Exercise-Induced Neuroprotection of the Nigrostriatal Dopamine System in Parkinson's Disease

Epidemiological studies indicate that physical activity and exercise may reduce the risk of developing Parkinson's disease (PD), and clinical observations suggest that physical exercise can reduce the motor symptoms in PD patients. In experimental animals, a profound observation is that exercise of appropriate timing, duration, and intensity can reduce toxin-induced lesion of the nigrostriatal dopamine (DA) system in animal PD models, although negative results have also been reported, potentially due to inappropriate timing and intensity of the exercise regimen. Exercise may also minimize DA denervation-induced medium spiny neuron (MSN) dendritic atrophy and other abnormalities such as enlarged corticostriatal synapse and abnormal MSN excitability and spiking activity. Taken together, epidemiological studies, clinical observations, and animal research indicate that appropriately dosed physical activity and exercise may not only reduce the risk of developing PD in vulnerable populations but also benefit PD patients by potentially protecting the residual DA neurons or directly restoring the dysfunctional cortico-basal ganglia motor control circuit, and these benefits may be mediated by exercise-triggered production of endogenous neuroprotective molecules such as neurotrophic factors. Thus, exercise is a universally available, side effect-free medicine that should be prescribed to vulnerable populations as a preventive measure and to PD patients as a component of treatment. Future research needs to establish standardized exercise protocols that can reliably induce DA neuron protection, enabling the delineation of the underlying cellular and molecular mechanisms that in turn can maximize exercise-induced neuroprotection and neurorestoration in animal PD models and eventually in PD patients

Combination Of The Immune Modulator Fingolimod With Alteplase In Acute Ischemic Stroke: A Pilot Trial

Background-Inflammatory and immune responses triggered by brain ischemia worsen clinical outcomes of stroke and contribute to hemorrhagic transformation, massive edema, and reperfusion injury associated with intravenous alteplase. We assessed whether a combination of the immune-modulator fingolimod and alteplase is safe and effective in attenuating reperfusion injury in patients with acute ischemic stroke treated within the first 4.5 hours of symptom onset. Methods and Results-In this multicenter trial, we randomly assigned 25 eligible patients with hemispheric ischemic stroke stemming from anterior or middle cerebral arterial occlusion to receive alteplase alone and 22 patients to receive alteplase plus oral fingolimod 0.5 mg daily for 3 consecutive days within 4.5 hours of the onset of ischemic stroke. Compared with patients who received alteplase alone, patients who received the combination of fingolimod with alteplase exhibited lower circulating lymphocytes, smaller lesion volumes (10.1 versus 34.3 mL; P=0.04), less hemorrhage (1.2 versus 4.4 mL; P=0.01), and attenuated neurological deficits in National Institute of Health Stroke Scales (4 versus 2; P=0.02) at day 1. Furthermore, restrained lesion growth from day 1 to 7 (-2.3 versus 12.1 mL; P\u3c0.01) with a better recovery at day 90 (modified Rankin Scale score 0-1, 73% versus 32%; P\u3c0.01) was evident in patients given fingolimod and alteplase. No serious adverse events were recorded in all patients. Conclusions-In this pilot study, combination therapy of fingolimod and alteplase was well tolerated, attenuated reperfusion injury, and improved clinical outcomes in patients with acute ischemic stroke. These findings need to be tested in further clinical trials. Clinical Trial Registration-URL: http://www.clinicaltrials.gov. Unique identifier: NCT02002390

Neutron-Diffraction and Mössbauer-Effect Studies of Pr₂(Fe₁₋ₓMnₓ)₁₄B

A neutron-diffraction investigation of a series of Pr2(Fe 1-xMnx)14B samples, with x values of 0.00, 0.11, 0.22, 0.30, and 0.35, reveals a preference for the manganese to occupy the 8j2 transition-metal site,the transition-metal site with the largest Wigner-Seitz cell volume. Similar site occupancies have been reported previously for Er2(Fe1-xMnx) 14B and Y2(Fe1-xMnx) 14B. An analysis of the 295-K Mössbauer spectrum of Pr2(Fe0.89Mn0.11)14B indicates that the internal hyperfine fields on the six iron sites are more substantially reduced from those found in Pr2Fe1 4B than would be expected from a simple magnetic dilution with manganese. The extent of the field reduction for a specific site increases with the number of manganese near neighbors for the site. Fits of the Mössbauer spectra of Pr2(Fe0.78Mn0.22)1 4B, Pr2(Fe0.70Mn0.30) 14B, and Pr2(Fe0.65Mn 0.35)14B, which are paramagnetic at room temperature, give quadrupole splittings consistent with the quadrupole interactions in Pr2Fe14B

Genome-Wide Detection for Runs of Homozygosity in Baoshan Pigs Using Whole Genome Resequencing

Baoshan pigs (BS) are a local breed in Yunnan Province that may face inbreeding owing to its limited population size. To accurately evaluate the inbreeding level of the BS pig population, we used whole-genome resequencing to identify runs of homozygosity (ROH) regions in BS pigs, calculated the inbreeding coefficient based on pedigree and ROH, and screened candidate genes with important economic traits from ROH islands. A total of 22,633,391 SNPS were obtained from the whole genome of BS pigs, and 201 ROHs were detected from 532,450 SNPS after quality control. The number of medium-length ROH (1–5 Mb) was the highest (98.43%), the number of long ROH (>5 Mb) was the lowest (1.57%), and the inbreeding of BS pigs mainly occurred in distant generations. The inbreeding coefficient FROH, calculated based on ROH, was 0.018 ± 0.016, and the FPED, calculated based on the pedigree, was 0.027 ± 0.028, which were positively correlated. Forty ROH islands were identified, containing 507 genes and 891 QTLs. Several genes were associated with growth and development (IGFALS, PTN, DLX5, DKK1, WNT2), meat quality traits (MC3R, ACSM3, ECI1, CD36, ROCK1, CACNA2D1), and reproductive traits (NPW, TSHR, BMP7). This study provides a reference for the protection and utilization of BS pigs

Une intallation simple et pratique d'elution par gradient et son application a la separation des elements des terres rares

Translated from He Huaxne Yu Fancshe Huaxne, China, May 1980, v. 2(2) p. 116-122SIGLEAvailable from CEN Saclay, Service de Documentation, 91191 - Gif-sur-Yvette Cedex (France) / INIST-CNRS - Institut de l'Information Scientifique et TechniqueFRFranc

Facile synthesis of water-soluble, highly fluorescent graphene quantum dots as a robust biological label for stem cells

We present a facile electrochemical method for synthesizing uniform sized graphene quantum dots (GQDs) with a strong yellow emission at 14% quantum yield. This approach has enabled a large-scale production of aqueous GQD solution without the need for polymeric or surfactant stabilizers. The structure and emission mechanism of the GQDs have been studied by combining extensive characterization techniques, rigorous control experiments and theoretical calculations. We further demonstrate the distinctive advantages of such GQDs for direct and efficient stem cell labeling, opening up great opportunities for their bio-medical applications

Brain structural and functional alterations in MOG antibody disease

BACKGROUND: The impact of myelin oligodendrocyte glycoprotein antibody disease (MOGAD) on brain structure and function is unknown. OBJECTIVES: The aim of this study was to study the multimodal brain MRI alterations in MOGAD and to investigate their clinical significance. METHODS: A total of 17 MOGAD, 20 aquaporin-4 antibody seropositive neuromyelitis optica spectrum disorders (AQP4 + NMOSD), and 28 healthy controls (HC) were prospectively recruited. Voxel-wise gray matter (GM) volume, fractional anisotropy (FA), mean diffusivity (MD), and degree centrality (DC) were compared between groups. Clinical associations and differential diagnosis were determined using partial correlation and stepwise logistic regression. RESULTS: In comparison with HC, MOGAD had GM atrophy in frontal and temporal lobe, insula, thalamus, and hippocampus, and WM fiber disruption in optic radiation and anterior/posterior corona radiata; DC decreased in cerebellum and increased in temporal lobe. Compared to AQP4 + NMOSD, MOGAD presented lower GM volume in postcentral gyrus and decreased DC in cerebellum. Hippocampus/parahippocampus atrophy associated with Expanded Disability Status Scale (R = -0.55, p = 0.04) and California Verbal Learning Test (R = 0.62, p = 0.031). The differentiation of MOGAD from AQP4 + NMOSD achieved an accuracy of 95% using FA in splenium of corpus callosum and DC in occipital gyrus. CONCLUSION: Distinct structural and functional alterations were identified in MOGAD. Hippocampus/parahippocampus atrophy associated with clinical disability and cognitive impairment