The gap gene of Rhizobium etli is required for both free life and symbiosis with common beans.

Glyceraldehyde-3-phosphate dehydrogenase (GAPDH or Gap) is a ubiquitous enzyme essential for carbon and energy metabolism in most organisms. Despite its primary role in sugar metabolism, GAPDH is recognized for its involvement in diverse cellular processes, being considered a paradigm among multifunctional/moonlighting proteins. Besides its canonical cytoplasmic location, GAPDH has been detected on cell surfaces or as a secreted protein in prokaryotes, yet little is known about its possible roles in plant symbiotic bacteria. Here we report that Rhizobium etli, a nitrogen-fixing symbiont of common beans, carries a single gap gene responsible for both GAPDH glycolytic and gluconeogenic activities. An active Gap protein is required throughout all stages of the symbiosis between R. etli and its host plant Phaseolus vulgaris. Both glycolytic and gluconeogenic Gap metabolic activities likely contribute to bacterial fitness during early and intermediate stages of the interaction, whereas GAPDH gluconeogenic activity seems critical for nodule invasion and nitrogen fixation. Although the R. etli Gap protein is secreted in a c-di-GMP related manner, no involvement of the R. etli gap gene in c-di-GMP related phenotypes, such as flocculation, biofilm formation or EPS production, was observed. Notably, the R. etli gap gene fully complemented a double gap1/gap2 mutant of Pseudomonas syringae for free life growth, albeit only partially in planta, suggesting potential specific roles for each type of Gap protein. Nevertheless, further research is required to unravel additional functions of the R. etli Gap protein beyond its essential metabolic roles.

Plasticity of Gene Expression and Thermal Tolerance: Implications for Climate Change Vulnerability in a Tropical Forest Lizard.

AbstractTropical ectotherms are thought to be especially vulnerable to climate change because they have evolved in temporally stable thermal environments and therefore have decreased tolerance for thermal variability. Thus, they are expected to have narrow thermal tolerance ranges, live close to their upper thermal tolerance limits, and have decreased thermal acclimation capacity. Although models often predict that tropical forest ectotherms are especially vulnerable to rapid environmental shifts, these models rarely include the potential for plasticity of relevant traits. We measured phenotypic plasticity of thermal tolerance and thermal preference as well as multitissue transcriptome plasticity in response to warmer temperatures in a species that previous work has suggested is highly vulnerable to climate warming, the Panamanian slender anole lizard (Anolis apletophallus). We found that many genes, including heat shock proteins, were differentially expressed across tissues in response to short-term warming. Under long-term warming, the voluntary thermal maxima of lizards also increased, although thermal preference exhibited only limited plasticity. Using these data, we modeled changes in the activity time of slender anoles through the end of the century under climate change and found that plasticity should delay declines in activity time by at least two decades. Our results suggest that slender anoles, and possibly other tropical ectotherms, can alter the expression of genes and phenotypes when responding to shifting environmental temperatures and that plasticity should be considered when predicting the future of organisms under a changing climate.

The role of microbiota on rheumatoid arthritis onset.

Rheumatoid arthritis (RA) is a chronic autoimmune disease that causes inflammation and pain, which can lead to the loss of normal joint function. Although the exact cause of the disease is not yet fully understood, both environmental factors and genetics may play a role in its development. Moreover, research suggests microbiota contributes to the onset and progression of RA. People with RA show higher quantities of bacteria such as Porphyromonas gingivalis, Aggregatibacter actinomycetemcomitans, Prevotella copri, Proteus mirabilis, and Lactobacillus salivarius compared to healthy individuals. Conversely, studies propose that Lactobacillus casei, a probiotic bacterium with immunomodulatory properties, has beneficial effects for RA in murine and human models. Therefore, this work reviews the potential role of the gut microbiota in the development of RA and explores the feasibility of using probiotic bacteria as a supplementary treatment for this disease.

Functional electrical stimulation therapy controlled by a P300-based brain-computer interface, as a therapeutic alternative for upper limb motor function recovery in chronic post-stroke patients. A non-randomized pilot study.

Introduction: Up to 80% of post-stroke patients present upper-limb motor impairment (ULMI), causing functional limitations in daily activities and loss of independence. UMLI is seldom fully recovered after stroke when using conventional therapeutic approaches. Functional Electrical Stimulation Therapy (FEST) controlled by Brain-Computer Interface (BCI) is an alternative that may induce neuroplastic changes, even in chronic post-stroke patients. The purpose of this work was to evaluate the effects of a P300-based BCI-controlled FEST intervention, for ULMI recovery of chronic post-stroke patients. Methods: A non-randomized pilot study was conducted, including 14 patients divided into 2 groups: BCI-FEST, and Conventional Therapy. Assessments of Upper limb functionality with Action Research Arm Test (ARAT), performance impairment with Fugl-Meyer assessment (FMA), Functional Independence Measure (FIM) and spasticity through Modified Ashworth Scale (MAS) were performed at baseline and after carrying out 20 therapy sessions, and the obtained scores compared using Chi square and Mann-Whitney U statistical tests (𝛼 = 0.05). Results: After training, we found statistically significant differences between groups for FMA (p = 0.012), ARAT (p < 0.001), and FIM (p = 0.025) scales. Discussion: It has been shown that FEST controlled by a P300-based BCI, may be more effective than conventional therapy to improve ULMI after stroke, regardless of chronicity. Conclusion: The results of the proposed BCI-FEST intervention are promising, even for the most chronic post-stroke patients often relegated from novel interventions, whose expected recovery with conventional therapy is very low. It is necessary to carry out a randomized controlled trial in the future with a larger sample of patients.

Antioxidant and Renin Inhibitory Activities of Peptides from Food Proteins on Hypertension: A Review.

Hypertension is a condition induced by oxidative stress causing an alteration in the endothelium, which increases the risk of suffering from other degenerative diseases. This review compiles the findings on peptides from food proteins with antioxidant and antihypertensive activities. Antihypertensive peptides are mainly focused on renin inhibition. Peptides containing hydrophobic amino acids have antioxidant and renin inhibitory activities, as reported by studies on the biological activity of peptides from various food sources evaluated separately and simultaneously. Peptides from food sources can present multiple biological activities. Moreover, antioxidant peptides have the potential to be evaluated against renin, offering an alternative for hypertension therapy without causing adverse side effects.

Chemopreventive Effect of Cooked Chickpea on Colon Carcinogenesis Evolution in AOM/DSS-Induced Balb/c Mice.

Chickpeas are one of the most widely consumed legumes worldwide and they might prevent diseases such as cancer. Therefore, this study evaluates the chemopreventive effect of chickpea (Cicer arietinum L.) on the evolution of colon carcinogenesis induced with azoxymethane (AOM) and dextran sodium sulfate (DSS) in a mice model at 1, 7, and 14 weeks after induction. Accordingly, the expression of biomarkers-such as argyrophilic nucleolar organizing regions (AgNOR), cell proliferation nuclear antigen (PCNA), ß-catenin, inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2)-was assessed in the colon of BALB/c mice fed diets supplemented with 10 and 20% cooked chickpea (CC). The results showed that a 20% CC diet significantly reduced tumors and biomarkers of proliferation and inflammation in AOM/DSS-induced colon cancer mice. Moreover, body weight loss decreased and the disease activity index (DAI) was lower than the positive control. Lastly, tumor reduction was more evident at week 7 in the groups fed a 20% CC diet. In conclusion, both diets (10% and 20% CC) exert a chemopreventive effect.

FleQ, FleN and c-di-GMP coordinately regulate cellulose production in Pseudomonas syringae pv. tomato DC3000.

The second messenger cyclic di-GMP (c-di-GMP) controls the transition between motility and sessility in many bacterial species by a variety of mechanisms, including the production of multiple exopolysaccharides. Pseudomonas syringae pv. tomato (Pto) DC3000 is a plant pathogenic bacteria able to synthesize acetylated cellulose under high c-di-GMP levels thanks to the expression of the wssABCDEFGHI operon. Increased cellulose production enhances air-liquid biofilm formation and generates a wrinkled colony phenotype on solid media. We previously showed that under low levels of c-di-GMP, the regulators FleQ and AmrZ bound to adjacent sequences at the wss promoter inhibiting its expression, but only FleQ responded to the presence of c-di-GMP by activating cellulose production. In the present work, we advance in the knowledge of this complex regulation in Pto DC3000 by shedding light over the role of FleN in this process. The distinctive features of this system are that FleN and FleQ are both required for repression and activation of the wss operon under low and high c-di-GMP levels, respectively. We have also identified three putative FleQ binding sites at the wss promoter and show that FleQ/FleN-ATP binds at those sites under low c-di-GMP levels, inducing a distortion of DNA, impairing RNA polymerase binding, and repressing wss transcription. However, binding of c-di-GMP induces a conformational change in the FleQ/FleN-ATP complex, which relieves the DNA distortion, allows promoter access to the RNA polymerase, and leads to activation of wss transcription. On the other hand, AmrZ is always bound at the wss promoter limiting its expression independently of FleQ, FleN and c-di-GMP levels.

ZnO recovered from spent alkaline batteries as antimicrobial additive for waterborne paints.

Biocides are employed to prevent biodeterioration in waterborne paints. In the present study, we used zinc oxide nanoparticles (obtained from spent alkaline batteries) as biocide for indoor waterborne paint at 1.5% of the total solid content in paint. Two different zinc oxides synthesized from spent alkaline batteries, which showed photocatalyst activity, were employed as an antimicrobial agents. After leaching the anode of alkaline batteries, zinc was precipitated from the leachate liquor by introducing oxalic acid (O-ZnO) or sodium carbonate (C-ZnO). The antimicrobial properties of the prepared oxides were tested against Staphylococcus aureus (bacteria), Chaetomium globosum, and Aspergillus fumigatus (fungi) using agar well diffusion method. C-ZnO inhibited the growth of all the strains studied and presented enhanced activity than O-ZnO. The better performance as antimicrobial agent of C-ZnO compared to O-ZnO was attributed to its lower crystallite size, higher amount of oxygen monovacancies, and to its lower band gap energy. The oxide with the best performance in antimicrobial activity, C-ZnO, was employed for the formulation of waterborne acrylic paints. It was observed that 1.5% C-ZnO improved the antifungal properties and antibacterial properties compared to the control sample.

Alternative and complementary medicine in neurological disorders and neurological disability patients: Prevalence, factors, opinions and reasons.

OBJECTIVES: This cross-sectional study is aimed to investigate the prevalence of the use of complementary and alternative medicine (CAM), types of CAMs used, as well as reasons and factors found in patients with neurological diseases or neurological disability. METHODS: An anonymous, self-administered survey was designed to collect information about demographics, personal medical history, CAM usage habits, and different opinions about CAM vs. conventional medicine (CM). The survey was applied by non-medical personnel in a rehabilitation hospital to patients older than 18 years, with a confirmed diagnosis of neurological disorder or neurological disability. RESULTS: 453 patients were included, 59.7 % were female. Mean age: 49 years (SD: 18.2). 200 patients (44.2 %) had a history of chronic diseases. Depression was found in 139 patients (30.7 %). Neurological disorders were: peripheral neuropathy: 97 (21.4 %), headache or migraine: 78 (17.2 %), neurodegenerative diseases: 69 (15.2 %) and stroke: 58 (12.8 %). 60.2 % (n = 273) had some degree of disability. Prevalence of CAM use was 36 % (n = 163). Most common CAMs were: Biological therapies: 133 (71.1 %), energy-based therapies: 63 (33.7 %) and body manipulation therapies: 51 (27.3 %). Reasons to use CAM were: "to complement the pharmacological treatment" (45 = 27.6 %), and "treatment failure with CM" (43 = 26.4 %). Finally, older age (p = 0.0280) and having a chronic disease (p = 0.0229) or depression (p < 0.001) were the factors associated with the current use of CAM. CONCLUSION: One third of patients with neurological pathologies use CAM, the most popular type of CAM is biologic therapies. As in other pathologies, CAM use was associated with older age, history of depression, and chronic diseases. Therefore, it is suggested that physicians routinely ask patients about the use of CAM, if they need more information about CAM, and even verify the possibility of drug interactions or adverse effects.

Sclerosing mesenteritis due to Mycobacterium genavense infection: A case report.

RATIONALE: Since its first identification in the early 1990s, Mycobacterium genavense has been considered and opportunistic pathogen. It mainly causes gastrointestinal symptoms, but also disseminated infections in severely immunosuppressed patients. Sclerosing mesenteritis is a long-term complication with high morbidity and mortality. As it is a rare condition, there are no specific guidelines for its management. We report a challenging case of persistent M. genavense infection, and propose surgery as an alternative treatment strategy. PATIENT CONCERNS: A 38-year-old Caucasian man presented to the emergency room with fever, abdominal pain, and night sweats for 3 months. HIV screening revealed a previously unknown HIV-1 infection, with a CD4 cell count of 216 cell/µL and viral load of 361.000 copies/mL at diagnosis. A body CT-scan showed mild splenomegaly as well as mesenteric and retroperitoneal enlarged lymph nodes. Fine needle aspiration revealed the presence of acid-fast bacilli, but mycobacterial cultures were negative. In the second sample, 16S RNA sequencing yielded a diagnosis of M. genavense infection. Despite 2 years of corticosteroids and antimycobacterial treatment excluding rifampicin due to a severe cutaneous reaction, there was no clinical improvement and an increase in the mesenteric lymph node size was observed, with a sclerosing transformation of the mesentery. A surgical approach was proposed to release small bowel loops and to remove fibrin. A second surgery was required due to an acute peritonitis ought to yeyunal segmental isquemia and perforation. Finally, the patient evolved favorably, and antimycobacterial drugs were suspended without relapse. LESSONS: Despite a prolonged multidrug strategy, some patients develop persistent M. genavense infection. Once sclerosing mesenteritis is established, clinicians have few treatment options. Surgery should be considered in patients with sclerosing mesenteritis or bowel obstruction. The combination of medical and surgical treatment could be a potential cure for these patients.

Microbiome Impact on Amyloidogenesis.

Our life is closely linked to microorganisms, either through a parasitic or symbiotic relationship. The microbiome contains more than 1,000 different bacterial species and outnumbers human genes by 150 times. Worryingly, during the last 10 years, it has been observed a relationship between alterations in microbiota and neurodegeneration. Several publications support the hypothesis that amyloid structures formed by microorganisms may trigger host proteins aggregation. In this review, we collect pieces of evidence supporting that the crosstalk between human and microbiota amyloid proteins could be feasible and, probably, a more common event than expected before. The combination of their outnumbers, the long periods of time that stay in our bodies, and the widespread presence of amyloid proteins in the bacteria Domain outline a worrying scenario. However, the identification of the exact microorganisms and the mechanisms through with they can influence human disease also opens the door to developing a new and diverse set of therapeutic strategies.

Biological functions of peptides from legumes in gastrointestinal health. A review legume peptides with gastrointestinal protection.

Extensively consumed worldwide, legumes such as beans, soybeans, chickpeas, and peas represent a great source of protein. Legume-derived proteins provide bioactive peptides, small sequences of amino acids produced by enzymatic hydrolysis, gastrointestinal digestion, fermentation, or germination. Recent studies showed diverse biological effects of these peptides as antioxidants, antihypertensives, anti-inflammatory, antimicrobial, antithrombotic, antidiabetic, hypocholesterolemic, and even immunomodulators. These beneficial effects aid in preventing and treating chronic illnesses, particularly inflammatory disorders, obesity, and cardiovascular diseases. Thus, this work discusses these biological functions in gastrointestinal digestion health of bioactive peptides obtained from common beans, soybeans, chickpeas, peas, and other legumes. PRACTICAL APPLICATIONS: Knowledge of the nutraceutical properties of legumes can encourage the use of these seeds as ingredients in the development and design of functional foods.

Creation of a functional unc-11/PICALM GFP knock-in by CRISPR.

unc-11 is the only C. elegans ortholog of mammalian PICALM/AP180, paralogs that play an important role in Clathrin-Mediated Endocytosis (CME) and the recycling of a subset of SNAREs, the vesicle-associated membrane proteins (VAMPs). In this publication we report the creation of a new unc-11 allele that is endogenously-tagged with GFP just upstream of the stop codon. Moreover, we demonstrate that the UNC-11::GFP fusion protein functions like wild type with an expression pattern similar to UNC-11 antibody staining described previously.

Distinctive features of the Gac-Rsm pathway in plant-associated Pseudomonas.

Productive plant-bacteria interactions, either beneficial or pathogenic, require that bacteria successfully sense, integrate and respond to continuously changing environmental and plant stimuli. They use complex signal transduction systems that control a vast array of genes and functions. The Gac-Rsm global regulatory pathway plays a key role in controlling fundamental aspects of the apparently different lifestyles of plant beneficial and phytopathogenic Pseudomonas as it coordinates adaptation and survival while either promoting plant health (biocontrol strains) or causing disease (pathogenic strains). Plant-interacting Pseudomonas stand out for possessing multiple Rsm proteins and Rsm RNAs, but the physiological significance of this redundancy is not yet clear. Strikingly, the components of the Gac-Rsm pathway and the controlled genes/pathways are similar, but the outcome of its regulation may be opposite. Therefore, identifying the target mRNAs bound by the Rsm proteins and their mode of action (repression or activation) is essential to explain the resulting phenotype. Some technical considerations to approach the study of this system are also given. Overall, several important features of the Gac-Rsm cascade are now understood in molecular detail, particularly in Pseudomonas protegens CHA0, but further questions remain to be solved in other plant-interacting Pseudomonas.

Exploring the expression and functionality of the rsm sRNAs in Pseudomonas syringae pv. tomato DC3000.

The Gac-rsm pathway is a global regulatory network that governs mayor lifestyle and metabolic changes in gamma-proteobacteria. In a previous study, we uncovered the role of CsrA proteins promoting growth and repressing motility, alginate production and virulence in the model phytopathogen Pseudomonas syringae pv. tomato (Pto) DC3000. Here, we focus on the expression and regulation of the rsm regulatory sRNAs, since Pto DC3000 exceptionally has seven variants (rsmX1-5, rsmY and rsmZ). The presented results offer further insights into the functioning of the complex Gac-rsm pathway and the interplay among its components. Overall, rsm expressions reach maximum levels at high cell densities, are unaffected by surface detection, and require GacA for full expression. The rsm levels of expression and GacA-dependence are determined by the sequences found in their -35/-10 promoter regions and GacA binding boxes, respectively. rsmX5 stands out for being the only rsm in Pto DC3000 whose high expression does not require GacA, constituting the main component of the total rsm pool in a gacA mutant. The deletion of rsmY and rsmZ had minor effects on Pto DC3000 motility and virulence phenotypes, indicating that rsmX1-5 can functionally replace them. On the other hand, rsmY or rsmZ overexpression in a gacA mutant did not revert its phenotype. Additionally, a negative feedback regulatory loop in which the CsrA3 protein promotes its own titration by increasing the levels of several rsm RNAs in a GacA-dependent manner has been disclosed as part of this work.

Outcomes of Infants With Severe Refractory Food Protein-induced Allergic Proctocolitis Treated With Mesalamine.

This retrospective chart review evaluates the outcomes of mesalamine treatment in infants with severe food protein-induced allergic proctocolitis (FPIAP) and persistent clinical symptoms despite the use of elemental formulas. Patients received mesalamine in a 40-60 mg/kg/d dose for an average of 100 days. This group showed significantly higher rates of improvement in the most common symptoms of FPIAP compared with the control group. In addition, the mesalamine group was less likely to need pharmacological treatment for gastroesophageal reflux disease and more likely to successfully transition to whole milk or soy milk after 1 year of age. In conclusion, using mesalamine can be a useful addition to the treatment of severe refractory cases of FPIAP.

Modification of In Vitro and In Vivo Antioxidant Activity by Consumption of Cooked Chickpea in a Colon Cancer Model.

Chickpea has been classified as a nutraceutical food due to its phytochemical compounds, showing antioxidant, anti-inflammatory, and anticancer activity. To investigate this, we evaluated the effect of cooking on the nutritional and non-nutritional composition and the in vitro and in vivo antioxidant activity of chickpea seed. The latter was determined by the variation in the concentration of nitric oxide (NO), oxidized carbonyl groups (CO), malondialdehyde (MDA), and the expression of 4-hydroxy-2-nonenal (4-HNE) in the colon of male BALB/c mice fed with a standard diet with 10 and 20% cooked chickpea (CC). We induced colon cancer in mice by administering azoxymethane/dextran sulfate sodium (AOM/DSS); for the evaluation, these were sacrificed 1, 7, and 14 weeks after the induction. Results show that cooking does not significantly modify (p < 0.05) nutritional compounds; however, it decreases the concentration of non-nutritional ones and, consequently, in vitro antioxidant activity. The in vivo evaluation showed that animals administered with AOM/DSS presented higher concentrations of NO, CO, MDA, and 4-HNE than those in animals without AOM/DSS administration. However, in the three evaluated times, these markers were significantly reduced (p < 0.05) with CC consumption. The best effect on the oxidation markers was with the 20% CC diet, demonstrating the antioxidant potential of CC.

Biological Activities of Chickpea in Human Health (Cicer arietinum L.). A Review.

Chickpea is one of the most consumed legumes worldwide. Among their benefits are the high protein concentration that reflects not only at the nutritional level but also on the supply of active peptides; besides, it presents different metabolites with pharmacological activities. Some biological activities identified in the different compounds of chickpea are antioxidant, antihypertensive, hypocholesterolemic, and anticancer. Although most reports are based on the effects of the proteins and their hydrolysates, alcoholic extracts have also been proven that contain phenolic compounds, saponins, phytates, among others; therefore, their consumption has been dubbed as an alternative for the prevention of chronic degenerative diseases. In the present review, we summarize the nutritional composition of the chickpea and describe the main biological activities reported for this legume, revealing some of its beneficial effects on health, of which there is still much to be elucidated.

AmrZ and FleQ Co-regulate Cellulose Production in Pseudomonas syringae pv. Tomato DC3000.

Pseudomonas syringae pv. tomato DC3000 carries the wssABCDEFGHI operon for the synthesis of acetylated cellulose, whose production is stimulated by increasing the intracellular levels of the second messenger c-di-GMP. This enhances air-liquid biofilm formation and generates a wrinkly colony morphotype in solid media. In the present study we show that cellulose production is a complex process regulated at multiple levels and involving different players in this bacterium. Using different in vitro approaches, including Electrophoretic Mobility Shift Assay (EMSA) and footprint analysis, we demonstrated the interrelated role of two transcriptional regulators, AmrZ and FleQ, over cellulose production in Pto DC3000 and the influence of c-di-GMP in this process. Under physiological c-di-GMP levels, both regulators bind directly to adjacent regions at the wss promoter inhibiting its expression. However, just FleQ responds to c-di-GMP releasing from its wss operator site and converting from a repressor to an activator of cellulose production. The additive effect of the double amrZ/fleQ mutation on the expression of wss, together with the fact that they are not cross-regulated at the transcriptional level, suggest that FleQ and AmrZ behave as independent regulators, unlike what has been described in other Pseudomonas species. Furthermore, this dual co-regulation exerted by AmrZ and FleQ is not limited to cellulose production, but also affects other important phenotypes in Pto DC3000, such as motility and virulence.