Design,synthesis, and evaluation of guanylhydrazones as potential inhibitors or reactivators of acetylcholinesterase

Analogs of pralidoxime, which is a commercial antidote for intoxication from neurotoxic organophosphorus compounds, were designed, synthesized, characterized, and tested as potential inhibitors or reactivators of acetylcholinesterase (AChE) using the Ellman’s test, nuclear magnetic resonance, and molecular modeling. These analogs include 1-methylpyridine-2-carboxaldehyde hydrazone, 1-methylpyridine-2-carboxaldehyde guanylhydrazone, and six other guanylhydrazones obtained from different benzaldehydes. The results indicate that all compounds are weak AChE reactivators but relatively good AChE inhibitors. The most effective AChE inhibitor discovered was the guanylhydrazone derived from 2,4-dinitrobenzaldehyde and was compared with tacrine, displaying similar activity to this reference material. These results indicate that guanylhydrazones as well as future similar derivatives may function as drugs for the treatment of Alzheimer's disease.     

Structural mutation analysis of PTEN and its genotype‐phenotype correlations in endometriosis and cancer

The phosphatase and tensin homolog deleted on chromosome ten (PTEN) gene encodes a tumor suppressor phosphatase that has recently been found to be frequently mutated in patients with endometriosis, endometrial cancer and ovarian cancer. Here, we present the first computational analysis of 13 somatic missense PTEN mutations associated with these phenotypes. We found that a majority of the mutations are associated in conserved positions within the active site and are clustered within the signature motif, which contain residues that play a crucial role in loop conformation and are essential for catalysis. In silico analyses were utilized to identify the putative effects of these mutations. In addition, coarse‐grained models of both wild‐type (WT) PTEN and mutants were constructed using elastic network models to explore the interplay of the structural and global dynamic effects that the mutations have on the relationship between genotype and phenotype. The effects of the mutations reveal that the local structure and interactions affect polarity, protein structure stability, electrostatic surface potential, and global dynamics of the protein. Our results offer new insight into the role in which PTEN missense mutations contribute to the molecular mechanism and genotypic‐phenotypic correlation of endometriosis, endometrial cancer, and ovarian cancer. Proteins 2016; 84:1625–1643. © 2016 Wiley Periodicals, Inc.     

Trichoderma aureoviride URM 5158 and Trichoderma hamatum URM 6656 are Biocontrol Agents that act against Cassava Root rot through different Mechanisms

Trichoderma has been used to manage a large number of pathogens, but there is a gap in the mechanisms used by these biocontrol agents regarding the physiological response of cassava plants (Manihot esculenta) when it is subjected to cassava root rot. The aims of this study were to investigate the antagonist activity of ten Trichoderma isolates against Fusarium solani on potato dextrose Agar (PDA), to quantify the chitinase production, to select and test in vivo the best isolate from each experiment and to assess the physiological response of cassava to the production of oxidative enzyme complex production (ascorbate peroxidase, catalase, peroxidase and polyphenol oxidase). All Trichoderma isolates have shown competitive capability against F. solani, and Trichoderma hamatum URM 6656 showed the highest inhibition of pathogen growth (88.91%). All isolates have shown chitinase activity, but Trichoderma aureoviride URM 5158 produced the highest amount of chitinase. T. hamatum URM 6656 and T. aureoviride URM 5158 were selected to be applied in vivo. The two Trichoderma strains reduced 64 and 60% of the disease severity in the shoot and 82 and 84% in the root. Cassava plants infected with Trichoderma have shown the highest peroxidase and ascorbate peroxidase production. Our results have indicated that T. aureoviride URM 5158 is an effective biocontrol agent against cassava root rot caused by F. solani, because it presented competitive antagonist capability in vitro, the highest chitinase production, and reduced the cassava root rot severity. The application of T. aureoviride has led to the maximum enzyme activity of reactive oxygen species group in cassava plants.     

Photocatalytic Properties under Sunlight of Heterostructures AgCl/CuO Obtained by Sonochemical Method

Plasmonics - AgCl/CuO heterostructures were synthesized via a sonochemical method. AgCl/CuO molar compositions of 1:1 and 2:1 were prepared, respectively. Such compositions were prepared using...     

Methane yield and species diversity dynamics of perennial wild plant mixtures established alone,under cover crop maize (Zea mays L.), and after spring barley (Hordeum vulgare L.)

The cultivation of perennial wild plant mixtures (WPMs) in biogas cropping systems dominated by maize (Zea mays L.) restores numerous ecosystem functions and improves both spatial and temporal agrobiodiversity. In addition, the colorful appearance of WPM can help enhance landscape beauty. However, their methane yield per hectare (MYH) varies greatly and amounts to only about 50% that of maize. This study aimed at decreasing MYH variability and increasing accumulated MYH of WPM by optimizing the establishment method. A field trial was established in southwest Germany in 2014, and is still running. It tested the effects of three WPM establishment procedures (E1: alone [without maize, in May], E2: undersown in cover crop maize [in May], E3: WPM sown after whole‐crop harvest of spring barley [Hordeum vulgare L.] in June) on both MYH and species diversity of two WPMs [S1, S2]). Mono‐cropped maize and cup plant (Silphium perfoliatum L.) were used as reference crops. Of the WPM treatments tested, S2E2 achieved the highest (19,296 , 60.5% of maize) and S1E1 the lowest accumulated MYH (8,156 , 25.6% of maize) in the years 2014–2018. Cup plant yielded slightly higher than S2E2 (19,968 , 62.6% of maize). In 2014, the WPM sown under maize did not significantly affect the cover crop performance. From 2015 onward, E1 and E2 had comparable average annual MYH and average annual number of WPM species. With a similar accumulated MYH but significantly higher number of species (3.5–10.2), WPM S2E2 outperformed cup plant. Overall, the long‐term MYH performance of WPM cultivation for biogas production can be significantly improved by undersowing with maize as cover crop. This improved establishment method could help facilitate the implementation of WPM cultivation for biogas production and thus reduce the trade‐off between bioenergy and biodiversity.     

Intracellular accumulation of amino acids increases synaptic potentials in rat hippocampal slices

Amino Acids - The application of high concentrations of taurine induces long-lasting potentiation of synaptic responses and axon excitability. This phenomenon seems to require the contribution of a...     

Metabolism and foraging strategies of mid‐latitude mesozooplankton during cyanobacterial blooms as revealed by fatty acids,amino acids,and their stable carbon isotopes

Increasing sea surface temperatures (SST) and blooms of lipid‐poor, filamentous cyanobacteria can change mesozooplankton metabolism and foraging strategies in marine systems. Lipid shortage and imbalanced diet may challenge the build‐up of energy pools of lipids and proteins, and access to essential fatty acids (FAs) and amino acids (AAs) by copepods. The impact of cyanobacterial blooms on individual energy pools was assessed for key species temperate Temora longicornis and boreal Pseudo‐/Paracalanus spp. that dominated field mesozooplankton communities isolated by seasonal stratification in the central Baltic Sea during the hot and the cold summer. We looked at (a) total lipid and protein levels, (b) FA trophic markers and AA composition, and (c) compound‐specific stable carbon isotopes (δ¹³C) in bulk mesozooplankton and in a subset of parameters in particulate organic matter. Despite lipid‐poor cyanobacterial blooms, the key species were largely able to cover both energy pools, yet a tendency of lipid reduction was observed in surface animals. Omni‐ and carnivory feeding modes, FA trophic makers, and δ¹³C patterns in essential compounds emphasized that cyanobacterial FAs and AAs have been incorporated into mesozooplankton mainly via feeding on mixo‐ and heterotrophic (dino‐) flagellates and detrital complexes during summer. Foraging for essential highly unsaturated FAs from (dino‐) flagellates may have caused night migration of Pseudo‐/Paracalanus spp. from the deep subhalocline waters into the upper waters. Only in the hot summer (SST>19.0°C) was T. longicornis submerged in the colder subthermocline water (~4°C). Thus, the continuous warming trend and simultaneous feeding can eventually lead to competition on the preferred diet by key copepod species below the thermocline in stratified systems. A comparison of δ¹³C patterns of essential AAs in surface mesozooplankton across sub‐basins of low and high cyanobacterial biomasses revealed the potential of δ¹³C‐AA isoscapes for studies of commercial fish feeding trails across the Baltic Sea food webs.     

Metabolically similar cohorts of bacteria exhibit strong cooccurrence patterns with diet items and eukaryotic microbes in lizard guts

Gut microbiomes perform essential services for their hosts, including helping them to digest food and manage pathogens and parasites. Performing these services requires a diverse and constantly changing set of metabolic functions from the bacteria in the microbiome. The metabolic repertoire of the microbiome is ultimately dependent on the outcomes of the ecological interactions of its member microbes, as these interactions in part determine the taxonomic composition of the microbiome. The ecological processes that underpin the microbiome's ability to handle a variety of metabolic challenges might involve rapid turnover of the gut microbiome in response to new metabolic challenges, or it might entail maintaining sufficient diversity in the microbiome that any new metabolic demands can be met from an existing set of bacteria. To differentiate between these scenarios, we examine the gut bacteria and resident eukaryotes of two generalist‐insectivore lizards, while simultaneously identifying the arthropod prey each lizard was digesting at the time of sampling. We find that the cohorts of bacteria that occur significantly more or less often than expected with arthropod diet items or eukaryotes include bacterial species that are highly similar to each other metabolically. This pattern in the bacterial microbiome could represent an early step in the taxonomic shifts in bacterial microbiome that occur when host lineages change their diet niche over evolutionary timescales.