Specific subsystems of the inferior parietal lobule are associated with hand dysfunction following stroke: A cross-sectional resting-state fMRI study

Aim The inferior parietal lobule (IPL) plays important roles in reaching and grasping during hand movements, but how reorganizations of IPL subsystems underlie the paretic hand remains unclear. We aimed to explore whether specific IPL subsystems were disrupted and associated with hand performance after chronic stroke. Methods In this cross-sectional study, we recruited 65 patients who had chronic subcortical strokes and 40 healthy controls from China. Each participant underwent the Fugl-Meyer Assessment of Hand and Wrist and resting-state fMRI at baseline. We mainly explored the group differences in resting-state effective connectivity (EC) patterns for six IPL subregions in each hemisphere, and we correlated these EC patterns with paretic hand performance across the whole stroke group and stroke subgroups. Moreover, we used receiver operating characteristic curve analysis to distinguish the stroke subgroups with partially (PPH) and completely (CPH) paretic hands. Results Stroke patients exhibited abnormal EC patterns with ipsilesional PFt and bilateral PGa, and five sensorimotor-parietal/two parietal–temporal subsystems were positively or negatively correlated with hand performance. Compared with CPH patients, PPH patients exhibited abnormal EC patterns with the contralesional PFop. The PPH patients had one motor-parietal subsystem, while the CPH patients had one sensorimotor-parietal and three parietal-occipital subsystems that were associated with hand performance. Notably, the EC strength from the contralesional PFop to the ipsilesional superior frontal gyrus could distinguish patients with PPH from patients with CPH. Conclusions The IPL subsystems manifest specific functional reorganization and are associated with hand dysfunction following chronic stroke.Natural Science Foundation of Zhejiang Province, Grant/Award Number: LGF19H270001; Shanghai Sailing Program, Grant/Award Number: 20YF144510

Recent Walker Circulation strengthening and Pacific cooling amplified by Atlantic warming

An unprecedented strengthening of Pacific trade winds since the late 1990s (ref. 1) has caused widespread climate perturbations, including rapid sea-level rise in the western tropical Pacific, strengthening of Indo-Pacific ocean currents, and an increased uptake of heat in the equatorial Pacific thermocline. The corresponding intensification of the atmospheric Walker circulation is also associated with sea surface cooling in the eastern Pacific, which has been identified as one of the contributors to the current pause in global surface warming. In spite of recent progress in determining the climatic impacts of the Pacific trade wind acceleration, the cause of this pronounced trend in atmospheric circulation remains unknown. Here we analyse a series of climate model experiments along with observational data to show that the recent warming trend in Atlantic sea surface temperature and the corresponding trans-basin displacements of the main atmospheric pressure centres were key drivers of the observed Walker circulation intensification, eastern Pacific cooling, North American rainfall trends and western Pacific sea-level rise. Our study suggests that global surface warming has been partly offset by the Pacific climate response to enhanced Atlantic warming since the early 1990s

The Werner Syndrome Helicase/Exonuclease Processes Mobile D-Loops through Branch Migration and Degradation

RecQ DNA helicases are critical for preserving genome integrity. Of the five RecQ family members identified in humans, only the Werner syndrome protein (WRN) possesses exonuclease activity. Loss of WRN causes the progeroid disorder Werner syndrome which is marked by cancer predisposition. Cellular evidence indicates that WRN disrupts potentially deleterious intermediates in homologous recombination (HR) that arise in genomic and telomeric regions during DNA replication and repair. Precisely how the WRN biochemical activities process these structures is unknown, especially since the DNA unwinding activity is poorly processive. We generated biologically relevant mobile D-loops which mimic the initial DNA strand invasion step in HR to investigate whether WRN biochemical activities can disrupt this joint molecule. We show that WRN helicase alone can promote branch migration through an 84 base pair duplex region to completely displace the invading strand from the D-loop. However, substrate processing is altered in the presence of the WRN exonuclease activity which degrades the invading strand both prior to and after release from the D-loop. Furthermore, telomeric D-loops are more refractory to disruption by WRN, which has implications for tighter regulation of D-loop processing at telomeres. Finally, we show that WRN can recognize and initiate branch migration from both the 5′ and 3′ ends of the invading strand in the D-loops. These findings led us to propose a novel model for WRN D-loop disruption. Our biochemical results offer an explanation for the cellular studies that indicate both WRN activities function in processing HR intermediates

Evolutionary Emergence of microRNAs in Human Embryonic Stem Cells

Human embryonic stem (hES) cells have unique abilities to divide indefinitely without differentiating and potential to differentiate into more than 200 cell types. These properties make hES cells an ideal model system for understanding early human development and for regenerative medicine. Molecular mechanisms including cellular signaling and transcriptional regulation play important roles in hES cell differentiation. However, very little information is available on posttranscriptional regulation of hES cell pluripotency, self-renewal, and early decisions about cell fate. microRNAs (miRNAs), 22-nt long non-coding small RNAs found in plants and animals, regulate gene expression by targeting mRNAs for cleavage or translation repression. In hES cells we found that 276 miRNAs were expressed; of these, a set of 30 miRNAs had significantly changed expression during differentiation. Using a representative example, miR-302b, we show that miRNAs in human ES cells assemble into a bona fide RISC that contains Ago2 and can specifically cleave perfectly matched target RNA. Our results demonstrate that human ES cell differentiation is accompanied by changes in the expression of a unique set of miRNAs, providing a glimpse of a new molecular circuitry that may regulate early development in humans. Chromosomes 19 and X contained 98 and 40 miRNA genes, respectively, indicating that majority of miRNA genes in hES cells were expressed from these two chromosomes. Strikingly, distribution analysis of miRNA gene loci across six species including dog, rat, mouse, rhesus, chimpanzee, and human showed that miRNA genes encoded in chromosome 19 were drastically increased in chimpanzees and humans while miRNA gene loci on other chrosmomes were decreased as compared with dog, rat, and mouse. Comparative genomic studies showed 99% conservation of chromosome 19 miRNA genes between chimpanzees and humans. Together, these findings reveal the evolutionary emergence, ∼5 million years ago, of miRNAs involved in regulating early human development. One could imagine that this burst of miRNA gene clusters at specific chromosomes was part of an evolutionary event during species divergence

Upregulation of miR-196b Confers a Poor Prognosis in Glioblastoma Patients via Inducing a Proliferative Phenotype

PURPOSE: To explore the expression pattern, prognostic value and functional role of miR-196b in glioblastoma (GBM) patients using large cohorts. EXPERIMENTAL DESIGN: MiR-196b expression was measured using the Human v2.0 miRNA Expression BeadChip (Illumina) in 198 frozen glioma tissues. The expression levels of miR-196b were also validated in an independent cohort containing 128 formalin-fixed paraffin-embedded (FFPE) glioma samples using qRT-PCR. The presence of other molecular prognostic indicators was assessed centrally in the glioma samples. Whole genome gene profiling was performed to investigate the underlying biological behavior. MiR-196b functional analyses were performed in U87 and U251 cell lines. RESULTS: The expression levels of miR-196b were inversely correlated with overall survival in GBM patients. Gene set enrichment analysis (GSEA) showed that the gene sets relating to cell cycle were significantly enriched in the cases with miR-196b overexpression. Functional analyses in U87 and U251 cells revealed that miR-196b was involved in cell proliferation. CONCLUSIONS: MiR-196b is overexpressed and confers a poor prognosis via promoting cellular proliferation in GBM patients

Treatment of myofascial trigger points in common shoulder disorders by physical therapy: A randomized controlled trial [ISRCTN75722066]

Contains fulltext : 52454.pdf (publisher's version ) (Open Access

A Global Characterization and Identification of Multifunctional Enzymes

Multi-functional enzymes are enzymes that perform multiple physiological functions. Characterization and identification of multi-functional enzymes are critical for communication and cooperation between different functions and pathways within a complex cellular system or between cells. In present study, we collected literature-reported 6,799 multi-functional enzymes and systematically characterized them in structural, functional, and evolutionary aspects. It was found that four physiochemical properties, that is, charge, polarizability, hydrophobicity, and solvent accessibility, are important for characterization of multi-functional enzymes. Accordingly, a combinational model of support vector machine and random forest model was constructed, based on which 6,956 potential novel multi-functional enzymes were successfully identified from the ENZYME database. Moreover, it was observed that multi-functional enzymes are non-evenly distributed in species, and that Bacteria have relatively more multi-functional enzymes than Archaebacteria and Eukaryota. Comparative analysis indicated that the multi-functional enzymes experienced a fluctuation of gene gain and loss during the evolution from S. cerevisiae to H. sapiens. Further pathway analyses indicated that a majority of multi-functional enzymes were well preserved in catalyzing several essential cellular processes, for example, metabolisms of carbohydrates, nucleotides, and amino acids. What’s more, a database of known multi-functional enzymes and a server for novel multi-functional enzyme prediction were also constructed for free access at http://bioinf.xmu.edu.cn/databases/MFEs/index.htm