Quantitative image mean squared displacement (iMSD) analysis of the dynamics of profilin 1 at the membrane of live cells.

Image mean square displacement analysis (iMSD) is a method allowing the mapping of diffusion dynamics of molecules in living cells. However, it can also be used to obtain quantitative information on the diffusion processes of fluorescently labelled molecules and how their diffusion dynamics change when the cell environment is modified. In this paper, we describe the use of iMSD to obtain quantitative data of the diffusion dynamics of a small cytoskeletal protein, profilin 1 (pfn1), at the membrane of live cells and how its diffusion is perturbed when the cells are treated with Cytochalasin D and/or the interactions of pfn1 are modified when its actin and polyphosphoinositide binding sites are mutated (pfn1-R88A). Using total internal reflection fluorescence microscopy images, we obtained data on isotropic and confined diffusion coefficients, the proportion of cell areas where isotropic diffusion is the major diffusion mode compared to the confined diffusion mode, the size of the confinement zones and the size of the domains of dynamic partitioning of pfn1. Using these quantitative data, we could demonstrate a decreased isotropic diffusion coefficient for the cells treated with Cytochalasin D and for the pfn1-R88A mutant. We could also see changes in the modes of diffusion between the different conditions and changes in the size of the zones of pfn1 confinements for the pfn1 treated with Cytochalasin D. All of this information was acquired in only a few minutes of imaging per cell and without the need to record thousands of single molecule trajectories

National Beef Tenderness Survey—2022: Consumer Sensory Panel Evaluations and Warner-Bratzler Shear Force of Beef Steaks From Retail and Foodservice

Beef retail steaks from establishments across 11 US cities and beef foodservice steaks from establishments in 6 US cities were evaluated by consumer sensory evaluations and Warner-Bratzler shear (WBS) force analyses. The retail tenderloin had the lowest (P<0.05) WBS force value compared to other retail cuts. The retail steak with the greatest (P<0.05) WBS force value was the top sirloin. Foodservice ribeye and top loin steaks had greater (P<0.05) WBS force values compared to the tenderloin. All retail top blade, bone-in ribeye, Porterhouse, and tenderloin steaks were categorized as“very tender” (<31.4 N). There were no (P>0.05) differences in WBS force values among USDA quality grade groups for foodservice steaks. Retail tenderloin steaks received the highest (P<0.05) consumer rating for overall like/dislike, tenderness like/dislike,tenderness level, flavor like/dislike, and juiciness like/dislike compared to all other retail cuts. There were no (P>0.05)differences among the 4 foodservice cuts for consumer sensory ratings of overall like/dislike, tenderness like/dislike, tenderness level, flavor like/dislike, and juiciness like/dislike. There were no (P>0.05) USDA quality grade differences for ribeye, top loin, top sirloin, and tenderloin foodservice steaks for overall like/dislike, tenderness like/dislike, tenderness level, flavor like/dislike, and juiciness like/dislike. Regardless of source (foodservice or retail), USDA grade group, or beef cut, measures of tenderness in this survey reveal ratings and values that should meet most consumer expectations in the marketplace

Mothers' AdvocateS In the Community (MOSAIC)- non-professional mentor support to reduce intimate partner violence and depression in mothers: a cluster randomised trial in primary care

Background : Effective interventions to increase safety and wellbeing of mothers experiencing intimate partner violence (IPV) are scarce. As much attention is focussed on professional intervention, this study aimed to determine the effectiveness of non-professional mentor support in reducing IPV and depression among pregnant and recent mothers experiencing, or at risk of IPV.Methods : MOSAIC was a cluster randomised trial in 106 primary care (maternal and child health nurse and general practitioner) clinics in Melbourne, Australia. 63/106 clinics referred 215 eligible culturally and linguistically diverse women between January 2006 and December 2007. 167 in the intervention (I) arm, and 91 in the comparison (C) arm. 174 (80.9%) were recruited. 133 (76.4%) women (90 I and 43 C) completed follow-up at 12 months.Intervention: 12 months of weekly home visiting from trained and supervised local mothers, (English &amp; Vietnamese speaking) offering non-professional befriending, advocacy, parenting support and referrals.Main outcome measures: Primary outcomes; IPV (Composite Abuse Scale CAS) and depression (Edinburgh Postnatal Depression Scale EPDS); secondary measures included wellbeing (SF-36), parenting stress (PSI-SF) and social support (MOS-SF) at baseline and follow-up.Analysis: Intention-to-treat using multivariable logistic regression and propensity scoring.Results : There was evidence of a true difference in mean abuse scores at follow-up in the intervention compared with the comparison arm (15.9 vs 21.8, AdjDiff -8.67, CI -16.2 to -1.15). There was weak evidence for other outcomes, but a trend was evident favouring the intervention: proportions of women with CAS scores &ge;7, 51/88 (58.4%) vs 27/42 (64.3%) AdjOR 0.47, CI 0.21 to 1.05); depression (EPDS score &ge;13) (19/85, 22% (I) vs 14/43, 33% (C); AdjOR 0.42, CI 0.17 to 1.06); physical wellbeing mean scores (PCS-SF36: AdjDiff 2.79; CI -0.40 to 5.99); mental wellbeing mean scores (MCS-SF36: AdjDiff 2.26; CI -1.48 to 6.00). There was no observed effect on parenting stress. 82% of women mentored would recommend mentors to friends in similar situations.Conclusion : Non-professional mentor mother support appears promising for improving safety and enhancing physical and mental wellbeing among mothers experiencing intimate partner violence referred from primary care.<br /

Large-Scale Gene-Centric Meta-Analysis across 39 Studies Identifies Type 2 Diabetes Loci

To identify genetic factors contributing to type 2 diabetes (T2D), we performed large-scale meta-analyses by using a custom similar to 50,000 SNP genotyping array (the ITMAT-Broad-CARe array) with similar to 2000 candidate genes in 39 multiethnic population-based studies, case-control studies, and clinical trials totaling 17,418 cases and 70,298 controls. First, meta-analysis of 25 studies comprising 14,073 cases and 57,489 controls of European descent confirmed eight established T2D loci at genome-wide significance. In silico follow-up analysis of putative association signals found in independent genome-wide association studies (including 8,130 cases and 38,987 controls) performed by the DIAGRAM consortium identified a T2D locus at genome-wide significance (GATAD2A/CILP2/PBX4; p = 5.7 x 10(-9)) and two loci exceeding study-wide significance (SREBF1, and TH/INS; p <2.4 x 10(-6)). Second, meta-analyses of 1,986 cases and 7,695 controls from eight African-American studies identified study-wide-significant (p = 2.4 x 10(-7)) variants in HMGA2 and replicated variants in TCF7L2 (p = 5.1 x 10(-15)). Third, conditional analysis revealed multiple known and novel independent signals within five T2D-associated genes in samples of European ancestry and within HMGA2 in African-American samples. Fourth, a multiethnic meta-analysis of all 39 studies identified T2D-associated variants in BCL2 (p = 2.1 x 10(-8)). Finally, a composite genetic score of SNPs from new and established T2D signals was significantly associated with increased risk of diabetes in African-American, Hispanic, and Asian populations. In summary, large-scale meta-analysis involving a dense gene-centric approach has uncovered additional loci and variants that contribute to T2D risk and suggests substantial overlap of T2D association signals across multiple ethnic groups

Profilin: many facets of a small protein

Profilin is a ubiquitously expressed protein well known as a key regulator of actin polymerisation. The actin cytoskeleton is involved in almost all cellular processes including motility, endocytosis, metabolism, signal transduction and gene transcription. Hence, profilin’s role in the cell goes beyond its direct and essential function in regulating actin dynamics. This review will focus on the interactions of Profilin 1 and its ligands at the plasma membrane, in the cytoplasm and the nucleus of the cells and the regulation of profilin activity within those cell compartments. We will discuss the interactions of profilin in cell signalling pathways and highlight the importance of the cell context in the multiple functions that this small essential protein has in conjunction with its role in cytoskeletal organisation and dynamics. We will review some of the mechanisms that control profilin expression and the implications of changed expression of profilin in the light of cancer biology and other pathologies

Cofilin and profilin: partners in cancer aggressiveness

This review covers aspects of cofilin and profilin regulations and their influence on actin polymerisation responsible for cell motility and metastasis. The regulation of their activity by phosphorylation and nitration, miRs, PI(4,5)P2 binding, pH, oxidative stress and post-translational modification is described. In this review, we have highlighted selected similarities, complementarities and differences between the two proteins and how their interplay affects actin filament dynamics

Quantitative image mean squared displacement (iMSD) analysis of the dynamics of profilin 1 at the membrane of live cells.

Image mean square displacement analysis (iMSD) is a method allowing the mapping of diffusion dynamics of molecules in living cells. However, it can also be used to obtain quantitative information on the diffusion processes of fluorescently labelled molecules and how their diffusion dynamics change when the cell environment is modified. In this paper, we describe the use of iMSD to obtain quantitative data of the diffusion dynamics of a small cytoskeletal protein, profilin 1 (pfn1), at the membrane of live cells and how its diffusion is perturbed when the cells are treated with Cytochalasin D and/or the interactions of pfn1 are modified when its actin and polyphosphoinositide binding sites are mutated (pfn1-R88A). Using total internal reflection fluorescence microscopy images, we obtained data on isotropic and confined diffusion coefficients, the proportion of cell areas where isotropic diffusion is the major diffusion mode compared to the confined diffusion mode, the size of the confinement zones and the size of the domains of dynamic partitioning of pfn1. Using these quantitative data, we could demonstrate a decreased isotropic diffusion coefficient for the cells treated with Cytochalasin D and for the pfn1-R88A mutant. We could also see changes in the modes of diffusion between the different conditions and changes in the size of the zones of pfn1 confinements for the pfn1 treated with Cytochalasin D. All of this information was acquired in only a few minutes of imaging per cell and without the need to record thousands of single molecule trajectories

Grade 1 microtia, wide anterior fontanel and novel type tracheo-esophageal fistula in methimazole embryopathy.

Carbimazole (CMZ) and its active metabolite methimazole (MMI) are antithyroid medications, which can result in MMI/CMZ embryopathy in susceptible individuals. The incidence of birth defects related to MMI/CMZ embryopathy remains unclear as several epidemiologic studies failed to prove a correlation, despite positive case-control studies and numerous case reports. Malformations reported in exposed individuals and commonly recognized as MMI/CMZ embryopathy include cutis aplasia of the scalp, choanal atresia, esophageal atresia (EA), tracheo-esophageal fistula (TEF), persistent vitelline duct, athelia/hypothelia, and subtle facial dysmorphisms including sparse or arched eyebrows. Here, we report on individuals with early pregnancy exposure to MMI, with microtia and various other anomalies associated with MMI embryopathy, suggesting that microtia is also seen with increased frequency after prenatal MMI exposure. Additional unusual malformations among our patients include a previously unreported type of TEF with three separate esophageal pouches and a fistula connecting the middle pouch to the trachea in one child, and absence of the gall bladder in another. An enlarged anterior fontanel was seen in three patients, and clinodactyly of the fifth finger was noted in three. The similarities between our three patients with microtia after MMI exposure and the two previously reported with microtia after CMZ exposure support the concept of microtia being related to the MMI/CMZ exposure. Recognition of microtia as a manifestation of MMI/CMZ embryopathy will likely increase the number of diagnosed cases and thus affect ascertainment. We propose diagnostic criteria for MMI/CMZ embryopathy, including the presence of at least one major characteristic finding