The ins and outs of CO₂

© 2015 The Author 2015. Published by Oxford University Press on behalf of the Society for Experimental Biology. It is difficult to distinguish influx and efflux of inorganic C in photosynthesizing tissues; this article examines what is known and where there are gaps in knowledge. Irreversible decarboxylases produce CO2, and CO2 is the substrate/product of enzymes that act as carboxylases and decarboxylases. Some irreversible carboxylases use CO2; others use HCO3-. The relative role of permeation through the lipid bilayer versus movement through CO2-selective membrane proteins in the downhill, non-energized, movement of CO2 is not clear. Passive permeation explains most CO2 entry, including terrestrial and aquatic organisms with C3 physiology and biochemistry, terrestrial C4 plants and all crassulacean acid metabolism (CAM) plants, as well as being part of some mechanisms of HCO3- use in CO2 concentrating mechanism (CCM) function, although further work is needed to test the mechanism in some cases. However, there is some evidence of active CO2 influx at the plasmalemma of algae. HCO3- active influx at the plasmalemma underlies all cyanobacterial and some algal CCMs. HCO3- can also enter some algal chloroplasts, probably as part of a CCM. The high intracellular CO2 and HCO3- pools consequent upon CCMs result in leakage involving CO2, and occasionally HCO3-. Leakage from cyanobacterial and microalgal CCMs involves up to half, but sometimes more, of the gross inorganic C entering in the CCM; leakage from terrestrial C4 plants is lower in most environments. Little is known of leakage from other organisms with CCMs, though given the leakage better-examined organisms, leakage occurs and increases the energetic cost of net carbon assimilation

Unifying view of mechanical and functional hotspots across class A GPCRs

G protein-coupled receptors (GPCRs) are the largest superfamily of signaling proteins. Their activation process is accompanied by conformational changes that have not yet been fully uncovered. Here, we carry out a novel comparative analysis of internal structural fluctuations across a variety of receptors from class A GPCRs, which currently has the richest structural coverage. We infer the local mechanical couplings underpinning the receptors' functional dynamics and finally identify those amino acids whose virtual deletion causes a significant softening of the mechanical network. The relevance of these amino acids is demonstrated by their overlap with those known to be crucial for GPCR function, based on static structural criteria. The differences with the latter set allow us to identify those sites whose functional role is more clearly detected by considering dynamical and mechanical properties. Of these sites with a genuine mechanical/dynamical character, the top ranking is amino acid 7x52, a previously unexplored, and experimentally verifiable key site for GPCR conformational response to ligand binding. \ua9 2017 Ponzoni et al

Prevalencia de Retinopatia en pacientes del programa integral de diabetes del centro de Salud San Genaro de Villa, Chorillos: Prevalence and factors associated with retinopathy in patients of the integral diabetes program of the san genaro de villa Chorillos health center, Lima-Peru

Objectives: To determine the prevalence and factors associated with retinopathy in patients of the Comprehensive Diabetes Program of the San Genaro Health Center in Villa Chorrillos. Methods: Descriptive, observational, cross-sectional, prospective study; with a sample of 119 adults and older adults. Non-probabilistic convenience sampling was used. The variables studied were diabetic retinopathy, type of diabetic retinopathy, degree of diabetic retinopathy, age, sex, educational level, time of illness, time belonging to the program, type of treatment, personal history of arterial hypertension, personal history of dyslipidemia, mean systolic blood pressure (SBP), mean diastolic blood pressure (DBP), Body Mass Index (BMI), Glycosylated Hemoglobin (HbA1c), Total Cholesterol, LDL Cholesterol, HDL Cholesterol, Triglycerides, creatinine clearance, microalbuminuria, visual efficiency of Snell-Sterling, associated ocular pathology and ocular pressure. Descriptive statistical methods were used. Results: The prevalence of diabetic retinopathy (DR) was 15.1%, of which 77.8% is nonproliferative RD and 22.2% proliferative RD. In relation to the degrees in Non-Proliferative DR, 64.3% is mild and 35.7% moderate; and in Proliferative DR, 25% is early, 25% high risk and 50% severe. The biochemical value that showed a considerable difference was microalbuminuria, reaching a value of 356.9 mg/dl/24hrs. Conclusions: The prevalence of retinopathy is 15.1%, of which 77.8% is non-proliferative retinopathy and 22.2% proliferative retinopathy and the associated factors were systolic blood pressure (p<0.001) and microalbuminuria(p<0.001).Objetivos: Determinar la prevalencia y los factores asociados a retinopatía en pacientes del Programa Integral de Diabetes del Centro de Salud San Genaro de Villa Chorrillos. Métodos: Estudio descriptivo, observacional, transversal, prospectivo; con una muestra de 119 adultos y adultos mayores. Se utilizo el muestreo no probabilístico por conveniencia. Las variables estudiadas fueron retinopatía diabética, Tipo de retinopatía diabética, grado de retinopatía diabética, edad, sexo, grado de instrucción, tiempo de enfermedad, tiempo de pertenencia la programa, tipo de tratamiento, antecedente personal de hipertensión arterial, antecedente personal de dislipidemia, presión arterial sistólica (PAS) promedio, presión arterial diastólica (PAD) promedio, Índice de masa corporal (IMC), Hemoglobina Glicosilada (HbA1c), Colesterol total, Colesterol LDL, Colesterol HDL, Triglicéridos, depuración de creatinina, microalbuminuria, eficiencia visual de Snell-Sterlling, patología ocular asociada y presión ocular. Se emplearon métodos estadísticos descriptivos. Resultados: La prevalencia de retinopatía diabética (RD) fue de 15,1% de los cuales el 77,8% es RD No proliferativa y el 22,2% RD proliferativa. En relación a los grados en la RD No Proliferativa el 64,3% es leve y el 35,7% moderada; y en la RD Proliferativa el 25% es temprana, el 25% de alto riesgo y el 50% severa. El valor bioquímico que mostro una considerable diferencia fue la microalbuminuria alcanzando un valor de 356,9 mg/dl/24hrs. Conclusiones: La prevalencia de retinopatía es de 15,1% de los cuales el 77,8%% es retinopatía no proliferativa y de 22,2% retinopatía proliferativa y los factores asociados fueron la presión arterial sistólica (p<0,001) y la microalbuminuria (p<0,001)

Post-Translational Modifications of the Serotonin Type 4 Receptor Heterologously Expressed in Mouse Rod Cells

G-Protein-coupled serotonin receptor type 4 (5-HT₄R) is a pharmacological target implicated in a variety of gastrointestinal and nervous system disorders. As for many other integral membrane proteins, structural and functional studies of this receptor could be facilitated by its heterologous overexpression in eukaryotic systems that can perform appropriate post-translational modifications (PTMs) on the protein. We previously reported the development of an expression system that employs rhodopsin’s biosynthetic machinery in rod cells of the retina to express heterologous G-protein-coupled receptors (GPCRs) in a pharmacologically functional form. In this study, we analyzed the glycosylation, phosphorylation, and palmitoylation of 5-HT₄R heterologously expressed in rod cells of transgenic mice. We found that the glycosylation pattern in 5-HT₄R was more complex than in murine and bovine rhodopsin. Moreover, overexpression of this exogenous GPCR in rod cells also affected the glycosylation pattern of coexisting native rhodopsin. These results highlight not only the occurrence of heterogeneous PTMs on transgenic proteins but also the complications that non-native PTMs can cause in the structural and functional characterization of both endogenous and heterologous protein targets