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Valentin Ortega posted an update 4 hours, 21 minutes ago
Recently, the arylsulfatase A (ARSA) variant c.899 T > C (p.L300S) was identified to be segregated with Parkinson’s disease (PD) in one family of Japanese descent. And the variant c.1055A > G (p.N352S) of ARSA was reported as a risk reduction factor for PD in a Japanese population. To further investigate the relationship between ARSA and PD, we screened these two loci of the ARSA gene in 407 sporadic PD patients and 471 healthy controls from a Chinese Han population. However, we did not detect the ARSA p.L300S variant in either PD patients or healthy controls. see more Moreover, in case-control association analysis, the p.N325S variant showed no significant association with PD. Therefore, these results suggested that these ARSA variants may not be common genetic factors for sporadic PD in Chinese Han population.Aging is associated with an increased risk for Parkinson’s disease and dementia with Lewy bodies, in which α-synuclein (α-syn) oligomerization plays key pathogenic roles. Here, we show that oligomeric α-syn levels increase with age in the human brain and are accompanied by a decrease in the activity of glucocerebrosidase (GCase), a lysosomal enzyme whose dysfunction is linked to the accumulation of oligomeric α-syn. The inverse relationship between oligomeric α-syn levels and GCase activity was more evident in brain regions susceptible to neurodegeneration (i.e., the striatum and hippocampus) than those that are less vulnerable (i.e., the cerebellum and occipital cortex). GCase could potentially regulate α-syn oligomerization, as demonstrated by the decrease in oligomeric α-syn levels caused by a GCase agonist. In vitro experiments showed that GCase activity was more potently inhibited by oligomeric than monomeric α-syn in the lysosome-enriched fractions isolated from brain tissues and cultured neuronal cells. Alterations in oligomeric α-syns and their association with GCase in aging brains may explain the vulnerability of certain brain regions to neurodegeneration in Parkinson’s disease and dementia with Lewy bodies.Purpose To identify the local spatiotemporal consistency of spontaneous brain activity of attention-deficit/hyperactivity disorder (ADHD) adolescents and its relation with clinical performance. Materials and methods A cohort of 50 adolescents with ADHD-I or ADHD-C and a cohort of age- and gender- matched 46 typical development controls (TDC) were recruited from ADHD-200 dataset. FOur-dimensional (spatiotemporal) Consistency of local neural Activities (FOCA) metric was used to analyze the local spatiotemporal consistency, which integrating local temporal homogeneity and regional stability of brain activity states. The difference of normalized FOCA (nFOCA) values among ADHD-Inattentive (ADHD-I), ADHD-Combined (ADHD-C) and TDC were detected using ANOVA and post-hoc analysis. Furthermore, partial correlations were analyzed to investigate the relationship between nFOCA values and clinical manifestations. Results Compared with TDC, ADHD-C and ADHD-I adolescents demonstrated alterations of FOCA in bilateral middle temporal gyrus, superior occipital gyrus, postcentral gyrus, precuneus, and right inferior temporal gyrus, lingual gyrus, superior frontal gyrus, left middle cingulum gyrus, middle occipital gyrus and cerebellum area. Conclusions Our study suggests that the FOCA method perhaps has potential to provide important insights into understanding the pathophysiological mechanism of ADHD and its subtypes.Previous studies have demonstrated that nonspatial repetition inhibition can occur across modalities. However, the underlying mechanism of such cross-modal nonspatial repetition inhibition is unknown. The present experiment adopted a cross-modal prime-neutral cue-target paradigm in which in consecutive trials the prime and the target were matched or mismatched, not only in identity but also in modality. Meanwhile, event-related potentials (ERPs) to visual and auditory targets were recorded. The present study aimed to answer two questions which ERP components reflect nonspatial repetition inhibition across modalities, and is the ERP component modality specific or supramodal? The results showed that for visual targets, robust nonspatial repetition inhibition occurred similarly for both unimodal (visual-visual) and cross-modal (audio-visual) target pairings, as indexed by an N400 repetition-induced increment in the typical N400 window but null effects during the N2 epoch. For auditory targets, similar modulation of cross-modal nonspatial repetition inhibition on the auditory-evoked N400 repetition-induced increment was observed. These results suggest that the N400 repetition-induced increment occurs during the N400 epoch that underlies cross-modal nonspatial repetition inhibition and that this N400 component is a supramodal component.Objectives The emergence and outbreak of colistin-resistant CRKP (carbapenem-resistant Klebsiella pneumoniae) have been the major global public threat in recent years. Present study emphasized the genome-wide distribution, characterization of drug resistance virulence genes in an extremely drug-resistant (XDR) Klebsiella pneumoniae strain isolated from a patient with drug-induced hepatitis, hospitalized in a tertiary care facility in India. Methods The total genomic DNA was sequenced using the Illumina Hiseq platform. De novo assembly of reads was done using CLC genomics workbench. Genome annotation was performed using PROKKA. Sequence typing (ST), virulence-related genes and antimicrobial resistance genes were predicted from genome sequences. Phenotypic evaluation of efflux pump function was done in presence of colistin and efflux pump inhibitor (EPI). Result Antibiogram analysis confirmed the isolate to be XDR. The number of contigs in assembly file was found to be 867 with a total of 6,060,836 bases and a total of 5547 coding sequences. The isolate exhibited high resistance to colistin due to mutations in two-component systems and predicted to be efflux mediated. The sequence typing of Klebsiella pneumoniae SDL79 is assigned to ST147. Conclusion This is the first whole genome analysis of XDR Klebsiella pneumoniae ST147 from a hospital conferring co-resistance to last resort drugs. However, the detailed molecular mechanism behind the drug resistance will be carried out in our future endeavors.