Does GPER1 play a role in sexual dimorphism?

Estrogens are critical in driving sex-typical social behaviours that are ethologically relevant in mammals. This is due to both production of local estrogens and signaling by these ligands, particularly in an interconnected set of nuclei called the social behavioural network (SBN). The SBN is a sexually dimorphic network studied predominantly in rodents that is thought to underlie the display of social behaviour in mammals. Signalling by the predominant endogenous estrogen, 17b-estradiol, can be either via the classical genomic or non-classical rapid pathway. In the classical genomic pathway, 17bestradiol binds the intracellular estrogen receptors (ER) a and b which act as liganddependent transcription factors to regulate transcription. In the non-genomic pathway, 17b-estradiol binds a putative plasma membrane ER (mER) such as GPR30/GPER1 to rapidly signal via kinases or calcium flux. Though GPER1’s role in sexual dimorphism has been explored to a greater extent in cardiovascular physiology, less is known about its role in the brain. In the last decade, activation of GPER1 has been shown to be important for lordosis and social cognition in females. In this review we will focus on several mechanisms that may contribute to sexually dimorphic behaviors including the colocalization of these estrogen receptors in the SBN, interplay between the signaling pathways activated by these different estrogen receptors, and the role of these receptors in development and the maintenance of the SBN, all of which remain underexplored

Investigation into the Aroma of Rosemary using Multi-Channel Silicone Rubber Traps, Off-line Olfactometry and Comprehensive Two-dimensional Gas Chromatography-Mass Spectrometry

Multi-channel polydimethylsiloxane rubber traps were used to sample the headspace of rosemary samples (two essential oils from different sources, one oleoresin and one dried herb) followed by comprehensive two-dimensional gas chromatography – time of flight mass spectrometry(GCxGC-TOFMS)orGC-MSanalyses. The aromaof different headspace samples was characterized using a custom-built olfactory apparatus. The differences between the aroma profiles were evident from bubble plots of the perceived aroma at different temperatures. The samples were heat-treated to simulate cooking of food products, and were then reassessed to determine any changes in the aroma profile. It was found that the intense menthol and cooling aromas subsided in all the samples with heating. GCxGC-TOFMS allowed for separation of the numerous components in the headspace samples. Manyterpenes and aliphatics were thus tentatively identified and the relative peak areas were compared to better understand the mixture that contributes to the rosemary aroma.KEYWORDS Rosemary, multi-channel silicone rubber traps, GCxGC-TOFMS, essential oil, off-line olfactometry

The Asian-African film connection: cross-cultural imaginaries, shared sources, parallel histories

This Dossier is inspired by two urgent needs in Film and Screen Studies, particularly within the UK context, but also globally – the need to transform the content of what we research and teach, and the need to transform the methodologies through which we research and teach. The articles presented here emerged out of “The Asian-African Film Connection” workshop held at SOAS University of London in July 2018 – an event specifically designed to bring UK-based African and Asian film scholars into conversation with one another, to explore cinematic sources, themes and aesthetics that both link and divide these two regions

Little angels: The mediation of parenting

This Article does not have an abstract

Exploring the contribution of lifestyle to the impact of education on the risk of cancer through Mendelian randomization analysis

Data availability: UK Biobank individual level data used in this work can be accessed after applying for access at https://www.ukbiobank.ac.uk/enable-your-research/apply-for-access. Genetic association data are publicly available in the original studies.Supplementary Information is available online at: https://link.springer.com/article/10.1038/s41598-024-54259-7#Sec17 .Educational attainment (EA) has been linked to the risk of several types of cancer, despite having no expected direct biological connection. In this paper, we investigate the mediating role of alcohol consumption, smoking, vegetable consumption, fruit consumption and body mass index (BMI) in explaining the effect of EA on 7 cancer groupings. Large-scale genome wide association study (GWAS) results were used to construct the genetic instrument for EA and the lifestyle factors. We conducted GWAS in the UK Biobank sample in up to 335,024 individuals to obtain genetic association data for the cancer outcomes. Univariable and multivariable two-sample Mendelian randomization (MR) analyses and mediation analyses were then conducted to explore the causal effect and mediating proportions of these relations. MR mediation analysis revealed that reduced lifetime smoking index accounted for 81.7% (49.1% to 100%) of the protective effect of higher EA on lower respiratory cancer. Moreover, the effect of higher EA on lower respiratory cancer was mediated through vegetable consumption by 10.2% (4.4% to 15.9%). We found genetic evidence that the effect of EA on groups of cancer is due to behavioural changes in avoiding well established risk factors such as smoking and vegetable consuming.Brunel Research Initiative and Enterprise Fund to FD. This research has been conducted using the UK Biobank Resource under project 44566 (https://www.ukbiobank.ac.uk/2018/12/genetic-and-non-genetic-factors-able-to-predict-and-modify-the-risk-of-different-types-of-cancer/)

Inhibition of αvβ5 Integrin Attenuates Vascular Permeability and Protects against Renal Ischemia-Reperfusion Injury

Ischemia-reperfusion injury (IRI) is a leading cause of AKI. This common clinical complication lacks effective therapies and can lead to the development of CKD. The αvβ5 integrin may have an important role in acute injury, including septic shock and acute lung injury. To examine its function in AKI, we utilized a specific function-blocking antibody to inhibit αvβ5 in a rat model of renal IRI. Pretreatment with this anti-αvβ5 antibody significantly reduced serum creatinine levels, diminished renal damage detected by histopathologic evaluation, and decreased levels of injury biomarkers. Notably, therapeutic treatment with the αvβ5 antibody 8 hours after IRI also provided protection from injury. Global gene expression profiling of post-ischemic kidneys showed that αvβ5 inhibition affected established injury markers and induced pathway alterations previously shown to be protective. Intravital imaging of post-ischemic kidneys revealed reduced vascular leak with αvβ5 antibody treatment. Immunostaining for αvβ5 in the kidney detected evident expression in perivascular cells, with negligible expression in the endothelium. Studies in a three-dimensional microfluidics system identified a pericyte-dependent role for αvβ5 in modulating vascular leak. Additional studies showed αvβ5 functions in the adhesion and migration of kidney pericytes in vitro Initial studies monitoring renal blood flow after IRI did not find significant effects with αvβ5 inhibition; however, future studies should explore the contribution of vasomotor effects. These studies identify a role for αvβ5 in modulating injury-induced renal vascular leak, possibly through effects on pericyte adhesion and migration, and reveal αvβ5 inhibition as a promising therapeutic strategy for AKI

Identification Of A Germline F692L Drug Resistance Variant In Cis With Flt3-ITD In Knock-In Mice

Letter to the Editor.-- Dovey, Oliver M. et al.Internal tandem duplication (ITD) mutations in the juxtamembrane domain of the fms-like tyrosine kinase 3 (FLT3) gene occur in approximately one quarter of cases of acute myeloid leukemia (AML), are associated with constitutive activation of the kinase and confer a poor prognosis.BC is funded by the >China Scholarship Council> for his visiting studies in UK. AM is funded by the Kay Kendall Leukaemia Fund project grant. CG was funded by a Bloodwise Clinical Research Training Fellowship. IV is funded by Spanish Ministerio de Economía y Competitividad subprograma Ramón y Cajal. We thank Servicio Santander Supercomputación for their support. OMD, JLC and GSV are funded by a Wellcome Trust Senior Fellowship in Clinical Science (WT095663MA) and this work was also funded by the Wellcome Trust Sanger InstitutePeer Reviewe

Identification Of A Germline F692L Drug Resistance Variant In Cis With Flt3-ITD In Knock-In Mice

Letter to the Editor.-- Dovey, Oliver M. et al.Internal tandem duplication (ITD) mutations in the juxtamembrane domain of the fms-like tyrosine kinase 3 (FLT3) gene occur in approximately one quarter of cases of acute myeloid leukemia (AML), are associated with constitutive activation of the kinase and confer a poor prognosis.BC is funded by the >China Scholarship Council> for his visiting studies in UK. AM is funded by the Kay Kendall Leukaemia Fund project grant. CG was funded by a Bloodwise Clinical Research Training Fellowship. IV is funded by Spanish Ministerio de Economía y Competitividad subprograma Ramón y Cajal. We thank Servicio Santander Supercomputación for their support. OMD, JLC and GSV are funded by a Wellcome Trust Senior Fellowship in Clinical Science (WT095663MA) and this work was also funded by the Wellcome Trust Sanger InstitutePeer Reviewe

Prostate cancer biomarkers: a practical review based on different clinical scenarios

Traditionally, diagnosis and staging of prostate cancer (PCa) have been based on prostate-specific antigen (PSA) level, digital rectal examination (DRE), and transrectal ultrasound (TRUS) guided prostate biopsy. Biomarkers have been introduced into clinical practice to reduce the overdiagnosis and overtreatment of low-grade PCa and increase the success of personalized therapies for high-grade and high-stage PCa. The purpose of this review was to describe available PCa biomarkers and examine their use in clinical practice. A nonsystematic literature review was performed using PubMed and Scopus to retrieve papers related to PCa biomarkers. In addition, we manually searched websites of major urological associations for PCa guidelines to evaluate available evidence and recommendations on the role of biomarkers and their potential contribution to PCa decision-making. In addition to PSA and its derivates, thirteen blood, urine, and tissue biomarkers are mentioned in various PCa guidelines. Retrospective studies have shown their utility in three main clinical scenarios: (1) deciding whether to perform a biopsy, (2) distinguishing patients who require active treatment from those who can benefit from active surveillance, and (3) defining a subset of high-risk PCa patients who can benefit from additional therapies after RP. Several validated PCa biomarkers have become commercially available in recent years. Guidelines now recommend offering these tests in situations in which the assay result, when considered in combination with routine clinical factors, is likely to affect management. However, the lack of direct comparisons and the unproven benefits, in terms of long-term survival and cost-effectiveness, prevent these biomarkers from being integrated into routine clinical use