A Human Torque Teno Virus Encodes a MicroRNA That Inhibits Interferon Signaling

Rodney P. Kincaid, James M. Burke, Jennifer C. Cox, Christopher S. Sullivan, The University of Texas at Austin, Molecular Genetics and Microbiology, Austin, Texas, United States of AmericaEthel-Michele de Villiers, Division for the Characterization of Tumorviruses, Deutsches Krebsforschungszentrum, Heidelberg, GermanyTorque teno viruses (TTVs) are a group of viruses with small, circular DNA genomes. Members of this family are thought to ubiquitously infect humans, although causal disease associations are currently lacking. At present, there is no understanding of how infection with this diverse group of viruses is so prevalent. Using a combined computational and synthetic approach, we predict and identify miRNA-coding regions in diverse human TTVs and provide evidence for TTV miRNA production in vivo. The TTV miRNAs are transcribed by RNA polymerase II, processed by Drosha and Dicer, and are active in RISC. A TTV mutant defective for miRNA production replicates as well as wild type virus genome; demonstrating that the TTV miRNA is dispensable for genome replication in a cell culture model. We demonstrate that a recombinant TTV genome is capable of expressing an exogenous miRNA, indicating the potential utility of TTV as a small RNA vector. Gene expression profiling of host cells identifies N-myc (and STAT) interactor (NMI) as a target of a TTV miRNA. NMI transcripts are directly regulated through a binding site in the 3′UTR. SiRNA knockdown of NMI contributes to a decreased response to interferon signaling. Consistent with this, we show that a TTV miRNA mediates a decreased response to IFN and increased cellular proliferation in the presence of IFN. Thus, we add Annelloviridae to the growing list of virus families that encode miRNAs, and suggest that miRNA-mediated immune evasion can contribute to the pervasiveness associated with some of these viruses.This work was supported by grants RO1AI077746 from the National Institutes of Health, RP110098 from the Cancer Prevention and Research Institute of Texas, a Burroughs Wellcome Investigators in Pathogenesis Award to CSS, a UT Austin Powers Graduate Fellowship to RPK, a UT Austin Institute for Cellular and Molecular Biology fellowship, and the DKFZ for EMdV. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.Molecular BiosciencesMicrobiologyEmail: [email protected]

INDDGO: Integrated Network Decomposition & Dynamic programming for Graph Optimization

It is well-known that dynamic programming algorithms can utilize tree decompositions to provide a way to solve some \emph{NP}-hard problems on graphs where the complexity is polynomial in the number of nodes and edges in the graph, but exponential in the width of the underlying tree decomposition. However, there has been relatively little computational work done to determine the practical utility of such dynamic programming algorithms. We have developed software to construct tree decompositions using various heuristics and have created a fast, memory-efficient dynamic programming implementation for solving maximum weighted independent set. We describe our software and the algorithms we have implemented, focusing on memory saving techniques for the dynamic programming. We compare the running time and memory usage of our implementation with other techniques for solving maximum weighted independent set, including a commercial integer programming solver and a semi-definite programming solver. Our results indicate that it is possible to solve some instances where the underlying decomposition has width much larger than suggested by the literature. For certain types of problems, our dynamic programming code runs several times faster than these other methods

FCPA Enforcement Against U.S. and Non-U.S. Companies

This Article explores how U.S. authorities have enforced the FCPA against non-U.S. companies and tests the perception that the FCPA disproportionately impacts U.S. businesses. After briefly discussing the FCPA, its enforcement, and its reach, this Article examines corporate FCPA enforcement activity since the statute’s enactment in 1977. It finds that foreign firms have actually fared worse under the FCPA despite the fact that DOJ and the SEC have brought more enforcement actions against domestic companies in absolute terms. The average cost of resolving an FCPA enforcement action to non-U.S. corporations of resolving an FCPA enforcement action has been more than four times higher than it has been for domestic corporations: $72.3 million to$17.6 million. In recent years, the difference has been even more pronounced—in 2017, the averages were $150.3 million and$16.1 million, respectively. This Article also explores other ways in which FCPA enforcement has more dramatically affected foreign companies. For instance, U.S. enforcement authorities have more frequently required post-resolution obligations for foreign corporations. Between 2004 and 2018, nearly 60 percent of foreign companies involved in FCPA enforcement actions were subject to post-resolution obligations in the form of an independent compliance monitor, self-reporting, or a combination of the two, compared to only 54 percent of domestic companies. Finally, this Article offers some theories to explain these data

Dyadic Characteristics and Intimate Partner Violence among Men Who Have Sex with Men

Objective: Although the research community has begun to recognize intimate partner violence (IPV) as an important issue in same-sex relationships, there has been a lack of attention to characteristics of these relationships that may be associated with IPV. In particular, there has been a lack of attention paid to the associations between dyadic characteristics and IPV in same-sex relationships. This paper examined associations between dyadic characteristics, including relationship satisfaction, communal coping and efficacy, and perpetrating and experiencing IPV among a sample of United States men who have sex with men (MSM). Methods: We collected data via an online survey with 528 MSM, who were greater than 18 years of age and reported at least one male sex partner in the last 12 months. The analysis examined dyadic factors associated with reporting of experiencing and perpetrating emotional violence, physical violence, and sexual violence. Results: The prevalence of violence in the sample ranged from nine percent reporting perpetrating sexual violence to 33% of men reporting experiencing emotional violence. MSM who reported greater satisfaction with their relationship or who reported a higher degree of concordance with their partner on lifestyle choices were less likely to report experiencing or perpetrating emotional violence. MSM who perceived a stigma to being in a male same-sex couple were less likely to report experiencing or perpetrating sexual violence. Conclusion: The results presented here demonstrate high levels of IPV among MSM and that dyadic characteristics are associated with the occurrence of IPV. Understanding relationship characteristics associated with increased IPV among same-sex male couples can contribute to the development of more accurate IPV screening tools, and more sensitively and appropriately designed intervention messages. [West J Emerg Med. 2011;12(3):324-332.

Dyadic Characteristics and Intimate Partner Violence among Men Who Have Sex with Men.

OBJECTIVE: Although the research community has begun to recognize intimate partner violence (IPV) as an important issue in same-sex relationships, there has been a lack of attention to characteristics of these relationships that may be associated with IPV. In particular, there has been a lack of attention paid to the associations between dyadic characteristics and IPV in same-sex relationships. This paper examined associations between dyadic characteristics, including relationship satisfaction, communal coping and efficacy, and perpetrating and experiencing IPV among a sample of United States men who have sex with men (MSM). METHODS: We collected data via an online survey with 528 MSM, who were greater than 18 years of age and reported at least one male sex partner in the last 12 months. The analysis examined dyadic factors associated with reporting of experiencing and perpetrating emotional violence, physical violence, and sexual violence. RESULTS: The prevalence of violence in the sample ranged from nine percent reporting perpetrating sexual violence to 33% of men reporting experiencing emotional violence. MSM who reported greater satisfaction with their relationship or who reported a higher degree of concordance with their partner on lifestyle choices were less likely to report experiencing or perpetrating emotional violence. MSM who perceived a stigma to being in a male same-sex couple were less likely to report experiencing or perpetrating sexual violence. CONCLUSION: The results presented here demonstrate high levels of IPV among MSM and that dyadic characteristics are associated with the occurrence of IPV. Understanding relationship characteristics associated with increased IPV among same-sex male couples can contribute to the development of more accurate IPV screening tools, and more sensitively and appropriately designed intervention messages

Charting self-esteem during marital dissolution.

ObjectiveThe purpose of this study was to chart changes in self-esteem before and after marital dissolution to identify the factors that shape individuals' self-esteem during this life transition.MethodWe analyzed 10 annual waves of self-esteem data from 291 divorcees from a nationally representative panel study of the Netherlands (N ~ 13,000). We charted the course of self-esteem before and after marital dissolution and tested a broad set of moderator variables that may shape individuals' self-esteem trajectories.ResultsThe average divorcee experienced significant decrease in self-esteem preceding marital dissolution and remained stable afterward. There were substantial individual differences in self-esteem trajectories, both before and after marital separation. Divorcees who experienced financial hardship, were affiliated with a church or religion, or scored low in Conscientiousness showed the most pronounced decrease in self-esteem during the years approaching marital dissolution.ConclusionThis study highlights the importance of assessing people multiple times before and after marital dissolution to dissect how people approach and respond to this life event. Results are consistent with perspectives that view divorce as an opportunity to abate the strains of an unhappy marriage

Characterizing and prognosticating chronic lymphocytic leukemia in the elderly: prospective evaluation on 455 patients treated in the United States.

BACKGROUND: Median age at diagnosis of patients with chronic lymphocytic leukemia (CLL) is \u3e 70 years. However, the majority of clinical trials do not reflect the demographics of CLL patients treated in the community. We examined treatment patterns, outcomes, and disease-related mortality in patients ≥ 75 years with CLL (E-CLL) in a real-world setting. METHODS: The Connect® CLL registry is a multicenter, prospective observational cohort study, which enrolled 1494 adult patients between 2010-2014, at 199 US sites. Patients with CLL were enrolled within 2 months of initiating first line of therapy (LOT1) or a subsequent LOT (LOT ≥ 2). Kaplan-Meier methods were used to evaluate overall survival. CLL- and infection-related mortality were assessed using cumulative incidence functions (CIF) and cause-specific hazards. Logistic regression was used to develop a classification model. RESULTS: A total of 455 E-CLL patients were enrolled; 259 were enrolled in LOT1 and 196 in LOT ≥ 2. E-CLL patients were more likely to receive rituximab monotherapy (19.3 vs. 8.6%; p \u3c 0.0001) and chemotherapy-alone regimens (p \u3c 0.0001) than younger patients. Overall and complete responses were lower in E-CLL patients than younger patients when given similar regimens. With a median follow-up of 3 years, CLL-related deaths were higher in E-CLL patients than younger patients in LOT1 (12.6 vs. 5.1% p = 0.0005) and LOT ≥ 2 (31.3 vs. 21.5%; p = 0.0277). Infection-related deaths were also higher in E-CLL patients than younger patients in LOT1 (7.4 vs. 2.7%; p = 0.0033) and in LOT ≥ 2 (16.2 vs. 11.2%; p = 0.0786). A prognostic score for E-CLL patients was developed: time from diagnosis to treatment \u3c 3 months, enrollment therapy other than bendamustine/rituximab, and anemia, identified patients at higher risk of inferior survival. Furthermore, higher-risk patients experienced an increased risk of CLL- or infection-related death (30.6 vs 10.3%; p = 0.0006). CONCLUSION: CLL- and infection-related mortality are higher in CLL patients aged ≥ 75 years than younger patients, underscoring the urgent need for alternative treatment strategies for these understudied patients. TRIAL REGISTRATION: The Connect CLL registry was registered at clinicaltrials.gov: NCT01081015 on March 4, 2010