Biochemical and structural characterization of enzymes in the 4-hydroxybenzoate catabolic pathway of lignin-degrading white-rot fungi.

White-rot fungi (WRF) are the most efficient lignin-degrading organisms in nature. However, their capacity to use lignin-related aromatic compounds, such as 4-hydroxybenzoate, as carbon sources has only been described recently. Previously, the hydroxyquinol pathway was proposed for the bioconversion of these compounds in fungi, but gene- and structure-function relationships of the full enzymatic pathway remain uncharacterized in any single fungal species.

Understanding the Catalytic Efficiency of Two Polyester Degrading Enzymes: An Experimental and Theoretical Investigation.

The discovery of novel plastic degrading enzymes commonly relies on comparing features of the primary sequence to those of known plastic degrading enzymes. However, this approach cannot always guarantee success. This is exemplified by the different degradation rates of the two polymers poly(ethylene terephthalate) (PET) and polybutylene succinate (PBS) by two hydrolases: PETase from and Cut from .

Kalata B1 Enhances Temozolomide Toxicity to Glioblastoma Cells.

Glioblastoma (GBM) is the most aggressive cancer originating in the brain, but unfortunately combination treatments with resection, radiation, and chemotherapy are relatively ineffective. Therefore, novel methods of adjuvant therapy are critically needed. Cyclotides are plant-derived circular peptides that chemosensitize drug-resistant breast cancer to doxorubicin.

A microRNA diagnostic biomarker for amyotrophic lateral sclerosis.

Blood-based diagnostic biomarkers for amyotrophic lateral sclerosis will improve patient outcomes and positively impact novel drug development. Critical to the development of such biomarkers is robust method validation, optimization and replication with adequate sample sizes and neurological disease comparative blood samples. We sought to test an amyotrophic lateral sclerosis biomarker derived from diverse samples to determine if it is disease specific.

Cyanotoxin accumulation and growth patterns of biocrust communities under variable environmental conditions.

Biocrusts dominate the soil surface in deserts and are composed of diverse microbial communities that provide important ecosystem services. Cyanobacteria in biocrusts produce many secondary metabolites, including the neurotoxins BMAA, AEG, DAB, anatoxin-a() (guanitoxin), and the microcystin hepatotoxins, all known or suspected to cause disease or illness in humans and other animals. We examined cyanobacterial growth and prevalence of these toxins in biocrusts at millimeter-scales, under a desert-relevant illumination gradient.

Synthesis of the large pore aluminophosphate STA-1 and its application as a catalyst for the Beckmann rearrangement of cyclohexanone oxime.

The preparation of stable large pore aluminophosphate (AlPO) zeotypes offers materials for applications in adsorption and catalysis. Here we report the synthesis of the pure AlPO with the SAO topology type (AlPO STA-1) using ,'-diethylbicyclo[2.2.

Cyanotoxin Analysis of Air Samples from the Great Salt Lake.

The Great Salt Lake in Utah is the largest saline lake in the Western hemisphere and one of the largest terminal lakes in the world. Situated at the eastern edge of the Great Basin, it is a remnant of the freshwater Lake Bonneville whose water level precipitously lowered about 12,000 years ago due to a natural break in Red Rock pass to the north. It contains a diverse assemblage of cyanobacteria which vary spatially dependent on salinity.

The Effects of Long-term, Low-dose β-N-methylamino-L-alanine (BMAA) Exposures in Adult SOD Transgenic Zebrafish.

β-N-Methylamino-L-alanine (BMAA) is a non-proteinogenic amino acid produced by cyanobacteria, which has been implicated in several neurodegenerative diseases, including amyotrophic lateral sclerosis (ALS). It is postulated that chronic exposure to BMAA can lead to formation of protein aggregates, oxidative stress, and/or excitotoxicity, which are mechanisms involved in the etiology of ALS. While specific genetic mutations are identified in some instances of ALS, it is likely that a combination of genetic and environmental factors, such as exposure to the neurotoxin BMAA, contributes to disease.

L1CAM immunocapture generates a unique extracellular vesicle population with a reproducible miRNA fingerprint.

Micro RNAs (miRNAs) are short, non-coding RNAs with significant potential as diagnostic and prognostic biomarkers. However, a lack of reproducibility across studies has hindered their introduction into clinical settings. Inconsistencies between studies include a lack of consensus on the miRNAs associated with a specific disease and the direction of regulation.

Detection of β-N-methylamino-l-alanine in postmortem olfactory bulbs of Alzheimer's disease patients using UHPLC-MS/MS: An autopsy case-series study.

Introduction: Cyanobacterial blooms produce toxins that may become aerosolized, increasing health risks through inhalation exposures. Health related effects on the lower respiratory tract caused by these toxins are becoming better understood. However, nasal exposures to cyanotoxins remain understudied, especially for those with neurotoxic potential.

L-Serine Influences Epigenetic Modifications to Improve Cognition and Behaviors in Growth Hormone-Releasing Hormone Knockout Mice.

Neurodegenerative diseases feature changes in cognition, and anxiety-like and autism-like behaviors, which are associated with epigenetic alterations such as DNA methylation and histone modifications. The amino acid L-serine has been shown to have beneficial effects on neurological symptoms. Here, we found that growth hormone-releasing hormone knockout (GHRH-KO) mice, a GH-deficiency mouse model characterized by extended lifespan and enhanced insulin sensitivity, showed a lower anxiety symptom and impairment of short-term object recognition memory and autism-like behaviors.

Sourcing thermotolerant poly(ethylene terephthalate) hydrolase scaffolds from natural diversity.

Enzymatic deconstruction of poly(ethylene terephthalate) (PET) is under intense investigation, given the ability of hydrolase enzymes to depolymerize PET to its constituent monomers near the polymer glass transition temperature. To date, reported PET hydrolases have been sourced from a relatively narrow sequence space. Here, we identify additional PET-active biocatalysts from natural diversity by using bioinformatics and machine learning to mine 74 putative thermotolerant PET hydrolases.

miRNA extracted from extracellular vesicles is a robust biomarker of amyotrophic lateral sclerosis.

Background And Objectives: We examined miRNA biomarkers for ALS extracted from extracellular vesicles in blood samples using a large and diverse patient and control population. Different blood collection and storage protocols by different investigators could impact repeatability of miRNA analysis. We tested the hypotheses that miRNA extracted from extracellular vesicles using immunoaffinity purification techniques are robust and repeatable across investigators, laboratories and in a broad ALS population.

Understanding the Anion-Templated, OSDA-Free, Interzeolite Conversion Synthesis of High Silica Zeolite ZK-5.

High silica zeolite ZK-5 (framework Si/Al=4.8) has been prepared by interzeolite conversion from ultrastable zeolite Y via a co-templating route using alkali metal cations and nitrate anions but without organic structure directing agents. The mechanism, which involves zeolite framework - alkali metal cation - nitrate anion ordering, has been established by a combination of chemical and thermal analyses, Raman spectroscopy, computational modelling, and X-ray powder diffraction.

A possible blood plasma biomarker for early-stage Alzheimer's disease.

We sought to identify a usable biomarker from blood samples to characterize early-stage Alzheimer's disease (AD) patients, in order to facilitate rapid diagnosis, early therapeutic intervention, and monitoring of clinical trials. We compared metabolites from blood plasma in early-stage Alzheimer's disease patients with blood plasma from healthy controls using two different analytical platforms: Amino Acid Analyzer and Tandem Mass-Spectrometer. Early-stage Alzheimer's patient blood samples were obtained during an FDA-approved Phase IIa clinical trial (Clinicaltrial.

Cyclotides Chemosensitize Glioblastoma Cells to Temozolomide.

Glioblastoma multiforme (GBM) is the most aggressive cancer originating in the brain, with a median survival of 12 months. Most patients do not respond to or develop resistance to the only effective chemotherapeutic drug, temozolomide (TMZ), used to treat gliomas. Novel treatment methods are critically needed.

BMAA, Methylmercury, and Mechanisms of Neurodegeneration in Dolphins: A Natural Model of Toxin Exposure.

Dolphins are well-regarded sentinels for toxin exposure and can bioaccumulate a cyanotoxin called β--methylamino-l-alanine (BMAA) that has been linked to human neurodegenerative disease. The same dolphins also possessed hallmarks of Alzheimer's disease (AD), suggesting a possible association between toxin exposure and neuropathology. However, the mechanisms of neurodegeneration in dolphins and the impact cyanotoxins have on these processes are unknown.

Cyanotoxins and the Nervous System.

Cyanobacteria are capable of producing a wide range of bioactive compounds with many considered to be toxins. Although there are a number of toxicological outcomes with respect to cyanobacterial exposure, this review aims to examine those which affect the central nervous system (CNS) or have neurotoxicological properties. Such exposures can be acute or chronic, and we detail issues concerning CNS entry, detection and remediation.

A comparison of the efficiency of RNA extraction from extracellular vesicles using the Qiagen RNeasy MinElute versus Enzymax LLC RNA Tini Spin columns and qPCR of miRNA.

One consequence of the current severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic is an interruption to the supply of laboratory consumables, particularly those used for RNA extraction. This category includes column-based RNA extraction kits designed to retain short RNA species (defined as having fewer than 200 nucleotides), from small sample volumes, e.g.

BMAA, Neurodegeneration, and Neuroprotection.

In this volume, studies springing from a BMAA symposium held in Salt Lake City, Utah, in April 2019 are presented. Although most studies of neurotoxicity consider the effects of BMAA as an isolated molecule, it is now known that environmental exposures can be to a combination of BMAA-related molecules, including enantiomers, isomers, other co-occurring cyanotoxins, and BMAA carbamates. Within the body, BMAA may exist in equilibrium with α- and β-carbamates formed in the presence of bicarbonate.

An miRNA fingerprint using neural-enriched extracellular vesicles from blood plasma: towards a biomarker for amyotrophic lateral sclerosis/motor neuron disease.

Biomarkers for amyotrophic lateral sclerosis/motor neuron disease (ALS/MND) are currently not clinically available for disease diagnosis or analysis of disease progression. If identified, biomarkers could improve patient outcomes by enabling early intervention and assist in the determination of treatment efficacy. We hypothesized that neural-enriched extracellular vesicles could provide microRNA (miRNA) fingerprints with unequivocal signatures of neurodegeneration.