19,854 research outputs found
Visual Responses in Mice Lacking Critical Components of All Known Retinal Phototransduction Cascades
The mammalian visual system relies upon light detection by outer-retinal rod/cone photoreceptors and melanopsin-expressing retinal ganglion cells. Gnat1(-/-); Cnga3(-/-); Opn4(-/-) mice lack critical elements of each of these photoreceptive mechanisms via targeted disruption of genes encoding rod alpha transducin (Gnat1); the cone-specific alpha 3 cyclic nucleotide gated channel subunit (Cnga3); and melanopsin (Opn4). Although assumed blind, we show here that these mice retain sufficiently widespread retinal photoreception to drive a reproducible flash electroretinogram (ERG). The threshold sensitivity of this ERG is similar to that of cone-based responses, however it is lost under light adapted conditions. Its spectral efficiency is consistent with that of rod opsin, but not cone opsins or melanopsin, indicating that it originates with light absorption by the rod pigment. The TKO light response survives intravitreal injection of U73122 (a phospholipase C antagonist), but is inhibited by a missense mutation of cone alpha transducin (Gnat2(cpfl3)), suggesting Gnat2-dependence. Visual responses in TKO mice extend beyond the retina to encompass the lateral margins of the lateral geniculate nucleus and components of the visual cortex. Our data thus suggest that a Gnat1-independent phototransduction mechanism downstream of rod opsin can support relatively widespread responses in the mammalian visual system. This anomalous rod opsin-based vision should be considered in experiments relying upon Gnat1 knockout to silence rod phototransduction
Constipation in children
Constipation in children is a universal problem, occurring in 0.7-28% of the population. The exact aetiology is unknown, but the majority of children have a functional, rather than organic, aetiology. Symptoms associated with constipation include abdominal pain, a poor appetite and faecal incontinence, all of which interfere with the quality of life of the child and his or her family. Early intervention with appropriate management is necessary to prevent ongoing sequelae. Once an organic cause has been excluded, a programme of intervention should be implemented, namely evacuation of any faecal mass present, followed by regular maintenance therapy to encourage evacuation of a daily soft stool for at least 2-3 months, prior to gradual withdrawal. Emotional support, exercise and dietary modification are linked to the therapy and will ensure a successful outcome. Failure to implement the protocol may result in ongoing problems in up to 50% of children as theyenter adulthood
De novo bronchiectasis in haematological malignancies: patient characteristics, risk factors and survival
A proposal for a comprehensive grading of Parkinson's disease severity combining motor and non-motor assessments: meeting an unmet need.
Non-motor symptoms are present in Parkinson's disease (PD) and a key determinant of quality of life. The Non-motor Symptoms Scale (NMSS) is a validated scale that allows quantifying frequency and severity (burden) of NMS. We report a proposal for using NMSS scores to determine levels of NMS burden (NMSB) and to complete PD patient classification
Determination of density and concentration from fluorescent images of a gas flow
A fluorescent image analysis procedure to determine the distribution of
species concentration and density in a gas flow is proposed. The fluorescent
emission is due to the excitation of atoms/molecules of a gas that is
intercepted by an electron blade. The intensity of the fluorescent light is
proportional to the local number density of the gas. When the gas flow is a
mixture of different species, this proportionality can be exploited to extract
the contribution associated to the species from the spectral superposition
acquired by a digital camera. This yields a method that simultaneously reveals
species concentrations and mass density of the mixture. The procedure is
applied to two under-expanded sonic jets discharged into a different gas
ambient - Helium into Argon and Argon into Helium - to measure the
concentration and density distribution along the jet axis and across it. A
comparison with experimental and numerical results obtained by other authors
when observing under-expanded jets at different Mach numbers is made with the
density distribution along the axis of the jet. This density distribution
appears to be self-similar.Comment: New figures in portable .eps forma
Exit humidity of wet scrubbers for underground coal mines
A wet scrubber is a device used in underground coal mines for the exhaust treatment system of various internal combustion engines (generally diesel) primarily as a spark arrestor with a secondary function to remove pollutants from the exhaust gas. A pool of scrubbing liquid (generally water based) is used in conjunction with a Diesel Particulate Filter (DPF). Scrubbers are widely used in underground applications of diesel engines as their exhaust contains high concentration of harmful diesel particulate matter (DPM) and other pollutant gases. Currently the DPFs have to be replaced frequently because moisture output from the wet scrubber blocks the filter media and causes reduced capacity. This paper presents experimental and theoretical studies on the heat and mass transfer mechanisms of the exhaust flow both under and above the water surface, aiming at finding the cause and effects of the moisture reaching the filters and employing a solution to reduce the humidity and DPM output, and to prolong the change-out period of the DPF. By assuming a steady flow condition, heat transfer from the inlet exhaust gas balances energy required for the water evaporation. Hence the exit humidity will decrease with the increase of exit temperature. Experiments on a real scrubber are underway
Effects of Expression of Streptococcus pneumoniae PspC on the Ability of Streptococcus mitis to Evade Complement-Mediated Immunity
Streptococcus pneumoniae and Streptococcus mitis are genetically closely related and both frequently colonise the naso-oropharynx, yet S. pneumoniae is a common cause of invasive infections whereas S. mitis is only weakly pathogenic. We hypothesise that sensitivity to innate immunity may underlie these differences in virulence phenotype. We compared the sensitivity of S. pneumoniae and S. mitis strains to complement-mediated immunity, demonstrating S. mitis strains were susceptible to complement-mediated opsonophagocytosis. S. pneumoniae resistance to complement is partially dependent on binding of the complement regulator Factor H by the surface protein PspC. However, S. mitis was unable to bind factor H. The S. pneumoniae TIGR4 strain pspC was expressed in the S. mitis SK142 strain to create a S. mitis pspC+ strain. Immunoblots demonstrated the S. mitis pspC+ strain expressed PspC, and flow cytometry confirmed this resulted in Factor H binding to S. mitis, reduced susceptibility to complement and improved survival in whole human blood compared to the wild-type S. mitis strain. However, in mouse models the S. mitis pspC+ strain remained unable to establish persistent infection. Unlike S. pneumoniae strains, culture in serum or blood did not support increased CFU of the S. mitis strains. These results suggest S. mitis is highly sensitive to opsonisation with complement partially due to an inability to bind Factor H, but even when complement sensitivity was reduced by expression of pspC, poor growth in physiological fluid limited the virulence of S. mitis in mice
Regulation of neutrophilic inflammation by proteinase-activated receptor 1 during bacterial pulmonary infection
Neutrophils are key effector cells of the innate immune response to pathogenic bacteria, but excessive neutrophilic inflammation can be associated with bystander tissue damage. The mechanisms responsible for neutrophil recruitment to the lungs during bacterial pneumonia are poorly defined. In this study, we focus on the potential role of the major high-affinity thrombin receptor, proteinase-activated receptor 1 (PAR-1), during the development of pneumonia to the common lung pathogen Streptococcus pneumoniae. Our studies demonstrate that neutrophils were indispensable for controlling S. pneumoniae outgrowth but contributed to alveolar barrier disruption. We further report that intra-alveolar coagulation (bronchoalveolar lavage fluid thrombin-antithrombin complex levels) and PAR-1 immunostaining were increased in this model of bacterial lung infection. Functional studies using the most clinically advanced PAR-1 antagonist, SCH530348, revealed a key contribution for PAR-1 signaling in influencing neutrophil recruitment to lung airspaces in response to both an invasive and noninvasive strain of S. pneumoniae (D39 and EF3030) but that PAR-1 antagonism did not impair the ability of the host to control bacterial outgrowth. PAR-1 antagonist treatment significantly decreased pulmonary levels of IL-1β, CXCL1, CCL2, and CCL7 and attenuated alveolar leak. Ab neutralization studies further demonstrated a nonredundant role for IL-1β, CXCL1, and CCL7 in mediating neutrophil recruitment in response to S. pneumoniae infection. Taken together, these data demonstrate a key role for PAR-1 during S. pneumoniae lung infection that is mediated, at least in part, by influencing multiple downstream inflammatory mediators
The role of non-thermal plasma technique in NOx treatment : a review
Non-thermal plasma (NTP) has been introduced over the past several years as a promising method for nitrogen oxide (NOx) removal. The intent, when using NTP, is to selectively transfer input electrical energy to the electrons, and to not expend this in heating the entire gas stream, which generates free radicals through collisions, and promotes the desired chemical changes in the exhaust gases. The generated active species react with the pollutant molecules and decompose them. This paper reviews and summarizes relevant literature regarding various aspects of the application of NTP technology on NOx removal from exhaust gases. A comprehensive description of available scientific literature on NOx removal using NTP technology is presented, including various types of NTP, e.g. dielectric barrier discharge, corona discharge and electron beam. Furthermore, the combination of NTP with catalyst and adsorbent for better NOx removal efficiency is presented in detail. The removal of NOx from both simulated gases and real diesel engines is also considered in this review paper. As NTP is a new technique and is not yet commercialized, there is a need for more studies to be performed in this field
Mutation of TBCK causes a rare recessive developmental disorder
OBJECTIVE: To characterize the underlying genetic defect in a family with 3 siblings affected by a severe, yet viable, congenital disorder. METHODS: Extensive genetic and metabolic investigations were performed, and the affected children were imaged at different ages. Whole-genome genotyping and whole-exome sequencing were undertaken. A single large region (>8 Mb) of homozygosity in chromosome 4 (chr4:100,268,553-108,609,628) was identified that was shared only in affected siblings. Inspection of genetic variability within this region led to the identification of a novel mutation. Sanger sequencing confirmed segregation of the mutation with disease. RESULTS: All affected siblings share homozygosity for a novel 4-bp deletion in the gene TBCK (NM_033115:c.614_617del:p.205_206del). CONCLUSIONS: This finding provides the genetic cause of a severe inherited disease in a family and extends the number of mutations and phenotypes associated with this recently identified disease gene
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