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Strychnine is a natural product that, through isolation, structural elucidation and synthetic efforts, shaped the field of organic chemistry. Currently, strychnine is used as a pesticide to control rodents1 because of its potent neurotoxicity2,3. The polycyclic architecture of strychnine has inspired chemists to develop new synthetic transformations and strategies to access this molecular scaffold4, yet it is still unknown how plants create this complex structure. Here we report the biosynthetic pathway of strychnine, along with the related molecules brucine and diaboline. Moreover, we successfully recapitulate strychnine, brucine and diaboline biosynthesis in Nicotiana benthamiana from an upstream intermediate, thus demonstrating that this complex, pharmacologically active class of compounds can now be harnessed through metabolic engineering approaches.

Internet-based surveys can be programmed and advertised in multiple languages to reach non-English-speaking individuals, but it is unclear the extent to which this enhances the diversity of participants and supports inclusion of individuals at higher risk for HIV. We sought to examine how language of survey completion (English or Spanish) was associated with sociodemographic characteristics and indicators of HIV risk and prevention among cisgender Latino sexual minority men (SMM). We analyzed national and Washington State data using the Understanding New Infections through Targeted Epidemiology (UNITE) Cohort Study (2017 and 2018) and the Washington HIV/STI Prevention Project (WHSPP) survey (2017 and 2018/2019), respectively. Latino SMM who completed online surveys in Spanish differed from those who completed surveys in English across several sociodemographic characteristics including age, education, and income. After adjusting for sociodemographic characteristics and HIV-related risk factors, Spanish language respondents in UNITE were less likely to have tested for HIV in the past year, and those in WHSPP were more likely to report a recent STI diagnosis. Findings suggest that Latino SMM who complete surveys in Spanish comprise a unique subgroup that may have a specific HIV health and risk behavior profile. Our results suggest a need for increased and tailored efforts to recruit and include Spanish-speaking Latino SMM for local and national research and public health programming.Encuestas por internet pueden ser programadas y anunciadas para alcanzar a personas que no hablan inglés, pero no queda claro si esto pueda mejorar la diversidad de los participantes de investigación y apoyar la inclusión de los individuos de alto riesgo a infección con el VIH. En este estudio examinamos la relación del idioma de completar la encuesta en línea (inglés o español) entre hombres Latinos de minorías sexuales (HLMS) cisgénero con características sociodemográficas y determinantes para el riesgo y prevención del VIH. Analizamos los datos nacionales y estatales con el estudio de cohorte de Understanding New Infections through Targeted Epidemiology (UNITE) (2017 y 2018) y El Proyecto de Washington para la Prevención del VIH/Infecciones de Transmisión Sexual (WHSPP) (2017 y 2018/2019), respectivamente. Los HLSM quienes completaron las encuestas por internet en español fueron diferentes a los que completaron las encuestas en inglés por varias características sociodemográficas incluso la edad, la educación, y el ingreso. Después de ajustar por las características sociodemográficas y los factores de riesgo asociados con el VIH, los participantes de UNITE que respondieron en español tuvieron menos probabilidad de haberse hecho la prueba de VIH en el año pasado y los que participaron en el WHSPP eran más probable que reportaran un diagnóstico de ITS. Los resultados indican que los HLSM quienes completan las encuestas en español representan un subgrupo distinto que tiene un perfil específico de comportamiento de riesgo y salud respecto al VIH. Los resultados demuestran la necesidad de mayores esfuerzos especializados para reclutar e incluir los HLSM quienes hablan español para que participen en las investigaciones en línea a nivel local y nacional y la programación de la salud pública.

Background HIV prevention interventions which support engagement in care and increased awareness of biomedical options, including pre-exposure prophylaxis (PrEP), are highly desired for disproportionately affected Black/African American, Hispanic/Latinx and gay, bisexual, and other men who have sex with men (GBMSM) populations in the United States (US). However, in almost 40 years of HIV research, few interventions have been developed directly by and for these priority populations in domestic counties most at risk. We submit that interventions developed by early-career scientists who identify with and work directly with affected subgroups, and which include social and structural determinants of health, are vital as culturally tailored HIV prevention and care tools. Methods We reviewed and summarized interventions developed from 2007 to 2020 by historically underrepresented early-career HIV prevention scientists in a federally funded research mentoring program. We mapped these interventions to determine which were in jurisdictions deemed as high priority (based on HIV burden) by national prevention strategies. Results We summarized 11 HIV interventions; 10 (91%) of the 11 interventions are in geographic areas where HIV disparities are most concentrated and where new HIV prevention and care activities are focused. Each intervention addresses critical social and structural determinants of health disparities, and successfully reaches priority populations. Conclusion Focused funding that supports historically underrepresented scientists and their HIV prevention and care intervention research can help facilitate reaching national goals to reduce HIV-related disparities and end the HIV epidemic. Maintaining these funding streams should remain a priority as one of the tools for national HIV prevention.

Young Latino men who have sex with men (MSM) are a highly vulnerable population for HIV infection. Pre-exposure prophylaxis (PrEP) is a novel biomedical HIV prevention tool that may aid in reducing the disparity in HIV incidence among Latino MSM. However, PrEP use is disproportionally low among Latino MSM and, therefore, identifying barriers along the PrEP continuum of care (the “PrEP cascade”) would provide insight into how to best deploy PrEP interventions. Syndemics theory is a prominent framework employed in HIV prevention; however, to date, no known studies have applied this theory to PrEP. Thus, the aim of the current study was to explore the association between syndemics and the PrEP cascade, including the degree to which psychosocial and structural syndemic constructs are related to the PrEP cascade. Participants were 151 young Latino MSM (M age = 24 years; SD = 3) residing in San Diego, California, who completed a battery of online self-report measures. Results indicated high levels of syndemic indicators and varying levels of engagement across the PrEP cascade. As syndemic indicators increased, the odds of engagement across the PrEP cascade were significantly lowered. Psychosocial and structural syndemic factors accounted for unique variance in the PrEP cascade. Results highlight the need for combination interventions that address both psychosocial and structural barriers to PrEP use and persistence among young Latino MSM.

The effect of non-injection substance use on HIV viral load (VL) is understudied in international settings. Data are from HPTN063, a longitudinal observational study of HIV-infected individuals in Brazil, Thailand, and Zambia, with focus on men with VL data (Brazil = 146; Thailand = 159). Generalized linear mixed models (GLMM) assessed whether non-injection substance use (stimulants, cannabis, alcohol, polysubstance) was associated with VL undetectability. ART adherence and depressive symptoms were examined as mediators of the association. In Thailand, substance use was not significantly associated with VL undetectability or ART adherence, but alcohol misuse among MSM was associated with increased odds of depression (AOR = 2.75; 95% CI 1.20, 6.32, p = 0.02). In Brazil, alcohol misuse by MSM was associated with decreased odds of undetectable VL (AOR = 0.34; 95% CI 0.13, 0.92, p = 0.03). Polysubstance use by heterosexual men in Brazil was associated with decreased odds of ART adherence (AOR = 0.25; 95% CI 0.08, 0.78, p = 0.02). VL suppression appears attainable among non-injection substance users. Substance use interventions among HIV-positive men should address depression, adherence, and VL undetectability.

Early and sustained antiretroviral therapy (ART) adherence can suppress the HIV virus in individuals and reduce onward transmission of HIV in the population. Religiosity has been associated with better HIV clinical outcomes. Data are from a longitudinal, observational study of 749 HIV-infected individuals from Brazil, Zambia, and Thailand (HPTN 063). Ordered logistic regression assessed whether religious service attendance was associated with ART adherence (self-reported and plasma HIV-RNA) and moderated the association between alcohol problems and ART adherence. In each country, > 80% of participants reported high self-reported ART adherence (good/very good/excellent). Religious service attendance exceeded 85% but was statistically unrelated to adherence. In combined-country models, (p = 0.03) as alcohol problems increased, the probability of high self-reported ART adherence, as well as viral-load, became weaker at higher compared to low service attendance frequency. Future studies should evaluate spirituality variables and replicate the moderation analyses between religious attendance and alcohol problems.

Interventions aiming to improve access to and retention in HIV care are optimized when they are tailored to clients' needs. This paper describes an initiative of interventions implemented by ten demonstration sites using a transnational framework to tailor services for Mexicans and Puerto Ricans living with HIV. Transnationalism describes how immigrants (and their children) exist in their "receiving" place (e.g., continental U.S.) while simultaneously maintaining connections to their country or place of origin (e.g., Mexico). We describe interventions in terms of the strategies used, the theory informing design and the tailoring, and the integration of transnationalism. We argue how applying the transnational framework may improve the quality and effectiveness of services in response to the initiative's overall goal, which is to produce innovative, robust, evidence-informed strategies that go beyond traditional tailoring approaches for HIV interventions with Latino/as populations.

An experimental study evaluating the effect of bioaugmentation and antibiotic (oxytetracycline) application on pesticide degradation and microbial community structure of a biomixture used in a biopurification system (BPR) was conducted. The bioaugmentation employed a carbofuran-degrading bacterial consortium. The non-bioaugmented biomixture showed excellent performance for removal of atrazine (t1/2: 9.9 days), carbendazim (t1/2: 3.0 days), carbofuran (t1/2: 2.8 days), and metalaxyl (t1/2: 2.7 days). Neither the addition of oxytetracycline nor bioaugmentation affected the efficiency of pesticide removal or microbial community (bacterial and fungal) structure, as determined by DGGE analysis. Instead, biomixture aging was mainly responsible for microbial population shifts. Even though the bioaugmentation did not enhance the biomixtures′ performance, this matrix showed a high capability to sustain initial stresses related to antibiotic addition; therefore, simultaneous elimination of this particular mixture of pesticides together with oxytetracycline residues is not discouraged.

Biopurification systems (BPS) are employed for the treatment of pesticide-containing wastewaters. In this work, a biomixture (active core of BPS) complemented by the addition of the fungus Trametes versicolor was evaluated for the elimination of a mixture of pesticides under different treatment conditions. The biomixture achieved high removal of all the pesticides assayed after 16 d: atrazine (68.4%, t1/2: 9.6 d), carbendazim (96.7%, t1/2: 3.6 d), carbofuran (98.7%, t1/2: 3.1 d) and metalaxyl (96.7%, t1/2: 3.8 d). Variations in the treatment conditions including addition of the antibiotic oxytetracycline and co-bioaugmentation with a bacterial consortium did not significantly affect the removal performance of the biomixture. Bacterial and fungal community profiles determined by DGGE analyses revealed changes that responded to biomixture aging, and not to antibiotic or pesticide addition. The proposed biomixture exhibits very efficient elimination during simultaneous pesticide application; moreover, the matrix is highly stable during stressful conditions such as the co-application of antibiotics of agricultural use. UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro en Investigación en Contaminación Ambiental (CICA)

Pesticide biopurification systems contain a biologically active matrix (biomixture) responsible for the accelerated elimination of pesticides in wastewaters derived from pest control in crop fields. Biomixtures have been typically prepared using the volumetric composition 50:25:25 (lignocellulosic substrate/humic component/soil); nonetheless, formal composition optimization has not been performed so far. Carbofuran is an insecticide/nematicide of high toxicity widely employed in developing countries. Therefore, the composition of a highly efficient biomixture (composed of coconut fiber, compost, and soil, FCS) for the removal of carbofuran was optimized by means of a central composite design and response surface methodology. The volumetric content of soil and the ratio coconut fiber/compost were used as the design variables. The performance of the biomixture was assayed by considering the elimination of carbofuran, the mineralization of 14C-carbofuran, and the residual toxicity of the matrix, as response variables. Based on the models, the optimal volumetric composition of the FCS biomixture consists of 45:13:42 (coconut fiber/compost/soil), which resulted in minimal residual toxicity and ∼99 % carbofuran elimination after 3 days. This optimized biomixture considerably differs from the standard 50:25:25 composition, which remarks the importance of assessing the performance of newly developed biomixtures during the design of biopurification systems. Ministerio de Ciencia, Tecnología y Telecomunicaciones/[FI-093-13/802-B4-503]/MICITT/ Costa Rica Food and Agriculture Organization/[TC COS5/029]/FAO/Costa Rica Universidad de Costa Rica/[802-B2-046]/UCR/Costa Rica Universidad de Costa Rica/[802-B4-503]/UCR/Costa Rica UCR::Vicerrectoría de Investigación::Unidades de Investigación::Ciencias Básicas::Centro en Investigación en Contaminación Ambiental (CICA)

Much of what is known about commercial sexual encounters between men is based on data gathered from escorts. With few exceptions, studies have not compared male clients' reports of behavior during commercial sexual encounters with male escorts'. The present study draws from two datasets, a 2012 survey of clients (n = 495) and a 2013 survey of escorts (n = 387)--both used virtually identical measures of sexual behavior during the most recent commercial sexual encounter. For clients and escorts, the majority eschewed having sex without a condom, and kissing and oral sex were among the most common behaviors reported. Using logistic regression, both samples were compared across 15 sexual behaviors, finding significant differences in six--the escort sample had greater odds of reporting their last commercial sexual encounter involved watching the client masturbate, viewing porn, role play (dad/son, dominant/submissive), and having prior sexual experience with their commercial partner. The escort sample had lower odds of reporting that the client watched the escort masturbate, and being told partner's HIV status. In multivariable modeling, both samples did not significantly differ in reports of condomless anal sex. Male-male commercial sexual encounters appear to be involved in a wide range of sexual behaviors, many of which convey low-to-no risk of HIV transmission.

Degradation and mineralization behavior of selected nematicides was studied in soil samples from fields cultivated with banana, potato, and coffee. Degradation assays in most of the studied soils revealed shorter half-lives for carbofuran (CBF) and ethoprophos (ETP) in samples with a history of treatment with these compounds, which may have been caused by enhanced biodegradation. A short half-life value for CBF degradation was also observed in a banana field with no previous exposure to this pesticide, but with a recent application of the carbamate insecticide oxamyl, which supports the hypothesis that preexposure to oxamyl may cause microbial adaptation towards degradation of CBF, an observation of a phenomenon not yet tested according to the literature reviewed. Mineralization assays for CBF and terbufos (TBF) revealed that history of treatment with these nematicides did not cause higher mineralization rates in preexposed soils when compared to unexposed ones, except in the case of soils from coffee fields. Mineralization half-lives for soils unexposed to these pesticides were significantly shorter than most reports in the literature in the same conditions. Mineralization rates for soils with a previous exposure to these pesticides were also obtained, adding to the very few reports found. This paper contributes valuable data to the low number of reports dealing with pesticide fate in soils from tropical origin.

There has been limited research on the types of programs that male-for-male escorts would want for themselves. In 2013, 418 Internet-based male escorts completed an online survey. Participants were presented with a description of an ongoing outreach program for male sex workers called “Rent University” and asked to select workshop topics that they would be interested in (from a list of 14). Participants selected, on average, six workshops. The most commonly selected workshops centered around enhancing one’s career/wealth as an escort (e.g., “Attracting the ‘right’ clients and keeping them” 65.0 %, “Escorting and legal matters” 64.0 %, “How best to market yourself online” 62.7 %, “Financial planning and planning for the future” 52.7 %). More often than not, demographic characteristics were unassociated with selecting individual topics. Being younger, having less than a college degree, being gay identified, and having used club drugs in the past 12 months were associated with expressing interest in a greater number of workshops. Those seeking to provide such services might be well served to ensure that materials are at an appropriate reading level and culturally acceptable for younger, gay-identified men.

Puerto Rican college-aged individuals experience high rates of sexually transmitted infections. Understanding how and why these individuals search for safer sex information will allow to effectively reach them through appropriate communication channels. This study explored the safer sex information-seeking behaviors of 20 Puerto Rican undergraduate college students at the University of Puerto Rico’s Rio Piedras campus through semi-structured, one-on-one in-depth interviews. A thematic analysis revealed that students were motivated to seek information for both personal reasons (e.g., being sexually active) and external reasons (e.g., a high school assignment). Results also suggest that source characteristics were more important than the sources themselves when searching for specific information. These findings align with Johnson’s Comprehensive Model of Information Seeking (Johnson, 1997), adding “external factors” to the model's antecedents. By adding this component, the model takes into consideration the unique information-seeking behaviors of college students. Our findings may help develop effective and appropriate health communication strategies and policies that target sexual health and safer sex behaviors among this understudied population, contributing to the scarce literature available on the topics of sexual health and health communications in the Puerto Rican community as a whole.

Within the context of mixture modeling, the normal distribution is typically used as the components distribution. However, if a cluster is skewed or heavy tailed, then the normal distribution will be inefficient and many may be needed to model a single cluster. In this paper, we present an attempt to solve this problem. We define a cluster, in the absence of further information, to be a group of data which can be modeled by a unimodal density function. Hence, our intention is to use a family of univariate distribution functions, to replace the normal, for which the only constraint is unimodality. With this aim, we devise a new family of nonparametric unimodal distributions, which has large support over the space of univariate unimodal distributions. The difficult aspect of the Bayesian model is to construct a suitable MCMC algorithm to sample from the correct posterior distribution. The key will be the introduction of strategic latent variables and the use of the Product Space view of Reversible Jump methodology.