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Arid and semi-arid areas are among the most threatened ecosystems on the planet. The Tehuacán-Cuicatlán Biosphere Reserve (TCBR), in southeastern Mexico, is an arid and semi-arid area with high biological diversity and human settlements of eight ethnic groups. Two rivers drain the reserve, Río Grande (RG) and Río Salado (RS), which are not subject to water quality monitoring by government agencies; however, measures of water quality of these rivers are needed to focus conservation actions on this resource. This work aimed to test the effectiveness of participatory water quality monitoring with the participation of three actors: Reserve management leaders, local communities, and academics, to monitoring water quality in the rivers of the TCBR. Ninety-two residents were trained to carry out water quality biomonitoring using the Biological Monitoring Working Party (BMWP) index calibrated for the reserve. The BMWP uses macroinvertebrate families to display numerical and categorical water quality scores. Additionally, the Water Quality Index (WQI) was assessed and the Normalized Difference Vegetation Index (NDVI) of the riparian zones was estimated in each study site. The mean WQI scores were 69.24 for RS (no treatment necessary for most crops and necessary treatment for public water supply) and 75.16 for RG (minor purification for crops requiring high-quality water and necessary treatment for public water supply). The BMWP showed five water quality categories (Excellent, Very Good, Good, Fair, and Poor), showing higher water quality scores in the upper portion of the basins and capable of discriminating study sites with lower scores close to human settlements. At one study site, data from participatory monitoring impelled actions taken to address a pollution source and influenced policy focus, reaching the maximum level of participatory-based monitoring. This led to avoid the discharge of wastewater into the river to conserve and protect the water resource. WQI is closely related to BMWP; however, the latter was far more sensitive to detecting areas affected by domestic water discharges. The NDVI presented low values for the TCBR, being lower in RS (the driest area). Although the NDVI showed a weak relationship with BMWP values, areas with higher NDVI values generally achieved higher BMWP values. The results of this study highlight the high sensitivity of the BMWP to detect several water quality conditions in the rivers running through the TCBR when compared to WQI. In addition, the usefulness of biomonitoring using the BMWP index was evident, as well as the importance of the participation of local inhabitants contributing to the knowledge of water quality in biosphere reserves and carrying out timely measures that allow the rivers in these reserves to be maintained in good condition., (© 2024. The Author(s).)

Salmonella enterica serovar Typhimurium causes gastroenteritis and systemic infections in humans. For this bacterium the expression of a type III secretion system (T3SS) and effector proteins encoded in the Salmonella pathogenicity island-1 (SPI-1), is keystone for the virulence of this bacterium. Expression of these is controlled by a regulatory cascade starting with the transcriptional regulators HilD, HilC and RtsA that induce the expression of HilA, which then activates expression of the regulator InvF, a transcriptional regulator of the AraC/XylS family. InvF needs to interact with the chaperone SicA to activate transcription of SPI-1 genes including sicA, sopB, sptP, sopE, sopE2, and STM1239. InvF very likely acts as a classical activator; however, whether InvF interacts with the RNA polymerase alpha subunit RpoA has not been determined. Results from this study confirm the interaction between InvF with SicA and reveal that both proteins interact with the RNAP alpha subunit. Thus, our study further supports that the InvF/SicA complex acts as a classical activator. Additionally, we showed for the first time an interaction between a chaperone of T3SS effectors (SicA) and the RNAP., (© 2024. The Author(s).)

Our work group designed and synthesized a promissory compound N-(2-hydroxyphenyl)-2-propylpentanamide (HO-AAVPA). The HO-AAVPA is a HDAC1 inhibitor and antiproliferative in cancer cell lines. However, HO-AAVPA is poor water solubility and enzymatically metabolized. In this work, the fourth-generation poly(amidoamine) dendrimer (PAMAM-G4) was used as a drug deliver carrier of HO-AAVPA. Moreover, HO-AAVPA and HO-AAVPA-PAMAM complex were submitted to forced degradation studies (heat, acid, base, oxidation and sunlight). Also, the HO-AAVPA-PAMAM-G4 complex was assayed as antiproliferative in a breast cancer cell line (MCF-7). The HO-AAVPA-PAMAM-G4 complex was obtained by docking and experimentally using three pH conditions: acid (pH = 3.0), neutral (pH = 7.0) and basic (pH = 9.0) showing that PAMAM-G4 captureand protect the HO-AAVPA from forced degradation, it is due to sunlight yielded a by-product from HO-AAVPA. In addition, the PAMAM-G4 favored the HO-AAVPA water solubility under basic and neutral pH conditions with significant difference (F (2,18)  = 259.9, p < 0.001) between the slopes of the three conditions being the basic condition which solubilizes the greatest amount of HO-AAVPA. Finally, the HO-AAVPA-PAMAM-G4 complex showed better antiproliferative effects on MCF-7 (IC 50  = 75.3 μM) than HO-AAVPA (IC 50  = 192 μM). These results evidence that PAMAM-G4 complex improve the biological effects of HO-AAVPA., (© 2023. The Author(s).)

Mast cells (MC) play a central role in the early containment of bacterial infections, such as that caused by Listeria monocytogenes (L.m). The mechanisms of MC activation induced by L.m infection are well known, so it is possible to evaluate whether they are susceptible to targeting and modulation by different drugs. Recent evidence indicates that valproic acid (VPA) inhibits the immune response which favors L.m pathogenesis in vivo. Herein, we examined the immunomodulatory effect of VPA on L.m-mediated MC activation. To this end, bone marrow-derived mast cells (BMMC) were pre-incubated with VPA and then stimulated with L.m. We found that VPA reduced MC degranulation and cytokine release induced by L.m. MC activation during L.m infection relies on Toll-Like Receptor 2 (TLR2) engagement, however VPA treatment did not affect MC TLR2 cell surface expression. Moreover, VPA was able to decrease MC activation by the classic TLR2 ligands, peptidoglycan and lipopeptide Pam3CSK4. VPA also reduced cytokine production in response to Listeriolysin O (LLO), which activates MC by a TLR2-independent mechanism. In addition, VPA decreased the activation of critical events on MC signaling cascades, such as the increase on intracellular Ca 2+ and phosphorylation of p38, ERK1/2 and -p65 subunit of NF-κB. Altogether, our data demonstrate that VPA affects key cell signaling events that regulate MC activation following L.m infection. These results indicate that VPA can modulate the functional activity of different immune cells that participate in the control of L.m infection., (© 2022. The Author(s).)

We produced and characterised biochar made from Caribbean pine sawdust as raw material. The biochar (BC 500 ) was used as biocompatible support to co-inoculate phosphate solubilizing bacteria (PSB) (BC 500 /PSB) on Allium cepa L., plants at a greenhouse scale for four months. The three biomaterials study included proximate analysis, elemental analysis, aromaticity analysis, scanning electron microscopy, Fourier transform infrared spectroscopy (FTIR), adsorption studies at different pH and PSB stability as a function of time. The results indicated that BC 500 is suitable as organic support or solid matrix to maintain the viability of PSB able to solubilise P from phosphate rock (PR). The biofertilizer (BC 500 /PSB) allows increasing germination, seedling growth, nutrient assimilation, and growth of Allium cepa L., because PSB immobilised on BC 500 promoted nutrient mobilisation, particularly P, during cultivation of Allium cepa L., at pots scale. The two treatments to evaluate the biofertilizer (BC 500 /PSB) showed the highest concentrations of total P with 1.25 ± 0.13 and 1.38 ± 0.14 mg bulb -1 in A. cepa L. This work presents the benefits of a new product based on bacteria naturally associated with onion and an organic material (BC 500 ) serving as a bacterial carrier that increases the adsorption area of highly reactive nutrients, reducing their leaching or precipitation with other nutrients and fixation to the solid matrix of the soil., (© 2022. The Author(s).)

Mining is one of the major pollution sources worldwide, causing huge disturbances to the environment. Industrial and artisanal mining activities are widespread in Mexico, a major global producer of various metals. This study aimed to assess the ecological impairments resulting from mining activities using aquatic macroinvertebrates assemblages (MA). A multiple co-inertia analysis was applied to determine the relationships between environmental factors, habitat quality, heavy metals, and aquatic macroinvertebrates in 15 study sites in two different seasons (dry and wet) along two rivers running across the Central Plateau of Mexico. The results revealed three contrasting environmental conditions associated with different MAs. High concentrations of heavy metals, nutrients, and salinity limit the presence of several families of seemingly sensitive macroinvertebrates. These factors were found to influence structural changes in MAs, showing that not only mining activities, but also agriculture and presence of villages in the basin, exert adverse effects on macroinvertebrate assemblages. Diversity indices showed that the lowest diversity matched both the most polluted and the most saline rivers. The rivers studied displayed high alkalinity and hardness levels, which can reduce the availability of metals and cause adverse effects on periphyton by inhibiting photosynthesis and damaging MAs. Aquatic biomonitoring in rivers, impacted by mining and other human activities, is critical for detecting the effect of metals and other pollutants to improve management and conservation strategies. This study supports the design of cost-effective and accurate water quality biomonitoring protocols in developing countries., (© 2022. The Author(s).)

3-Hydroxy-3-methylglutaryl-coenzyme A reductase (HMGR) is a crucial enzyme in the ergosterol biosynthesis pathway. The aim of this study was to obtain, purify, characterize, and overexpress five point mutations in highly conserved regions of the catalytic domain of Candida glabrata HMGR (CgHMGR) to explore the function of key amino acid residues in enzymatic activity. Glutamic acid (Glu) was substituted by glutamine in the E680Q mutant (at the dimerization site), Glu by glutamine in E711Q (at the substrate binding site), aspartic acid by alanine in D805A, and methionine by arginine in M807R (the latter two at the cofactor binding site). A double mutation, E680Q-M807R, was included. Regarding recombinant and wild-type CgHMGR, in vitro enzymatic activity was significantly lower for the former, as was the in silico binding energy of simvastatin, alpha-asarone and the HMG-CoA substrate. E711Q displayed the lowest enzymatic activity and binding energy, suggesting the importance of Glu 711 (in the substrate binding site). The double mutant CgHMGR E680Q-M807R exhibited the second lowest enzymatic activity. Based on the values of the kinetic parameters K M and V max , the mutated amino acids appear to participate in binding. The current findings provide insights into the role of residues in the catalytic site of CgHMGR., (© 2021. The Author(s).)

Canine parvovirus type II (CPV-2) infection induces canine parvoviral enteritis (CPE), which in turn promotes sepsis and systemic inflammatory response syndrome (SIRS). Mortality in this disease is usually registered within 48-72 h post-hospitalization, the critical period of the illness. It has been recently described that the use of an immunomodulator, whose major component is monomeric ubiquitin (mUb) without the last two glycine residues (Ub∆GG), in pediatric human patients with sepsis augments survival. It is known that CXCR4 is the cell receptor of extracellular ubiquitin in humans. This work aimed to explore the effect of one immunomodulator (human Dialyzable Leukocyte Extract-hDLE) as a therapeutic auxiliary in puppies with sepsis and SIRS induced by CPE. We studied two groups of puppies with CPV-2 infection confirmed by polymerase chain reaction. The first group received conventional treatment (CT) and vehicle (V), while the second group received CT plus the immunomodulator (I). We assessed both groups' survival, clinical condition, number of erythrocytes, neutrophils, and lymphocytes during the hospitalization period. In addition, hematocrit, hemoglobin, plasma proteins and cortisol values, as well as norepinephrine/epinephrine and serotonin concentration were determined. Puppies treated with CT + I showed 81% survival, mild clinical signs, and a significant decrease in circulating neutrophils and lymphocytes in the critical period of the treatment. In contrast, the CT + V group presented a survival of 42%, severe clinical status, and no improvement of the parameters evaluated in the critical period of the disease. We determined in silico that human Ub∆GG can bind to dog CXCR4. In conclusion, the administration of a human immunomodulator (0.5 mg/day × 5 days) to puppies with CPE under six months of age reduces the severity of clinical signs, increases survival, and modulates inflammatory cell parameters. Further studies are necessary to take full advantage of these clinical findings, which might be mediated by the human Ub∆GG to canine CXCR4 interaction., (© 2021. The Author(s).)

The four new briarane diterpenoids 2-butyryloxybriarane B-3 (2), 9-acetylbriarenolide S (3), briarenolide W (4), and 12-isobriarenolide P (5), along with briarane B-3 (1) and the five known diterpenes 6-10 were isolated from the gorgonian coral Briareum asbestinum collected from the Mexican Caribbean Sea. The structures were elucidated by 1D and 2D NMR and MS measurements. Since the structure of briarane B-3 (1) was only suggested and published without any spectroscopic support, it was herein confirmed, and the supporting data are now provided. In addition, 1 provided the opportunity to explore the sensitivity of vibrational circular dichroism (VCD) to determine the configuration of a single stereogenic center in the presence of eight other stereogenic centers in a molecule possessing a highly flexible ten-member ring. A single-crystal X-ray diffraction study, in which the Flack and Hooft parameters of 1 were determined, further confirmed that briarane B-3 is (1S,2S,6S,7R,8R,9S,10S,11R,17R)-1. This paper reports for first time the use of VCD in briarane diterpenes and with the presence of chlorine atoms. Biological evaluation of seven isolated compounds evidenced a moderate anti-inflammatory activity for compounds 6 and 9 but it did not show any cytotoxic, antiviral, antibacterial, and topoisomerase inhibitory activity.

Valproic acid (VPA) is a drug commonly used for epileptic seizure control. Recently, it has been shown that VPA alters the activation of several immune cells, including Natural Killer (NK) cells, which play an important role in the containment of viruses and intracellular bacteria. Although VPA can increase susceptibility to extracellular pathogens, it is unknown whether the suppressor effect of VPA could affect the course of intracellular bacterial infection. This study aimed to evaluate the role of VPA during Listeria monocytogenes (L.m) infection, and whether NK cell activation was affected. We found that VPA significantly augmented mortality in L.m infected mice. This effect was associated with increased bacterial load in the spleen, liver, and blood. Concurrently, decreased levels of IFN-γ in serum and lower splenic indexes were observed. Moreover, in vitro analysis showed that VPA treatment decreased the frequency of IFN-γ-producing NK cells within L.m infected splenocytes. Similarly, VPA inhibited the production of IFN-γ by NK cells stimulated with IL-12 and IL-18, which is a crucial system for early IFN-γ production in listeriosis. Finally, VPA decreased the phosphorylation of STAT4, p65, and p38, without affecting the expression of IL-12 and IL-18 receptors. Altogether, our results indicate that VPA increases the susceptibility to Listeria monocytogenes infection and suggest that NK cell is one of the main targets of VPA, but further work is needed to ascertain this effect.

UV light is a group of high-energy waves from the electromagnetic spectrum. There are three types of UV radiations: UV-A, -B and -C. UV-C light are the highest in energy, but most are retained by the ozone layer. UV-A and -B reach the earth's surface and cause damage on living organisms, being considered as mutagenic physical agents. Numerous test models are used to study UV mutagenicity; some include special lamps, cell cultures and mathematical modeling. Mercury lamps are affordable and useful sources of UV-C light due to their emission at near the maximum absorption peak of nucleic acids. E. coli cultures are widely used because they have DNA-damage and -repairing mechanisms fairly similar to humans. In here we present two simple models that describe UV-C light incidence on a genome matrix, using fundamental quantum-mechanical concepts and considering light as a particle with a discontinuous distribution. To test the accuracy of our equations, stationary phase cultures of several E. coli strains were exposed to UV-C light in 30 s-intervals. Surviving CFUs were counted and survival/mortality curves were constructed. These graphs adjusted with high goodness of fit to the regression predictions. Results were also analyzed using three main parameters: quantum yield, specific speed and time of mortality.

Cytochrome P450s from the CYP52 family participate in the assimilation of alkanes and fatty acids in fungi. In this work, the evolutionary history of a set of orthologous and paralogous CYP52 proteins from Saccharomycetales yeasts was inferred. Further, the phenotypic assimilation profiles were related with the distribution of cytochrome CYP52 members among species. The maximum likelihood phylogeny of CYP52 inferred proteins reveled a frequent ancient and modern duplication and loss events that generated orthologous and paralogous groups. Phylogeny and assimilation profiles of alkanes and fatty acids showed a family expansion in yeast isolated from hydrophobic-rich environments. Docking analysis of deduced ancient CYP52 proteins suggests that the most ancient function was the oxidation of C4-C11 alkanes, while the oxidation of >10 carbon alkanes and fatty acids is a derived character. The ancient CYP52 paralogs displayed partial specialization and promiscuous interaction with hydrophobic substrates. Additionally, functional optimization was not evident. Changes in the interaction of ancient CYP52 with different alkanes and fatty acids could be associated with modifications in spatial orientations of the amino acid residues that comprise the active site. The extended family of CYP52 proteins is likely evolving toward functional specialization, and certain redundancy for substrates is being maintained.

Murine leprosy, caused by Mycobacterium lepraemurium (MLM), is a chronic disease that closely resembles human leprosy. Even though this disease does not directly involve the nervous system, we investigated a possible effect on working memory during this chronic infection in Balb/c mice. We evaluated alterations in the dorsal region of the hippocampus and measured peripheral levels of cytokines at 40, 80, and 120 days post-infection. To evaluate working memory, we used the T-maze while a morphometric analysis was conducted in the hippocampus regions CA1, CA2, CA3, and dentate gyrus (DG) to measure morphological changes. In addition, a neurochemical analysis was performed by HPLC. Our results show that, at 40 days post-infection, there was an increase in the bacillary load in the liver and spleen associated to increased levels of IL-4, working memory deterioration, and changes in hippocampal morphology, including degeneration in the four subregions analyzed. Also, we found a decrease in neurotransmitter levels at the same time of infection. Although MLM does not directly infect the nervous system, these findings suggest a possible functional link between the immune system and the central nervous system.

Dendroctonus bark beetles comprise 20 taxonomically recognized species, which are one of the most destructive pine forest pests in North and Central America, and Eurasia. The aims of this study were to characterize the gut bacterial diversity, to determine the core bacteriome and to explore the ecological association between these bacteria and bark beetles. A total of five bacterial phyla were identified in the gut of 13 Dendroctonus species; Proteobacteria was the most abundant, followed by Firmicutes, Fusobacteria, Actinobacteria and Deinococcus-Thermus. The α-diversity was low as demonstrated in previous studies and significant differences in β-diversity were observed. The core bacteriome was composed of Enterobacter, Pantoea, Pseudomonas, Rahnella, Raoultella, and Serratia. The tanglegram between bacteria and bark beetles suggests that members of bacterial community are acquired from the environment, possibly from the host tree. These findings improve the knowledge about the bacterial community composition, and provide the bases to study the metabolic functions of these bacteria, as well as their interaction with these bark beetles.

Glatiramer Acetate (GA) is an immunomodulatory medicine approved for the treatment of multiple sclerosis, whose mechanisms of action are yet to be fully elucidated. GA is comprised of a complex mixture of polypeptides with different amino acid sequences and structures. The lack of sensible information about physicochemical characteristics of GA has contributed to its comprehensiveness complexity. Consequently, an unambiguous determination of distinctive attributes that define GA is of highest relevance towards dissecting its identity. Herein we conducted a study of characteristic GA heterogeneities throughout its manufacturing process (process signatures), revealing a strong impact of critical process parameters (CPPs) on the reactivity of amino acid precursors; reaction initiation and polymerization velocities; and peptide solubility, susceptibility to hydrolysis, and size-exclusion properties. Further, distinctive GA heterogeneities were correlated to defined immunological and toxicological profiles, revealing that GA possesses a unique repertoire of active constituents (epitopes) responsible of its immunological responses, whose modification lead to altered profiles. This novel approach established CPPs influence on intact GA peptide mixture, whose physicochemical identity cannot longer rely on reduced properties (based on complete or partial GA degradation), providing advanced knowledge on GA structural and functional relationships to ensure a consistent manufacturing of safe and effective products.

Diversification between islands and ecological radiation within islands are postulated to have occurred in the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) on the Canary Islands. In this study, the biogeographical pattern of 11 species of subsect. Macaronesicae and the genetic differentiation among five species were investigated to distinguish the potential mode and mechanism of diversification and speciation. The biogeographical patterns and genetic structure were examined using statistical dispersal-vicariance analysis, Bayesian phylogenetic analysis, reduced median-joining haplotype network analysis, and discriminant analysis of principal components. The gene flow between related species was evaluated with an isolation-with-migration model. The ancestral range of the species of subsect. Macaronesicae was inferred to be Tenerife and the Cape Verde Islands, and Tenerife-La Gomera acted as sources of diversity to other islands of the Canary Islands. Inter-island colonization of E. lamarckii among the western islands and a colonization of E. regis-jubae from Gran Canaria to northern Africa were revealed. Both diversification between islands and radiation within islands have been revealed in the Euphorbia species (sect. Aphyllis subsect. Macaronesicae) of the Canary Islands. It was clear that this group began the speciation process in Tenerife-La Gomera, and this process occurred with gene flow between some related species.