We previously determined that the predicted risk of radiogenic second cancer in the bladder and rectum after proton arc therapy (PAT) was less than or equal to that after volumetric modulated arc therapy (VMAT) with photons, but we did not consider the impact of margin size on that risk. The current study was thus conducted to evaluate margin size’s effect on the predicted risks of second cancer for the two modalities and the relative risk between them. Seven treatment plans with margins ranging from 0 mm in all directions to 6 mm posteriorly and 8 mm in all other directions were considered for both modalities. We performed risk analyses using three risk models with varying amounts of cell sterilization and calculated ratios of risk for the corresponding PAT and VMAT plans. We found that the change in risk with margin size depended on the risk model but that the relative risk remained nearly constant with margin size, regardless of the amount of cell sterilization modeled. We conclude that while margin size influences the predicted risk of a second cancer for a given modality, it appears to affect both modalities in roughly equal proportions so that the relative risk between PAT and VMAT is approximately equivalent.
second cancer; second malignant neoplasm; volumetric modulated arc therapy; VMAT; proton arc therapy; proton therapy; prostate cancer; margin size
Serum response factor (SRF) is a transcription factor that transactivates actin associated genes, and has been implicated in oligodendrocyte (OL) differentiation. To date, it has not been investigated in cerebral ischemia. We investigated the dynamics of SRF expression after stroke in vivo and the role of SRF in oligodendrocyte differentiation in vitro. Using immunohistochemistry, we found that SRF was upregulated in OLs and OL precursor cells (OPCs) after stroke. Moreover, upregulation of SRF was concurrent with downregulation of the microRNAs (miRNAs) miR-9 and the miR-200 family in the ischemic white matter region, the corpus callosum. Inhibition of SRF activation by CCG-1423, a specific inhibitor of SRF function, blocked OPCs from differentiating into OLs. Over-expression of miR-9 and miR-200 in cultured OPCs suppressed SRF expression and inhibited OPC differentiation. Moreover, co-expression of miR-9 and miR-200 attenuated activity of a luciferase reporter assay containing the Srf 3′ untranslated region (UTR). Collectively, this study is the first to show that stroke upregulates SRF expression in OPCs and OLs, and that SRF levels are mediated by miRNAs and regulate OPC differentiation.
Satellite cells function as skeletal muscle stem cells to support postnatal muscle growth and regeneration following injury or disease. There is great promise for the improvement of muscle performance in livestock and for the therapy of muscle pathologies in humans by the targeting of myostatin (MSTN) in this cell population. Human diet contains many histone deacetylase (HDAC) inhibitors, such as the bioactive component sulforaphane (SFN), whose epigenetic effects on MSTN gene in satellite cells are unknown. Therefore, we aimed to investigate the epigenetic influences of SFN on the MSTN gene in satellite cells. The present work provides the first evidence, which is distinct from the effects of trichostatin A (TSA), that SFN supplementation in vitro not only acts as a HDAC inhibitor but also as a DNA methyltransferase (DNMT) inhibitor in porcine satellite cells. Compared with TSA and 5-aza-2′-deoxycytidine (5-aza-dC), SFN treatment significantly represses MSTN expression, accompanied by strongly attenuated expression of negative feedback inhibitors of the MSTN signaling pathway. miRNAs targeting MSTN are not implicated in posttranscriptional regulation of MSTN. Nevertheless, a weakly enriched myoblast determination (MyoD) protein associated with diminished histone acetylation in the MyoD binding site located in the MSTN promoter region may contribute to the transcriptional repression of MSTN by SFN. These findings reveal a new mode of epigenetic repression of MSTN by the bioactive compound SFN. This novel pharmacological, biological activity of SFN in satellite cells may thus allow for the development of novel approaches to weaken the MSTN signaling pathway, both for therapies of human skeletal muscle disorders and for livestock production improvement.
Sulforaphane; satellite cell; myostatin; epigenetic repression; pig
Peripheral neuropathy is one of the most common complications of diabetes mellitus. Using a mouse model of diabetic peripheral neuropathy, we tested the hypothesis that thymosin β 4 (Tβ4) ameliorates diabetes–induced neurovascular dysfunction in the sciatic nerve and promotes recovery of neurological function from diabetic peripheral neuropathy. Tβ4 treatment of diabetic mice increased functional vascular density and regional blood flow in the sciatic nerve, and improved nerve function. Tβ4 upregulated angiopoietin-1 (Ang1) expression, but suppressed Ang2 expression in endothelial and Schwann cells in the diabetic sciatic nerve. In vitro, incubation of Human Umbilical Vein Endothelial Cells (HUVECs) with Tβ4 under high glucose condition completely abolished high glucose-downregulated Ang1 expression and high glucose-reduced capillary-like tube formation. Moreover, incubation of HUVECs under high glucose with conditioned medium collected from Human Schwann cells (HSCs) treated with Tβ4 significantly reversed high glucose-decreased capillary-like tube formation. PI3K/Akt signaling pathway is involved in Tβ4-regulated Ang1 expression on endothelial and Schwann cells. These data indicate that Tβ4 likely acts on endothelial cells and Schwann cells to preserve and/or restore vascular function in the sciatic nerve which facilitates improvement of peripheral nerve function under diabetic neuropathy. Thus, Tβ4 has potential for the treatment of diabetic peripheral neuropathy.
Tβ4; peripheral neuropathy; diabetes; mice
The origin of sinoatrial node (SAN) pacemaker activity in the heart is controversial. The leading candidates are diastolic depolarization by “funny” current (If) through HCN4 channels (the “Membrane Clock“ hypothesis), depolarization by cardiac Na-Ca exchange (NCX1) in response to intracellular Ca cycling (the "Calcium Clock" hypothesis), and a combination of the two (“Coupled Clock”). To address this controversy, we used Cre/loxP technology to generate atrial-specific NCX1 KO mice. NCX1 protein was undetectable in KO atrial tissue, including the SAN. Surface ECG and intracardiac electrograms showed no atrial depolarization and a slow junctional escape rhythm in KO that responded appropriately to β-adrenergic and muscarinic stimulation. Although KO atria were quiescent they could be stimulated by external pacing suggesting that electrical coupling between cells remained intact. Despite normal electrophysiological properties of If in isolated patch clamped KO SAN cells, pacemaker activity was absent. Recurring Ca sparks were present in all KO SAN cells, suggesting that Ca cycling persists but is uncoupled from the sarcolemma. We conclude that NCX1 is required for normal pacemaker activity in murine SAN.
Common spatial pattern (CSP) is one of the most popular and effective feature extraction methods for motor imagery-based brain-computer interface (BCI), but the inherent drawback of CSP is that the estimation of the covariance matrices is sensitive to noise. In this work, local temporal correlation (LTC) information was introduced to further improve the covariance matrices estimation (LTCCSP). Compared to the Euclidean distance used in a previous CSP variant named local temporal CSP (LTCSP), the correlation may be a more reasonable metric to measure the similarity of activated spatial patterns existing in motor imagery period. Numerical comparisons among CSP, LTCSP, and LTCCSP were quantitatively conducted on the simulated datasets by adding outliers to Dataset IVa of BCI Competition III and Dataset IIa of BCI Competition IV, respectively. Results showed that LTCCSP achieves the highest average classification accuracies in all the outliers occurrence frequencies. The application of the three methods to the EEG dataset recorded in our laboratory also demonstrated that LTCCSP achieves the highest average accuracy. The above results consistently indicate that LTCCSP would be a promising method for practical motor imagery BCI application.
The miR-513 subfamily belongs to an X-linked primate-specific miR506-514 cluster. Across primate species, there have been several duplication events and different species each possess a variety of miR-513 copies, indicating it underwent rapid evolution. Evidence suggests that this subfamily is preferentially expressed in the testis, but otherwise, to date, the evolutionary history and functional significance of this miRNA subfamily has remained largely unexplored.
We analyzed the evolutionary pattern of gene duplications and their functional consequence for the miR-513 subfamily in primates. Sequence comparisons showed that the duplicated copies of miR-513 were derived from transposable element (MER91C). Moreover, duplication events of the miR-513 subfamily seem to have occurred independently in Platyrrhini (New World monkeys) and Catarrhini (Old World monkeys, apes and humans) after they diverged. Different copies of the miR-513 subfamily (miR-513a/b/c) have different seed sequences, due to after-duplication sequence divergences, which eventually led to functional divergences. The results of functional assays indicated that miR-513b could inhibit the expression of its target gene, the down-regulator of transcription 1 (DR1) at both the mRNA and protein levels. In the developing testis of rhesus macaques, we observed a temporal coupling of expression levels between miR-513b and DR1, suggesting that miR-513b could affect male sexual maturation by negatively regulating the development-stage related functioning of DR1.
The miR-513 subfamily underwent multiple independent gene duplications among five different lineages of primates. The after-duplication sequence divergences among the different copies of miR-513 led to functional divergence of these copies in primates.
miR-513; Primate-specific; Rapid evolution; Testis; DR1
Diabetic patients on peritoneal dialysis (PD) have lower survival and are more likely complicated with inflammation than their non-diabetic counterparts. Here, we explored the interaction effects between diabetes and inflammation on the survival of PD patients.
Overall, 2,264 incident patients were enrolled from a retrospective cohort study in China. Patients were grouped according to the baseline levels of high-sensitive C-reactive protein (hsCRP, ≤3 mg/L or >3 mg/L) or serum albumin (SA, ≥38 g/L or <38 g/L). Then, several multivariable adjusted stratified Cox regression models were constructed for these groups to explore the predicted role of diabetes on all-cause or cardiovascular death under inflammatory or non-inflammatory conditions.
Diabetics on PD were more likely to have inflammation than non-diabetics on PD, and they presented with elevated hsCRP (52.7% vs. 47.3%, P = 0.03) or decreased SA (77.9% vs. 62.7%, P < 0.001) levels. After stratification by size of center and controlling for confounding factors, diabetes was found to predict all-cause death in patients with hsCRP >3 mg/L or SA <38 g/L but not in patients with hsCRP ≤3 mg/L or SA ≥38 g/L. Similarly, the presence of diabetes was an indication of cardiovascular death in patients with hsCRP >3 mg/L or SA <38 g/L. However, if further adjusted by baseline cardiovascular disease, the predicted role of diabetes on death related to cardiovascular disease in patients with SA <38 g/L disappeared.
Diabetic patients could do as well as non-diabetic patients without inflammation on peritoneal dialysis. Active strategies should be implemented to improve inflammation status in diabetic patients on PD.
Nonrigid image registration is a prerequisite for various medical image process and analysis applications. Much effort has been devoted to thoracic image registration due to breathing motion. Recently, scale-invariant feature transform (SIFT) has been used in medical image registration and obtained promising results. However, SIFT is apt to detect blob features. Blobs key points are generally detected in smooth areas which may contain few diagnostic points. In general, diagnostic points used in medical image are often vessel crossing points, vascular endpoints, and tissue boundary points, which provide abundant information about vessels and can reflect the motion of lungs accurately. These points generally have high gradients as opposed to blob key points and can be detected by Harris. In this work, we proposed a hybrid feature detection method which can detect tissue features of lungs effectively based on Harris and SIFT. In addition, a novel method which can remove mismatched landmarks is also proposed. A series of thoracic CT images are tested by using the proposed algorithm, and the quantitative and qualitative evaluations show that our method is statistically significantly better than conventional SIFT method especially in the case of large deformation of lungs during respiration.
Podoviruses that infect marine picocyanobacteria are abundant and could play a significant role on regulating host populations due to their specific phage-host relationship. Genome sequencing of cyanophages has unveiled that many marine cyanophages encode certain photosynthetic genes like psbA. It appears that psbA is only present in certain groups of cyanopodovirus isolates. In order to better understand the prevalence of psbA in cyanobacterial podoviruses, we searched the marine metagenomic database (GOS, BATS, HOT and MarineVirome). Our study suggests that 89% of recruited cyanopodovirus scaffolds from the GOS database contained the psbA gene, supporting the ecological relevance of the photosynthesis gene for surface oceanic cyanophages. Diversification between Clade A and B are consistent with recent finding of two major groups of cyanopodoviruses. All the data also shows that Clade B cyanopodoviruses dominate the surface ocean water, while Clade A cyanopodoviruses become more important in the coastal and estuarine environments.
Artemether is one of the artemisinin derivatives that are active ingredients in antimalarial drugs. Counterfeit and substandard antimalarial drugs have become a serious problem, which demands reliable analytical tools and implementation of strict regulation of drug quality. Structural similarity among artemisinin analogs is a challenge to develop immunoassays that are specific to artemisinin derivatives. To produce specific antibodies to artemether, we used microbial fermentation of artemether to obtain 9-hydroxyartemether, which was subsequently used to prepare a 9-O-succinylartemether hapten for conjugation with ovalbumin as the immunogen. A monoclonal antibody (mAb), designated as 2G12E1, was produced with high specificity to artemether. 2G12E1 showed low cross reactivities to dihydroartemisinin, artemisinin, artesunate and other major antimalarial drugs. An indirect competitive enzyme linked immunosorbent assay (icELISA) developed showed a concentration causing 50% of inhibition for artemether as 3.7 ng mL−1 and a working range of 0.7–19 ng mL−1. The icELISA was applied for determination of artemether content in different commercial drugs and the results were comparable to those determined by high-performance liquid chromatography analysis. In comparison with reported broad cross activity of anti-artemisinin mAbs, the most notable advantage of the 2G12E1-based ELISA is its high specificity to artemether only.
Glutathione S-transferases (GSTs) are a family of multifunctional enzymes that are involved in the metabolism of many xenobiotics, including a wide range of environmental carcinogens. While the null genotypes in GSTM1 and GSTT1 have been implicated in tumorigenesis, it remains inconsistent and inconclusive. Herein, we aimed to assess the possible associations of the GSTM1 and GSTT1 null genotype in cancer risks.
A meta-analysis based on 506 case-control studies was performed. Odds ratios (OR) with corresponding 95% confidence intervals (CIs) were used to assess the association.
The null genotypes of GSTM1 and GSTT1 polymorphisms were associated with a significantly increased risk in cancer (for GSTM1: OR = 1.17; 95%CI = 1.14–1.21; for GSTT1: OR = 1.16; 95%CI = 1.11–1.21, respectively). When the analysis was performed based on their smoking history, the risk associated of GSTM1 null and GSTT1 null genotypes with cancer is further increased (for GSTM1: OR = 2.66; 95%CI = 2.19–3.24; for GSTT1: OR = 2.46; 95%CI = 1.83–3.32, respectively).
These findings indicate that GSTM1 and GSTT1 polymorphisms may play critical roles in the development of cancer, especially in smokers.
Prostate cancer patients who undergo radiotherapy are at an increased risk to develop a radiogenic second cancer. Proton therapy has been shown to reduce the predicted risk of second cancer when compared to intensity modulated radiotherapy. However, it is unknown if this is also true for the rotational therapies proton arc therapy and volumetric modulated arc therapy (VMAT). The objective of this study was to compare the predicted risk of cancer following proton arc therapy and VMAT for prostate cancer. Proton arc therapy and VMAT plans were created for 3 patients. Various risk models were combined with the dosimetric data (therapeutic and stray dose) to predict the excess relative risk (ERR) of cancer in the bladder and rectum. Ratios of ERR values (RRR) from proton arc therapy and VMAT were calculated. RRR values ranged from 0.74 to 0.99, and all RRR values were shown to be statistically less than 1, except for the value calculated with the linear-non-threshold risk model. We conclude that the predicted risk of cancer in the bladder or rectum following proton arc therapy for prostate cancer is either less than or approximately equal to the risk following VMAT, depending on which risk model is applied.
second cancer; second malignant neoplasm; volumetric modulated arc therapy; VMAT; proton arc therapy; proton therapy; prostate cancer
Lung cancer, especially non-small cell lung cancer, is a leading cause of malignant tumor death worldwide. Understanding the mechanisms employed by the main regulators, such as microRNAs (miRNAs) and transcription factors (TFs), still remains elusive. The patterns of their cooperation and biological functions in the synergistic regulatory network have rarely been studied.
Here, we describe the first miRNA-TF synergistic regulation network in human lung cancer. We identified important regulators (MYC, NFKB1, miR-590, and miR-570) and significant miRNA-TF synergistic regulatory motifs by random simulations. The two most significant motifs were the co-regulation of miRNAs and TFs, and TF-mediated cascade regulation. We also developed an algorithm to uncover the biological functions of the human lung cancer miRNA-TF synergistic regulatory network (regulation of apoptosis, cellular protein metabolic process, and cell cycle), and the specific functions of each miRNA-TF synergistic subnetwork. We found that the miR-17 family exerted important effects in the regulation of non-small cell lung cancer, such as in proliferation and cell cycle regulation by targeting the retinoblastoma protein (RB1) and forming a feed forward loop with the E2F1 TF. We proposed a model for the miR-17 family, E2F1, and RB1 to demonstrate their potential roles in the occurrence and development of non-small cell lung cancer.
This work will provide a framework for constructing miRNA-TF synergistic regulatory networks, function analysis in diseases, and identification of the main regulators and regulatory motifs, which will be useful for understanding the putative regulatory motifs involving miRNAs and TFs, and for predicting new targets for cancer studies.
Regulatory network; MicroRNA; Transcription factor; Motif; Cell cycle; miR-17 family; Non-small cell lung cancer
Background and Aims
Disturbances occur in most ecological systems, and play an important role in biological invasions. We delimit five key disturbance aspects: intensity, frequency, timing, duration and extent. Few studies address more than one of these aspects, yet interactions and interdependence between aspects may lead to complex outcomes.
In a two-cohort experimental study, we examined how multiple aspects (intensity, frequency and timing) of a mowing disturbance regime affect the survival, phenology, growth and reproduction of an invasive thistle Carduus nutans (musk thistle).
Our results show that high intensity and late timing strongly delay flowering phenology and reduce plant survival, capitulum production and plant height. A significant interaction between intensity and timing further magnifies the main effects. Unexpectedly, high frequency alone did not effectively reduce reproduction. However, a study examining only frequency and intensity, and not timing, would have erroneously attributed the importance of timing to frequency.
We used management of an invasive species as an example to demonstrate the importance of a multiple-aspect disturbance framework. Failure to consider possible interactions, and the inherent interdependence of certain aspects, could result in misinterpretation and inappropriate management efforts. This framework can be broadly applied to improve our understanding of disturbance effects on individual responses, population dynamics and community composition.
Carduus nutans; thistle; disturbance timing; frequency; intensity; invasive species; mowing; population biology
Novel large, rod-shaped magnetotactic bacteria (MTB) were discovered in intertidal sediments of the Yellow Sea, China. They biomineralized more than 300 rectangular magnetite magnetosomes per cell. Phylogenetic analysis based on the 16S rRNA gene sequence revealed that they are affiliated with the Alphaproteobacteria and may represent a new genus of MTB.
Folypolyglutamate synthase (FPGS) catalyzes the polyglutamation of folates and antifolates, such as methotrexate (MTX), to produce highly active metabolites. FPGS tag SNP rs1544105C > T is located in the gene promoter. The aim of the present study was to investigate the impact of rs1544105 polymorphism on the treatment outcome in pediatric B-cell precursor acute lymphoblastic leukemia (BCP-ALL).
This study enrolled 164 children with BCP-ALL. We genotyped the FPGS SNP rs1544105, and analyzed the associations between its genotypes and treatment outcome. We also examined FPGS mRNA levels by real-time PCR in 64 of the 164 children, and investigated the function of this polymorphism on gene expression.
We found significantly poor relapse-free survival (RFS) (p = 0.010) and poor event-free survival (EFS) (p = 0.046) in carriers of CC genotype. Multivariable Cox regression analyses adjusted for possible confounding variables showed that, relative to the CT + TT genotypes, the CC genotype was an independent prognostic factor for poor RFS (hazard ratio [HR], 4.992.; 95% CI, 1.550-16.078; p = 0.007). No association was found between any toxicity and rs1544105 polymorphism. Quantitative PCR results showed that individuals with the T allele had lower levels of FPGS transcripts.
Our study indicates that FPGS rs1544105C > T polymorphism might influence FPGS expression and affect treatment outcome in BCP-ALL patients.
Folypolyglutamate synthase (FPGS); Methotrexate (MTX); Polymorphism; Treatment outcome; Acute lymphoblastic leukemia (ALL)
Carbon-based TiO2 composites have many advantages as photocatalysts. However, they suffer from low light efficiency due to the low contrast of TiO2 with carbon. We synthesized a novel type of anatase-type TiO2-C hybrid aerogel by a one-pot sol-gel method, which shows a photocatalytic activity for methylene degradation up to 4.23 times that of P25, a commercial photocatalyst from Degussa Inc. The hybrid aerogels are prepared from TiCl4 and resorcinol–furfural, and have a tunable macropore size from 167 to 996 nm. They are formed of submicrometer particles that consist of interwoven anatase and carbon nanoparticles. The anatase nanoparticles have a size of 8–9 nm and a tunable oxygen vacancy from 7.2 to 18.0%. The extremely high activity is ascribed to the large light absorption caused by macropore scattering and oxygen vacancies in the anatase. These findings may open up a new avenue and stimulate further research to improve photocatalytic performance.
Cells respond to perturbations in the microenvironment of the endoplasmic reticulum (ER), and to the overloading of its capacity to process secretory and membrane-associate proteins, by activating the Unfolded Protein Response (UPR). Genes that mediate the UPR are regulated by three basic leucine-zipper (bLZip) motif-containing transcription factors – Xbp1s, ATF4 and ATF6. A failure of the UPR to achieve homeostasis and its continued stimulation leads to apoptosis. Mechanisms must therefore exist to turn off the UPR if it successfully restores normalcy. The bLZip protein Zhangfei/CREBZF/SMILE is known to suppress the ability of several, seemingly structurally unrelated, transcription factors. These targets include Luman/CREB3 and CREBH, ER-resident bLZip proteins known to activate the UPR in some cell types. Here we show that Zhangfei had a suppressive effect on most UPR genes activated by the calcium ionophore thapsigargin. This effect was at least partially due to the interaction of Zhangfei with Xbp1s. The leucine zipper of Zhangfei was required for this interaction, which led to the subsequent proteasomal degradation of Xbp1s. Zhangfei suppressed the ability of Xbp1s to activate transcription from a promoter containing unfolded protein response elements and significantly reduced the ability to Xbp1s to activate the UPR as measured by RNA and protein levels of UPR-related genes. Finally, specific suppression of endogenous Zhangfei in thapsigargin-treated primary rat sensory neurons with siRNA directed to Zhangfei transcripts, led to a significant increase in transcripts and proteins of UPR genes, suggesting a potential role for Zhangfei in modulating the UPR.
Fetal spinal magnetic resonance imaging (MRI) is a prenatal routine for proper assessment of fetus development, especially when suspected spinal malformations occur while ultrasound fails to provide details. Limited by hardware, fetal spine MR images suffer from its low resolution.
High-resolution MR images can directly enhance readability and improve diagnosis accuracy. Image interpolation for higher resolution is required in clinical situations, while many methods fail to preserve edge structures. Edge carries heavy structural messages of objects in visual scenes for doctors to detect suspicions, classify malformations and make correct diagnosis. Effective interpolation with well-preserved edge structures is still challenging.
In this paper, we propose an edge-directed interpolation (EDI) method and apply it on a group of fetal spine MR images to evaluate its feasibility and performance. This method takes edge messages from Canny edge detector to guide further pixel modification. First, low-resolution (LR) images of fetal spine are interpolated into high-resolution (HR) images with targeted factor by bi-linear method. Then edge information from LR and HR images is put into a twofold strategy to sharpen or soften edge structures. Finally a HR image with well-preserved edge structures is generated. The HR images obtained from proposed method are validated and compared with that from other four EDI methods. Performances are evaluated from six metrics, and subjective analysis of visual quality is based on regions of interest (ROI).
All these five EDI methods are able to generate HR images with enriched details. From quantitative analysis of six metrics, the proposed method outperforms the other four from signal-to-noise ratio (SNR), peak signal-to-noise ratio (PSNR), structure similarity index (SSIM), feature similarity index (FSIM) and mutual information (MI) with seconds-level time consumptions (TC). Visual analysis of ROI shows that the proposed method maintains better consistency in edge structures with the original images.
The proposed method classifies edge orientations into four categories and well preserves structures. It generates convincing HR images with fine details and is suitable in real-time situations. Iterative curvature-based interpolation (ICBI) method may result in crisper edges, while the other three methods are sensitive to noise and artifacts.
Magnetic resonance imaging; Fetal spine; Edge-directed interpolation
ChuZ–haemin complex crystals belonged to space group C2221, with unit-cell parameters a = 106.474, b = 106.698, c = 52.464 Å, α = β = γ = 90°. Diffraction data have been collected to 2.4 Å resolution.
The haem oxygenase ChuZ from Campylobacter jejuni, a major enteric pathogen in humans, is part of the iron-acquisition mechanism that is involved in bacterial survival and persistence in hosts. The ChuZ–haemin complex has been purified and crystallized and diffraction data have been collected to 2.4 Å resolution. The ChuZ–haemin complex crystals belonged to space group C2221, with unit-cell parameters a = 106.474, b = 106.698, c = 52.464 Å, α = β = γ = 90°. The asymmetric unit contained one ChuZ monomer, with a Matthews coefficient of 2.58 Å3 Da−1.
haem oxygenases; Campylobacter jejuni; iron acquisition; pathogenesis
Insect chitinases are hydrolytic enzymes that are required for the degradation of glycosidic bonds of chitin. In this study, we identified and characterized a full-length cDNA of the chitinase gene (BdCht2) in the oriental fruit fly, Bactrocera dorsalis. The cDNA contains an open reading frame (ORF) of 1449 bp that encodes 483 amino acid residues and 126- and 296-bp non-coding regions at the 5′- and 3′-ends, respectively. The BdCht2 genome has four exons and three introns. The predicted molecular mass of the deduced BdCht2 is approximately 54.3 kDa, with an isoelectric point of 5.97. The 977 bp 5′ flanking region was identified and the transcription factor binding sites were predicted. Bioinformatic analyses showed that the deduced amino acid sequence of BdCht2 had 34%–66% identity to that of chitinases identified in other insect species. Quantitative real-time PCR (qPCR) analyses indicated that BdCht2 was mainly expressed during the larval-pupal and pupal-adult transitions. The tissue-specific expression showed that the highest expression was in the integument, followed by the fat body and other tissues. Moreover, the expression of BdCht2 was upregulated significantly upon 20-hydroxyecdysone (20E) at different dose injections after 8 h compared to that of the control. Starvation also increased the expression of BdCht2 in the third-instar larvae and was suppressed again by re-feeding the insects. These results suggest that BdCht2 plays an important role in the molting process of B. dorsalis larvae and can be regulated by 20E.
Bactrocera dorsalis; chitinase; expression pattern; 20-hydroxyecdysone; starvation
Microglia activation is the major component of inflammation that constitutes the characteristic of neurodegenerative disease. A large amount of researches have demonstrated that inflammation involved in the pathogenesis of PD process activated microglia acting on the neurons through the release of a variety of inflammatory factors. However, the molecular mechanism underlying how it does work on neurons is still unclear. Here, we show that intracerebral injections of LPS induced Parkinson's disease pathology in C57BL/6J mice. Furthermore, study on the dynamic changes in Synaptic vesicle-associated protein and axonal transport Protein in this process. The results indicated that after administration of LPS in the brain, the inflammatory levels of TNF-α and IL-1β both are elevated, and have a time-dependent.
Acute treatment of stroke with HDAC inhibitors has been shown to reduce ischemic cell damage; however, it is unclear whether delayed treatment with HDAC inhibitors will contribute to the brain repair and plasticity. In the present study, we investigated the effects of delayed treatment of stroke with a pan HDAC inhibitor, valproic acid (VPA), on white matter injury and neurogenesis during stroke recovery. Administration of VPA at a dose of 100 mg/kg for 7 days starting 24 hours after middle cerebral artery occlusion (MCAo) in rats significantly improved neurological outcome measured 7 to 28 days post-MCAo. In addition, the VPA treatment significantly increased oligodendrocyte survival and newly generated oligodendrocytes, which was associated with elevation of myelinated axonal density in the ischemic boundary 28 days after MCAo. VPA treatment also increased the expression of glutamate transporter 1 (GLT1) in the ischemic boundary after stroke, and increased acetylated histone H4 expression in neuroblasts and the number of new neurons in striatal ischemic boundary region. This study provides new evidence that the delayed VPA treatment enhances white matter repair and neurogenesis in ischemic brain, which may contribute to improved functional outcome.
Valproic acid; oligodendrocyte; axon; neural progenitor cells; subventricular zone (SVZ); stroke