Youth chances: integrated report

This document provides an overview of the key findings from this five-year ground-breaking research project about the experiences of lesbian, gay, bisexual, trans and questioning (LGBTQ) 16-25year olds in England funded by the Big Lottery Fund and conducted by METRO Charity in collaboration with Ergo Consulting and the University of Greenwich. Methods: The project surveyed 7,126 young people aged 16-25. Of these 6,514 were LGBTQ young people. 612 were heterosexual non-trans young people and 956 were trans young people. 29 commissioners of services for young people and 52 relevant service providers across England were also surveyed. Findings: Show high levels of discrimination, abuse and mental health issues that young LGBTQ people face which indicate a need for more to be done to improve the lives of LGBTQ young people. Sections of the report are: 1. Being different Over half of LGBQ respondents (53%) knew they were LGBQ by the age of 13. Over half of trans respondents (58%) knew they were trans by the same age. When coming out as LGBQ or trans, over four fifths of LGBQ respondents (81%) and nearly two thirds of trans respondents (62%) told a friend first. Over a quarter of LGBQ young people (29%) have not told their mother, nearly a half (45%) have not told their father, and 5% have not told anybody. Approximately half of trans respondents have not told parents or siblings that they are trans and 28% have not told anybody. Young people tell us that they most want emotional support to help them when they are coming out but most are not getting it. The second most important thing to them is to meet other LGBTQ people and again over half of them did not get this opportunity. 2. Participation LGBTQ young people are twice as likely not to feel accepted in the area where they currently live, compared to heterosexual non-trans young people. 59% of LGBTQ young people that would be interested in joining a religious organisation have stopped or reduced their involvement owing to their sexuality or gender identity. Over a third of LGBTQ young people (34%) are not able to be open about their sexuality or gender identity at a sports club they are involved in. 3. Staying safe 73% of the LGBTQ sample agreed that discrimination against LGB people is still common and 90% of the LGBTQ sample agreed that discrimination against trans people is still common. About three quarters of LGBTQ young people (74%) have experienced name calling, nearly a half (45%) have experienced harassment or threats and intimidation and almost a quarter (23%) have experienced physical assault. 88% of LGBTQ young people do not report incidents to the police and when cases are reported only 10% lead to a conviction. 29% of LGBTQ respondents reported domestic or familial abuse, compared to 25% of the heterosexual non trans group. Over a third (36%) of LGBTQ respondents cited their sexuality or gender identity as at least a contributing factor in the abuse. Almost one in five (18%) LGBTQ young people have experienced some form of sexual abuse, compared with one in ten (11%) of non-trans heterosexuals in our sample. Most LGBTQ respondents who have experienced sexual abuse (79%) have not received any help or support. Nearly one in ten LGBTQ young people report that they have had to leave home for reasons relating to their sexuality or gender identity. 4. Enjoying and achieving Nearly half of LGBTQ young people (49%) reported that their time at school was affected by discrimination or fear of discrimination. Consequences reported included missing lessons, achieving lower grades, feeling isolated and left out and having to move schools are all reported. 61% reported name calling because they were LGBTQ or people thought they were. This figure includes the experiences of heterosexual non-trans respondents: it is an issue for all young people. About one in five LGBTQ young people experience physical attack at school on account of their sexual identity or gender identity. The majority do not report this and only a small proportion of those who do experience resolution. For some reporting the abuse means that it gets worse. Around two thirds of LGBTQ young people say they learn a lot about relationships and safer sex between a man and a woman, compared to less than 5% who say they learn a lot about same sex relationships and safer sex. 89% of LGBTQ young people report learning nothing about bisexuality issues and 94% report learning nothing about transgender issues. Only 25% of LGBTQ young people report that they learned anything at school about safer sex for a male couple

First findings and molecular data of phlebotomus mascittii (diptera: Psychodidae) in the cantabrian cornice (northern spain)

Phlebotomus (Transphlebotomus) mascittii Grassi, 1908 (Diptera: Psychodidae) has been found in several European countries. In Spain, sporadic records were reported in the early ''80s in Catalonia (Northeast Spain), and it was never detected again. Recent entomological surveys carried out between 2004 and 2020 revealed the presence of several specimens of P. mascittii in Spain. The species identification was confirmed by both morphological and molecular analyses. The analyzed specimens belonged to the haplotype (COI_2) defined by one polymorphic site compared to other European specimens. Phlebotomus mascittii was found in low population densities in rural areas associated with livestock farms and in an urban cemetery during the summer season. This study provides the first records of this species in various localities along the Cantabrian cornice (Northern Spain) and represents its westernmost observation in the Palearctic region. The implications of the finding of this uncommon species are discussed at different levels, with emphasis on its suspected role in the transmission of leishmaniosis. © The Author(s) 2021

Domestic chicken diversity: Origin, distribution, and adaptation

Chicken is the most numerous among the domesticated livestock species. Across cultures, religions, and societies, chicken is widely accepted with little or no taboo compared to other domestic animals. Its adaptability to diverse environmental conditions and demonstrated potential for breeding improvement provide a unique genetic resource for addressing the challenges of food security in a world impacted by climatic change and human population growth. Recent studies, shedding new knowledge on the chicken genomes, have helped reconstruct its past evolutionary history. Here, we review the literature concerning the origin, dispersion, and adaptation of domestic chicken. We highlight the role of human and natural selection in shaping the diversity of the species and provide a few examples of knowledge gaps that may be the focus of future research

Efficient coupler between silicon photonic and metal-insulator-silicon-metal plasmonic waveguides

We report the experimental realization of a compact, efficient coupler between silicon waveguides and vertical metal-insulator-silicon-metal (MISM) plasmonic waveguides. Devices were fabricated using complementary metal-oxide-silicon technology processes, with copper layers that support low-loss plasmonic modes in the MISM structures at a wavelength of 1550 nm. By implementing a short (0.5 μm) optimized metal-insulator-silicon-insulator structure inserted between the photonic and plasmonic waveguide sections, we demonstrate experimental coupling loss of 2.5 dB, despite the high optical confinement of the MISM mode and mismatch with the silicon waveguide mode

Galectin-1 Deactivates Classically Activated Microglia and Protects from Inflammation-Induced Neurodegeneration

SummaryInflammation-mediated neurodegeneration occurs in the acute and the chronic phases of multiple sclerosis (MS) and its animal model, experimental autoimmune encephalomyelitis (EAE). Classically activated (M1) microglia are key players mediating this process. Here, we identified Galectin-1 (Gal1), an endogenous glycan-binding protein, as a pivotal regulator of M1 microglial activation that targets the activation of p38MAPK-, CREB-, and NF-κB-dependent signaling pathways and hierarchically suppresses downstream proinflammatory mediators, such as iNOS, TNF, and CCL2. Gal1 bound to core 2 O-glycans on CD45, favoring retention of this glycoprotein on the microglial cell surface and augmenting its phosphatase activity and inhibitory function. Gal1 was highly expressed in the acute phase of EAE, and its targeted deletion resulted in pronounced inflammation-induced neurodegeneration. Adoptive transfer of Gal1-secreting astrocytes or administration of recombinant Gal1 suppressed EAE through mechanisms involving microglial deactivation. Thus, Gal1-glycan interactions are essential in tempering microglial activation, brain inflammation, and neurodegeneration, with critical therapeutic implications for MS

Determinants of the current and future distribution of the West Nile virus mosquito vector Culex pipiens in Spain

Changes in environmental conditions, whether related or not to human activities, are continuously modifying the geographic distribution of vectors, which in turn affects the dynamics and distribution of vector-borne infectious diseases. Determining the main ecological drivers of vector distribution and how predicted changes in these drivers may alter their future distributions is therefore of major importance. However, the drivers of vector populations are largely specific to each vector species and region. Here, we identify the most important human-activity-related and bioclimatic predictors affecting the current distribution and habitat suitability of the mosquito Culex pipiens and potential future changes in its distribution in Spain. We determined the niche of occurrence (NOO) of the species, which considers only those areas lying within the range of suitable environmental conditions using presence data. Although almost ubiquitous, the distribution of Cx. pipiens is mostly explained by elevation and the degree of urbanization but also, to a lesser extent, by mean temperatures during the wettest season and temperature seasonality. The combination of these predictors highlights the existence of a heterogeneous pattern of habitat suitability, with most suitable areas located in the southern and northeastern coastal areas of Spain, and unsuitable areas located at higher altitude and in colder regions. Future climatic predictions indicate a net decrease in distribution of up to 29.55%, probably due to warming and greater temperature oscillations. Despite these predicted changes in vector distribution, their effects on the incidence of infectious diseases are, however, difficult to forecast since different processes such as local adaptation to temperature, vector-pathogen interactions, and human-derived changes in landscape may play important roles in shaping the future dynamics of pathogen transmission.info:eu-repo/semantics/acceptedVersio

Polarized secretion of Leukemia Inhibitory Factor

<p>Abstract</p> <p>Background</p> <p>The direction of cytokine secretion from polarized cells determines the cytokine's cellular targets. Leukemia inhibitory factor (LIF) belongs to the interleukin-6 (IL-6) family of cytokines and signals through LIFR/gp130. Three factors which may regulate the direction of LIF secretion were studied: the site of stimulation, signal peptides, and expression levels. Stimulation with IL-1β is known to promote IL-6 secretion from the stimulated membrane (apical or basolateral) in the human intestinal epithelial cell line Caco-2. Since LIF is related to IL-6, LIF secretion was also tested in Caco-2 following IL-1β stimulation. Signal peptides may influence the trafficking of LIF. Two isoforms of murine LIF, LIF-M and LIF-D, encode different signal peptides which have been associated with different locations of the mature protein in fibroblasts. To determine the effect of the signal peptides on LIF secretion, secretion levels were compared in Madin-Darby canine kidney (MDCK) clones which expressed murine LIF-M or LIF-D or human LIF under the control of an inducible promoter. Low and high levels of LIF expression were also compared since saturation of the apical or basolateral route would reveal specific transporters for LIF.</p> <p>Results</p> <p>When Caco-2 was grown on permeable supports, LIF was secreted constitutively with around 40% secreted into the apical chamber. Stimulation with IL-1β increased LIF production. After treating the apical surface with IL-1β, the percentage secreted apically remained similar to the untreated, whereas, when the cells were stimulated at the basolateral surface only 20% was secreted apically. In MDCK cells, an endogenous LIF-like protein was detected entirely in the apical compartment. The two mLIF isoforms showed no difference in their secretion patterns in MDCK. Interestingly, about 70% of murine and human LIF was secreted apically from MDCK over a 400-fold range of expression levels within clones and a 200,000-fold range across clones.</p> <p>Conclusion</p> <p>The site of stimulation affected the polarity of LIF secretion, while, signal peptides and expression levels did not. Exogenous LIF is transported in MDCK without readily saturated steps.</p

Feasibility, acceptability, and effectiveness of non-pharmaceutical interventions against infectious diseases among crisis-affected populations: a scoping review

BACKGROUND: Colonization of large part of Europe by the Asian tiger mosquito Aedes albopictus is causing autochthonous transmission of chikungunya and dengue exotic arboviruses. While pyrethroids are recommended only to reduce/limit transmission, they are widely implemented to reduce biting nuisance and to control agricultural pests, increasing the risk of insurgence of resistance mechanisms. Worryingly, pyrethroid resistance (with mortality < 70%) was recently reported in Ae. albopictus populations from Italy and Spain and associated with the V1016G point mutation in the voltage-sensitive sodium channel gene conferring knockdown resistance (kdr). Genotyping pyrethroid resistance-associated kdr mutations in field mosquito samples represents a powerful approach to detect early signs of resistance without the need for carrying out phenotypic bioassays which require availability of live mosquitoes, dedicated facilities and appropriate expertise. METHODS: Here we report results on the PCR-genotyping of the V1016G mutation in 2530 Ae. albopictus specimens from 69 sampling sites in 19 European countries. RESULTS: The mutation was identified in 12 sites from nine countries (with allele frequencies ranging from 1 to 8%), mostly distributed in two geographical clusters. The western cluster includes Mediterranean coastal sites from Italy, France and Malta as well as single sites from both Spain and Switzerland. The eastern cluster includes sites on both sides of the Black Sea in Bulgaria, Turkey and Georgia as well as one site from Romania. These results are consistent with genomic data showing high connectivity and close genetic relationship among West European populations and a major barrier to gene flow between West European and Balkan populations. CONCLUSIONS: The results of this first effort to map kdr mutations in Ae. albopictus on a continental scale show a widespread presence of the V1016G allele in Europe, although at lower frequencies than those previously reported from Italy. This represents a wake-up call for mosquito surveillance programs in Europe to include PCR-genotyping of pyrethroid resistance alleles, as well as phenotypic resistance assessments, in their routine activities

Geographic distribution of the V1016G knockdown resistance mutation in aedes albopictus. A warning bell for Europe

Background: Colonization of large part of Europe by the Asian tiger mosquito Aedes albopictus is causing autochthonous transmission of chikungunya and dengue exotic arboviruses. While pyrethroids are recommended only to reduce/limit transmission, they are widely implemented to reduce biting nuisance and to control agricultural pests, increasing the risk of insurgence of resistance mechanisms. Worryingly, pyrethroid resistance (with mortality &lt; 70%) was recently reported in Ae. albopictus populations from Italy and Spain and associated with the V1016G point mutation in the voltage-sensitive sodium channel gene conferring knockdown resistance (kdr). Genotyping pyrethroid resistance-associated kdr mutations in field mosquito samples represents a powerful approach to detect early signs of resistance without the need for carrying out phenotypic bioassays which require availability of live mosquitoes, dedicated facilities and appropriate expertise.Methods: Here we report results on the PCR-genotyping of the V1016G mutation in 2530 Ae. albopictus specimens from 69 sampling sites in 19 European countries.Results: The mutation was identified in 12 sites from nine countries (with allele frequencies ranging from 1 to 8%), mostly distributed in two geographical clusters. The western cluster includes Mediterranean coastal sites from Italy, France and Malta as well as single sites from both Spain and Switzerland. The eastern cluster includes sites on both sides of the Black Sea in Bulgaria, Turkey and Georgia as well as one site from Romania. These results are consistent with genomic data showing high connectivity and close genetic relationship among West European populations and a major barrier to gene flow between West European and Balkan populations.Conclusions: The results of this first effort to map kdr mutations in Ae. albopictus on a continental scale show a widespread presence of the V1016G allele in Europe, although at lower frequencies than those previously reported from Italy. This represents a wake-up call for mosquito surveillance programs in Europe to include PCR-genotyping of pyrethroid resistance alleles, as well as phenotypic resistance assessments, in their routine activities

Structure and Function of ABCG2-Rich Extracellular Vesicles Mediating Multidrug Resistance

Multidrug resistance (MDR) is a major impediment to curative cancer chemotherapy. The ATP-Binding Cassette transporters ABCG2, ABCB1 and ABCC2 form a unique defense network against multiple structurally and functionally distinct chemotherapeutics, thereby resulting in MDR. Thus, deciphering novel mechanisms of MDR and their overcoming is a major goal of cancer research. Recently we have shown that overexpression of ABCG2 in the membrane of novel extracellular vesicles (EVs) in breast cancer cells results in mitoxantrone resistance due to its dramatic sequestration in EVs. However, nothing is known about EVs structure, biogenesis and their ability to concentrate multiple antitumor agents. To this end, we here found that EVs are structural and functional homologues of bile canaliculi, are apically localized, sealed structures reinforced by an actin-based cytoskeleton and secluded from the extracellular milieu by the tight junction proteins occludin and ZO-1. Apart from ABCG2, ABCB1 and ABCC2 were also selectively targeted to the membrane of EVs. Moreover, Ezrin-Radixin-Moesin protein complex selectively localized to the border of the EVs membrane, suggesting a key role for the tethering of MDR pumps to the actin cytoskeleton. The ability of EVs to concentrate and sequester different antitumor drugs was also explored. Taking advantage of the endogenous fluorescence of anticancer drugs, we found that EVs-forming breast cancer cells display high level resistance to topotecan, imidazoacridinones and methotrexate via efficient intravesicular drug concentration hence sequestering them away from their cellular targets. Thus, we identified a new modality of anticancer drug compartmentalization and resistance in which multiple chemotherapeutics are actively pumped from the cytoplasm and highly concentrated within the lumen of EVs via a network of MDR transporters differentially targeted to the EVs membrane. We propose a composite model for the structure and function of MDR pump-rich EVs in cancer cells and their ability to confer multiple anticancer drug resistance