The genome of Entamoeba histolytica encodes approximately 50 Cysteine Proteases (CPs) whose activity is regulated by two Inhibitors of Cysteine Proteases (ICPs), EhICP1 and EhICP2. The main ...difference between both EhICPs is the acquisition of a 17 N-terminal targeting signal in EhICP2 and three exposed cysteine residues in EhICP1. The three exposed cysteines in EhICP1 potentiate the formation of cross-linking species that drive heterogeneity. Here we solved the NMR structure of EhICP1 using a mutant protein without accessible cysteines. Our structural data shows that EhICP1 adopts an immunoglobulin fold composed of seven β-strands, and three solvent exposed loops that resemble the structures of EhICP2 and chagasin. EhICP1 and EhICP2 are able to inhibit the archetypical cysteine protease papain by intercalating their BC loops into the protease active site independently of the character of the residue (serine or threonine) responsible to interact with the active site of papain. EhICP1 and EhICP2 present signals of functional divergence as they clustered in different clades. Two of the three exposed cysteines in EhICP1 are located at the DE loop that intercalates into the CP substrate-binding cleft. We propose that the solvent exposed cysteines of EhICP1 play a role in regulating its inhibitory activity and that in oxidative conditions, the cysteines of EhICP1 react to form intra and intermolecular disulfide bonds that render an inactive inhibitor. EhICP2 is not subject to redox regulation, as this inhibitor does not contain a single cysteine residue. This proposed redox regulation may be related to the differential cellular localization between EhICP1 and EhICP2.
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•EhICP1 harbors three cysteines thatt render an inactive inhibitor•EhICP1 adopts an immunoglobulin fold and three solvent exposed loops that resemble the structures of EhICP2 and chagasin•EhICP1 is subject to redox regulation that correlates with its cytosolic localization
The effect of exogenous application of jasmonic acid (JA) on the concentration of main terpenes and density of glandular trichomes was investigated in the Mexican oregano, propagated from seeds from ...3 localities. JA 1 mM was applied locally and to the whole plant. JA locally applied increased the number of trichomes, with a mean of 20 trichomes more with respect to the controls in plants from Tecomavaca and Zapotitlán Salinas, and significantly increased the thymol concentration by 185% systemically and 255% locally, compared to the control. JA applied to the whole plant decreased the number of trichomes and increased the concentration of caryophyllene from 0.79 to 1.7 mg g
−1
, and α-caryophyllene from 0.3 to 0.8 mg g
−1
in plants from San Rafael with reference to water control. The results suggest a plasticity of morphologic and phytochemical responses, and a potential use of JA to improve phenolic monoterpenes and sesquiterpenes production.
Abstract Regardless of the low concentrations at which amino acids are present in floral nectar of bat-pollinated plants, their role as nectar flavor providers and their influence on bats’ foraging ...decisions have been recognized. Nevertheless, variation in the free amino acids among bat-pollinated plant species has been less studied. The goal of this study was to analyze the nectar free amino acids and to determine its variability among 8 bat-pollinated plant species from 5 families in a Tropical Dry Forest in Mexico. Nectar collections were made opportunistically depending on plants flowering season. We quantified 17 amino acids by HPLC. All 17 free amino acids were present in nectar from the 8 analyzed plant species. The concentration of 12 amino acids is explained by plant species by 19-58%. Analyses showed that Ceiba grandiflora (Malvaceae) was significantly different in asparagine content when compared to Bahuinia pauletia (Fabaceae) and Ceiba aesculifolia (Malvaceae), and in glutamic acid when compared to Ipomoea ampullacea (Convolvulaceae). We discuss the importance of free amino acids in nectar among plant species and their influence on bat pollination ecology.
When colonizing new ranges, plant populations may benefit from the absence of the checks imposed by the enemies, herbivores, and pathogens that regulated their numbers in their original range. ...Therefore, rates of plant damage or infestation by natural enemies are expected to be lower in the new range. Exposing both non-native and native plant populations in the native range, where native herbivores are present, can be used to test whether resistance mechanisms have diverged between populations. Datura stramonium is native to the Americas but widely distributed in Spain, where populations show lower herbivore damage than populations in the native range. We established experiments in two localities in the native range (Mexico), exposing two native and two non-native D. stramonium populations to natural herbivores. Plant performance differed between the localities, as did the abundance of the main specialist herbivore, Lema daturaphila. In Teotihuacán, where L. daturaphila is common, native plants had significantly more adult beetles and herbivore damage than non-native plants. The degree of infestation by the specialist seed predator Trichobaris soror differed among populations and between sites, but the native Ticumán population always had the lowest level of infestation. The Ticumán population also had the highest concentration of the alkaloid scopolamine. Scopolamine was negatively related to the number of eggs deposited by L. daturaphila in Teotihuacán. There was among-family variation in herbivore damage (resistance), alkaloid content (scopolamine), and infestation by L. daturaphila and T. soror, indicating genetic variation and potential for further evolution. Although native and non-native D. stramonium populations have not yet diverged in plant resistance/constitutive defense, the differences between ranges (and the two experimental sites) in the type and abundance of herbivores suggest that further research is needed on the role of resource availability and adaptive plasticity, specialized metabolites (induced, constitutive), and the relationship between genealogical origin and plant defense in both ranges.
The Interleukin (IL)-1 family of cytokines plays a key role in the inflammatory response. Genes coding for IL-1α, IL-1β, and IL-1Ra are located together as a block gene known as the IL-1 cluster. ...This genomic region shows wide nucleotide variability, and some polymorphisms have been widely studied and associated with features related to the metabolic syndrome.
Eight polymorphisms within three genes of the IL-1 cluster, including IL1A (rs3783553, rs17561, and rs1800587), IL1B (rs1143634, rs1143627, and rs16944) and IL1RN (rs419598 and rs2234663) were genotyped in 460 Mexican adolescents. Genotype and haplotype frequencies are reported, as well as the linkage disequilibrium analysis. Genetic associations with some anthropometric and metabolic traits were evaluated.
Allele frequencies were similar to those found in other populations, and genotype proportions were according to the Hardy-Weinberg equilibrium. Seven haplotypes were observed at frequencies ≥5%. Of the entire cluster, only the rs17561-rs1800587 and rs1143627-rs16944 pairs showed highest and significant linkage disequilibrium values. An haplotype of IL1A, rs17561T–rs1800587T, was significantly associated with increase in body mass index in males (p <0.008), whereas IL1B and IL1RN variants showed associations with insulin, and hs-CRP (p <0.05).
Some MetS parameters seem to be influenced by variations in the IL-1 gene cluster in Mexican adolescents. These variations may confer risk for metabolic alterations from early ages, and and these risks may be different when variables such as sex are considered. Strategies leading to generate protective behaviors could be designed to take into account specific variations in the IL-1 gene cluster and biological conditions such as sex.
This paper presents a dynamic approach to the synthesis of a crank-rocker four-bar mechanism, that is obtained by an optimization problem and its solution using the Bio-inspired algorithm called ...Differential Evolution (DE). The proposed dynamic approach states a mono-objective dynamic optimization problem (MODOP), in order to obtain a set of optimal parameters of the system. In this MODOP, the kinematic and dynamic models of the whole system are considered as well as a set of constraints including a dynamic constraint. The DE algorithm is adapted to solve the optimization problem by adding a suitable constraint-handling mechanism that is able to incorporate the kinematic and dynamic constraints of the system. A set of independent computational runs were carried out in order to validate the dynamic approach. An analysis from the mechanical and computational point of view is presented, based on the obtained results. From the analysis of the simulation and its results, it is shown that the solutions for the proposed algorithm lead to a more suitable design based on the dynamic approach.
Designs for determining nociceptive response in rodents are of great use in neurology and experimental neuroscience. Immersing mice's tails in warm water is one of the most widely used procedures to ...evaluate this response; however, a wide range of temperatures are used in different studies. Knowing the temperature that produces a powerful nociceptive response in the tail of BALB/c mice is extremely useful.
Eight 2-month-old male BALB/c mice were used. A 14-cm high beaker was filled with water up to 13 cm. The animals' tails were immersed in the container with a starting temperature of 36°C. The water temperature was raised in 1°C increments until we identified the temperatures that produced nociceptive responses. That response was determined by counting the time taken before the mouse shook its tail to remove it from the water.
Six of the 8 mice began shaking their tails at the temperature of 51°C. All animals removed their tails from the water at the temperatures of 54°C, 55°C, and 56°C, taking a mean time of 8.54, 7.99, and 5.33seconds, respectively. ANOVA applied to the response times for each of the 3 temperatures indicated revealed a value of F=2.8 (P=.123).
The response time was statistically similar for the temperatures of 54°C, 55°C, and 56°C; however, the data were less dispersed for the latter temperature.
Vascular changes after acute spinal cord trauma are important factors that predispose quadriplegia, in most cases irreversible. Repair of the spinal blood flow helps the spinal cord recovery. The ...average time to arrive and perform surgery is 3 h in most cases. It is important to determine the critical ischemia time in order to offer better functional prognosis. A spinal cord section and vascular clamping of the spinal anterior artery at C5-C6 model was used to determine critical ischemia time. The objective was to establish a critical ischemia time in a model of acute spinal cord section. Four groups of dogs were used, anterior approach and vascular clamp of spinal anterior artery with 1, 2, 3, and 4 h of ischemia and posterior hemisection of spinal cord at C5-C6 was performed. Clinical evaluation was made during 12 weeks and morphological evaluation at the end of this period. We obtained a maximal neurological coordination at 23 days average. Two cases showed sequels of right upper limb paresis at 1 and 3 ischemia hours. There was nerve conduction delay of 56% at 3 h of ischemia. Morphological examination showed 25% of damaged area. The VIII and IX Rexed's laminae were the most affected. The critical ischemia time was 3 h. Dogs with 4 h did not exhibit any recovery.
Objectives
Maraviroc (MVC) is a suitable drug for aviraemic subjects on antiretroviral treatment (ART) developing toxicity. Its prescription requires prior tropism testing. It is unknown if proviral ...DNA genotypic tropism testing is reliable for guiding MVC initiation in aviraemic subjects, so this study was carried out to address this issue.
Methods
PROTEST was a phase 4, prospective, single‐arm clinical trial carried out in 24 HIV care centres in Spain. MVC‐naïve HIV‐1‐infected patients with HIV‐1 RNA < 50 copies/mL on stable ART during the previous 6 months who required an ART change because of toxicity and who had R5 HIV, as determined by proviral DNA genotypic tropism testing, initiated MVC with two nucleoside reverse transcriptase inhibitors (NRTIs) and were followed for 48 weeks. Virological failure was defined as two consecutive viral load measurements > 50 copies/mL.
Results
Tropism results were available for 141 of 175 (80.6%) subjects screened: 60% had R5 and 85% of these (n = 74) were finally included in the study. Previous ART included protease inhibitors (PIs) in 62% of subjects, nonnucleoside reverse transcriptase inhibitors (NNRTIs) in 36%, and integrase inhibitors (INIs) in 2%. Main reasons for treatment change were dyslipidaemia (42%), gastrointestinal symptoms (22%) and liver toxicity (15%). MVC was given alongside tenofovir (TDF)/emtricitabine (FTC) (54%) and abacavir (ABC)/lamivudine (3TC) (40%) in most patients. Eighty‐four per cent of patients maintained a viral load < 50 copies/mL to week 48, whereas 16% discontinued treatment: two withdrew informed consent, one had an R5 to X4 shift between screening and baseline, one was lost to follow‐up, one developed an adverse event (rash), two died from non‐study‐related causes, and five developed protocol‐defined virological failure.
Conclusions
Initiation of MVC plus two NRTIs in aviraemic subjects based on genotypic tropism testing of proviral HIV‐1 DNA is associated with low rates of virological failure for up to 1 year.
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