Abstract Remote ischemic postconditioning (RIPoC) attenuates ischemia/reperfusion (I/R) injury in the heart, lung and hind limb. RIPoC performed in the hind limb reduces brain injury following focal ...cerebral ischemia in rats. Whether RIPoC has a neuroprotective effect with respect to global cerebral I/R injury is, however, unknown, and the mechanism of neuroprotection needs further elucidation. Here we investigated whether RIPoC could reduce global cerebral I/R injury in rats and whether this neuroprotective effect was induced by up-regulating endothelial nitric oxide synthase (eNOS) through the phosphatidylinositol-3 kinase/Akt (PI3K/Akt) pathway. Global cerebral ischemia was performed via 8 min of four-vessel occlusion. Neuronal density, terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL)-positive cells and expression of Bcl-2 and Bax in the hippocampal CA1 region were assessed after reperfusion. Morris water maze task was used to quantify spatial learning and memory deficits after reperfusion. The expression of eNOS, phosphorylated eNOS (Ser1177), Akt and phosphorylated Akt (Ser473) in the CA1 region was measured after reperfusion. RIPoC significantly attenuated delayed neuronal death and reduced the spatial learning and memory deficits associated with global cerebral ischemia. Pre-administration of N(ω)-nitro- l -arginine methyl ester (a nonselective NOS inhibitor) significantly abolished the neuroprotective effect of RIPoC. Moreover, pre-administration of LY294002 (a highly selective inhibitor of PI3K) not only significantly reversed the neuroprotective effect of RIPoC, but also obviously inhibited the up-regulation of eNOS induced by RIPoC. Our findings suggest that RIPoC protects the brain against global cerebral I/R injury and that this neuroprotection is mediated by up-regulating eNOS through the PI3K/Akt pathway.
ABSTRACT Dysregulation of the homeostatic balance of histone H3 di- and tri-methyl lysine 27 (H3K27me2/3) levels caused by the mis-sense mutation of histone H3 (H3K27M) is reported to be associated ...with various types of cancers. In this study, we found that reduction in H3K27me2/3 caused by H3.1K27M, a mutation of H3 variants found in patients with diffuse intrinsic pontine glioma (DIPG), dramatically attenuated the presence of 53BP1 (also known as TP53BP1) foci and the capability of non-homologous end joining (NHEJ) in human dermal fibroblasts. H3.1K27M mutant cells showed increased rates of genomic insertions/deletions and copy number variations, as well as an increase in p53-dependent apoptosis. We further showed that both hypo-H3K27me2/3 and H3.1K27M interacted with FANCD2, a central player in the choice of DNA repair pathway. H3.1K27M triggered the accumulation of FANCD2 on chromatin, suggesting an interaction between H3.1K27M and FANCD2. Interestingly, knockdown of FANCD2 in H3.1K27M cells recovered the number of 53BP1-positive foci, NHEJ efficiency and apoptosis rate. Although these findings in HDF cells may differ from the endogenous regulation of the H3.1K27M mutant in the specific tumor context of DIPG, our results suggest a new model by which H3K27me2/3 facilitates NHEJ and the maintenance of genome stability. This article has an associated First Person interview with the first author of the paper.
Generally, most of adaptive nonuniformity correction algorithms have the ghosting artifact problem. In this paper, the cause of ghosting artifacts in Neural Network nonuniformity correction (NN-NUC) ...algorithm for infrared focal plane array (IRFPA) was studied. Based on the analysis, a novel algorithm for eliminating the ghosting artifact was proposed, which replaces the linear spatial average filter in the NN-NUC algorithm with the partial differential equation (PDE)-based nonlinear filter to estimate the desired image. The comparison experiment using real IRFPA infrared image shows that the proposed algorithm can effectively remove the ghosting artifact. Compared with several deghosting algorithms, the proposed algorithm converges much faster.
Acute ischemic stroke is one of the leading causes of death in developed countries and the most common cause of disability in adults worldwide. Despite advances in the understanding of stroke ...pathophysiology, therapeutic options remain limited. In this study, we explored the interaction of Shrm4 and the metabotropic gamma-aminobutyric acid (GABA) receptors (GABA
) in ischemic stroke. A transient middle cerebral artery occlusion (MCAO) model was induced by filament insertion in Shrm4+/+ and wild-type C57BL/6J mice, followed by reperfusion for up to 7 days. Baclofen was administered was used to activate GABA
in vivo during reperfusion. Neurological deficits, motor and memory functions, and infarct volume were determined in the various mouse groups. Furthermore, we also developed an oxygen-glucose deprivation (OGD) cell model in primary neurons to test Shrm4/GABA
interactions in vitro. Shrm4 was observed to decrease infarct volume and neuronal cell loss in penumbra, and rescue neurological deficits in MCAO mice. Notably, Shrm4 also increased pole climbing speed, reduced foot faults, and increased escape latency in the Morris water maze test, while reducing neuron autophagy through an interaction with GABA
receptors. GABA
activation using baclofen further reduced OGD-induced neuron damage in culture and stroke outcomes of MCAO, relative to Shrm4 alone. Taken together, Shrm4-mediated GABA
activation confers neuroprotection by reducing neuronal autophagy in acute ischemic stroke.
Semi-dwarfism is an agronomically important trait in breeding for resistance to damage by wind and rain (lodging resistance) and for stable high yields. Dwarf Polish wheat (Triticum polonicum L., 2n ...= 4x = 28, AABB AS304) is a potential donor of dwarfing and other traits for common wheat improvement. A genetic analysis using an F₂ population derived from a cross of AS304 and tall cultivar AS302 and derived F∧2:3 lines indicated that AS304 carries a recessive dwarfing gene, temporarily designated Rht-dp. Molecular markers and bulked segregant analysis were used to characterize and map the gene. Eight polymorphic SSR markers (Xwmc511, Xgwm495, Xgwm113, Xgwm192, Xgpw7026, Xgpw3017, Xgpw1108 and Xgpw7521) on chromosome arm 4BS and two AFLP markers (M∧8/E∧5 and M₄/E₃) were mapped relative to the dwarfing locus. The closest linked markers, Xgpw3017 and M∧8/E∧5 at 0.5 and 3.5 cM, respectively, from Rht-dp will enable its marker assisted transfer to wheat breeding populations. Allelic tests indicated that Rht-dp was allelic to Rht-B1b; hence it may be an alternative allele at the Rht-B1 locus.
Breast lumpectomy is usually performed under general or local anesthesia. To the best of our knowledge, whether conscious sedation with intranasal dexmedetomidine and local anesthesia is an effective ...anesthetic technique has not been studied. Thus, the present study aimed to investigate the effectiveness of conscious sedation with intranasal dexmedetomidine combined with local anesthesia in breast lumpectomy, and to identify its optimal dose. A prospective randomized, double-blinded, placebo-controlled, single-center study was designed, and patients undergoing breast lumpectomies were recruited based on the inclusion and exclusion criteria. All patients were randomly allocated to four groups: i) Local anesthesia with 0.9% intranasal saline (placebo); local anesthesia with ii) 1 microg.kg.sup.-1; iii) 1.5 microg.kg.sup.-1; or iv) 2 microg.kg.sup.-1 intranasal dexmedetomidine. The sedation status, pain relief, vital signs, adverse events, and satisfaction of patient and surgeon were recorded. Patients in the three dexmedetomidine groups were significantly more sedated and experienced less pain compared with the placebo group 45 min after intranasal dexmedetomidine administration and during 30 min in the post-anesthesia care unit. Patients in the 1.5 microg.kg.sup.-1 group were more sedated compared with the 1 microg.kg.sup.-1 group (without reaching statistical significance), whereas the 1.5microg.kg.sup.-1 group exhibited a similar level of sedation 45 min after intranasal dexmedetomidine administration compared with the 2 microg.kg.sup.-1 group. In addition, patients in the 1 and 1.5microg.kg.sup.-1 group experienced no adverse hemodynamic effects. Patient and surgeon satisfaction were greater in the 1.5microg.kg' group compared with the 1 and 2 microg.kg.sup.-1 groups. Taken together, the results of the present study suggested that conscious sedation with intranasal dexmedetomidine and local anesthesia may be an effective anesthetic for breast lumpectomy surgery, and that the optimal dose for intranasal dexmedetomidine administration may be 1.5 microg.kg.sup.-1, as it resulted in good sedation and patient satisfaction without adverse effects.
The cause of the target fade-out in the traditional neural network nonuniformity correction algorithms for infrared focal plane array(IRFPA)was studied. A new combinational algorithm for ...nonuniformity correction was proposed on the basis of analyzing the strengths and limitations of edge-directed NN scheme(ED-NN-NUC) and nonuniformity correction combining one-point calibration and NN-NUC. The new algorithm includes three modules which are pre-correction, rough correction and accurate correction. The real infrared image including dim targets was used to validate the proposed algorithm. The results show that the proposed algorithm can effectively eliminate the target fade-out, and it is less time consuming than ED-NN-NUC.
Breast lumpectomy is usually performed under general or local anesthesia. To the best of our knowledge, whether conscious sedation with intranasal dexmedetomidine and local anesthesia is an effective ...anesthetic technique has not been studied. Thus, the present study aimed to investigate the effectiveness of conscious sedation with intranasal dexmedetomidine combined with local anesthesia in breast lumpectomy, and to identify its optimal dose. A prospective randomized, double-blinded, placebo-controlled, single-center study was designed, and patients undergoing breast lumpectomies were recruited based on the inclusion and exclusion criteria. All patients were randomly allocated to four groups: i) Local anesthesia with 0.9% intranasal saline (placebo); local anesthesia with ii) 1 microg.kg.sup.-1; iii) 1.5 microg.kg.sup.-1; or iv) 2 microg.kg.sup.-1 intranasal dexmedetomidine. The sedation status, pain relief, vital signs, adverse events, and satisfaction of patient and surgeon were recorded. Patients in the three dexmedetomidine groups were significantly more sedated and experienced less pain compared with the placebo group 45 min after intranasal dexmedetomidine administration and during 30 min in the post-anesthesia care unit. Patients in the 1.5 microg.kg.sup.-1 group were more sedated compared with the 1 microg.kg.sup.-1 group (without reaching statistical significance), whereas the 1.5microg.kg.sup.-1 group exhibited a similar level of sedation 45 min after intranasal dexmedetomidine administration compared with the 2 microg.kg.sup.-1 group. In addition, patients in the 1 and 1.5microg.kg.sup.-1 group experienced no adverse hemodynamic effects. Patient and surgeon satisfaction were greater in the 1.5microg.kg' group compared with the 1 and 2 microg.kg.sup.-1 groups. Taken together, the results of the present study suggested that conscious sedation with intranasal dexmedetomidine and local anesthesia may be an effective anesthetic for breast lumpectomy surgery, and that the optimal dose for intranasal dexmedetomidine administration may be 1.5 microg.kg.sup.-1, as it resulted in good sedation and patient satisfaction without adverse effects.
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