Interlobular and intralobular mammary stroma: Genotype may not reflect phenotype

<p>Abstract</p> <p>Background</p> <p>The normal growth and function of mammary epithelial cells depend on interactions with the supportive stroma. Alterations in this communication can lead to the progression or expansion of malignant growth. The human mammary gland contains two distinctive types of fibroblasts within the stroma. The epithelial cells are surrounded by loosely connected intralobular fibroblasts, which are subsequently surrounded by the more compacted interlobular fibroblasts. The different proximity of these fibroblasts to the epithelial cells suggests distinctive functions for these two subtypes. In this report, we compared the gene expression profiles between the two stromal subtypes.</p> <p>Methods</p> <p>Fresh normal breast tissue was collected from reduction mammoplasty patients and immediately placed into embedding medium and frozen on dry ice. Tissue sections were subjected to laser capture microscopy to isolate the interlobular from the intralobular fibroblasts. RNA was prepared and subjected to microarray analysis using the Affymetrix Human Genome U133 GeneChip^®. Data was analyzed using the Affy and Limma packages available from Bioconductor. Findings from the microarray analysis were validated by RT-PCR and immunohistochemistry.</p> <p>Results</p> <p>No statistically significant difference was detected between the gene expression profiles of the interlobular and intralobular fibroblasts by microarray analysis and RT-PCR. However, for some of the genes tested, the protein expression patterns between the two subtypes of fibroblasts were significantly different.</p> <p>Conclusion</p> <p>This study is the first to report the gene expression profiles of the two distinct fibroblast populations within the human mammary gland. While there was no significant difference in the gene expression profiles between the groups, there was an obvious difference in the expression pattern of several proteins tested. This report also highlights the importance of studying gene regulation at both the transcriptional and post-translational level.</p

On the Commutative Equivalence of Context-Free Languages

The problem of the commutative equivalence of context-free and regular languages is studied. In particular conditions ensuring that a context-free language of exponential growth is commutatively equivalent with a regular language are investigated

Disruption of a Proto-Planetary Disk by the Black Hole at the Milky Way Centre

Recently, an ionized cloud of gas was discovered plunging toward the supermassive black hole, SgrA*, at the centre of the Milky Way. The cloud is being tidally disrupted along its path to closest approach at ~3100 Schwarzschild radii from the black hole. Here, we show that the observed properties of this cloud of gas can naturally be produced by a proto-planetary disk surrounding a low-mass star, which was scattered from the observed ring of young stars orbiting SgrA*. As the young star approaches the black hole, its disk experiences both photo-evaporation and tidal disruption, producing a cloud. Our model implies that planets form in the Galactic centre, and that tidal debris from proto-planetary disks can flag low mass stars which are otherwise too faint to be detected.Comment: Accepted to Nature Communications; new Figure 4b provides predicted Br-gamma emission as a function of tim

A Review of Studies Evaluating Insecticide Barrier Treatments for Mosquito Control From 1944 to 2018

Background and Purpose: Barrier insecticide treatments have a long history in mosquito control programs but have been used more frequently in the United States in recent years for control of invasive “backyard� species (eg, Aedes albopictus) and increases in incidence of vector-borne diseases (eg, Zika). Methods: We reviewed the published literature for studies investigating barrier treatments for mosquito control during the last 74 years (1944-2018). We searched databases such as PubMed, Web of Science, and Google Scholar to retrieve worldwide literature on barrier treatments. Results: Forty-four studies that evaluated 20 active ingredients (AIs) and 21 formulated products against multiple mosquito species are included. Insecticides investigated for efficacy included organochlorines (dichlorodiphenyltrichloroethane [DDT], β-hexachlorocyclohexane [BHC]), organophosphates (malathion), and pyrethroids (bifenthrin, deltamethrin, permethrin, lambda-cyhalothrin) as AIs. Study design varied with multiple methods used to evaluate effectiveness of barrier treatments. Barrier treatments were effective at lowering mosquito populations although there was variation between studies and for different mosquito species. Factors other than AI, such as exposure to rainfall and application equipment used, also influenced control efficacy. Conclusions: Many of the basic questions on the effectiveness of barrier insecticide applications have been answered, but several important details still must be investigated to improve precision and impact on vector-borne pathogen transmission. Recommendations are made to assist future evaluations of barrier treatments for mosquito control and to limit the potential development of insecticide resistance

Unsupervised Bayesian linear unmixing of gene expression microarrays

Background: This paper introduces a new constrained model and the corresponding algorithm, called unsupervised Bayesian linear unmixing (uBLU), to identify biological signatures from high dimensional assays like gene expression microarrays. The basis for uBLU is a Bayesian model for the data samples which are represented as an additive mixture of random positive gene signatures, called factors, with random positive mixing coefficients, called factor scores, that specify the relative contribution of each signature to a specific sample. The particularity of the proposed method is that uBLU constrains the factor loadings to be non-negative and the factor scores to be probability distributions over the factors. Furthermore, it also provides estimates of the number of factors. A Gibbs sampling strategy is adopted here to generate random samples according to the posterior distribution of the factors, factor scores, and number of factors. These samples are then used to estimate all the unknown parameters. Results: Firstly, the proposed uBLU method is applied to several simulated datasets with known ground truth and compared with previous factor decomposition methods, such as principal component analysis (PCA), non negative matrix factorization (NMF), Bayesian factor regression modeling (BFRM), and the gradient-based algorithm for general matrix factorization (GB-GMF). Secondly, we illustrate the application of uBLU on a real time-evolving gene expression dataset from a recent viral challenge study in which individuals have been inoculated with influenza A/H3N2/Wisconsin. We show that the uBLU method significantly outperforms the other methods on the simulated and real data sets considered here. Conclusions: The results obtained on synthetic and real data illustrate the accuracy of the proposed uBLU method when compared to other factor decomposition methods from the literature (PCA, NMF, BFRM, and GB-GMF). The uBLU method identifies an inflammatory component closely associated with clinical symptom scores collected during the study. Using a constrained model allows recovery of all the inflammatory genes in a single factor

Generation of germline ablated male pigs by CRISPR/Cas9 editing of the NANOS2 gene

Genome editing tools have revolutionized the generation of genetically modified animals including livestock. In particular, the domestic pig is a proven model of human physiology and an agriculturally important species. In this study, we utilized the CRISPR/Cas9 system to edit the NANOS2 gene in pig embryos to generate offspring with mono-allelic and bi-allelic mutations. We found that NANOS2 knockout pigs phenocopy knockout mice with male specific germline ablation but other aspects of testicular development are normal. Moreover, male pigs with one intact NANOS2 allele and female knockout pigs are fertile. From an agriculture perspective, NANOS2 knockout male pigs are expected to serve as an ideal surrogate for transplantation of donor spermatogonial stem cells to expand the availability of gametes from genetically desirable sires

Paediatric obsessive-compulsive disorder and depressive symptoms: clinical correlates and CBT treatment outcomes.

Depression frequently co-occurs with paediatric obsessive-compulsive disorder (OCD), yet the clinical correlates and impact of depression on CBT outcomes remain unclear. The prevalence and clinical correlates of depression were examined in a paediatric specialist OCD-clinic sample (N = 295; Mean = 15 [7 - 18] years, 42 % female), using both dimensional (Beck Depression Inventory-youth; n = 261) and diagnostic (Development and Wellbeing Assessment; n = 127) measures of depression. The impact of depressive symptoms and suspected disorders on post-treatment OCD severity was examined in a sub-sample who received CBT, with or without SSRI medication (N = 100). Fifty-one per-cent of patients reported moderately or extremely elevated depressive symptoms and 26 % (95 % CI: 18 - 34) met criteria for a suspected depressive disorder. Depressive symptoms and depressive disorders were associated with worse OCD symptom severity and global functioning prior to CBT. Individuals with depression were more likely to be female, have had a psychiatric inpatient admission and less likely to be attending school (ps < 0.01). OCD and depressive symptom severity significantly decreased after CBT. Depressive symptoms and depressive disorders predicted worse post-treatment OCD severity (βs = 0.19 and 0.26, ps < 0.05) but became non-significant when controlling for pre-treatment OCD severity (βs = 0.05 and 0.13, ns). Depression is common in paediatric OCD and is associated with more severe OCD and poorer functioning. However, depression severity decreases over the course of CBT for OCD and is not independently associated with worse outcomes, supporting the recommendation for treatment as usual in the presence of depressive symptoms

The dynamical evolution of molecular clouds near the Galactic Centre - II. Spatial structure and kinematics of simulated clouds

The evolution of molecular clouds in galactic centres is thought to differ from that in galactic discs due to a significant influence of the external gravitational potential. We present a set of numerical simulations of molecular clouds orbiting on the 100-pc stream of the Central Molecular Zone (the central $\sim500$ pc of the Galaxy) and characterise their morphological and kinematic evolution in response to the background potential and eccentric orbital motion. We find that the clouds are shaped by strong shear and torques, by tidal and geometric deformation, and by their passage through the orbital pericentre. Within our simulations, these mechanisms control cloud sizes, aspect ratios, position angles, filamentary structure, column densities, velocity dispersions, line-of-sight velocity gradients, spin angular momenta, and kinematic complexity. By comparing these predictions to observations of clouds on the Galactic Centre 'dust ridge', we find that our simulations naturally reproduce a broad range of key observed morphological and kinematic features, which can be explained in terms of well-understood physical mechanisms. We argue that the accretion of gas clouds onto the central regions of galaxies, where the rotation curve turns over and the tidal field is fully compressive, is accompanied by transformative dynamical changes to the clouds, leading to collapse and star formation. This can generate an evolutionary progression of cloud collapse with a common starting point, which either marks the time of accretion onto the tidally-compressive region or of the most recent pericentre passage. Together, these processes may naturally produce the synchronised starbursts observed in numerous (extra)galactic nuclei

Primary retroperitoneal mucinous cystadenoma with sarcoma-like mural nodule: A case report and review of the literature

Primary retroperitoneal cystadenomas are extremely rare. This is the first report in literature to describe a primary retroperitoneal cystadenoma with a sarcoma-like mural nodule. A 45-year-old woman complained of a left-sided abdominal mass. A computed tomography scan revealed a cystic mass with a mural nodule, which seemed to originate from the tail of the pancreas. At laparotomy the cyst was not adhered to the pancreas but localized retroperitoneally. Histologic examination showed a mucinous cystadenoma with only foci of borderline malignancy with a mural “sarcoma-like” nodule. In view of the surgical and histopathological findings, the mucinous cystadenoma was regarded as primary retroperitoneal. This case demonstrates that in the era of radiological preoperative refinement, pathological diagnosis remains of utmost importance, especially for rare cases