Recent Advances on the Machine Learning Methods in Identifying DNA Replication Origins in Eukaryotic Genomics

The initiate site of DNA replication is called origins of replication (ORI) which is regulated by a set of regulatory proteins and plays important roles in the basic biochemical process during cell growth and division in all living organisms. Therefore, the study of ORIs is essential for understanding the cell-division cycle and gene expression regulation so that scholars can develop a new strategy against genetic diseases by using the knowledge of DNA replication. Thus, the accurate identification of ORIs will provide key clues for DNA replication research and clinical medicine. Although, the conventional experiments could provide accurate results, they are time-consuming and cost ineffective. On the contrary, bioinformatics-based methods can overcome these shortcomings. Especially, with the emergence of DNA sequences in the post-genomic era, it is highly expected to develop high throughput tools to identify ORIs based on sequence information. In this review, we will summarize the current progress in computational prediction of eukaryotic ORIs including the collection of benchmark dataset, the application of machine learning-based techniques, the results obtained by these methods, and the construction of web servers. Finally, we gave the future perspectives on ORIs prediction. The review provided readers with a whole background of ORIs prediction based on machine learning methods, which will be helpful for researchers to study DNA replication in-depth and drug therapy of genetic defect

Ammonium 2-(2,4-dichloro­phen­oxy)acetate hemihydrate

The title compound, NH4 +·C8H7Cl2O6 −·0.5H2O, was prepared by the reaction of 2-(2,4-dichloro­phen­oxy)­acetic acid and ammonia in water at 367 K. The mol­ecular structure and packing are stabilized by N—H⋯O and O—H⋯O inter­molecular hydrogen-bond inter­actions

The genetic variants at the HLA-DRB1 gene are associated with primary IgA nephropathy in Han Chinese

BACKGROUND: Immunoglobulin A nephropathy (IgAN), an immune-complex-mediated glomerulonephritis defined immunohistologically by the presence of glomerular IgA deposits, is the most common primary glomerular disease worldwide and a significant cause of end-stage renal disease. Familial clustering of patients with IgAN suggests a genetic predisposition. METHODS: In this study, 192 patients with IgAN and 192 normal controls in the Sichuan cohort and 935 patients with IgAN and 2,103 normal controls in the Beijing cohort were investigated. HLA-DRB1*01–DRB1*10 specificities were genotyped by the PCR–SSP technique in both cohorts. Based on the HLA-DRB1*04-positive results, the subtypes of HLA-DRB1*04 were analyzed using sequencing-based typing (SBT) in 291 IgAN cases and 420 matched controls. RESULTS: The frequency of HLA-DRB1*04 in the IgAN group was significantly higher than that in the control group (0.129 vs. 0.092, P = 8.29 × 10(-5), odds ratio (OR) =1.381, 95% confidence interval (CI) 1.178–1.619). Other alleles at the HLA-DRB1 locus were observed with no significant differences between the case and control groups. The dominant alleles of the HLA-DRB1*04 subtypes were DRB1*0405 in both cohorts. The frequencies of HLA-DRB1*0405 and 0403 were significantly increased in the patients compared to healthy subjects. CONCLUSION: HLA-DRB1*04 was significantly associated with primary IgAN in Chinese population. This result implies that HLA-DRB1 gene plays a major role in primary IgAN

Complete sequence and organization of Antheraea pernyi nucleopolyhedrovirus, a dr-rich baculovirus

<p>Abstract</p> <p>Background</p> <p>The completion and reporting of baculovirus genomes is extremely important as it advances our understanding of gene function and evolution. Due to the large number of viral genomes now sequenced it is very important that authors present significantly detailed analyses to advance the understanding of the viral genomes. However, there is no report of the <it>Antheraea pernyi </it>nucleopolyhedrovirus (AnpeNPV) genome.</p> <p>Results</p> <p>The genome of AnpeNPV, which infects Chinese tussah silkworm (<it>Antheraea pernyi</it>), was sequenced and analyzed. The genome was 126,629 bp in size. The G+C content of the genome, 53.4%, was higher than that of most of the sequenced baculoviruses. 147 open reading frames (ORFs) that putatively encode proteins of 50 or more amino acid residues with minimal overlap were determined. Of the 147 ORFs, 143 appeared to be homologous to other baculovirus genes, and 4 were unique to AnpeNPV. Furthermore, there are still 29 and 33 conserved genes present in all baculoviruses and all lepidopteran baculoviruses respectively. In addition, the total number of genes common to all lepidopteran NPVs is sill 74, however the 74 genes are somewhat different from the 74 genes identified before because of some new sequenced NPVs. Only 6 genes were found exclusively in all lepidopteran NPVs and 12 genes were found exclusively in all Group I NPVs. AnpeNPV encodes <it>v-trex</it>(Anpe115, a 3' to 5' repair exonuclease), which was observed only in CfMNPV and CfDEFNPV in Group I NPVs. This gene potentially originated by horizontal gene transfer from an ancestral host. In addition, AnpeNPV encodes two <it>conotoxin</it>-like gene homologues (<it>ctls</it>), <it>ctl1 </it>and <it>ctl2</it>, which were observed only in HycuNPV, OpMNPV and LdMNPV. Unlike other baculoviruses, only 3 typical homologous regions (<it>hr</it>s) were identified containing 2~9 repeats of a 30 bp-long palindromic core. However, 24 perfect or imperfect direct repeats (<it>dr</it>s) with a high degree of AT content were found within the intergenic spacer regions that may function as non-<it>hr</it>, <it>ori</it>-like regions found in GrleGV, CpGV and AdorGV. 9 <it>dr</it>s were also found in intragenic spacer regions of AnpeNPV.</p> <p>Conclusion</p> <p>AnpeNPV belongs to Group I NPVs and is most similar to HycuNPV, EppoNPV, OpMNPV and CfMNPV based on gene content, genome arrangement, and amino acid identity. In addition, analysis of genes that flank <it>hr</it>s supported the argument that these regions are involved in the transfer of sequences between the virus and host.</p

Protectin conjugates in tissue regeneration 1 alleviates sepsis-induced acute lung injury by inhibiting ferroptosis

Background: Acute lung injury (ALI) is a common and serious complication of sepsis with high mortality. Ferroptosis, categorized as programmed cell death, contributes to the development of lung injury. Protectin conjugates in tissue regeneration 1 (PCTR1) is an endogenous lipid mediator that exerts protective effects against multiorgan injury. However, the role of PCTR1 in the ferroptosis of sepsis-related ALI remains unknown. Methods: A pulmonary epithelial cell line and a mouse model of ALI stimulated with lipopolysaccharide (LPS) were established in vitro and in vivo. Ferroptosis biomarkers, including ferrous (Fe2+), glutathione (GSH), malondialdehyde (MDA) and 4-Hydroxynonenal (4-HNE), were assessed by relevant assay kits. Glutathione peroxidase 4 (GPX4) and prostaglandin-endoperoxide synthase 2 (PTGS2) protein levels were determined by western blotting. Lipid peroxides were examined by fluorescence microscopy and flow cytometry. Cell viability was determined by a CCK-8 assay kit. The ultrastructure of mitochondria was observed with transmission electron microscopy. Morphology and inflammatory cytokine levels predicted the severity of lung injury. Afterward, related inhibitors were used to explore the potential mechanism by which PCTR1 regulates ferroptosis. Results: PCTR1 treatment protected mice from LPS-induced lung injury, which was consistent with the effect of the ferroptosis inhibitor ferrostatin-1. PCTR1 treatment decreased Fe2+, PTGS2 and lipid reactive oxygen species (ROS) contents, increased GSH and GPX4 levels and ameliorated mitochondrial ultrastructural injury. Administration of LPS or the ferroptosis agonist RSL3 resulted in reduced cell viability, which was rescued by PCTR1. Mechanistically, inhibition of the PCTR1 receptor lipoxin A4 (ALX), protein kinase A (PKA) and transcription factor cAMP-response element binding protein (CREB) partly decreased PCTR1 upregulated GPX4 expression and a CREB inhibitor blocked the effects ofPCTR1 on ferroptosis inhibition and lung protection. Conclusion: This study suggests that PCTR1 suppresses LPS-induced ferroptosis via the ALX/PKA/CREB signaling pathway, which may offer promising therapeutic prospects in sepsis-related ALI

Potential Nexus of Non-alcoholic Fatty Liver Disease and Type 2 Diabetes Mellitus: Insulin Resistance Between Hepatic and Peripheral Tissues

The liver is the central metabolic organ and plays a pivotal role in regulating homeostasis of glucose and lipid metabolism. Aberrant liver metabolism promotes insulin resistance, which is reported to be a common characteristic of metabolic diseases such as non-alcoholic fatty liver disease (NAFLD) and type 2 diabetes mellitus (T2DM). There is a complex and bidirectional relationship between NAFLD and T2DM. NAFLD patients with hepatic insulin resistance generally share a high risk of impaired fasting glucose associated with early diabetes; most patients with T2DM experience non-alcoholic fatty liver (NAFL), non-alcoholic steatohepatitis (NASH), and other more severe liver complications such as cirrhosis and hepatocellular carcinoma (HCC). Additionally, hepatic insulin resistance, which is caused by diacylglycerol-mediated activation of protein kinase C epsilon (PKC), may be the critical pathological link between NAFLD and T2DM. Therefore, this review aims to illuminate current insights regarding the complex and strong association between NAFLD and T2DM and summarize novel and emerging targets for the treatment of hepatic insulin resistance based on established mechanistic knowledge

A multi-objective genetic algorithm for optimisation of energy consumption and shop floor production performance

Increasing energy price and requirements to reduce emission are new chal-lenges faced by manufacturing enterprises. A considerable amount of energy is wasted by machines due to their underutilisation. Consequently, energy saving can be achieved by turning off the machines when they lay idle for a comparatively long period. Otherwise, turning the machine off and back on will consume more energy than leave it stay idle. Thus, an effective way to reduce energy consumption at the system level is by employing intelligent scheduling techniques which are capable of integrating fragmented short idle periods on the machines into large ones. Such scheduling will create opportunities for switching off underutilised resources while at the same time maintaining the production performance. This paper introduces a model for the bi-objective optimisation problem that minimises the total non-processing electricity consumption and total weighted tardiness in a job shop. The Turn off/Turn on is applied as one of the electricity saving approaches. A novel multi-objective genetic algorithm based on NSGA-II is developed. Two new steps are introduced for the purpose of expanding the solution pool and then selecting the elite solutions. The research presented in this paper is focused on the classical job shop envi-ronment, which is widely used in the manufacturing industry and provides considerable opportunities for energy saving. The algorithm is validated on job shop problem instances to show its effectiveness. Keywords: Energy efficient production plannin