The Octavolateralis System and Mauthner Cell: Interactions and Questions

This paper is an overview of some of the major points to arise in the accompanying contributions of this special symposium issue. The symposium papers arose out of discussions among investigators interested in the inner ear and Mauthner cell, with the focus on hydrodynamic components that activate the Mauthner cell through the octavolateralis system. The intention of the symposium was to investigate the possibility of using our knowledge of the Mauthner system to help understand acoustic processing by the ear, and of using, our knowledge of fish hearing to better understand Mauthner cell function. This is the first attempt to take a broad look at both systems to see how they might function together. As such, these proceedings can serve as a mini-tutorial for investiaators interested in one system or the other. In this summary paper we also identify some of the major uncertainties in our understanding of the ear-Mauthner connection. These include questions about: (1) the identity of the acoustic stimuli that are neuroethologically relevant to the Mauthner system; (2) the relative importance of the various octavolateralis inputs (acoustic, vestibular, or lateral line); (3) the contribution of the different various acoustic endorgans to the Mauthner system; (4) whether the Mauthner system can distinguish sound source location; and (5) whether Mauthner neurobiology is compatible with the prevailing model (the phase model) for determining sound source location by fishes. We believe these issues provide potentially useful avenues of future investigation that should give important insights into both acoustic processing by fish and the function of the Mauthner system

The importance of the hydrophilic region of PsbL for the plastoquinone electron acceptor complex of Photosystem II

AbstractThe PsbL protein is a 4.5kDa subunit at the monomer–monomer interface of Photosystem II (PS II) consisting of a single membrane-spanning domain and a hydrophilic stretch of ~15 residues facing the cytosolic (or stromal) side of the photosystem. Deletion of conserved residues in the N-terminal region has been used to investigate the importance of this hydrophilic extension. Using Synechocystis sp. PCC 6803, three deletion strains: ∆(N6–N8), ∆(P11–V12) and ∆(E13–N15), have been created. The ∆(N6–N8) and ∆(P11–V12) strains remained photoautotrophic but were more susceptible to photodamage than the wild type; however, the ∆(E13–N15) cells had the most severe phenotype. The Δ(E13–N15) mutant showed decreased photoautotrophic growth, a reduced number of PS II centers, impaired oxygen evolution in the presence of PS II-specific electron acceptors, and was highly susceptible to photodamage. The decay kinetics of chlorophyll a variable fluorescence after a single turnover saturating flash and the sensitivity to low concentrations of PS II-directed herbicides in the Δ(E13–N15) strain indicate that the binding of plastoquinone to the QB-binding site had been altered such that the affinity of QB is reduced. In addition, the PS II-specific electron acceptor 2,5-dimethyl-p-benzoquinone was found to inhibit electron transfer through the quinone-acceptor complex of the ∆(E13–N15) strain. The PsbL Y20A mutant was also investigated and it exhibited increased susceptibility to photodamage and increased herbicide sensitivity. Our data suggest that the N-terminal hydrophilic region of PsbL influences forward electron transfer from QA through indirect interactions with the D–E loop of the D1 reaction center protein. Our results further indicate that disruption of interactions between the N-terminal region of PsbL and other PS II subunits or lipids destabilizes PS II dimer formation. This article is part of a Special Issue entitled: Photosynthesis Research for Sustainability: Keys to Produce Clean Energy

Aldosterone modulates the association between NCC and ENAC

Distal sodium transport is a final step in the regulation of blood pressure. As such, understanding how the two main sodium transport proteins, the thiazide-sensitive sodium chloride cotransporter (NCC) and the epithelial sodium channel (ENaC), are regulated is paramount. Both are expressed in the late distal nephron; however, no evidence has suggested that these two sodium transport proteins interact. Recently, we established that these two sodium transport proteins functionally interact in the second part of the distal nephron (DCT2). Given their co-localization within the DCT2, we hypothesized that NCC and ENaC interactions might be modulated by aldosterone (Aldo). Aldo treatment increased NCC and αENaC colocalization (electron microscopy) and interaction (coimmunoprecipitation). Finally, with co-expression of the Aldo-induced protein serum- and glucocorticoid-inducible kinase 1 (SGK1), NCC and αENaC interactions were increased. These data demonstrate that Aldo promotes increased interaction of NCC and ENaC, within the DCT2 revealing a novel method of regulation for distal sodium reabsorption

Interest-based Negotiations at Kaiser Permanente

In 1997 Kaiser Permanente (KP) and a coalition of 26 local unions representing nearly 70,000 Kaiser employees created what is now the nation's largest and most ambitious labor-management partnership. In 2000, the parties faced the major challenge of negotiating their first labor agreement under the new Partnership. They designed and implemented what is also the largest and most complex interest-based negotiations (IBN) process carried out to date in the field of labor-management relations. We describe this case here, both to provide an historical account of the process and to explore the lessons that might be learned from how these parties addressed a series of generic challenges encountered when introducing IBN principles into collective bargainin

NiftyNet: a deep-learning platform for medical imaging

Medical image analysis and computer-assisted intervention problems are increasingly being addressed with deep-learning-based solutions. Established deep-learning platforms are flexible but do not provide specific functionality for medical image analysis and adapting them for this application requires substantial implementation effort. Thus, there has been substantial duplication of effort and incompatible infrastructure developed across many research groups. This work presents the open-source NiftyNet platform for deep learning in medical imaging. The ambition of NiftyNet is to accelerate and simplify the development of these solutions, and to provide a common mechanism for disseminating research outputs for the community to use, adapt and build upon. NiftyNet provides a modular deep-learning pipeline for a range of medical imaging applications including segmentation, regression, image generation and representation learning applications. Components of the NiftyNet pipeline including data loading, data augmentation, network architectures, loss functions and evaluation metrics are tailored to, and take advantage of, the idiosyncracies of medical image analysis and computer-assisted intervention. NiftyNet is built on TensorFlow and supports TensorBoard visualization of 2D and 3D images and computational graphs by default. We present 3 illustrative medical image analysis applications built using NiftyNet: (1) segmentation of multiple abdominal organs from computed tomography; (2) image regression to predict computed tomography attenuation maps from brain magnetic resonance images; and (3) generation of simulated ultrasound images for specified anatomical poses. NiftyNet enables researchers to rapidly develop and distribute deep learning solutions for segmentation, regression, image generation and representation learning applications, or extend the platform to new applications.Comment: Wenqi Li and Eli Gibson contributed equally to this work. M. Jorge Cardoso and Tom Vercauteren contributed equally to this work. 26 pages, 6 figures; Update includes additional applications, updated author list and formatting for journal submissio

A fast Metropolis-Hastings method for generating random correlation matrices

We propose a novel Metropolis-Hastings algorithm to sample uniformly from the space of correlation matrices. Existing methods in the literature are based on elaborated representations of a correlation matrix, or on complex parametrizations of it. By contrast, our method is intuitive and simple, based the classical Cholesky factorization of a positive definite matrix and Markov chain Monte Carlo theory. We perform a detailed convergence analysis of the resulting Markov chain, and show how it benefits from fast convergence, both theoretically and empirically. Furthermore, in numerical experiments our algorithm is shown to be significantly faster than the current alternative approaches, thanks to its simple yet principled approach.Comment: 8 pages, 3 figures, 2018 conferenc

Contractile force is enhanced in Aortas from pendrin null mice due to stimulation of angiotensin II-dependent signaling.

Pendrin is a Cl-/HCO3- exchanger expressed in the apical regions of renal intercalated cells. Following pendrin gene ablation, blood pressure falls, in part, from reduced renal NaCl absorption. We asked if pendrin is expressed in vascular tissue and if the lower blood pressure observed in pendrin null mice is accompanied by reduced vascular reactivity. Thus, the contractile responses to KCl and phenylephrine (PE) were examined in isometrically mounted thoracic aortas from wild-type and pendrin null mice. Although pendrin expression was not detected in the aorta, pendrin gene ablation changed contractile protein abundance and increased the maximal contractile response to PE when normalized to cross sectional area (CSA). However, the contractile sensitivity to this agent was unchanged. The increase in contractile force/cross sectional area observed in pendrin null mice was due to reduced cross sectional area of the aorta and not from increased contractile force per vessel. The pendrin-dependent increase in maximal contractile response was endothelium- and nitric oxide-independent and did not occur from changes in Ca2+ sensitivity or chronic changes in catecholamine production. However, application of 100 nM angiotensin II increased force/CSA more in aortas from pendrin null than from wild type mice. Moreover, angiotensin type 1 receptor inhibitor (candesartan) treatment in vivo eliminated the pendrin-dependent changes contractile protein abundance and changes in the contractile force/cross sectional area in response to PE. In conclusion, pendrin gene ablation increases aorta contractile force per cross sectional area in response to angiotensin II and PE due to stimulation of angiotensin type 1 receptor-dependent signaling. The angiotensin type 1 receptor-dependent increase in vascular reactivity may mitigate the fall in blood pressure observed with pendrin gene ablation

5,10-Methylenetetrahydrofolate Reductase 677 and 1298 Polymorphisms, Folate Intake, and Microsatellite Instability in Colon Cancer

The 5,10-methylenetetrahydrofolate reductase (MTHFR) gene plays a critical role in folate metabolism. Studies on the association between MTHFR polymorphisms and length changes in short tandem repeat DNA sequences [microsatellite instability (MSI)] are inconsistent. Using data from colon cancer cases (n = 503) enrolled as part of an existing population-based case-control study, we investigated the association between MTHFR 677 and MTHFR 1298 polymorphisms and MSI. We also examined whether the association was modified by folate intake. Participants were case subjects enrolled as part of the North Carolina Colon Cancer Study. Consenting cases provided information about lifestyle and diet during in-home interviews as well as blood specimens and permission to obtain tumor blocks. DNA from normal and tumor tissue sections was used to determine microsatellite status (MSI). Tumors were classified as MSI if two or more microsatellite markers (BAT25, BAT26, D5S346, D2S123, and D17S250) had changes in the number of DNA sequence repeats compared with matched nontumor tissue. Tumors with one positive marker (MSI-low) or no positive markers (microsatellite stable) were grouped together as non-MSI tumors (microsatellite stable). MTHFR 677 and MTHFR 1298 genotypes were determined by real-time PCR using the 5′ exonuclease (Taqman) assay. Logistic regression was used to calculate odds ratio (OR) and 95% confidence intervals (95% CI). MSI was more common in proximal tumors (OR, 3.8; 95% CI, 1.7–8.4) and in current smokers (OR, 4.0; 95% CI, 1.6–9.7). Compared with MTHFR 677 CC referent, MTHFR 677 CT/TT genotype was inversely associated with MSI among White cases (OR, 0.36; 95% CI, 0.16–0.81) but not significant among African Americans. Although not statistically significant, a similar inverse association was observed between MTHFR 677 CT/TT genotype and MSI among the entire case subjects (OR, 0.54; 95% CI, 0.26–1.10). Among those with adequate folate intake (>400 μg total folate), we found strong inverse associations between combined MTHFR genotypes and MSI (677 CC + 1298 AC/CC, OR, 0.09; 95% CI, 0.01–0.59; 677 CT/TT + 1298 AA, OR, 0.13; 95% CI, 0.02–0.85) compared with the combined wild-type genotypes (677 CC + 1298 AA). This protective effect was not evident among those with low folate (<400 μg total folate) intake. Our results suggest that MTHFR variant genotypes are associated with reduced risk of MSI tumors under conditions of adequate folate intake, although the data are imprecise due to small numbers. These results indicate that the relationship between MTHFR genotypes and MSI is influenced by folate status