A homologous genetic basis of the murine cpfl1 mutant and human achromatopsia linked to mutations in the PDE6C gene

Retinal cone photoreceptors mediate fine visual acuity, daylight vision, and color vision. Congenital hereditary conditions in which there is a lack of cone function in humans cause achromatopsia, an autosomal recessive trait, characterized by low vision, photophobia, and lack of color discrimination. Herein we report the identification of mutations in the PDE6C gene encoding the catalytic subunit of the cone photoreceptor phosphodiesterase as a cause of autosomal recessive achromatopsia. Moreover, we show that the spontaneous mouse mutant cpfl1 that features a lack of cone function and rapid degeneration of the cone photoreceptors represents a homologous mouse model for PDE6C associated achromatopsia.     

Markers of inflammation in women on different hormone replacement therapies

BACKGROUND AND AIM. To measure inflammatory markers in postmenopausal women on different forms of hormone replacement therapy (HRT). METHOD. C-reactive protein (CRP), fibrinogen, plasma viscosity (PV), albumin and white blood cell (WBC) count were determined in 749 postmenopausal women. RESULTS. CRP concentration was significantly higher in women on estrogen monotherapy (difference of the median (d) 0.96 &#114 mg/l, P &#114 = &#114 0.013), compared to those without HRT, but there was no difference in women on combined HRT. Fibrinogen concentration was significantly lower in women on estrogen monotherapy (d 0.25 &#114 g/l, P &#114 = &#114 0.004) and combined HRT (d 0.4 &#114 g/l, P &#114 < &#114 0.001), compared to women without HRT. Similarly, PV was significantly lower in women on estrogen monotherapy (d 0.017 &#114 mPa·s, P &#114 = &#114 0.007) and women on combined HRT (d 0.039 &#114 mPa·s, P &#114 < &#114 0.001), compared to those without HRT. No differences were found for WBC count and the negative acute phase marker albumin in the various treatment groups. In contrast to oral estrogen administration, levels of CRP, fibrinogen and PV in women on transdermal estrogen therapy did not differ from the no-HRT group. There was no association between these markers of inflammation and plasma estrogen levels. CONCLUSION. Oral estrogen monotherapy was associated with highest concentrations of CRP. In contrast, other markers of inflammation were either similar or lower in the oral HRT group, compared to the group of women without HRT, suggesting that higher CRP concentrations reflect estrogen effects on CRP expression rather than a systemic pro-inflammatory effect.     

VOx Phase Mixture of Reduced Single Crystalline V2O5: VO2 Resistive Switching

The strongly correlated electron material, vanadium dioxide (VO2), has seen considerable attention and research application in metal-oxide electronics due to its metal-to-insulator transition close to room temperature. Vacuum annealing a V2O5(010) single crystal results in Wadsley phases (VnO2n+1, n > 1) and VO2. The resistance changes by a factor of 20 at 342 K, corresponding to the metal-to-insulator phase transition of VO2. Macroscopic voltage-current measurements with a probe separation on the millimetre scale result in Joule heating-induced resistive switching at extremely low voltages of under a volt. This can reduce the hysteresis and facilitate low temperature operation of VO2 devices, of potential benefit for switching speed and device stability. This is correlated to the low resistance of the system at temperatures below the transition. High-resolution transmission electron microscopy measurements reveal a complex structural relationship between V2O5, VO2 and V6O13 crystallites. Percolation paths incorporating both VO2 and metallic V6O13 are revealed, which can reduce the resistance below the transition and result in exceptionally low voltage resistive switching.     

Anatomical basis of glial cell line-derived neurotrophic factor expression in the striatum and related basal ganglia during postnatal development of the rat

There is increasing evidence that glial cell line-derived neurotrophic factor (GDNF) plays a role as a limiting, striatal target-derived neurotrophic factor for dopamine neurons of the substantia nigra pars compacta (SNpc) by regulating the magnitude of the first phase of postnatal natural cell death which occurs in these neurons. While it has been shown that GDNF mRNA is relatively abundant in postnatal striatum, the cellular basis of its expression has been unknown. We therefore used nonradioactive in situ hybridization and immunohistochemistry to examine the cellular basis of GDNF mRNA and protein expression, respectively, in postnatal striatum and related structures. We found that GDNF mRNA is expressed within medium-sized striatal neurons. Expression in glia was not observed. At the protein level, regionally, GDNF expression in striatum was observed in striosomal patches, as previously described. At a cellular level a few neurons were observed, but they do not account for the striosomal pattern. This pattern is predominantly due to GDNF-positive neuropil. Some of this neuropil arises from tyrosine hydroxylase-positive nigro-striatal dopaminergic afferents. Astrocytic processes do not appear to contribute to the striosomal pattern. GDNF-positive fibers are identified not only within intrinsic striatal neuropil, but also in fibers within the major striatal efferent targets: the globus pallidus, the entopeduncular nucleus, and the SN pars reticulata. We conclude that during normal postnatal development, medium-sized neurons are the principal source of GDNF within the striatum.     

Extravasating Contrast Material on Angiography Following Carotid Angioplasty and Stenting: Not Necessarily Subarachnoid Hemorrhage

We describe a case of asymptomatic extravasation of iodinated contrast material into the sulci on digital subtraction angiography following carotid angioplasty and stenting resulting in sulcal hyperdensity on computed tomography (CT). We believe the mechanism for this observation is hyperperfusion injury and that in the absence of any associated clinical signs, it should not be considered alarming for subarachnoid hemorrhage.     

“Driven and Tense,Stressed Out and Anxious”: Clinicians’ Perceptions of Post-Traumatic Stress Disorder Symptom Expressions in Adults with Autism and Intellectual Disability

ABSTRACT

Introduction

Individuals with autism spectrum disorder (ASD) and intellectual disability (ID) seem to be at increased risk for post-traumatic stress disorder (PTSD), but knowledge is sparse regarding its identification in this population. Previous research indicates that certain symptoms of PTSD may be more easily recognized, and that identifying reexperiencing and avoidance is particularly challenging.     

Axo–axonic GABA-immunopositive synapses on the primary afferent fibers in frogs

In three frog species Rana esculenta, Rana temporaria and Xenopus laevis, the contacts established by γ-aminobutyric acid and glutamate decarboxylase immunoreactive (-ir) terminals upon primary afferent fibers were studied using confocal and electron microscopy. For confocal microscopy, the primary afferent fibers were labeled through the dorsal root with Dextran–Texas Red, whereas γ-aminobutyric acid and glutamate decarboxylase immunoreactivity were revealed with fluorescein isothiocyanate. Appositions of γ-aminobutyric acid and glutamate decarboxylase immunoreactive profiles onto primary afferent fibers were observed and were considered as putative axo–axonic contacts of GABAergic terminals upon primary afferents. The latter was confirmed by the ultrastructural finding of axo–axonic synapses from γ-aminobutyric acid immunopositive boutons upon the HRP-labeled primary afferent fibers in postembedding immunoelectron microscopic study. Such synapses may represent the morphological basis of GABAergic presynaptic inhibition of primary afferent fibers.     

A novel nuclear marker,Pm-int9, for phylogenetic studies of <Emphasis Type="Italic">Opisthorchis felineus</Emphasis>, <Emphasis Type="Italic">Opisthorchis viverrini</Emphasis>, and <Emphasis Type="Italic">Clonorchis sinensis</Emphasis> (Opisthorchiidae,Trematoda)

Opisthorchis felineus, O. viverrini, and Clonorchis sinensis, the trematodes of the family Opisthorchiidae, are important human parasites. Two previous studies (Kang et al. Parasitol Int 57:191–197, 2008; Katokhin et al. Dokl Biochem Biophys 421:214–217, 2008) have provided evidence using ribosomal and mitochondrial sequences that O. viverrini, O. felineus, and C. sinensis are closely related. We developed a novel nuclear marker, Pm-int9, which included the ninth intron of the paramyosin gene and flanking exon sequences. Samples of O. felineus from four localities of West Siberia, C. sinensis from the Russian Far East, and O. viverrini from Thailand were genotyped by Pm-int9. Little variation was detected in exon sequences, however, intron sequences turned out to be more variable than ribosomal internal transcribed spacers. We can conclude that Pm-int9 is valuable for interspecific variation studies. Phylogenetic analysis based on Pm-int9 revealed that O. viverrini and C. sinensis were closer to each other than either of them to O. felineus, supporting the opinion that C. sinensis should be considered the sister species of Opisthorchis spp.     

Nerve growth factor improves spatial learning and restores hippocampal cholinergic fibers in rats withdrawn from chronic treatment with ethanol

The cholinergic septohippocampal pathway has long been known to be important for learning and memory. Prolonged intake of ethanol causes enduring memory deficits, which are paralleled by partial depletion of hippocampal cholinergic afferents. We hypothesized that exogenous supply of nerve growth factor (NGF), known to serve as a trophic substance for septal cholinergic neurons, can revert the ethanol-induced changes in the septohippocampal cholinergic system. Adult rats were given a 20% ethanol solution as their only source of fluid for 6 months. During the first 4 weeks after the animals were withdrawn from ethanol, they were intraventricularly infused with either NGF or vehicle alone via implanted osmotic minipumps. The vehicle-infused withdrawn animals showed impaired performance on a spatial reference memory version of the Morris water maze task, both during the task acquisition and on the retention test. In contrast, NGF-treated withdrawn rats were able to learn the task as well as controls, and significantly outperformed the vehicle-infused withdrawn rats. The histological analysis revealed that, in the latter group, the length density of fibers immunoreactive to choline acetyltransferase was reduced relative to control values by approximately 25%, as measured in the dentate gyrus and regio superior of the hippocampal formation. However, in NGF-treated withdrawn rats, the length density of these fibers was identical to that of control rats. These data provide support to the notion that NGF is capable of ameliorating memory deficits and restoring septohippocampal cholinergic projections following chronic treatment with ethanol. Electronic Publication     

Cytokine-deficient mice as a model for generation of autologous anti-cytokine monoclonal antibodies

The possibility of inducing immune responses to murine interleukin-4 (IL-4) and IL-13 and generating anti-cytokine monoclonal antibodies (mAbs) was studied in IL-4- and IL-13-knockout mice. The minimal doses of IL-4 or IL-13 that could induce significant anti-cytokine responses with titers of 5000-10,000 were 20 microg per injection with the total doses of 100 microg. The highest titers in a range of 20,480-40,960 were achieved by triple immunization of IL-13-knockout mice with 30 microg of IL-13 per injection. Anti-IL-4 mAbs were generated at an antibody serum titer about 400; however, only 0.5% of primary hybridoma clones were anti-IL-4-positive. Anti-IL-13 cell fusions were successful at titers of 20,480 and 40,960 with 50% of the primary clones positive. Both hybridomas secreted low-affinity IgMkappa mAbs and were IL-6-dependent. These data demonstrate that IL-4- and IL-13-deficient mice may develop high polyclonal immune responses to "syngeneic" murine cytokines but fail to generate high-affinity mAbs at the tested conditions.