A review of hyperandrogenism state in polycystic ovarian syndrome

Polycystic ovary syndrome is one of the most prevalent endocrinopathy in premenopausal women. The pathophysiology of PCOS is not clear, however disturbance in the hypothalamic-pituitary-ovarian axis and abnormal steroidogenesis along with genetic and environmental factors act as main contributors to this disorder. The steroidogenic pathway is affected by the overexpression of the CYP11A, CYP17, and CYP19 genes in PCOS, which results in a hyperandrogenic condition. The initial effect of too much androgen in PCOS is impaired folliculogenesis. The most frequent clinical manifestations of hyperandrogenism in women with PCOS include hirsutism, acne, and androgenic alopecia. Women with PCOS may have an excess of androgen during foetal life due to the elevated expression of P450c17a during the whole pregnancy. PCOS is believed to be formed in utero by the influence of androgen excess on gene expression in adolescence and adulthood, which offers more solid evidence that real PCOS can be induced by prenatal androgenization. A prenatal androgen excess-induced epigenetic phenomena is suggested by the current theory of PCOS's developmental genesis. It is currently believed that the many tiny follicles seen in polycystic ovaries and the considerable irregularity in the very early stages of folliculogenesis are associated to the formation of anovulation in PCOS

The TANAMI Program

TANAMI (Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry) is a monitoring program to study the parsec-scale structures and dynamics of relativistic jets in active galactic nuclei (AGN) of the Southern Hemisphere with the Long Baseline Array and associated telescopes. Extragalactic jets south of -30 degrees declination are observed at 8.4 GHz and 22 GHz every two months at milliarcsecond resolution. The initial TANAMI sample is a hybrid radio and gamma-ray selected sample since the combination of VLBI and gamma-ray observations is crucial to understand the broadband emission characteristics of AGN.Comment: Confernce Proceedings for "X-ray Astronomy 2009" (Bologna), 3 pages, 3 figures, needs cls-fil

TANAMI: Tracking Active Galactic Nuclei with Austral Milliarcsecond Interferometry. III. First-epoch S band images

With the emergence of very high energy astronomy (VHE; E>100 GeV), new open questions were presented to astronomers studying the multi-wavelength emission from blazars. Answers to these open questions, such as the Doppler crisis, and finding the location of the high-energy activity have eluded us thus far. Recently, quasi-simultaneous multi-wavelength monitoring programs have shown considerable success in investigating blazar activity. After the launch of the Fermi Gamma-ray Space Telescope in 2008, such quasi-simultaneous observations across the electromagnetic spectrum became possible. In addition, with very long baseline interferometry (VLBI) observations we can resolve the central parsec region of active galactic nuclei (AGN) and compare morphological changes to the gamma-ray activity to study high-energy emitting blazars. To achieve our goals, we need sensitive, long-term VLBI monitoring of a complete sample of VHE detected AGN. We performed VLBI observations of TeV-detected AGN and high likelihood neutrino associations as of December of 2021 with the Long Baseline Array (LBA) and other southern hemisphere radio telescopes at 2.3 GHz. In this paper we present first light TANAMI S-band images, focusing on the TeV-detected sub-sample of the full TANAMI sample. Apart from these very high energy-detected sources, we also show images of the two flux density calibrators and two additional sources included in the observations. We study the redshift, 0.1-100 GeV photon flux and S-band core brightness temperature distributions of the TeV-detected objects, and find that flat spectrum radio quasars and low synchrotron peaked sources on average show higher brightness temperatures than high-synchrotron-peaked BL Lacs. Sources with bright GeV gamma-ray emission also show higher brightness temperature values than gamma-low sources

The Antarctic Submillimeter Telescope and Remote Observatory (AST/RO)

AST/RO, a 1.7 m diameter telescope for astronomy and aeronomy studies at wavelengths between 200 and 2000 microns, was installed at the South Pole during the 1994-1995 Austral summer. The telescope operates continuously through the Austral winter, and is being used primarily for spectroscopic studies of neutral atomic carbon and carbon monoxide in the interstellar medium of the Milky Way and the Magellanic Clouds. The South Pole environment is unique among observatory sites for unusually low wind speeds, low absolute humidity, and the consistent clarity of the submillimeter sky. Four heterodyne receivers, an array receiver, three acousto-optical spectrometers, and an array spectrometer are installed. A Fabry-Perot spectrometer using a bolometric array and a Terahertz receiver are in development. Telescope pointing, focus, and calibration methods as well as the unique working environment and logistical requirements of the South Pole are described.Comment: 57 pages, 15 figures. Submitted to PAS

Claudin-1, A Double-Edged Sword in Cancer.

Claudins, a group of membrane proteins involved in the formation of tight junctions, are mainly found in endothelial or epithelial cells. These proteins have attracted much attention in recent years and have been implicated and studied in a multitude of diseases. Claudins not only regulate paracellular transepithelial/transendothelial transport but are also critical for cell growth and differentiation. Not only tissue-specific but the differential expression in malignant tumors is also the focus of claudin-related research. In addition to up- or down-regulation, claudin proteins also undergo delocalization, which plays a vital role in tumor invasion and aggressiveness. Claudin (CLDN)-1 is the most-studied claudin in cancers and to date, its role as either a tumor promoter or suppressor (or both) is not established. In some cancers, lower expression of CLDN-1 is shown to be associated with cancer progression and invasion, while in others, loss of CLDN-1 improves the patient survival. Another topic of discussion regarding the significance of CLDN-1 is its localization (nuclear or cytoplasmic vs perijunctional) in diseased states. This article reviews the evidence regarding CLDN-1 in cancers either as a tumor promoter or suppressor from the literature and we also review the literature regarding the pattern of CLDN-1 distribution in different cancers, focusing on whether this localization is associated with tumor aggressiveness. Furthermore, we utilized expression data from The Cancer Genome Atlas (TCGA) to investigate the association between CLDN-1 expression and overall survival (OS) in different cancer types. We also used TCGA data to compare CLDN-1 expression in normal and tumor tissues. Additionally, a pathway interaction analysis was performed to investigate the interaction of CLDN-1 with other proteins and as a future therapeutic target

SAMHD1 promotes DNA end resection to facilitate DNA repair by homologous recombination

DNA double-strand break (DSB) repair by homologous recombination (HR) is initiated by CtIP/MRN-mediated DNA end resection to maintain genome integrity. SAMHD1 is a dNTP triphosphohydrolase, which restricts HIV- 1 infection, and mutations are associated with Aicardi-Goutières syndrome and cancer. We show that SAMHD1 has a dNTPase-independent function in promoting DNA end resection to facilitate DSB repair by HR. SAMHD1 deficiency or Vpx-mediated degradation causes hypersensitivity to DSB-inducing agents, and SAMHD1 is recruited to DSBs. SAMHD1 complexes with CtIP via a conserved C-terminal domain and recruits CtIP to DSBs to facilitate end resection and HR. Significantly, a cancer-associated mutant with impaired CtIP interaction, but not dNTPase-inactive SAMHD1, fails to rescue the end resection impairment of SAMHD1 depletion. Our findings define a dNTPase-independent function for SAMHD1 in HR-mediated DSB repair by facilitating CtIP accrual to promote DNA end resection, providing insight into how SAMHD1 promotes genome integrity