Gene expression profiling in a mouse model of infantile neuronal ceroid lipofuscinosis reveals upregulation of immediate early genes and mediators of the inflammatory response

<p>Abstract</p> <p>Background</p> <p>The infantile form of neuronal ceroid lipofuscinosis (also known as infantile Batten disease) is caused by hereditary deficiency of a lysosomal enzyme, palmitoyl-protein thioesterase-1 (PPT1), and is characterized by severe cortical degeneration with blindness and cognitive and motor dysfunction. The PPT1-deficient knockout mouse recapitulates the key features of the disorder, including seizures and death by 7–9 months of age. In the current study, we compared gene expression profiles of whole brain from PPT1 knockout and normal mice at 3, 5 and 8 months of age to identify temporal changes in molecular pathways implicated in disease pathogenesis.</p> <p>Results</p> <p>A total of 267 genes were significantly (approximately 2-fold) up- or downregulated over the course of the disease. Immediate early genes (Arc, Cyr61, c-fos, jun-b, btg2, NR4A1) were among the first genes upregulated during the presymptomatic period whereas immune response genes dominated at later time points. Chemokine ligands and protease inhibitors were among the most transcriptionally responsive genes. Neuronal survival factors (IGF-1 and CNTF) and a negative regulator of neuronal apoptosis (DAP kinase-1) were upregulated late in the course of the disease. Few genes were downregulated; these included the α2 subunit of the GABA-A receptor, a component of cortical and hippocampal neurons, and Hes5, a transcription factor important in neuronal differentiation.</p> <p>Conclusion</p> <p>A molecular description of gene expression changes occurring in the brain throughout the course of neuronal ceroid lipofuscinosis suggests distinct phases of disease progression, provides clues to potential markers of disease activity, and points to new targets for therapy.</p

Photoperiod-responsive changes in chromatin accessibility in phloem companion and epidermis cells of Arabidopsis leaves

Photoperiod plays a key role in controlling the phase transition from vegetative to reproductive growth in flowering plants. Leaves are the major organs perceiving day-length signals, but how specific leaf cell types respond to photoperiod remains unknown. We integrated photoperiod-responsive chromatin accessibility and transcriptome data in leaf epidermis and vascular companion cells of Arabidopsis thaliana by combining isolation of nuclei tagged in specific cell/tissue types with assay for transposase-accessible chromatin using sequencing and RNA-sequencing. Despite a large overlap, vasculature and epidermis cells responded differently. Long-day predominantly induced accessible chromatin regions (ACRs); in the vasculature, more ACRs were induced and these were located at more distal gene regions, compared with the epidermis. Vascular ACRs induced by long days were highly enriched in binding sites for flowering-related transcription factors. Among the highly ranked genes (based on chromatin and expression signatures in the vasculature), we identified TREHALOSE-PHOSPHATASE/SYNTHASE 9 (TPS9) as a flowering activator, as shown by the late flowering phenotypes of T-DNA insertion mutants and transgenic lines with phloem-specific knockdown of TPS9. Our cell-type-specific analysis sheds light on how the long-day photoperiod stimulus impacts chromatin accessibility in a tissue-specific manner to regulate plant development

Phylogenetic analysis of porcine parvoviruses from swine samples in China

<p>Abstract</p> <p>Background</p> <p>Porcine parvovirus (PPV) usually causes reproductive failure in sows. The objective of the present study was to analyze the phylogenetic distribution and perform molecular characterization of PPVs isolated in China, as well as to identify two field strains, LZ and JY. The data used in this study contained the available sequences for NS1 and VP2 from GenBank, as well as the two aforementioned Chinese strains.</p> <p>Results</p> <p>Phylogenetic analysis shows that the PPV sequences are divided into four groups. The early Chinese PPV isolates are Group I viruses, and nearly all of the later Chinese PPV isolates are Group II viruses. LZ belongs to group II, whereas the JY strain is a Group III virus. This is the first report on the isolation of a Group III virus in China. The detection of selective pressures on the PPV genome shows that the NS1 and VP2 genes are under purifying selection and positive selection, respectively. Moreover, the amino acids in the VP2 capsid are highly variable because of the positive selection.</p> <p>Conclusions</p> <p>Our study provides new molecular data on PPV strains in China, and emphasizes the importance of etiological studies of PPV in pigs.</p

Ecotoxicity and sustainability of emerging Pb-based photovoltaics

Emerging Pb-based photovoltaic (PV) technologies, including in particular solution processed halide perovskite solar cells (PSCs) and Pb chalcogenide quantum dot solar cells (QDSCs), are among the most promising next-generation PV technologies for a range of disruptive energy and electronic applications. However, the potential toxicity and leakage of hazardous Pb species have become one of the main barriers to their large-scale application. When solar cells are subject to physical damage or failure of encapsulation, rapid leakage of Pb may occur, which can be accelerated by exposure to external environmental weathering conditions such as rainfall and elevated temperature. Herein, an in-depth investigation on the essential role of Pb in PSCs and QDSCs, as well as common causes of Pb leakage, is undertaken. The hazardous effects of Pb toxicity on soil plants, bacteria, animals, and human cells are also evaluated. Recent progress in developing effective strategies for Pb leakage reduction, such as Pb-free or Pb-less perovskite materials, device architecture design, encapsulation absorbers for PSCs, and core–shell structure and ligand exchange method for QDSCs, in addition to Pb recycling strategies of end-of-life solar cells are summarized. This review provides quantitative insights into the future development of eco-friendly emerging Pb-based PV technologies

Polymorphic genetic characterization of the ORF7 gene of porcine reproductive and respiratory syndrome virus (PRRSV) in China

<p>Abstract</p> <p>Background</p> <p>Porcine reproductive and respiratory syndrome virus (PRRSV) exhibits extensive genetic variation. The outbreak of a highly pathogenic PRRS in 2006 led us to investigate the extent of PRRSV genetic diversity in China. To this end, we analyzed the Nsp2 and ORF7 gene sequences of 98 Chinese PRRSV isolates.</p> <p>Results</p> <p>Preliminary analysis indicated that highly pathogenic PRRSV strains with a 30-amino acid deletion in the Nsp2 protein are the dominant viruses circulating in China. Further analysis based on ORF7 sequences revealed that all Chinese isolates were divided into 5 subgroups, and that the highly pathogenic PRRSVs were distantly related to the MLV or CH-1R vaccine, raising doubts about the efficacy of these vaccines. The ORF7 sequence data also showed no apparent associations between geographic or temporal origin and heterogeneity of PRRSV in China.</p> <p>Conclusion</p> <p>These findings enhance our knowledge of the genetic characteristics of Chinese PRRSV isolates, and may facilitate the development of effective strategies for monitoring and controlling PRRSV in China.</p

In-vitro and in-vivo phenotype of type Asia 1 foot-and-mouth disease viruses utilizing two non-RGD receptor recognition sites

<p>Abstract</p> <p>Background</p> <p>Foot-and-mouth disease virus (FMDV) uses a highly conserved Arg-Gly-Asp (RGD) triplet for attachment to host cells and this motif is believed to be essential for virus viability. Previous sequence analyses of the 1D-encoding region of an FMDV field isolate (Asia1/JS/CHA/05) and its two derivatives indicated that two viruses, which contained an Arg-Asp-Asp (RDD) or an Arg-Ser-Asp (RSD) triplet instead of the RGD integrin recognition motif, were generated serendipitously upon short-term evolution of field isolate in different biological environments. To examine the influence of single amino acid substitutions in the receptor binding site of the RDD-containing FMD viral genome on virus viability and the ability of non-RGD FMDVs to cause disease in susceptible animals, we constructed an RDD-containing FMDV full-length cDNA clone and derived mutant molecules with RGD or RSD receptor recognition motifs. Following transfection of BSR cells with the full-length genome plasmids, the genetically engineered viruses were examined for their infectious potential in cell culture and susceptible animals.</p> <p>Results</p> <p>Amino acid sequence analysis of the 1D-coding region of different derivatives derived from the Asia1/JS/CHA/05 field isolate revealed that the RDD mutants became dominant or achieved population equilibrium with coexistence of the RGD and RSD subpopulations at an early phase of type Asia1 FMDV quasispecies evolution. Furthermore, the RDD and RSD sequences remained genetically stable for at least 20 passages. Using reverse genetics, the RDD-, RSD-, and RGD-containing FMD viruses were rescued from full-length cDNA clones, and single amino acid substitution in RDD-containing FMD viral genome did not affect virus viability. The genetically engineered viruses replicated stably in BHK-21 cells and had similar growth properties to the parental virus. The RDD parental virus and two non-RGD recombinant viruses were virulent to pigs and bovines that developed typical clinical disease and viremia.</p> <p>Conclusions</p> <p>FMDV quasispecies evolving in a different biological environment gained the capability of selecting different receptor recognition site. The RDD-containing FMD viral genome can accommodate substitutions in the receptor binding site without additional changes in the capsid. The viruses expressing non-RGD receptor binding sites can replicate stably in vitro and produce typical FMD clinical disease in susceptible animals.</p

Targeted metabolomic profiles of serum amino acids and acylcarnitines related to gastric cancer

Background Early diagnosis and treatment are imperative for improving survival in gastric cancer (GC). This work aimed to assess the ability of human serum amino acid and acylcarnitine profiles in distinguishing GC cases from atrophic gastritis (AG) and control superficial gastritis (SG) patients. Methods Sixty-nine GC, seventy-four AG and seventy-two SG control patients treated from May 2018 to May 2019 in Gansu Provincial Hospitalwere included. The levels of 42 serum metabolites in the GC, AG and SG groups were detected by liquid chromatography-tandem mass spectrometry (LC–MS/MS). Then, orthogonal partial least squares discriminant analysis (OPLS-DA) and the Kruskal-Wallis H test were used to identify a metabolomic signature among the three groups. Metabolites with highest significance were examined for further validation. Receiver operating characteristic (ROC) curve analysis was carried out for evaluating diagnostic utility. Results The metabolomic analysis found adipylcarnitine (C6DC), 3-hydroxy-hexadecanoylcarnitine (C16OH), hexanoylcarnitine (C6), free carnitine (C0) and arginine (ARG) were differentially expressed (all VIP >1) and could distinguish GC patients from AG and SG cases. In comparison with the AG and SG groups, GC cases had significantly higher C6DC, C16OH, C6, C0 and ARG amounts. Jointly quantitating these five metabolites had specificity and sensitivity in GC diagnosis of 98.55% and 99.32%, respectively, with an area under the ROC curve (AUC) of 0.9977. Conclusion This study indicates C6DC, C16OH, C6, C0 and ARG could effectively differentiate GC cases from AG and SG patients, and may jointly serve as a valuable circulating multi-marker panel for GC detection

Effect of Sciadonic Acid on Hepatic Lipid Metabolism in Obese Mice Induced by A High-fat Diet

Objective: To investigate the potential beneficial effects of sciadonic acid (SA) on improving obesity induced by a high-fat diet in mice. Methods: Forty-eight male C57BL/6 mice were adaptively fed for one week and then randomly divided into the following groups: Control group (C), positive control group (S), model group (M), low-dose sciadonic acid group (LSA), medium-dose sciadonic acid group (MSA), and high-dose sciadonic acid group (HSA). The modeling process lasted for 16 weeks, and the low and high-dose groups were orally administered different doses of SA solution at a fixed time each day. After the modeling period, potential mechanisms of SA in regulating lipid metabolism in obese mice were explored, including aspects such as blood lipid metabolism, hepatic fat metabolism, hepatic oxidative stress, hepatic lipid synthesis, and expression of metabolism-related genes. Results: The high-dose SA intervention in obese mice significantly decreased the levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) in serum, while increasing high-density lipoprotein cholesterol (HDL-C) (P<0.05). It inhibited weight gain, reduced epididymal fat accumulation, and improved liver tissue damage. Additionally, SA significantly increased the activities of antioxidant enzymes such as superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) in mice (P<0.05), and significantly reduced the production of oxidative end products MDA (P<0.05), alleviated oxidative stress in vivo, and inhibited lipid synthesis by regulating the expression of genes related to lipid metabolism to improve lipid metabolism. Conclusion: SA could improve lipid metabolism disorders in obese mice by suppressing fat accumulation, alleviate oxidative stress, regulate lipid synthesis and metabolism