Single molecule Lipid Biosensors Mitigate Inhibition of Endogenous Effector Proteins.

Genetically encoded lipid biosensors are essential cell biological tools. They are the only technique that provide real time, spatially resolved kinetic data for lipid dynamics in living cells. Despite clear strengths, these tools also carry significant drawbacks; most notably, lipid molecules bound to biosensors cannot engage with their effectors, causing inhibition.

Identifying the sex chromosome and sex determination genes in the cattle tick, Rhipicephalus (Boophilus) microplus.

Rhipicephalus (Boophilus) microplus is globally one of the most economically important ectoparasites of cattle costing the agriculture industry billions of dollars annually. Resistance to chemical control measures has prompted the development of novel methods of control. Recent advancements in genetic control measures for human and other animal vectors have utilized sex determination research to manipulate sex ratios, which have shown promising results in mosquitoes namely Aedes aegypti and Anopheles stephensi.

Twice weekly dosing with Sebelipase alfa (Kanuma®) rescues severely ill infants with Wolman disease.

Background: Sebelipase alfa (Kanuma®) is approved for patients with Wolman disease (WD) at a dosage of 3-5 mg/kg once weekly. Survival rates in the second of two clinical trials was greater, despite recruiting more severely ill patients, probably related to higher initial and maximal doses. We aimed to evaluate the effective pharmacokinetics and pharmacodynamics of Sebelipase alfa when administered to patients with severe WD at 5 mg/kg twice weekly, an intensive regimen which was not assessed in the trials.

Consensus guidelines for the diagnosis and management of isolated sulfite oxidase deficiency and molybdenum cofactor deficiencies.

Sulfite intoxication is the hallmark of four ultrarare disorders that are caused by impaired sulfite oxidase activity due to genetic defects in the synthesis of the molybdenum cofactor or of the apoenzyme sulfite oxidase. Delays on the diagnosis of these disorders are common and have been caused by their unspecific presentation of acute neonatal encephalopathy with high early mortality, followed by the evolution of dystonic cerebral palsy and also by the lack of easily available and reliable diagnostic tests. There is significant variation in survival and in the quality of symptomatic management of affected children.

Experience with a hybrid recruitment approach of patient-facing web portal screening and subsequent phone and medical record review for a neurosurgical intervention trial for chronic ischemic stroke disability (PISCES III).

Background: Recruitment of participants is the greatest risk to completion of most clinical trials, with 20-40% of trials failing to reach the targeted enrollment. This is particularly true of trials of central nervous system (CNS) therapies such as intervention for chronic stroke. The PISCES III trial was an invasive trial of stereotactically guided intracerebral injection of CTX0E03, a fetal derived neural stem cell line, in patients with chronic disability due to ischemic stroke.

Coproduction of Phase-Separated Carotenoids and β-Farnesene as a Yeast Biomass Valorization Strategy.

Valorization, the process whereby waste materials are converted into more valuable products, is rarely practiced in industrial fermentation. We developed a model valorization system whereby that had previously been engineered to produce high concentrations (>100 g/L) of extracellular β-farnesene was further engineered to simultaneously produce intracellular carotenoids, both products being isoprenoids. Thus, a single fermentation generates two valuable products, namely, β-farnesene in the liquid phase and carotenoids in the solid biomass phase.

Changes in practice and management of placenta accreta spectrum disorder: A 20-year retrospective cohort study.

Background: Placenta accreta spectrum disorder is an increasingly prevalent cause of maternal morbidity in developed countries.

Aims: This study aimed to review the management and outcomes of cases of placenta accreta spectrum, and compare blood loss and blood transfusion rates, over time after an institutional change in planned primary surgeon from gynaecological oncologists to experienced obstetricians.

Methods: This retrospective cohort study included all cases of suspected or confirmed placenta accreta spectrum disorder (PASD) between 1999 and 2021 at Monash Health.

A Review of l-Methylfolate as Adjunctive Therapy in the Treatment of Major Depressive Disorder.

To examine the potential of using l-methylfolate (LMF) as an adjunctive therapy for major depressive disorder (MDD) and assess its role in filling current treatment gaps for patients who are overweight/obese and have chronic inflammation. The PubMed database was searched using the key words l-methylfolate, , and to identify studies published from January 2000 to April 2021. Identified studies included 2 randomized controlled trials (RCTs), an open-label extension of these RCTs, and a real-world prospective study.

Three-dimensional time-domain Green's functions and spatial impulse responses for the van Wijngaarden wave equation.

An exact analytical three-dimensional time-domain Green's function is introduced for the van Wijngaarden wave equation when the coefficients of the two loss terms satisfy a specific relationship. This analytical Green's function, which describes frequency-squared attenuation in acoustic media such as water, enables the subsequent derivation of new expressions that describe the lossy spatial impulse response for a circular piston. Initial time-domain assessments, which compare the Green's functions for the van Wijngaarden, Stokes, and power law wave equations using the attenuation and sound speed for water, indicate that these three lossy wave equations yield nearly identical results at distances greater than or equal to 10 μm.

Differential Gene Expression of Innate Immune Response Genes Consequent to Solenopsis invicta Virus-3 Infection.

The red imported fire ant Buren (fire ant hereafter) is a global pest that inflicts billions of dollars in damages to the United States economy and poses a major threat on a global scale. Concerns with the broad-spectrum application of insecticides have facilitated the hunt for natural enemy-mediated controls. One of these, the virus virus-3 (SINV-3 hereafter) is exceptionally virulent in laboratory settings.

Environmental DNA detects Spawning Habitat of an ephemeral migrant fish (Anadromous Rainbow Smelt: Osmerus mordax).

Background: Anadromous rainbow smelt (Osmerus mordax) have experienced a large range reduction in recent decades and the status of remnant spawning populations is poorly known in Maine, where these fish have significant ecological, cultural, and commercial relevance. Defining the remnant range of anadromous smelt is more difficult than for many declining fish species because adults are only ephemerally present while spawning in small coastal streams at night during spring runoff periods when traditional assessments can be unreliable or even hazardous. We hypothesized that eDNA might facilitate improved survey efforts to define smelt spawning habitat, but that detection could also face challenges from adult eDNA quickly flushing out of these small stream systems.

The Genomic Basis of Evolutionary Novelties in a Leafhopper.

Evolutionary innovations generate phenotypic and species diversity. Elucidating the genomic processes underlying such innovations is central to understanding biodiversity. In this study, we addressed the genomic basis of evolutionary novelties in the glassy-winged sharpshooter (Homalodisca vitripennis, GWSS), an agricultural pest.

A Convenient, Rapid, Conventional Heating Route to MIDA Boronates.

A cheap, conventional, sealed heating reactor proved to be a useful alternative to a microwave reactor in the synthesis of a >20-member MIDA boronate library (MIDA = N-methyliminodiacetic acid). Reaction times were 10 min and work-ups were minimal, saving on energy and solvent usage.

Carbohydrate quantity is more closely associated with glycaemic control than weight in pregnant women with type 1 diabetes: Insights from the Diabetes and Pre-eclampsia Intervention Trial (DAPIT).

Background: The present study aimed to explore the relationships between carbohydrate intake, body mass index (BMI) and glycaemic control (HbA1c) in pregnant women with type 1 diabetes mellitus (T1DM) METHODS: Secondary analysis of data was undertaken to assess dietary intake in a cohort of women who participated in a randomised controlled trial (RCT) of antioxidant supplementation to prevent preeclampsia (DAPIT ). Study-specific peripheral venous blood samples were obtained for HbA1c at 26 and 34 weeks. Diet was collected using a validated semiquantitative food frequency questionnaire at 26-28 weeks of gestation which assessed dietary intake over 2 weeks.

Pediatric ionized calcium reference intervals from archived radiometer data.

Background: Measurement of ionized calcium (iCa) reflects bioavailable calcium and has significant utility in children. However, robust pediatric iCa reference intervals (RI) have not been well-established. In this study, we retrospectively calculated RI for iCa in a pediatric population by accessing archived data acquired on Radiometer instruments and applying stringent exclusion criteria.

FKBPL and SIRT-1 Are Downregulated by Diabetes in Pregnancy Impacting on Angiogenesis and Endothelial Function.

Diabetes in pregnancy is associated with adverse pregnancy outcomes including preterm birth. Although the mechanisms leading to these pregnancy complications are still poorly understood, aberrant angiogenesis and endothelial dysfunction play a key role. FKBPL and SIRT-1 are critical regulators of angiogenesis, however, their roles in pregnancies affected by diabetes have not been examined before in detail.

Twenty plus Years of Data Demonstrating Virus Filtration as an Effective and Robust Step for Large Virus Removal.

Virus filtration has been demonstrated to be an effective and robust dedicated viral clearance step that is used in biopharmaceutical manufacturing processes. Here we present virus filtration data from a multicompany collaboration with data compiled from WuXi Advanced Therapies' and Charles River Laboratories' internal viral clearance databases spanning more than 25 years. The data were sorted by virus removal and type and then further subdivided into murine leukemia virus only, pseudorabies virus only, and reovirus type 3 only categories to allow for analyses of viral clearance results.

Glycemic excursion minimization in the management of type 2 diabetes: a novel intervention tested in a randomized clinical trial.

Introduction: This study of adults with type 2 diabetes employed a non-inferiority hypothesis to investigate whether an innovative lifestyle focused on minimizing postnutrient blood glucose (BG) excursions (glycemic excursion minimization (GEM)) would be equivalent or superior to conventional weight loss (WL) therapy in regard to reducing HbA1c, and superior to WL when investigating physical, behavioral and psychological secondary outcomes. The impact of BG feedback on GEM efficacy was also investigated.

Research Design And Methods: 178 adults with type 2 diabetes for ≤10 years, HbA1c ≥6.

Group antenatal care (Pregnancy Circles) for diverse and disadvantaged women: study protocol for a randomised controlled trial with integral process and economic evaluations.

Background: Group antenatal care has been successfully implemented around the world with suggestions of improved outcomes, including for disadvantaged groups, but it has not been formally tested in the UK in the context of the NHS. To address this the REACH Pregnancy Circles intervention was developed and a randomised controlled trial (RCT), based on a pilot study, is in progress.

Methods: The RCT is a pragmatic, two-arm, individually randomised, parallel group RCT designed to test clinical and cost-effectiveness of REACH Pregnancy Circles compared with standard care.

Role of A Novel Angiogenesis FKBPL-CD44 Pathway in Preeclampsia Risk Stratification and Mesenchymal Stem Cell Treatment.

Context: Preeclampsia is a leading cardiovascular complication in pregnancy lacking effective diagnostic and treatment strategies.

Objective: To investigate the diagnostic and therapeutic target potential of the angiogenesis proteins, FK506-binding protein like (FKBPL) and CD44.

Design And Intervention: FKBPL and CD44 plasma concentration or placental expression were determined in women pre- or postdiagnosis of preeclampsia.

Measuring Genome Sizes Using Read-Depth, k-mers, and Flow Cytometry: Methodological Comparisons in Beetles (Coleoptera).

Measuring genome size across different species can yield important insights into evolution of the genome and allow for more informed decisions when designing next-generation genomic sequencing projects. New techniques for estimating genome size using shallow genomic sequence data have emerged which have the potential to augment our knowledge of genome sizes, yet these methods have only been used in a limited number of empirical studies. In this project, we compare estimation methods using next-generation sequencing (k-mer methods and average read depth of single-copy genes) to measurements from flow cytometry, a standard method for genome size measures, using ground beetles (Carabidae) and other members of the beetle suborder Adephaga as our test system.

Weighing as part of your care: a feasibility study exploring the re-introduction of weight measurements during pregnancy as part of routine antenatal care.

Background: The UK does not currently have guidelines on gestational weight gain owing to gaps in the evidence base. Reintroducing routine weighing of women throughout pregnancy would begin to provide the evidence needed to fill this gap. The aim of this research was to re-introduce measurement of weight at each routine antenatal appointment in a small scale study, in order to determine the feasibility and acceptability of implementing the practice on a larger scale.

Thoracic underreplication in Drosophila species estimates a minimum genome size and the dynamics of added DNA.

Many cells in the thorax of Drosophila were found to stall during replication, a phenomenon known as underreplication. Unlike underreplication in nuclei of salivary and follicle cells, this stall occurs with less than one complete round of replication. This stall point allows precise estimations of early-replicating euchromatin and late-replicating heterochromatin regions, providing a powerful tool to investigate the dynamics of structural change across the genome.