Tyr‐Asp inhibition of glyceraldehyde 3‐phosphate dehydrogenase affects plant redox metabolism

How organisms integrate metabolism with the external environment is a central question in biology. Here, we describe a novel regulatory small molecule, a proteogenic dipeptide Tyr‐Asp, which improves plant tolerance to oxidative stress by directly interfering with glucose metabolism. Specifically, Tyr‐Asp inhibits the activity of a key glycolytic enzyme, glyceraldehyde 3‐phosphate dehydrogenase (GAPC), and redirects glucose toward pentose phosphate pathway (PPP) and NADPH production. In line with the metabolic data, Tyr‐Asp supplementation improved the growth performance of both Arabidopsis and tobacco seedlings subjected to oxidative stress conditions. Moreover, inhibition of Arabidopsis phosphoenolpyruvate carboxykinase (PEPCK) activity by a group of branched‐chain amino acid‐containing dipeptides, but not by Tyr‐Asp, points to a multisite regulation of glycolytic/gluconeogenic pathway by dipeptides. In summary, our results open the intriguing possibility that proteogenic dipeptides act as evolutionarily conserved small‐molecule regulators at the nexus of stress, protein degradation, and metabolism.     

Stress-coping and cortisol analysis in patients with non-syndromic cleft lip and palate: an explorative study

Background

Non-syndromic clefts of the orofacial region occur in approximately 1 per 500 to 2,500 live births, depending on geographical area and ethnicity. It can be supposed that the disruption of the normal facial structure and the long-standing pressure of treatment from birth to adulthood bring about a range of life stressors which may lead to a long-lasting impact on affected subjects throughout their lives. Therefore, the present study aimed to assess different aspects of psychosocial stress in affected individuals.

Methods

The study was divided into two parts: first, the Trier Social Stress Test which involves uncontrollability and high levels of social-evaluative stress under real conditions and second, the query of various aspects of coping with psychosocial stress. The test group consisted of 30 affected adult subjects, and an equally sized control group of unaffected volunteers. Cortisol dysregulation was determined by saliva samples before and after stress induction. Meanwhile, participants were asked to complete the SVF 120 stress-coping questionnaire.

Results

The analysis of saliva samples showed a similar baseline concentration as well as a similar increase in cortisol levels after stress induction for both groups. Subsequently, the decline in cortisol concentrations was significantly faster in the CLP group (course: p<0.001; groups: p = 0.102; interaction: p = 0.167). The evaluation of the stress-coping questionnaire revealed a significantly shorter rumination about a stressful event in individuals with CLP-related malformations (p = 0.03).

Conclusion

We conclude that adults with CLP have significantly better stress-coping strategies than their healthy peers.

Trial Registration

German Clinical Trials Organization DRKS00003466     

Metabolic syndrome is inversely related to cardiorespiratory fitness in male career firefighters

Cardiovascular disease (CVD) accounts for 45% of on-duty fatalities among firefighters, occurring primarily in firefighters with excess CVD risk factors in patterns resembling the metabolic syndrome (MetSyn). Additionally, firefighters have a high prevalence of obesity and sedentary behavior suggesting that MetSyn is also common. Therefore, we assessed the prevalence of MetSyn in firefighters and its association with cardiorespiratory fitness (CRF) in a cross-sectional study of 957 male career firefighters. The CRF was measured by maximal exercise tolerance testing (standard metabolic equivalent [METS]). The MetSyn was defined according to modified criteria from the Joint Scientific Statement. Group differences were compared using χ-test and logistic regression. The prevalence of MetSyn was 28.3%. Firefighters in the lowest fitness category (METS ≤ 10) had a nearly 10-fold higher prevalence of MetSyn (51.2%) compared with colleagues in the highest fitness category (METS > 14) (MetSyn prevalence 5.2%) (p value < 0.0001, adjusted for age). In multivariate regression models, every 1-unit increase in METS decreased the odds of having the MetSyn by 31% (odds ratio 0.69 [95% confidence interval 0.63-0.76] [age adjusted]), whereas age had no significant effect after adjusting for CRF. We found a high prevalence of the MetSyn in this group of career emergency responders expected to be more active, fit, and relatively younger than the general population. Moreover, there is a highly significant inverse, dose-response association with CRF. Firefighters should be given strong incentives to improve their fitness, which would decrease prevalent MetSyn, a likely precursor of on-duty CVD events and contributor to CVD burden in this population.     

Gastric cancer: basic aspects

The worldwide incidence and mortality of gastric cancer (GC) remain high, and new concepts for diagnosis and treatment are needed. In this review, we summarize recent studies that applied next-generation sequencing approaches and also report the latest development in microRNA research. Two recently published studies identified somatic mutations in ARID1A gene in GC using exome sequencing. On the other hand, dysregulation of microRNA expression can alter processes such as proliferation, apoptosis, invasion, and metastasis. These novel markers may prove to be useful in earlier diagnosis and as prognostic or predictive markers in patients with GC .     

Tricellulin Forms a Barrier to Macromolecules in Tricellular Tight Junctions without Affecting Ion Permeability

Tricellulin is a tight junction protein localized in tricellular tight junctions (tTJs), the meeting points of three cells, but also in bicellular tight junctions (bTJs). To investigate its specific barrier functions in bTJs and tTJs, TRIC-a was expressed in low-level tricellulin–expressing cells, and MDCK II, either in all TJs or only in tTJs. When expressed in all TJs, tricellulin increased paracellular electrical resistance and decreased permeability to ions and larger solutes, which are associated with enhanced ultrastructural integrity of bTJs toward enhanced strand linearity. In tTJs in contrast, ultrastructure was unchanged and tricellulin minimized permeability to macromolecules but not to ions. This paradox is explained by properties of the tTJ central tube which is wide enough for passage of macromolecules, but too rare to contribute significantly to ion permeability. In conclusion, at low tricellulin expression the tTJ central tube forms a pathway for macromolecules. At higher expression, tricellulin forms a barrier in tTJs effective only for macromolecules and in bTJs for solutes of all sizes.     

Characterization of genes for a second Mo-dependent nitrogenase in the cyanobacterium Anabaena variabilis.

Anabaena variabilis ATCC 29413 is a filamentous heterocystous cyanobacterium that fixes nitrogen under a variety of environmental conditions. Under aerobic growth conditions, nitrogen fixation depends upon differentiation of heterocysts and expression of either a Mo-dependent nitrogenase or a V-dependent nitrogenase in those specialized cells. Under anaerobic conditions, a second Mo-dependent nitrogenase gene cluster, nifII, was expressed in vegetative cells long before heterocysts formed. A strain carrying a mutant gene in the nifII cluster did not fix nitrogen under anaerobic conditions until after heterocysts differentiated. The nifII cluster was similar in organization to the nifI cluster that is expressed in heterocysts and that includes nifBSUHDKENXW as well as three open reading frames that are conserved in both cyanobacterial nif clusters.     

The critical role of adenosine A2A receptors in downregulation of inflammation and immunity in the pathogenesis of infectious diseases

Adenosine can be described as a retaliatory metabolite, the production and release of which is usually enhanced under adverse environmental conditions. Binding via specific receptors, adenosine activates endogenous protective mechanisms aiming at the restoration of tissue homeostasis. While adenosinergic downregulation of tissue damage is beneficial in acute inflammation, chronic suppression of the immune system by adenosine may account for immunoparalysis in long-term septic patients.     

High light-induced switch from C(3)-photosynthesis to Crassulacean acid metabolism is mediated by UV-A/blue light

The high light-induced switch in Clusia minor from C(3)-photosynthesis to Crassulacean acid metabolism (CAM) is fast (within a few days) and reversible. Although this C(3)/CAM transition has been studied intensively, the nature of the photoreceptor at the beginning of the CAM-induction signal chain is still unknown. Using optical filters that only transmit selected wavelengths, the CAM light induction of single leaves was tested. As controls the opposite leaf of the same leaf pair was studied in which CAM was induced by high unfiltered radiation (c. 2100 micromol m(-2) s(-1)). To evaluate the C(3)-photosynthesis/CAM transition, nocturnal CO(2) uptake, daytime stomatal closure and organic acid levels were monitored. Light at wavelengths longer than 530 nm was not effective for the induction of the C(3)/CAM switch in C. minor. In this case CAM was present in the control leaf while the opposite leaf continued performing C(3)-photosynthesis, indicating that CAM induction triggered by high light conditions is wavelength-dependent and a leaf internal process. Leaves subjected to wavelengths in the range of 345-530 nm performed nocturnal CO(2) uptake, (partial) stomatal closure during the day (CAM-phase III), and decarboxylation of citric acid within the first 2 d after the switch to high light conditions. Based on these experiments and evidence from the literature, it is suggested that a UV-A/blue light receptor mediates the light-induced C(3)-photosynthesis/CAM switch in C. minor.     

Vacuolar malate uptake is mediated by an anion-selective inward rectifier

Electrophysiological studies using the patch‐clamp technique were performed on isolated vacuoles from leaf mesophyll cells of the crassulacean acid metabolism (CAM) plant Kalanchoë daigremontiana to characterize the malate transport system responsible for nocturnal malic acid accumulation. In the presence of malate on both sides of the membrane, the current–voltage relations of the tonoplast were dominated by a strongly inward‐rectifying anion‐selective channel that was active at cytoplasmic‐side negative voltages. Rectification of the macroscopic conductance was reflected in the voltage‐dependent gating of a 3‐pS malate‐selective ion channel, which showed a half‐maximal open probability at ?43 mV. Also, the time‐averaged unitary currents following a step to a negative voltage corresponded to the time‐dependent kinetics of the macroscopic currents, suggesting that the activity of this channel underlies the anion‐selective inward rectifier. The inward rectifier showed saturation kinetics with respect to malate (apparent K_m of 2.5 mm malate^2? activity), a selectivity sequence of fumarate^2? > malate^2? > Cl^? > maleate^2– ≈ citrate^3–, and greater activity at higher pH values (with an apparent pK of 7.1 and maximum activity at around pH 8.0). All these properties were in close agreement with the characteristics of malate transport observed in isolated tonoplast vesicles. Further, 100 µm niflumate reversibly blocked the activity of the 3‐pS channel and inhibited both macroscopic currents and malate transport into tonoplast vesicles to the same extent. The macroscopic current densities recorded at physiological voltages and the estimated channel density of 0.2 µm^?2 are sufficient to account for the observed rates of nocturnal malic acid accumulation in this CAM plant, suggesting that the 3‐pS, inward‐rectifying, anion‐selective channel represents the principal pathway for malate influx into the vacuole.     

Predation rates of nemertean predators: the case of a rocky shore hoplonemertean feeding on amphipods

Estimates of the predation rates of benthic nemerteans are often based on observations of single individuals, and consequently they may not be representative for all members of a population of these predators. Herein we conducted controlled and repeatable laboratory experiments on the predation rate of the hoplonemertean Amphiporus nelsoni Sánchez 1973, which is common at exposed rocky shores along the central Chilean coast. During the austral fall (April, May 2000), nemerteans were observed in relatively high numbers crawling in the intertidal zone during early morning or late-afternoon low tides. When these nemerteans were offered living amphipods held by a forceps, they immediately attacked the amphipods and fed on them. In the laboratory experiments, nemerteans preferred the amphipod Hyale maroubrae Stebbing, 1899, which is also very common in the natural habitat of A. nelsoni. The nemerteans preyed to a higher extent on small males and non-ovigerous females than would have been expected from their abundance. We suggest that these (non-reproductive) stages of H. maroubrae are very mobile and therefore have a high likelihood of encounters with nemerteans. Predation rates reached maxima when nemerteans were provided prey densities of four or more of their preferred prey species, H. maroubrae, furthermore indicating that encounter rates with prey may affect predation rates. In long-term laboratory experiments, A. nelsoni consumed more amphipods during low tide conditions than during high tide conditions. Many nemerteans in the field prefer particular environmental conditions (e.g. nocturnal low tides), which restricts the time available for successful feeding. In the long-term experiment, predation rates of A. nelsoni never exceeded 0.5 amphipods nemertean^–1 d^–1. Maximum feeding events were 3 or 4 amphipods nemertean^–1 d^–1, but this only occurred during 10 out of a possible 2634 occasions. Nemerteans that had consumed 3 or 4 amphipods during 1 day, consumed substantially less prey during the following days. Towards the end of the long-term experiment, average predation rates decreased to 0.2 amphipods nemertean^–1 d^–1, corresponding to predation rates reported for other nemertean species (0.1–0.3 prey items nemertean^–1 d^–1). We suggest that predation rates from laboratory experiments represent maximum estimates that may not be directly transferable to field populations. Additionally, low predator–prey encounter rates with preferred prey in the field may further limit the predation impact of nemertean predators in natural habitats.