High-throughput optimisation of protein secretion in yeast via an engineered biosensor.

Secretion of high-value proteins and enzymes is fundamental to the synthetic biology economy, allowing continuous fermentation during production and protein purification without cell lysis. Most eukaryotic protein secretion is encoded by an N-terminal signal peptide (SP); however, the strong impact of SP sequence variation on the secretion efficiency of a given protein is not well defined. Despite high natural SP sequence diversity, most recombinant protein secretion systems use only a few well-characterised SPs.

Sex-specific Regulation of Fentanyl Reward by the Circadian Transcription Factor NPAS2.

Synthetic opioids like fentanyl are highly potent and prevalent in the illicit drug market, leading to tolerance, dependence, and opioid use disorder (OUD). Chronic opioid use disrupts sleep and circadian rhythms, which persist even during treatment and abstinence, increasing the risk of relapse. The body's molecular clock, regulated by transcriptional and translational feedback loops, controls various physiological processes, including the expression of endogenous opioids and their receptors.

Getting help early: An online mental health self-assessment tool for young people.

Background: Online self-assessments are becoming more popular. They can serve as a screening tool for specific conditions or assess mental health more broadly but often lack in depth evaluation.

Methods: This study presents preliminary data from an online self-assessment tool for young people within the age range of 12-30 years (Link: redcap.

Delayed development of spinal stenosis at the spinal cord stimulator percutaneous lead entry point: case report and literature review.

Background: Spinal cord stimulation (SCS) is an efficacious treatment for various refractory chronic pain syndromes. Serious complications including spinal cord compression (SCC) are rare with 19 previous reports which are mainly attributed to fibrotic scar tissue formation at the distal end of the leads at the location of the contacts. We report a case of SCC following SCS implantation at the lead entry location secondary to a delayed progression of spinal canal stenosis.

Controlled oxygen delivery to power tissue regeneration.

Oxygen plays a crucial role in human embryogenesis, homeostasis, and tissue regeneration. Emerging engineered regenerative solutions call for novel oxygen delivery systems. To become a reality, these systems must consider physiological processes, oxygen release mechanisms and the target application.

Identification and Characterization of a Bacterial Periplasmic Solute Binding Protein That Binds l-Amino Acid Amides.

Periplasmic solute-binding proteins (SBPs) are key ligand recognition components of bacterial ATP-binding cassette (ABC) transporters that allow bacteria to import nutrients and metabolic precursors from the environment. Periplasmic SBPs comprise a large and diverse family of proteins, of which only a small number have been empirically characterized. In this work, we identify a set of 610 unique uncharacterized proteins within the SBP_bac_5 family that are found in conserved operons comprising genes encoding (i) ABC transport systems and (ii) putative amidases from the FmdA_AmdA family.

Improving feedback literacy in a primary care rotation.

Primary care education is a unique clinical experience for medical students. It is community-based and provides an opportunity for students to learn consultation skills with multiple sources of workplace-based feedback. Meaningful and demonstrable utilisation of this feedback by students remains an educational challenge.

Forensic investigations of disasters: Past achievements and new directions.

Unlabelled: In the 2020s, understanding disaster risk requires a strong and clear recognition of values and goals that influence the use of political and economic power and social authority to guide growth and development. This configuration of values, goals, power and authority may also lead to concrete drivers of risk at any one time. Building on previous disaster risk frameworks and experiences from practice, since 2010, the 'Forensic Investigations of Disasters (FORIN)' approach has been developed to support transdisciplinary research on the transformational pathways societies may follow to recognise and address root causes and drivers of disaster risk.

Development and implementation of the lung volume reduction pulmonary rehabilitation tool to identify eligibility for lung volume reduction in people with chronic obstructive pulmonary disease during pulmonary rehabilitation.

Background: Completion of pulmonary rehabilitation is recognised in chronic obstructive pulmonary disease (COPD) guidelines as a key opportunity to consider systematically whether a respiratory review to assess potential suitability for a lung volume reduction (LVR) procedure might be appropriate. We describe the development of a simple decision-support tool (the LVR-PR tool) to aid clinicians working in pulmonary rehabilitation, to operationalise this process.

Methods: We took an iterative mixed methods approach, which was partnership-based and involved an initial consensus survey, focus groups and an observational study cohort at multiple pulmonary rehabilitation centres.

The extinct Sicilian wolf shows a complex history of isolation and admixture with ancient dogs.

The Sicilian wolf remained isolated in Sicily from the end of the Pleistocene until its extermination in the 1930s-1960s. Given its long-term isolation on the island and distinctive morphology, the genetic origin of the Sicilian wolf remains debated. We sequenced four nuclear genomes and five mitogenomes from the seven existing museum specimens to investigate the Sicilian wolf ancestry, relationships with extant and extinct wolves and dogs, and diversity.

Oxygen in interstitial lung diseases.

Domiciliary oxygen is essential in the care of hypoxaemic interstitial lung disease (ILD) patients. Guidelines concur in advising prescription of long-term oxygen therapy (LTOT) for ILD patients with severe hypoxaemia at rest, in view of its beneficial impact on breathlessness/disability and extrapolating potential survival benefits seen in COPD patients. A less severe hypoxaemia threshold for initiation of LTOT is recommended for patients with pulmonary hypertension (PH)/right heart failure, requiring careful evaluation in all ILD patients.

Chemistry-led investigations into the mode of action of NAMPT activators, resulting in the discovery of non-pyridyl class NAMPT activators.

The cofactor nicotinamide adenine dinucleotide (NAD) plays a key role in a wide range of physiological processes and maintaining or enhancing NAD levels is an established approach to enhancing healthy aging. Recently, several classes of nicotinamide phosphoribosyl transferase (NAMPT) activators have been shown to increase NAD levels and and to demonstrate beneficial effects in animal models. The best validated of these compounds are structurally related to known urea-type NAMPT inhibitors, however the basis for the switch from inhibitory activity to activation is not well understood.

An overview of dynamical methods for studying transitions between states in sheared plasma flows.

The self-organization of structures in a tokamak plasma as it undergoes an [Formula: see text]-mode transition shows properties similar to simpler shear flow configurations. We will describe recent dynamical studies of plasma shear flows, including the idea of tracking the edge of chaos that separates two bistable states, computing the nonlinear minimal seed that can lead to turbulence, finding the attractor solution on the edge and seeing how starting from this solution we can understand the stability of relative period orbits that permeate the turbulent basin of attraction. We present a modus operandi developed for these simple configurations that can be adapted to understand the [Formula: see text]-mode transition.

for fairness in digital health apps.

Digital mental health applications promise scalable and cost-effective solutions to mitigate the gap between the demand and supply of mental healthcare services. However, very little attention is paid on differential impact and potential discrimination in digital mental health services with respect to different sensitive user groups (e.g.

Cat Scratch Disease: 9 Years of Experience at a Pediatric Center.

Background: A more complete understanding of the epidemiology, risk factors, and clinical features of cat scratch disease (CSD) in children could help guide patient care.

Methods: We conducted a retrospective analysis of children presenting to a tertiary pediatric hospital system in Atlanta, Georgia between January 1, 2010 and December 31, 2018 who had serology, polymerase chain reaction, and/or cytopathological results consistent with a infection. We also retrospectively reviewed veterinary diagnostic results performed at the University of Georgia from 2018 to 2020 to ascertain the burden of bartonellosis in companion animals within the state.

The effect of renewable energy incorporation on power grid stability and resilience.

Contemporary proliferation of renewable power generation is causing an overhaul in the topology, composition, and dynamics of electrical grids. These low-output, intermittent generators are widely distributed throughout the grid, including at the household level. It is critical for the function of modern power infrastructure to understand how this increasingly distributed layout affects network stability and resilience.

Discovery and structure-activity relationships of a novel oxazolidinone class of bacterial type II topoisomerase inhibitors.

There is an increasingly urgent and unmet medical need for novel antibiotic drugs that tackle infections caused by multidrug-resistant (MDR) pathogens. Novel bacterial type II topoisomerase inhibitors (NBTIs) are of high interest due to limited cross-resistance with fluoroquinolones, however analogues with Gram-negative activity often suffer from hERG channel inhibition. A novel series of bicyclic-oxazolidinone inhibitors of bacterial type II topoisomerase were identified which display potent broad-spectrum anti-bacterial activity, including against MDR strains, along with an encouraging in vitro safety profile.

An Evaluation of the Effect of Activation Methods on the Release of Growth Factors from Platelet-Rich Plasma.

Background: Activation of platelets in platelet-rich plasma may improve growth factor release, thus enhancing regenerative properties. The authors investigated whether different methods of platelet-rich plasma activation affected growth factor release kinetics over time.

Methods: Platelet-rich plasma from 20 healthy volunteers was processed by six different methods: (1) control (nonactivated); (2) activation with calcium chloride; (3) activation with calcium chloride and ethanol; (4) activation with calcium chloride and ethanol at 4°C; (5) activation with calcium chloride and ethanol with vitamin C; (6) activation with calcium chloride and ethanol with vitamin C at 4°C.

E-technology social support programs for autistic children: Can they work?

Autism is a neurodevelopmental condition with associated difficulties that present differently across individuals. One such difficulty is recognizing basic and complex facial expressions. Research has previously found that there are many evidence-based support programs available for building non-verbal communication skills.