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[ Lesbian, Gay, Bisexual, and Transgendered ] Open Question :  Am I a lesbian?

I'll try to keep this short: So I have always dated guys. Yet when I am not dating guys, my best friend and I; who's a girl, hook up. We've been doing this for about 5 years, we met at the age of 15, and 5 yrs later I had my first lesbian experience with her, and then 5 years it became a fairly regular thing. 5 years is obviously a long time. But when I'm not dating a guy, I always go back to her. And she's the only woman I have ever been with. That's why I am confused about this. I do not know if I'm straight or a lesbian?




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transgender charge heavy money and using slangs,abusing me because

sir on dated 4 th January 2020 I have a baby child born ,after 2 weeks some transgender came to my home and demanding huge mone a sums of 30000 and when I had refused to give then are using slang languages and doing mischevious activities
like doing toilet infront of my home,harassing us .sir what are punishement according to Indian law for Them,please tell so that from next time I will take the steps against for them.
from Kolkata




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Low-level presence of transgenic plants in seed and grain commodities: Environmental risk/safety Assessment, and availability and use of information

This Biosafety document aims to serve as an aid to risk assessors and regulators; providing guidance on handling the aspects of an environmental safety assessment, accessing and using information in situations of low-level presence (LLP) of transgenic plants in seed and grain commodities.




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Safety Assessment of Foods and Feeds Derived from Transgenic Crops, Volume 1

Volume I of this series compiles the science-based consensus documents of the OECD Task Force for the Safety of Novel Foods and Feeds from 2002 to 2008.




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Transgender inmates have carried out seven sex attacks on women in jail

Official figures show for the first time the true scale of offending by criminals who were born male but were allowed to move into female jails after changing gender. Convicted rapist Karen White pictured.




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Transgender inmates have carried out seven sex attacks on women in jail

Official figures show for the first time the true scale of offending by criminals who were born male but were allowed to move into female jails after changing gender. Convicted rapist Karen White pictured.




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In meso crystallogenesis. Compatibility of the lipid cubic phase with the synthetic digitonin analogue, glyco-diosgenin

Digitonin has long been used as a mild detergent for extracting proteins from membranes for structure and function studies. As supplied commercially, digitonin is inhomogeneous and requires lengthy pre-treatment for reliable downstream use. Glyco-diosgenin (GDN) is a recently introduced synthetic surfactant with features that mimic digitonin. It is available in homogeneously pure form. GDN is proving to be a useful detergent, particularly in the area of single-particle cryo-electron microscopic studies of membrane integral proteins. With a view to using it as a detergent for crystallization trials by the in meso or lipid cubic phase method, it was important to establish the carrying capacity of the cubic mesophase for GDN. This was quantified in the current study using small-angle X-ray scattering for mesophase identification and phase microstructure characterization as a function of temperature and GDN concentration. The data show that the lipid cubic phase formed by hydrated monoolein tolerates GDN to concentrations orders of magnitude in excess of those used for membrane protein studies. Thus, having GDN in a typical membrane protein preparation should not deter use of the in meso method for crystallogenesis.




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Pakistan opens first school for transgender students

The Gender Guardian offers 12 years of education, from elementary school to college.




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Fiori is a New Social Networking App For Trans People and Their Cisgender Allies

App developers have always struggled to create a safe networking space that suits transgender and non-binary people. Fiori has finally made this possible.




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Justice Department Charges Two Defendants with Carjacking and Carrying a Firearm in Relation to a Crime of Violence in Connection with the Death of Two Transgender Individuals

The Justice Department announced today that Juan Carlos Pagán Bonilla (Pagan), 21, and Sean Díaz de León (Diaz), 19, have been charged by a criminal complaint in federal district court with carjacking and with using and carrying a firearm during and in relation to a crime of violence in connection with the death of two transgender individuals. Pagan and Diaz are now in federal custody.




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Soybean plant and seed corresponding to transgenic event MON87769 and methods for detection thereof

The present invention provides transgenic soybean event MON87769, and cells, seeds, and plants comprising DNA diagnostic for the soybean event. The invention also provides compositions comprising nucleotide sequences that are diagnostic for said soybean event in a sample, methods for detecting the presence of said soybean event nucleotide sequences in a sample, probes and primers for use in detecting nucleotide sequences that are diagnostic for the presence of said soybean event in a sample, growing the seeds of such soybean event into soybean plants, and breeding to produce soybean plants comprising DNA diagnostic for the soybean event.




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'Love and Hip Hop' Star Joseline Hernandez's New Videos Fuel Transgender Rumors

The videos in question, which are taken during what looks like a photo shoot, show the actress/reality TV star appearing to have a bulge underneath her form-fitting jeans.




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Transgender woman had to tick Australian Tax Office's mental illness box to get early access to super

Why does the Australian Tax Office require people to tick a mental illness box for early access to their superannuation to fund gender transition surgery?




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Transgender law reform to allow Victorians to change birth certificate gender without surgery

The Victorian Government prepares to reintroduce a bill which would make it easier for people to alter the sex recorded on their birth certificate to male, female or any other gender descriptor of their choice.




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Penny Whetton, wife of Senator Janet Rice, climate scientist and transgender woman, dies

Victorian Greens Senator Janet Rice announces her wife, renowned climate scientist and transgender woman Penny Whetton, has died suddenly at their home in northern Tasmania.




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Modern transgender family: The naturally conceived Canberra baby with DNA from both of his parents

The Sutherlands hope that telling their story will help transgender parents be accepted to the point where, one day, "no-one bats an eyelid".



  • ABC Radio Canberra
  • canberra
  • Community and Society:All:All
  • Community and Society:Family and Children:All
  • Community and Society:Family and Children:Marriage
  • Community and Society:Sexuality:All
  • Health:All:All
  • Health:Reproduction and Contraception:All
  • Health:Reproduction and Contraception:Pregnancy and Childbirth
  • Australia:ACT:All
  • Australia:ACT:Canberra 2600

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Transgender Woman Nina Pop Murdered in Missouri

On Sunday, May 3rd, the body of 28-year-old transgender woman Nina Pop was found in her apartment in Sikestown, Missouri. She had been stabbed multiple times, according to police. While police have not determined a motive, they are looking into the possibility of a hate crime. The LGBTQ advocacy group Human Rights Campaign reported that Pop’s murder is at least the 10th violent death of a transgender or gender nonconforming person this year, and the fifth in the past month. All five of the recent victims were transgender women of color. Tori Cooper, director of community engagement for HRC’s Transgender Justice Initiative, wrote in a blog post, “for the past four weeks, we have seen the deaths of five transgender women of color in this country. We are seeing an epidemic of violence that can no longer be ignored. Transgender and gender-nonconforming people, especially trans women of color, risk our lives by living as our true selves — and we are being violently killed for doing so”. Transgender and gender nonconforming people lack expansive, explicit federal legal protections to safeguard against the vast discrimination they receive. While they are covered under the state’s hate crimes legislation, they are not explicitly […]




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Transgender woman housed with men repeatedly raped in Brooklyn federal lockup: lawsuit

A transgender woman awaiting trial on charges that she swindled elderly women out of their savings was raped repeatedly in jail after she was housed against her will with rowdy male inmates, according to a new lawsuit.




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Pioneering transgender actor Brian Michael Smith social distances far from home

A regular in Fox's '9-1-1: Lone Star,' Smith has gotten a lot of reading done as he waits out the pandemic in a friend's guestroom.




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Mario Lopez criticized for saying it’s ‘dangerous’ for parents to accept their young kids as transgender

The “Saved by the Bell” star later apologized for stirring controversy in a resurfaced interview with conservative Candace Owens.




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{alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease]

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.




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{alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are maȷor seed-competent species [Molecular Bases of Disease]

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.




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Effects of Gender-Affirming Hormone Therapy on Insulin Sensitivity and Incretin Responses in Transgender People

OBJECTIVE

The long-term influences of sex hormone administration on insulin sensitivity and incretin hormones are controversial. We investigated these effects in 35 transgender men (TM) and 55 transgender women (TW) from the European Network for the Investigation of Gender Incongruence (ENIGI) study.

RESEARCH DESIGN AND METHODS

Before and after 1 year of gender-affirming hormone therapy, body composition and oral glucose tolerance tests (OGTTs) were evaluated.

RESULTS

In TM, body weight (2.8 ± 1.0 kg; P < 0.01), fat-free mass (FFM) (3.1 ± 0.9 kg; P < 0.01), and waist-to-hip ratio (–0.03 ± 0.01; P < 0.01) increased. Fasting insulin (–1.4 ± 0.8 mU/L; P = 0.08) and HOMA of insulin resistance (HOMA-IR) (2.2 ± 0.3 vs. 1.8 ± 0.2; P = 0.06) tended to decrease, whereas fasting glucose (–1.6 ± 1.6 mg/dL), glucose-dependent insulinotropic polypeptide (GIP) (–1.8 ± 1.0 pmol/L), and glucagon-like peptide 1 (GLP-1) (–0.2 ± 1.1 pmol/L) were statistically unchanged. Post-OGTT areas under the curve (AUCs) for GIP (2,068 ± 1,134 vs. 2,645 ± 1,248 [pmol/L] x min; P < 0.01) and GLP-1 (2,352 ± 796 vs. 2,712 ± 1,015 [pmol/L] x min; P < 0.01) increased. In TW, body weight tended to increase (1.4 ± 0.8 kg; P = 0.07) with decreasing FFM (–2.3 ± 0.4 kg; P < 0.01) and waist-to-hip ratio (–0.03 ± 0.01; P < 0.01). Insulin (3.4 ± 0.8 mU/L; P < 0.01) and HOMA-IR (1.7 ± 0.1 vs. 2.4 ± 0.2; P < 0.01) rose, fasting GIP (–1.4 ± 0.8 pmol/L; P < 0.01) and AUC GIP dropped (2,524 ± 178 vs. 1,911 ± 162 [pmol/L] x min; P < 0.01), but fasting glucose (–0.3 ± 1.4 mg/dL), GLP-1 (1.3 ± 0.8 pmol/L), and AUC GLP-1 (2,956 ± 180 vs. 2,864 ± 93 [pmol/L] x min) remained unchanged.

CONCLUSIONS

In this cohort of transgender persons, insulin sensitivity but also post-OGTT incretin responses tend to increase with masculinization and to decrease with feminization.




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I’m a Cisgender Woman and My Husband Watches Trans Porn: Does That Mean He’s Not Into Me?

A reader submitted the following question: “I recently discovered that my husband is attracted to transsexuals (MTF - non op). This is the only type of porn that he looks at. He also role plays online with men for sexual play and chat. I discovered this after I started snooping because I had some red flags. He is very embarrassed and uncomfortable discussing it. He has apologized for the online chatting (as we had agreed this was out of bounds for our relationship). He says he likes them because they are feminine but his primary attraction is to women (with female parts). However, I just am not sure I believe him. I am terrified that when we are intimate (which I have to pretty much beg for), he can only do it when its dark and I am fearful he is fantasizing that I have a penis. This bothers me deeply on a number of different levels. Are there men who are only interested in transsexuals? Is it possible he is no longer turned on by my female genitalia?” There’s a lot to unpack in this question, but let’s start here: over the years, I’ve received several emails from women describing similar stories and concerns, so you’re not alone in feeling the way that you do.



  • Sex Question Friday
  • Sexual Problems and Solutions

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Groups seek injunction to stop Idaho transgender sports ban




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Groups seek injunction to stop Idaho transgender sports ban




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Trump Administration Weighs In On Lawsuit Against State's Transgender-Athlete Policy

The Trump administration weighed into a lawsuit, arguing that a state's transgender-athlete policy forces "biological girls to compete against biological boys who publicly identify with the female gender and want to compete on sex-specific athletic teams."




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Federal Appeals Court Upholds Oregon District's Pro-Transgender 'Safety Plan'

A federal appeals court rejected a multi-pronged challenge to a school district plan allowing transgender students to use restrooms and other facilities that match their gender identity.




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This State Just Became the First to Restrict Transgender Student Athletes' Participation

Idaho became the first state in the country to prohibit transgender girls from participating in girls' school sports after Gov. Brad Little, a Republican, signed the "Fairness in Women's Sports Act" into law Tuesday.




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Groups seek injunction to stop Idaho transgender sports ban




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Parce que, travestis et transgenres, notre regard sur le mode et les autres se veut teinté de respect et de douceur / Hommefleur.

Châtillon, France : Association Hommefleur, [date of publication not identified]




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Transgender and gender nonconforming health and aging

9783319950310 (electronic bk.)




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High-Level Neuronal Expression of A{beta}1-42 in Wild-Type Human Amyloid Protein Precursor Transgenic Mice: Synaptotoxicity without Plaque Formation

Lennart Mucke
Jun 1, 2000; 20:4050-4058
Cellular




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MECP2 Duplication Causes Aberrant GABA Pathways, Circuits and Behaviors in Transgenic Monkeys: Neural Mappings to Patients with Autism

MECP2 gain-of-function and loss-of-function in genetically engineered monkeys recapitulates typical phenotypes in patients with autism, yet where MECP2 mutation affects the monkey brain and whether/how it relates to autism pathology remain unknown. Here we report a combination of gene–circuit–behavior analyses including MECP2 coexpression network, locomotive and cognitive behaviors, and EEG and fMRI findings in 5 MECP2 overexpressed monkeys (Macaca fascicularis; 3 females) and 20 wild-type monkeys (Macaca fascicularis; 11 females). Whole-genome expression analysis revealed MECP2 coexpressed genes significantly enriched in GABA-related signaling pathways, whereby reduced β-synchronization within fronto-parieto-occipital networks was associated with abnormal locomotive behaviors. Meanwhile, MECP2-induced hyperconnectivity in prefrontal and cingulate networks accounted for regressive deficits in reversal learning tasks. Furthermore, we stratified a cohort of 49 patients with autism and 72 healthy controls of 1112 subjects using functional connectivity patterns, and identified dysconnectivity profiles similar to those in monkeys. By establishing a circuit-based construct link between genetically defined models and stratified patients, these results pave new avenues to deconstruct clinical heterogeneity and advance accurate diagnosis in psychiatric disorders.

SIGNIFICANCE STATEMENT Autism spectrum disorder (ASD) is a complex disorder with co-occurring symptoms caused by multiple genetic variations and brain circuit abnormalities. To dissect the gene–circuit–behavior causal chain underlying ASD, animal models are established by manipulating causative genes such as MECP2. However, it is unknown whether such models have captured any circuit-level pathology in ASD patients, as demonstrated by human brain imaging studies. Here, we use transgenic macaques to examine the causal effect of MECP2 overexpression on gene coexpression, brain circuits, and behaviors. For the first time, we demonstrate that the circuit abnormalities linked to MECP2 and autism-like traits in the monkeys can be mapped to a homogeneous ASD subgroup, thereby offering a new strategy to deconstruct clinical heterogeneity in ASD.




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Transgender Students, Athletics, Bullying: What the Equality Act Would Mean for Schools

Supporters of the bill say it would extend critical civil rights protections to more students. But opponents say it ignores parents' rights in schools and could lead to confusing situations for some children.




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Narrow Definition of Sex Could Affect Transgender Students

The Trump administration's move to narrowly define gender according to sex assigned at birth could impact transgender students and schools' policies with respect to their rights.




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Feds Probing Transgender Policy, Alleged Assault

The Education Department's office for civil rights will investigate whether a Georgia elementary school's policy for transgender students contributed to the alleged assault of a girl.




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When School's a Battleground for Transgender Kids, Teachers Learn to Protect, Affirm Them

Equipping teachers to help transgender students feel safe and included requires special training, advocates say.




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Transgender Youth Experiences and Perspectives Related to HIV Preventive Services

BACKGROUND:

In the United States, transgender youth are at especially high risk for HIV infection. Literature regarding HIV prevention strategies for this vulnerable, often-hidden population is scant. Before effective, population-based HIV prevention strategies may be adequately developed, it is necessary to first enhance the contextual understanding of transgender youth HIV risk and experiences with HIV preventive services.

METHODS:

Two 3-day, online, asynchronous focus groups were conducted with transgender youth from across the United States to better understand participant HIV risk and experiences with HIV preventive services. Participants were recruited by using online advertisements posted via youth organizations. Qualitative data were analyzed by using content analysis.

RESULTS:

A total of 30 transgender youth participated. The average age was 18.6 years, and youth reported a wide range of gender identities (eg, 27% were transgender male, 17% were transgender female, and 27% used ≥1 term) and sexual orientations. Four themes emerged: (1) barriers to self-efficacy in sexual decision-making; (2) safety concerns, fear, and other challenges in forming romantic and/or sexual relationships; (3) need for support and education; and (4) desire for affirmative and culturally competent experiences and interactions (eg, home, school, and health care).

CONCLUSIONS:

Youth discussed experiences and perspectives related to their gender identities, sexual health education, and HIV preventive services. Findings should inform intervention development to improve support and/or services, including the following: (1) increasing provider knowledge and skills to provide gender-affirming care, (2) addressing barriers to services (eg, accessibility and affordability as well as stigma and discrimination), and (3) expanding sexual health education to be inclusive of all gender identities, sexual orientations, and definitions of sex and sexual activity.




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Transgender Adolescent Suicide Behavior

Russell B. Toomey
Oct 1, 2018; 142:e20174218-e20174218
ARTICLES




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Mental Health of Transgender Children Who Are Supported in Their Identities

Kristina R. Olson
Mar 1, 2016; 137:e20153223-e20153223
ARTICLES




sgen

Groups seek injunction to stop Idaho transgender sports ban




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Transgender Teachers Speak Out on What They Need From School Leaders

In a recent video message, transgender teachers urge school leaders to make schools more welcoming by examining their own biases and implementing inclusive policies.




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Top Egyptian actor speaks out about transgender son


Hesham Selim's appearance on the TV show led to yet another wave of support for LGBTQ rights in Egypt on social media, with many praising the actor for his support for his son.




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Covid-19 a reminder for the need of transgenders inclusion in society

Islamabad : The coronavirus pandemic has increased the transgender persons' socioeconomic vulnerability and isolation, so short and long-term measures, especially by the government, are imperative to support them and ensure alternate means of livelihood in the changing environment.This was the...




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Addressing Needs of Transgender Patients: The Role of Family Physicians

There are approximately 1 million transgender and gender-diverse adults in the United States. Despite increased awareness and acceptance, they frequently encounter medical settings that are not welcoming and/or health care providers who are not knowledgeable about their health needs. Use of correct terminology, following best practices for name and pronoun use, and knowledge of gender-affirming interventions can create office environments that are welcoming to transgender clients. Health disparities faced by transgender patients that impact access to care include higher rates of mental health issues, substance use disorders, violence, and poverty. Transgender women are at greater risk for HIV acquisition and are less likely to achieve viral suppression compared with cisgender (nontransgender) individuals. Medical providers can facilitate HIV prevention efforts by offering pre- and postexposure prophylaxis to transgender patients at risk for HIV infection. Improving health outcomes requires attention to cultural competency and an understanding of lived experiences and priorities of transgender people.




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Human recreation decreases antibody titre in bird nestlings: an overlooked transgenerational effect of disturbance [RESEARCH ARTICLE]

Yves Bötsch, Zulima Tablado, Bettina Almasi, and Lukas Jenni

Outdoor recreational activities are booming and most animals perceive humans as predators, which triggers behavioural and/or physiological reactions [e.g. heart rate increase, activation of the hypothalamic–pituitary–adrenal (HPA) axis]. Physiological stress reactions have been shown to affect the immune system of an animal and therefore may also affect the amount of maternal antibodies a female transmits to her offspring. A few studies have revealed that the presence of predators affects the amount of maternal antibodies deposited into eggs of birds. In this study, using Eurasian blue and great tit offspring (Cyanistes caeruleus and Parus major) as model species, we experimentally tested whether human recreation induces changes in the amount of circulating antibodies in young nestlings and whether this effect is modulated by habitat and competition. Moreover, we investigated whether these variations in antibody titre in turn have an impact on hatching success and offspring growth. Nestlings of great tit females that had been disturbed by experimental human recreation during egg laying had lower antibody titres compared with control nestlings. Antibody titre of nestling blue tits showed a negative correlation with the presence of great tits, rather than with human disturbance. The hatching success was positively correlated with the average amount of antibodies in great tit nestlings, independent of the treatment. Antibody titre in the first days of life in both species was positively correlated with body mass, but this relationship disappeared at fledging and was independent of treatment. We suggest that human recreation may have caused a stress-driven activation of the HPA axis in breeding females, chronically increasing their circulating corticosterone, which is known to have an immunosuppressive function. Either, lower amounts of antibodies are transmitted to nestlings or impaired transfer mechanisms lead to lower amounts of immunoglobulins in the eggs. Human disturbance could, therefore, have negative effects on nestling survival at early life-stages, when nestlings are heavily reliant on maternal antibodies, and in turn lead to lower breeding success and parental fitness. This is a so far overlooked effect of disturbance on early life in birds.




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{alpha}-Synuclein filaments from transgenic mouse and human synucleinopathy-containing brains are ma&#x0237;or seed-competent species [Molecular Bases of Disease]

Assembled α-synuclein in nerve cells and glial cells is the defining pathological feature of neurodegenerative diseases called synucleinopathies. Seeds of α-synuclein can induce the assembly of monomeric protein. Here, we used sucrose gradient centrifugation and transiently transfected HEK 293T cells to identify the species of α-synuclein from the brains of homozygous, symptomatic mice transgenic for human mutant A53T α-synuclein (line M83) that seed aggregation. The most potent fractions contained Sarkosyl-insoluble assemblies enriched in filaments. We also analyzed six cases of idiopathic Parkinson's disease (PD), one case of familial PD, and six cases of multiple system atrophy (MSA) for their ability to induce α-synuclein aggregation. The MSA samples were more potent than those of idiopathic PD in seeding aggregation. We found that following sucrose gradient centrifugation, the most seed-competent fractions from PD and MSA brains are those that contain Sarkosyl-insoluble α-synuclein. The fractions differed between PD and MSA, consistent with the presence of distinct conformers of assembled α-synuclein in these different samples. We conclude that α-synuclein filaments are the main driving force for amplification and propagation of pathology in synucleinopathies.




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NO-Releasing Nanoparticles Ameliorate Detrusor Overactivity in Transgenic Sickle Cell Mice via Restored NO/ROCK Signaling [Cellular and Molecular]

Sickle cell disease (SCD) is associated with overactive bladder (OAB). Detrusor overactivity, a component of OAB, is present in an SCD mouse, but the molecular mechanisms for this condition are not well-defined. We hypothesize that nitric oxide (NO)/ ras homolog gene family (Rho) A/Rho-associated kinase (ROCK) dysregulation is a mechanism for detrusor overactivity and that NO-releasing nanoparticles (NO-nps), a novel NO delivery system, may serve to treat this condition. Male adult SCD transgenic, combined endothelial NO synthases (eNOSs) and neuronal NOS (nNOS) gene-deficient (dNOS–/–), and wild-type (WT) mice were used. Empty nanoparticle or NO-np was injected into the bladder, followed by cystometric studies. The expression levels of phosphorylated eNOS (Ser-1177), protein kinase B (Akt) (Ser-473), nNOS (Ser-1412), and myosin phosphatase target subunit 1 (MYPT1) (Thr-696) were assessed in the bladder. SCD and dNOS–/– mice had a greater (P < 0.05) number of voiding and nonvoiding contractions compared with WT mice, and they were normalized by NO-np treatment. eNOS (Ser-1177) and AKT (Ser-473) phosphorylation were decreased (P < 0.05) in the bladder of SCD compared with WT mice and reversed by NO-np. Phosphorylated MYPT1, a marker of the RhoA/ROCK pathway, was increased (P < 0.05) in the bladder of SCD mice compared with WT and reversed by NO-np. nNOS phosphorylation on positive (Ser-1412) regulatory site was decreased (P < 0.05) in the bladder of SCD mice compared with WT and was not affected by NO-np. NO-nps did not affect any of the measured parameters in WT mice. In conclusion, dysregulation of NO and RhoA/ROCK pathways is associated with detrusor overactivity in SCD mice; NO-np reverses these molecular derangements in the bladder and decreases detrusor overactivity.

SIGNIFICANCE STATEMENT

Voiding abnormalities commonly affect patients with sickle cell disease (SCD) but are problematic to treat. Clarification of the science for this condition in an animal model of SCD may lead to improved interventions for it. Our findings suggest that novel topical delivery of a vasorelaxant agent nitric oxide into the bladder of these mice corrects overactive bladder by improving deranged bladder physiology regulatory signaling.




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Brazil cooks up transgenic bean

Approval draws criticism over transparency and safety tests.