In this study, data from breast MRI-guided near infrared spectroscopy (NIRS) exams delivered to 44 patients scheduled for surgical resection (ending in 16 benign and 28 malignant diagnoses) were analyzed using a spatial sensitivity metric to quantify the adequacy of the optical measurements for interrogating the tumor region of interest, as derived from the concurrent MRI scan. Along with positional sensitivity, the incorporation of spectral priors and the selection of an appropriate regularization parameter in the image reconstruction were considered, and found to influence the diagnostic accuracy of the recovered images. Once optimized, the MRI/NIRS data was able to differentiate the malignant from benign lesions through both total hemoglobin (p = 0.0037) and tissue optical index (p = 0.00019), but required the relative spatial sensitivity of the optical measurement data to each lesion to be above 1%. Spectral constraints implemented during the reconstruction were required to obtain statistically significant diagnostic information from images of H2O, lipids, and Tissue Optical Index (TOI). These results confirm the need for optical systems that have homogenous spatial coverage of the breast while still being able to accommodate the normal range of breast sizes.
Point source pollution is one of the main threats to regional environmental health. Based on a water quality model, a methodology to assess the regional risk of point source pollution is proposed. The assessment procedure includes five parts: (1) identifying risk source units and estimating source emissions using Monte Carlo algorithms; (2) observing hydrological and water quality data of the assessed area, and evaluating the selected water quality model; (3) screening out the assessment endpoints and analyzing receptor vulnerability with the Choquet fuzzy integral algorithm; (4) using the water quality model introduced in the second step to predict pollutant concentrations for various source emission scenarios and analyzing hazards of risk sources; and finally, (5) using the source hazard values and receptor vulnerability scores to estimate overall regional risk. The proposed method, based on the Water Quality Analysis Simulation Program (WASP), was applied in the region of the Taipu River, which is in the Taihu Basin, China. Results of source hazard and receptor vulnerability analysis allowed us to describe aquatic ecological, human health, and socioeconomic risks individually, and also integrated risks in the Taipu region, from a series of risk curves. Risk contributions of sources to receptors were ranked, and the spatial distribution of risk levels was presented. By changing the input conditions, we were able to estimate risks for a range of scenarios. Thus, the proposed procedure may also be used by decisionmakers for long-term dynamic risk prediction.
Anaplasma bovis is one of the most important tick-borne pathogens in China. In the first report of A. bovis in China, we describe infection in eight of 17 wild Reeves' muntjac (Muntiacus reevesi) from Guangxi, southwest China.
We announce the genome sequence of Borrelia garinii strain SZ, isolated from Dermacentor ticks collected in northeastern China. B. garinii strain SZ carries numerous plasmids, both 10 circular and 9 linear plasmids. The 902,487-bp linear chromosome (28.2% GC content) contains 820 open reading frames, 33 tRNAs, and 4 complete rRNAs. The plasmid cp32-10 contains one clustered regularly interspaced short palindromic repeat (CRISPR) with four repeats.
The use of peptide?based vaccines as therapeutics aims to elicit immune responses through antigenic epitopes derived from tumor antigens. Peptide?based vaccines are easily synthesized and chemically stable entities, and of note, they are absent of oncogenic potential. However, their application is more complicated as the success of an effective peptide?based vaccine is determined by numerous parameters. The success thus far has been limited by the choice of tumor antigenic peptides, poor immunogenicity and incorporation of strategies to reverse cancer?mediated immune suppression. In the present review, an overview of the mechanisms of peptide?based vaccines is provided and antigenic peptides are categorized with respect to their tissue distribution in order to determine their usefulness as targets. Furthermore, certain approaches are proposed that induce and maintain T cells for immunotherapy. The recent progress indicates that peptide?based vaccines are preferential for targeted therapy in cancer patients.
Reverse-genetic engineering of foot and mouth disease virus (FMDV) can improve the productivity, antigen matching, antigen stability, immune response ability, and biological safety of vaccines, so vaccine candidates with anticipated biological characteristics can be promptly achieved. Negative influence in taming of virulent strains can also be decreased or avoided. Reverse genetics not only make up for deficiencies like limitation of viral nature, low success rate, and time and energy consuming, but also realize more active designing of vaccines. Therefore, reverse genetics is significant in improving integral quality and efficiency of vaccines. In this review, we use FMDV vaccines as an example to summarize improvement in biological characteristics of virulent strains and provide a reference for related researches.
Nearly all patients with tuberous sclerosis complex (TSC) develop renal angiomyolipomas, although the tumor cell of origin is unknown. We observed decreased renal angiomyolipoma development in patients with TSC2- polycystic kidney disease 1 deletion syndrome and hypertension that were treated from an early age with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers compared with patients who did not receive this therapy. TSC-associated renal angiomyolipomas expressed ANG II type 1 receptors, platelet-derived growth factor receptor-?, desmin, ?-smooth muscle actin, and VEGF receptor 2 but did not express the adipocyte marker S100 or the endothelial marker CD31. Sera of TSC patients exhibited increased vascular mural cell-secreted peptides, such as VEGF-A, VEGF-D, soluble VEGF receptor 2, and collagen type IV. These findings suggest that angiomyolipomas may arise from renal pericytes. ANG II treatment of angiomyolipoma cells in vitro resulted in an exaggerated intracellular Ca(2+) response and increased proliferation, which were blocked by the ANG II type 2 receptor antagonist valsartan. Blockade of ANG II signaling may have preventative therapeutic potential for angiomyolipomas.
Breast cancer has been considered to be a multifactorial disease with a wide array of well-characterized gene mutations and chromosomal abnormalities. However, it is becoming evident that the onset or development of breast cancer also depends on epigenetic factors, although the mechanisms have not been fully elucidated. We performed a genome-wide analysis of DNA methylation of breast carcinomatous tissues and paired normal tissues to examine the differences in methylation between them. Methylation-specific polymerase chain reaction (MSP) was used to validate the hypermethylated genes screened out by DNA methylation microarray. We found that hypomethylation and hypermethylation occurred in 2753 and 1795 genes, respectively, in breast carcinomatous tissues. Meanwhile, gene ontology analysis and ingenuity pathway analysis revealed the function and pathway of several genes whose methylation status was altered in breast carcinomatous tissues. In addition, we investigated the promoter methylation status of four genes in breast carcinomatous tissue and paired normal tissues (n=30) by MSP. Promoter hypermethylation of CRABP1, HOXB13, IFNGR2, and PIK3C3 was found in 37% (11/30), 23% (7/30), 17% (5/30), and 2% (2/30) of the carcinomas, respectively. Mutation of these four important genes was critical to many types of cancer. Our results suggest that DNA methylation mechanisms may be involved in regulating the occurrence and development of breast cancer.
DNA from liver samples of 17 free-ranging wild Reeves' muntjac (Muntiacus reevesi) was used for PCR amplification of piropalsm 18S rRNA gene. Of 17 samples, 14 (82.4%) showed a specific PCR product which were cloned and sequenced. BLAST analysis of the sequences obtained showed similarities to Babesia sp., Theileria capreoli, Theileria uilenbergi and Theileria sp. BO302-SE. Phylogenetic analysis showed that the Babesia sp. detected in the present study was distantly separated from known Babesia species of wild and domestic animals. Six sequences showed 100% similarity to T. capreoli while five sequences were separated from all known Theileria species and constituted an independent clade with Theileria sp. BO302-SE derived from roe deer in Italy; two sequences were close to T. uilenbergi with 97% similarity. This is the first description of hemoparasite infection in free-ranging wild Reeves' muntjac in China. Our results indicate that wild Reeves' muntjac may play an important reservoir role for hemoparasites.
Dermacentor everestianus Hirst, 1926, is only reported in Northwestern China and Nepal. Few researches about this species have been involved, especially for molecular characteristics. The taxonomy studies of D.everestianus are mainly based on morphological features, and its taxonomic status is an ongoing controversy. To clarify the molecular characteristics and phylogenetic status of D.everestianus and other related species, the sequences of mitochondrial 16S ribosomal DNA (rDNA) and cox1 fragments were analyzed in the present study. Analysis of 16S rDNA and cox1 sequences showed 99.3-100% identity within D.everestianus individuals, with the genetic divergence among them was 0-0.0086. The interspecific distance of 16S rDNA and cox1 between D.everestianus and some other Palaearctic species including D. silvarum, D. nuttalli, and D. marginatus was much smaller than that between D.everestianus and Nearctic Dermacentor ticks (D.albipictus, D.nitens, and D.variabilis). Such relationships of these ticks were also verified in the phylogenetic analysis. Two major clades were recovered within Dermacentor spp. with more than 90% bootstrap support in the phylogenetic trees. D.everestianus together with D.silvarum, D.nuttalli, and D.marginatus were included in the clade I (Eurasia lineage). Other analyzed tick species including D.variabilis, D.nitens, and D.albipictus formed clade II, which are distributed in Nearctic realm. These indicated that the genus Dermacentor was at least composed of two lineages. Thus, further researches including additionally molecular markers on all Dermacentor species globally should be taken to precisely resolve relationships within Dermacentor.
Perfluorooctanoic acid (PFOA) is widely used because of its stain-resistant and water-repellant properties. This study aimed to explore the molecular mechanisms undergoing the stimulation effects of PFOA on cancer cell invasion and matrix metalloproteinases (MMPs) expression. Trans-well filter assay showed that PFOA exposure (?5 nM) evidently enhanced the invasion ability of the breast cancer cells MDA-MB-231. Luciferase reporter assay, quantitative real-time PCR, western blotting and gelatin zymography consistently demonstrated that mRNA and protein levels of MMP-2/-9 were increased in the cells after PFOA treatment (P<0.05 each). Western blotting revealed that PFOA could activate nuclear factor kappaB (NF-?B) by accelerating NF-?B translocation into the nucleus. Furthermore, addition of NF-?B inhibitor in culture medium could suppress the breast cancer cells invasiveness enhancement and MMP-2/-9 overexpression. This study indicates that PFOA can stimulate breast cancer cells invasion and up-regulate matrix metalloproteinase-2/-9 expression mediated by activating NF-?B, which deserves more environmental health concerns.
Classical swine fever (CSF), or hog cholera, is a highly contagious disease that emerged in the first half of the nineteenth century. To fight against the disease and protect pigs, different vaccines were developed, including early generation of lapinized Rovac strain and the later development of the "Chinese" strain (C-strain). However, details of the development of these vaccines are lost in history. In order to investigate the phylogenetic relationship between the Rovac and other lapinized vaccines, this study determined the genome sequences of the Rovac, which comprised 12,304 nucleotides, notably with the 3'untranslated region (3'UTR) containing a 13-nucleotide insertion. The near-complete genome of Russian vaccine strain LK-VNIVViM was determined by next-generation sequencing on Illumina MiSeq platform. Whole genome phylogenetic analysis revealed a closer relationship of the Rovac strain with the Russian LK-VNIVViM, CS strain and its derivative RUCSFPLUM (genotype 1.2), rather than with the C-strain (genotype 1.1). In addition, it also demonstrated an ancestry role of the LK-VNIVViM in relation to the CS strain and RUCSFPLUM. The study suggested that the Rovac vaccine is the possible ancestor of the Russian vaccine strains but not the C-strain vaccine.
Haemaphysalis bispinosa Neumann has been considered to exist in China, especially in the southern part of the country. However, H. bispinosa referred to in many Chinese research papers may in fact be H. longicornis, which is widely distributed in most regions of China. In order to clarify the occurrence of H. bispinosa, Haemaphysalis ticks collected from 18 of 23 provinces of China (Hebei, Henan, Hubei, Guangxi, Gansu, Yunnan, Xinjiang, Anhui, Zhejiang, Shannxi, Guizhou, Sichuan, Shanxi, Shandong, Ningxia, Fujian, Qinghai and Jiangxi) were examined based on morphological and molecular characteristics. We found no evidence of H. bispinosa being present in China. Our results indicate that all of the so called "H. bispinosa" ticks reported in China are in fact H. longicornis.
The satellite fault diagnosis has an important role in enhancing the safety, reliability, and availability of the satellite system. However, the problem of enormous parameters and multiple faults makes a challenge to the satellite fault diagnosis. The interactions between parameters and misclassifications from multiple faults will increase the false alarm rate and the false negative rate. On the other hand, for each satellite fault, there is not enough fault data for training. To most of the classification algorithms, it will degrade the performance of model. In this paper, we proposed an improving SVM based on a hybrid voting mechanism (HVM-SVM) to deal with the problem of enormous parameters, multiple faults, and small samples. Many experimental results show that the accuracy of fault diagnosis using HVM-SVM is improved.
BackgroundThe identification of specific epitopes targeted by the host antibody response is important for understanding the natural response to infection and for the development of epitope-based marker vaccines and diagnostic tools for toxoplasmosis. In this study, Toxoplasma gondii GRA4 epitopes were identified using software-based prediction and a synthetic peptide technique.MethodsThe complete GRA4 gene sequence was obtained from T. gondii of the Gansu Jingtai strain of tachyzoites. The potential B cell epitopes of GRA4 was predicted using the PROTEAN subroutine in the DNASTAR software package. The peptides with good hydrophilicity, high accessibility, high flexibility and strong antigenicity were chemically synthesized and assessed by ELISA using pig sera from different time points after infection.ResultsThe potential B cell epitopes of GRA4 predicted by bioinformatics tools focused on six regions of GRA4, 52¿77 aa, 93¿112 aa, 127¿157 aa, 178¿201 aa, 223¿252 aa and 314¿333 aa. Eleven shorter peptides from the six regions were synthesized and assessed by ELISA using pig sera from different time points after infection. Three of the eleven peptides (amino acids 62¿77, 233¿252 and 314¿333) tested were recognized by all sera.ConclusionsWe precisely located the T. gondii GRA4 epitopes using pig sera collected at different time points after infection. The identified epitopes may be useful for additional studies of epitope-based vaccines and diagnostic reagents.
Oncogenic mutations in isocitrate dehydrogenase 1 and 2 (IDH1/2) occur in several types of cancer, but the metabolic consequences of these genetic changes are not fully understood. In this study, we performed (13)C metabolic flux analysis on a panel of isogenic cell lines containing heterozygous IDH1/2 mutations. We observed that under hypoxic conditions, IDH1-mutant cells exhibited increased oxidative tricarboxylic acid metabolism along with decreased reductive glutamine metabolism, but not IDH2-mutant cells. However, selective inhibition of mutant IDH1 enzyme function could not reverse the defect in reductive carboxylation activity. Furthermore, this metabolic reprogramming increased the sensitivity of IDH1-mutant cells to hypoxia or electron transport chain inhibition in vitro. Lastly, IDH1-mutant cells also grew poorly as subcutaneous xenografts within a hypoxic in vivo microenvironment. Together, our results suggest therapeutic opportunities to exploit the metabolic vulnerabilities specific to IDH1 mutation.
Two new monoterpenes, (7S)-p-cymene-2,7,8-triol (1) and (3R,4R,6S)-p-menth-1-ene-3,6,10-triol (2), were isolated from the fruits of Amomum kravanh. Their structures were established by spectroscopic data. The absolute configuration of the 7,8-diol moiety in 1 was assigned by CD data after addition of Mo2(OAc)4 in dimethyl sulfoxide (DMSO) solution. Compounds 1 and 2 exhibited weak activity of anti-platelet aggregation in vitro.
Foot-and-mouth disease (FMD) is a highly contagious and economically devastating disease of cloven-hoofed animals in the world. The disease can be effectively controlled by vaccination of susceptible animals with the conventional inactivated vaccine. However, one major concern of the inactivated FMD virus (FMDV) vaccine is that it does not allow serological discrimination between infected and vaccinated animals, and therefore interferes with serologic surveillance and the epidemiology of disease. A marker vaccine has proven to be of great value in disease eradication and control programs. In this study, we constructed a marker FMDV containing a deletion of residues 93 to 143 in the nonstructural protein 3A using a recently developed FMDV infectious cDNA clone. The marker virus, r-HN/3A93-143, had similar growth kinetics as the wild type virus in culture cell and caused a symptomatic infection in pigs. Pigs immunized with chemically inactivated marker vaccine were fully protected from the wild type virus challenge, and the potency of this marker vaccine was 10 PD50 (50% pig protective dose) per dose, indicating it could be an efficacious vaccine against FMDV. In addition, we developed a blocking ELISA targeted to the deleted epitope that could clearly differentiate animals infected with the marker virus from those infected with the wild type virus. These results indicate that a marker FMDV vaccine can be potentially developed by deleting an immunodominant epitope in NSP 3A.
Oxysterols have recently been identified as natural ligands for a G protein-coupled receptor called EBI2 (aka GPR183) ( Nature 2011 , 475 , 524 ; 519 ). EBI2 is highly expressed in immune cells ( J. Biol. Chem. 2006 , 281 , 13199 ), and its activation has been shown to be critical for the adaptive immune response and has been genetically linked to autoimmune diseases such as type I diabetes ( Nature 2010 , 467 , 460 ). Here we describe the isolation of a potent small molecule antagonist for the EBI2 receptor. First, we identified a small molecule agonist NIBR51 (1), which enabled identification of inhibitors of receptor activation. One antagonist called NIBR127 (2) was used as a starting point for a medicinal chemistry campaign, which yielded NIBR189 (4m). This compound was extensively characterized in binding and various functional signaling assays. Furthermore, we have used 4m to block migration of a monocyte cell line called U937, suggesting a functional role of the oxysterol/EBI2 pathway in these immune cells.
Abstract The complete mitochondrial genome of Ceracris versicolor is determined here. It is 15,616?bp in length and contains 75.2% AT. All 13 mitochondrial PCGs share the start codon ATN, except for cox1 (CCG start codon). The usual termination codons (TAA) and incomplete stop codons (T) are found from 13 protein-coding genes. All tRNA genes could be folded into the typical cloverleaf secondary structure, except trnS (AGN) lacking of the dihydrouridine arm. The most frequent amino acids in the PCGs of C. versicolor are Leucine (14.45%), Isoleucine (10.50%), Serine (9.53%), Phenylalanine (9.26%), and the total content of these amino acids was 43.74%. The sizes of the large and small ribosomal RNA genes are 1315 and 781?bp, respectively. The AT content of the A?+?T-rich region is 87.5%.
Social anhedonia (SA), the diminished pleasure from social relationships, is a prominent characteristic of the vulnerability and manifestation of schizophrenia disorder. However, SA can develop for multiple reasons and little is known about its neural basis; these 2 issues hinder the utility and sensitivity of SA as a marker of schizophrenia pathology. This study investigated whether lateral prefrontal cortex (LPFC) deficits in social reward processing are associated with both SA and other schizophrenia-spectrum symptoms. During functional MRI (fMRI), a community sample of healthy adults (N = 30) with high and low SA viewed positive, negative, and neutral facial expressions. Afterward, participants completed an online daily diary in which they rated schizophrenia-spectrum symptoms and occurrence of interpersonal conflict each day for 21 days. Compared with low SA, high SA participants had less ventral (V)LPFC activity to positive versus neutral expressions. In addition, participants with a combination of high SA and low VLPFC activity to positive versus neutral expressions had worse daily diary ratings of schizophrenia-spectrum symptoms, including worse cognition, paranoia, motivation/productivity, and vigor/positive affect (i.e., psychomotor activation). Finally, among high SA participants, VLPFC activity predicted the daily relationship between distress from interpersonal conflict and symptom-severity; specifically, high SA participants with low VLPFC activity had worse paranoia on days of high conflict distress. These findings indicate that VLPFC deficits in positive emotion are associated with both SA and other schizophrenia-spectrum symptoms and that understanding the interaction of SA, VLPFC function, and social stress could facilitate the use of SA in the prevention and treatment of schizophrenia.
Abstract The complete mitochondrial genome of Phlaeoba tenebrosa was sequenced. Its 15,648 bp nucleotides encode 37 typical mitochondrial genes and contain 73.8% AT. All 13 mitochondrial protein coding genes (PCGs) share the start codon ATN, except for cox1 (CCG start codon). The usual termination codons (TAA or TAG) and incomplete stop codons (T or TA) are found from 13 protein-coding genes. The most frequent amino acids in the PCGs are Leucine (14.02%), Serine (9.64%), Phenylalanine (9.13%), Isoleucine (10.44%), and the total content of these amino acids was 43.23%. All tRNA genes could be folded into the typical cloverleaf secondary structure, except trnS(AGN) lacking of the dihydrouridine arm. The sizes of the large and small rRNA genes are 1319?bp and 841?bp, respectively. The AT content of the A?+?T-rich region is 82.6%.
Abstract The complete mitochondrial genome of Kingdonella bicollina, which was collected from the Tibetan Plateau, is determined here. It is 15,630?bp in length and contains 75.6% AT. All 13 mitochondrial PCGs share the start codon ATN, except for cox1 (CCG start codon). The termination codons include TAA, TAG and T. All tRNA genes could be folded into the typical cloverleaf secondary structure, except trnS(AGN) lacking of dihydrouridine arm. The sizes of the large and small ribosomal RNA genes are 1312 and 859?bp, respectively. The A+T-rich region is 739?bp in length contains 79.7% AT content.
Abstract The complete mitochondrial genome of Pacris xizangensis, which was collected from Tibetan Plateau, is reported here. It is 15,622?bp in length and contains 75.0% AT. All P. xizangensis protein-coding sequences except for the cox1 start with a typical ATN codon. The usual termination codons (TAA or TAG) and incomplete stop codons (T or TA) are found from 13 protein-coding genes. All tRNA genes could be folded into the typical cloverleaf secondary structure, except trnS(AGN) lacking of dihydrouridine arm. The sizes of the large and small ribosomal RNA genes are 1314 and 846?bp, respectively. The AT content of the A?+?T-rich region is 83.4%.
An enzyme-linked immunosorbent assay (ELISA) based on a recombinant Theileria uilenbergi immunodominant protein (rTuIP) was validated for detection of antibodies in 188 positive and 198 negative reference serum samples, respectively. The cut-off value was determined at 32.7% with 95% and 90% accuracy levels by two-graphic receiver-operating characteristic (TG-ROC). The equal diagnostic sensitivity (Se) and specificity (Sp) were calculated to be 98.4%. Further validation of the repeatability with positive and negative reference samples indicated the reliable performance of the assay. Monitoring the antibody dynamics of sheep experimentally infected with Theileria luwenshuni showed the efficient detection of antibody response against the pathogen at the early infection stage and up until two months post infection. Application of this assay for detection of antibody in field sera from previous unknown Theileria endemic regions in Suizhou and Guiyang showed 17.8% and 11.6% seroprevalence, respectively, and presence of the pathogen was confirmed by identification of the 18S rRNA gene in the corresponding blood of the seropositive animals. These data support that the rTuIP ELISA could be a useful tool to study the epidemiology of theileriosis caused by T. uilenbergi and/or T. luwenshuni.
Diabetes mellitus substantially increases the risk of stroke and enhances brain's vulnerability to ischemia insult. Electroacupuncture (EA) pretreatment was proved to induce cerebral ischemic tolerance in normal stroke models. Whether EA could attenuate cerebral ischemia injury in diabetic mice and the possible underlying mechanism are still unrevealed. Male C57BL/6 mice were subjected to streptozotocin (STZ) for diabetic models. After inducing focal cerebral ischemia model, the levels of plasma and cerebral adiponectin (APN) were measured as well as the expression of cerebral adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2). The neurobehavioral score, infarction volume, and cellular apoptosis were evaluated with or without AdipoR1 short interfering RNA (siRNA). The role of phosphorylation of glycogen synthesis kinase 3 beta (GSK-3?) at Ser-9 in the EA pretreatment was also assessed. EA pretreatment increased both plasma and cerebral APN levels and enhanced neuronal AdipoR1 in diabetic mice. In addition, EA reduced infarct size, improved neurological outcomes, and inhibited cell apoptosis after reperfusion. These beneficial effects were reversed by AdipoR1 knockdown. Furthermore, EA increased GSK-3? phosphorylation (p-GSK-3?) in the ipsilateral penumbra. Augmented p-GSK-3? induced neuroprotective effects similar to those of EA pretreatment. In contrast, dampened p-GSK-3? could reverse the neuroprotective effects of EA. In addition, the increase in p-GSK-3? by EA was abolished by AdipoR1 knockdown. We conclude that EA pretreatment increases the production of APN, which induce protective effects against cerebral ischemia-reperfusion injury through neuronal AdipoR1-mediated phosphorylation of GSK-3? in diabetic mice.
Haemaphysalis qinghaiensis, a prevalent tick species in China, causes severe economic losses. In this study, we investigated the pathogenicity of six isolates of the fungus Metarhizium anisopliae to engorged female H. qinghaiensis using concentrations of 10(6), 10(7) and 10(8) conidia ml(-1). The results indicated that M.aAT08 and M.aAT13 isolates were highly virulent against the ticks. Metarhizium anisopliae has potential for biocontrol of H. qinghaiensis.
Theileria and Babesia protozoan parasites are transmitted mainly by tick vectors. These parasites cause heavy economic losses to the live-stock industry, as well as affecting the health of wild animals in parasite-endemic areas. Identification of infectious agents in wild animals is not only crucial for species preservation, but also provides valuable information on parasite epidemiology. Here, we conducted a molecular surveillance study in Northwestern China to assess the prevalence of blood pathogens in cervids.
In this study, two pairs of oligonucleotide primers were designed according to the nucleotide sequence of the internal transcribed spacers (ITSs) of Babesia bigemina and B. bovis isolates from China. The primers were used in a multiplex PCR to detect parasite DNA in blood samples from cattle. There was no cross reactions with B. ovata, B. major, B. sp. Kashi, Theileria annulata, T. sergenti, T. sinensis or normal bovine DNA. The sensitivity of multiplex PCR assay was 1 pg and 10 pg DNA for B. bigemina and B. bovis, respectively. A total of 260 field blood samples collected from cattle in five provinces of China were analyzed by multiplex PCR and light microscopy. PCR testing revealed that 7.3% (19/260) and 5.8% (15/260) of cattle were positive for B. bigemina and B. bovis and 1.2% (3/260) of cattle were co-infected with B. bigemina and B. bovis. Using light microscopy, 2.3% (6/260) and 1.5% (4/260) of cattle were infected by B. bigemina and B. bovis, respectively, and no co-infection was found. The results showed that the multiplex PCR developed in the present study could be an alternative diagnostic tool for the detection of B. bovis and B. bigemina infection in cattle.
Standard treatments for AMR-rituximab, intravenous immunoglobulin, and/or plasmapheresis-aim to suppress the production and modulate the effect of donor-specific antibodies and remove them, respectively. Proteasome inhibitors such as bortezomib are potent therapeutic agents that target plasma cells more effectively than rituximab to reduce measurable donor-specific antibody production. Little is known in adults, and no data exist in children about effects of proteasome inhibition to treat AMR on protective antibody titers. We present a pediatric renal transplant recipient who received bortezomib for relatively early AMR and whose antibody titers to measles and tetanus were tracked. The AMR was treated successfully, and we noted no clinical decrease in the overall level of protective immunity from pretransplant baseline levels at almost one yr after AMR treatment cessation. Larger studies will elucidate more clearly how proteasome inhibition to treat AMR affects protective immunity in pediatric transplant recipients.
Haemaphysalis qinghaiensis Teng (Acta Zootaxon Sin 5:144-149, 1980) is an endemic species in China. This tick species was first described based on engorged or semi-engorged specimens, and the drawings and description in words of morphological characteristics were poor. Therefore, the present study aims to redescribe morphological characteristics of all active stages of this tick species in detail by scanning electron microscopy. Additionally, a comparison between H. qinghaiensis and other sympatric Haemaphysalis species was also analyzed. Males of H. qinghaiensis can be distinguished from sympatric Haemaphysalis species by the following characters: palpi less salient laterally and curved in contour; ventrointernal setae of palpal segment II thin, number <7; the tips of palpal segment III not so strongly recurved inward to become "pincerlike" and lacking dorsal spur; dental formula 5/5; lateral grooves enclose first festoon; coxa IV with a short, broadly triangular spur; tarsi somewhat humped; and spiracular plates long comma-shaped. Females of H. qinghaiensis can be distinguished by palpi less salient laterally and curved in contour; ventrointernal setae of palpal segment II thin, number <7; segment III of palpi lacking dorsal spur; dental formula 4/4; scutum subcircula; and tarsi somewhat humped. Nymphs of H. qinghaiensis can be distinguished from those of other species by palpi less salient laterally and curved in contour; dental formula 2/2; basis capituli rectangular, with distinct dorsal cornua, without ventral cornua; and spiracular plates with short and narrow dorsal prolongation. Larvae of H. qinghaiensis can be distinguished by palpi less salient laterally and curved in contour; basis capituli rectangular, without distinct cornua.
Bovine viral diarrhea virus (BVDV) is a pestivirus which infects both domestic animals and wildlife species worldwide. In China, cattle are often infected with BVDV of different genotypes, but there is very limited knowledge regarding BVDV infection in Chinese yaks and the genetic diversity of the virus. The objectives of this study were to detect viral infection in yaks in Qinghai, China and to determine the genotypes of BVDV based on analysis of the 5'untranslated region (5'UTR) and N-terminal protease (N(pro)) region.
Abstract The complete mitochondrial genome of Mekongiella kingdoni, which was collected from the Tibetan Plateau, is determined here. It is 15,932?bp in length and contains 73.1% AT. All M. kingdoni protein-coding sequences except for the cox1 start with a typical ATN codon. Instead, CCG, which is a rare but possible initiation codon, is located at the initiation context of cox1. The usual termination codons (TAA and TAG) and incomplete stop codons (TA or T) are found from 13 PCGs. All tRNA genes can be folded into the typical cloverleaf secondary structure, except trnS(AGN) due to the lacking of dihydrouridine arm. The sizes of the large and small ribosomal RNA genes are 1313 and 837?bp, respectively. The AT content of the A?+?T-rich region is 78.4%.
The combination of docetaxel and gemcitabine is frequently used to treat recurrent bone sarcoma. Nanoparticle albumin-bound paclitaxel (nab-paclitaxel) is less toxic and more active than docetaxel or paclitaxel for breast cancer patients. The combination of nab-paclitaxel and gemcitabine has preclinical synergy and is approved to treat pancreatic cancer. We observed growth inhibition and improved survival with nab-paclitaxel in a Ewing sarcoma xenograft, and activity was additive with gemcitabine in an osteosarcoma model. Primary Ewing sarcoma tumors expressed the transport protein SPARC, previously associated with nab-paclitaxel activity. These findings provide rationale for further evaluation of nab-paclitaxel with gemcitabine for bone sarcoma.
Abstract The complete mitochondrial genome of Gryllotalpa unispina was 15,513?bp in length and contained 70.9% AT. All G. unispina protein-coding sequences except for the nad2 started with a typical ATN codon. The usual termination codons (TAA) and incomplete stop codons (T) were found from 13 protein-coding genes. All tRNA genes were folded into the typical cloverleaf secondary structure, except trnS(AGN) lacking the dihydrouridine arm. The sizes of the large and small ribosomal RNA genes were 1245 and 725?bp, respectively. The A?+?T-rich region was 917?bp in length with 76.8%. The orientation and gene order of the G. unispina mitogenome were identical to the G. orientalis and G. pluvialis, there was no phenomenon of "DK rearrangement" which has been widely reported in Caelifera.
An immunological tick control approach has been proved to be the most promising alternative strategy compared to the current usage of acaricides that suffers from a number of serious limitations. The success of this method is mainly dependent on the identification of tick antigen candidates. Here, the complete sequence of a positive clone Hq15 that we screened from a cDNA library of Haemaphysalis qinghaiensis was cloned by using rapid amplification of cDNA ends. Hq15 contains an open reading frame (ORF) of 1851 bp that codes for 616 amino acid residues with a coding capacity of 61 kDa. The deduced Hq15 amino acid sequence was characterized by a high content of alanine (13.80%), proline (12.82%), glycine (12.18%), threonine (10.71%), and serine (10.06%). Sequence similarity and phylogenetic analyses indicated that Hq15 might encode a novel protein of the tick. Expression analysis by reverse transcription polymerase chain reaction indicated that the gene was expressed in every developmental stage of the tick in its salivary glands, but not in the midgut. The cDNA was expressed as glutathione S-transferase-fused protein in a prokaryotic system. Vaccination of sheep with rHq15 conferred a significant protective immunity in sheep, resulting in a reduction of the amount of eggs laid by each tick compared to the controls. These results show that rHq15 might be one of the candidate vaccine molecules for the control of ticks.
Abstract The complete mitochondrial genome of Orinhippus tibetanus, which was collected from the Tibetan Plateau, is reported here. It is 15,611?bp in length and contains 74.2% AT. All O. tibetanus protein-coding sequences except for the cox1 start with a typical ATN codon. The usual termination codons (TAA or TAG) and incomplete stop codons (T or TA) are found from 13 protein-coding genes. All tRNA genes could be folded into the typical cloverleaf secondary structure, except trnS(AGN) lacking of dihydrouridine (D) arm. The sizes of the large and small ribosomal RNA genes are 1317 and 854?bp, respectively. The AT content of the A?+?T-rich region is 84.8%.
Abstract The complete mitochondrial genome of Peripolus nepalensis, which was collected from the Tibetan Plateau, is reported here. It is 15,858?bp in length and contains 74.3% AT. All P. nepalensis protein-coding sequences start with a typical ATN codon. The usual termination codons (TAA or TAG) and incomplete stop codons (T or TA) were found from 13 protein-coding genes. All tRNA genes could be folded into the typical clover-leaf secondary structure, excluding trnS(AGN) which forms another structure. The sizes of the large and small ribosomal RNA genes were 1324 and 862?bp, respectively. The AT content of the A?+?T-rich region was 83.8%.
We investigated the protective effect of electroacupuncture (EA) on cerebral ischemic injury in diabetic mice, and explored the role of NADPH oxidase-mediated oxidative stress. Male C57BL/6 mice were injected streptozotocin to induce diabetes. The mice were pretreated with EA at acupoint "Baihui" for 30 min. Two hours after the end of EA pretreatment, focal cerebral ischemia was induced following 24h reperfusion. The neurobehavioral scores and infarction volumes, malondialdehyde (MDA), reactive oxygen species (ROS), and activation of NADPH oxidase were determined in the presence or absence of the NADPH oxidase inhibitor apocynin or activator tetrabromocinnamic acid (TBCA). EA pretreatment reduced infarct size and improved neurological outcomes 24h after reperfusion in the diabetic mice. EA also decreased cerebral MDA and ROS levels compared with the control group, and inhibited the NADPH oxidase activation. The beneficial effects were abolished by TBCA while pretreatment with apocynin mimicked the neuroprotective and anti-oxidative effects of EA. Our results demonstrated that EA attenuated cerebral ischemic injury by inhibiting NAPDH oxidase-mediated oxidative damage in diabetic mice. These results suggest a novel mechanism of EA pretreatment-induced tolerance in diabetic cerebral ischemia.
Toxoplasma gondii is an obligate intracellular parasitic protozoan that has a wide host range and causes a zoonotic parasitosis called toxoplasmosis. This infection causes significant morbidity, costs for care and loss of productivity and suffering. The most effective measures to minimize this parasite's harm to patients are prompt diagnosis and treatment and preventing infection. A parasite surface antigen, SAG1, is considered an important antigen for the development of effective diagnostic tests or subunit vaccines. This review covers several aspects of this antigen, including its gene structure, contribution to host invasion, mechanisms of the immune responses and its applications for diagnosis and vaccine development. This significant progress on this antigen provides foundations for further development of more effective and precise approaches to diagnose toxoplasmosis in the clinic, and also have important implications for exploring novel measures to control toxoplasmosis in the near future.
Lhermitte-Duclos disease (LDD) is a rare, non-cancerous entity characterized by enlarged, abnormally developed cerebellar folia containing dysplastic cells. Symptomatic LDD is commonly observed in adults (adult-onset LDD, aLDD) as an isolated condition or associated with Cowden's disease (CD). The present study aimed to investigate the magnetic resonance imaging (MRI) characteristics and the underlying pathological findings in 7 cases of aLDD, with emphasis on the association with CD and the need for active cancer surveillance once the diagnosis of LDD is confirmed. The MRI findings along with the clinical and histopathological data collected from 7 patients with aLDD were retrospectively reviewed. The diagnosis of CD was based on a range of clinical characteristics, according to the International Cowden Consortium Criteria. A thorough review of the published data was conducted and our results indicated that all 7 cases shared similar MRI characteristics, whether the aLDD was sporadic (2 cases) or associated with CD (5 cases), including a highly typical non-enhancing striated MRI appearance of thickened folia, consisting of alternating bands on T1- and T2-weighted images. On gross examination, the involved cerebellar folia were distorted and enlarged, whereas the histopathological examination revealed that the molecular layer was widened and occupied by abnormal ganglion cells. Moreover, a reduction in the number or absence of the Purkinje cells and hypertrophy of the granular cell layer were observed. Our findings were consistent with the diagnosis of LDD. Variable levels of vacuolization of the white matter and the molecular layer were observed in all the cases. Notably, CD34 immunohistochemical analysis revealed the presence of angiogenesis within the lesions. aLDD associated with CD exhibited no pathological or immunohistochemical characteristics that were distinct from those of isolated aLDD. Of the 7 cases of aLDD, 5 presented with symptoms suggestive of CD, which is a syndrome associated with a high risk of multiple benign and malignant neoplasms. In conclusion, aLDD exhibits characteristic MRI and histopathological findings and displays a strong association with CD. Therefore, we recommend that the MRI diagnosis of aLDD triggers active cancer surveillance and preventive care.
Recent studies have demonstrated that wheat peptides protected rats against non-steroidal anti-inflammatory drugs-induced small intestinal epithelial cells damage, but the mechanism of action is unclear. In the present study, an indomethacin-induced oxidative stress model was used to investigate the effect of wheat peptides on the nuclear factor-?B(NF-?B)-inducible nitric oxide synthase-nitric oxide signal pathway in intestinal epithelial cells-6 cells. IEC-6 cells were treated with wheat peptides (0, 125, 500 and 2000 mg/L) for 24 h, followed by 90 mg/L indomethacin for 12 h. Wheat peptides significantly attenuated the indomethacin-induced decrease in superoxide dismutase and glutathione peroxidase activity. Wheat peptides at 2000 mg/L markedly decreased the expression of the NF-?B in response to indomethacin-induced oxidative stress. This study demonstrated that the addition of wheat peptides to a culture medium significantly inhibited the indomethacin-induced release of malondialdehyde and nitrogen monoxide, and increased antioxidant enzyme activity in IEC-6 cells, thereby providing a possible explanation for the protective effect proposed for wheat peptides in the prevention of indomethacin-induced oxidative stress in small intestinal epithelial cells.
Theileria sp. OT3 was firstly detected and identified from clinically healthy sheep in Xinjiang Uygur Autonomous Region of China (XUAR) through comparing the complete 18S rDNA gene sequences available in GenBank database and the phylogenetic status based on the internal transcribed spacers (ITS1, ITS2) as well as the intervening 5.8S coding region of the rRNA gene by the methods of a partitioned multi-locus analysis in BEAST and Maximum likelihood analysis in PhyML. Moreover, the findings were confirmed by the species-specific PCR for Theileria sp. OT3 and the prevalence of Theileria sp. OT3 was 14.9% in the north of XUAR. This study is the first report on the occurrence of Theileria sp. OT3 in China.
Proteins that are post-translationally adducted with 2-(?-carboxyethyl)pyrrole (CEP) have been proposed to play a pathogenic role in age-related macular degeneration, by inducing angiogenesis in a Toll Like Receptor 2 (TLR2)-dependent manner. We have investigated the involvement of CEP adducts in angiogenesis and TLR activation, to assess the therapeutic potential of inhibiting CEP adducts and TLR2 for ocular angiogenesis. As tool reagents, several CEP-adducted proteins and peptides were synthetically generated by published methodology and adduction was confirmed by NMR and LC-MS/MS analyses. Structural studies showed significant changes in secondary structure in CEP-adducted proteins but not the untreated proteins. Similar structural changes were also observed in the treated unadducted proteins, which were treated by the same adduction method except for one critical step required to form the CEP group. Thus some structural changes were unrelated to CEP groups and were artificially induced by the synthesis method. In biological studies, the CEP-adducted proteins and peptides failed to activate TLR2 in cell-based assays and in an in vivo TLR2-mediated retinal leukocyte infiltration model. Neither CEP adducts nor TLR agonists were able to induce angiogenesis in a tube formation assay. In vivo, treatment of animals with CEP-adducted protein had no effect on laser-induced choroidal neovascularization. Furthermore, in vivo inactivation of TLR2 by deficiency in Myeloid Differentiation factor 88 (Myd88) had no effect on abrasion-induced corneal neovascularization. Thus the CEP-TLR2 axis, which is implicated in other wound angiogenesis models, does not appear to play a pathological role in a corneal wound angiogenesis model. Collectively, our data do not support the mechanism of action of CEP adducts in TLR2-mediated angiogenesis proposed by others.
Mammary fat is the main composition of breast, and is the most probable candidate to affect tumor behavior because the fat produces hormones, growth factors and adipokines, a heterogeneous group of signaling molecules. Gene expression profiling and functional characterization of mammary fat in Chinese women has not been reported. Thus, we collected the mammary fat tissues adjacent to breast tumors from 60 subjects, among which 30 subjects had breast cancer and 30 had benign lesions. We isolated and cultured the stromal vascular cell fraction from mammary fat. The expression of genes related to adipose function (including adipogenesis and secretion) was detected at both the tissue and the cellular level. We also studied mammary fat browning. The results indicated that fat tissue close to malignant and benign lesions exhibited distinctive gene expression profiles and functional characteristics. Although the mammary fat of breast tumors atrophied, it secreted tumor growth stimulatory factors. Browning of mammary fat was observed and browning activity of fat close to malignant breast tumors was greater than that close to benign lesions. Understanding the diversity between these two fat depots may possibly help us improve our understanding of breast cancer pathogenesis and find the key to unlock new anticancer therapies.
Epidemiology and transmission patterns of hepatitis C virus (HCV) are important subjects as we enter a new era of treatment with directly acting antivirals (DAAs). The highest prevalence of HCV in developed countries is found among intravenous drug users (IDUs), where unsafe needle sharing practices provide the main route of infection. Efforts to prohibit the continuous spread of HCV among these groups have been initiated by the community services and health care providers. Our goal was to understand how HCV was transmitted among IDUs within a limited population group. We provide a retrospective study (2005-2007) of the HCV transmission patterns in a population of IDUs in the Uppsala region of Sweden.
A novel palladium-catalyzed ortho-C(sp(2))-H olefination protocol has been developed by the use of sulfoxide as the directing group. Importantly, relatively remote coordination can be accessed to achieve the ortho olefination of benzyl, 2-arylethyl, and 3-arylpropenyl sulfoxide substrates, and the olefinated sulfoxide can be easily transformed to other functionalities.
Cancer cells rely on aerobic glycolysis to maintain cell growth and proliferation via the Warburg effect. Phosphoglycerate dehydrogenase (PHDGH) catalyzes the first step of the serine biosynthetic pathway downstream of glycolysis, which is a metabolic gatekeeper both for macromolecular biosynthesis and serine-dependent DNA synthesis. Here, we report that PHDGH is overexpressed in many ER-negative human breast cancer cell lines. PHGDH knockdown in these cells leads to a reduction of serine synthesis and impairment of cancer cell proliferation. However, PHGDH knockdown does not affect tumor maintenance and growth in established breast cancer xenograft models, suggesting that PHGDH-dependent cancer cell growth may be context-dependent. Our findings suggest that other mechanisms or pathways may bypass exclusive dependence on PHGDH in established human breast cancer xenografts, indicating that PHGDH is dispensable for the growth and maintenance and of tumors in vivo.
Introduction: The dysfunctions of three very important monoamine neurotransmitters, serotonin (5-HT), norepinephrine (NE) and dopamine (DA), are associated with some of important CNS diseases such as depression; developing the triple reuptake inhibitors (TRIs) that can rebalance 5-HT, NE and DA through the inhibition of the monoamine reuptake transporters will lead to a more effective and safer antidepressant. Areas covered: This article reviews past 7 years advances in the development of TRIs; a patent review (2006 - 2012), covering the discovery of new chemical entities, and development status of leading TRI clinical candidates. Expert opinion: The development of TRIs has several challenges, including discovering a "single" agent that has the activities against all three monoamine reuptake transporters SERT, NET and DAT. More important is that the agent must have a "right ratio" to be safer and better tolerated for the treatment of depression. The TRIs can potentially be used for the treatment of other CNS diseases, such as pain, Parkinsons and attention deficit hyperactivity disorder (ADHD), depending on ratios of SERT, NET and DAT.
The Eph family of receptor tyrosine kinases and their ephrin ligands are membrane-bound cell-signaling proteins and they play critical regulatory roles in embryonic development and carcinogenesis. Eph receptors require direct cell to cell interaction for activation and they are divided into EphA and EphB receptor classes, depending on their preferential binding affinity for EphrinA or EphrinB ligands. Eph receptors have been documented in breast cancer, but the Ephrin ligands have not been thoroughly investigated.
Poor prognosis of sepsis is associated with bacterial lipopolysaccharide (LPS)-induced intravascular inflammation, microvascular thrombosis, thrombocytopenia, and disseminated intravascular coagulation. Platelets are critical for thrombosis, and there has been increasing evidence of the importance of platelets in endotoxemia. The platelet adhesion receptor, the glycoprotein Ib-IX complex (GPIb-IX), mediates platelet adhesion to inflammatory vascular endothelium and exposed subendothelium. Thus, we have investigated the role of GPIb-IX in LPS-induced platelet adhesion, thrombosis, and thrombocytopenia.
Abstract The complete mitochondrial genome of Xya japonica (Haan, 1842), which was collected from Hebei province of China, is reported here. It is 15,352?bp in length and contains 71.2% AT. All X. japonica protein-coding sequences start with a typical ATN codon except for the cytochrome oxidase subunit I (cox1), which start with CCG. The usual termination codon TAA and TAG were found from 13 protein-coding genes. All tRNA genes have the typical clover leaf structure, excluding trnS(AGN) that lacks the dihydrouracil arm. The sizes of the large and small ribosomal RNA genes are 1289 and 747?bp, respectively. The AT content of the A?+?T-rich region is 75.0%. The orientation and gene order of the X. japonica mitogenome is identical to Ellipes minuta and Gryllotalpa orientalis, there is no phenomenon of "DK rearrangement" which has been wide reported in Caelifera.
NANOGP8 is a retrogene which encodes a full-length protein similar to the NANOG1 gene. The expression of NANOGP8 has been documented in several cancers and is related to cell proliferation and tumor development. However, the regulation of NANOGP8 expression has not been investigated. Therefore, the role of NANOGP8 in cell proliferation has not been completely understood.
A new palladium-catalyzed free-amine directed arylation of C(sp(2))-H bonds in the presence of AgOAc and TFA is described. Biaryl-2-amines react with various aryl iodides to give the corresponding mono- or diarylated products with exclusive regioselectivity.
Infections with Theileria sp. may cause significant economic losses to the sheep industry. Species identification based on microscopic examination is difficult, and more suitable methods are required for the rapid detection and identification of Theileria sp, in clinical specimens. In this study, a multiplex polymerase chain reaction (mPCR) assay was developed to simultaneously identify three individual Theileria species in small ruminants. Three pairs of specific, sensitive primers were designed on the basis of the 5.8S ribosomal RNA gene (Theileria luwenshuni and Theileria ovis) and the 18S ribosomal RNA gene (Theileria uilenbergi) to generate target products of 303, 884, and 530 bp, respectively. Standard DNA for each of the three species was extracted from blood recovered from infected sheep, and a preliminary study was conducted on 56 sheep to verify the reliability of the system. Optimal PCR conditions, including primer concentration, annealing time, and the number of amplification cycles, were established. The assay sensitivity under these conditions was 10(-3) % parasitemia, and its specificity was 100 %. The results of the study suggest that mPCR represents a simple, efficient test method as a practical alternative for the rapid detection and identification of Theileria species in small ruminants.
It has been demonstrated that tachyzoite-pooled excreted-secreted antigens (ESAs) of Toxoplasma gondii are highly immunogenic and can be used in vaccine development. However, most of the information regarding protective immunity induced by immunization with ESAs is derived from studies using mouse model systems. These results cannot be extrapolated to pigs due to important differences in the susceptibility and immune response mechanisms between pigs and mice. We show that the immunization of pigs with ESAs emulsified in Freunds adjuvant induced not only a humoral immune response but also a cellular response. The cellular immune response was associated with the production of IFN-? and IL-4. The humoral immune response was mainly directed against the antigens with molecular masses between 34 and 116 kDa. After intraperitoneal challenge with 10(7) T. gondii of the Gansu Jingtai strain (GJS) of tachyzoites, the immunized pigs remained clinically normal except for a brief low-grade fever (?40.5 °C), while the control pigs developed clinical signs of toxoplasmosis (cough, anorexia, prostration, and high fever). At necropsy, visible lesions were found at multiple locations (enlarged mesenteric lymph nodes, an enlarged spleen with focal necrosis, and enlarged lungs with miliary or focal necrosis and off-white lesions) in all of the control pigs but not in the pigs that had been immunized. We also found that immunization with ESAs reduced tissue cyst formation in the muscle (P < 0.01). Our data demonstrate that immunization with ESAs can trigger a strong immune response against T. gondii infection in pigs.
Newly synthesized epitopes are one of the most promising antigens for the development of diagnostic kits and peptide vaccines. Very little is known about the B cell epitopes on GRA1 of Toxoplasma gondii, which are recognized by the humoral immune response in pigs. In this study, epitopes derived from GRA1 of T. gondii were identified using synthetic peptide techniques and bioinformatics. Three (PG10, PG13 and PG18) out of the eighteen peptides tested were recognized by all pig sera from different time points after infection, and the other peptides were recognized by select sera from various time points after infection. Our data indicate that many regions of GRA1, and in particular, the regions represented by the peptides PG10, PG13 and PG18, are involved in the pig antibody response. The identification of specific epitopes targeted by the host antibody response is important both for understanding the natural response to infection and for the development of epitope-based marker vaccines and diagnostic tools for toxoplasmosis.
We demonstrate a simple and effective approach to control the diameter of ultrathin ZnO nanowires with high aspect ratios and high densities over large areas. Diblock copolymer-based nanoparticle arrays exhibiting a high degree of hexagonal order and offering easy control of particle size (typically 1-10 nm) and interparticle spacing (25-150 nm) are utilized as nanocatalysts for the subsequent growth of semiconductor nanowires. The as-grown ZnO nanowires exhibit a single crystal hexagonal wurtzite structure and grow along the  direction. Facetted catalyst particles were observed at the tip of the nanowires after synthesis, thus suggesting a catalyst-assisted vapor-solid-solid (VSS) rather than a vapor-liquid-solid (VLS) growth mechanism, the latter being frequently used in semiconductor nanowire production. Such a growth process allows us to easily prepare ultrathin ZnO nanowires with tunable diameters well below 10 nm by taking advantage of the inherent size control of the micellar method during deposition of the catalyst nanoparticles. Raman spectroscopy reveals a phonon confinement effect as the diameter of nanowires decreases. Photoluminescence spectra of these ultrathin nanowires indicate a blue shift of the free excitons and their phonon replicas by 37 meV induced by quantum confinement.
To investigate the changes in arterial oxygenation and intrapulmonary shunt during one-lung ventilation (OLV) with intravenous infusion of dexmedetomidine combined with isoflurane inhalation. ASA I-II 60 patients aged 18-70 year, undergoing OLV during elective thoracic surgery were randomly allocated to two groups: (1) isoflurane + saline (group NISO, n = 30) and (2) isoflurane + dexmedetomidine (group DISO, n = 30). After induction, anesthesia was maintained with intravenous infusion of remifentanil 0.1-0.2 ?g kg(-1) min(-1) and inhalation isoflurane (1.0-2.0 %). In addition, anesthesia was maintained with intravenous infusion of dexmedetomidine 0.7 ?g kg(-1) h(-1) in DISO group and saline 0.25 ml kg(-1) h(-1) in NISO group. Bispectral Index values were maintained within 40-60 by changing the concentration of isoflurane in all groups. Arterial blood gas samples and central venous blood gas samples were taken as follows: during two-lung ventilation before OLV and during the first 40 min of OLV. 45 Patients completed the study, with 23 patients in DISO group and 22 patients in NISO group. The two groups were comparable in terms of demographic variables, hemodynamic, PaO2, Qs/QT, end expiration isoflurane and BIS levels during the operation. Compared with patients in the group NISO, there were significant increases with PaO2, significant decrease with Qs/QT, significant decrease with end expiration isoflurane, and significant decrease with HR in the group DISO during the first 40 min of OLV (P < 0.05). Dexmedetomidine infusions decrease the requirement for isoflurane, decrease intrapulmonary shunt, and moderate the change in PaO2 and may be useful in managing OLV.
Mammography has been confirmed as the only effective mode to improve the prognosis of patients with breast cancer in Western developed countries, but might not be a good choice in other areas of the world. One of the major challenges in China is to determine an optimal imaging modality for breast cancer screening. This study was designed to clarify the sensitivity of ultrasonography compared with that of mammography in rural China.
Foot-and-mouth disease virus (FMDV) causes a highly contagious infection in cloven-hoofed animals. The format of FMD virus-like particles (VLP) as a non-replicating particulate vaccine candidate is a promising alternative to conventional inactivated FMDV vaccines. In this study, we explored a prokaryotic system to express and assemble the FMD VLP and validated the potential of VLP as an FMDV vaccine candidate. VLP composed entirely of FMDV (Asia1/Jiangsu/China/2005) capsid proteins (VP0, VP1 and VP3) were simultaneously produced as SUMO fusion proteins by an improved SUMO fusion protein system in E. coli. Proteolytic removal of the SUMO moiety from the fusion proteins resulted in the assembly of VLP with size and shape resembling the authentic FMDV. Immunization of guinea pigs, swine and cattle with FMD VLP by intramuscular inoculation stimulated the FMDV-specific antibody response, neutralizing antibody response, T-cell proliferation response and secretion of cytokine IFN-?. In addition, immunization with one dose of the VLP resulted in complete protection of these animals from homologous FMDV challenge. The 50% protection dose (PD50) of FMD VLP in cattle is up to 6.34. These results suggest that FMD VLP expressed in E. coli are an effective vaccine in guinea pigs, swine and cattle and support further development of these VLP as a vaccine candidate for protection against FMDV.
Babesiosis is a frequent infection of animals worldwide by tick borne pathogen Babesia, and several species are responsible for ovine babesiosis. Recently, several Babesia motasi-like isolates were described in sheep in China. In this study, we sequenced the multigenic rap-1 gene locus of one of these isolates, Babesia sp. BQ1 Lintan. The RAP-1 proteins are involved in the process of red blood cells invasion and thus represent a potential target for vaccine development. A complex composition and organization of the rap-1 locus was discovered with: (1) the presence of 3 different types of rap-1 sequences (rap-1a, rap-1b and rap-1c); (2) the presence of multiple copies of rap-1a and rap-1b; (3) polymorphism among the rap-1a copies, with two classes (named rap-1a61 and rap-1a67) having a similarity of 95.7%, each class represented by two close variants; (4) polymorphism between rap-1a61-1 and rap-1a61-2 limited to three nucleotide positions; (5) a difference of eight nucleotides between rap-1a67-1 and rap-1a67-2 from position 1270 to the putative stop site of rap-1a67-1 which might produce two putative proteins of slightly different sizes; (6) the ratio of rap-1a copies corresponding to one rap-1a67, one rap-1a61-1 and one rap-1a61-2; (7) the presence of three different intergenic regions separating rap-1a, rap-1b and rap-1c; (8) interspacing of the rap-1a copies with rap-1b copies; and (9) the terminal position of rap-1c in the locus. A 31kb locus composed of 6 rap-1a sequences interspaced with 5 rap-1b sequences and with a terminal rap-1c copy was hypothesized. A strikingly similar sequence composition (rap-1a, rap-1b and rap-1c), as well as strong gene identities and similar locus organization with B. bigemina were found and highlight the conservation of synteny at this locus in this phylogenetic clade.
The excitation power dependence of radiative transitions in the type-II GaSb/GaAs quantum dots structure has been studied by the photoluminescence (PL) at different temperatures. The QDs photoluminescence exhibits a strong blue-shift with increasing the excitation power and the peak energy (E(PL)) is proportional to the third root of excitation power. With the increase of excitation power, the nonlinear change for both the PL peak and the intensity was observed, which is attributed to the excited state transition. The thermal process and activation energy (E(a)) of electron-hole pairs at different excitation powers has also been studied for GaSb QDs. As the excitation power increases, the activation energy decreases, while E(PL) +E(a) keeps nearly constant, which is smaller than the band gap of GaAs. The decrease of E(a) is probably caused by the band bending effect.
Various genospecies of Borrelia burgdorferi sensu lato (s.l.) have been identified from patients and animals worldwide. Genospecies-related dissemination of disease has been reported. The present study aimed to elucidate the pathogenicity of infections caused by B. garinii SZ isolated in China. B. burgdorferi B31 and B. afzelii BO23 were used for comparison.
A loop-mediated isothermal amplification (LAMP) assay allows rapid diagnosis of Toxoplasma gondii infection. In the present study, the LAMP assay was evaluated using blood from both naturally and experimentally infected pigs. The sensitivity of the LAMP assay was compared with that of Q-PCR. Both assays detected T. gondii in the blood of experimentally infected pigs, with 100% agreement. In infected blood samples, the parasite was detected as early as 2 days post-infection and reached a peak in 3-5 days. In 216 field serum samples, the detection rates of LAMP and Q-PCR assays were 6.9% and 7.8%, respectively. This result indicates that the sensitivity of the LAMP assay was slightly lower than that of the Q-PCR assay. However, the LAMP may be an attractive diagnostic method in conditions where sophisticated and expensive equipment is unavailable. This assay could be a powerful supplement to current diagnostic methods.
A total of 16 Taenia multiceps isolates collected from naturally infected sheep or goats in Gansu Province, China were characterized by sequences of mitochondrial cytochrome c oxidase subunit 1 (cox1) gene. The complete cox1 gene was amplified for individual T. multiceps isolates by PCR, ligated to pMD18T vector, and sequenced. Sequence analysis indicated that out of 16 T. multiceps isolates 10 unique cox1 gene sequences of 1,623 bp were obtained with sequence variation of 0.12-0.68%. The results showed that the cox1 gene sequences were highly conserved among the examined T. multiceps isolates. However, they were quite different from those of the other Taenia species. Phylogenetic analysis based on complete cox1 gene sequences revealed that T. multiceps isolates were composed of 3 genotypes and distinguished from the other Taenia species.
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