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Motivation Predicting protein–ligand binding affinity is crucial in new drug discovery and development. However, most existing models rely on acquiring 3D structures of elusive proteins. Combining amino acid sequences with ligand sequences and better highlighting active sites are also significant challenges. Results We propose an innovative neural network model called DEAttentionDTA, based on dynamic word embeddings and a self-attention mechanism, for predicting protein–ligand binding affinity. DEAttentionDTA takes the 1D sequence information of proteins as input, including the global sequence features of amino acids, local features of the active pocket site, and linear representation information of the ligand molecule in the SMILE format. These three linear sequences are fed into a dynamic word-embedding layer based on a 1D convolutional neural network for embedding encoding and are correlated through a self-attention mechanism. The output affinity prediction values are generated using a linear layer. We compared DEAttentionDTA with various mainstream tools and achieved significantly superior results on the same dataset. We then assessed the performance of this model in the p38 protein family. Availability and implementation The resource codes are available at https://github.com/whatamazing1/DEAttentionDTA. [ABSTRACT FROM AUTHOR]

Previous studies have indicated that non-SMC condensin I complex, subunit D2 (NCAPD2), an important protein in chromosome condensation, gene polymorphisms are associated with Alzheimer's disease. But no study has shown the relationship between NCAPD2 polymorphisms and Parkinson's disease. Here, we conducted a case-control study to investigate the relationship between NCAPD2 polymorphisms and the risk of Parkinson's disease in a Han Chinese population. Two single nuclear polymorphisms (SNPs) of NCAPD2 (rs7311174 and rs2072374) showed significant p values (p = 0.046 and p = 0.043, respectively) in 265 patients and 267 controls. Further analysis showed an effect of age and gender on the relationship between the two SNPs and the risk for Parkinson's disease. The A allele of rs7311174 and the T allele of rs2072374 were protective in the male patients (p = 0.016 and p = 0.019, respectively). The frequencies of the T allele of rs7311174 and the C allele of rs2072374 were significantly associated with late-onset Parkinson's disease (p = 0.048 and p = 0.044, respectively). This research demonstrates a positive relationship between the NCAPD2 gene and the risk for Parkinson's disease in a Han Chinese population and provides a potential genetic marker for sporadic Parkinson's disease. Key words: single nuclear polymorphisms, SNaPshot, non-SMC condensin I complex subunit D2, Parkinson's disease, genetic risk factor. Des etudes anterieures ont montre que la sous-unite D2 du complexe de la condensine I sans SMC (NCAPD2) est une proteine qui joue un role important dans la condensation des chromosomes et dont certains polymorphismes ont ete associes a la maladie d'Alzheimer. Aucune etude n'a encore demontre de lien entre le polymorphisme au sein de NCAPD2 et la maladie de Parkinson. Dans ce travail, les auteurs ont realise une etude cas-temoins pour explorer la relation entre le polymorphisme au sein de NCAPD2 et le risque de maladie de Parkinson chez les Chinois Han. Deux polymorphismes mononucleotidiques (SNP) dans legene NCAPD2 (rs7311174 et rs2072374) ont affiche des valeurs p significatives (p = 0,046 et p = 0,043, respectivement) au sein de 265 cas et 267 temoins. Des analyses subsequentes ont montre un effet de l'age et du sexe sur la relation entre ces deux SNP et le risque de maladie de Parkinson. L'allele A du SNP rs7311174 et l'allele T du SNP rs2072374 conferaient une protection chez les males (p = 0,016 et p = 0,019, respectivement). Les frequences des alleles T de rs7311174 et C de rs2072374 montraient une association significative avec le maladie de Parkinson tardif (p = 0,048 et p = 0,044, respectivement). Ce travail montre une relation positive entre le gene NCAPD2 et le risque de maladie de Parkinson chez les Chinois Han et fournit un possible marqueur genetique pour le maladie de Parkinson sporadique. [Traduit par la Redaction] Mots-cles : polymorphisme mononucleotidique, SNaPshot, complexe de la condensine I sans SMC sous-unite D2, maladie de Parkinson, facteur de risque genetique., Introduction Parkinson's disease (PD) is an age-related neurodegenerative disease, characterized by the loss of dopaminergic (DA) neurons in the substantial nigra and DA terminals in the striatum and the formation [...]

Abstract Background Mutations of the glucocerebrosidase (GBA) gene have reportedly been associated with Parkinson disease (PD) in various ethnic populations such as Singaporean, Japanese, Formosan, Canadian, American, Portuguese, Greek, Brazilian, British, Italian, Ashkenazi Jewish, southern and southwestern Chinese. The purpose of this study is to determine in central China whether or not the reported GBA mutations remain associated with PD. Methods In this project, we conducted a controlled study in a cohort of 208 central Chinese PD patients and 298 controls for three known GBA mutations (L444P, N370S and R120W). Results Our data reveals a significantly higher frequency of L444P mutation in GBA gene of PD cases (3.4%) compared with the controls (0.3%) (P = 0.007, OR = 10.34, 95% CI = 1.26 - 84.71). Specifically, the frequency of L444P mutation was higher in the late onset PD (LOPD) cases compared with that in control subjects. The N370S and R120W mutations were detected in neither the PD group nor the control subjects. Conclusions Our observations demonstrated that the GBA L444P mutation confers genetic risk for PD, especially LOPD, among the population in the central China area.

Parkinson's disease (PD) is a common progressive neurodegenerative disorder. Up to now, several single-nucleotide polymorphisms (SNPs) located in virulence gene sites have been reported linked to PD. Candidate gene association studies and genome-wide association studies have identified rs3129882, rs4248166 in HLA-DRA and rs34372695 in SYT11 as risk factors for familial or sporadic PD. However, the association between variants of HLA-DRA, SYT11 and PD are still controversial, especially in the Central Chinese population. We here performed a case-control study to investigate whether HLA-DRA and SYT11 genes could predispose to sporadic PD in the Chinese population. We investigate 486 PD patients and 457 age- and sex-matched controls from Central China to assess this association. In the allele model, the odds ratio (OR) result of rs3129882 was 0.905 (p = 0.287). Moreover, no significant difference was observed in the association between rs424816 (OR = 0.864, p = 0.106) and rs34372695 (p = 1.0) with PD risk. Genotypic analysis in SNP rs3129882, rs4248166 and rs34372695 indicated no significant association with PD. Subgroup analysis of our data showed age-onset and gender were not associated with either genotype or minor allele frequencies of rs3129882 and rs4248166. Moreover, the negative results were also observed in a meta-analysis of studies of rs3129882 from mainland China and Taiwanese population. Our results reveal that rs3129882, rs4248166 and rs34372695 do not confer significant risks for sporadic PD in the Central Chinese population. [ABSTRACT FROM AUTHOR]

Abstract Background Cerebral venous sinus thrombosis (CVST) is a relatively rare cerebrovascular condition which accounts for 0.5% of all strokes. Risk of CVST has been documented in patients with numerous conditions including central nervous system infections, however, Japanese encephalitis (JE, epidemic encephalitis type B) with CVST has not been reported previously. Case Presentation Here, we present a case of JE with CVST in a 17-year-old man. On admission, the patient was initially diagnosed as intracranial infection, and soon after, brain magnetic resonance (MR) imaging (MRI) and MR Venography (MRV) confirmed the diagnosis of CVST. Moreover, the blood JE-specific IgM antibody which proved weakly positive at first, turned positive one week later. Consequently, our patient was diagnosed as CVST accompanied by JE. Anticoagulant and anti-infective therapy were initiated, which eventually lead to gradual recovery of the patient. Conclusions To our knowledge, this is the first case report of CVST associated with JE. MRI and MRV represent a prime method for the diagnosis of CVST, while the positivity of JE virus IgM antibody, especially increased antibody levels within a short period, is of great significance to diagnose JE. The early diagnosis and timely treatment of this potentially lethal condition would improve its prognosis significantly.