Role of Androgens in Female Genitourinary Tissue Structure and Function: Implications in the Genitourinary Syndrome of Menopause.

Abstract Introduction Genitourinary conditions in women increase in prevalence with age. Androgens are prerequisite hormones of estrogen biosynthesis, are produced in larger amounts than estrogens in women, and decrease throughout adulthood. However, research and treatment for genitourinary complaints have traditionally focused on estrogens to the exclusion of other potential hormonal influences. Aim To summarize and evaluate the evidence that androgens are important for maintaining genitourinary health in women and that lack of androgenic activity can contribute to the development of symptoms of the genitourinary syndrome of menopause. Methods The role of androgens in the pathophysiology, diagnosis, and treatment of genitourinary syndrome of menopause was discussed by an international and multidisciplinary panel during a consensus conference organized by the International Society for the Study of Women's Sexual Health. A subgroup further examined publications from the PubMed database, giving preference to clinical studies or to basic science studies in human tissues. Main Outcome Measures Expert opinion evaluating trophic and functional effects of androgens, their differences from estrogenic effects, and regulation of androgen and estrogen receptor expression in female genitourinary tissues. Results Androgen receptors have been detected throughout the genitourinary system using immunohistochemical, western blot, ligand binding, and gene expression analyses. Lower circulating testosterone and estradiol concentrations and various genitourinary conditions have been associated with differential expression of androgen and estrogen receptors. Supplementation of androgen and/or estrogen in postmenopausal women (local administration) or in ovariectomized animals (systemic administration) induces tissue-specific responses that include changes in androgen and estrogen receptor expression, cell growth, mucin production, collagen turnover, increased perfusion, and neurotransmitter synthesis. Conclusion Androgens contribute to the maintenance of genitourinary tissue structure and function. The effects of androgens can be distinct from those of estrogens or can complement estrogenic action. Androgen-mediated processes might be involved in the full or partial resolution of genitourinary syndrome of menopause symptoms in women. Traish AM, Vignozzi L, Simon JA, et al. Role of Androgens in Female Genitourinary Tissue Structure and Function: Implications in the Genitourinary Syndrome of Menopause. Sex Med Rev 2018;6:558–571

Leigh syndrome mimicking neuromyelitis optica spectrum disorder (NMOSD)

We report two children with molecularly confirmed mitochondrial disease mimicking Neuromyelitis Optica Spectrum Disorder (NMOSD). The first patient presented at the age of 15 months with acute deterioration following a pyrexial illness with clinical features localising to the brainstem and spinal cord. The second patient presented at 5 years with acute bilateral visual loss. In both cases, MOG and AQP4 antibodies were negative. Both patients died within a year of symptoms onset from respiratory failure. Arriving at an early genetic diagnosis is important for redirection of care and avoiding potentially harmful immunosuppressant therapies

Reefs of tomorrow: nutrients drive coral biodiversity in an urbanized seascape

Session - Human ImpactsMarine ecosystems have experienced dramatic changes since the 1850s in response to human activities. This epoch, often referred to as the Anthropocene, has witnessed the punctuated loss of reef-building corals worldwide. Coral reef degradation may induce subtle changes which remain un-witnessed; this is particularly true when the water quality is altered. Deteriorated water quality hampers coral larvae recruitment, amplifies bio-erosion, favors coral diseases and reduces the threshold of thermal …published_or_final_versio

Acoustic Emission Analysis of SCS-6 Fiber Fracture in Titanium Matrix Composites

One aspect of successful composite design involves development of a detailed knowledge of damage evolution. In metal matrix composites, cracking and/or plastic deformation of one or more constituents together with fiber-matrix interfacial debonding and sliding generally occur prior to catastrophic failure [1, 2]. The nature and severity of these damage processes controls mechanical performance. In ductile matrix systems having a low fiber-matrix interfacial strength, the failure process can involve successive fragmentation of the fibers with increasing load. Broken fibers shed load (equally among the unbroken fibers in the case of global load sharing) until the fiber fracture density reaches some critical value and the sample catastrophically fails. Characterization of damage development has been slowed by a lack of NDE techniques. Here, the use of acoustic emission (AE) techniques is explored to further understand and quantify failure processes of this type.</p

Revisiting Date and Party Hubs: Novel Approaches to Role Assignment in Protein Interaction Networks

The idea of 'date' and 'party' hubs has been influential in the study of protein-protein interaction networks. Date hubs display low co-expression with their partners, whilst party hubs have high co-expression. It was proposed that party hubs are local coordinators whereas date hubs are global connectors. Here we show that the reported importance of date hubs to network connectivity can in fact be attributed to a tiny subset of them. Crucially, these few, extremely central, hubs do not display particularly low expression correlation, undermining the idea of a link between this quantity and hub function. The date/party distinction was originally motivated by an approximately bimodal distribution of hub co-expression; we show that this feature is not always robust to methodological changes. Additionally, topological properties of hubs do not in general correlate with co-expression. Thus, we suggest that a date/party dichotomy is not meaningful and it might be more useful to conceive of roles for protein-protein interactions rather than individual proteins. We find significant correlations between interaction centrality and the functional similarity of the interacting proteins.Comment: 27 pages, 5 main figures, 4 supplementary figure

Profiling allele-specific gene expression in brains from individuals with autism spectrum disorder reveals preferential minor allele usage.

One fundamental but understudied mechanism of gene regulation in disease is allele-specific expression (ASE), the preferential expression of one allele. We leveraged RNA-sequencing data from human brain to assess ASE in autism spectrum disorder (ASD). When ASE is observed in ASD, the allele with lower population frequency (minor allele) is preferentially more highly expressed than the major allele, opposite to the canonical pattern. Importantly, genes showing ASE in ASD are enriched in those downregulated in ASD postmortem brains and in genes harboring de novo mutations in ASD. Two regions, 14q32 and 15q11, containing all known orphan C/D box small nucleolar RNAs (snoRNAs), are particularly enriched in shifts to higher minor allele expression. We demonstrate that this allele shifting enhances snoRNA-targeted splicing changes in ASD-related target genes in idiopathic ASD and 15q11-q13 duplication syndrome. Together, these results implicate allelic imbalance and dysregulation of orphan C/D box snoRNAs in ASD pathogenesis

Cancer cells exploit an orphan RNA to drive metastatic progression.

Here we performed a systematic search to identify breast-cancer-specific small noncoding RNAs, which we have collectively termed orphan noncoding RNAs (oncRNAs). We subsequently discovered that one of these oncRNAs, which originates from the 3' end of TERC, acts as a regulator of gene expression and is a robust promoter of breast cancer metastasis. This oncRNA, which we have named T3p, exerts its prometastatic effects by acting as an inhibitor of RISC complex activity and increasing the expression of the prometastatic genes NUPR1 and PANX2. Furthermore, we have shown that oncRNAs are present in cancer-cell-derived extracellular vesicles, raising the possibility that these circulating oncRNAs may also have a role in non-cell autonomous disease pathogenesis. Additionally, these circulating oncRNAs present a novel avenue for cancer fingerprinting using liquid biopsies

Prompt atmospheric neutrino fluxes: perturbative QCD models and nuclear effects

We evaluate the prompt atmospheric neutrino flux at high energies using three different frameworks for calculating the heavy quark production cross section in QCD: NLO perturbative QCD, $k_T$ factorization including low-$x$ resummation, and the dipole model including parton saturation. We use QCD parameters, the value for the charm quark mass and the range for the factorization and renormalization scales that provide the best description of the total charm cross section measured at fixed target experiments, at RHIC and at LHC. Using these parameters we calculate differential cross sections for charm and bottom production and compare with the latest data on forward charm meson production from LHCb at $7$ TeV and at $13$ TeV, finding good agreement with the data. In addition, we investigate the role of nuclear shadowing by including nuclear parton distribution functions (PDF) for the target air nucleus using two different nuclear PDF schemes. Depending on the scheme used, we find the reduction of the flux due to nuclear effects varies from $10\%$ to $50 \%$ at the highest energies. Finally, we compare our results with the IceCube limit on the prompt neutrino flux, which is already providing valuable information about some of the QCD models.Comment: 61 pages, 25 figures, 11 table