GPR120 is an important inflammatory regulator in the development of osteoarthritis.

BACKGROUND: The aim of this study was to investigate the regulatory role of G-protein coupled receptor 120 (GPR120) in the development and progression of osteoarthritis (OA). METHODS: GPR120 knockout (KO) and wild-type (WT) mice were used to create an animal model of OA by means of anterior cruciate ligament transection (ACLT) surgery. The severity of OA was staged and evaluated by histological examination, microcomputed tomography scan and enzyme-linked immunosorbent assay (ELISA). The anti-inflammatory effects of the GPR120 agonist docosahexaenoic acid (DHA) on human chondrocytes were further evaluated by specific inflammatory markers. In addition, the healing progression of a skin defect model was determined with histological assays. RESULTS: The GPR120-KO mice displayed an accelerated development of OA after ACLT. The secondary inflammation, cartilage degeneration, and subchondral bone aberrant changes were significantly elevated in the early phase of OA in KO mice relative to those in WT mice. In addition, we found that GPR120 levels were downregulated in OA patients compared with control subjects, whereas GPR120 activation with DHA exhibited anti-inflammatory effects in primary human chondrocytes in vitro. Moreover, results from the skin defect model showed that GPR120 agonism with DHA enhanced wound repair in mice, as shown by the downregulation of the number of CD68+ cells. CONCLUSIONS: Our study suggests that GPR120 is an important inflammatory mediator during the development of OA, and that it is a potential marker for the diagnosis of high-risk patients with OA

Six-Digit Stroke-based Chinese Input Method

Abstract-During the last three decades, more than one thousand Chinese input methods have been developed. However, people are still looking for better input methods in terms of easy to use, easy to remember, high input speed and small keypad implementation on handheld devices. The well-known strokebased Chinese input method using only five basic stroke types could achieve low learning curve and small numeric keypad implementation but its input speed is limited for complex Chinese characters with a lot of strokes. To tackle this problem, simplified stroke-based Chinese character and phrase coding methods using (3+3) rules are proposed in this paper. The proposed method only uses the first 3 stroke codes and the last 3 stroke codes to represent the first and last radical information of the character for achieving lower average code length and higher hit rate of first character on the candidate list. To further enhance the input speed, a very user-friendly (3+3) phrase coding rule is also proposed for inputting Chinese phrases in terms of 2-character, 3-character and long-character phrases. Three special key assignment designs are developed for practical implementation of the proposed Chinese character and phrase input method using conventional QWERTY keyboard, PC's numeric keypad and mobile phone 12-key keypad. Experimental results have shown that the proposed character coding can achieve lower average code length and higher Hit Rate of First Character as compared with conventional stroke-based method and some well-known Chinese input methods. The proposed coding rules are also very easy to use and remember

Graphic loans: East Asia and beyond

The national languages of East Asia (Chinese, Japanese, Korean and Vietnamese) have made extensive use of a type of linguistic borrowing sometimes referred to as a 'graphic loan'. Such loans have no place in the conventional classification of loans based on Haugen (1950) or Weinreich (1953), and research on loan word theory and phonology generally overlooks them. The classic East Asian phenomenon is discussed and a framework is proposed to describe its mechanism. It is argued that graphic loans are more than just 'spelling pronunciations', because they are a systematic and widespread process, independent of but not inferior to phonological borrowing. The framework is then expanded to cover a range of other cases of borrowing between languages to show that graphic loans are not a uniquely East Asian phenomenon, and therefore need to be considered as a major category of loan

The genetic architecture of the human cerebral cortex

The cerebral cortex underlies our complex cognitive capabilities, yet little is known about the specific genetic loci that influence human cortical structure. To identify genetic variants that affect cortical structure, we conducted a genome-wide association meta-analysis of brain magnetic resonance imaging data from 51,665 individuals. We analyzed the surface area and average thickness of the whole cortex and 34 regions with known functional specializations. We identified 199 significant loci and found significant enrichment for loci influencing total surface area within regulatory elements that are active during prenatal cortical development, supporting the radial unit hypothesis. Loci that affect regional surface area cluster near genes in Wnt signaling pathways, which influence progenitor expansion and areal identity. Variation in cortical structure is genetically correlated with cognitive function, Parkinson's disease, insomnia, depression, neuroticism, and attention deficit hyperactivity disorder

Guidelines for the use and interpretation of assays for monitoring autophagy (4th edition)1.

In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monitoring autophagy in different organisms. Despite numerous reviews, there continues to be confusion regarding acceptable methods to evaluate autophagy, especially in multicellular eukaryotes. Here, we present a set of guidelines for investigators to select and interpret methods to examine autophagy and related processes, and for reviewers to provide realistic and reasonable critiques of reports that are focused on these processes. These guidelines are not meant to be a dogmatic set of rules, because the appropriateness of any assay largely depends on the question being asked and the system being used. Moreover, no individual assay is perfect for every situation, calling for the use of multiple techniques to properly monitor autophagy in each experimental setting. Finally, several core components of the autophagy machinery have been implicated in distinct autophagic processes (canonical and noncanonical autophagy), implying that genetic approaches to block autophagy should rely on targeting two or more autophagy-related genes that ideally participate in distinct steps of the pathway. Along similar lines, because multiple proteins involved in autophagy also regulate other cellular pathways including apoptosis, not all of them can be used as a specific marker for bona fide autophagic responses. Here, we critically discuss current methods of assessing autophagy and the information they can, or cannot, provide. Our ultimate goal is to encourage intellectual and technical innovation in the field

Pan-cancer analysis of whole genomes

Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale(1-3). Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4-5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter(4); identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation(5,6); analyses timings and patterns of tumour evolution(7); describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity(8,9); and evaluates a range of more-specialized features of cancer genomes(8,10-18).Peer reviewe

Quantitative 18F-AV1451 Brain Tau PET Imaging in Cognitively Normal Older Adults, Mild Cognitive Impairment, and Alzheimer's Disease Patients

Recent developments of tau Positron Emission Tomography (PET) allows assessment of regional neurofibrillary tangles (NFTs) deposition in human brain. Among the tau PET molecular probes, 18F-AV1451 is characterized by high selectivity for pathologic tau aggregates over amyloid plaques, limited non-specific binding in white and gray matter, and confined off-target binding. The objectives of the study are (1) to quantitatively characterize regional brain tau deposition measured by 18F-AV1451 PET in cognitively normal older adults (CN), mild cognitive impairment (MCI), and AD participants; (2) to evaluate the correlations between cerebrospinal fluid (CSF) biomarkers or Mini-Mental State Examination (MMSE) and 18F-AV1451 PET standardized uptake value ratio (SUVR); and (3) to evaluate the partial volume effects on 18F-AV1451 brain uptake.Methods: The study included total 115 participants (CN = 49, MCI = 58, and AD = 8) from the Alzheimer's Disease Neuroimaging Initiative (ADNI). Preprocessed 18F-AV1451 PET images, structural MRIs, and demographic and clinical assessments were downloaded from the ADNI database. A reblurred Van Cittertiteration method was used for voxelwise partial volume correction (PVC) on PET images. Structural MRIs were used for PET spatial normalization and region of interest (ROI) definition in standard space. The parametric images of 18F-AV1451 SUVR relative to cerebellum were calculated. The ROI SUVR measurements from PVC and non-PVC SUVR images were compared. The correlation between ROI 18F-AV1451 SUVR and the measurements of MMSE, CSF total tau (t-tau), and phosphorylated tau (p-tau) were also assessed.Results:18F-AV1451 prominently specific binding was found in the amygdala, entorhinal cortex, parahippocampus, fusiform, posterior cingulate, temporal, parietal, and frontal brain regions. Most regional SUVRs showed significantly higher uptake of 18F-AV1451 in AD than MCI and CN participants. SUVRs of small regions like amygdala, entorhinal cortex and parahippocampus were statistically improved by PVC in all groups (p < 0.01). Although there was an increasing tendency of 18F-AV-1451 SUVRs in MCI group compared with CN group, no significant difference of 18F-AV1451 deposition was found between CN and MCI brains with or without PVC (p > 0.05). Declined MMSE score was observed with increasing 18F-AV1451 binding in amygdala, entorhinal cortex, parahippocampus, and fusiform. CSF p-tau was positively correlated with 18F-AV1451 deposition. PVC improved the results of 18F-AV-1451 tau deposition and correlation studies in small brain regions.Conclusion: The typical deposition of 18F-AV1451 tau PET imaging in AD brain was found in amygdala, entorhinal cortex, fusiform and parahippocampus, and these regions were strongly associated with cognitive impairment and CSF biomarkers. Although more deposition was observed in MCI group, the 18F-AV-1451 PET imaging could not differentiate the MCI patients from CN population. More tau deposition related to decreased MMSE score and increased level of CSF p-tau, especially in ROIs of amygdala, entorhinal cortex and parahippocampus. PVC did improve the results of tau deposition and correlation studies in small brain regions and suggest to be routinely used in 18F-AV1451 tau PET quantification

Epidemiology and geographical distribution of child abuse in Hong Kong

Objectives: The objectives of this study are 1) To study the epidemiology and geographical distribution of child abuse in Hong Kong. 2) To study the district differences in co-morbidities of child abuse. Methods: Children under 19 years old with diagnostic codes for child abuse and child maltreatment from 1st January 2001 to 31st December 2010 were retrieved from Hospital Authority database. Demographics, hospital admission data and co-morbidities diagnosis were retrieved. The data were further analyzed according to districts of Hong Kong. Results: A total of 8055 episodes of child abuse were retrieved. 4241 (52.7%) were female and 3814 (47.3%) were male. There was a significant increasing trend of child abuse steadily in the whole territory over the study period. There were significant differences in the number of child abuse cases among different districts (p = 0.0038). Yuen Long, followed by Tuen Mun, constituted the highest numbers of child abuse cases, with 970 cases (12%) and 896 cases (11.1%) identified respectively. The mean age of onset of child abuse was 8.5 years old, while the mean number of hospital admission was 2.3 episodes during the study period. For length of hospital stay, the overall mean was 6.5 days. There was no significant difference among the clusters. The overall rate of suicidal attempt was 1.6%. The rate of suicidal attempt in New Territory west cluster (2.5%) was 2.8 times of that of Hong Kong west cluster (0.9%) (p<0.0001). The number of injury diagnosis, mental health problem, developmental delay, behavioral problem, antisocial or conduct problem, were also significantly different among different clusters. (p<0.05). Conclusion: There was a significant increasing trend of child abuse in the past decade in Hong Kong. In addition, the present study demonstrated a significant geographical variation in the number of child abuse cases as well as their associated co-morbidities. The identification of areas with higher rates of child abuse and associated co-morbidities poses important implication on service planning and policy making.published_or_final_versionPaediatrics and Adolescent MedicineMasterMaster of Medical Science

Transcriptional regulation of the human secretin receptor gene expression

published_or_final_versionZoologyMasterMaster of Philosoph