Chemical communication in the Mozambique tilapia: a role for amino acids

The Mozambique tilapia (Oreochromis mossambicus) is a maternal mouthbrooding cichlid from the southern Africa. The olfactory sensitivity of the species to 20 amino acids was assessed using the electro-olfactogram (EOG). We estimated whether the olfactory potency of the polar fraction of male urine can be explained by the presence of identified amino acids. In addition, filtrate and amino acid mixture of the urine of Nile tilapia were used to estimate their olfactory potency for O.mossambicus. Finally, concentrations of the main amino acids were measured in the urine of males of different social status and the correlations between amino acid concentration and hierarchical status were explored. L-cysteine, L-glutamine and L-threonine were the most potent stimuli at M while L-proline and L-aspartate were the least potent. Four groups of amino acids were identified according to their thresholds of detection and three groups – according to the similarity of their ɣ-factors. The estimated threshold of detection for O.mossambicus mixture was higher than that for the filtrate. On the contrary, the threshold of detection for the mixture of Nile tilapia was lower than that for the filtrate The concentration of L-arginine in the urine was positively correlated with fish dominance index. Both L-arginine and L-glutamic acid concentrations had much greater variability in dominant males (DI˃0.5) than in subordinate males (DI˂0.5). The urinary concentrations of L-phenylalanine had similar variability in dominant and subordinate groups. The Mozambique tilapia has olfactory sensitivity to all twenty amino acids tested. The fish showed more acute sensitivity to conspecific urine filtrate than to the heterospecific. Olfactory potency of O.mossambicus filtrate can be largely but not fully explained by the presence of L-arginine, L-glutamic acid and L-phenylalanine. Larginine and L-glutamic acid may indicate the dominance status of the fish and, possibly, individual identity.A tilápia de Moçambique (Oreochromis mossambicus) é um ciclídeo africano que apresenta incubação bucal maternal, e que se encontra naturalmente distribuída em cursos de água no sul de África. Os machos dominantes apresentam grandes bexigas urinárias, que têm a capacidade de armazenar uma quantidade substancialmente superior do urina do que a das fêmeas, que é libertada em contexto apropriado (cortejo ou agressividade macho-macho). Demonstrou-se que os machos são capazes de diferenciar o odor de fêmeas em processo pré-ovulatório das que estão em processo pós-ovulatório, o que provoca um aumento do processo de libertação de urina em machos; e que os machos dominantes apresentam uma urina com maior potência olfativa do que a de outros machos (subordinados). Isto sugere que a urina poderá ter um papel importante na comunicação química entre elementos desta espécie. Pesquisas anteriores efetuadas no nosso laboratório identificaram um esteroide glicurónico na urina de machos, e que age como feromona (endócrino) em fêmeas. Este composto pode representar a maior parte da potência olfativa da parte nãopolar da urina, e a concentração do mesmo poderá estar positivamente correlacionada com a dominância dos machos. No entanto, a fração polar também contém odoríferos. Porém, estão ainda por identificar os compostos responsáveis pela potência olfativa nesta fração. Esta investigação tem como objetivo estabelecer quais poderão ser os aminoácidos responsáveis pela potência olfativa na parte polar da urina de tilápia de Moçambique. O primeiro passo realizado foi verificar a sensibilidade olfativa da tilápia de Moçambique a 20 aminoácidos, usando para tal um electro-olfactograma (EOG). O segundo passo foi identificar os aminoácidos presentes na urina nos machos de tilápia de Moçambique. Como terceiro passo, estimamos se a potência olfativa da fração polar da urina dos machos poderá ser explicada por esses aminoácidos, ou se outros odoríferos – ainda não identificados – estão também presentes; adicionalmente, um filtrado de urina e uma mistura artificial de aminoácidos de urina de tilápia do Nilo (uma espécie filogeneticamente próxima da tilápia de Moçambique) foram usadas para verificar a sua potência em O. mossambicus, e para comparar os resultados obtidos para as duas espécies de tilápia. Finalmente, mediu-se a concentração de aminoácidos na urina de machos provenientes de diferentes estratos sociais, para explorar possíveis correlações entre a concentração de aminoácidos na urina e a hierarquia dos machos na sociedade. Como resultado, os aminoácidos L-cisteína, L-glutamina e L-treonina produziram o estímulo mais potente na concentração mais alta testada ( M), e os aminoácidos L-prolina e L-aspartato foram os que produziram o estímulo menos potente em O. mossambicus. Para identificar os aminoácidos presentes na urina dos machos dominantes, as amostras de urina foram submetidas a um processo de derivatização, e a concentração de aminoácidos foi calculada através de cromatografia gasosa e espectroscopia de massa (GC-MS). O mesmo processo foi aplicado para quantificar os aminoácidos predominantes (L-arginina, L-ácido glutâmico e L-fenilalanina) na urina de machos originários de diferentes estratos sociais. Entre os três aminoácidos mencionados acima, o mais abundante na urina de machos dominantes de tilápia de Moçambique foi a L-arginina, com a potência olfativa mais alta ( M). Quatro grupos de aminoácidos (a, b, c, d) foram identificados de acordo com os seus limites de deteção, e três outros grupos foram identificados pela similaridade dos seus fatores ɣ. Os aminoácidos de natureza básica obtiveram os limites de deteção mais baixos, e os que continham grupos imino ou grupos acídicos apresentaram menor potência. Os aminoácidos de natureza básica geralmente apresentavam também valores mais baixos de fatores ɣ que os aminoácidos de outras classes. Por oposição, os fatores ɣ dos odoríferos das classes acídicas e hidroxilo eram geralmente altas. A potência olfativa do filtrado de urina de O. mossambicus foi significativamente mais alta do que a da mistura artificial de aminoácidos, preparada com base na concentração de aminoácidos previamente identificada na urina da pool de machos dominantes por GC-MS. O limite de deteção estimado para a mistura de urina de O. mossambicus foi obtido para uma diluição de , e para o filtrado de urina foi de . A comparação estatística da potência olfativa entre o filtrado de urina de tilápia de Moçambique e a mistura artificial de aminoácidos de urina de tilápia do Nilo identificaram que o limite de deteção para a mistura (diluição a ) era inferior ao filtrado (diluição a ). Os fatores ɣ não foram estatisticamente diferentes nem para a mistura e filtrado de urina de O. mossambicus, nem para a mistura ou filtrado de urina de O. niloticus. O filtrado de urina de tilápia do Nilo foi menos potente para o sistema olfativo de tilápia de Moçambique que o filtrado coespecífico (Limites de diluição de e , correspondentemente). A concentração de L-arginina na urina foi positivamente correlacionada com o índice de dominância dos peixes (R=0.495; P˂0.05).O aminoácido L-arginina estava presente em concentrações substancialmente mais altas na urina de machos dominantes, em relação aos grupos intermédio e subordinado. Este apresentava também uma maior variabilidade de concentrações em machos dominantes (DI˃0.5), do que em machos subordinados (DI˂0.5). De maneira similar ao aminoácido L-arginina, as concentrações de L-ácido glutâmico apresentaram também uma maior variabilidade de concentrações em machos dominantes do que em machos subordinados. No entanto, não se verificou nenhuma correlação com a dominância (R=0.399; P=0.0657). A concentração na urina de L-fenilalanina apresentar uma variabilidade similar nos grupos de machos dominantes e machos subordinados, e não apresenta correlação com o índice de dominância (R= -0.385, P=0.0769). Em todos os grupos as concentrações de L-fenilalanina na urina foram inferiores às de L-arginina e Lácido glutâmico. Podemos então concluír que: 1. A tilápia de Moçambique tem sensitividade olfativa aos vinte aminoácidos essenciais e não-essenciais, mas a capacidade e habilidade dos aminoácidos para provocarem uma resposta olfativa aguda através de mudanças na sua concentração são diferentes entre si. 2. A tilápia de Moçambique tem uma maior sensitividade ao filtrado de urina coespecífica, do que ao filtrado heteroespecífico de tilápia do Nilo. A potência olfativa do filtrado de O. mossambicus pode ser largamente, mas não completamente, explicada pela presença de determinados aminoácidos (L-arginina, L-ácido glutâmico e L-fenilalanina). No entanto, outros compostos odoríferos polares deverão também estar presentes. 3. Os aminoácidos L-arginina e L-ácido glutâmico são componentes importantes do odor da urina do macho de tilápia de Moçambique, e poderão indicar o status de dominância do peixe na comunidade e definir, possivelmente, a sua identidade individual

Development of the City Public Service Model on the Basis of Integrated Transport Flow Indicators

The problem of modeling public services based on architectural and planning decisions is considered, the role of traffic in the formation of a model of city services is analyzed. An integrated criterion for the quality of public services is proposed. A method has been developed for determining segmented public services taking into account the transport areas of the city, which will make it possible to evenly disperse public service centers. The basis is a socio-planning organization, as a material-spatial system containing anthropogenic and natural components – the territory and institutions where the functional processes that take place in the urban planning environment take place. The described model has certain versatility, and is simultaneously suitable for characterizing various categories of service institutions. Thus, the task of optimizing the quality of public services in the city is reduced to a mathematical model for which, by setting the basic design criteria, the optimal result can be obtained.On the basis of a questionnaire survey and analysis of statistical data, calculation of traffic intensity, the demand and supply of the level of public services фre studied. The structural elements of this model: population, territory, transport and service institutions, are in dialectical interaction, which is described by the mathematical model in this study. The model is based on the calculation of the minimum population in the service area, which allows to have i-th type establishments using the social potential method, as well as a graph-analytical method in determining the optimal location of service institutions in the city.As a result of the research, a conceptual model of public services for cities is built, a layout of supermarkets in the territory of Uzhhorod and distribution of service areas of these institutions is proposed. This optimization will ensure uniform domestic servicing of the territory, optimal performance indicators of service establishments and minimum average service radii of points

DEVELOPMENT OF THE CITY PUBLIC SERVICE MODEL ON THE BASIS OF INTEGRATED TRANSPORT FLOW INDICATORS

The problem of modeling public services based on architectural and planning decisions is considered, the role of traffic in the formation of a model of city services is analyzed. An integrated criterion for the quality of public services is proposed. A method has been developed for determining segmented public services taking into account the transport areas of the city, which will make it possible to evenly disperse public service centers. The basis is a socio-planning organization, as a material-spatial system containing anthropogenic and natural components – the territory and institutions where the functional processes that take place in the urban planning environment take place. The described model has certain versatility, and is simultaneously suitable for characterizing various categories of service institutions. Thus, the task of optimizing the quality of public services in the city is reduced to a mathematical model for which, by setting the basic design criteria, the optimal result can be obtained. On the basis of a questionnaire survey and analysis of statistical data, calculation of traffic intensity, the demand and supply of the level of public services фre studied. The structural elements of this model: population, territory, transport and service institutions, are in dialectical interaction, which is described by the mathematical model in this study. The model is based on the calculation of the minimum population in the service area, which allows to have i-th type establishments using the social potential method, as well as a graph-analytical method in determining the optimal location of service institutions in the city. As a result of the research, a conceptual model of public services for cities is built, a layout of supermarkets in the territory of Uzhhorod and distribution of service areas of these institutions is proposed. This optimization will ensure uniform domestic servicing of the territory, optimal performance indicators of service establishments and minimum average service radii of points

DEVELOPMENT OF THE CITY PUBLIC SERVICE MODEL ON THE BASIS OF INTEGRATED TRANSPORT FLOW INDICATORS

The problem of modeling public services based on architectural and planning decisions is considered, the role of traffic in the formation of a model of city services is analyzed. An integrated criterion for the quality of public services is proposed. A method has been developed for determining segmented public services taking into account the transport areas of the city, which will make it possible to evenly disperse public service centers. The basis is a socio-planning organization, as a material-spatial system containing anthropogenic and natural components – the territory and institutions where the functional processes that take place in the urban planning environment take place. The described model has certain versatility, and is simultaneously suitable for characterizing various categories of service institutions. Thus, the task of optimizing the quality of public services in the city is reduced to a mathematical model for which, by setting the basic design criteria, the optimal result can be obtained.On the basis of a questionnaire survey and analysis of statistical data, calculation of traffic intensity, the demand and supply of the level of public services фre studied. The structural elements of this model: population, territory, transport and service institutions, are in dialectical interaction, which is described by the mathematical model in this study. The model is based on the calculation of the minimum population in the service area, which allows to have i-th type establishments using the social potential method, as well as a graph-analytical method in determining the optimal location of service institutions in the city.As a result of the research, a conceptual model of public services for cities is built, a layout of supermarkets in the territory of Uzhhorod and distribution of service areas of these institutions is proposed. This optimization will ensure uniform domestic servicing of the territory, optimal performance indicators of service establishments and minimum average service radii of points

Effect of Immunomodulating Adjuvant Dzherelo (Immunoxel) in HIV Infected Patients Receiving Standard Antiretroviral Therapy

Open-label, matched-case, comparative trial was conducted in 40 HIV-infected patients to evaluate the adjunct effect of Dzherelo (Immunoxel) on immune and viral parameters. Arm A (n=20) received anti-retroviral therapy (ART) consisting of zidovudine, lamivudine, and efavirenz and arm B (n=20) received ART with Dzherelo. After 2 months total T-lymphocytes increased in ART recipients from 664 to 819 cells/μl (P=0.06), whereas in Dzherelo recipients they rose from 595 to 785(P=0.03). The CD4 T-cells expanded by 57.3% (218 to 343; P=0.002) in the ART arm and by 93.5% (184 to 356; P=0.004) in the Dzherelo arm. The accrual in absolute and relative number of CD8+ lymphocytes in ART and in the Dzherelo recipients was 43.2% (2.7%) and 50.4% (-0.5%) respectively. The CD4/CD8 ratio in Dzherelo recipients increased from 1.495 to 1.940 (P=0.03) but insignificant in the control: 1.418 to 1.613 (P=0.14). Activated CD3+ HLADR+ T-cells increased from 209 to 264 (P=0.02) and from 161 to 348 (P=0.0007) in ART and Dzherelo recipients respectively. No changes in CD20+ B-lymphocytes were seen in the control, but in Dzherelo patients they declined from 509 to 333 (P=0.00008). The proportion of CD3- CD16+CD56+ NK cells was not affected by ART but addition of Dzherelo raised NK cells from 11.2% to 17.1% (P=0.0001). About three-quarters (14/19) of patients on ART displayed decrease in viral load (1718 to 1419 copies/ml; P=0.008), while 95% of patients on Dzherelo had a decrease (1793 to 1368; P=0.001). Dzherelo has a favorable effect on the immune status and viral burden when given as an immunomodulating adjunct to ART

The prevalence and predictive value of dipstick urine protein in HIV-positive persons in Europe

INTRODUCTION: Proteinuria (PTU) is an important marker for the development and progression of renal disease, cardiovascular disease and death, but there is limited information about the prevalence and factors associated with confirmed PTU in predominantly white European HIV+ persons, especially in those with an estimated glomerular filtration rate (eGFR) of 60 mL/min/1.73 m(2). PATIENTS AND METHODS: Baseline was defined as the first of two consecutive dipstick urine protein (DPU) measurements during prospective follow-up >1/6/2011 (when systematic data collection began). PTU was defined as two consecutive DUP >1+ (>30 mg/dL) >3 months apart; persons with eGFR 90) and those with prior abacavir use had lower odds of PTU (Figure 1). CONCLUSIONS: One in 25 persons with eGFR>60 had confirmed proteinuria at baseline. Factors associated with PTU were similar to those associated with CKD. The lack of association with antiretrovirals, particularly tenofovir, may be due to the cross-sectional design of this study, and additional follow-up is required to address progression to PTU in those without PTU at baseline. It may also suggest other markers are needed to capture the deteriorating renal function associated with antiretrovirals may be needed at higher eGFRs. Our findings suggest PTU is an early marker for impaired renal function

Improving the evidence for indicator condition guided HIV testing in Europe: Results from the HIDES II Study - 2012 - 2015

BACKGROUND: It is cost-effective to perform an HIV test in people with specific indicator conditions (IC) with an undiagnosed HIV prevalence of at least 0.1%. Our aim was to determine the HIV prevalence for 14 different conditions across 20 European countries. METHODS: Individuals aged 18-65 years presenting for care with one of 14 ICs between January 2012 and June 2014 were included and routinely offered an HIV test. Logistic regression assessed factors associated with testing HIV positive. Patients presenting with infectious mononucleosis-like syndrome (IMS) were recruited up until September 2015. RESULTS: Of 10,877 patients presenting with an IC and included in the analysis, 303 tested positive (2.8%; 95% CI 2.5-3.1%). People presenting with an IC in Southern and Eastern Europe were more likely to test HIV positive as were people presenting with IMS, lymphadenopathy and leukocytopenia/ thrombocytopenia. One third of people diagnosed with HIV after presenting with IMS reported a negative HIV test in the preceding 12 months. Of patients newly diagnosed with HIV where data was available, 92.6% were promptly linked to care; of these 10.4% were reported lost to follow up or dead 12 months after diagnosis. CONCLUSION: The study showed that 10 conditions had HIV prevalences > 0.1%. These 10 ICs should be adopted into HIV testing and IC specialty guidelines. As IMS presentation can mimic acute HIV sero-conversion and has the highest positivity rate, this IC in particular affords opportunities for earlier diagnosis and public health benefit

Infection-related and -unrelated malignancies, HIV and the aging population

Funding Information: Conflicts of interest: JR reports personal fees from Abbvie, Bionor, BMS, Boehringer, Gilead, Merck, Janssen, Tobira, Tibotec and ViiV, outside the submitted work. OK has received honoraria, consultancy and/or lecture fees from Abbott, Gilead, GSK, Janssen, Merck, Tibotec and Viiv outside the submitted work. All other authors state no commercial or other associations that may pose a conflict of interest. Funding: Primary support for EuroSIDA is provided by the European Commission BIOMED 1 (CT94-1637), BIOMED 2 (CT97-2713), 5th Framework (QLK2-2000-00773), 6th Framework (LSHP-CT-2006-018632) and 7th Framework (FP7/2007?2013; EuroCoord n? 260694) programmes. Current support also includes unrestricted grants from Janssen R&D, Merck and Co. Inc., Pfizer Inc. and GlaxoSmithKline LLC. The participation of centres in Switzerland was supported by The Swiss National Science Foundation (Grant 108787). The authors have no financial disclosures to make. Author contributions: LS developed the project, analysed the data, and was responsible for writing the manuscript. ?HB and OK contributed to the study design and analysis, interpretation of the data and writing of the manuscript. JL proposed the project and contributed to the study design, ideas for analysis, interpretation of the data and writing of the manuscript. BL, PD, AC, JR, BK, JT and IK contributed to national coordination, study design and writing of the manuscript. AM supervised the project and contributed to the study design and analysis, interpretation of the data and writing of the manuscript. Publisher Copyright: © 2016 British HIV AssociationObjectives: HIV-positive people have increased risk of infection-related malignancies (IRMs) and infection-unrelated malignancies (IURMs). The aim of the study was to determine the impact of aging on future IRM and IURM incidence. Methods: People enrolled in EuroSIDA and followed from the latest of the first visit or 1 January 2001 until the last visit or death were included in the study. Poisson regression was used to investigate the impact of aging on the incidence of IRMs and IURMs, adjusting for demographic, clinical and laboratory confounders. Linear exponential smoothing models forecasted future incidence. Results: A total of 15 648 people contributed 95 033 person-years of follow-up, of whom 610 developed 643 malignancies [IRMs: 388 (60%); IURMs: 255 (40%)]. After adjustment, a higher IRM incidence was associated with a lower CD4 count [adjusted incidence rate ratio (aIRR) CD4 count < 200 cells/μL: 3.77; 95% confidence interval (CI) 2.59, 5.51; compared with ≥ 500 cells/μL], independent of age, while a CD4 count < 200 cells/μL was associated with IURMs in people aged < 50 years only (aIRR: 2.51; 95% CI 1.40–4.54). Smoking was associated with IURMs (aIRR: 1.75; 95% CI 1.23, 2.49) compared with never smokers in people aged ≥ 50 years only, and not with IRMs. The incidences of both IURMs and IRMs increased with older age. It was projected that the incidence of IRMs would decrease by 29% over a 5-year period from 3.1 (95% CI 1.5–5.9) per 1000 person-years in 2011, whereas the IURM incidence would increase by 44% from 4.1 (95% CI 2.2–7.2) per 1000 person-years over the same period. Conclusions: Demographic and HIV-related risk factors for IURMs (aging and smoking) and IRMs (immunodeficiency and ongoing viral replication) differ markedly and the contribution from IURMs relative to IRMs will continue to increase as a result of aging of the HIV-infected population, high smoking and lung cancer prevalence and a low prevalence of untreated HIV infection. These findings suggest the need for targeted preventive measures and evaluation of the cost−benefit of screening for IURMs in HIV-infected populations.publishersversionPeer reviewe

Non-AIDS defining cancers in the D:A:D Study-time trends and predictors of survival : a cohort study

BACKGROUND:Non-AIDS defining cancers (NADC) are an important cause of morbidity and mortality in HIV-positive individuals. Using data from a large international cohort of HIV-positive individuals, we described the incidence of NADC from 2004-2010, and described subsequent mortality and predictors of these.METHODS:Individuals were followed from 1st January 2004/enrolment in study, until the earliest of a new NADC, 1st February 2010, death or six months after the patient's last visit. Incidence rates were estimated for each year of follow-up, overall and stratified by gender, age and mode of HIV acquisition. Cumulative risk of mortality following NADC diagnosis was summarised using Kaplan-Meier methods, with follow-up for these analyses from the date of NADC diagnosis until the patient's death, 1st February 2010 or 6 months after the patient's last visit. Factors associated with mortality following NADC diagnosis were identified using multivariable Cox proportional hazards regression.RESULTS:Over 176,775 person-years (PY), 880 (2.1%) patients developed a new NADC (incidence: 4.98/1000PY [95% confidence interval 4.65, 5.31]). Over a third of these patients (327, 37.2%) had died by 1st February 2010. Time trends for lung cancer, anal cancer and Hodgkin's lymphoma were broadly consistent. Kaplan-Meier cumulative mortality estimates at 1, 3 and 5 years after NADC diagnosis were 28.2% [95% CI 25.1-31.2], 42.0% [38.2-45.8] and 47.3% [42.4-52.2], respectively. Significant predictors of poorer survival after diagnosis of NADC were lung cancer (compared to other cancer types), male gender, non-white ethnicity, and smoking status. Later year of diagnosis and higher CD4 count at NADC diagnosis were associated with improved survival. The incidence of NADC remained stable over the period 2004-2010 in this large observational cohort.CONCLUSIONS:The prognosis after diagnosis of NADC, in particular lung cancer and disseminated cancer, is poor but has improved somewhat over time. Modifiable risk factors, such as smoking and low CD4 counts, were associated with mortality following a diagnosis of NADC