In Silico Selection and In Vitro Evaluation of New Molecules That Inhibit the Adhesion of <i>Streptococcus mutants</i> through Antigen I/II

Streptococcus mutans is the main early colonizing cariogenic bacteria because it recognizes salivary pellicle receptors. The Antigen I/II (Ag I/II) of S. mutans is among the most important adhesins in this process, and is involved in the adhesion to the tooth surface and the bacterial co-aggregation in the early stage of biofilm formation. However, this protein has not been used as a target in a virtual strategy search for inhibitors. Based on the predicted binding affinities, drug-like properties and toxicity, molecules were selected and evaluated for their ability to reduce S. mutans adhesion. A virtual screening of 883,551 molecules was conducted; cytotoxicity analysis on fibroblast cells, S. mutans adhesion studies, scanning electron microscopy analysis for bacterial integrity and molecular dynamics simulation were also performed. We found three molecules ZINC19835187 (ZI-187), ZINC19924939 (ZI-939) and ZINC19924906 (ZI-906) without cytotoxic activity, which inhibited about 90% the adhesion of S. mutans to polystyrene microplates. Molecular dynamic simulation by 300 nanoseconds showed stability of the interaction between ZI-187 and Ag I/II (PDB: 3IPK). This work provides new molecules that targets Ag I/II and have the capacity to inhibit in vitro the S. mutans adhesion on polystyrene microplates

Expanding the knowledge on lignocellulolytic and redox enzymes of worker and soldier castes from the lower termite coptotermes gestroi

Termites are considered one of the most efficient decomposers of lignocelluloses on Earth due to their ability to produce, along with its microbial symbionts, a repertoire of carbohydrate-active enzymes (CAZymes). Recently, a set of Pro-oxidant, Antioxidant, and Detoxification enzymes (PAD) were also correlated with the metabolism of carbohydrates and lignin in termites. The lower termite Coptotermes gestroi is considered the main urban pest in Brazil, causing damage to wood constructions. Recently, analysis of the enzymatic repertoire of C. gestroi unveiled the presence of different CAZymes. Because the gene profile of CAZy/PAD enzymes endogenously synthesized by C. gestroi and also by their symbiotic protists remains unclear, the aim of this study was to explore the eukaryotic repertoire of these enzymes in worker and soldier castes of C. gestroi. Our findings showed that worker and soldier castes present similar repertoires of CAZy/PAD enzymes, and also confirmed that endo-glucanases (GH9) and beta-glucosidases (GH1) were the most important glycoside hydrolase families related to lignocellulose degradation in both castes. Classical cellulases such as exo-glucanases (GH7) and endo-glucanases (GH5 and GH45), as well as classical xylanases (GH10 and GH11), were found in both castes only taxonomically related to protists, highlighting the importance of symbiosis in C. gestroi. Moreover, our analysis revealed the presence of Auxiliary Activity enzyme families (AAs), which could be related to lignin modifications in termite digestomes. In conclusion, this report expanded the knowledge on genes and proteins related to CAZy/PAD enzymes from worker and soldier castes of lower termites, revealing new potential enzyme candidates for second-generation biofuel processes7CONSELHO NACIONAL DE DESENVOLVIMENTO CIENTÍFICO E TECNOLÓGICO - CNPQFUNDAÇÃO DE AMPARO À PESQUISA DO ESTADO DE SÃO PAULO - FAPESP140796/2013-4; 310186/2014-5; 442333/2014-511/20977-3; 15/06971-3; 12/19040-0; 14/10351-8; 06/59086-8; 14/20576- 7; 13/03061-0; 10/11469-1; 08/58037-9; 14/50371-8; 08/50114-

Prey detection and prey capture in copepod nauplii

Copepod nauplii are either ambush feeders that feed on motile prey or they produce a feeding current that entrains prey cells. It is unclear how ambush and feeding-current feeding nauplii perceive and capture prey. Attack jumps in ambush feeding nauplii should not be feasible at low Reynolds numbers due to the thick viscous boundary layer surrounding the attacking nauplius. We use high-speed video to describe the detection and capture of phytoplankton prey by the nauplii of two ambush feeding species (Acartia tonsa and Oithona davisae) and by the nauplii of one feeding-current feeding species (Temora longicornis). We demonstrate that the ambush feeders both detect motile prey remotely. Prey detection elicits an attack jump, but the jump is not directly towards the prey, such as has been described for adult copepods. Rather, the nauplius jumps past the prey and sets up an intermittent feeding current that pulls in the prey from behind towards the mouth. The feeding-current feeding nauplius detects prey arriving in the feeding current but only when the prey is intercepted by the setae on the feeding appendages. This elicits an altered motion pattern of the feeding appendages that draws in the prey

Senescence and Sexual Selection in a Pelagic Copepod

The ecology of senescence in marine zooplankton is not well known. Here we demonstrate senescence effects in the marine copepod Oithona davisae and show how sex and sexual selection accelerate the rate of ageing in the males. We show that adult mortality increases and male mating capacity and female fertility decrease with age and that the deterioration in reproductive performance is faster for males. Males have a limited mating capacity because they can fertilize < 2 females day−1 and their reproductive life span is 10 days on average. High female encounter rates in nature (>10 day−1), a rapid age-dependent decline in female fertility, and a high mortality cost of mating in males are conducive to the development of male choosiness. In our experiments males in fact show a preference for mating with young females that are 3 times more fertile than 30-day old females. We argue that this may lead to severe male-male competition for young virgin females and a trade-off that favours investment in mate finding over maintenance. In nature, mate finding leads to a further elevated mortality of males, because these swim rapidly in their search for attractive partners, further relaxing fitness benefits of maintenance investments. We show that females have a short reproductive period compared to their average longevity but virgin females stay fertile for most of their life. We interpret this as an adaptation to a shortage of males, because a long life increases the chance of fertilization and/or of finding a high quality partner. The very long post reproductive life that many females experience is thus a secondary effect of such an adaptation

Gastrointestinal physiological changes and their relationship to weight loss following the POSE procedure.

BACKGROUND: Primary Obesity Surgery Endolumenal (POSE) is a novel bariatric endoscopic procedure that has been shown to reduce weight safely through 12 months. The study investigated potential mechanisms of weight loss following POSE. METHODS: Patients with class I-II obesity received transmural plications in the gastric fundus and distal gastric body. Patients were evaluated at baseline and at 2- and 6-month follow-up with gastric-emptying (GE) scintigraphy, a validated test of intake capacity (kcal) and plasma glucose homeostasis hormones/gastrointestinal peptides. Weight was recorded through 15 months. Mean data and 95 % CIs are reported. Regression modeling assessed variables that influenced total weight loss (%TWL) and excess weight loss (%EWL). RESULTS: POSE was performed on 18 patients (14 F/4 M); mean age 39 years (34-44), body mass index (BMI, kg/m(2)) 36 (95 % CI, 35; 37). At 15 months (n = 15), mean TWL was 19.1 ± 6.6 % (15.5; 22.8) and EWL was 63.7 ± 25.1 % (49.8; 77.6). At 2 and 6 months (n = 18), intake capacity decreased significantly from 901 (685; 1117) to 473 (345; 600) and 574 kcal (418; 730), respectively (p < 0.001). At 2 months, GE was delayed but returned to baseline levels at 6 months (n = 18). Glucose/insulin ratio improved (p < 0.05). Postprandial decrease in ghrelin was enhanced (p = 0.03) as well as postprandial increase in PYY (p = 0.001). The best model for EWL prediction 15 months after POSE (R (2): 66 %, p = 0.006) included pre-POSE BMI, post-POSE GE, and postprandial PYY increase. CONCLUSIONS: The POSE procedure was followed by significant sustained weight loss and improved glucose homeostasis and satiation peptide responses. Weight loss following POSE may be mediated through changes in gastrointestinal neuro-endocrine physiology.Manuscript development was financially supported by USGI Medical, Inc., US

Tratamiento endoscópico de la obesidad: Técnica POSE utilizando la plataforma endoscópica sin incisiones (IOP). Estudio piloto prospectivo: Eficacia clínica y repercusión fisiológica

Está estructurada siguiendo las directrices de la normativa para la Presentación de tesis doctorales como un compendio de Publicaciones aprobado por el Consejo del Departamento de Medicina de la Universidad de Barcelona. Artículos de la tesis: ARTICULO 1. Early Experience with the Incisionless Operating Platform TM (IOP) for the Treatment of Obesity. The Primary Obesity Surgery Endolumenal (POSE) Procedure. J. C. Espinós & R. Turró & A. Mata & M. Cruz & M. da Costa & V. Villa & J. N. Buchwald & J. Turró Obesity Surgery. 2013 Sep; 23(9):1375-83 ARTICULO 2. Gastrointestinal Physiological Changes and Their Relationship to Weight Loss Following the POSE Procedure. J. C. Espinós & R. Turró & G. Moragas & A. Bronstone & J. N. Buchwald & F. Mearin & A. Mata & H. Uchima & J. Turró & S. Delgado-Aros. Obesity Surgery. DOI 10.1007/s11695-015-1863-8 En el estudio 1 "Early Experience with the Incisionless Operating PlatformTM(IOP) for the Treatment of Obesity. The Primary Obesity Surgery Endolumenal (POSE) Procedure" se realiza el seguimiento de una serie consecutiva de 45 pacientes con obesidad tipos 1, II y III a los que se les realiza la intervención endoscópica "POSE" con la plataforma endoscópica "IOP" como tratamiento primario de su obesidad. Es la primera serie publicada a nivel mundial utilizando la técnica POSE como tratamiento primario de la obesidad. Los resultados confirman las hipótesis de realización y seguridad de la técnica al conseguirse realizar en el 100% de los casos con un tiempo medio de 63 minutos, con alta antes de las 24 horas en todos los casos y solo dos interconsultas por dolor en las primeras 48 horas como efectos adversos. La media de Porcentaje de sobrepeso perdido fué de 49,4+-21 % y del % de peso total de un 15,5+-6,1, resultados muy similares a los de las distintas técnicas quirúrgicas en el mismo plazo de tiempo. En el estudio 2 se realiza un estudio de capacidad de ingesta calórica (test de saciedad), estudio de vaciamiento gástrico y de hormonas que participan en los mecanismos de hambre-saciedad (leptina, PYY, Ghrelina, péptido c, insulina, Glucosa) antes y a los 2 y seis meses post tratamiento endoscópico POSE de la obesidad. Se estudian 18 pacientes y se evidencia que a los 15 meses de seguimiento la pérdida de peso llega al 60% del sobrepeso y al 20 % del peso total. Se evidencia una disminución de casi el 50 % de la capacidad de ingesta calórica a los 2 y 6 meses con normalización y mejora de los valores basales y tras ingesta de glucosa, péptido c, insulina, grhelina y PYY. Se concluye que: 1.- La utilización de la plataforma endoscópica IOP para la realización de plicaturas en estómago (Método POSE) como tratamiento primario de la obesidad, es una técnica realizable en un 100% de los casos en un tiempo limitado con muy buena tolerancia y sin efectos secundarios. 2. Los pacientes sometidos a este tratamiento presentan sensación de saciedad precoz y presentan una pérdida de peso significativa a los 6 meses y que se mantiene y aumenta a los 15 meses. 3.- Los mecanismos fisiológicos de acción del método POSE pasan por la disminución de la adaptabilidad del fundus gástrico, provocando una disminución de la capacidad de ingesta calórica. A este hecho se acompaña una disminución basal de la PYY pero con un importante aumento postpandrial. Como conclusión final, el método POSE es una técnica prometedora en el tratamiento endoscópico de la obesidad y reúne todas las condiciones requeridas de eficacia y seguridad tanto de las técnicas endoscópicas como de las quirúrgicas. Los estudios de seguimiento a largo plazo y los estudios comparativos controlados con otras técnicas permitirán delimitar la población de pacientes que se beneficiará más de esta técnica.Obesity Endoscopic treatment. POSE with the endoscopic Incisionless platform (10P). PILOT PROSPECTIVE STUDY. Clinical efficacy and physiological repercussion. This doctoral thesis is structured according to the guidelines of the rules for the Presentation of doctoral thesis as a compendium of Publications approved by the Council of the Department of Medicine of the University of Barcelona. Articles of the thesis: ARTICLE 1. Early Experience with the Incisionless Operating Platform TM (10P) for the Treatment of Obesity. The Primary Obesity Surgery Endolumenal (POSE) Procedure. J. C. EspinOs & r. TurrO A. Mata M. Cruz & M. da Costa & V. Villa & J. N. Buchwald & j. TurrO Obesity Surgery. 2013 Sep; 23 (9): 1375-83 ARTICLE 2. Gastrointestinal Physiological Changes and Their Relationship to Weight Loss Following the POSE Procedure. J. C. Espin6s & r. TurrO & g. Moragas & A. Bronstone &J. N. F. Mearin, Buchwald & H. Uchima & A. Mata & j. TurrO & S. delgado-Aros. Obesity Surgery. DOI 10.1007/s11695-015-1863-8 Study 1: We analyze a series of 45 patients to whom we performed the endoscopic intervention "POSE" with the endoscopic platform "10P" as primary treatment for their obesity. It is the first series published worldwide using the POSE as primary treatment of obesity The results confirm the hypothesis of performance and safety of the technique to be performed in 100% of cases with an average time 63 minutes, with no side effects. The average percentage of overweight lost was 49, 4 ± 21% and % of total weight of 15, 5 ± 6, 1, results very similar to those of the different surgical techniques in the same time frame. In the second paper we performed a study of the caloric intake capacity (test of satiety), a study of gastric emptying and hormones involved in the mechanisms of hunger and satiety (leptin, PYY, ghrelin, insulin, c-peptide, glucose) before and 2 and six months post POSE endoscopic treatment of obesity. We studied 18 patients and there was evidence that 15 months weight loss reaches 60% of overweight and 20% of the total weight. A decrease of almost 50% of the caloric intake capacity at 2 and 6 months with standardization and improvement of the baseline and after ingestion levels of glucose, c-peptide, insulin, ghrelin and PYY happened after the POSE procedure. It is concluded that: 1. The use of endoscopic 10P platform for the realization of plication's in stomach (method POSE) as primary treatment of obesity is a workable technique in 100% of cases in a time-limited with very good tolerance and without side effects. 2. Patients undergoing this treatment have feeling of early satiety and presented a significant weight loss at six months and stay and increases up to 15 months. 3. The physiological action of the POSE method mechanisms go through the decrease of the adaptability of the fundus of the stomach, causing a decrease in caloric intake capacity. This fact is accompanied by a basal decrease the PYY but with an important increase in others. As a final conclusion, the POSE method is a promising technique in the Endoscopic treatment of obesity. Long-term follow-up and controlled studies will allow delimiting the population of patients that will benefit more of this technique

Prevalence and Predictors of Overweight and Obesity among Young Children in the Children’s Healthy Living Study on Guam

This study is part of the Children&rsquo;s Healthy Living program in U.S. Affiliated Pacific region. The objectives were to estimate overweight and obesity (OWOB) prevalence and identify possible related risk factors among ethnic groups in Guam. In 2013, 865 children (2&ndash;8 years) were recruited via community-based sampling from select communities in Guam. Children&rsquo;s demographic and health behavior information; dietary intake; and anthropometric measurements were collected. Logistic regression, odds ratio, t-tests, and chi-square tests were used to determine differences and assess covariates of OWOB. The results indicate that 58% of children were living below the poverty level, 80% were receiving food assistance, and 51% experienced food insecurity. The majority of children surveyed did not meet recommendations for: sleep duration (59.6%), sedentary screen-time (83.11%), or fruit (58.7%) and vegetable (99.1%) intake, and consumed sugar sweetened beverages (SSB) (73.7%). OWOB affected 27.4% of children. Children affected by OWOB in this study were statistically more likely (p = 0.042) to suffer from sleep disturbances (p = 0.042) and consume marginally higher amounts (p value = 0.07) of SSB compared to children with healthy weight. Among Other Micronesians, children from families who considered themselves &lsquo;integrated&rsquo; into the culture were 2.05 (CI 0.81&ndash;5.20) times more likely to be affected by OWOB. In conclusion, the OWOB prevalence among 2&ndash;8-year-olds in Guam was 27.4%; and compared with healthy weight children, children with OWOB were more likely to have educated caregivers and consume more SSBs. Results provide a basis for health promotion and obesity prevention guidance for children in Guam