The analysis of bodily fluids using SELDI-TOF MS has been reported to identify signatures of spectral peaks that can be used to differentiate patients with a specific disease from normal or control patients. This report is the 2nd of 2 companion articles describing a validation study of a SELDI-TOF MS approach with IMAC surface sample processing to identify prostatic adenocarcinoma.
We sought to derive a decision algorithm for classification of prostate cancer from SELDI-TOF MS spectral data from a new retrospective sample cohort of 400 specimens. This new cohort was selected to minimize possible confounders identified in the previous study described in the companion paper.
The resulting new classifier failed to separate patients with prostate cancer from biopsy-negative controls; nor did it separate patients with prostate cancer with Gleason scores <7 from those with Gleason scores ≥7.
In this, the 2nd stage of our planned validation process, the SELDI-TOF MS– based protein expression profiling approach did not perform well enough to advance to the 3rd (prospective study) stage. We conclude that the results from our previous studies—in which differentiation between prostate cancer and noncancer was demonstrated—are not generalizable. Earlier study samples likely had biases in sample selection that upon removal, as in the present study, resulted in inability of the technique to discriminate cancer from non-cancer cases.
Clostridium botulinum produces heat-resistant endospores that may germinate and outgrow into neurotoxic cultures in foods. Sporulation is regulated by the transcription factor Spo0A and the alternative sigma factors SigF, SigE, SigG, and SigK in most spore formers studied to date. We constructed mutants of sigF, sigE, and sigG in C. botulinum ATCC 3502 and used quantitative reverse transcriptase PCR and electron microscopy to assess their expression of the sporulation pathway on transcriptional and morphological levels. In all three mutants the expression of spo0A was disrupted. The sigF and sigE mutants failed to induce sigG and sigK beyond exponential-phase levels and halted sporulation during asymmetric cell division. In the sigG mutant, peak transcription of sigE was delayed and sigK levels remained lower than that in the parent strain. The sigG mutant forespore was engulfed by the mother cell and possessed a spore coat but no peptidoglycan cortex. The findings suggest that SigF and SigE of C. botulinum ATCC 3502 are essential for early sporulation and late-stage induction of sigK, whereas SigG is essential for spore cortex formation but not for coat formation, as opposed to previous observations in B. subtilis sigG mutants. Our findings add to a growing body of evidence that regulation of sporulation in C. botulinum ATCC 3502, and among the clostridia, differs from the B. subtilis model.
To evaluate the role of intensity modulated radiotherapy (IMRT) for locally advanced pancreatic cancer (LAPC) and metastatic pancreatic cancer (MPC), and the prognostic factors in the setting of multidisciplinary approach strategies.
63 patients with LAPC and MPC receiving IMRT in our institution were retrospectively identified. Information on patient baseline, treatment characteristics and overall survival (OS) time were collected. Data of pain relief and toxicity were evaluated. Univariate and multivariate analyses were conducted to investigate the prognostic factors.
All patients received IMRT with a median dose of 46.0 Gy. The median OS for LAPC and MPC patients were 15.7 months and 8.0 months, respectively (p = 0.029). Symptomatic improvements were observed in the 44 patients with abdominal/back pain after radiotherapy (RT) or concurrent chemoradiotherapy (CCRT), particularly in those with severe pain. Only 13.9% and 14.8% cases presented Grade ≥ 3 hematologic toxicities in RT and CCRT group, while no cases developed Grade ≥ 3 non-hematologic toxicities in both groups. Multivariate analysis indicated that tumors located in pancreas body/tail (HR 0.28, p = 0.008), pretreatment CA19-9 < 1000 U/mL (HR 0.36, p = 0.029) and concurrent chemotherapy (HR 0.37, p = 0.016) were independent favorable predictors for OS.
CCRT further improved OS for LAPC and MPC with acceptable toxicities, and use of RT markedly alleviated pain. Tumors located in pancreas body/tail, pretreatment CA19-9 level of < 1000 U/mL and CCRT were associated with better OS. However, regional intra-arterial chemotherapy did not show any survival benefit in our study.
Locally advanced pancreatic cancer; Metastatic pancreatic cancer; Concurrent chemoradiotherapy; Intensity modulated radiotherapy; Regional intra-arterial chemotherapy
A novel recombinant coxsackievirus A6 (CVA6) strain was isolated during a coxsackievirus A6 outbreak in Shanghai, China, in 2013. Genomic sequence and similarity plot analysis showed that the novel CVA6 strain shared higher similarity with a recent CVA4 strain rather than the recent CVA6 strain in the 2C and 3′ untranslated regions (UTRs).
Engineered nanomaterials (ENM) have desirable properties that make them well suited for many commercial applications. However, a limited understanding of how ENM’s properties influence their molecular interactions with biomembranes hampers efforts to design ENM that are both safe and effective. This paper describes the use of a tethered bilayer lipid membrane (tBLM) to characterize biomembrane disruption by functionalized silica-core nanoparticles. Electrochemical impedance spectroscopy was used to measure the time trajectory of tBLM resistance following nanoparticle exposure. Statistical analysis of parameters from an exponential resistance decay model was then used to quantify and analyze differences between the impedance profiles of nanoparticles that were unfunctionalized, amine-functionalized, or carboxyl-functionalized. All of the nanoparticles triggered a decrease in membrane resistance, indicating nanoparticle-induced disruption of the tBLM. Hierarchical clustering allowed the potency of nanoparticles for reducing tBLM resistance to be ranked in the order amine > carboxyl ~ bare silica. Dynamic light scattering analysis revealed that tBLM exposure triggered minor coalescence for bare and amine-functionalized silica nanoparticles but not for carboxyl-functionalized silica nanoparticles. These results indicate that the tBLM method can reproducibly characterize ENM-induced biomembrane disruption and can distinguish the BLM-disruption patterns of nanoparticles that are identical except for their surface functional groups. The method provides insight into mechanisms of molecular interaction involving biomembranes and is suitable for miniaturization and automation for high-throughput applications to help assess the health risk of nanomaterial exposure or identify ENM having a desired mode of interaction with biomembranes.
silica nanoparticle; lipid bilayer; electrochemical impedance; resistance; aggregation
Oct4 is critical to maintain the pluripotency of human embryonic stem cells (hESCs), however, the underlying mechanism remains to be fully understood. Here we report that silencing of Oct4 in hESCs leads to the activation of tumor suppressor p53, inducing the differentiation of hESCs since acute disruption of p53 in p53 conditional knockout (p53CKO) hESCs prevents the differentiation of hESCs after Oct4 depletion. We further discovered that the silencing of Oct4 significantly reduces the expression of Sirt1, a deacetylase known to inhibit p53 activity and the differentiation of ESCs, leading to increased acetylation of p53 at lysine 120 and 164. The importance of Sirt1 in mediating Oct4-dependent pluripotency is revealed by the finding that the ectopic expression of Sirt1 in Oct4-silenced hESCs prevents p53 activation and hESC differentiation. In addition, employing knock-in approach, we revealed that the acetylation of p53 at lysine 120 and 164 is required for both stabilization and activity of p53 in hESCs. In summary, our findings reveal a novel role of Oct4 in maintaining the pluripotency of hESCs by suppressing pathways that induce differentiation. Considering that p53 suppresses pluripotency after DNA damage response in ESCs, our findings further underscore the stringent mechanism to coordinate DNA damage response pathways and pluripotency pathways in order to maintain the pluripotency and genomic stability of hESCs.
pluripotency; differentiation; human ES cells; DNA damage response; p53; acetylation
Background: Clinically, it is still challenging to differentiate aggressive from non-aggressive prostate cancers (Pca) by non-invasive approaches. Our recent studies showed that overexpression of alpha (1-6) fucosyltransferase played an important role in Pca cells. In this study, we have investigated levels of glycoproteins and their fucosylated glycoforms in sera of Pca patients, as well as the potential utility of fucosylated glycoproteins in the identification of aggressive Pca.
Material and Methods: Serum samples from histomorphology-proven Pca cases were included. Prostate-specific antigen (PSA), tissue inhibitor of metallopeptidase 1 (TIMP1) and tissue plasminogen activator (tPA), and their fucosylated glycoforms were captured by Aleuria Aurantia Lectin (AAL), followed by the multiplex magnetic bead-based immunoassay. The level of fucosylated glycoproteins was correlated with patients' Gleason score of the tumor.
Result: Among three fucosylated glycoproteins, the fucosylated PSA was significantly increased and correlated with the tumor Gleason score (p<0.05). The ratio of fucosylated PSA showed a marked increase in aggressive tumors in comparison to non-aggressive tumors. ROC analysis also showed an improved predictive power of fucosylated PSA in the identification of aggressive Pca.
Conclusions: Our data demonstrated that fucosylated PSA has a better predictive power to differentiate aggressive tumors from non-aggressive tumors, than that of native PSA and two other glycoproteins. The fucosylated PSA has the potential to be used as a surrogate biomarker.
prostate cancer; multiplex immunoassay; fucosylated glycoprotein; prostate-specific antigen; TIMP1.
Hantavirus; seroprevalence; shrew; rodent; China; viruses
Although many epidemiology studies have investigated the methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and their associations with lung cancer (LC), definite conclusions cannot be drawn. To clarify the effects of MTHFR polymorphisms on the risk of LC, we performed a meta-analysis in Chinese populations.
Related studies were identified from PubMed, Springer Link, Ovid, Chinese Wanfang Data Knowledge Service Platform, Chinese National Knowledge Infrastructure (CNKI), and Chinese Biology Medicine (CBM) until 16 February 2014. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to assess the strength of the associations.
A total of 11 studies with 2487 LC cases and 3228 controls were included in this meta-analysis. Overall, no significant association was found between MTHFR C677T polymorphism and LC risk when all studies in Chinese populations were pooled into this meta-analysis. In subgroup analyses stratified by geographical location and source of controls, significantly increased risk was found in North China (T vs. C: OR=1.28, 95% CI: 1.14–1.44; TT vs. CC: OR=1.67, 95% CI: 1.33–2.10; TT + CT vs. CC, OR=1.39, 95% CI=1.15–1.69; TT vs. CC + CT: OR=1.46, 95% CI: 1.03–2.06) and in population-based studies (TT vs. CC: OR=1.37, 95% CI: 1.14–1.65; TT vs. CC + CT: OR=1.25, 95% CI: 1.07–1.45).
This meta-analysis provides evidence that MTHFR C677T polymorphism may contribute to LC development in North China. Studies with larger sample sizes and wider spectrum of populations are warranted to verify this finding.
5,10-Methylenetetrahydrofolate Reductase (FADH2); Lung Neoplasms; Meta-Analysis
The neutrophil-lymphocyte ratio (NLR) has been proposed as an indicator of systemic inflammatory response and may predict the clinical outcome in some cancers, such as head and neck cancer and gastric cancer. However, the value of this ratio is variable in different cancers. Studies of the relationship between NLR and both survival and response to chemoradiation have been limited with respect to locally advanced rectal cancer.
Methods and materials
From 2006 to 2011, 199 consecutive locally advanced rectal cancer patients who were treated with neoadjuvant chemoradiation in the Shanghai Cancer Center were enrolled and analysed retrospectively. Tumor response was evaluated by pathological findings. The baseline total white blood cell count (WBC) and the neutrophil, lymphocyte, platelet counts were recorded. The neutrophil-lymphocyte ratio (NLR) and the relationship with clinical outcomes such as overall survival (OS) and disease-free survival (DFS) was analyzed.
With ROC analysis, the baseline NLR value was found to significantly predict prognosis in terms of OS well in locally advanced rectal cancer patients. A multivariate analysis identified that a cut-off value of NLR ≥ 2.8 could be used as an independent factor to indicate decreased OS (HR, 2.123; 95% CI, 1.140-3.954; P = 0.018). NLR ≥ 2.8 was also associated with worse DFS in univariate analysis (HR, 1.662; 95% CI, 1.037-2.664; P = 0.035), though it was not significant in the multivariate analysis (HR, 1.363; 95% CI, 0.840-2.214; P = 0.210). There was no observed significant correlation of mean value of NLR to the response to neoadjuvant chemoradiation. The mean NLR in the ypT0-2 N0 group was 2.68 ± 1.38, and it was 2.77 ± 1.38 in the ypT3-4/N+ group, with no statistical significance (P = 0.703). The mean NLR in the TRG 0–1 group was 2.68 ± 1.42, and it was 2.82 ± 1.33 in the TRG 2–3 group with no statistical significance (P = 0.873).
An elevated baseline NLR is a valuable and easily available prognostic factor for OS in addition to tumor response after neoadjuvant therapy. Baseline NLR could be a useful candidate factor for stratifying patients and making treatment decisions in locally advanced rectal cancer.
Rectal cancer; Neoadjuvant chemoradiation; Neutrophil-lymphocyte ratio
Aims: To investigate the clinical significance of Tbx3 in colorectal cancer (CRC) and the possible association between Tbx3 expression and Epithelial- Transition Mesenchymal (EMT) phenotype. Methods: Quantitative real-time reverse transcription polymerase chain reaction (qRT-PCR) and western blotting were employed to evaluate the expression of Tbx3 in 30 fresh CRC and matched normal tissues. Using immunochemistry, protein level of Tbx3 and EMT markers (E-cadherin and N-cadherin) were identified in 150 pairs of paraffin-embedded specimen. Results: The results of qRT-PCR and western blotting showed that Tbx3 expression was higher in CRC tissues than in corresponding normal tissues. The statistical analysis based on immunohistochemical evaluation suggested that Tbx3 aberrant expression was significantly associated with tumor size (P=0.049), differentiation (P=0.032), invasion (P=0.019), lymph node metastasis (P=0.049) and TNM stage (P=0.018). Patients who displayed high expression of Tbx3 may achieve a poorer overall survival (OS) and disease-free survival (DFS), compared to those with low expression of Tbx3. This tendency was also observed in patients with intermediate levels of disease (II and III stage). The multivariate analysis indicated Tbx3 expression could independently predict the outcome of CRC patients. Interestingly, correlation analysis suggested Tbx3 expression was negatively correlated with E-cadherin expression, but positively correlated with N-cadherin expression. Conclusion: Tbx3 may promote CRC progression by involving EMT program and has the potential to be an effective prognostic predictor for CRC patients.
Tbx3; Epithelial-Mesenchymal Transition; colorectal cancer; prognosis; biomarker
This study was conducted to investigate the local effects and toxicity of accelerated hyperfractionated intensity-modulated radiotherapy for recurrent/unresectable rectal cancer in patients with previous pelvic irradiation.
Twenty-two patients with recurrent/unresectable rectal cancer who previously received pelvic irradiation were enrolled in our single-center trial between January 2007 and August 2012. Reirradiation was scheduled for up to 39 Gy in 30 fractions using intensity-modulated radiotherapy plans. The dose was delivered via a hyperfractionation schedule of 1.3 Gy twice daily. Patient follow-up was performed by clinical examination, CT/MRI, or PET/CT every 3 months for the first 2 years and every 6 months thereafter. Tumor response was evaluated 1 month after reirradiation by CT/MRI based on the RECIST criteria. Adverse events were assessed using the National Cancer Institute (NCI) common toxicity criteria (version 3.0).
The median time from the end of the initial radiation therapy to reirradiation was 30 months (range, 18-93 months). Overall local responses were observed in 9 patients (40.9%). None of the patients achieved a complete response (CR), and 9 patients (40.9%) had a partial response (PR). Thirteen patients failed to achieve a clinical response: 12 (54.5%) presented with stable disease (SD) and 1 (4.5%) with progressive disease (PD). Among all the patients who underwent reirradiation, partial or complete symptomatic relief was achieved in 6 patients (27.3%) and 13 patients (59.1%), respectively. Grade 4 acute toxicity and treatment-related deaths were not observed. The following grade 3 acute toxicities were observed: diarrhea (2 patients, 9.1%), cystitis (1 patient, 4.5%), dermatitis (1 patient, 4.5%), and intestinal obstruction (1 patient, 4.5%). Late toxicity was infrequent. Chronic severe diarrhea, small bowel obstruction, and dysuria were observed in 2 (9.1%), 1 (4.5%) and 2 (9.1%) of the patients, respectively.
This study showed that accelerated hyperfractionated intensity-modulated radiotherapy significantly relieved local symptoms and led to a promising local response with an acceptable toxicity profile in patients with recurrent/unresectable rectal cancer and previous pelvic irradiation. Innovative treatment regimens should be evaluated in future studies to improve the clinical outcome while avoiding excessive toxicity in patients with recurrent rectal cancer and previous pelvic irradiation.
Rectal cancer; Local recurrence; Reirradiation; Hyperfractionation; Intensity-modulated radiotherapy
Protein glycosylation has long been recognized as one of the most common post-translational modifications. Most membrane proteins and extracellular proteins are N-linked glycosylated and they account for the majority of current clinical diagnostic markers or therapeutic targets. Quantitative proteomic analysis of detectable N-linked glycoproteins from cells or tissues using mass spectrometry has the potential to provide biological basis for disease development and identify disease associated glycoproteins. However, the information of low abundance but important peptides is lost due to the lack of MS/MS fragmentation or low quality of MS/MS spectra for low abundant peptides. Here, we show the feasibility of formerly N-glycopeptide identification and quantification at MS1 level using genomic N-glycosite prediction (GenoGlyco) coupled with stable isotopic labeling and accurate mass matching. The GenoGlyco Analyzer software uses accurate precursor masses of detected N-deglycopeptide peaks to match them to N-linked deglycopeptides which are predicted from genes expressed in the cells. This method results in more robust glycopeptide identification compared to MS/MS based identification. Our results showed that over three times the quantity of N-deglycopeptide assignments from the same mass spectrometry data could be produced in ovarian cancer cell lines compared to a MS/MS fragmentation method. Furthermore, the method was also applied to N-deglycopeptide analysis of ovarian tumors using the identified deglycopeptides from the two ovarian cell lines as heavy standards. We show that the described method has a great potential in the analysis of detectable N-glycoproteins from cells and tissues.
glycosylation; prediction; genome-wide; SILAC; accurate mass matching; ovarian cancer; mass spectrometry
To evaluate the role of small mammals as hosts of severe fever with thrombocytopenia syndrome virus (SFTSV), we tested serum samples from rodents and shrews in China, collected in 2013. SFTSV antibodies and RNA were detected, suggesting that rodents and shrews might be hosts for SFTSV.
severe fever with thrombocytopenia syndrome virus; SFTS virus; bunyavirus; seroprevalence; shrews; rodents; viruses; animal hosts; China
We reported the case of a 70-year-old man who was admitted to neurologic wards for recurrent syncope for 3 years. Unfortunately, just 2 hours after his admission, he suddenly collapsed and failed to return of spontaneous circulation (ROSC) after a 100-minute standard cardiopulmonary resuscitation (CPR). Fortunately, he was timely suspected to have pulmonary embolism (PE) based on his sedentary lifestyle, elevated D-dimer and markedly enlarged right ventricle chamber on bedside echocardiography. After a rescue thrombolytic alteplase therapy, he was successfully resuscitated and good neurological recovery was achieved.
Cardiac arrest; pulmonary embolism (PE); thrombolysis
Applying Ethosomal Gels (EGs) in transdermal drug delivery systems has evoked considerable interest because of their good water-solubility and biocompatibility. However, there has not been an explicit description of applying EGs as a vehicle for hypertrophic scars treatment. Here, a novel transdermal EGs loaded with 5-fluorouracil (5-FU EGs) was successfully prepared and characterized. The stability assay in vitro revealed that 5-FU EGs stored for a period of 30 days at 4 ± 1 °C had a better size stability than that at 25 ± 1 °C. Furthermore, using confocal laser scanning microscopy, EGs labeled with Rhodamine 6 G penetrated into the deep dermis of the hypertrophic scar within 24 h in the rabbit ear hypertrophic model suggested that the EGs were an optional delivery carrier through scar tissues. In addition, the value of the Scar Elevation Index (SEI) of 5-FU EGs group in the rabbit ear scar model was lower than that of 5-FU Phosphate Buffered Saline gel and Control groups. To conclude, these results suggest that EGs delivery system loaded 5-fluorouracil is a perfect candidate drug for hypertrophic scars therapy in future.
drug delivery; ethosome; 5-fluorouracil; gel; hypertrophic scars penetration
Objective: LGGs (low-grade gliomas) are sometimes encountered by chance during radiological examinations. These incidentally discovered LGGs (IDLGGs) were relatively under-studied in the literature. The purpose of current study is to review a cohort of patients with IDLGGs surgically treated in our institution for their clinical and histological aspects and determine their IDH1 and 1p19q status. Methods: All patients with hemispheric LGGs receiving operation in our institution between 2001 and 2004 were reviewed. Clinical, radiological and treatment data of the patients were collected and IDLGGs were retrieved and compared with symptomatic LGGs. Histological review was carried out and formalin-fixed paraffin embedded (FFPE) tissues of IDLGGs were examined for IDH1/IDH2 mutation and 1p/19q codeletion. Results: Twenty three IDLGGs (10.4%) were identified while 196 patients had symptomatic LGGs. The reasons for patients with IDLGGs having radiological examination included trauma (47.8%), dizziness (26.1%), unrelated headache (21.7%), and health checkup (4.4%). Clinically, patients with IDLGGs had higher preoperative KPS (P < 0.001), smaller tumor volume (P = 0.014), lower frequency of eloquent areas involvement (P < 0.001) and higher rate of complete resection (P = 0.037) comparing to those with symptomatic LGGs. Histologically, there is a preponderance of oligodendroglial differentiation with 6 oligodendrogliomas and 11 oligoastrocytomas but there were also 6 astrocytomas. IDH1 mutation and 1p/19q co-deletion were detected in 95.7% (22/23) and 69.6% (16/23) of IDLGGs, respectively. The latter encompassed all but one of the cases of oligodendroglial tumors. Patients with IDLGGs had longer overall survival than those with symptomatic LGGs (P = 0.027). Conclusions: We conclude that the majority of IDLGGs are IDH1 mutated and are predominantly oligodendroglial tumors. With a median follow-up of 9.3 years to our series, we conclude that patients with IDLGGs had better prognosis than those with symptomatic LGGs. The favorable prognosis of IDLGGs may be accounted by the higher practicability of extensive resection, non-eloquent tumor location and smaller tumor volume. Frequent IDH1 mutation and 1p/19q co-deletion in IDLGGs may also contribute to the favorable prognosis of this subgroup of patients.
Low-grade glioma; incidental; surgery; pathology; prognosis
Both the gene expression and activity of water channel protein can control transmembrane water movement. We have reported the overexpression of CaTIP1-1, which caused a decrease in chilling tolerance in transgenic plants by increasing the size of the stomatal pore. CaTIP1-1 expression was strongly induced by salt and mannitol stresses in pepper (Capsicum annuum). However, its biochemical and physiological functions are still unknown in transgenic tobacco. In this study, transient expression of CaTIP1-1-GFP in tobacco suspension cells revealed that the protein was localized in the tonoplast. CaTIP1-1 overexpressed in radicle exhibited vigorous growth under high salt and mannitol treatments more than wild-type plants. The overexpression of CaTIP1-1 pepper gene in tobacco enhanced the antioxidant enzyme activities and increased transcription levels of reactive oxygen species-related gene expression under osmotic stresses. Moreover, the viability of transgenic tobacco cells was higher than the wild-type after exposure to stress. The pepper plants with silenced CaTIP1-1 in P70 decreased tolerance to salt and osmotic stresses using the detached leaf method. We concluded that the CaTIP1-1 gene plays an important role in response to osmotic stresses in tobacco.
osmotic stress; antioxidant enzymes; Capsicum annuum L.; CaTIP1-1; tobacco
To assess the antiviral efficacy of lamivudine (LAM), entecavir (ETV), telbivudine (LDT), and lamivudine and adefovir dipivoxil (CLA) combination in previously untreated hepatitis B patients at different time points during a 52-week treatment period.
Patients and Methods:
A total of 164 patients were included in this prospective, open-label, head-to-head study. Serum levels of alanine transaminase (ALT), hepatitis B virus (HBV) DNA, and hepatitis B e antigen (HBeAg) were measured at baseline, and at 12, 24, and 52 weeks of treatment.
Median reductions in serum HBV DNA levels at 52 weeks (log10 copies/mL) were as follows: LAM, 3.98; ETV, 3.89; LDT, 4.11; and CLA, 3.36. The corresponding HBV DNA undetectability rates were 83%, 96%, 91%, and 89%, respectively. These two measures showed no significant intergroup differences. Clinical efficacy appeared related to HBV DNA level reduction after 24 weeks of therapy. Patients were divided into three groups based on HBV DNA levels at week 24: Undetectable (<103 copies/mL), detectable but <104 copies/mL, and >104 copies/mL. Patients with levels below quantitation limit (QL) were analyzed at 52 weeks for HBV DNA undetectability rate (94%), ALT normalization rate (83%), and viral breakthrough rate (0%). The corresponding values in the QL-104 copies/mL group were 50%, 75%, and 13%, whereas those in the above 104 copies/mL group were 53%, 65%, and 18%. There were significant differences at week 52 for HBV DNA levels and viral breakthrough rate between the three groups.
Different nucleos(t)ide (NUC) analogues tested exhibited no significant differences in effectiveness for Chinese NUC-naive HBV patients during 1-year treatment period.
Adefovir dipivoxil; antiviral therapy; chronic hepatitis B; entecavir; lamivudine; telbivudine
Dopamine neurons in the ventral tegmental area (VTA) govern reward and motivation and dysregulated dopaminergic transmission may account for anhedonia and other symptoms of depression. Cyclin-dependent kinase 5 (Cdk5) is a proline-directed serine/threonine kinase that regulates a broad range of brain functions through phosphorylation of a myriad of substrates, including tyrosine hydroxylase (TH), the rate-limiting enzyme for dopamine synthesis. We investigated whether and how Cdk5 activity in VTA dopamine neurons regulated depression-related behaviors in mice. Using the Cre/LoxP system to selectively delete Cdk5 in the VTA or in midbrain dopamine neurons in Cdk5loxP/loxP mice, we showed that Cdk5 loss of function in the VTA induced anxiety- and depressive-like behaviors that were associated with decreases in TH phosphorylation at Ser31 and Ser40 in the VTA and dopamine release in its target region, the nucleus accumbens. The decreased phosphorylation of TH at Ser31 was a direct effect of Cdk5 deletion, whereas decreased phosphorylation of TH at Ser40 was likely caused by impaired cAMP/protein kinase A (PKA) signaling, because Cdk5 deletion decreased cAMP and phosphorylated cAMP response element-binding protein (p-CREB) levels in the VTA. Using Designer Receptors Exclusively Activated by Designer Drugs (DREADD) technology, we showed that selectively increasing cAMP levels in VTA dopamine neurons increased phosphorylation of TH at Ser40 and CREB at Ser133 and reversed behavioral deficits induced by Cdk5 deletion. The results suggest that Cdk5 in the VTA regulates cAMP/PKA signaling, dopaminergic neurotransmission, and depression-related behaviors.
cAMP; Cdk5; depression; dopamine; DREADD; tyrosine hydroxylase
Since Feb, 2013, more than 100 human beings had been infected with novel H7N9 avian influenza virus. As of May 2013, several H7N9 viruses had been found in retail live bird markets (LBMs) in Guangdong province of southern China where several human cases were confirmed later. However, the real avian influenza virus infection status especially H7N9 in Guangzhou remains unclear. Therefore, a cross-sectional study of avian influenza in commercial poultry farms, the wholesale LBM and retail LBMs in one district of Guangzhou was conducted from October to November, 2013. A total of 1505 cloacal and environmental samples from 52 commercial poultry farms, 1 wholesale LBM and 18 retail LBMs were collected and detected using real-time RT-PCR for type A, H7, H7N9 and H9 subtype avian influenza virus, respectively. Of all the flocks randomly sampled, 6 farms, 12 vendors of the wholesale LBM and 18 retail LBMs were type A avian influenza virus positive with 0, 3 and 11 positive for H9, respectively. The pooled prevalence and individual prevalence of type A avian influenza virus were 33.9% and 7.9% which for H9 subtype was 7.6% and 1.6%, respectively. None was H7 and H7N9 subtype virus positive. Different prevalence and prevalence ratio were found in different poultry species with partridges having the highest prevalence for both type A and H9 subtype avian influenza virus. Our results suggest that LBM may have a higher risk for sustaining and transmission of avian influenza virus than commercial poultry farms. The present study also indicates that different species may play different roles in the evolution and transmission of avian influenza virus. Therefore, risk-based surveillance and management measures should be conducted in future in this area.
Mass spectrometry based glycoproteomics has become a major means of identifying and characterizing previously N-linked glycan attached loci (glycosites). In the bottom-up approach, several factors which include but not limited to sample preparation, mass spectrometry analyses, and protein sequence database searches result in previously N-linked peptide spectrum matches (PSMs) of varying lengths. Given that multiple PSM scan map to a glycosite, we reason that identified PSMs are varying length peptide species of a unique set of glycosites. Because associated spectra of these PSMs are typically summed separately, true glycosite associated spectra counts are lost or complicated. Also, these varying length peptide species complicate protein inference as smaller sized peptide sequences are more likely to map to more proteins than larger sized peptides or actual glycosite sequences. Here, we present XGlycScan. XGlycScan maps varying length peptide species to glycosites to facilitate an accurate quantification of glycosite associated spectra counts. We observed that this reduced the variability in reported identifications of mass spectrometry technical replicates of our sample dataset. We also observed that mapping identified peptides to glycosites provided an assessment of search-engine identification. Inherently, XGlycScan reported glycosites reduce the complexity in protein inference. We implemented XGlycScan in the platform independent Java programing language and have made it available as open source. XGlycScan's source code is freely available at https://bitbucket.org/paiyetan/xglycscan/src and its compiled binaries and documentation can be freely downloaded at https://bitbucket.org/paiyetan/xglycscan/downloads. The graphical user interface version can also be found at https://bitbucket.org/paiyetan/xglycscangui/src and https://bitbucket.org/paiyetan/xglycscangui/downloads respectively.
Bioinformatics; Peptide; Glycopeptide; Glycosite; Protein identification; Proteomics; Quality assessment
Proteome Discoverer is one of many tools used for protein database search and peptide to spectrum assignment in mass spectrometry-based proteomics. However, the inadequacy of conversion tools makes it challenging to compare and integrate its results to those of other analytical tools. Here we present M2Lite, an open-source, light-weight, easily pluggable and fast conversion tool. M2Lite converts proteome discoverer derived MSF files to the proteomics community defined standard – the mzIdentML file format. M2Lite’s source code is available as open-source at https://bitbucket.org/paiyetan/m2lite/src and its compiled binaries and documentation can be freely downloaded at https://bitbucket.org/paiyetan/m2lite/downloads.
Bioinformatics; Peptide identification; Proteome Discoverer; MSF; Proteomics; mzIdentML; pepXML; IDPicker
Circulating tumor cells (CTCs) are metastatic cells disseminated into the bloodstreams. They have been proposed to monitor disease progression for decades. However, the prognostic value of CTCs in gastric cancer (GC) remains controversial. We performed a meta-analysis to investigate the topic.
A systematic search was made for relevant studies in academic data bases, involving the Medline, Embase, and Science Citation Index. Data on prognosis of GC patients, such as recurrence-free survival (RFS) and overall survival (OS), were extracted when possible. The meta-analysis was performed with the random effects model and the pooled hazard ratios (HRs) and their associated 95% confident intervals (95%CIs) were computed as effect measures.
Twenty six studies (including 40 subgroups) with peripheral blood samples of 1950 cases from 10 countries were included in the final analysis. The pooled results showed that GC patients with detectable CTCs (including circulating miRNAs) had a tendency to experience shortened RFS (HR = 2.91, 95% CI [1.84-4.61], I2 = 52.18%, n = 10). As for patient deaths, we found a similar association of CTC (including circulating miRNAs) presence with worse OS (HR = 1.78, 95% CI [1.49-2.12], I2 = 30.71%, n = 30). Additionally, subgroup analyses indicated strong prognostic powers of CTCs, irrespective of geographical, methodological, detection time and sample size differences of the studies.
Our meta-analysis shows that CTCs (including circulating miRNAs) can predict the survival of GC patients. Large prospective studies are warranted to determine the best sampling time points, detection methods in homogeneous patients with GC in the future.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2407-14-773) contains supplementary material, which is available to authorized users.
Decomposition of soil organic matter (SOM) is sensitive to vegetation and climate change. Here, we investigated the influence of changes in forest types on the mineralization of soil carbon (C) and nitrogen (N), and their temperature sensitivity (Q10) and coupling relationships by using a laboratory soil incubation experiments. We sampled soils from four forest types, namely, a primary Quercus liaotungensis forest (QL), Larix principis-rupprechtii plantation (LP), Pinus tabulaeformis plantation (PT), and secondary shrub forest (SS) in temperate northern China. The results showed that soil C and N mineralization differed significantly among forest types. Soil C and N mineralization were closely coupled in all plots, and C:N ratios of mineralized SOM ranged from 2.54 to 4.12. Forest type significantly influenced the Q10 values of soil C and N mineralization. The activation energy (Ea) of soil C and N mineralization was negatively related to the SOM quality index in all forest types. The reverse relationships suggested that the carbon quality-temperature (CQT) hypothesis was simultaneously applicable to soil C and N mineralization. Our findings show that the coupled relationships of soil C and N mineralization can be affected by vegetation change.