Overcoming Challenges with Biochemical Studies of Selenocysteine and Selenoproteins.

Selenocysteine (Sec) is an essential amino acid that distinguishes itself from cysteine by a selenium atom in place of a sulfur atom. This single change imparts distinct chemical properties to Sec which are crucial for selenoprotein (Sec-containing protein) function. These properties include a lower p, enhanced nucleophilicity, and reversible oxidation.

High-throughput transposon mutagenesis in the family Enterobacteriaceae reveals core essential genes and rapid turnover of essentiality.

The Enterobacteriaceae are a scientifically and medically important clade of bacteria, containing the model organism , as well as major human pathogens including and . Essential gene sets have been determined for several members of the Enterobacteriaceae, with the Keio single-gene deletion library often regarded as a gold standard. However, it remains unclear how gene essentiality varies between related strains and species.

Rigid Macrocycle Metal Complexes as CXCR4 Chemokine Receptor Antagonists: Influence of Ring Size.

Understanding the role of chemokine receptors in health and disease has been of increasing interest in recent years. Chemokine receptor CXCR4 has been extensively studied because of its defined role in immune cell trafficking, HIV infection, inflammatory diseases, and cancer progression. We have developed high affinity rigidified CXCR4 antagonists that incorporate metal ions to optimize the binding interactions with the aspartate side chains at the extracellular surface of the CXCR4 chemokine receptor and increase the residence time.

A synthetic peptide mimic kills Candida albicans and synergistically prevents infection.

More than two million people worldwide are affected by life-threatening, invasive fungal infections annually. Candida species are the most common cause of nosocomial, invasive fungal infections and are associated with mortality rates above 40%. Despite the increasing incidence of drug-resistance, the development of novel antifungal formulations has been limited.

The Perspectives of Individuals with Chronic Stroke on Motor Recovery: A Qualitative Analysis.

The priorities of individuals with chronic stroke are not always reflected in clinical practice. This study provides insight into meaningful factors related to long-term motor recovery in stroke survivors. Thirty individuals with chronic stroke participated in semi-structured interviews about movement, recovery, and barriers to and facilitators of mobility and paretic arm use.

Spectrum of activity and mechanisms of azole-bisphosphonate synergy in pathogenic .

Unlabelled: Candidiasis places a significant burden on human health and can range from common superficial vulvovaginal and oral infections to invasive diseases with high mortality. The most common species implicated in human disease is , but other species like are emerging. The use of azole antifungals for treatment is limited by increasing rates of resistance.

High-precision screening and sorting of double emulsion droplets.

Mounting evidence suggests that cell populations are extremely heterogeneous, with individual cells fulfilling different roles within the population. Flow cytometry (FC) is a high-throughput tool for single-cell analysis that works at high optical resolution. Sub-populations with unique properties can be screened, isolated and sorted through fluorescence-activated cell sorting (FACS), using intracellular fluorescent products or surface-tagged fluorescent products of interest.

Transposons Carrying the Aminoglycoside and Beta-Lactam Resistance Genes in .

This study examines the genetic contexts and evolutionary steps responsible for the formation of the widely spread transposon Tn carrying and which confers resistance to beta-lactam and aminoglycoside antibiotics in Gram-negative bacteria. The and genes were found in several transposons. They were first observed within an IS bounded 3.

The 3' UTR of vigR is required for virulence in Staphylococcus aureus and has expanded through STAR sequence repeat insertions.

Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) are alarmingly common, and treatment is confined to last-line antibiotics. Vancomycin is the treatment of choice for MRSA bacteremia, and treatment failure is often associated with vancomycin-intermediate S. aureus isolates.

Low-molecular-weight thiol transferases in redox regulation and antioxidant defence.

Low-molecular-weight (LMW) thiols are produced in all living cells in different forms and concentrations. Glutathione (GSH), coenzyme A (CoA), bacillithiol (BSH), mycothiol (MSH), ergothioneine (ET) and trypanothione T(SH) are the main LMW thiols in eukaryotes and prokaryotes. LMW thiols serve as electron donors for thiol-dependent enzymes in redox-mediated metabolic and signaling processes, protect cellular macromolecules from oxidative and xenobiotic stress, and participate in the reduction of oxidative modifications.

A method to correct for local alterations in DNA copy number that bias functional genomics assays applied to antibiotic-treated bacteria.

Functional genomics techniques, such as transposon insertion sequencing and RNA-sequencing, are key to studying relative differences in bacterial mutant fitness or gene expression under selective conditions. However, certain stress conditions, mutations, or antibiotics can directly interfere with DNA synthesis, resulting in systematic changes in local DNA copy numbers along the chromosome. This can lead to artifacts in sequencing-based functional genomics data when comparing antibiotic treatment to an unstressed control.

Wearable Technology to Capture Arm Use of People With Stroke in Home and Community Settings: Feasibility and Early Insights on Motor Performance.

Objective: The objectives of this study were to establish the short-term feasibility and usability of wrist-worn wearable sensors for capturing the arm and hand activity of people with stroke and to explore the association between factors related to the use of the paretic arm and hand.

Methods: Thirty people with chronic stroke were monitored with wrist-worn wearable sensors for 12 hours per day for a 7-day period. Participants also completed standardized assessments to capture stroke severity, arm motor impairments, self-perceived arm use, and self-efficacy.

Timing of High-Dose-Rate Brachytherapy With External Beam Radiation Therapy in Patients With Intermediate- and High-Risk Localized Prostate Cancer and Its Effects on Toxicity and Quality of Life: A Randomized Controlled Trial (THEPCA).

Purpose: High-dose-rate brachytherapy (HDR-BT) and external beam radiation therapy (EBRT) are effective treatments for prostate cancer but cause genitourinary (GU) and gastrointestinal (GI) toxicities. There is no consensus on the timing of HDR-BT in relation to EBRT and the effect of sequencing on patients. The primary objective was to assess differences, if any, in the incidence of grade (G) 3 or higher GU toxicities from treatment.

A figurational approach to environmental sustainability in the context of sport.

Discourses around environmental sustainability and climate change are increasingly prominent in the sports sector, with a growing range of sports organisations developing policies to address these issues. This paper contends that figurational (or process) sociology can offer a useful framework for examining the development of policy as a process in the context of sport and, specifically, mega-events. The Olympic Games serve as an example for purposes of contextualisation, illustrating four interconnected dimensions of figurational sociology: lengthening chains of interdependence, established-outsider power relations, internalisation of social values, and unintended consequences.

Deciphering the Role of Selenoprotein M.

Selenocysteine (Sec), the 21st amino acid, is structurally similar to cysteine but with a sulfur to selenium replacement. This single change retains many of the chemical properties of cysteine but often with enhanced catalytic and redox activity. Incorporation of Sec into proteins is unique, requiring additional translation factors and multiple steps to insert Sec at stop (UGA) codons.

A metric for characterizing the arm nonuse workspace in poststroke individuals using a robot arm.

An overreliance on the less-affected limb for functional tasks at the expense of the paretic limb and in spite of recovered capacity is an often-observed phenomenon in survivors of hemispheric stroke. The difference between capacity for use and actual spontaneous use is referred to as arm nonuse. Obtaining an ecologically valid evaluation of arm nonuse is challenging because it requires the observation of spontaneous arm choice for different tasks, which can easily be influenced by instructions, presumed expectations, and awareness that one is being tested.

Systematic analyses identify modes of action of ten clinically relevant biocides and antibiotic antagonism in Acinetobacter baumannii.

Concerns exist that widespread use of antiseptic or disinfectant biocides could contribute to the emergence and spread of multidrug-resistant bacteria. To investigate this, we performed transposon-directed insertion-site sequencing (TraDIS) on the multidrug-resistant pathogen, Acinetobacter baumannii, exposed to a panel of ten structurally diverse and clinically relevant biocides. Multiple gene targets encoding cell envelope or cytoplasmic proteins involved in processes including fatty acid biogenesis, multidrug efflux, the tricarboxylic acid cycle, cell respiration and cell division, were identified to have effects on bacterial fitness upon biocide exposure, suggesting that these compounds may have intracellular targets in addition to their known effects on the cell envelope.

Infrared thermography as a diagnostic tool to detect cranial cruciate ligament deficiency in dogs.

Cranial cruciate ligament (CCL) disease is the leading cause of canine lameness. Diagnosis is based on physical examination and diagnostic imaging findings. Limitations of diagnostic modalities, including patient temperament, cost, availability, and need for general anesthesia, preclude their use for many patients.

The Antimicrobial Properties of Pd - and Ru -pyta Complexes.

Infections associated with antimicrobial resistance (AMR) are poised to become the leading cause of death in the next few decades, a scenario that can be ascribed to two phenomena: antibiotic over-prescription and a lack of antibiotic drug development. The crowd-sourced initiative Community for Open Antimicrobial Drug Discovery (CO-ADD) has been testing research compounds contributed by researchers around the world to find new antimicrobials to combat AMR, and during this campaign has found that metallodrugs might be a promising, yet untapped source. To this end, we submitted 18 Pd - and Ru -pyridyl-1,2,3-triazolyl complexes that were developed as catalysts to assess their antimicrobial properties.

Portrait of a killer: Uncovering resistance mechanisms and global spread of Acinetobacter baumannii.

Antibiotic resistance is a growing global concern in the field of medicine as it renders bacterial infections difficult to treat and often more severe. Acinetobacter baumannii is a gram-negative bacterial pathogen causing a wide range of infections, including pneumonia, sepsis, urinary tract infections, and wound infections. A.

Demonstration of the Managing for Daily Improvement Quality Improvement Methodology in an Alcohol Withdrawal Protocol Audit.

Background: The Clinical Institute Withdrawal Assessment for Alcohol, Revised (CIWA-Ar) is an assessment tool designed to standardize care and minimize the risk of complications in patients experiencing alcohol withdrawal. After discovering an increase in medication errors and late assessments under this protocol, pharmacists at a 218-bed community hospital performed an audit of protocol compliance using a performance improvement methodology known as Managing for Daily Improvement (MDI).

Methods: A daily audit of CIWA-Ar protocol compliance was performed across all hospital units, followed by discussions with frontline nurses regarding barriers to compliance.