Dissecting the determinants of light sensitivity in amphioxus microvillar photoreceptors : possible evolutionary implications for melanopsin signaling

© The Author(s), 2012. This article is distributed under the terms of the Creative Commons Attribution License. The definitive version was published in Journal of Neuroscience 32 (2012): 17977-17987, doi:10.1523/JNEUROSCI.3069-12.2012.Melanopsin, a photopigment related to the rhodopsin of microvillar photoreceptors of invertebrates, evolved in vertebrates to subserve nonvisual light-sensing functions, such as the pupillary reflex and entrainment of circadian rhythms. However, vertebrate circadian receptors display no hint of a microvillar specialization and show an extremely low light sensitivity and sluggish kinetics. Recently in amphioxus, the most basal chordate, melanopsin-expressing photoreceptors were characterized; these cells share salient properties with both rhabdomeric photoreceptors of invertebrates and circadian receptors of vertebrates. We used electrophysiology to dissect the gain of the light-transduction process in amphioxus and examine key features that help outline the evolutionary transition toward a sensor optimized to report mean ambient illumination rather than mediating spatial vision. By comparing the size of current fluctuations attributable to single photon melanopsin isomerizations with the size of single-channels activated by light, we concluded that the gain of the transduction cascade is lower than in rhabdomeric receptors. In contrast, the expression level of melanopsin (gauged by measuring charge displacements during photo-induced melanopsin isomerization) is comparable with that of canonical visual receptors. A modest amplification in melanopsin-using receptors is therefore apparent in early chordates; the decrease in photopigment expression—and loss of the anatomical correlates—observed in vertebrates subsequently enabled them to attain the low photosensitivity tailored to the role of circadian receptors.This work was supported by National Science Foundation Grant 0918930.2013-06-1

Phytochemical researches and antimicrobial activity of Clinopodium nubigenum Kunth (Kuntze) raw extracts

The essential oil of the species Clinopodium nubigenum (Kunth) Kuntze, Lamiaceae, was analyzed by GC-MS and GC-FID, taking into account the more recent literature. Among the seventy compounds identified, the majority are oxygenated monoterpenoids. The essential oil, tested for antimicrobial activity, resulted effective in vitro against Candida albicans. From the aqueous MeOH extract of the aerial parts of the plant two nonvolatile compounds, named schizonepetoside A and schizonepedoside C, have been isolated. They are rare glycosyl terpenoids, which were previously isolated from only one plant, but never found before in the genus Clinopodium

Comparative pharmacognostic study of leaves, stems, and roots of Urera baccifera (L.) Gaudich. ex Wedd.

369-374The quality control of drugs is necessary to guaranty the safety and efficacy of natural products. In this sense, the present investigation is led to compare the pharmacognostic parameters and preliminary phytochemical composition of the leaves, stems and roots of Urera baccifera, a medicinal plant with gastroprotective, anti-inflammatory, analgesic, and antimicrobial activities. The morphological characteristics and physicochemical parameters were evaluated for three organs, according to well-established methods for vegetal drugs. In addition, phytochemical screening was made. In microscopical analysis, different types of crystals were observed in each organ. Also, the leaves showed the highest percentage of total ashes and soluble constituents. Water was the better extraction solvent. The micromorphological characteristics and physicochemical parameters were reported for the first time for this species. The hydroalcoholic extract of three organs showed the presence of lactones, triterpenes, flavonoids, amino acids, phenols and sugar reducing. Based on the results, the leaves are proposed for the development of future phyto drugs from U. baccifera, in contrast with the ethnomedical information, where the roots are used

Caracterización clínica de gestantes con embarazo de alto riesgo en hospital de referencia del Departamento del Cauca

Background: Maternal mortality is an indicator of quality of care for pregnant and is considered a public health problem due to the impact it has on infants and their families. Its main triggering factor is high-risk pregnancy. Objective: To identify the conditions that led to the diagnosis of high-risk pregnancy and to describe the health alterations in pregnant women in a level III hospital. Methods: Retrospective study in pregnant women who consulted for high-risk pregnancy during 2017. Results: The mean age of the patients was 26 years; 54% were from urban areas; 72.7% belonged to the subsidized regime; the most frequent personal history was previous surgery (20.9%); the mean number of prenatal check-ups was 4.7 initiated around week 11.7. The condition that originated the diagnosis of high-risk pregnancy was insufficient prenatal control with 25.6%, determined during gestation. The most common type of delivery was spontaneous vaginal with 38.8% and there were no maternal deaths. Conclusion: According to the epidemiological profile of pregnant women with high-risk pregnancies, insufficient prenatal control is highlighted as the main cause, which suggests reinforcing or redesigning care strategies by the actors involved to implement quality controls in the characterization and care of pregnant women in the Department.Antecedentes: La mortalidad materna es un indicador de calidad en la atención de las embarazadas y se considera un problema de salud pública por las repercusiones que tiene para los infantes y sus familias. Su principal factor desencadenante es el embarazo de alto riesgo. Objetivo: Identificar las condiciones que llevaron al diagnóstico de embarazo de alto riesgo y describir las alteraciones de salud en las gestantes de un hospital de nivel III. Métodos: Estudio retrospectivo en embarazadas que consultaron por embarazo de alto riesgo durante el 2017. Resultados: La edad media de las pacientes fue 26 años; 54% procedían del área urbana; el 72.7% pertenecían al régimen subsidiado, el antecedente personal más frecuente fue la cirugía previa (20.9%); la media de controles prenatales fue de 4.7 iniciados alrededor de la semana 11.7. La condición que originó el diagnóstico de embarazo de alto riesgo fue el control prenatal insuficiente con un 25.6%, determinado durante la gestación. El tipo de parto más común fue el vaginal espontáneo con un 38.8% y no se presentaron muertes maternas. Conclusión: De acuerdo con perfil epidemiológico de las gestantes con embarazo de alto riesgo, se resalta el control prenatal insuficiente como principal causa, lo que sugiere reforzar o rediseñar las estrategias de atención por parte de los actores involucrados que permitan implementar controles de calidad en la caracterización y cuidado de las gestantes del Departamento

Metabolomics analysis of type 2 diabetes remission identifies 12 metabolites with predictive capacity: a CORDIOPREV clinical trial study.

Type 2 diabetes mellitus (T2DM) is one of the most widely spread diseases, affecting around 90% of the patients with diabetes. Metabolomics has proven useful in diabetes research discovering new biomarkers to assist in therapeutical studies and elucidating pathways of interest. However, this technique has not yet been applied to a cohort of patients that have remitted from T2DM. All patients with a newly diagnosed T2DM at baseline (n = 190) were included. An untargeted metabolomics approach was employed to identify metabolic differences between individuals who remitted (RE), and those who did not (non-RE) from T2DM, during a 5-year study of dietary intervention. The biostatistical pipeline consisted of an orthogonal projection on the latent structure discriminant analysis (O-PLS DA), a generalized linear model (GLM), a receiver operating characteristic (ROC), a DeLong test, a Cox regression, and pathway analyses. The model identified a significant increase in 12 metabolites in the non-RE group compared to the RE group. Cox proportional hazard models, calculated using these 12 metabolites, showed that patients in the high-score tercile had significantly (p-value < 0.001) higher remission probabilities (Hazard Ratio, HR, high versus low = 2.70) than those in the lowest tercile. The predictive power of these metabolites was further studied using GLMs and ROCs. The area under the curve (AUC) of the clinical variables alone is 0.61, but this increases up to 0.72 if the 12 metabolites are considered. A DeLong test shows that this difference is statistically significant (p-value = 0.01). Our study identified 12 endogenous metabolites with the potential to predict T2DM remission following a dietary intervention. These metabolites, combined with clinical variables, can be used to provide, in clinical practice, a more precise therapy. ClinicalTrials.gov, NCT00924937.The CORDIOPREV study is supported by the Ministerio de Economia y Competitividad, Spain, under the grants AGL2012/39615, PIE14/00005, and PIE14/00031 associated to J.L.-M.; AGL2015-67896-P to J.L.-M. and A.C.; CP14/00114 to A.C.; PI19/00299 to A.C.; DTS19/00007 to A.C.; FIS PI13/00023 to J.D.-L., PI16/01777 to F.P.-J. and P.P.-M.; Antonio Camargo is supported by an ISCIII research contract (Programa Miguel-Servet CPII19/00007); Marina Mora-Ortiz has received funding from the European Union’s Horizon 2020 research and innovation programme under the Marie Skłodowska-Curie grant agreement No 847468; ‘Fundacion Patrimonio Comunal Olivarero’, Junta de Andalucía (Consejería de Salud, Consejeria de Agricultura y Pesca, Consejería de Innovacion, Ciencia y Empresa), ‘Diputaciones de Jaen y Cordoba’, ‘Centro de Excelencia en Investigación sobre Aceite de Oliva y Salud’ and ‘Ministerio de Medio Ambiente, Medio Rural y Marino’, Gobierno de España; ‘Consejeria de Innovación, Ciencia y Empresa, Proyectos de Investigación de Excelencia’, Junta de Andalucía under the grant CVI-7450 obtaiend by J.L.-M.; and we would also like to thank the ‘Fondo Europeo de Desarrollo Regional (FEDER)’.S

Nano positioning system reveals the course of upstream and nontemplate DNA within the RNA polymerase II elongation complex

Crystallographic studies of the RNA polymerase II (Pol II) elongation complex (EC) revealed the locations of downstream DNA and the DNA-RNA hybrid, but not the course of the nontemplate DNA strand in the transcription bubble and the upstream DNA duplex. Here we used single-molecule Fluorescence Resonance Energy Transfer (smFRET) experiments to locate nontemplate and upstream DNA with our recently developed Nano Positioning System (NPS). In the resulting complete model of the Pol II EC, separation of the nontemplate from the template strand at position +2 involves interaction with fork loop 2. The nontemplate strand passes loop β10-β11 on the Pol II lobe, and then turns to the other side of the cleft above the rudder. The upstream DNA duplex exits at an approximately right angle from the incoming downstream DNA, and emanates from the cleft between the protrusion and clamp. Comparison with published data suggests that the architecture of the complete EC is conserved from bacteria to eukaryotes and that upstream DNA is relocated during the initiation–elongation transition

Hypothalamic AMPK-ER Stress-JNK1 Axis Mediates the Central Actions of Thyroid Hormones on Energy Balance

Thyroid hormones (THs) act in the brain to modulate energy balance. We show that central triiodothyronine (T3) regulates de novo lipogenesis in liver and lipid oxidation in brown adipose tissue (BAT) through the parasympathetic (PSNS) and sympathetic nervous system (SNS), respectively. Central T3 promotes hepatic lipogenesis with parallel stimulation of the thermogenic program in BAT. The action of T3 depends on AMP-activated protein kinase (AMPK)-induced regulation of two signaling pathways in the ventromedial nucleus of the hypothalamus (VMH): decreased ceramide-induced endoplasmic reticulum(ER) stress, which promotes BAT thermogenesis, and increased c-Jun N-terminal kinase (JNK) activation, which controls hepatic lipid metabolism. Of note, ablation of AMPK alpha 1 in steroidogenic factor 1 (SF1) neurons of the VMH fully recapitulated the effect of central T3, pointing to this population in mediating the effect of central THs on metabolism. Overall, these findings uncover the underlying pathways through which central T3 modulates peripheral metabolism.Peer reviewe

Global injury morbidity and mortality from 1990 to 2017 : results from the Global Burden of Disease Study 2017

Correction:Background Past research in population health trends has shown that injuries form a substantial burden of population health loss. Regular updates to injury burden assessments are critical. We report Global Burden of Disease (GBD) 2017 Study estimates on morbidity and mortality for all injuries. Methods We reviewed results for injuries from the GBD 2017 study. GBD 2017 measured injury-specific mortality and years of life lost (YLLs) using the Cause of Death Ensemble model. To measure non-fatal injuries, GBD 2017 modelled injury-specific incidence and converted this to prevalence and years lived with disability (YLDs). YLLs and YLDs were summed to calculate disability-adjusted life years (DALYs). Findings In 1990, there were 4 260 493 (4 085 700 to 4 396 138) injury deaths, which increased to 4 484 722 (4 332 010 to 4 585 554) deaths in 2017, while age-standardised mortality decreased from 1079 (1073 to 1086) to 738 (730 to 745) per 100 000. In 1990, there were 354 064 302 (95% uncertainty interval: 338 174 876 to 371 610 802) new cases of injury globally, which increased to 520 710 288 (493 430 247 to 547 988 635) new cases in 2017. During this time, age-standardised incidence decreased non-significantly from 6824 (6534 to 7147) to 6763 (6412 to 7118) per 100 000. Between 1990 and 2017, age-standardised DALYs decreased from 4947 (4655 to 5233) per 100 000 to 3267 (3058 to 3505). Interpretation Injuries are an important cause of health loss globally, though mortality has declined between 1990 and 2017. Future research in injury burden should focus on prevention in high-burden populations, improving data collection and ensuring access to medical care.Peer reviewe