Conformation and membrane interaction studies of the potent antimicrobial and anticancer peptide palustrin-Ca.

Palustrin-Ca (GFLDIIKDTGKEFAVKILNNLKCKLAGGCPP) is a host defence peptide with potent antimicrobial and anticancer activities, first isolated from the skin of the American bullfrog Lithobates catesbeianus. The peptide is 31 amino acid residues long, cationic and amphipathic. Two-dimensional NMR spectroscopy was employed to characterise its three-dimensional structure in a 50/50% water/2,2,2-trifluoroethanol-[Formula: see text] mixture.

Bacterial degradation of the anti-depressant drug fluoxetine produces trifluoroacetic acid and fluoride ion.

Fluoxetine (FLX) is a blockbuster drug with annual sales in the billions of dollars. Its widespread use has resulted in its detection in water courses, where it impacts aquatic life. Investigations on the biodegradation of FLX by microorganisms are important, since augmentation of secondary wastewater treatment by an effective degrader may be one method of improving the drug's removal.

Biophysical study of the structure and dynamics of the antimicrobial peptide maximin 1.

Maximin 1 is a cationic, amphipathic antimicrobial peptide found in the skin secretions and brains of the Chinese red belly toad Bombina maxima. The 27 amino acid residue-long peptide is biologically interesting as it possesses a variety of biological activities, including antibacterial, antifungal, antiviral, antitumour and spermicidal activities. Its three-dimensional structural model was obtained in a 50/50% water/2,2,2-trifluoroethanol-d mixture using two-dimensional NMR spectroscopy.

ISGylation drives basal breast tumour progression by promoting EGFR recycling and Akt signalling.

ISG15 is an ubiquitin-like modifier that is associated with reduced survival rates in breast cancer patients. The mechanism by which ISG15 achieves this however remains elusive. We demonstrate that modification of Rab GDP-Dissociation Inhibitor Beta (GDI2) by ISG15 (ISGylation) alters endocytic recycling of the EGF receptor (EGFR) in non-interferon stimulated cells using CRISPR-knock out models for ISGylation.

A novel automated image analysis pipeline for quantifying morphological changes to the endoplasmic reticulum in cultured human cells.

Background: In mammalian cells the endoplasmic reticulum (ER) comprises a highly complex reticular morphology that is spread throughout the cytoplasm. This organelle is of particular interest to biologists, as its dysfunction is associated with numerous diseases, which often manifest themselves as changes to the structure and organisation of the reticular network. Due to its complex morphology, image analysis methods to quantitatively describe this organelle, and importantly any changes to it, are lacking.

Molecular Subtyping Combined with Biological Pathway Analyses to Study Regorafenib Response in Clinically Relevant Mouse Models of Colorectal Cancer.

Purpose: Regorafenib (REG) is approved for the treatment of metastatic colorectal cancer, but has modest survival benefit and associated toxicities. Robust predictive/early response biomarkers to aid patient stratification are outstanding. We have exploited biological pathway analyses in a patient-derived xenograft (PDX) trial to study REG response mechanisms and elucidate putative biomarkers.

Functional Metagenomic Screening for Antimicrobial Resistance in the Oral Microbiome.

A large proportion of bacteria, from a multitude of environments, are not yet able to be grown in the laboratory, and therefore microbiological and molecular biological investigations of these bacteria are challenging. A way to circumvent this challenge is to analyze the metagenome, the entire collection of DNA molecules that can be isolated from a particular environment or sample. This collection of DNA molecules can be sequenced and assembled to determine what is present and infer functional potential, or used as a PCR template to detect known target DNA and potentially unknown regions of DNA nearby those targets; however assigning functions to new or conserved hypothetical, functionally cryptic, genes is difficult.

APPTEST is a novel protocol for the automatic prediction of peptide tertiary structures.

Good knowledge of a peptide's tertiary structure is important for understanding its function and its interactions with its biological targets. APPTEST is a novel computational protocol that employs a neural network architecture and simulated annealing methods for the prediction of peptide tertiary structure from the primary sequence. APPTEST works for both linear and cyclic peptides of 5-40 natural amino acids.

Bacterial and Bacteriophage Antibiotic Resistance in Marine Bathing Waters in Relation to Rivers and Urban Streams.

Fecal pollution of surface water may introduce bacteria and bacteriophages harboring antibiotic resistance genes (ARGs) into the aquatic environment. Watercourses discharging into the marine environment, especially close to designated bathing waters, may expose recreational users to fecal pollution and therefore may increase the likelihood that they will be exposed to ARGs. This study compares the bacterial and bacteriophage ARG profiles of two rivers (River Tolka and Liffey) and two small urban streams (Elm Park and Trimleston Streams) that discharge close to two marine bathing waters in Dublin Bay.

PRR11 unveiled as a top candidate biomarker within the RBM3-regulated transcriptome in pancreatic cancer.

The outlook for patients with pancreatic cancer remains dismal. Treatment options are limited and chemotherapy remains standard of care, leading to only modest survival benefits. Hence, there is a great need to further explore the mechanistic basis for the intrinsic therapeutic resistance of this disease, and to identify novel predictive biomarkers.

Sex and brain region-specific regulation of serotonin transporter activity in synaptosomes in guanine nucleotide-binding protein G(q) alpha knockout mice.

The regulation of the serotonin transporter (SERT) by guanine nucleotide-binding protein alpha (Gα) q was investigated using Gαq knockout mice. In the absence of Gαq, SERT-mediated uptake of 5-hydroxytryptamine (5HT) was enhanced in midbrain and frontal cortex synaptosomes, but only in female mice. The mechanisms underlying this sexual dimorphism were investigated using quantitative western blot analysis revealing brain region-specific differences.

ENNAVIA is a novel method which employs neural networks for antiviral and anti-coronavirus activity prediction for therapeutic peptides.

Viruses represent one of the greatest threats to human health, necessitating the development of new antiviral drug candidates. Antiviral peptides often possess excellent biological activity and a favourable toxicity profile, and therefore represent a promising field of novel antiviral drugs. As the quantity of sequencing data grows annually, the development of an accurate in silico method for the prediction of peptide antiviral activities is important.

Direct Regulons of AtxA, the Master Virulence Regulator of Bacillus anthracis.

AtxA, the master virulence regulator of Bacillus anthracis, regulates the expression of three toxins and genes for capsule formation that are required for the pathogenicity of B. anthracis. Recent transcriptome analyses showed that AtxA affects a large number of genes on the chromosome and plasmids, suggesting a role as a global regulator.

Identifying Sources of Faecal Contamination in a Small Urban Stream Catchment: A Multiparametric Approach.

Small urban streams discharging in the proximity of bathing waters may significantly contribute to the deterioration of water quality, yet their impact may be overlooked. This study focuses on the Elm Park stream in the city of Dublin that is subject to faecal contamination by unidentified sources. The aim of the study was to identify a minimum number of "sentinel" sampling stations in an urban catchment that would provide the maximum amount of information regarding faecal pollution in the catchment.

Harnessing the Role of HDAC6 in Idiopathic Pulmonary Fibrosis: Design, Synthesis, Structural Analysis, and Biological Evaluation of Potent Inhibitors.

Idiopathic pulmonary fibrosis (IPF) is an interstitial lung disease characterized by a progressive-fibrosing phenotype. IPF has been associated with aberrant HDAC activities confirmed by our immunohistochemistry studies on HDAC6 overexpression in IPF lung tissues. We herein developed a series of novel HDAC6 inhibitors, having low inhibitory potency over HDAC1 and HDAC8, as potential pharmacological tools for IPF treatment.

Cunninghamella spp. produce mammalian-equivalent metabolites from fluorinated pyrethroid pesticides.

Cunninghamella spp. are fungi that are routinely used to model the metabolism of drugs. In this paper we demonstrate that they can be employed to generate mammalian-equivalent metabolites of the pyrethroid pesticides transfluthrin and β-cyfluthrin, both of which are fluorinated.

Decay of infectious SARS-CoV-2 and surrogates in aquatic environments.

The introduction of SARS-CoV-2 containing human stool and sewage into water bodies may raise public health concerns. However, assessment of public health risks by faecally contaminated water is limited by a lack of knowledge regarding the persistence of infectious SARS-CoV-2 in water. In the present study the decay rates of viable infectious SARS-CoV-2 and SARS-CoV-2 RNA were determined in river and seawater at 4 and 20°C.

Regulatory Mechanisms of the RNA Modification mA and Significance in Brain Function in Health and Disease.

RNA modifications have emerged as an additional layer of regulatory complexity governing the function of almost all species of RNA. -methyladenosine (mA), the addition of methyl groups to adenine residues, is the most abundant and well understood RNA modification. The current review discusses the regulatory mechanisms governing mA, how this influences neuronal development and function and how aberrant mA signaling may contribute to neurological disease.

Prognostic value of the 6-gene OncoMasTR test in hormone receptor-positive HER2-negative early-stage breast cancer: Comparative analysis with standard clinicopathological factors.

Aim: The aim of the study was to assess the prognostic performance of a 6-gene molecular score (OncoMasTR Molecular Score [OMm]) and a composite risk score (OncoMasTR Risk Score [OM]) and to conduct a within-patient comparison against four routinely used molecular and clinicopathological risk assessment tools: Oncotype DX Recurrence Score, Ki67, Nottingham Prognostic Index and Clinical Risk Category, based on the modified Adjuvant! Online definition and three risk factors: patient age, tumour size and grade.

Methods: Biospecimens and clinicopathological information for 404 Irish women also previously enrolled in the Trial Assigning Individualized Options for Treatment [Rx] were provided by 11 participating hospitals, as the primary objective of an independent translational study. Gene expression measured via RT-qPCR was used to calculate OMm and OM.

crAssphage as a human molecular marker to evaluate temporal and spatial variability in faecal contamination of urban marine bathing waters.

Bathing water quality may be negatively impacted by diffuse pollution arising from urban and agricultural activities and wildlife, it is therefore important to be able to differentiate between biological and geographical sources of faecal pollution. crAssphage was recently described as a novel human-associated microbial source tracking marker. This study aimed to evaluate the performance of the crAssphage marker in designated bathing waters.

Regulation of spp. biofilm growth by tryptophol and tyrosol.

Fungi belonging to the genus are often used as microbial models of mammalian metabolism owing to their ability to transform a range of xenobiotic compounds. Furthermore, under specific growth conditions species such as and grow as biofilms enabling a convenient semi-continuous production of valuable drug metabolites. However, the molecular mechanism of biofilm regulation is not understood, thus controlling biofilm thickness limits the productive applications of it.

Mycosands: Fungal diversity and abundance in beach sand and recreational waters - Relevance to human health.

The goal of most studies published on sand contaminants is to gather and discuss knowledge to avoid faecal contamination of water by run-offs and tide-retractions. Other life forms in the sand, however, are seldom studied but always pointed out as relevant. The Mycosands initiative was created to generate data on fungi in beach sands and waters, of both coastal and freshwater inland bathing sites.

3-Hydroxytyrosol regulates biofilm growth in Cunninghamella elegans.

In contrast to yeast biofilms, those of filamentous fungi are relatively poorly understood, in particular with respect to their regulation. Cunninghamella elegans is a filamentous fungus that is of biotechnological interest as it catabolises drugs and other xenobiotics in an analogous manner to animals; furthermore, it can grow as a biofilm enabling repeated batch biotransformations. Precisely how the fungus switches from planktonic to biofilm growth is unknown and the aim of this study was to shed light on the possible mechanism of biofilm regulation.

F NMR as a tool in chemical biology.

We previously reviewed the use of F NMR in the broad field of chemical biology [Cobb, S. L.; Murphy, C.

CHD2-Related CNS Pathologies.

Epileptic encephalopathies (EE) are severe epilepsy syndromes characterized by multiple seizure types, developmental delay and even regression. This class of disorders are increasingly being identified as resulting from de novo genetic mutations including many identified mutations in the family of chromodomain helicase DNA binding (CHD) proteins. In particular, several de novo pathogenic mutations have been identified in the gene encoding chromodomain helicase DNA binding protein 2 (CHD2), a member of the sucrose nonfermenting (SNF-2) protein family of epigenetic regulators.