute to archaeobotany in understanding the role traditional Eurasian pulse crops had in the everyday life of ancient Europeans. It was found that the Proto-Indo-European language^8,9^ had the largest number of roots directly related to pulses, such as *arnk(')- (a leguminous plant), *bhabh- (field bean), *erəgw[h]- (a kernel of leguminous plant; pea), *ghArs- (a leguminous plant), *kek-, *k'ik'- (pea) and *lent- (lentil)^10,11,12^, numerous words subsequently related to pulses^13,14^ and borrowings from one branch to another^15^, confirming their essential place in the nutrition of Proto-Indo-Europeans^16,17,18^. It was also determined that pea was the most important among Proto-Uralic people^19,20,21^, while pea and lentil were the most significant in the agriculture of Proto-Altaic people^22,23,24^. Pea and bean were most common among Caucasians^25,26^, Basques^27,28^ and their hypothetical common forefathers^29^ and bean and lentil among the Afro-Asiatic ancestors of modern Maltese^30^. Our results demonstrate that pulses were common among the ancestors of present European nations and that paleolinguistics and its lexicological and etymological analysis may be useful in better understanding the earliest days of traditional Eurasian crops. We believe our results could be a basis for advanced multidisciplinary approach to the pulse crop domestication, involving plant scientists, archaeobotanists and linguists, and for reconstructing even earlier periods of pulse history

The miR-17-92 cluster and its target THBS1 are differentially expressed in angiosarcomas dependent on MYC amplification

Angiosarcomas (ASs) represent a heterogeneous group of malignant vascular tumors that may occur spontaneously as primary tumors or secondarily after radiation therapy or in the context of chronic lymphedema. Most secondary ASs have been associated with MYC oncogene amplification, whereas the role of MYC abnormalities in primary AS is not well defined. Twenty-two primary and secondary ASs were analyzed by array-comparative genomic hybridization (aCGH) and by deep sequencing of small RNA libraries. By aCGH and subsequently confirmed by fluorescence in situ hybridization, MYC amplification was identified in three out of six primary tumors and in 8 out of 12 secondary AS. We have also found MAML1 as a new potential oncogene in MYC-amplified AS. Significant upregulation of the miR-17-92 cluster was observed in MYC-amplified AS compared to AS lacking MYC amplification and the control group (other vascular tumors, nonvascular sarcomas). Moreover, MYC-amplified ASs were associated with a significantly lower expression of thrombospondin-1 (THBS1) than AS without MYC amplification or controls. Altogether, our study implicates MYC amplification not only in the pathogenesis of secondary AS but also in a subset of primary AS. Thus, MYC amplification may play a crucial role in the angiogenic phenotype of AS through upregulation of the miR-17-92 cluster, which subsequently downregulates THBS1, a potent endogenous inhibitor of angiogenesis. © 2012 Wiley Periodicals, Inc

TET-mediated DNA hydroxymethylation is negatively influenced by the PARP-dependent PARylation

Background Poly(ADP-ribosyl)ation (PARylation), a posttranslational modification introduced by PARP-1 and PARP-2, has first been implicated in DNA demethylation due to its role in base excision repair. Recent evidence indicates a direct influence of PARP-dependent PARylation on TET enzymes which catalyse hydroxymethylation of DNA—the first step in DNA demethylation. However, the exact nature of influence that PARylation exerts on TET activity is still ambiguous. In our recent study, we have observed a negative influence of PARP-1 on local TET-mediated DNA demethylation of a single gene and in this study, we further explore PARP–TET interplay. Results Expanding on our previous work, we show that both TET1 and TET2 can be in vitro PARylated by PARP-1 and PARP-2 enzymes and that TET1 PARylation negatively affects the TET1 catalytic activity in vitro. Furthermore, we show that PARylation inhibits TET-mediated DNA demethylation at the global genome level in cellulo. Conclusions According to our findings, PARP inhibition can positively influence TET activity and therefore affect global levels of DNA methylation and hydroxymethylation. This gives a strong rationale for future examination of PARP inhibitors' potential use in the therapy of cancers characterised by loss of 5-hydroxymethylcytosine

EpiCRISPR targeted methylation of Arx gene initiates transient switch of mouse pancreatic alpha to insulin-producing cells

Introduction: Beta cell dysfunction by loss of beta cell identity, dedifferentiation, and the presence of polyhormonal cells are main characteristics of diabetes. The straightforward strategy for curing diabetes implies reestablishment of pancreatic beta cell function by beta cell replacement therapy. Aristaless-related homeobox (Arx) gene encodes protein which plays an important role in the development of pancreatic alpha cells and is a main target for changing alpha cell identity. Results: In this study we used CRISPR/dCas9-based epigenetic tools for targeted hypermethylation of Arx gene promoter and its subsequent suppression in mouse pancreatic αTC1-6 cell line. Bisulfite sequencing and methylation profiling revealed that the dCas9-Dnmt3a3L-KRAB single chain fusion constructs (EpiCRISPR) was the most efficient. Epigenetic silencing of Arx expression was accompanied by an increase in transcription of the insulin gene (Ins2) mRNA on 5th and 7th post-transfection day, quantified by both RT-qPCR and RNA-seq. Insulin production and secretion was determined by immunocytochemistry and ELISA assay, respectively. Eventually, we were able to induce switch of approximately 1% of transiently transfected cells which were able to produce 35% more insulin than Mock transfected alpha cells. Conclusion: In conclusion, we successfully triggered a direct, transient switch of pancreatic alpha to insulin-producing cells opening a future research on promising therapeutic avenue for diabetes management. 1 Introductio

Lysine acetylation of major Chlamydia trachomatis antigens

Chlamydia trachomatis (Ct) is a human pathogen causing trachoma and infertility. We investigated acetylation at lysine residues of chlamydial antigenic proteins: major outer membrane protein (MOMP), 60 kDa chaperonin (chlamydial Hsp60), elongation factor G (EF-G), enolase and the polymorphic membrane proteins PmpB, PmpE and PmpF. 60 kDa chaperonin, EF-G and PmpB showed the highest degree of acetylation. Our data show that important Ct antigens could be post-translationally modified by acetylation of lysine residues at multiple sites. Further studies are needed to investigate total acetylome of Ct and the impact PTMs might have on Ct biology and pathogenicity