Increased Expression of PITX2 Transcription Factor Contributes to Ovarian Cancer Progression

BACKGROUND: Paired-like homeodomain 2 (PITX2) is a bicoid homeodomain transcription factor which plays an essential role in maintaining embryonic left-right asymmetry during vertebrate embryogenesis. However, emerging evidence suggests that the aberrant upregulation of PITX2 may be associated with tumor progression, yet the functional role that PITX2 plays in tumorigenesis remains unknown. PRINCIPAL FINDINGS: Using real-time quantitative RT-PCR (Q-PCR), Western blot and immunohistochemical (IHC) analyses, we demonstrated that PITX2 was frequently overexpressed in ovarian cancer samples and cell lines. Clinicopathological correlation showed that the upregulated PITX2 was significantly associated with high-grade (P = 0.023) and clear cell subtype (P = 0.011) using Q-PCR and high-grade (P<0.001) ovarian cancer by IHC analysis. Functionally, enforced expression of PITX2 could promote ovarian cancer cell proliferation, anchorage-independent growth ability, migration/invasion and tumor growth in xenograft model mice. Moreover, enforced expression of PITX2 elevated the cell cycle regulatory proteins such as Cyclin-D1 and C-myc. Conversely, RNAi mediated knockdown of PITX2 in PITX2-high expressing ovarian cancer cells had the opposite effect. CONCLUSION: Our findings suggest that the increased expression PITX2 is involved in ovarian cancer progression through promoting cell growth and cell migration/invasion. Thus, targeting PITX2 may serve as a potential therapeutic modality in the management of high-grade ovarian tumor.published_or_final_versio

Depression and Sexual Orientation During Young Adulthood: Diversity Among Sexual Minority Subgroups and the Role of Gender Nonconformity.

Sexual minority individuals are at an elevated risk for depression compared to their heterosexual counterparts, yet less is known about how depression status varies across sexual minority subgroups (i.e., mostly heterosexuals, bisexuals, and lesbians and gay men). Moreover, studies on the role of young adult gender nonconformity in the relation between sexual orientation and depression are scarce and have yielded mixed findings. The current study examined the disparities between sexual minorities and heterosexuals during young adulthood in concurrent depression near the beginning of young adulthood and prospective depression 6 years later, paying attention to the diversity within sexual minority subgroups and the role of gender nonconformity. Drawn from the National Longitudinal Study of Adolescent Health (N = 9421), we found that after accounting for demographics, sampling weight, and sampling design, self-identified mostly heterosexual and bisexual young adults, but not lesbians and gay men, reported significantly higher concurrent depression compared to heterosexuals; moreover, only mostly heterosexual young adults were more depressed than heterosexuals 6 years later. Furthermore, while young adult gender nonconforming behavior was associated with more concurrent depression regardless of sexual orientation, its negative impact on mental health decreased over time. Surprisingly, previous gender nonconformity predicted decreased prospective depression among lesbians and gay men whereas, among heterosexual individuals, increased gender nonconformity was not associated with prospective depression. Together, the results suggested the importance of investigating diversity and the influence of young adult gender nonconformity in future research on the mental health of sexual minorities.The authors acknowledge support for this research: the University of Arizona Norton School of Family and Consumer Sciences Fitch Nesbitt Endowment and a University of Arizona Graduate Access Fellowship to the second author. This research uses data from Add Health, a program project directed by Kathleen Mullan Harris and designed by J. Richard Udry, Peter S. Bearman, and Kathleen Mullan Harris at the University of North Carolina at Chapel Hill, and funded by grant P01-HD31921 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development, with cooperative funding from 23 other federal agencies and foundations. Special acknowledgment is due Ronald R. Rindfuss and Barbara Entwisle for assistance in the original design. Information on how to obtain the Add Health data files is available on the Add Health website (http://​www.​cpc.​unc.​edu/​addhealth). No direct support was received from grant P01-HD31921 for this analysis. The authors thank Noel Card and Susan Stryker for comments on the previous versions of this article and Richard Lippa and Katerina Sinclair for methodological and statistical consult. The authors also thank the anonymous reviewers and the Editor for their helpful comments.This is the accepted manuscript of a paper published in Archives of Sexual Behavior (Li G, Pollitt AM, Russell ST, Archives of Sexual Behavior 2015, doi:10.1007/s10508-015-0515-3). The final version is available at http://dx.doi.org/10.1007/s10508-015-0515-3

Gender Nonconformity During Adolescence:Links with Stigma, Sexual Minority Status, and Psychosocial Outcomes

Both gender nonconformity and sexual minority status during adolescence are associated with elevated levels of victimization and harassment, experiences that have serious consequences for adolescent psychosocial outcomes. While gender nonconformity and sexual minority status reflect separate constructs, they are associated because (1) sexual minority youth report higher levels of gender nonconformity and (2) gender nonconformity is frequently used to attribute sexual minority status by others. Following from classic stigma theory, the current chapter focuses on the role of gender nonconformity in explaining variation in social exclusion and victimization among both sexual minority and sexual majority youth. Of particular interest is the potential for gender nonconformity to mediate or moderate the association between sexual minority status and individual mental health and wellbeing outcomes. Gender differences will also be discussed, focusing on differences between girls and boys in the links between sexual minority status, gender nonconformity, experiences of victimization, and negative psychosocial outcomes. Additionally, the emerging literature on conceptualizing gender nonconformity among trans and non-binary youth will be addressed. Finally, the current chapter will finish with a discussion of how and why gender nonconformity must be taken into consideration in the development of programs aimed at reducing homophobia among adolescent populations

Updated measurements of exclusive J/ψ and ψ(2S) production cross-sections in pp collisions at √s = 7 TeV

The differential cross-section as a function of rapidity has been measured for the exclusive production of J/ψ and ψ(2S) mesons in proton–proton collisions at √s = 7 TeV, using data collected by the LHCb experiment, corresponding to an integrated luminosity of 930 pb−1. The cross-sections times branching fractions to two muons having pseudorapidities between 2.0 and 4.5 are measured to be where the first uncertainty is statistical and the second is systematic. The measurements agree with next-to-leading order QCD predictions as well as with models that include saturation effects

First Measurement of the Charge Asymmetry in Beauty-Quark Pair Production

The difference in the angular distributions between beauty quarks and antiquarks, referred to as the charge asymmetry, is measured for the first time in b (b) over bar pair production at a hadron collider. The data used correspond to an integrated luminosity of 1.0 fb(-1) collected at 7 TeV center-of-mass energy in proton-proton collisions with the LHCb detector. The measurement is performed in three regions of the invariant mass of the b (b) over bar system. The results obtained are A(C)(b (b) over bar) (40 10(5) GeV/c(2)) = 1.6 +/- 1.7 +/- 0.6%,where A(C)(b (b) over bar) is defined as the asymmetry in the difference in rapidity between jets formed from the beauty quark and antiquark, where in each case the first uncertainty is statistical and the second systematic. The beauty jets are required to satisfy 2 20 GeV, and have an opening angle in the transverse plane Delta phi > 2.6 rad. These measurements are consistent with the predictions of the standard model

Observation of B(s)0→J/ψpp¯ decays and precision measurements of the B(s)0 masses

The first observation of the decays B 0 ( s ) → J / ψ p ¯ p is reported, using proton-proton collision data corresponding to an integrated luminosity of 5.2     fb − 1 , collected with the LHCb detector. These decays are suppressed due to limited available phase space, as well as due to Okubo-Zweig-Iizuka or Cabibbo suppression. The measured branching fractions are B ( B 0 → J / ψ p ¯ p ) = [ 4.51 ± 0.40 ( stat ) ± 0.44 ( syst ) ] × 10 − 7 , B ( B 0 s → J / ψ p ¯ p ) = [ 3.58 ± 0.19 ( stat ) ± 0.39 ( syst ) ] × 10 − 6 . For the B 0 s meson, the result is much higher than the expected value of O ( 10 − 9 ) . The small available phase space in these decays also allows for the most precise single measurement of both the B 0 mass as 5279.74 ± 0.30 ( stat ) ± 0.10 ( syst )     MeV and the B 0 s mass as 5366.85 ± 0.19 ( stat ) ± 0.13 ( syst )     MeV

Measurement of D s ^± production asymmetry in pp collisions at √s=7 and 8 TeV

The inclusive $D_s^{\pm}$ production asymmetry is measured in $pp$ collisions collected by the LHCb experiment at centre-of-mass energies of $\sqrt{s} =7$ and 8 TeV. Promptly produced $D_s^{\pm}$ mesons are used, which decay as $D_s^{\pm}\to\phi\pi^{\pm}$, with $\phi\to K^+K^-$. The measurement is performed in bins of transverse momentum, $p_{\rm T}$, and rapidity, $y$, covering the range $2.5<p_{\rm T}<25.0$ GeV$/c$ and $2.0<y<4.5$. No kinematic dependence is observed. Evidence of nonzero $D_s^{\pm}$ production asymmetry is found with a significance of 3.3 standard deviations.Comment: All figures and tables, along with any supplementary material and additional information, are available at https://cern.ch/lhcbproject/Publications/p/LHCb-PAPER-2018-010.htm

Observation of the decay Λ _b ⁰ → ψ(2S)pπ⁻

International audienceThe Cabibbo-suppressed decay Λ$_{b}^{0}$  → ψ(2S)pπ$^{−}$ is observed for the first time using a data sample collected by the LHCb experiment in proton-proton collisions corresponding to 1.0, 2.0 and 1.9 fb$^{−1}$ of integrated luminosity at centre-of-mass energies of 7, 8 and 13 TeV, respectively. The ψ(2S) mesons are reconstructed in the μ$^{+}$μ$^{−}$ final state. The branching fraction with respect to that of the Λ$_{b}^{0}$  → ψ(2S)pK$^{−}$ decay mode is measured to b

Search for CP violation in Λb0→pK− and Λb0→pπ− decays

A search for CP violation in Λb0→pK− and Λb0→pπ− decays is presented using a sample of pp collisions collected with the LHCb detector and corresponding to an integrated luminosity of 3.0fb−1. The CP -violating asymmetries are measured to be ACPpK−=−0.020±0.013±0.019 and ACPpπ−=−0.035±0.017±0.020, and their difference ACPpK−−ACPpπ−=0.014±0.022±0.010, where the first uncertainties are statistical and the second systematic. These are the most precise measurements of such asymmetries to date

Evidence for an nc(1S)ff- resonance in B0 yc(1S)K+ decays

A Dalitz plot analysis of B0→ηc(1S)K+π- decays is performed using data samples of pp collisions collected with the LHCb detector at centre-of-mass energies of s=7,8 and 13TeV , corresponding to a total integrated luminosity of 4.7fb-1 . A satisfactory description of the data is obtained when including a contribution representing an exotic ηc(1S)π- resonant state. The significance of this exotic resonance is more than three standard deviations, while its mass and width are 4096±20-22+18MeV and 152±58-35+60MeV , respectively. The spin-parity assignments JP=0+ and JP=1- are both consistent with the data. In addition, the first measurement of the B0→ηc(1S)K+π- branching fraction is performed and gives B(B0→ηc(1S)K+π-)=(5.73±0.24±0.13±0.66)×10-4, where the first uncertainty is statistical, the second systematic, and the third is due to limited knowledge of external branching fractions