Purkinje cells originate from cerebellar ventricular zone progenitors positive for Neph3 and E-cadherin

AbstractGABAergic Purkinje cells (PCs) provide the primary output from the cerebellar cortex, which controls movement and posture. Although the mechanisms of PC differentiation have been well studied, the precise origin and initial specification mechanism of PCs remain to be clarified. Here, we identified a cerebellar and spinal cord GABAergic progenitor-selective cell surface marker, Neph3, which is a direct downstream target gene of Ptf1a, an essential regulator of GABAergic neuron development. Using FACS, Neph3+ GABAergic progenitors were sorted from the embryonic cerebellum, and the cell fate of this population was mapped by culturing in vitro. We found that most of the Neph3+ populations sorted from the mouse E12.5 cerebellum were fated to differentiate into PCs while the remaining small fraction of Neph3+ cells were progenitors for Pax2+ interneurons, which are likely to be deep cerebellar nuclei GABAergic neurons. These results were confirmed by short-term in vivo lineage-tracing experiments using transgenic mice expressing Neph3 promoter-driven GFP. In addition, we identified E-cadherin as a marker selectively expressed by a dorsally localized subset of cerebellar Neph3+ cells. Sorting experiments revealed that the Neph3+ E-cadherinhigh population in the embryonic cerebellum defined PC progenitors while progenitors for Pax2+ interneurons were enriched in the Neph3+ E-cadherinlow population. Taken together, our results identify two spatially demarcated subregions that generate distinct cerebellar GABAergic subtypes and reveal the origin of PCs in the ventricular zone of the cerebellar primordium

Implications of a bioresorbable vascular scaffold implantation on vessel wall strain of the treated and the adjacent segments

Background: Metallic stents change permanently the mechanical properties of the vessel wall. However little is known about the implications of bioresorbable vascular scaffolds (BVS) on the vessel wall strain. Methods: Patients (n = 53) implanted with an Absorb BVS that had palpographic evaluation at any time point [before device implantation, immediate after treatment, at short-term (6-12 months) or mid-term follow-up (24-36 months)] were included in the current analysis. The palpographic data were used to estimate the mean of the maximum strain values and the obtained measurements were classified using the Rotterdam classification (ROC) score and expressed as ROC/mm. Results: Scaffold implantation led to a significant decrease of the vessel wall strain in the treated segment [0.35 (0.20, 0.38) vs. 0.19 (0.09, 0.29); P = 0.005] but it did not affect the proximal and distal edge. In patients who had serial palpographic examination the vessel wall strain continued to decrease in the scaffolded segment at short-term [0.20 (0.12, 0.29) vs. 0.14 (0.08, 0.20); P = 0.048] and mid-term follow-up [0.20 (0.12, 0.29) vs. 0.15 (0.10, 0.19), P = 0.024]. No changes were noted with time in the mechanical properties of the vessel wall at the proximal and distal edge. Conclusions: Absorb BVS implantation results in a permanent alteration of the mechanical properties of the vessel wall in the treated segment. Long term follow-up data are needed in order to examine the clinical implications of these findings

Chiral Ice Crystals in Space

We observed the formation of CO, CH3OH, and H2O ices using a cryogenic transmission electron microscope, to determine if chiral ice crystals could form under the conditions of interstellar molecular clouds and young stellar objects (protoplanetary disks) and to clarify the crystalline structure of these ices. Our results suggest that the following ice crystals are chiral: crystalline CO (α-CO) formed on amorphous H2O (a-H2O) grains in a 10-K molecular cloud, crystalline CH3OH formed by the heating of amorphous CH3OH on a-H2O grains at 40–60 K in young stellar objects, and several polymorphs of hydrogen-ordered cubic ice crystals formed by the heating of a-H2O at 80–100 K and direct condensation at 120–140 K in protoplanetary disks. We also investigated candidates for other chiral ices using published data. We found that NH3 I and NH3·H2O I are chiral at low temperature and pressure conditions. If one-handed circularly polarized light is irradiated during the nucleation of these chiral ice crystals, homochiral crystals can be formed. These results have important implications for the origin of interstellar organic molecule homochirality

Early and late optical coherence tomography findings following everolimus-eluting bioresorbable vascular scaffold implantation in myocardial infarction: A preliminary report

Introduction: Although bioresorbable vascular scaffolds (BVS) have been used with promising results in patients with stable and unstable angina, little is known about the acute vascular response following BVS implantation in myocardial infarction. We present angiographic and OCT findings from the first patients undergoing bioresorbable vascular scaffold (BVS) implantation for non-ST-elevation myocardial infarction (NSTEMI) or ST-elevation myocardial infarction (STEMI) in our institution. Methods: The first 5 patients with NSTEMI and the first 5 patients with STEMI who underwent BVS implantation in our institution, followed by optical coherence tomography (OCT) imaging of the treated culprit vessel, were included in this series. All patients underwent angiographic analysis pre- and post- BVS implantation, as well as OCT analysis, including qualitative and quantitative assessment. Results: Implantation was successful in all cases, as assessed by angiography and OCT. There were no cases with coronary spasm, distal embolization or no-reflow. No adverse clinical events were recorded in any patient at the 6-month follow up. Specific illustrative cases demonstrating the challenges of BVS implantation in myocardial infarction are presented. Conclusions: BVS implantation can potentially be used in the setting of thrombotic lesions encountered in myocardial infarction; however, the role of this treatment approach warrants systematic evaluation in prospective studies

Everolimus-eluting bioresorbable vascular scaffolds for treatment of patients presenting with ST-segment elevation myocardial infarction: BVS STEMI first study

AimsWe evaluated the feasibility and the acute performance of the everolimus-eluting bioresorbable vascular scaffolds (BVS) for the treatment of patients presenting with ST-segment elevation myocardial infarction (STEMI).Methods and resultsThe present investigation is a prospective, single-arm, single-centre study, reporting data after the BVS implantation in STEMI patients. Quantitative coronary angiography and optical coherence tomography (OCT) data were evaluated. Clinical outcomes are reported at the 30-day follow-up. The intent-to-treat population comprises a total of 49 patients. The procedural success was 97.9%. Pre-procedure TIMI-flow was 0 in 50.0% of the patients; after the BVS implantation, a TIMI-flow III was achieved in 91.7% of patients and the post-procedure percentage diameter stenosis was 14.7 ± 8.2%. No patients had angiographically visible residual thrombus at the end of the procedure. Optical coherence tomography analysis performed in 31 patients showed that the post-procedure mean lumen area was 8.02 ± 1.92 mm2, minimum lumen area 5.95 ± 1.61 mm2, mean incomplete scaffold apposition area 0.118 ± 0.162 mm2, mean intraluminal defect area 0.013 ± 0.017 mm2, and mean percentage malapposed struts per patient 2.80 ± 3.90%. Scaffolds with >5% malapposed struts were 7. At the 30-day follow-up, target-lesion failure rate was 0%. Non-target-vessel revascularization and target-vessel myocardial infarction (MI) were reported. A non-target-vessel non-Q-wave MI occurred. No cases of cardiac death or scaffold thrombosis were observed.ConclusionIn the present series, the BVS implantation in patients presenting with acute MI appeared feasible, with high rate of final TIMI-flow III and good scaffold apposition. Larger studies are currently needed to confirm these preliminary data

Laminin-based cell adhesion anchors microtubule plus ends to the epithelial cell basal cortex through LL5α/β

A newly discovered interaction between LL5s, laminins, and integrins reveals how the extracellular matrix directs microtubule polarity in epithelial tissues

Neointimal characteristics comparison between biodegradable-polymer and durable-polymer drug-eluting stents: 3-month follow-up optical coherence tomography light property analysis from the RESTORE registry

We aimed to quantitatively assess a possible difference of the neointimal quality between biodegradable polymer- (BP-) and durable polymer drug-eluting stents (DP-DESs). We conducted a single-center all-comer prospective cohort study: the RESTORE registry (UMIN000033009). All patients who received successful OCT examination at planned 3-month follow-up after DES implantation were analyzed. Study population was divided into 2 groups, BP-DES versus DP-DES groups. We evaluated standard OCT variables, coverage percent, and the quantitative light property values including light intensity, attenuation, and backscatter. We performed OCT analyses of 121 lesions in 98 patients (BP-DES 55 lesions in 51 patients vs. DP-DES 66 lesions in DP-DES 53 patients). Lesion and procedural characteristics were overall well-balanced between both groups. At 3-month follow-up, neointimal thickness (BP-DES 49.3 [38.2, 57.7] µm versus DP-DES 54.7 [45.1, 70.7] µm, p = 0.059) and coverage percent (BP-DES 94.5 [89.8, 97.0]% vs. DP-DES 95.8 [91.1, 98.1]%, p = 0.083) did not significantly differ. Light intensity of superficial neointima in the BP-DES was lower than that in the DP-DES, whereas that of deep neointima did not differ between both groups

Two genetic variants of CD38 in subjects with autism spectrum disorder and controls

金沢大学医薬保健研究域医学系The neurobiological basis of autism spectrum disorder (ASD) remains poorly understood. Given the role of CD38 in social recognition through oxytocin (OT) release, we hypothesized that CD38 may play a role in the etiology of ASD. Here, we first examined the immunohistochemical expression of CD38 in the hypothalamus of post-mortem brains of non-ASD subjects and found that CD38 was colocalized with OT in secretory neurons. In studies of the association between CD38 and autism, we analyzed 10 single nucleotide polymorphisms (SNPs) and mutations of CD38 by re-sequencing DNAs mainly from a case-control study in Japan, and Caucasian cases mainly recruited to the Autism Genetic Resource Exchange (AGRE). The SNPs of CD38, rs6449197 (p 70; designated as high-functioning autism (HFA)) in the U.S. 104 AGRE family trios, but not with Japanese 188 HFA subjects. A mutation that caused tryptophan to replace arginine at amino acid residue 140 (R140W; (rs1800561, 4693C>T)) was found in 0.6-4.6% of the Japanese population and was associated with ASD in the smaller case-control study. The SNP was clustered in pedigrees in which the fathers and brothers of T-allele-carrier probands had ASD or ASD traits. In this cohort OT plasma levels were lower in subjects with the T allele than in those without. One proband with the T allele who was taking nasal OT spray showed relief of symptoms. The two variant CD38 poloymorphysms tested may be of interest with regard of the pathophysiology of ASD. © 2010 Elsevier Ireland Ltd and the Japan Neuroscience Society