The Effect of Vaccination on the Competitive Advantage of Two Strains of an Infectious Disease.

We investigate the impact of differential vaccine effectiveness, waning immunity, and natural cross-immunity on the capacity for vaccine-induced strain replacement in two-strain models of infectious disease spread. We focus specifically on the case where the first strain is more transmissible but the second strain is more immune-resistant. We consider two cases on vaccine-induced immunity: (1) a monovalent model where the second strain has immune escape with respect to vaccination; and (2) a bivalent model where the vaccine remains equally effective against both strains.

Cerebellar-driven cortical dynamics can enable task acquisition, switching and consolidation.

The brain must maintain a stable world model while rapidly adapting to the environment, but the underlying mechanisms are not known. Here, we posit that cortico-cerebellar loops play a key role in this process. We introduce a computational model of cerebellar networks that learn to drive cortical networks with task-outcome predictions.

Duration of physical activity required to Ameliorate hyperglycemia without causing hypoglycemia in type 1 diabetes: A T1DEXI adults and pediatric cohort analyses.

Aims: To estimate physical activity (activity) duration required to lower glucose from above target range (>180 mg/dL) to within target range (TIR: 70-180 mg/dL) in individuals with type 1 diabetes (T1D).

Methods: Continuous glucose monitoring and activity data were collected from 404 adults (28-day observation) and 149 adolescents (10-day observation) with T1D. Activities (N = 1902) with a starting glucose between 181-300 mg/dL, duration 10-60 min, and no reported meals during activity were included in the analysis.

Postoperative Outcomes of Enucleation without Closure of the Conjunctiva.

Purpose: To evaluate the long-term outcomes of enucleation without conjunctival closure in a large patient cohort.

Methods: A retrospective chart review was conducted from January 2011 to January 2024, examining 144 eyes of 143 patients who underwent enucleation without conjunctival closure by a single oculoplastic surgeon. Data collected included patient demographics, indications for surgery, implant types, and complications.

Molecular basis for plasma membrane recruitment of PI4KA by EFR3.

The lipid kinase phosphatidylinositol 4 kinase III α (PI4KIIIα/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B.

The Use of Automated Insulin Delivery around Physical Activity and Exercise in Type 1 Diabetes: A Position Statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD).

Regular physical activity and exercise (PA) are cornerstones of diabetes care for individuals with type 1 diabetes. In recent years, the availability of automated insulin delivery (AID) systems has improved the ability of people with type 1 diabetes to achieve the recommended glucose target ranges. PA provides additional health benefits but can cause glucose fluctuations, which challenges current AID systems.

The use of automated insulin delivery around physical activity and exercise in type 1 diabetes: a position statement of the European Association for the Study of Diabetes (EASD) and the International Society for Pediatric and Adolescent Diabetes (ISPAD).

Regular physical activity and exercise (PA) are cornerstones of diabetes care for individuals with type 1 diabetes. In recent years, the availability of automated insulin delivery (AID) systems has improved the ability of people with type 1 diabetes to achieve the recommended glucose target ranges. PA provide additional health benefits but can cause glucose fluctuations, which challenges current AID systems.

The Need for Standardization of Continuous Glucose Monitoring Performance Evaluation: An Opinion by the International Federation of Clinical Chemistry and Laboratory Medicine Working Group on Continuous Glucose Monitoring.

Metrics derived from continuous glucose monitoring (CGM) systems are often discordant between systems. A major cause is that CGM systems are not standardized; they use various algorithms and calibration methods, leading to discordant CGM readings across systems. This discordance can be addressed by standardizing CGM performance assessments: If manufacturers aim their CGM systems at the same target, then CGM readings will align across systems.

Divergent age-related changes in parasite infection occur independently of behaviour and demography in a wild ungulate.

As animals age, they exhibit a suite of phenotypic changes, often including reductions in movement and social behaviour ('behavioural ageing'). By altering an individual's exposure to parasites, behavioural ageing may influence infection status trajectories over the lifespan. However, these processes could be confounded by age-related changes in other phenotypic traits, or by selective disappearance of certain individuals owing to parasite-induced mortality.

Antler size in red deer: declining selection and increasing genetic variance with age, but little senescence.

While senescence is a common occurrence in wild populations, not all traits decline with age simultaneously and some do not show any senescence. A lack of senescence in secondary sexual traits is thought to be due to their importance for reproductive success. However, if reproductive success senesces, why would secondary sexual traits apparently not senesce? Here, we explored this question in a wild population of red deer (Cervus elaphus) using antler form (number of points), a secondary sexual trait which shows little senescence, despite the occurrence of reproductive senescence.

Detecting context dependence in the expression of life history trade-offs.

Life history trade-offs are one of the central tenets of evolutionary demography. Trade-offs, depicting negative covariances between individuals' life history traits, can arise from genetic constraints, or from a finite amount of resources that each individual has to allocate in a zero-sum game between somatic and reproductive functions. While theory predicts that trade-offs are ubiquitous, empirical studies have often failed to detect such negative covariances in wild populations.

Genome-wide SNP assessment of contemporary European red deer genetic structure highlights the distinction of peripheral populations and the main admixture zones in Europe.

Genome-wide technologies open up new possibilities to clarify questions on genetic structure and phylogeographic history of taxa previously studied with microsatellite loci and mitochondrial sequences. Here, we used 736 individual red deer (Cervus elaphus) samples genotyped at 35,701 single nucleotide polymorphism loci (SNPs) to assess the population structure of the species throughout Europe. The results identified 28 populations, with higher degrees of genetic distinction in peripheral compared to mainland populations.

Innovative solution or cause for concern? The use of continuous glucose monitors in people not living with diabetes: A narrative review.

Aims: Continuous glucose monitors (CGMs) have expanded their scope beyond indicated uses for diabetes management and are gaining traction among people not living with diabetes (PNLD). CGMs track in time glucose levels and are proposed as tools for the early detection of abnormal glucose and a potential solution for its normalisation through behavioural change, particularly, diet personalisation and motivation of physical activity. This becomes relevance given the growing incidence of metabolic conditions, such as type 2 diabetes mellitus (T2DM).

Phosphatidylserine enrichment in the nuclear membrane regulates key enzymes of phosphatidylcholine synthesis.

Phosphatidylserine (PS) is an important anionic phospholipid that is synthesized within the endoplasmic reticulum (ER). While PS shows the highest enrichment and serves important functional roles in the plasma membrane (PM) but its role in the nucleus is poorly explored. Using three orthogonal approaches, we found that PS is also uniquely enriched in the inner nuclear membrane (INM) and the nuclear reticulum (NR).

Enhancing equity in access to automated insulin delivery systems in an ethnically and socioeconomically diverse group of children with type 1 diabetes.

Introduction: Manufacturer-supported didactic teaching programmes offer effective automated insulin delivery (AID) systems onboarding in children and young people (CYP) with type 1 diabetes (T1D). However, this approach has limited flexibility to accommodate the needs of families requiring additional support.

Research Design And Methods: Evaluate the efficacy of an inperson manufacturer-supported didactic teaching programme (Group A), in comparison to a flexible flipped learning approach delivered virtually or inperson (Group B).

Molecular basis for plasma membrane recruitment of PI4KA by EFR3.

The lipid kinase phosphatidylinositol 4 kinase III alpha (PI4KIIIa/PI4KA) is a master regulator of the lipid composition and asymmetry of the plasma membrane. PI4KA exists primarily in a heterotrimeric complex with its regulatory proteins TTC7 and FAM126. Fundamental to PI4KA activity is its targeted recruitment to the plasma membrane by the lipidated proteins EFR3A and EFR3B.

Non-vesicular phosphatidylinositol transfer plays critical roles in defining organelle lipid composition.

Phosphatidylinositol (PI) is the precursor lipid for the minor phosphoinositides (PPIns), which are critical for multiple functions in all eukaryotic cells. It is poorly understood how phosphatidylinositol, which is synthesized in the ER, reaches those membranes where PPIns are formed. Here, we used VT01454, a recently identified inhibitor of class I PI transfer proteins (PITPs), to unravel their roles in lipid metabolism, and solved the structure of inhibitor-bound PITPNA to gain insight into the mode of inhibition.

Genetic architecture of inbreeding depression may explain its persistence in a population of wild red deer.

Inbreeding depression is of major concern in declining populations, but relatively little is known about its genetic architecture in wild populations, such as the degree to which it is composed of large or small effect loci and their distribution throughout the genome. Here, we combine fitness and genomic data from a wild population of red deer to investigate the genomic distribution of inbreeding effects. Based on the runs of homozygosity (ROH)-based inbreeding coefficient, F, we use chromosome-specific inbreeding coefficients (F) to explore whether the effect of inbreeding varies between chromosomes.

Purifying and balancing selection on embryonic semi-lethal haplotypes in a wild mammal.

Embryonic lethal mutations are arguably the earliest and most severe manifestation of inbreeding depression, but their impact on wild populations is not well understood. Here, we combined genomic, fitness, and life-history data from 5,925 wild Soay sheep sampled over nearly three decades to explore the impact of embryonic lethal mutations and their evolutionary dynamics. We searched for haplotypes that in their homozygous state are unusually rare in the offspring of known carrier parents and found three putatively semi-lethal haplotypes with 27%-46% fewer homozygous offspring than expected.

Defining the EM-signature of successful cell-transfection.

In this report, we describe the architecture of Lipofectamine 2000 and 3000 transfection- reagents, as they appear inside of transfected cells, using classical transmission electron microscopy (EM). We also demonstrate that they provoke consistent structural changes after they have entered cells, changes that not only provide new insights into the mechanism of action of these particular transfection-reagents, but also provide a convenient and robust method for identifying by EM which cells in any culture have been successfully transfected. This also provides clues to the mechanism(s) of their toxic effects, when they are applied in excess.

Nir1-LNS2 is a novel phosphatidic acid biosensor that reveals mechanisms of lipid production.

Despite various roles of phosphatidic acid (PA) in cellular functions such as lipid homeostasis and vesicular trafficking, there is a lack of high-affinity tools to study PA in live cells. After analysis of the predicted structure of the LNS2 domain in the lipid transfer protein Nir1, we suspected that this domain could serve as a novel PA biosensor. We created a fluorescently tagged Nir1-LNS2 construct and then performed liposome binding assays as well as pharmacological and genetic manipulations of HEK293A cells to determine how specific lipids affect the interaction of Nir1-LNS2 with membranes.