Honour based violence and the multi-agency approach in Nottingham: response of local agencies to honour based violence

The focus of the research was to gain an understanding of the current levels of HBV in Nottingham and the nature of the multi-agency response. The main aim of the research was to gain an understanding of practitioners' work with a range of issues relating to honour based violence (HBV)within partnership agencies. The revised Violence Against Women and Girls Strategy Action Plan published by the government in2010 (Home Office, 2010) gave precedence to a co-ordinated approach to ending all forms of violence against women including HBV and forced marriage

Disruption of beta cell acetyl-CoA carboxylase-1 in mice impairs insulin secretion and beta cell mass

Aims/hypothesis: Pancreatic beta cells secrete insulin to maintain glucose homeostasis, and beta cell failure is a hallmark of type 2 diabetes. Glucose triggers insulin secretion in beta cells via oxidative mitochondrial pathways. However, it also feeds mitochondrial anaplerotic pathways, driving citrate export and cytosolic malonyl-CoA production by the acetyl-CoA carboxylase 1 (ACC1) enzyme. This pathway has been proposed as an alternative glucose-sensing mechanism, supported mainly by in vitro data. Here, we sought to address the role of the beta cell ACC1-coupled pathway in insulin secretion and glucose homeostasis in vivo. Methods: Acaca, encoding ACC1 (the principal ACC isoform in islets), was deleted in beta cells of mice using the Cre/loxP system. Acaca floxed mice were crossed with Ins2cre mice (βACC1KO; life-long beta cell gene deletion) or Pdx1creER mice (tmx-βACC1KO; inducible gene deletion in adult beta cells). Beta cell function was assessed using in vivo metabolic physiology and ex vivo islet experiments. Beta cell mass was analysed using histological techniques. Results: βACC1KO and tmx-βACC1KO mice were glucose intolerant and had defective insulin secretion in vivo. Isolated islet studies identified impaired insulin secretion from beta cells, independent of changes in the abundance of neutral lipids previously implicated as amplification signals. Pancreatic morphometry unexpectedly revealed reduced beta cell size in βACC1KO mice but not in tmx-βACC1KO mice, with decreased levels of proteins involved in the mechanistic target of rapamycin kinase (mTOR)-dependent protein translation pathway underpinning this effect. Conclusions/interpretation: Our study demonstrates that the beta cell ACC1-coupled pathway is critical for insulin secretion in vivo and ex vivo and that it is indispensable for glucose homeostasis. We further reveal a role for ACC1 in controlling beta cell growth prior to adulthood.</p

Lipofection with Synthetic mRNA as a Simple Method for T-Cell Immunomonitoring.

The quantification of T-cell immune responses is crucial for the monitoring of natural and treatment-induced immunity, as well as for the validation of new immunotherapeutic approaches. The present study presents a simple method based on lipofection of synthetic mRNA in mononuclear cells as a method to determine in vitro T-cell responses. We compared several commercially available transfection reagents for their potential to transfect mRNA into human peripheral blood mononuclear cells and murine splenocytes. We also investigated the impact of RNA modifications in improving this method. Our results demonstrate that antigen-specific T-cell immunomonitoring can be easily and quickly performed by simple lipofection of antigen-coding mRNA in complex immune cell populations. Thus, our work discloses a convenient solution for the in vitro monitoring of natural or therapy-induced T-cell immune responses

Imputation of plasma lipid species to facilitate integration of lipidomic datasets

Recent advancements in plasma lipidomic profiling methodology have significantly increased specificity and accuracy of lipid measurements. This evolution, driven by improved chromatographic and mass spectrometric resolution of newer platforms, has made it challenging to align datasets created at different times, or on different platforms. Here we present a framework for harmonising such plasma lipidomic datasets with different levels of granularity in their lipid measurements. Our method utilises elastic-net prediction models, constructed from high-resolution lipidomics reference datasets, to predict unmeasured lipid species in lower-resolution studies. The approach involves (1) constructing composite lipid measures in the reference dataset that map to less resolved lipids in the target dataset, (2) addressing discrepancies between aligned lipid species, (3) generating prediction models, (4) assessing their transferability into the targe dataset, and (5) evaluating their prediction accuracy. To demonstrate our approach, we used the AusDiab population-based cohort (747 lipid species) as the reference to impute unmeasured lipid species into the LIPID study (342 lipid species). Furthermore, we compared measured and imputed lipids in terms of parameter estimation and predictive performance, and validated imputations in an independent study. Our method for harmonising plasma lipidomic datasets will facilitate model validation and data integration efforts

Zebrafish embryonic lipidomic analysis reveals that the yolk cell as metabolically active in processing lipid

The role of lipids in providing energy and structural cellular components during vertebrate development is poorly understood. To elucidate these roles further, we visualized lipid deposition and examined expression of key lipid-regulating genes during zebrafish embryogenesis. We also conducted a semiquantitative analysis of lipidomic composition using liquid chromatography (LC)-mass spectrometry. Finally, we analyzed processing of boron-dipyrromethene (BODIPY) lipid analogs injected into the yolk using thin layer chromatography. Our data reveal that the most abundant lipids in the embryo are cholesterol, phosphatidylcholine, and triglyceride. Moreover, we demonstrate that lipids are processed within the yolk prior to mobilization to the embryonic body. Our data identify a metabolically active yolk and body resulting in a dynamic lipid composition. This provides a foundation for studying lipid biology during normal or pharmacologically compromised embryogenesis

The Association Between Circulating Branched Chain Amino Acids and Temporal Risk of Developing Type 2 Diabetes Mellitus: A Systematic Review & Meta-Analysis

Introduction: Recent studies have concluded that elevated circulating branched chain amino acids (BCAA) are associated with the pathogenesis of type 2 diabetes mellitus (T2DM) and obesity. However, development of this association over time and the quantification of the strength of this association for individual BCAAs prior to T2DM diagnosis remains unexplored. Methods: A systematic search was conducted using the Healthcare Databases Advance Search (HDAS) via the National Institute for Health and Care Excellence (NICE) website. The data sources included EM- BASE, MEDLINE and PubMed for all papers from inception until November 2021. Nine studies were identified in this systematic review and meta-analysis. Stratification was based on follow-up times (0-6, 6-12 and 12 or more years) and controlling of body mass index (BMI) through the specific assessment of overweight cohorts was also undertaken. Results: The meta-analysis revealed a statistically significant positive association between BCAA concentrations and the development of T2DM, with valine OR=2.08 (95% CI=2.04-2.12, p<0.00001), leucine OR=2.25 (95% CI=1.76-2.87, p<0.00001) and isoleucine OR=2.12, 95% CI=2.00-2.25, p<0.00001. In addition, we demonstrated a positive consistent temporal association between circulating BCAA levels and the risk of developing T2DM with differentials in the respective follow-up times of 0-6 years, 6-12 years and ≥12 years follow-up for valine (OR=2.08, 1.86 & 2.14, p<0.05 each), leucine (OR=2.10, 2.25 & 2.16, p<0.05 each) and isoleucine (OR=2.12, 1.90 & 2.16, p<0.05 each) demonstrated. Conclusion: Plasma BCAA concentrations are associated with T2DM incidence, independent of the baseline plasma BCAA levels across all temporal subgroups. We suggest the potential utility of BCAAs as an early biomarker for T2DM irrespective of follow-up time

Ice sheet and palaeoclimate controls on drainage network evolution: an example from Dogger Bank, North Sea

Submerged landscapes on continental shelves archive drainage networks formed during periods of sea-level lowstand. The evolution of these postglacial drainage networks also reveals how past climate changes affected the landscape. Ice-marginal and paraglacial drainage networks on low-relief topography are susceptible to reorganisation of water supply, forced by ice-marginal rearrangement, precipitation and temperature variations, and marine inundation. A rare geological archive of climate-driven landscape evolution during the transition from ice-marginal (ca. 23 ka) to a fully submerged marine environment (ca. 8 ka) is preserved at Dogger Bank, in the southern North Sea. In this study, our analysis of high-resolution seismic reflection and cone penetration test data reveal a channel network over a 1330 km2 area that incised glacial and proglacial lake-fill sediments. The channel network sits below coastal and shallow marine sediments and is therefore interpreted to represent a terrestrial drainage network. When mapped out, the channel form morphology reveals two distinct sets. The first set comprises two low-sinuosity, wide (>400 m) channels that contain macroforms of braid and side bars. These channels are interpreted to have originated as proglacial rivers, which drained the ice-sheet margin to the north. The second set of channels (75–200 m wide, with one larger, ∼400 m wide) has higher sinuosity and forms a subdendritic network of tributaries to the proglacial channels. The timing of channel formation lacks chronostratigraphic control. However, the proglacial rivers must have formed as the ice sheet was still on Dogger Bank, before 23 ka, to supply meltwater to the rivers. Ice-sheet retreat from Dogger Bank led to reorganisation of meltwater drainage and abandonment of the proglacial rivers. Palaeoclimate simulations show a cold and dry period at Dogger Bank between 23 and 17 ka. After 17 ka, precipitation increased, and drainage of precipitation formed the second set of channels. The second set of rivers remained active until marine transgression of Dogger Bank at ca. 8.5–8 ka. Overall, this study provides a detailed insight into the evolution of river networks across Dogger Bank and highlights the interplay between external (climate) and internal (local) forcings in drainage network evolution

Tracing differences in iron supply to the Mid-Atlantic Ridge valley between hydrothermal vent sites: implications for the addition of iron to the deep ocean

Supply of iron (Fe) to the surface ocean supports primary productivity, and while hydrothermal input of Fe to the deep ocean is known to be extensive it remains poorly constrained. Global estimates of hydrothermal Fe supply rely on using dissolved Fe (dFe) to excess He (xs3He) ratios to upscale fluxes, but observational constraints on dFe/xs3He may be sensitive to assumptions linked to sampling and interpolation. We examined the variability in dFe/xs3He using two methods of estimation, for four vent sites with different geochemistry along the Mid-Atlantic Ridge. At both Rainbow and TAG, the plume was sampled repeatedly and the range of dFe/xs3He was 4 to 63 and 4 to 87 nmol:fmol, respectively, primarily due to differences in plume age. To account for background xs3He and shifting plume position, we calibrated He values using contemporaneous dissolved Mn (dMn). Applying this approach more widely, we found dFe/xs3He ratios of 12, 4–8, 4–44, and 4–86 nmol fmol−1 for the Menez Gwen, Lucky Strike, Rainbow, and TAG hydrothermal vent sites, respectively. Differences in plume dFe/xs3He across sites were not simply related to the vent endmember Fe and He fluxes. Within 40 km of the vents, the dFe/xs3He ratios decreased to 3–38 nmol fmol−1, due to the precipitation and subsequent settling of particulates. The ratio of colloidal Fe to dFe was consistently higher (0.67–0.97) than the deep N. Atlantic (0.5) throughout both the TAG and Rainbow plumes, indicative of Fe exchange between dissolved and particulate phases. Our comparison of TAG and Rainbow shows there is a limit to the amount of hydrothermal Fe released from vents that can form colloids in the rising plume. Higher particle loading will enhance the longevity of the Rainbow hydrothermal plume within the deep ocean assuming particles undergo continual dissolution/disaggregation. Future studies examining the length of plume pathways required to escape the ridge valley will be important in determining Fe supply from slow spreading mid-ocean ridges to the deep ocean, along with the frequency of ultramafic sites such as Rainbow. Resolving the ridge valley bathymetry and accounting for variability in vent sources in global biogeochemical models will be key to further constraining the hydrothermal Fe flux.</p

Tracing differences in iron supply to the Mid-Atlantic Ridge valley between hydrothermal vent sites: implications for the addition of iron to the deep ocean

Supply of iron (Fe) to the surface ocean supports primary productivity, and while hydrothermal input of Fe to the deep ocean is known to be extensive it remains poorly constrained. Global estimates of hydrothermal Fe supply rely on using dissolved Fe (dFe) to excess He (xs³He) ratios to upscale fluxes, but observational constraints on dFe/xs³He may be sensitive to assumptions linked to sampling and interpolation. We examined the variability in dFe/xs³He using two methods of estimation, for four vent sites with different geochemistry along the Mid-Atlantic Ridge. At both Rainbow and TAG, the plume was sampled repeatedly and the range of dFe/xs³He was 4 to 63 and 4 to 87 nmol:fmol, respectively, primarily due to differences in plume age. To account for background xs³He and shifting plume position, we calibrated He values using contemporaneous dissolved Mn (dMn). Applying this approach more widely, we found dFe/xs³He ratios of 12, 4–8, 4–44, and 4–86 nmol fmol−1 for the Menez Gwen, Lucky Strike, Rainbow, and TAG hydrothermal vent sites, respectively. Differences in plume dFe/xs³He across sites were not simply related to the vent endmember Fe and He fluxes. Within 40 km of the vents, the dFe/xs³He ratios decreased to 3–38 nmol fmol−1, due to the precipitation and subsequent settling of particulates. The ratio of colloidal Fe to dFe was consistently higher (0.67–0.97) than the deep N. Atlantic (0.5) throughout both the TAG and Rainbow plumes, indicative of Fe exchange between dissolved and particulate phases. Our comparison of TAG and Rainbow shows there is a limit to the amount of hydrothermal Fe released from vents that can form colloids in the rising plume. Higher particle loading will enhance the longevity of the Rainbow hydrothermal plume within the deep ocean assuming particles undergo continual dissolution/disaggregation. Future studies examining the length of plume pathways required to escape the ridge valley will be important in determining Fe supply from slow spreading mid-ocean ridges to the deep ocean, along with the frequency of ultramafic sites such as Rainbow. Resolving the ridge valley bathymetry and accounting for variability in vent sources in global biogeochemical models will be key to further constraining the hydrothermal Fe flux