Neurokinin-1 Receptor Immunoreactive Neuronal Elements in the Superficial Dorsal Horn of the Chicken Spinal Cord: With Special Reference to Their Relationship with the Tachykinin-containing Central Axon Terminals in Synaptic Glomeruli

Synaptic glomeruli that involve tachykinin-containing primary afferent central terminals are numerous in lamina II of the chicken spinal cord. Therefore, a certain amount of noxious information is likely to be modulated in these structures in chickens. In this study, we used immunohistochemistry with confocal and electron microscopy to investigate whether neurokinin-1 receptor (NK-1R)-expressing neuronal elements are in contact with the central primary afferent terminals in synaptic glomeruli of the chicken spinal cord. We also investigated which neuronal elements (axon terminals, dendrites, cell bodies) and which neurons in the spinal cord possess NK-1R, and are possibly influenced by tachykinin in the glomeruli. By confocal microscopy, NK-1R immunoreactivities were seen in a variety of neuronal cell bodies, their dendrites and smaller fibers of unknown origin. Some of the NK-1R immunoreactive profiles also expressed GABA immunoreactivities. A close association was observed between the NK-1R-immunoreactive neurons and tachykinin-immunoreactive axonal varicosities. By electron microscopy, NK-1R immunoreactivity was seen in cell bodies, conventional dendrites and vesicle-containing dendrites in laminae I and II. Among these elements, dendrites and vesicle-containing dendrites made contact with tachykinin-containing central terminals in the synaptic glomeruli. These results indicate that tachykinin-containing central terminals in the chicken spinal cord can modulate second-order neuronal elements in the synaptic glomeruli

Superconducting anisotropy and evidence for intrinsic pinning in single crystalline MgB2_2

We examine the superconducting anisotropy $\gamma_c = (m_c / m_{ab})^{1/2}$ of a metallic high-$T_c$ superconductor MgB$_2$ by measuring the magnetic torque of a single crystal. The anisotropy $\gamma_c$ does not depend sensitively on the applied magnetic field at 10 K. We obtain the anisotropy parameter $\gamma_c = 4.31 \pm 0.14$. The torque curve shows the sharp hysteresis peak when the field is applied parallel to the boron layers. This comes from the intrinsic pinning and is experimental evidence for the occurrence of superconductivity in the boron layers.Comment: REVTeX 4, To be published in Physical Review

Engineering Corynebacterium glutamicum for isobutanol production

The production of isobutanol in microorganisms has recently been achieved by harnessing the highly active 2-keto acid pathways. Since these 2-keto acids are precursors of amino acids, we aimed to construct an isobutanol production platform in Corynebacterium glutamicum, a well-known amino-acid-producing microorganism. Analysis of this host’s sensitivity to isobutanol toxicity revealed that C. glutamicum shows an increased tolerance to isobutanol relative to Escherichia coli. Overexpression of alsS of Bacillus subtilis, ilvC and ilvD of C. glutamicum, kivd of Lactococcus lactis, and a native alcohol dehydrogenase, adhA, led to the production of 2.6 g/L isobutanol and 0.4 g/L 3-methyl-1-butanol in 48 h. In addition, other higher chain alcohols such as 1-propanol, 2-methyl-1-butanol, 1-butanol, and 2-phenylethanol were also detected as byproducts. Using longer-term batch cultures, isobutanol titers reached 4.0 g/L after 96 h with wild-type C. glutamicum as a host. Upon the inactivation of several genes to direct more carbon through the isobutanol pathway, we increased production by ∼25% to 4.9 g/L isobutanol in a ∆pyc∆ldh background. These results show promise in engineering C. glutamicum for higher chain alcohol production using the 2-keto acid pathways

The influence of viscosity on the motility and sensory ability of the dinoflagellate Heterocapsa triquetra

Seawater viscosity is influenced by temperature as well as through excretion of exopolymers by some plankton. We examined the role of viscosity on the movement patterns and sensory abilities of the dinoflagellate Heterocapsa triquetra, manipulating the viscosity of seawater to simulate a 10+1.58C temperature change. In a second treatment, we seeded the water with microbeads to examine swimming behaviours in the presence of a mechanical stimulus. Increased viscosity reduced distances between conspecifics 4.7-fold and increased distances between protists and microbeads by 3.4-fold. Increased viscosity also affected other aspects of motility, with an overall reduction in swimming speed of 2.0- and 7.0-fold for treatments with and without mechanical stimuli. Higher viscosities were associated with upward vertical migration, in both the presence and absence of microbeads. Cells were highly sensitive to disturbances to the velocity field, by as little as 1.5%, and different approach distances of H. triquetra to conspecifics over mechanical stimuli suggest sensory capacity to distinguish types of particles. Mediation of motility and migratory behaviours through viscosity implies ramifications for the distribution of protists and their encounters with resources, predators and conspecifics triggered by events such as temperature changes and phytoplankton bloom events

Simulation-based analysis of micro-robots swimming at the center and near the wall of circular mini-channels

Swimming micro robots have great potential in biomedical applications such as targeted drug delivery, medical diagnosis, and destroying blood clots in arteries. Inspired by swimming micro organisms, micro robots can move in biofluids with helical tails attached to their bodies. In order to design and navigate micro robots, hydrodynamic characteristics of the flow field must be understood well. This work presents computational fluid dynamics (CFD) modeling and analysis of the flow due to the motion of micro robots that consist of magnetic heads and helical tails inside fluid-filled channels akin to bodily conduits; special emphasis is on the effects of the radial position of the robot. Time-averaged velocities, forces, torques, and efficiency of the micro robots placed in the channels are analyzed as functions of rotation frequency, helical pitch (wavelength) and helical radius (amplitude) of the tail. Results indicate that robots move faster and more efficiently near the wall than at the center of the channel. Forces acting on micro robots are asymmetrical due to the chirality of the robot’s tail and its motion. Moreover, robots placed near the wall have a different flow pattern around the head when compared to in-center and unbounded swimmers. According to simulation results, time-averaged for-ward velocity of the robot agrees well with the experimental values measured previously for a robot with almost the same dimensions

Phenotype Sequencing: Identifying the Genes That Cause a Phenotype Directly from Pooled Sequencing of Independent Mutants

Random mutagenesis and phenotype screening provide a powerful method for dissecting microbial functions, but their results can be laborious to analyze experimentally. Each mutant strain may contain 50–100 random mutations, necessitating extensive functional experiments to determine which one causes the selected phenotype. To solve this problem, we propose a “Phenotype Sequencing” approach in which genes causing the phenotype can be identified directly from sequencing of multiple independent mutants. We developed a new computational analysis method showing that 1. causal genes can be identified with high probability from even a modest number of mutant genomes; 2. costs can be cut many-fold compared with a conventional genome sequencing approach via an optimized strategy of library-pooling (multiple strains per library) and tag-pooling (multiple tagged libraries per sequencing lane). We have performed extensive validation experiments on a set of E. coli mutants with increased isobutanol biofuel tolerance. We generated a range of sequencing experiments varying from 3 to 32 mutant strains, with pooling on 1 to 3 sequencing lanes. Our statistical analysis of these data (4099 mutations from 32 mutant genomes) successfully identified 3 genes (acrB, marC, acrA) that have been independently validated as causing this experimental phenotype. It must be emphasized that our approach reduces mutant sequencing costs enormously. Whereas a conventional genome sequencing experiment would have cost $7,200 in reagents alone, our Phenotype Sequencing design yielded the same information value for only$1200. In fact, our smallest experiments reliably identified acrB and marC at a cost of only $110–$340

Selective targeting of activating and inhibitory Smads by distinct WWP2 ubiquitin ligase isoforms differentially modulates TGFβ signalling and EMT

Ubiquitin-dependent mechanisms have emerged as essential regulatory elements controlling cellular levels of Smads and TGFß-dependent biological outputs such as epithelial–mesenchymal transition (EMT). In this study, we identify a HECT E3 ubiquitin ligase known as WWP2 (Full-length WWP2-FL), together with two WWP2 isoforms (N-terminal, WWP2-N; C-terminal WWP2-C), as novel Smad-binding partners. We show that WWP2-FL interacts exclusively with Smad2, Smad3 and Smad7 in the TGFß pathway. Interestingly, the WWP2-N isoform interacts with Smad2 and Smad3, whereas WWP2-C interacts only with Smad7. In addition, WWP2-FL and WWP2-C have a preference for Smad7 based on protein turnover and ubiquitination studies. Unexpectedly, we also find that WWP2-N, which lacks the HECT ubiquitin ligase domain, can also interact with WWP2-FL in a TGFß-regulated manner and activate endogenous WWP2 ubiquitin ligase activity causing degradation of unstimulated Smad2 and Smad3. Consistent with our protein interaction data, overexpression and knockdown approaches reveal that WWP2 isoforms differentially modulate TGFß-dependent transcription and EMT. Finally, we show that selective disruption of WWP2 interactions with inhibitory Smad7 can stabilise Smad7 protein levels and prevent TGFß-induced EMT. Collectively, our data suggest that WWP2-N can stimulate WWP2-FL leading to increased activity against unstimulated Smad2 and Smad3, and that Smad7 is a preferred substrate for WWP2-FL and WWP2-C following prolonged TGFß stimulation. Significantly, this is the first report of an interdependent biological role for distinct HECT E3 ubiquitin ligase isoforms, and highlights an entirely novel regulatory paradigm that selectively limits the level of inhibitory and activating Smads

The association of cold weather and all-cause and cause-specific mortality in the island of Ireland between 1984 and 2007

This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.This article has been made available through the Brunel Open Access Publishing Fund.Background This study aimed to assess the relationship between cold temperature and daily mortality in the Republic of Ireland (ROI) and Northern Ireland (NI), and to explore any differences in the population responses between the two jurisdictions. Methods A time-stratified case-crossover approach was used to examine this relationship in two adult national populations, between 1984 and 2007. Daily mortality risk was examined in association with exposure to daily maximum temperatures on the same day and up to 6 weeks preceding death, during the winter (December-February) and cold period (October-March), using distributed lag models. Model stratification by age and gender assessed for modification of the cold weather-mortality relationship. Results In the ROI, the impact of cold weather in winter persisted up to 35 days, with a cumulative mortality increase for all-causes of 6.4% (95%CI=4.8%-7.9%) in relation to every 1oC drop in daily maximum temperature, similar increases for cardiovascular disease (CVD) and stroke, and twice as much for respiratory causes. In NI, these associations were less pronounced for CVD causes, and overall extended up to 28 days. Effects of cold weather on mortality increased with age in both jurisdictions, and some suggestive gender differences were observed. Conclusions The study findings indicated strong cold weather-mortality associations in the island of Ireland; these effects were less persistent, and for CVD mortality, smaller in NI than in the ROI. Together with suggestive differences in associations by age and gender between the two Irish jurisdictions, the findings suggest potential contribution of underlying societal differences, and require further exploration. The evidence provided here will hope to contribute to the current efforts to modify fuel policy and reduce winter mortality in Ireland

Chapter 6: Priority Infrastructure Opportunities for CO2 Utilization, in: Carbon Dioxide Utilization Markets and Infrastructure Status and Opportunities: A First Report

Building on the analyses of carbon dioxide (CO2)-derived products, infrastructure requirements, and policy, regulatory, and societal considerations discussed in Chapters 2 through 5, this chapter presents a summary of priority infrastructure opportunities to enable CO2 utilization. The chapter begins by describing options for CO2 utilization infrastructure funding based on current policy and regulatory regimes, and considering successful examples in related industries. It then examines near-term opportunities for CO2 utilization infrastructure investments, as well as near-term actions to enable longerterm deployment options. A primary consideration for these opportunities is the ability of CO2 utilization to participate in a future circular carbon economy, which depends on the type of CO2 source, CO2-derived product lifetime, and life cycle emissions of other process inputs. The chapt