Neuropeptide Y (NPY) has been implicated in the pathophysiology of certain mood disorders, including depression and anxiety. It is, however, not known which of the five cloned NPY receptors mediate ...these functions. We investigated the effect of Y2 receptor deletion on anxiety and stress‐related behaviours. In the elevated plus maze, Y2 knock out (Y2−/−) mice showed a 2.7‐fold higher frequency of entering into, and spent 3.8 times more time within, the open arms compared to controls, while entries into the closed arms did not differ. Similarly Y2−/− mice entered the central area of the open field 1.7 times more frequently and also spent 1.8 times more time there. In the light/dark test Y2−/− mice had a 4.8‐fold lower latency to enter the lit area but stayed there 2.6 times longer than control mice. Y2−/− mice displayed 3.2‐fold less immobility in the forced swim test, indicating improved stress coping ability. Y2 receptors are predominantly located presynaptically where they mediate feedback inhibition of neurotransmitter release. Deletion of these receptors may result in enhanced release of NPY, GABA and/or glutamate in brain areas linked to the manifestation of anxiety, and stress‐related behaviour such as the amygdala. Taken together, deletion of the Y2 receptor has revealed an important role of Y2 receptors in the generation of anxiety‐related and stress‐related behaviours in mice.
The helicity-dependent cross sections for the photoproduction of π0η pairs have been measured for the first time. The experiment was performed at the tagged photon facility of the Mainz MAMI ...accelerator with the combined Crystal Ball – TAPS calorimeter. The experiment used a polarized deuterated butanol target and a circularly polarized photon beam. This arrangement allowed the σ1/2 (photon and target spin antiparallel) and σ3/2 (parallel spins) components to be measured for quasi-free production of π0η pairs off protons and neutrons. The main finding is that the two helicity components contribute identically, within uncertainties, for both participant protons and neutrons. The absolute couplings for protons and neutrons are also identical. This means that nucleon resonances contributing to this reaction in the investigated energy range have almost equal electromagnetic helicity couplings, A1/2n,p and A3/2n,p. Identical couplings for protons and neutrons are typical for Δ resonances and identical A1/2 and A3/2 components are only possible for J≥3/2 states, which constrains possible contributions of nucleon resonances.
To evaluate the association between the interval from breast-conserving surgery (BCS) to radiotherapy (RT) and the clinical outcome among patients treated with adjuvant endocrine therapy.
Patient ...information was obtained from three International Breast Cancer Study Group trials. The analysis was restricted to 964 patients treated with BCS and adjuvant endocrine therapy. The patients were divided into two groups according to the median number of days between BCS and RT and into four groups according to the quartile of time between BCS and RT. The endpoints were the interval to local recurrence, disease-free survival, and overall survival. Proportional hazards regression analysis was used to perform comparisons after adjustment for baseline factors.
The median interval between BCS and RT was 77 days. RT timing was significantly associated with age, menopausal status, and estrogen receptor status. After adjustment for these factors, no significant effect of a RT delay ≤20 weeks was found. The adjusted hazard ratio for RT within 77 days vs. after 77 days was 0.94 (95% confidence interval CI, 0.47-1.87) for the interval to local recurrence, 1.05 (95% CI, 0.82-1.34) for disease-free survival, and 1.07 (95% CI, 0.77-1.49) for overall survival. For the interval to local recurrence the adjusted hazard ratio for ≤48, 49-77, and 78-112 days was 0.90 (95% CI, 0.34-2.37), 0.86 (95% CI, 0.33-2.25), and 0.89 (95% CI, 0.33-2.41), respectively, relative to ≥113 days.
A RT delay of ≤20 weeks was significantly associated with baseline factors such as age, menopausal status, and estrogen-receptor status. After adjustment for these factors, the timing of RT was not significantly associated with the interval to local recurrence, disease-free survival, or overall survival.
Bleomycin is a well known fibrogenic agent, provoking an initial adult respiratory distress syndrome-like injury with subsequent strong fibroproliferative response. Severe abnormalities of the ...alveolar surfactant system, which may be linked to the appearance of alveolar fibrin deposition, have been implicated in the pathogenetic sequence of events. Using a model of standardized aerosol delivery of 1.8 U bleomycin/kg body weight in rabbits, we investigated the influence of repetitive nebulization of heparin or urokinase-type plasminogen activator (u-PA) on the development of lung fibrosis. In an "early" (Days 2-12 postbleomycin) or "late" (Days 14-24 post-bleomycin) treatment protocol, approximately 3,500 U heparin or approximately 6,500 U u-PA was delivered to the bronchoalveolar space. Within four weeks, the bleomycin challenge provoked severe pulmonary fibrosis with reduction of lung compliance, marked increase in soluble collagen (bronchoalveolar lavage fluid) and hydroxyproline content (lung tissue), a typical reticular fibrosis pattern on high-resolution computed tomography, and typical histologic findings. Therapeutic intervention resulted in a far-reaching normalization of compliance, suppression of soluble collagen and hydroxyproline accumulation, and virtual abrogation of the computed tomography scan and histologic features of lung fibrosis, with most prominent effects seen in the early heparin and late u-PA administration. No bleeding complications occurred. These findings strongly support the concept that alveolar fibrin generation is an important event in the development of postbleomycin lung fibrosis. "Compartmentalized" anticoagulation and/or fibrinolysis via inhalational deposition of interventional agents in the alveolar compartment may thus offer a new therapeutic strategy for prevention of fibrosis.
Selective dealloying of metal nanoparticles results in rattle-type hollow carbon nanoshells enclosing platinum nanoparticles, which are able to perform size-selective catalysis. Selective ...functionalization of the outer graphene-like carbon surface prevents agglomeration and leads to well dispersible nanocatalysts in aqueous solutions. The synthesis starts with the production of nanoparticles with a cobalt-platinum-alloy core surrounded by graphene-like carbon
via
reducing flame spray synthesis. After surface functionalization, simultaneous pore formation in the shell-wall and dissolution of the cobalt results in platinum encapsulated in hollow carbon nanospheres. Catalytic oxidation of differently sized sugars (glucose and maltoheptaose) reveales size-selective catalytic properties of these platinum nanorattles.
Surface-functionalized hollow carbon nanobubbles containing platinum in their interior perform size-selective catalysis.
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•The use of Laurdan and spectral phasor analysis to study membrane fluidity in the presence of Hemoglobin is reported.•Laurdan Lifetime studies on whole erythrocytes are affected by ...the changes in Hemoglobin content as hemolysis progress.•Interaction of sucrose myristate with membrane induce an increase in fluid domains in the membrane.
The study of surfactant and bio membranes interaction is particularly complex due to the diversity in lipid composition and the presence of proteins in natural membranes. Even more difficult is the study of this interaction in vivo since cellular damage may complicate the interpretation of the results, therefore for most of the studies in this field either artificial or model systems are used. One of the model system most used to study biomembranes are erythrocytes due to their relatively simple structure (they lack nuclei and organelles having only the plasma membrane), their convenient experimental manipulation and availability.
In this context, we used rabbit erythrocytes as a model membrane and Laurdan (6-lauroyl-2-dimethylaminonaphthalene) as the fluorescent probe to study changes promoted in the membrane by the interaction with the sucrose monoester of myristic acid, β-d-fructofuranosyl-6-O-myristoyl-α-d-glucopyranoside (MMS). Surfactant and erythrocytes interaction was studied by measuring hemoglobin release and the changes in water content in the membrane sensed by Laurdan. Using two-photon excitation, three types of measurements were performed: Generalized Polarization (analyzed as average GP values), Fluorescence Lifetime Imaging, FLIM (analyzed using phasor plots) and Spectral imaging (analyzed using spectral phasor). Our data indicate that at sublytical concentration of surfactant (20μM MMS), there is a decrease of about 35% in erythrocytes size, without changes in Laurdan lifetime or emission spectra. We also demonstrate that as hemolysis progress, Laurdan lifetime increased due to the decrease in hemoglobin (strong quencher of Laurdan emission) content inside the erythrocytes. Under these conditions, Laurdan spectral phasor analyses can extract the information on the water content in the membrane in the presence of hemoglobin. Our results indicate an increase in membrane fluidity in presence of MMS.
To the Editor:
Zignol et al. (Sept. 15 issue)
1
suggest that within 10 years, molecular technologies will replace conventional phenotypic testing in surveys of drug resistance and surveillance of ...tuberculosis. To avoid the overestimation of drug resistance, wider implementation of testing for minimal inhibitory concentration (MIC) must occur first, for four main reasons. First, most commercial molecular assays do not provide information on the type of mutation. Second, different mutation types may be associated with different phenotypic MICs and different clinically relevant levels of resistance, which may lead to unnecessary discontinuation of a drug or incorrectly identifying a patient as . . .
Heterozygous mutations in the CASK gene in Xp11.4 have been shown to be associated with a distinct brain malformation phenotype in females, including disproportionate pontine and cerebellar ...hypoplasia.
The study characterised the CASK alteration in 20 new female patients by molecular karyotyping, fluorescence in situ hybridisation, sequencing, reverse transcriptase (RT) and/or quantitative real-time PCR. Clinical and brain imaging data of a total of 25 patients were reviewed.
11 submicroscopic copy number alterations, including nine deletions of ~11 kb to 4.5 Mb and two duplications, all covering (part of) CASK, four splice, four nonsense, and one 1 bp deletion are reported. These heterozygous CASK mutations most likely lead to a null allele. Brain imaging consistently showed diffuse brainstem and cerebellar hypoplasia with a dilated fourth ventricle, but of remarkably varying degrees. Analysis of 20 patients in this study, and five previously reported patients, revealed a core clinical phenotype comprising severe developmental delay/intellectual disability, severe postnatal microcephaly, often associated with growth retardation, (axial) hypotonia with or without hypertonia of extremities, optic nerve hypoplasia, and/or other eye abnormalities. A recognisable facial phenotype emerged, including prominent and broad nasal bridge and tip, small or short nose, long philtrum, small chin, and/or large ears.
These findings define the phenotypic spectrum associated with CASK loss-of-function mutations. The combination of developmental and brain imaging features together with mild facial dysmorphism is highly suggestive of this disorder and should prompt subsequent testing of the CASK gene.
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