A multidisciplinary weight management intervention for adults with severe mental illness in forensic psychiatric inpatient services (Motiv8): a single blind cluster-randomised wait-list controlled feasibility trial.

Background: People with severe mental illness experience physical health inequalities and a 15-20-year premature mortality rate. Forensic inpatients are particularly affected by restrictions on movement, long admissions, and obesogenic/sedative psychotropic medication. We aimed to establish the feasibility and acceptability of Motiv8, a multidisciplinary weight management intervention co-produced with service users for forensic inpatients.

Single-molecule visualization of sequence-specific RNA binding by a designer PPR protein.

Pentatricopeptide repeat proteins (PPR) are a large family of modular RNA-binding proteins, whereby each module can be modified to bind to a specific ssRNA nucleobase. As such, there is interest in developing 'designer' PPRs (dPPRs) for a range of biotechnology applications, including diagnostics or in vivo localization of ssRNA species; however, the mechanistic details regarding how PPRs search for and bind to target sequences is unclear. To address this, we determined the structure of a dPPR bound to its target sequence and used two- and three-color single-molecule fluorescence resonance energy transfer to interrogate the mechanism of ssRNA binding to individual dPPRs in real time.

CRISPRi-based circuits to control gene expression in plants.

The construction of synthetic gene circuits in plants has been limited by a lack of orthogonal and modular parts. Here, we implement a CRISPR (clustered regularly interspaced short palindromic repeats) interference (CRISPRi)-based reversible gene circuit platform in plants. We create a toolkit of engineered repressible promoters of different strengths and construct NOT and NOR gates in Arabidopsis thaliana protoplasts.

Insights into U-to-C RNA editing from the lycophyte Phylloglossum drummondii.

The lycophyte Phylloglossum drummondii is the sole inhabitant of its genus in the Huperzioideae group and one of a small minority of plants which perform uridine to cytidine RNA editing. We assembled the P. drummondii chloroplast and mitochondrial genomes and used RNA sequence data to build a comprehensive profile of organellar RNA editing events.

Motiv8: a study protocol for a cluster-randomised feasibility trial of a weight management intervention for adults with severe mental illness in secure forensic services.

Introduction: People with severe mental illness have physical comorbidities which result in significant reductions in quality of life and premature mortality. Effective interventions are required that are suitable for people in secure forensic mental health services. We conducted pilot work of a multidisciplinary weight management intervention (Motiv8) which showed improvements in physical and mental health and high levels of satisfaction.

Mitochondrial atp1 mRNA knockdown by a custom-designed pentatricopeptide repeat protein alters ATP synthase.

Spontaneous mutations are rare in mitochondria and the lack of mitochondrial transformation methods has hindered genetic analyses. We show that a custom-designed RNA-binding pentatricopeptide repeat (PPR) protein binds and specifically induces cleavage of ATP synthase subunit1 (atp1) mRNA in mitochondria, significantly decreasing the abundance of the Atp1 protein and the assembled F1Fo ATP synthase in Arabidopsis (Arabidopsis thaliana). The transformed plants are characterized by delayed vegetative growth and reduced fertility.

The prognostic role of PD-L1 expression and the presence of polyomavirus in Merkel cell carcinoma cases.

Background: Merkel cell carcinoma (MCC) comprises a rare malignant primary skin tumor presenting neuroendocrine differentiation. Recently, agents blocking the programmed cell death protein 1 and programmed cell death protein ligand 1 pathway (PD-1/PD-L1) have demonstrated objective and durable tumor regressions in patients presenting advanced MCC. This study aimed to describe the sociodemographic, clinical, and histopathological characteristics of MCC patients, also assessing the prevalence of PD-L1 expression and Merkel cell Polyomavirus (MCPyV), as well as their prognostic roles.

Applications of Synthetic Pentatricopeptide Repeat Proteins.

RNA-binding proteins play integral roles in the regulation of essential processes in cells and as such are attractive targets for engineering to manipulate gene expression at the RNA level. Expression of transcripts in chloroplasts and mitochondria is heavily regulated by pentatricopeptide repeat (PPR) proteins. The diverse roles of PPR proteins and their naturally modular architecture make them ideal candidates for engineering.

Alteration of Mitochondrial Transcript Expression in Using a Custom-Made Library of Pentatricopeptide Repeat Proteins.

Pentatricopeptide repeat (PPR) proteins are considered a potential tool for manipulating organelle gene expression in plants because they can recognise a wide range of different RNA sequences, and the molecular basis for this sequence recognition is partially known and understood. A library of redesigned PPR proteins related to restorer-of-fertility proteins was created and transformed into plants in order to target mitochondrial transcripts. Ninety different variants tested in vivo showed a wide range of phenotypes.

Environmental Factors Influencing Stem Rot Development in Peanut: Predictors and Action Thresholds for Disease Management.

Peanuts grown in tropical, subtropical, and temperate regions are susceptible to stem rot, which is a soilborne disease caused by . Due to the lack of reliable environmental-based scheduling recommendations, stem rot control relies heavily on fungicides that are applied at predetermined intervals. We conducted inoculated field experiments for six site-years in North Florida to examine the relationship between germination of sclerotia: the inoculum, stem rot symptom development in the peanut crop, and environmental factors such as soil temperature (ST), soil moisture, relative humidity (RH), precipitation, evapotranspiration, and solar radiation.

A unique C-terminal domain contributes to the molecular function of Restorer-of-fertility proteins in plant mitochondria.

Restorer-of-fertility (Rf) genes encode pentatricopeptide repeat (PPR) proteins that are targeted to mitochondria where they specifically bind to transcripts that induce cytoplasmic male sterility and repress their expression. In searching for a molecular signature unique to this class of proteins, we found that a majority of known Rf proteins have a distinct domain, which we called RfCTD (Restorer-of-fertility C-terminal domain), and its presence correlates with the ability to induce cleavage of the mitochondrial RNA target. A screen of 219 angiosperm genomes from 123 genera using a sequence profile that can quickly and accurately identify RfCTD sequences revealed considerable variation in RFL/RfCTD gene numbers across flowering plants.

Application of Hydrothermal Time Models to Predict Sclerotial Germination of .

, causal agent of "southern blight" disease, is a soilborne fungal pathogen with a wide host range of more than 500 species. This study's objectives were to (i) quantify the effects of two environmental factors, temperature and soil moisture, on germination of inoculum (sclerotia), which is a critical event for the onset of disease epidemics and (ii) predict the timing of sclerotial germination by applying population-based threshold-type hydrothermal time (HTT) models. We conducted in vitro germination experiments with three isolates of isolated from peanuts, which were tested at five temperatures (), ranging from 17 to 40°C, four matric potentials (Ψ) between -0.

Sensor-Based Quantification of Peanut Disease Defoliation Using an Unmanned Aircraft System and Multispectral Imagery.

Early leaf spot () and late leaf spot () are two of the most economically important foliar fungal diseases of peanut, often requiring seven to eight fungicide applications to protect against defoliation and yield loss. Rust () may also cause significant defoliation depending on season and location. Sensor technologies are increasingly being utilized to objectively monitor plant disease epidemics for research and supporting integrated management decisions.

Exploring biomarkers and prognostic factors in uterine carcinosarcoma: An insight into L1CAM, CDX2, p53, and MSI status.

Background: Uterine Carcinosarcomas (UCS) are a rare type of cancer composed of an admixture of high-grade carcinomatous and sarcomatous elements. Clinicopathological prognostic factors in UCS are well established, but studies that approach the impact of biomarkers in this unusual disease are scarce. The study objective was to evaluate the prevalence and prognostic impact of a panel of prominent biomarkers in uterine carcinosarcoma (UCS) using an immunohistochemical characterization with four biomarkers.

Implementation of a primary care asthma management quality improvement programme across 68 general practice sites.

Despite national and international guidelines, asthma is frequently misdiagnosed, control is poor and unnecessary deaths are far too common. Large scale asthma management programme such as that undertaken in Finland, can improve asthma outcomes. A primary care asthma management quality improvement programme was developed with the support of the British Lung Foundation (now Asthma + Lung UK) and Optimum Patient Care (OPC) Limited.

Evolution of cox2 introns in angiosperm mitochondria and efficient splicing of an elongated cox2i691 intron.

In angiosperms, the mitochondrial cox2 gene harbors up to two introns, commonly referred to as cox2i373 and cox2i691. We studied the cox2 from 222 fully-sequenced mitogenomes from 30 angiosperm orders and analyzed the evolution of their introns. Unlike cox2i373, cox2i691 shows a distribution among plants that is shaped by frequent intron loss events driven by localized retroprocessing.

MSP1 encodes an essential RNA-binding pentatricopeptide repeat factor required for nad1 maturation and complex I biogenesis in Arabidopsis mitochondria.

Mitochondrial biogenesis relies on nuclearly encoded factors, which regulate the expression of the organellar-encoded genes. Pentatricopeptide repeat (PPR) proteins constitute a major gene family in angiosperms that are pivotal in many aspects of mitochondrial (mt)RNA metabolism (e.g.

Plant organellar RNA maturation.

Plant organellar RNA metabolism is run by a multitude of nucleus-encoded RNA-binding proteins (RBPs) that control RNA stability, processing, and degradation. In chloroplasts and mitochondria, these post-transcriptional processes are vital for the production of a small number of essential components of the photosynthetic and respiratory machinery-and consequently for organellar biogenesis and plant survival. Many organellar RBPs have been functionally assigned to individual steps in RNA maturation, often specific to selected transcripts.

Effects of Grass-Based Crop Rotation, Nematicide, and Irrigation on the Nematode Community in Cotton.

Plant-parasitic and free-living nematodes - bacterivores, fungivores, omnivores, predators - comprise the nematode community. Nematicide application and crop rotation are important tools to manage plant-parasitic nematodes, but effects on free-living nematodes and nematode ecological indices need further study. The nematicide fluopyram was recently introduced in cotton () production and its effects on the nematode community need assessment.

The developmental mutant has a single nucleotide deletion in the gene .

The mutation was previously identified in a FLP/FRT screen of chromosome 2R for conditional growth regulators. Here we report the phenotypic characterization and genetic mapping of by undergraduate students participating in Fly-CURE, a pedagogical program that teaches the science of genetics through a classroom research experience. We find that creation of cell clones in the developing eye-antennal imaginal disc causes a headless adult phenotype, suggestive of both autonomous and non-autonomous effects on cell growth or viability.

Synthetic PPR proteins as tools for sequence-specific targeting of RNA.

In native systems, gene expression is regulated by RNA binding proteins. Such proteins have been the target of a great deal of recent research interest, due to the potential for harnessing these regulatory effects for the construction of new biotechnological tools. In particular, focus has been targeted on building synthetic RNA binding proteins for sequence-specific targeting of new RNA transcripts.

A patient-driven clinicogenomic partnership for metastatic prostate cancer.

Molecular profiling studies have enabled discoveries for metastatic prostate cancer (MPC) but have predominantly occurred in academic medical institutions and involved non-representative patient populations. We established the Metastatic Prostate Cancer Project (MPCproject, mpcproject.org), a patient-partnered initiative to involve patients with MPC living anywhere in the US and Canada in molecular research.

One Year Later: The Lasting Effect of the COVID-19 Pandemic on Elective Hip and Knee Arthroplasty.

Background: The severe acute respiratory syndrome coronavirus 2 (COVID-19) pandemic has continued to generate notable disruption in elective total hip arthroplasty (THA) and total knee arthroplasty (TKA). The purpose of this study was to determine whether there is any difference in patient characteristics, revenue, and clinical outcomes in patients undergoing THA and TKA after the start of the pandemic.

Methods: We reviewed a consecutive series of 26,493 patients undergoing primary and revision THA and TKA by 48 surgeons in a single arthroplasty practice.

Manipulation Under Anesthesia is Safe After Cementless Total Knee Arthroplasty: A Multicenter Study.

Background: Cementless total knee arthroplasty (TKA) is thought to facilitate durable, biological fixation between the bone and implant. However, the 4-12 weeks required for osseointegration coincides with the optimal timeframe to perform a manipulation under anesthesia (MUA) if a patient develops postoperative stiffness. This study aims to determine the impact of early MUA on cementless fixation by comparing functional outcomes and survivorship of cementless and cemented TKAs.

Serum Glucose Variability Increases the Risk of Complications Following Aseptic Revision Hip and Knee Arthroplasty.

Background: Increased serum glucose variability has been proposed as a risk factor for perioperative morbidity and mortality. Given the greater surgical complexity and complication risk of revision total joint arthroplasty (TJA), previous findings may not be generalizable to the revision population. The purpose of this study was to investigate the association between glucose variability and postoperative complications following aseptic revision TJA.