Computational engineering of previously crystallized pyruvate formate-lyase activating enzyme reveals insights into SAM binding and reductive cleavage.

Radical S-adenosyl-l-methionine (SAM) enzymes are ubiquitous in nature and carry out a broad variety of difficult chemical transformations initiated by hydrogen atom abstraction. Although numerous radical SAM (RS) enzymes have been structurally characterized, many prove recalcitrant to crystallization needed for atomic-level structure determination using X-ray crystallography, and even those that have been crystallized for an initial study can be difficult to recrystallize for further structural work. We present here a method for computationally engineering previously observed crystallographic contacts and employ it to obtain more reproducible crystallization of the RS enzyme pyruvate formate-lyase activating enzyme (PFL-AE). We show that the computationally engineered variant binds a typical RS [4Fe-4S]2+/+ cluster that binds SAM, with electron paramagnetic resonance properties indistinguishable from the native PFL-AE. The variant also retains the typical PFL-AE catalytic activity, as evidenced by the characteristic glycyl radical electron paramagnetic resonance signal observed upon incubation of the PFL-AE variant with reducing agent, SAM, and PFL. The PFL-AE variant was also crystallized in the [4Fe-4S]2+ state with SAM bound, providing a new high-resolution structure of the SAM complex in the absence of substrate. Finally, by incubating such a crystal in a solution of sodium dithionite, the reductive cleavage of SAM is triggered, providing us with a structure in which the SAM cleavage products 5'-deoxyadenosine and methionine are bound in the active site. We propose that the methods described herein may be useful in the structural characterization of other difficult-to-resolve proteins.

Micrococcin cysteine-to-thiazole conversion through transient interactions between the scaffolding protein TclI and the modification enzymes TclJ and TclN.

Ribosomally synthesized and post-translationally modified peptides (RiPPs) are a broad group of compounds mediating microbial competition in nature. Azole/azoline heterocycle formation in the peptide backbone is a key step in the biosynthesis of many RiPPs. Heterocycle formation in RiPP precursors is often carried out by a scaffold protein, an ATP-dependent cyclodehydratase, and an FMN-dependent dehydrogenase. It has generally been assumed that the orchestration of these modifications is carried out by a stable complex including the scaffold, cyclodehydratase, and dehydrogenase. The antimicrobial RiPP micrococcin begins as a precursor peptide (TclE) with a 35-amino acid N-terminal leader and a 14-amino acid C-terminal core containing six Cys residues that are converted to thiazoles. The putative scaffold protein (TclI) presumably presents the TclE substrate to a cyclodehydratase (TclJ) and a dehydrogenase (TclN) to accomplish the two-step installation of the six thiazoles. In this study, we identify a minimal TclE leader region required for thiazole formation, demonstrate complex formation between TclI, TclJ, and TclN, and further define regions of these proteins required for complex formation. Our results point to a mechanism of thiazole installation in which TclI associates with the two enzymes in a mutually exclusive fashion, such that each enzyme competes for access to the peptide substrate in a dynamic equilibrium, thus ensuring complete modification of each Cys residue in the TclE core. IMPORTANCE: Thiopeptides are a family of antimicrobial peptides characterized for having sulfur-containing heterocycles and for being highly post-translationally modified. Numerous thiopeptides have been identified; almost all of which inhibit protein synthesis in gram-positive bacteria. These intrinsic antimicrobial properties make thiopeptides promising candidates for the development of new antibiotics. The thiopeptide micrococcin is synthesized by the ribosome and undergoes several post-translational modifications to acquire its bioactivity. In this study, we identify key interactions within the enzymatic complex that carries out cysteine to thiazole conversion in the biosynthesis of micrococcin.

Sociodemographic Variables Can Guide Prioritized Testing Strategies for Epidemic Control in Resource-Limited Contexts.

BACKGROUND: Targeted surveillance allows public health authorities to implement testing and isolation strategies when diagnostic resources are limited, and can be implemented via the consideration of social network topologies. However, it remains unclear how to implement such surveillance and control when network data are unavailable. METHODS: We evaluated the ability of sociodemographic proxies of degree centrality to guide prioritized testing of infected individuals compared to known degree centrality. Proxies were estimated via readily available sociodemographic variables (age, gender, marital status, educational attainment, household size). We simulated severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) epidemics via a susceptible-exposed-infected-recovered individual-based model on 2 contact networks from rural Madagascar to test applicability of these findings to low-resource contexts. RESULTS: Targeted testing using sociodemographic proxies performed similarly to targeted testing using known degree centralities. At low testing capacity, using proxies reduced infection burden by 22%-33% while using 20% fewer tests, compared to random testing. By comparison, using known degree centrality reduced the infection burden by 31%-44% while using 26%-29% fewer tests. CONCLUSIONS: We demonstrate that incorporating social network information into epidemic control strategies is an effective countermeasure to low testing capacity and can be implemented via sociodemographic proxies when social network data are unavailable.

Predicting primate-parasite associations using exponential random graph models.

Ecological associations between hosts and parasites are influenced by host exposure and susceptibility to parasites, and by parasite traits, such as transmission mode. Advances in network analysis allow us to answer questions about the causes and consequences of traits in ecological networks in ways that could not be addressed in the past. We used a network-based framework (exponential random graph models or ERGMs) to investigate the biogeographic, phylogenetic and ecological characteristics of hosts and parasites that affect the probability of interactions among nonhuman primates and their parasites. Parasites included arthropods, bacteria, fungi, protozoa, viruses and helminths. We investigated existing hypotheses, along with new predictors and an expanded host-parasite database that included 213 primate nodes, 763 parasite nodes and 2319 edges among them. Analyses also investigated phylogenetic relatedness, sampling effort and spatial overlap among hosts. In addition to supporting some previous findings, our ERGM approach demonstrated that more threatened hosts had fewer parasites, and notably, that this effect was independent of hosts also having a smaller geographic range. Despite having fewer parasites, threatened host species shared more parasites with other hosts, consistent with loss of specialist parasites and threat arising from generalist parasites that can be maintained in other, non-threatened hosts. Viruses, protozoa and helminths had broader host ranges than bacteria, or fungi, and parasites that infect non-primates had a higher probability of infecting more primate species. The value of the ERGM approach for investigating the processes structing host-parasite networks provided a more complete view on the biogeographic, phylogenetic and ecological traits that influence parasite species richness and parasite sharing among hosts. The results supported some previous analyses and revealed new associations that warrant future research, thus revealing how hosts and parasites interact to form ecological networks.

Surrogate Wnt agonists that phenocopy canonical Wnt and ß-catenin signalling.

Wnt proteins modulate cell proliferation and differentiation and the self-renewal of stem cells by inducing ß-catenin-dependent signalling through the Wnt receptor frizzled (FZD) and the co-receptors LRP5 and LRP6 to regulate cell fate decisions and the growth and repair of several tissues. The 19 mammalian Wnt proteins are cross-reactive with the 10 FZD receptors, and this has complicated the attribution of distinct biological functions to specific FZD and Wnt subtype interactions. Furthermore, Wnt proteins are modified post-translationally by palmitoylation, which is essential for their secretion, function and interaction with FZD receptors. As a result of their acylation, Wnt proteins are very hydrophobic and require detergents for purification, which presents major obstacles to the preparation and application of recombinant Wnt proteins. This hydrophobicity has hindered the determination of the molecular mechanisms of Wnt signalling activation and the functional importance of FZD subtypes, and the use of Wnt proteins as therapeutic agents. Here we develop surrogate Wnt agonists, water-soluble FZD-LRP5/LRP6 heterodimerizers, with FZD5/FZD8-specific and broadly FZD-reactive binding domains. Similar to WNT3A, these Wnt agonists elicit a characteristic ß-catenin signalling response in a FZD-selective fashion, enhance the osteogenic lineage commitment of primary mouse and human mesenchymal stem cells, and support the growth of a broad range of primary human organoid cultures. In addition, the surrogates can be systemically expressed and exhibit Wnt activity in vivo in the mouse liver, regulating metabolic liver zonation and promoting hepatocyte proliferation, resulting in hepatomegaly. These surrogates demonstrate that canonical Wnt signalling can be activated by bi-specific ligands that induce receptor heterodimerization. Furthermore, these easily produced, non-lipidated Wnt surrogate agonists facilitate functional studies of Wnt signalling and the exploration of Wnt agonists for translational applications in regenerative medicine.

Demography's Changing Intellectual Landscape: A Bibliometric Analysis of the Leading Anglophone Journals, 1950-2020.

Much of what we know about the intellectual landscape of anglophone demography comes from two sources: subjective narratives authored by leaders in the field, whose reviews and observations are derived from their research experience and field-specific knowledge; and professional histories covering the field's foundational controversies, which tend to focus on individuals, institutions, and influence. Here we use bibliographic information from all articles published in the three leading journals of anglophone demography-Demography, Population Studies, and Population and Development Review-to survey the changing contours of anglophone demography's key research areas over the past 70 years. We characterize the field of demography by applying a two-pronged, data-grounded approach from the sociology of science. The first uses natural language processing that lets the substance of the field emerge from the contents of publication records and applies social network analyses to identify groups of papers that talk about the same thing. The second uses bibliometric tools to capture the "conversations" of demography with other disciplines. Our goals are to (1) identify the primary topics of demography since the discipline first gained prominence as an organized field; (2) assess changes in the field's intellectual cohesion and the topical areas that have grown or shrunk; and (3) examine how demographers place their work in relationship to other disciplines, the visibility and influence of demographic research in the broader scientific literature, and the cross-disciplinary translational reach of demographic research. Results provide a dynamic view of the field's scientific development in the second half of the twentieth century and the first two decades of the twenty-first century.

Scalable Strategies to Increase Efficiency and Augment Public Health Activities During Epidemic Peaks.

OBJECTIVE: Scalable strategies to reduce the time burden and increase contact tracing efficiency are crucial during early waves and peaks of infectious transmission. DESIGN: We enrolled a cohort of SARS-CoV-2-positive seed cases into a peer recruitment study testing social network methodology and a novel electronic platform to increase contact tracing efficiency. SETTING: Index cases were recruited from an academic medical center and requested to recruit their local social contacts for enrollment and SARS-CoV-2 testing. PARTICIPANTS: A total of 509 adult participants enrolled over 19 months (384 seed cases and 125 social peers). INTERVENTION: Participants completed a survey and were then eligible to recruit their social contacts with unique "coupons" for enrollment. Peer participants were eligible for SARS-CoV-2 and respiratory pathogen screening. MAIN OUTCOME MEASURES: The main outcome measures were the percentage of tests administered through the study that identified new SARS-CoV-2 cases, the feasibility of deploying the platform and the peer recruitment strategy, the perceived acceptability of the platform and the peer recruitment strategy, and the scalability of both during pandemic peaks. RESULTS: After development and deployment, few human resources were needed to maintain the platform and enroll participants, regardless of peaks. Platform acceptability was high. Percent positivity tracked with other testing programs in the area. CONCLUSIONS: An electronic platform may be a suitable tool to augment public health contact tracing activities by allowing participants to select an online platform for contact tracing rather than sitting for an interview.

Quantifying In Situ Structural Stabilities of Human Blood Plasma Proteins Using a Novel Iodination Protein Stability Assay.

Many of the diseases that plague society today are driven by a loss of protein quality. One method to quantify protein quality is to measure the protein folding stability (PFS). Here, we present a novel mass spectrometry (MS)-based approach for PFS measurement, iodination protein stability assay (IPSA). IPSA quantifies the PFS by tracking the surface-accessibility differences of tyrosine, histidine, methionine, and cysteine under denaturing conditions. Relative to current methods, IPSA increases protein coverage and granularity to track the PFS changes of a protein along its sequence. To our knowledge, this study is the first time the PFS of human serum proteins has been measured in the context of the blood serum (in situ). We show that IPSA can quantify the PFS differences between different transferrin iron-binding states in near in vivo conditions. We also show that the direction of the denaturation curve reflects the in vivo surface accessibility of the amino acid residue and reproducibly reports a residue-specific PFS. Along with IPSA, we introduce an analysis tool Chalf that provides a simple workflow to calculate the residue-specific PFS. The introduction of IPSA increases the potential to use protein structural stability as a structural quality metric in understanding the etiology and progression of human disease. Data is openly available at Chorusproject.org (project ID 1771).

Targeted maximum likelihood estimation of causal effects with interference: A simulation study.

Interference, the dependency of an individual's potential outcome on the exposure of other individuals, is a common occurrence in medicine and public health. Recently, targeted maximum likelihood estimation (TMLE) has been extended to settings of interference, including in the context of estimation of the mean of an outcome under a specified distribution of exposure, referred to as a policy. This paper summarizes how TMLE for independent data is extended to general interference (network-TMLE). An extensive simulation study is presented of network-TMLE, consisting of four data generating mechanisms (unit-treatment effect only, spillover effects only, unit-treatment and spillover effects, infection transmission) in networks of varying structures. Simulations show that network-TMLE performs well across scenarios with interference, but issues manifest when policies are not well-supported by the observed data, potentially leading to poor confidence interval coverage. Guidance for practical application, freely available software, and areas of future work are provided.

The role of informational support from women's social networks on antenatal care initiation: qualitative evidence from pregnant women in Uganda.

BACKGROUND: Early and appropriate use of antenatal care services is critical for reducing maternal and neonatal mortality and morbidity. Yet most women in sub-Saharan Africa, including Uganda, do not seek antenatal care until later during pregnancy. This qualitative study explored pregnant women's reliance on social ties for information about initiation of antenatal care. METHODS: We conducted semi-structured, in-depth interviews with 30 pregnant women seeking their first antenatal care visit at Kawempe Referral Hospital in Kampala, Uganda. Recruitment was done purposively to obtain variation by parity and whether women currently had a male partner. Study recruitment occurred from August 25th 2020 - October 26th, 2020. We used thematic analysis following a two-stage coding process, with both deductive and inductive codes. Deductive codes followed the key domains of social network and social support theory. RESULTS: We found that the most important source of information about antenatal care initiation was these women's mothers. Other sources included their mothers-in-law, female elders including grandmothers, and male partners. Sisters and female friends were less influential information sources about antenatal initiation. One of the primary reasons for relying on their own mothers, mothers-in-law, and elder women was due to these women's lived experience with pregnancy and childbirth. Trust in the relationship was also an important factor. Some pregnant women were less likely to rely on their sisters or female friends, either due to lack of trust or these women's lack of experience with pregnancy and childbirth. The advice that pregnant women received from their mothers and others on the ideal timing for antenatal care initiation varied significantly, including examples of misinformation about when to initiate antenatal care. Pregnant women seemed less likely to delay care when more than one social tie encouraged early antenatal care. CONCLUSIONS: Educating women's social networks, especially their mothers, mothers-in-law, and community elders, about the importance of early antenatal care initiation is a promising avenue for encouraging pregnant women to seek care earlier in pregnancy.

Network sampling coverage III: Imputation of missing network data under different network and missing data conditions.

Missing data is a common, difficult problem for network studies. Unfortunately, there are few clear guidelines about what a researcher should do when faced with incomplete information. We take up this problem in the third paper of a three-paper series on missing network data. Here, we compare the performance of different imputation methods across a wide range of circumstances characterized in terms of measures, networks and missing data types. We consider a number of imputation methods, going from simple imputation to more complex model- based approaches. Overall, we find that listwise deletion is almost always the worst option, while choosing the best strategy can be difficult, as it depends on the type of missing data, the type of network and the measure of interest. We end the paper by offering a set of practical outputs that researchers can use to identify the best imputation choice for their particular research setting.

Assortativity and Bias in Epidemiologic Studies of Contagious Outcomes: A Simulated Example in the Context of Vaccination.

Assortativity is the tendency of individuals connected in a network to share traits and behaviors. Through simulations, we demonstrated the potential for bias resulting from assortativity by vaccination, where vaccinated individuals are more likely to be connected with other vaccinated individuals. We simulated outbreaks of a hypothetical infectious disease and vaccine in a randomly generated network and a contact network of university students living on campus. We varied protection of the vaccine to the individual, transmission potential of vaccinated-but-infected individuals, and assortativity by vaccination. We compared a traditional approach, which ignores the structural features of a network, with simple approaches which summarized information from the network. The traditional approach resulted in biased estimates of the unit-treatment effect when there was assortativity by vaccination. Several different approaches that included summary measures from the network reduced bias and improved confidence interval coverage. Through simulations, we showed the pitfalls of ignoring assortativity by vaccination. While our example is described in terms of vaccines, our results apply more widely to exposures for contagious outcomes. Assortativity should be considered when evaluating exposures for contagious outcomes.

Provider Bias in prescribing opioid analgesics: a study of electronic medical Records at a Hospital Emergency Department.

BACKGROUND: Physicians do not prescribe opioid analgesics for pain treatment equally across groups, and such disparities may pose significant public health concerns. Although research suggests that institutional constraints and cultural stereotypes influence doctors' treatment of pain, prior quantitative evidence is mixed. The objective of this secondary analysis is therefore to clarify which institutional constraints and patient demographics bias provider prescribing of opioid analgesics. METHODS: We used electronic medical record data from an emergency department of a large U.S hospital during years 2008-2014. We ran multi-level logistic regression models to estimate factors associated with providing an opioid prescription during a given visit while controlling for ICD-9 diagnosis codes and between-patient heterogeneity. RESULTS: A total of 180,829 patient visits for 63,513 unique patients were recorded during the period of analysis. Overall, providers were significantly less likely to prescribe opioids to the same individual patient when the visit occurred during higher rates of emergency department crowding, later times of day, earlier in the week, later years in our sample, and when the patient had received fewer previous opioid prescriptions. Across all patients, providers were significantly more likely to prescribe opioids to patients who were middle-aged, white, and married. We found no bias towards women and no interaction effects between race and crowding or between race and sex. CONCLUSIONS: Providers tend to prescribe fewer opioids during constrained diagnostic situations and undertreat pain for patients from high-risk and marginalized demographic groups. Potential harms resulting from previous treatment decisions may accumulate by informing future treatment decisions.

The association between men's family planning networks and contraceptive use among their female partners: an egocentric network study in Madagascar.

BACKGROUND: Ensuring women have information, support and access to family planning (FP) services will allow women to exercise their reproductive autonomy and reduce maternal mortality, which remains high in countries such as Madagascar. Research shows that women's social networks - their ties with partners, family members, friends, and providers - affect their contraceptive use. Few studies have considered the role of men's social networks on women's contraceptive use. Insofar as women's contraceptive use may be influenced by their male partners, women's contraceptive use may also be affected by their partner's social networks. Men may differ by the types of ties they rely on for information and advice about FP. It is unknown whether differences in the composition of men's FP networks matter for couples' contraceptive use. This study assessed the association between men's FP networks and couples' contraceptive use. METHODS: This egocentric network study was conducted among married/partnered men (n = 178) in rural Madagascar. Study participants listed who they relied on for FP information and advice, including health providers and social ties. They provided ties' gender, age, relationship, and perceived support of contraceptive use. The primary outcome was couples' contraceptive use, and explanatory variables included FP networks and their composition (no FP network, social-only network, provider-only network, and mixed network of social and provider ties). Analyses used generalized linear models specifying a Poisson distribution, with covariate adjustment and cluster robust standard errors. RESULTS: Men who had FP networks were 1.9 times more likely to use modern contraception as a couple compared to men with no FP network (95% confidence interval [CI] 1.64-2.52; p ≤ 0.001). Compared to men with no FP network, men were more likely to use modern contraception if they had a social-only network, relative risk (RR) = 2.10 (95% CI, 1.65-2.68; p ≤ 0.001); a provider-only network, RR = 1.80 (95% CI, 1.54-2.11; p ≤ 0.001); or a mixed network, RR = 2.35 (95% CI, 1.97-2.80; p ≤ 0.001). CONCLUSIONS: Whether men have a FP network, be it provider or social ties, distinguishes if couples are using contraception. Interventions should focus on reaching men not only through providers but also through their social ties to foster communication and support for contraceptive use.

Molecular architecture of the Bardet-Biedl syndrome protein 2-7-9 subcomplex.

Bardet-Biedl syndrome (BBS) is a genetic disorder characterized by malfunctions in primary cilia resulting from mutations that disrupt the function of the BBSome, an 8-subunit complex that plays an important role in protein transport in primary cilia. To better understand the molecular basis of BBS, here we used an integrative structural modeling approach consisting of EM and chemical cross-linking coupled with MS analyses, to analyze the structure of a BBSome 2-7-9 subcomplex consisting of three homologous BBS proteins, BBS2, BBS7, and BBS9. The resulting molecular model revealed an overall structure that resembles a flattened triangle. We found that within this structure, BBS2 and BBS7 form a tight dimer through a coiled-coil interaction and that BBS9 associates with the dimer via an interaction with the α-helical domain of BBS2. Interestingly, a BBS-associated mutation of BBS2 (R632P) is located in its α-helical domain at the interface between BBS2 and BBS9, and binding experiments indicated that this mutation disrupts the BBS2-BBS9 interaction. This finding suggests that BBSome assembly is disrupted by the R632P substitution, providing molecular insights that may explain the etiology of BBS in individuals harboring this mutation.

Disparate foundations of scientists' policy positions on contentious biomedical research.

What drives scientists' position taking on matters where empirical answers are unavailable or contradictory? We examined the contentious debate on whether to limit experiments involving the creation of potentially pandemic pathogens. Hundreds of scientists, including Nobel laureates, have signed petitions on the debate, providing unique insights into how scientists take a public stand on important scientific policies. Using 19,257 papers published by participants, we reconstructed their collaboration networks and research specializations. Although we found significant peer associations overall, those opposing "gain-of-function" research are more sensitive to peers than are proponents. Conversely, specializing in fields directly related to gain-of-function research (immunology, virology) predicts public support better than specializing in fields related to potential pathogenic risks (such as public health) predicts opposition. These findings suggest that different social processes might drive support compared with opposition. Supporters are embedded in a tight-knit scholarly community that is likely both more familiar with and trusting of the relevant risk mitigation practices. Opponents, on the other hand, are embedded in a looser federation of widely varying academic specializations with cognate knowledge of disease and epidemics that seems to draw more heavily on peers. Understanding how scientists' social embeddedness shapes the policy actions they take is important for helping sides interpret each other's position accurately, avoiding echo-chamber effects, and protecting the role of scientific expertise in social policy.

First critical repressive H3K27me3 marks in embryonic stem cells identified using designed protein inhibitor.

The polycomb repressive complex 2 (PRC2) histone methyltransferase plays a central role in epigenetic regulation in development and in cancer, and hence to interrogate its role in a specific developmental transition, methods are needed for disrupting function of the complex with high temporal and spatial precision. The catalytic and substrate recognition functions of PRC2 are coupled by binding of the N-terminal helix of the Ezh2 methylase to an extended groove on the EED trimethyl lysine binding subunit. Disrupting PRC2 function can in principle be achieved by blocking this single interaction, but there are few approaches for blocking specific protein-protein interactions in living cells and organisms. Here, we describe the computational design of proteins that bind to the EZH2 interaction site on EED with subnanomolar affinity in vitro and form tight and specific complexes with EED in living cells. Induction of the EED binding proteins abolishes H3K27 methylation in human embryonic stem cells (hESCs) and at all but the earliest stage blocks self-renewal, pinpointing the first critical repressive H3K27me3 marks in development.

Our Buddies, Ourselves: The Role of Sexual Homophily in Adolescent Friendship Networks.

The present study tests the assumption that peers wield sufficient influence to induce sexual homophily (i.e., similarities in sexual experiences). Because girls face greater stigma for their sexual experiences than do boys, sexual homophily may be greater in girls' friendship networks than in boys'. Stochastic actor-based models were used to analyze network data (n = 2,566; ages 14-18) from two high schools in the National Longitudinal Study of Adolescent to Adult Health. Sexual homophily was present in friendship networks. Girls and boys were equally susceptible to their friends' influence, but the former exhibited a stronger preference for befriending same sexual debut status peers than the latter. The findings suggest that adolescents-particularly girls-"curate" their networks to minimize peer ostracism.

Social Ties Cut Both Ways: Self-Harm and Adolescent Peer Networks.

Peers play an important role in adolescence, a time when self-harm arises as a major health risk, but little is known about the social networks of adolescents who cut. Peer network positions can affect mental distress related to cutting or provide direct social motivations for self-harm. This study uses PROSPER survey data from U.S. high school students (n = 11,160, 48% male, grades 11 and 12), finding that social networks predict self-cutting net of demographics and depressive symptoms. In final models, bridging peers predicts higher self-cutting, while claiming more friends predicts lower cutting for boys. The findings suggest that researchers and practitioners should consider peer networks both a beneficial resource and source of risk associated with cutting for teens and recognize the sociostructural contexts of self-harm for adolescents more broadly.

Changes in Anxiety and Depression Symptoms Predict Sexual Risk Behaviors Among Young Men Living in Dar es Salaam, Tanzania.

Young men are important targets in HIV prevention in Tanzania and throughout sub-Saharan Africa. Anxiety and depression are common among youth and may be important predictors of HIV risk behaviors; evidence of these relationships in high-risk populations is needed. Using baseline and 1 year follow-up assessments from an HIV prevention trial we assessed the association between changes in symptoms of anxiety and depression and follow-up sexual risk behaviors (condom use and sexual partner concurrency) controlling for baseline sexual risk behaviors among 1113 male members of social groups known as "camps" in Dar es Salaam, Tanzania. Anxiety and depression were measured using the HSCL-25 and condom use and sexual partner concurrency were assessed through self-report. In separate models, increases in anxiety and depression were associated with sexual partner concurrency and with lower levels of condom use. In a combined model, both anxiety and depression appeared to independently affect concurrency but only depression was independently associated with condom use, with the association between anxiety and condom use being likely attributable to covariance with depression symptoms. The results of this study indicate the importance of screening and providing treatment for depression and anxiety disorders in high HIV-prevalence contexts, and the need to develop effective HIV prevention interventions targeting young men living with anxiety and depression.