This current work was to investigate the biological effects of acidic cosmetic water (ACW) on various biological assays. ACW was isolated from seawater and demonstrated several bio-functions at various concentration ranges. ACW showed a satisfactory effect against Staphylococcus aureus, which reduced 90% of bacterial growth after a 5-second exposure. We used cultured human peripheral blood mononuclear cells (PBMCs) to test the properties of ACW in inflammatory cytokine release, and it did not induce inflammatory cytokine release from un-stimulated, normal PBMCs. However, ACW was able to inhibit bacterial lipopolysaccharide (LPS)-induced inflammatory cytokine TNF-α released from PBMCs, showing an anti-inflammation potential. Furthermore, ACW did not stimulate the rat basophilic leukemia cell (RBL-2H3) related allergy response on de-granulation. Our data presented ACW with a strong anti-oxidative ability in a superoxide anion radical scavenging assay. In mass spectrometry information, magnesium and zinc ions demonstrated bio-functional detections for anti-inflammation as well as other metal ions such as potassium and calcium were observed. ACW also had minor tyrosinase and melanin decreasing activities in human epidermal melanocytes (HEMn-MP) without apparent cytotoxicity. In addition, the cell proliferation assay illustrated anti-growth and anti-migration effects of ACW on human skin melanoma cells (A375.S2) indicating that it exerted the anti-cancer potential against skin cancer. The results obtained from biological assays showed that ACW possessed multiple bioactivities, including anti-microorganism, anti-inflammation, allergy-free, antioxidant, anti-melanin and anticancer properties. To our knowledge, this was the first report presenting these bioactivities on ACW.
acidic cosmetic water (ACW); antioxidant activity; anti-microorganism; anti-inflammation; allergy-free; skin-whitening; anti-melanoma
Preferential CO oxidation (PROX) was investigated by using dealloyed nanoporous gold (NPG) catalyst under ambient conditions. Systematic investigations were carried out to characterize its catalytic performance by varying reaction parameters such as temperature and co-existence of CO2 and H2O, which revealed that NPG was a highly active and selective catalyst for PROX, especially at low temperature. At 20°C, the exit CO concentration could be reduced to less than 2 ppm with a turnover frequency of 4.1 × 10−2 s−1 at a space velocity of 120,000 mL h−1 g−1cat. and its high activity could retain for more than 24 hours. The presence of residual Ag species in the structure did not seem to improve the intrinsic activity of NPG for PROX; however, they contributed to the stabilization of the NPG structure and apparent catalytic activity. These results indicated that NPG might be readily applicable for hydrogen purification in fuel cell applications.
Microtubules (MTs) composed of αβ-tubulin heterodimers are highly dynamic polymers, whose stability can be regulated by numerous endogenous and exogenous factors. Both the anti-mitotic drug, Taxol, and microtubule-associated proteins (MAPs) stabilize this dynamicity by binding to and altering the conformation of MTs. In the current study, amide hydrogen/deuterium exchange coupled with mass spectrometry (HDX-MS) was used to examine the structural and dynamic properties of the MT complex with the microtubule binding domain of MAP4 (MTB-MAP4) in the presence and absence of Taxol. The changes in the HDX levels indicate that MTB-MAP4 may bind to both the outside and the luminal surfaces of the MTs, and that Taxol reduces both of these interactions. The MTB-MAP4 binding induces conformational rearrangements of α- and β-tubulin that promote an overall stabilization of MTs. Paradoxically, despite Taxol’s negative effects on MAP4 interactions with the MTs, its binding to the MTB-MAP4-MT complex further reduces the overall deuterium incorporation, suggesting that a more stable complex is formed in the presence of the drug.
Allergy is a complex disease that is likely to involve dysregulated CD4+ T cell activation. Here we propose a novel methodology to gain insight into how coordinated behaviour emerges between disease-dysregulated pathways in response to pathophysiological stimuli. Using peripheral blood mononuclear cells of allergic rhinitis patients and controls cultured with and without pollen allergens, we integrate CD4+ T cell gene expression from microarray data and genetic markers of allergic sensitisation from GWAS data at the pathway level using enrichment analysis; implicating the complement system in both cellular and systemic response to pollen allergens. We delineate a novel disease network linking T cell activation to the complement system that is significantly enriched for genes exhibiting correlated gene expression and protein-protein interactions, suggesting a tight biological coordination that is dysregulated in the disease state in response to pollen allergen but not to diluent. This novel disease network has high predictive power for the gene and protein expression of the Th2 cytokine profile (IL-4, IL-5, IL-10, IL-13) and of the Th2 master regulator (GATA3), suggesting its involvement in the early stages of CD4+ T cell differentiation. Dissection of the complement system gene expression identifies 7 genes specifically associated with atopic response to pollen, including C1QR1, CFD, CFP, ITGB2, ITGAX and confirms the role of C3AR1 and C5AR1. Two of these genes (ITGB2 and C3AR1) are also implicated in the network linking complement system to T cell activation, which comprises 6 differentially expressed genes. C3AR1 is also significantly associated with allergic sensitisation in GWAS data.
E-selectin-1 (ESL-1), also known as golgi complex-localized glycoprotein-1 (GLG1), homocysteine-rich fibroblast growth factor receptor (CGR-1), and latent transforming growth factor-β complex protein 1 (LTCP-1), is a multifunctional protein with widespread tissue distribution. To determine the functional consequences of ESL-1 deficiency, mice were generated carrying an ESL-1 gene trap. After backcrossing to C57BL6/J for 6 generations, mice heterozygous for the gene trap (ESL-1+/-) were intercrossed to produce ESL-1-/- mice, however ESL-1-/- mice were not viable, even at embryonic day E10.5. To determine the effect of heterozygous ESL-1 deficiency on atherosclerosis, apolipoprotein E deficient (ApoE-/-), ESL-1+/- mice were generated and fed western diet. Compared to ApoE-/-, ESL-1++ mice, atherosclerotic lesions from ApoE-/-, ESL-1+/- contained more collagen and fewer macrophages, suggesting increased plaque stability. In conclusion, heterozygous deficiency of ESL-1 is associated with features of increased atherosclerotic plaque stability while complete deficiency of ESL-1 leads to embryonic lethality.
leukocyte; selectins; macrophage; atherosclerosis; endothelium
Recent success in the derivation of haploid embryonic stem cells (haESCs) from mouse via parthenogenesis and androgenesis has enabled genetic screening in mammalian cells and generation of gene-modified animals. However, whether haESCs can be derived from primates remains unknown. Here, we report the derivation of haESCs from parthenogenetic blastocysts of Macaca fascicularis monkeys. These cells, termed as PG-haESCs, are pluripotent and can differentiate to cells of three embryonic germ layers in vitro or in vivo. Interestingly, the haploidy of one monkey PG-haESC line (MPH1) is more stable compared with that of the other one (MPH2), as shown by the existence of haploid cells for more than 140 days without fluorescence-activated cell sorting (FACS) enrichment of haploid cells. Importantly, transgenic monkey PG-haESC lines can be generated by lentivirus- and piggyBac transposon-mediated gene transfer. Moreover, genetic screening is feasible in monkey PG-haESCs. Our results demonstrate that PG-haESCs can be generated from monkeys, providing an ideal tool for genetic analyses in primates.
embryonic stem cell; haploid cells; monkey
In the title compound, [ZnI2(C34H31N3)], the ZnII atom is four-coordinated by two I atoms and the pyridine N atoms from the bidentate 6′-phenyl-2,2′-bipyridine ligand in a distorted tetrahedral geometry.
We sequenced small (s) RNAs from field collected honeybees (Apis mellifera) and bumblebees (Bombuspascuorum) using the Illumina technology. The sRNA reads were assembled and resulting contigs were used to search for virus homologues in GenBank. Matches with Varroadestructor virus-1 (VDV1) and Deformed wing virus (DWV) genomic sequences were obtained for A. mellifera but not B. pascuorum. Further analyses suggested that the prevalent virus population was composed of VDV-1 and a chimera of 5’-DWV-VDV1-DWV-3’. The recombination junctions in the chimera genomes were confirmed by using RT-PCR, cDNA cloning and Sanger sequencing. We then focused on conserved short fragments (CSF, size > 25 nt) in the virus genomes by using GenBank sequences and the deep sequencing data obtained in this study. The majority of CSF sites confirmed conservation at both between-species (GenBank sequences) and within-population (dataset of this study) levels. However, conserved nucleotide positions in the GenBank sequences might be variable at the within-population level. High mutation rates (Pi>10%) were observed at a number of sites using the deep sequencing data, suggesting that sequence conservation might not always be maintained at the population level. Virus-host interactions and strategies for developing RNAi treatments against VDV1/DWV infections are discussed.
The metabolic syndrome (MetS) is a constellation of clinical features that include central obesity, hypertension, atherogenic dyslipidemia, and insulin resistance (IR). However, the concept remains controversial; it has been debated whether MetS represents nothing more than simultaneous co-occurrence of individual risk factors, or whether there are common, shared pathophysiologic mechanisms that link the individual components.
Methods and Results
To investigate the emergence of metabolic and cardiovascular components during the development of MetS, we identified MetS-predisposed animals (n=35) in a large population of rhesus macaques (Macaca mulatta, 12.7 ± 2.9 years old, n=408), acclimated them to standardized conditions, and monitored the progression of individual component features over 18 months. In total 18 MetS animals with recently developed fasting hyperinsulinemia, central obesity, hypertension, and atherogenic dyslipidemia, we found that individual metabolic and cardiovascular components track together during the transition from pre-MetS to onset of MetS; MetS was associated with a 60% impairment of flow mediated dilation (FMD), establishing the mechanistic link with vascular dysfunction. Pioglitazone treatment (3 mg/kg body weight/day for 6 weeks), a PPARγ agonist, reversibly improved atherogenic dyslipidemia and IR, and fully restored FMD with persistent benefits.
Co-emergence of metabolic and cardiovascular components during MetS progression and complete normalization of vascular dysfunction with PPARγ agonists suggest shared underlying mechanisms rather than separate processes, arguing for the benefit of early intervention of MetS components. Predictive NHP models of MetS should be highly valuable in mechanistic and translational studies on the pathogenesis of MetS in relation to cardiovascular disease and diabetes.
Metabolic Syndrome (MetS); Nonhuman Primates; Cardiovascular Disease; Pathogenesis; PPARγ agonists
Listeria monocytogenes is a foodborne bacterial pathogen and the causative agent of an infectious disease, listeriosis. L. monocytogenes is ubiquitous in nature and has the ability to persist in food processing environments for extended periods of time by forming biofilms and resisting industrial sanitization. Human listeriosis outbreaks are commonly linked to contaminated dairy products, ready-to-eat meats, and in recent years, fresh produce such as lettuce and cantaloupes. We identified a putative Crp/Fnr family transcription factor Lmo0753 that is highly specific to human-associated genetic lineages of L. monocytogenes. Lmo0753 possesses two conserved functional domains similar to the major virulence regulator PrfA in L. monocytogenes. To determine if Lmo0753 is involved in environmental persistence-related mechanisms, we compared lmo0753 deletion mutants with respective wild type and complementation mutants of two fully sequenced L. monocytogenes genetic lineage II strains 10403S and EGDe for the relative ability of growth under different nutrient availability and temperatures, soil survival, biofilm productivity and attachment to select fresh produce surfaces including romaine lettuce leaves and cantaloupe rinds. Our results collectively suggested that Lmo0753 plays an important role in L. monocytogenes biofilm production and attachment to fresh produce, which may contribute to the environmental persistence and recent emergence of this pathogen in human listeriosis outbreaks linked to fresh produce.
Breathing programs have been reported to have positive effects in alleviating symptoms and optimizing pulmonary function in patients with chronic obstructive pulmonary disease (COPD). However, patients with stable disease may drop out of such programs if they are not modified to the individual’s exercise tolerance level, or if they are not easy to perform in the home. Little is known about the effectiveness of web-based home breathing programs for dyspnea. The purpose of this study was to evaluate the effectiveness of an online breathing program which included an animated diagram and video-guided instruction on pulmonary function, exercise capacity, and health-related quality of life in patients with COPD.
Sixty patients with stable COPD were randomized 1:1 to an experimental group (n = 30) or a control group (n = 30). Subjects in the experimental group trained for four months using an online program which included an animated diagram and video-guided instruction while the control group received conventional patient education on discharge from hospital. Forced expiratory volume, forced expiratory volume in one second (FEV1)/forced vital capacity (%), peak expiratory volume, six-minute walking distance test, and responses to the St George’s Respiratory Questionnaire were assessed before and after the intervention.
Patients in the two groups were well matched for demographic and clinical characteristics at baseline. All outcome measures showed significant improvement in the experimental group but not in the control group.
The online training program resulted in improved pulmonary function, exercise capacity, and health status. Therefore, it is strongly recommended that patients with stable COPD be trained with such programs.
chronic obstructive pulmonary disease; rehabilitation; adherence; family; nursing intervention; computerized programs
Acetylcholinesterase (AChE) is commonly used for the detection of organophosphate (OP) and carbamate (CB) insecticides. However, the cost of this commercially available enzyme is high, making high-throughput insecticide detection improbable. In this study we constructed a new AChE yeast expression system in Saccharomyces cerevisiae for the expression of a highly reactive recombinant AChE originating from Drosophila melanogaster (DmAChE). Specifically, the coding sequence of DmAChE was fused with the 3′-terminal half of an α-agglutinin anchor region, along with an antigen tag for the detection of the recombinant protein. The target sequence was cloned into the yeast expression vector pYes-DEST52, and the signal peptide sequence was replaced with a glucoamylase secretion region for induced expression. The resultant engineered vector was transformed into S. cerevisiae. DmAChE was expressed and displayed on the cell surface after galactose induction. Our results showed that the recombinant protein displayed activity comparable to the commercial enzyme. We also detected different types of OP and CB insecticides through enzyme inhibition assays, with the expressed DmAChE showing high sensitivity. These results show the construction of a new yeast expression system for DmAChE, which can subsequently be used for detecting OP and CB insecticides with reduced economic costs.
Cdk5/p25 hyperactivity has been demonstrated to lead to neuron apoptosis and degenerations. Chronic exposure to high glucose (HG) results in hyperactivity of Cdk5 and reduced insulin secretion. Here, we set out to determine whether abnormal upregulation of Cdk5/p25 activity may be induced in a pancreatic beta cell line, Min6 cells. We first confirmed that p25 were induced in overexpressed p35 cells treated with HG and increased time course dependence. Next, we showed that no p25 was detected under short time HG stimulation (4–12 hrs), however was detectable in the long exposure in HG cells (24 hrs and 48 hrs). Cdk5 activity in the above cells was much higher than low glucose treated cells and resulted in more than 50% inhibition of insulin secretion. We confirmed these results by overexpression of p25 in Min6 cells. As in cortical neurons, CIP, a small peptide, inhibited Cdk5/p25 activity and restored insulin secretion. The same results were detected in co-infection of dominant negative Cdk5 (DNCdk5) with p25. CIP also reduced beta cells apoptosis induced by Cdk5/p25. These studies indicate that Cdk5/p25 hyperactivation deregulates insulin secretion and induces cell death in pancreatic beta cells and suggests that CIP may serve as a therapeutic agent for type 2 diabetes.
Patients with systemic lupus erythematosus (SLE) have a striking increase in atherothrombotic cardiovascular disease (CVD), not explained by the Framingham risk equation. In vitro studies indicate that type-I Interferons (IFNs) may play prominent roles in increased CV risk in SLE. However, the in vivo relevance of these findings, with regards to the development of CVD, has not been characterized. We examined the role of type-I IFNs in endothelial dysfunction, aberrant vascular repair, and atherothrombosis in murine models of lupus and atherosclerosis.
Lupus-prone New Zealand Mixed-2328 mice (NZM) and atherosclerosis-prone Apolipoprotein-E-knockout mice (ApoE−/−) were compared to mice lacking type-I IFN-receptor (INZM and ApoEIFNR−/−, respectively) in their endothelial vasodilatory function, endothelial progenitor cell (EPC) function, in vivo neoangiogenesis, plaque development and occlusive thrombosis. Similar experiments were performed when NZM and ApoE−/− received an IFN-α-containing or an empty adenovirus.
Loss of type IIFN-receptor signaling improves endothelium-dependent vasorelaxation, lipoprotein parameters, EPC numbers and function and neoangiogenesis in lupus-prone mice, independent of disease activity or gender. Further, acute exposure to IFN-α impairs endothelial vasorelaxation and EPC function in lupus-prone and non-lupus-prone mice. ApoEIFNR−/− mice have decreased atherosclerosis severity and arterial inflammatory infiltrates and increased neoangiogenesis, compared to ApoE−/− mice, while NZM and ApoE−/− mice exposed to IFN-α develop accelerated thrombosis and platelet activation.
These results support the hypothesis that type I-IFNs play key roles in the development of premature CVD in SLE and, potentially, in the general population, through pleiotropic deleterious effects on the vasculature.
Angiogenesis; atherosclerosis; systemic lupus erythematosus
Background.Biomarkers of progression from latent Mycobacterium tuberculosis infection to active tuberculosis are needed. We assessed correlations between infection outcome and antibody responses in macaques and humans by high-throughput, proteome-scale serological studies.
Methods.Mycobacterium tuberculosis proteome microarrays were probed with serial sera from macaques representing various infection outcomes and with single-point human sera from tuberculosis suspects. Fluorescence intensity data were analyzed by calculating Z scores and associated P values. Temporal changes in macaque antibody responses were analyzed by polynomial regression. Correlations between human responses and sputum bacillary burden were assessed by quantile and hurdle regression.
Results.Macaque outcome groups exhibited distinct antibody profiles: early, transient responses in latent infection and stable antibody increase in active and reactivation disease. In humans, antibody levels and reactive protein numbers increased with bacillary burden. Responses to a subset of 10 proteins were more tightly associated with disease state than reactivity to the broader reactive proteome.
Conclusions.Integration of macaque and human data reveals dynamic properties of antibody responses in relation to outcome and leads to actionable findings for translational research. These include the potential of antibody responses to detect acute infection and preclinical tuberculosis and to identify serodiagnostic proteins for the spectrum of bacillary burden in tuberculosis.
The principal function of bacterial AB5 toxin B subunits is to interact with glycan receptors on the surfaces of target cells and mediate the internalization of holotoxin. However, B subunit-receptor interactions also have the potential to impact cell signaling pathways and, in so doing, contribute to pathogenesis independently of the catalytic (toxic) A subunits. Various Salmonella enterica serovars, including Salmonella enterica serovar Typhi, encode an AB5 toxin (ArtAB), the A subunit of which is an ADP-ribosyltransferase related to the S1 subunit of pertussis toxin. However, although the A subunit is able to catalyze ADP-ribosylation of host G proteins, a cytotoxic phenotype has yet to be identified for the holotoxin. We therefore examined the capacity of the purified B subunit (ArtB) from S. Typhi to elicit cytokine, chemokine, and adhesion molecule responses in human macrophage (U937), colonic epithelial (HCT-8) cell, and brain microvascular endothelial cell (HBMEC) lines. Secretion of the chemokines monocyte chemotactic protein 1 (MCP-1) and interleukin 8 (IL-8) was increased in all three tested cell lines, with macrophage inflammatory protein 1α (MIP-1α), MIP-1β, and granulocyte colony-stimulating factor (G-CSF) also significantly increased in U937 cells. ArtB also upregulated the cytokines tumor necrosis factor alpha (TNF-α) and IL-6 in HBMECs and HCT-8 cells, but not in U937 cells, while intercellular adhesion molecule 1 (ICAM-1) was upregulated in HCT-8 and U937 cells and vascular cell adhesion molecule 1 (VCAM-1) was upregulated in HBMECs. Thus, ArtB may contribute to pathogenesis independently of the A subunit by promoting and maintaining a strong inflammatory response at the site of infection.
Upon screening of plant-derived natural products against hepatitis C virus (HCV) in the replicon system, we demonstrate that lucidone, a phytocompound, isolated from the fruits of Lindera erythrocarpa Makino, significantly suppressed HCV RNA levels with 50% effective concentrations of 15 ± 0.5 μM and 20 ± 1.1 μM in HCV replicon and JFH-1 infectious assays, respectively. There was no significant cytotoxicity observed at high concentrations, with a 50% cytotoxic concentration of 620 ± 5 μM. In addition, lucidone significantly induced heme oxygenase-1 (HO-1) production and led to the increase of its product biliverdin for inducing antiviral interferon response and inhibiting HCV NS3/4A protease activity. Conversely, the anti-HCV activity of lucidone was abrogated by blocking HO-1 activity or silencing gene expression of HO-1 or NF-E2-related factor 2 (Nrf2) in the presence of lucidone, indicating that the anti-HCV action of lucidone was due to the stimulation of Nrf-2-mediated HO-1 expression. Moreover, the combination of lucidone and alpha interferon, the protease inhibitor telaprevir, the NS5A inhibitor BMS-790052, or the NS5B polymerase inhibitor PSI-7977, synergistically suppressed HCV RNA replication. These findings suggest that lucidone could be a potential lead or supplement for the development of new anti-HCV agent in the future.
A total of 146 group B streptococcus isolates from 8 cities across China belonged to four serotypes. Serotype Ia was more common in children. A high prevalence of resistance was observed for levofloxacin (37.7%), erythromycin (71.2%), clindamycin, (53.4%), and tetracycline (81.5%). The levofloxacin and clindamycin resistances among the 4 serotypes differed significantly. Eighty percent of fluoroquinolone-resistant isolates belonged to the sequence type 19 (ST19)/serotype III clone, with GyrA-ParC-ParE triple substitutions. This clone carried the erm(B), mef(E), and tet(M) genes.
Organisms have sophisticated subcellular compartments containing enzymes that function in tandem. These confined compartments ensure effective chemical transformation and transport of molecules, and the elimination of toxic metabolic wastes1,2. Creating functional enzyme complexes that are confined in a similar way remains challenging. Here we show that two or more enzymes with complementary functions can be assembled and encapsulated within a thin polymer shell to form enzyme nanocomplexes. These nanocomplexes exhibit improved catalytic efficiency and enhanced stability when compared with free enzymes. Furthermore, the co-localized enzymes display complementary functions, whereby toxic intermediates generated by one enzyme can be promptly eliminated by another enzyme. We show that nanocomplexes containing alcohol oxidase and catalase could reduce blood alcohol levels in intoxicated mice, offering an alternative antidote and prophylactic for alcohol intoxication.
NMDARs (N-methyl-D-aspartate receptors) mediate the predominantly excitatory neurotransmission in the CNS (central nervous system). Excessive release of glutamate and overactivation of NMDARs during brain ischemia and the hypoxia process are causally linked to excitotoxicity and neuronal damage. GluN3 subunits, the third member of the NMDAR family with two isoforms, GluN3A and GluN3B, have been confirmed to display an inhibitory effect on NMDAR activity. However, the effect of GluN3 subunits in brain ischemia and hypoxia is not clearly understood. In the present study, the influence of ischemia and hypoxia on GluN3 subunit expression was observed by using the 2VO (two-vessel occlusion) rat brain ischemia model and cell OGD (oxygen and glucose deprivation) hypoxia model. It was found that GluN3A protein expression in rat hippocampus and the prefrontal cortex was increased quickly after brain ischemia and remained at a high level for at least 24 h. However, the expression of the GluN3B subunit was not remarkably changed in both the animal and cell models. After OGD exposure, rat hippocampal neurons with GluN3A subunit overexpression displayed more viability than the wild-type neurons. NG108-15 cells overexpressing GluN3A presented pronounced resistance to glutamate insult. Blocking the increase of intracellular Ca2+ concentration may underlie the neuroprotective mechanism of up-regulated GluN3A subunit. Suppressing the generation of hydroxyl radicals and NO (nitric oxide) is probably also involved in the neuroprotection.
brain hypoxia and ischemia; excitotoxicity; GluN3A; N-methyl-D-aspartate receptor (NMDAR); oxygen and glucose deprivation (OGD); 2VO, two-vessel occlusion; CNS, central nervous system; DAPI, 4′,6-diamidino-2-phenylindole; FCM, flow cytometry; gDNA, genomic DNA; HBSS, Hanks’ balanced salt solution; MTT, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide; NMDAR, N-methyl-D-aspartate receptor; NO, nitric oxide; OGD, oxygen and glucose deprivation; PI, propidium iodide; RT, reverse transcription; S–D, Sprague–Dawley; TBST, TBS containing 0.1% Tween-20; TTC, triphenyltetrazolium chloride
Pacific white shrimp (Litopenaeus vannamei) is the most extensively farmed crustacean species in the world. White spot syndrome virus (WSSV) is one of the major pathogens in the cultured shrimp. However, the molecular mechanisms of the host-virus interaction remain largely unknown. In this study, the impact of WSSV infection on host gene expression in the hepatopancreas of L. vannamei was investigated through the use of 454 pyrosequencing-based RNA-Seq of cDNA libraries developed from WSSV-challenged shrimp or normal controls. By comparing the two cDNA libraries, we show that 767 host genes are significantly up-regulated and 729 genes are significantly down-regulated by WSSV infection. KEGG analysis of the differentially expressed genes indicated that the distribution of gene pathways between the up- and down-regulated genes is quite different. Among the differentially expressed genes, several are found to be involved in various processes of animal defense against pathogens such as apoptosis, mitogen-activated protein kinase (MAPK) signaling, toll-like receptor (TLR) signaling, Wnt signaling and antigen processing and presentation pathways. The present study provides valuable information on differential expression of L. vannamei genes following WSSV infection and improves our current understanding of this host-virus interaction. In addition, the large number of transcripts obtained in this study provides a strong basis for future genomic research on shrimp.
Two compounds, 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (BHPHTO) and bisdemethoxycurcumin (BDMC) they have been isolated from the rhizomes of Alpinia galangal, and the structures of both pure constituents were determined using spectroscopic analyses. The study examined the bioeffectivenesses of the two compounds on the human melanoma A2058 and showed that significantly inhibited the proliferation of melanoma cells in the cell viability assay. This research was also taken on the tests to B16-F10 cell line and showed minor inhibitory consequences of cellular tyrosinase activities and melanin contents. Our results revealed the anticancer effects of A. galangal compounds, and therefore, the target compounds could be potentially applied in the therapeutic application and the food industry.
Toll-like receptors (TLRs), as major innate immune mediators, may be involved in clearance of cerebral amyloid-β (Aβ) deposits. Recently, a novel TLR9 signaling pathway has been uncovered, which is functionally associated with the immune inflammatory response and reducing Aβ burden in Alzheimer’s disease (AD) mice. Therefore, TLR9 might represent a reasonable functional candidate gene for AD.
Our study investigated 1,133 sporadic late-onset AD (LOAD) and 1,159 healthy controls matched for sex and age in a large Han Chinese population. One selected functional rs187084 polymorphism within the TLR9 gene was genotyped by polymerase chain reaction-ligase detection reaction in a case–control associated study. The TLR9 rs187084 variant homozygote GG was significantly associated with a decreased LOAD risk after adjusting for age, gender, and ApoE ϵ4 status by logistic regression analysis (P = 0.035). Our result showed significant evidence of the interaction of ApoE ϵ4 with rs187084. When we further stratified our data by the ApoE ϵ4 status, we detected significant differences in the genotype and allele distributions of rs187084 between LOAD patients and controls in ApoE ϵ4 carriers (P < 0.001, P = 0.003, respectively). Moreover, we examined TLR9 expression in peripheral blood monocytes by flow cytometry, and the GG genotype of the TLR9 rs187084 polymorphism was associated with a higher TLR9 expression than two other genotypes in LOAD patients.
Our findings support the hypothesis that the TLR9 polymorphism may modify LOAD risk in the Han Chinese population.
Alzheimer’s disease; Polymorphisms; TLR9; rs187084; Expression; Association study
The grain aphid (Sitobion avenae F.) is a major agricultural pest which causes significant yield losses of wheat in China, Europe and North America annually. Transcriptome profiling of the grain aphid alimentary canal after feeding on wheat plants could provide comprehensive gene expression information involved in feeding, ingestion and digestion. Furthermore, selection of aphid-specific RNAi target genes would be essential for utilizing a plant-mediated RNAi strategy to control aphids via a non-toxic mode of action. However, due to the tiny size of the alimentary canal and lack of genomic information on grain aphid as a whole, selection of the RNAi targets is a challenging task that as far as we are aware, has never been documented previously.
In this study, we performed de novo transcriptome assembly and gene expression analyses of the alimentary canals of grain aphids before and after feeding on wheat plants using Illumina RNA sequencing. The transcriptome profiling generated 30,427 unigenes with an average length of 664 bp. Furthermore, comparison of the transcriptomes of alimentary canals of pre- and post feeding grain aphids indicated that 5490 unigenes were differentially expressed, among which, diverse genes and/or pathways were identified and annotated. Based on the RPKM values of these unigenes, 16 of them that were significantly up or down-regulated upon feeding were selected for dsRNA artificial feeding assay. Of these, 5 unigenes led to higher mortality and developmental stunting in an artificial feeding assay due to the down-regulation of the target gene expression. Finally, by adding fluorescently labelled dsRNA into the artificial diet, the spread of fluorescence signal in the whole body tissues of grain aphid was observed.
Comparison of the transcriptome profiles of the alimentary canals of pre- and post-feeding grain aphids on wheat plants provided comprehensive gene expression information that could facilitate our understanding of the molecular mechanisms underlying feeding, ingestion and digestion. Furthermore, five novel and effective potential RNAi target genes were identified in grain aphid for the first time. This finding would provide a fundamental basis for aphid control in wheat through plant mediated RNAi strategy.
Grain aphid (Sitobion avenae F.); Alimentary canal; Transcriptome profile; Double strand RNA (dsRNA); Artificial feeding assay; RNA interference (RNAi); Aphid control