LET-99 inhibits lateral posterior pulling forces during asymmetric spindle elongation in C. elegans embryos

GPR-1/2 (regulators of Gα signaling necessary for asymmetric cell division) receives a positional cue from Let-99, resulting in its appropriate distribution around the posterior cortex

A model describing diffusion in prostate cancer

PURPOSE: Quantitative diffusion MRI has frequently been studied as a means of grading prostate cancer. Interpretation of results is complicated by the nature of prostate tissue, which consists of four distinct compartments: vascular, ductal lumen, epithelium, and stroma. Current diffusion measurements are an ill-defined weighted average of these compartments. In this study, prostate diffusion is analyzed in terms of a model that takes explicit account of tissue compartmentalization, exchange effects, and the non-Gaussian behavior of tissue diffusion.  METHOD: The model assumes that exchange between the cellular (ie, stromal plus epithelial) and the vascular and ductal compartments is slow. Ductal and cellular diffusion characteristics are estimated by Monte Carlo simulation and a two-compartment exchange model, respectively. Vascular pseudodiffusion is represented by an additional signal at b = 0. Most model parameters are obtained either from published data or by comparing model predictions with the published results from 41 studies. Model prediction error is estimated using 10-fold cross-validation.  RESULTS: Agreement between model predictions and published results is good. The model satisfactorily explains the variability of ADC estimates found in the literature.  CONCLUSION: A reliable model that predicts the diffusion behavior of benign and cancerous prostate tissue of different Gleason scores has been developed. Magn Reson Med, 2016. © 2016 Wiley Periodicals, Inc

Benign Prostatic Hyperplasia/Obstruction Ameliorated Using a Soluble Guanylate Cyclase Activator

Benign prostatic hyperplasia (BPH) is a feature of ageing males. Up to half demonstrate bladder outlet obstruction (BOO) with associated lower urinary tract symptoms (LUTS) including bladder overactivity. Current therapies to reduce obstruction, such as α1-adrenoceptor antagonists and 5α-reductase inhibitors, are not effective in all patients. The phosphodiesterase-5 inhibitor (PDE5I) tadalafil is also approved to treat BPH and LUTS, suggesting a role for nitric oxide (NO•), soluble guanylate cyclase (sGC), and cGMP signalling pathways. However, PDE5I refractoriness can develop for reasons including nitrergic nerve damage and decreased NO• production, or inflammation-related oxidation of the sGC haem group, normally maintained in a reduced state by the cofactor cytochrome-b5-reductase 3 (CYB5R3). sGC activators, such as cinaciguat (BAY 58-2667), have been developed to enhance sGC activity in the absence of NO• or when sGC is oxidised. Accordingly, their effects on the prostate and LUT function of aged mice were evaluated. Aged mice (≥24 months) demonstrated a functional BPH/BOO phenotype, compared with adult animals (2–12 months), with low, delayed voiding responses and elevated intravesical pressures as measured by telemetric cystometry. This was consistent with outflow tract histological and molecular data that showed urethral constriction, increased prostate weight, greater collagen deposition, and cellular hyperplasia. All changes in aged animals were attenuated by daily oral treatment with cinaciguat for 2 weeks, without effect on serum testosterone levels. Cinaciguat had only transient (1 h) cardiovascular effects with oral gavage, suggesting a positive safety profile. The benefit of cinaciguat was suggested by its reversal of an overactive cystometric profile in CYB5R3 smooth muscle knockout mice that mirrors a profile of oxidative dysfunction where PDE5I may not be effective. Thus, the aged male mouse is a suitable model for BPH-induced BOO and cinaciguat has a demonstrated ability to reduce prostate-induced obstruction and consequent effects on bladder function

Interlingual annotation of parallel text corpora: a new framework for annotation and evaluation

This paper focuses on an important step in the creation of a system of meaning representation and the development of semantically annotated parallel corpora, for use in applications such as machine translation, question answering, text summarization, and information retrieval. The work described below constitutes the first effort of any kind to annotate multiple translations of foreign-language texts with interlingual content. Three levels of representation are introduced: deep syntactic dependencies (IL0), intermediate semantic representations (IL1), and a normalized representation that unifies conversives, nonliteral language, and paraphrase (IL2). The resulting annotated, multilingually induced, parallel corpora will be useful as an empirical basis for a wide range of research, including the development and evaluation of interlingual NLP systems and paraphrase-extraction systems as well as a host of other research and development efforts in theoretical and applied linguistics, foreign language pedagogy, translation studies, and other related disciplines