This research was designed to investigate the protective effects of TSPN on steroid-induced avascular necrosis of the femoral head (ANFH) and the likely mechanisms of those effects. As an in vivo study, TSPN was shown to be protective against steroid-induced ANFH due to the upregulation of VEGF-A. Furthermore, TSPN attenuated the apoptosis of osteocytes and reduced the expression of Caspase-3 relative to the model group. As an in vitro study, TSPN exerted a concentration-dependent protective effect against apoptosis in MC3T3-E1 cells. Moreover, TSPN (at a dose of 100 μg/mL) significantly reversed the dexamethasone-induced augmentation of Caspase-3 expression and activity. Therefore, our study demonstrated that TSPN had a protective effect against steroid-induced ANFH that was related to the upregulation of VEGF-A and the inhibition of apoptosis and Caspase-3 activation.
Plant viruses interact with their insect vectors directly and indirectly via host plants, and this tripartite interaction may produce fitness benefits to both the vectors and the viruses. Our previous studies show that the Middle East-Asia Minor 1 (MEAM1) species of the whitefly Bemisia tabaci complex improved its performance on tobacco plants infected by the Tomato yellow leaf curl China virus (TYLCCNV), which it transmits, although virus infection of the whitefly per se reduced its performance. Here, we use electrical penetration graph recording to investigate the direct and indirect effects of TYLCCNV on the feeding behaviour of MEAM1. When feeding on either cotton, a non-host of TYLCCNV, or uninfected tobacco, a host of TYLCCNV, virus-infection of the whiteflies impeded their feeding. Interestingly, when viruliferous whiteflies fed on virus-infected tobacco, their feeding activities were no longer negatively affected; instead, the virus promoted whitefly behaviour related to rapid and effective sap ingestion. Our findings show differential profiles of direct and indirect modification of vector feeding behaviour by a plant virus, and help to unravel the behavioural mechanisms underlying a mutualistic relationship between an insect vector and a plant virus that also has features reminiscent of an insect pathogen.
NIBP/TRAPPC9 is expressed in brain neurons, and human NIBP mutations are associated with neurodevelopmental disorders. The cellular distribution and function of NIBP in the enteric nervous system (ENS) remain unknown.
Western blot and RT-PCR analysis were used respectively to identify the protein and mRNA expression of NIBP and other neuronal markers. Multilabeled immunofluorescent microscopy and confocal image analysis were used to examine the cellular distribution of NIBP-like immunoreactivity (IR) in whole mount intestine. Enteric neuronal cell line (ENC) was infected with lentivirus carrying NIBP or its shRNA expression vectors and treated with vehicle or TNFα.
NIBP is expressed at both mRNA and protein levels in different regions and layers of the mouse intestine. NIBP-like-IR was co-localized with various neuronal markers, but not with glial, smooth muscular, or ICC markers. A small population of NIBP-expressing cells and fibers in extra-ganglionic and intra-ganglionic area were negative for pan-neuronal markers HuD or Peripherin. Relatively high NIBP-like-IR was found in 35-44% of myenteric neurons and 9-10% of submucosal neurons. Approximately 98%, 87% and 43% of these relatively high NIBP-expressing neurons were positive for ChAT, nNOS and Calretinin, respectively. NIBP shRNA knockdown in ENC inhibited TNFα-induced NFkB activation and neuronal differentiation, whereas NIBP overexpression promoted it.
Conclusions & Inferences
NIBP is extensively expressed in the ENS with relatively high level in a subpopulation of enteric neurons. Various NIBP expression levels in different neurons may represent dynamic trafficking or posttranslational modification of NIBP in some functionally-active neurons and ultimately regulate ENS plasticity.
Enteric nervous system; NFκB; TRAPPC9/NIBP; Cytokines; Immunohistochemistry; Confocal image; Enteric neuronal cell line
Background and Aims
Spatial (herkogamy) and temporal (dichogamy) separation of pollen presentation and stigma receptivity have been interpreted as reducing interference between male and female functions in hermaphroditic flowers. However, spatial separation leads to a potential conflict: reduced pollination accuracy, where pollen may be placed in a location on the pollinator different from the point of stigma contact.
To understand better how herkogamous flowers resolve this conflict, a study was made of a subalpine herb, Parnassia epunctulata, the nectariferous flowers of which exhibit sequential anther dehiscence (staggered pollen presentation) and stamen movements; usually one newly dehisced anther is positioned each day over the central gynoecium, while the older stamens bend away from the central position.
The open flowers were visited by a variety of pollinators, most of which were flies. Seed set was pollinator-dependent (bagged flowers set almost no seeds) and pollen-limited (manual pollination increased seed set over open pollination). Analyses of adaptive accuracy showed that coordinated stamen movements and style elongation (movement herkogamy) dramatically increased pollination accuracy. Specifically, dehiscing anthers and receptive stigmas were positioned accurately in the vertical and horizontal planes in relation to the opposite sexual structure and pollinator position. By contrast, the spatial correspondence between anthers and stigma was dramatically lower before the anthers dehisced and after stamens bent outwards, as well as before and after the period of stigmatic receptivity.
It is shown for the first time that a combination of movement herkogamy and dichogamy can maintain high pollination accuracy in flowers with generalized pollination. Staggered pollen and stigma presentation with spatial correspondence can both reduce sexual interference and improve pollination accuracy.
Adaptive accuracy; Celastraceae; dichogamy; generalist pollination; herkogamy; mating system; Parnassia epunctulata; Parnassiaceae; staggered pollen presentation; sexual interference; stamen movement
In order to develop non-ATP competitive CDK2/cyclin A inhibitors, the REPLACE strategy has been applied to generate fragment alternatives for the N-terminal tetrapeptide of the cyclin binding motif (HAKRRLIF) involved in substrate recruitment prior to phosphotransfer. The docking approach used for the prediction of small molecule mimics for peptide determinants was validated through reproduction of experimental binding modes of known inhibitors and provides useful information for evaluating binding to protein-protein interaction sites. Further to this, potential arginine isosteres predicted using the validated LigandFit docking method were ligated to the truncated C-terminal peptide, RLIF using solid phase synthesis and evaluated in a competitive binding assay. After testing, identified fragments were shown to represent not only appropriate mimics for a critical arginine residue but also to interact effectively with a minor hydrophobic pocket present in the binding groove. Further evaluation of binding modes was undertaken to optimize the potency of these compounds. Through further application of the REPLACE strategy in this study, peptide-small molecule hybrid CDK2 inhibitors were identified that are more drug-like and suitable for further optimization as anti-tumor therapeutics.
In their natural habitat, bacteria are consumed by bacterivorous nematodes; however, they are not simply passive preys. Here we report a defensive mechanism used by certain bacteria to mobilize nematode-trapping fungi to kill nematodes. These bacteria release urea, which triggers a lifestyle switch in the fungus Arthrobotrys oligospora from saprophytic to nematode–predatory form; this predacious form is characterized by formation of specialized cellular structures or ‘traps’. The bacteria significantly promote the elimination of nematodes by A. oligospora. Disruption of genes involved in urea transport and metabolism in A. oligospora abolishes the urea-induced trap formation. Furthermore, the urea metabolite ammonia functions as a signal molecule in the fungus to initiate the lifestyle switch to form trap structures. Our findings highlight the importance of multiple predator–prey interactions in prey defense mechanisms.
Certain soil fungi form specialized cellular structures or 'traps' to feed on nematodes, which in turn eat bacteria. Here, the authors show that urea released from bacteria induces trap formation in the fungi and this promotes nematode elimination.
Inflammation is a major mediator of CKD progression and is partly driven by altered gut microbiome and intestinal barrier disruption, events which are caused by: urea influx in the intestine resulting in dominance of urease-possessing bacteria; disruption of epithelial barrier by urea-derived ammonia leading to endotoxemia and bacterial translocation; and restriction of potassium-rich fruits and vegetables which are common sources of fermentable fiber. Restriction of these foods leads to depletion of bacteria that convert indigestible carbohydrates to short chain fatty acids which are important nutrients for colonocytes and regulatory T lymphocytes. We hypothesized that a high resistant starch diet attenuates CKD progression. Male Sprague Dawley rats were fed a chow containing 0.7% adenine for 2 weeks to induce CKD. Rats were then fed diets supplemented with amylopectin (low-fiber control) or high fermentable fiber (amylose maize resistant starch, HAM-RS2) for 3 weeks. CKD rats consuming low fiber diet exhibited reduced creatinine clearance, interstitial fibrosis, inflammation, tubular damage, activation of NFkB, upregulation of pro-inflammatory, pro-oxidant, and pro-fibrotic molecules; impaired Nrf2 activity, down-regulation of antioxidant enzymes, and disruption of colonic epithelial tight junction. The high resistant starch diet significantly attenuated these abnormalities. Thus high resistant starch diet retards CKD progression and attenuates oxidative stress and inflammation in rats. Future studies are needed to explore the impact of HAM-RS2 in CKD patients.
The minimum inhibitory
concentrations (MICs), mutation prevention concentrations (MPCs) and contribution of
quinolone resistance-determining region (QRDR) mutations to fluoroquinolone
(ciprofloxacin, enrofloxacin and orbifloxacin) susceptibility in 23 Pasteurella
multocida (Pm) isolates were investigated.
Fluoroquinolone-susceptible isolates (MICs ≤0.25 µg/ml,
9 isolates) had no QRDR mutations, and their respective MPCs were low.
Fluoroquinolone-intermediate isolates (MICs=0.5 µg/ml,
14 isolates) had QRDR mutations (Asp87 to Asn or Ala84 to Pro in gyrA),
and their respective MPCs were high (4–32 µg/ml).
First-step mutants (n=5) and laboratory-derived highly resistant fluoroquinolone mutants
(n=5) also had QRDR mutations. The MICs of fluoroquinolones for mutant-derived strains
were decreased in the presence of efflux inhibitors. The results indicated that the
fluoroquinolone resistance of Pm is mainly due to multiple target gene
mutations in gyrA and parC and the overexpression of
efflux pump genes.
efflux pump; fluoroquinolone resistance; Pasteurella multocida; plasmid; target mutation
To characterize prognostic and risk factors of central nervous system (CNS) metastases in patients with epithelial ovarian cancer (EOC).
A retrospective analysis of Xijing Hospital electronic medical records was conducted to identify patients with pathologically confirmed EOC and CNS metastases. In addition to patient demographics, tumor pathology, treatment regimens, and clinical outcomes, we compared putative cancer stem cell marker CD133 expression patterns in primary and metastatic lesions as well as in recurrent EOC with and without CNS metastases.
Among 1366 patients with EOC, metastatic CNS lesions were present in 29 (2.1%) cases. CD133 expression in primary tumor was the only independent risk factor for CNS metastases; whilst the extent of surgical resection of primary EOC and platinum resistance were two independent factors significantly associated with time to CNS metastases. Absence of CD133 expression in primary tumors was significantly associated with high platinum sensitivity in both patient groups with and without CNS metastases. Platinum resistance and CD133 cluster formation in CNS metastases were associated with decreased survival, while multimodal therapy including stereotactic radiosurgery (SRS) for CNS metastases was associated with increased survival following the diagnosis of CNS metastases.
These data suggest that there exist a positive association between CD133 expression in primary EOC, platinum resistance and the increased risk of CNS metastases, as well as a less favorable prognosis of EOC. The absence of CD133 clusters and use of multimodal therapy including SRS could improve the outcome of metastatic lesions. Further investigation is warranted to elucidate the true nature of the association between platinum sensitivity, CD133 expression, and the risk and prognosis of CNS metastases from EOC.
Brain metastases; Chemoresistance; Prognosis; Stem cell marker
Meso-Rex bypass (MRB) surgery is being increasingly used to treat chronic prehepatic portal hypertension secondary to extrahepatic portal vein thrombosis (EPVT) and cavernous transformation (EPVCT) in children. Rather than using the internal jugular vein (IJV, the traditional venous graft), we used an autogenous splenic vein segment graft for MRB.
We examined 25 children with extrahepatic portal hypertension and a history of recurrent upper gastrointestinal (GI) variceal bleeding despite previous endoscopic sclerotherapy. All patients had melena, splenomegaly, hypersplenism, or some combination thereof. Left portal vein (LPV) patency was verified in 22 patients using intraoperative direct portography through the umbilical vein. Partial splenectomy was performed to enable the harvest of the splenic vein trunk, which was anastomosed between the superior mesenteric vein (SMV) and the left portal vein (LPV). All patients were followed for 12–48 months (mean=25.6 months) and no patients were lost to follow-up.
Preoperative Doppler ultrasound (US) imaging indicated that 18/25 patients had adequate intrahepatic portal veins for shunting, with no blood flow in the LPVs of 7 patients. LPV patency in 22/25 patients was verified using intraoperative direct portography, with successful MRB. Shunting was converted into a portosystemic shunt in the remaining 3/25 patients with thrombosed LPVs. A Doppler US evaluation of the vein conduit revealed excellent postoperative flow. The patients’ mean hemoglobin, platelet, and white blood cell counts increased significantly, and in all cases the endoscopic status obviously improved after shunting. Occlusion or narrowing occurred in 2/22 patients after discharge. At 12 months (for 1 patient) and 24 months (for 1 patient), the shunt was converted into a portosystemic shunt. The cumulative graft patency rate was 91% (20/22).
Partial splenectomy and splenic vein autografting in MRB surgery can successfully resolve prehepatic portal hypertension and hypersplenism in children.
Autografts; Child; Hypertension; Portal; Splenic Vein
Acute liver failure (ALF) is a rapidly progressing critical illness with a high mortality rate. Circulating inflammatory cytokines, such as tumor necrosis factor-α (TNF-α), play a significant role in the pathophysiology of ALF through promoting hepatocellular apoptosis. Ginsenoside Rg1, the primary active ingredient in Panax ginseng (also termed Asian or Korean ginseng), has been reported to inhibit TNF-α production and has been shown to significantly attenuate liver fibrosis development. Here, we assessed ginsenoside Rg1's potential as a therapy for ALF by investigating the effect of ginsenoside Rg1 treatment on circulating inflammatory markers, hepatocellular apoptosis, and relevant apoptotic signaling pathways in a well-established murine ALF model. We found that ginsenoside Rg1 significantly reduces liver damage in a murine ALF model through inhibiting TNF-α-induced, caspase-dependent hepatocellular apoptosis. These results support the further investigation of ginsenoside Rg1 as a therapeutic candidate for ALF.
Recruitment of bone marrow derived endothelial progenitor cells (BMDEPCs) alleviates multiple organ injury (MOI) and improves outcomes. However, mechanisms mediating BMDEPC recruitment following septic MOI remain largely unknown. This study characterized the kinetics of BMDEPC recruitment and proliferation and defined the role of NF-κB in regulating BMDEPC recruitment and proliferation.
Methods and Main Findings
Chimeric mice with an intact or disrupted NF-κB p50 gene and BMDEPC-restricted expression of green fluorescent protein were created and injected with LPS (2 mg/kg, i.p.). BMDEPC recruitment and proliferation in multiple organs were quantified. BMDEPC recruitment and proliferation are highly organ-dependent. Lungs had the highest number of BMDEPC recruitment, whereas heart, liver and kidney had only a small fraction of the number of BMDEPCs in lungs. Number of proliferating BMDEPCs was several-fold higher in lungs than in other 3 organs. Kinetically, BMDEPC recruitment into different organs showed different time course profiles. NF-κB plays obligatory roles in mediating BMDEPC recruitment and proliferation. Universal deletion of NF-κB p50 gene inhibited LPS-induced BMDEPC recruitment and proliferation by 95% and 69% in heart. However, the contribution of NF-κB to these regulations varies significantly between organs. In liver, universal p50 gene deletion reduced LPS-induced BMDEPC recruitment and proliferation only by 49% and 35%. NF-κB activities in different tissue compartments play distinct roles. Selective p50 gene deletion either in stromal/parenchymal cells or in BM/blood cells inhibited BMDEPC recruitment by a similar extent. However, selective p50 gene deletion in BM/blood cells inhibited, but in stromal/parenchymal cells augmented BMDEPC proliferation.
BMDEPC recruitment and proliferation display different kinetics in different organs following endotoxemic MOI. NF-κB plays obligatory and organ-dependent roles in regulating BMDEPC recruitment and proliferation. NF-κB activities in different tissue compartments play distinct roles in regulating BMDEPC proliferation.
China has the largest number of the elderly in the world. As the proportion of elderly is rapidly increasing among national reported HIV/AIDS cases, it is a concern about HIV epidemic among older MSM in China. However, studies on HIV prevalence and unprotected anal intercourse (UAI) among Chinese older MSM were relatively few or generally had small sample sizes.
English and Chinese articles published in peer-reviewed journals were identified by systematically searching 5 electronic databases including PubMed and through cross-referencing. Summary prevalence rates of HIV infection and UAI with male sexual partners were calculated, and analyses were performed using the software Comprehensive Meta-Analysis V2.0 and SPSS V17.0. Subgroup analyses were performed separately by sample size, study year, study location, recruitment settings and sampling method.
Twenty eligible cross-sectional studies (3 in English and 17 in Chinese), published between 2005 and 2013, with a total of 2812 older MSM participants, were identified. Our meta-analyses showed that the prevalence of HIV, syphilis and UAI in the last 6 months were 11.6% (95% confidence interval [CI]: 8.0%-16.6%), 23.0% (95% CI: 15.8%-32.3%) and 79.5% (95% CI: 72.7%-84.9%), respectively. HIV prevalence increased over the study period (6.3% in 2003–2007; 8.6% in 2008–2009, and 11.5% in 2010–2011, trend test Chi-square = 7.02, p = 0.008). The pooled prevalence of HIV (11.6% vs. 5.2%, Chi-square value = 36.2, p < 0.001) and UAI (79.5% vs. 52.6%, Chi-square value = 440.04, p < 0.001) among older MSM were both significantly higher than among younger age group (age < 50 years).
Older Chinese MSM have high prevalence of HIV and syphilis. Unprotected anal sex is common and further puts them at high risks of acquiring and transmitting HIV, which was one of reasons for the rapid increasing of national reported older male HIV/AIDS cases. Prevention intervention programs should be specially tailored for this high risk MSM subgroup.
Electronic supplementary material
The online version of this article (doi:10.1186/1471-2334-14-531) contains supplementary material, which is available to authorized users.
HIV; Syphilis; Unprotected anal intercourse (UAI); Men who have sex with men (MSM); Older MSM; China
Methadone maintenance therapy is an established treatment for heroin dependence. This study tested the influence of functional genetic polymorphisms in CYP2C19 gene encoding a CYP450 enzyme that contributes to methadone metabolism on treatment dose, plasma concentration, and side effects of methadone. Two single nucleotide polymorphisms (SNPs), rs4986893 (exon 4) and rs4244285 (exon 5), were selected and genotyped in 366 patients receiving methadone maintenance therapy in Taiwan. The steady-state plasma concentrations of both methadone and its EDDP metabolite enantiomers were measured. SNP rs4244285 allele was significantly associated with the corrected QT interval (QTc) change in the electrocardiogram (p=0.021), and the Treatment Emergent Symptom Scale (TESS) total score (p=0.021) in patients who continued using heroin, as demonstrated with a positive urine opiate test. Using the gene dose (GD) models where the CYP2C19 SNPs were clustered into poor (0 GD) versus intermediate (1 GD) and extensive (2 GD) metabolizers, we found that the extensive metabolizers required a higher dose of methadone (p=0.035), and showed a lower plasma R-methadone/methadone dose ratio (p=0.007) in urine opiate test negative patients, as well as a greater QTc change (p=0.008) and higher total scores of TESS (p=0.018) in urine opiate test positive patients, than poor metabolizers. These results in a large study sample from Taiwan suggest that the gene dose of CYP2C19 may potentially serve as an indicator for the plasma R-methadone/methadone dose ratio and cardiac side effect in patients receiving methadone maintenance therapy. Further studies of pharmacogenetic variation in methadone pharmacokinetics and pharmacodynamics are warranted in different world populations.
Restricted space and close contact with conspecifics in captivity may be stressful for musk deer, as they are highly territorial and solitary in the wild. So we tested the effects of crowding on stress of forest musk deer (Moschus berezovskii) in heterosexual groups, using fecal cortisol analysis as a non-invasive method. 32 healthy adults during non-breeding seasons were chose as our experimental objects. Group 1 was defined as higher crowding condition, with 10-15 m2/deer (6 enclosures, 10♀ and 6♂); group 2 was defined as lower crowding condition, with 23-33 m2/deer (6 enclosures, 10♀ and 6♂). Every enclosure contained 1 male and 3 female. These patterns had been existed for years.
The results showed that females in lower crowding condition (217.1 ± 9.5 ug/g) had significantly higher fecal cortisol levels than those in higher crowding condition (177.2 ± 12.1 ug/g). Interestingly, crowding seemed have no effect on male fecal cortisol levels (148.1 ± 9.1 ug/g and 140.5 ± 13.3 ug/g, respectively). At both groups, cortisol was significantly lower in males than in females.
These results showed that chronic crowding may affect stress status of captive forest musk deer. The captive environment should consider the space need for musk deer.
Captivity; M. berezovskii; Fecal cortisol; Chronic stress; Crowding
The aim of the present study was to evaluate the safety and efficacy of administering cytokine-induced killer cells (termed allogeneic CIKs), obtained from the blood of the offspring of patients, for the treatment of non-small cell lung cancer. Symptoms, signs and laboratory assessment results for 303 cancer patients were collected prior to and following treatment with autologous or allogeneic CIKs. In addition, 54 patients with advanced non-small cell lung cancer (NSCLC) were enrolled and divided into allogeneic CIK and optimal support groups (n=27 per group) according to gender, age, Karnofsky performance status score, TNM stage and histological type. In addition, overall survival (OS) was compared between the two groups. A total of 303 patients were treated with CIKs for 647 cycles, with 308 and 339 cycles in the autologous and allogeneic CIK groups, respectively. The mean number of CIKs in the autologous and allogeneic groups was 2.11±0.32×1010 and 2.29±0.36×1010, respectively, with no marked differences identified between the two groups (t=1.147; P>0.05). The predominant adverse events included insomnia, fever, nausea, vomiting and mild abdominal pain, which were found, respectively, in nine (6.8%), eight (6.0%), two (1.5%) and one (0.8%) patients receiving autologous CIKs and 11 (6.5%), 10 (5.9%), one (0.6%) and one (0.6%) patients receiving allogeneic CIKs, with no marked differences identified between the two groups (P>0.05). Adverse events were not associated with cell count, frequency or duration of treatment. Following CIK treatment, the outcomes of routine blood tests, and liver and kidney function tests, as well as immune function and electrocardiogram examinations remained unchanged (P>0.05). The median OS was 11.0 months (95% confidence interval (CI), 8.6–13.4 months) and 8.0 months (95% CI, 5.3–10.7 months) for NSCLC patients receiving allogeneic CIKs and optimal support, respectively; a statistically significant difference was identified (χ2=5.618; P=0.018). The present study demonstrated that CIKs from human leukocyte antigen haploidentical donors are safe and prolong the survival of NSCLC patients.
cytokine-induced killer cells; immunotherapy; adoptive; allogeneic; malignant tumor; carcinoma; non-small cell lung
The study of population genetics among the Bemisia tabaci complex is limited due to the lack of conserved molecular markers. In this study, 358, 433 and 322 new polynucleotide microsatellites are separately identified from the transcriptome sequences of three cryptic species of the B. tabaci complex. The cross species transferability of 57 microsatellites was then experimentally validated. The results indicate that these markers are conserved and have high inter-taxon transferability. Thirteen markers were employed to assess the genetic relationships among six cryptic species of the B. tabaci complex. To our surprise, the inferred phylogeny was consistent with that of mitochondrial COI sequences, indicating that microsatellites have the potential to distinguish species of the B. tabaci complex. Our results demonstrate that development of microsatellites from transcriptome data is a fast and cost-effective approach. These markers can be used to analyze the population genetics and evolutionary patterns of the B. tabaci complex.
(1) To evaluate the recognition of words, phonemes and lexical tones in audiovisual (AV) and auditory-only (AO) modes in Mandarin-speaking adults with cochlear implants (CIs); (2) to understand the effect of presentation levels on AV speech perception; (3) to learn the effect of hearing experience on AV speech perception.
Thirteen deaf adults (age = 29.1±13.5 years; 8 male, 5 female) who had used CIs for >6 months and 10 normal-hearing (NH) adults participated in this study. Seven of them were prelingually deaf, and 6 postlingually deaf. The Mandarin Monosyllablic Word Recognition Test was used to assess recognition of words, phonemes and lexical tones in AV and AO conditions at 3 presentation levels: speech detection threshold (SDT), speech recognition threshold (SRT) and 10 dB SL (re:SRT).
The prelingual group had better phoneme recognition in the AV mode than in the AO mode at SDT and SRT (both p = 0.016), and so did the NH group at SDT (p = 0.004). Mode difference was not noted in the postlingual group. None of the groups had significantly different tone recognition in the 2 modes. The prelingual and postlingual groups had significantly better phoneme and tone recognition than the NH one at SDT in the AO mode (p = 0.016 and p = 0.002 for phonemes; p = 0.001 and p<0.001 for tones) but were outperformed by the NH group at 10 dB SL (re:SRT) in both modes (both p<0.001 for phonemes; p<0.001 and p = 0.002 for tones). The recognition scores had a significant correlation with group with age and sex controlled (p<0.001).
Visual input may help prelingually deaf implantees to recognize phonemes but may not augment Mandarin tone recognition. The effect of presentation level seems minimal on CI users' AV perception. This indicates special considerations in developing audiological assessment protocols and rehabilitation strategies for implantees who speak tonal languages.
Background: The new finding of the heterogeneous distribution of BRAFV600E mutation in primary papillary thyroid carcinoma suggested the percentage of BRAFV600E alleles should be taken into consideration when evaluating its association with clinicopathological features of papillary thyroid carcinoma. The aim of this study was to detect both the presence and the percentage of BRAFV600E alleles in fine-needle aspiration biopsy samples and to assess its association with clinicopathological characteristics of papillary thyroid carcinoma in a Chinese population. Materials and methods: Fine needle aspiration samples were collected in a total of 182 patients (132 conventional papillary thyroid carcinomas and 50 goiters). The associations of the presence and percentage of BRAFV600E alleles genotyped by pyrosequencing with clinicopathological characteristics were evaluated in papillary thyroid carcinomas. Results: 80 (60.61%) of papillary thyroid carcinomas exhibited BRAFV600E mutation in a range of 7.7% to 46.3% of the total BRAF alleles. The presence of BRAFV600E mutation was significantly associated with extrathyroidal invasion. There was no significant difference between the presence of BRAFV600E mutation and other clinicopathological features. It was not found that the significant relationship between percentage of BRAFV600E alleles and clinicopathological characteristics. Conclusion: We concluded that the presence of BRAFV600E could be preoperatively predictive of extrathyroidal invasion in a Chinese population.
Papillary thyroid carcinoma (PTC); percentage of BRAFV600E alleles; pyrosequencing; preoperative risk stratification
Products of the SOX gene family play important roles in the life process. One of the members, SOX7, is associated with the development of a variety of cancers as a tumor suppression factor, but its relevance with ovarian cancer was unclear. In this study, we investigated the involvement of SOX7 in the progression and prognosis of epithelial ovarian cancer (EOC) and the involved mechanisms.
Expression profiles in two independent microarray data sets were analyzed for SOX7 between malignant and normal tissues. The expression levels of SOX7 in EOC, borderline ovarian tumors and normal ovarian tissues were measured by immunohistochemistry. We also measured levels of COX2 and cyclin-D1 to examine their possible involvement in the same signal transduction pathway as SOX7.
The expression of SOX7 was significantly reduced in ovarian cancer tissues compared with normal controls, strongly indicating that SOX7 might be a negative regulator in the Wnt/β-catenin pathway in ovarian cancer. By immunohistochemistry staining, the protein expression of SOX7 showed a consistent trend with that of the gene expression microarray analysis. By contrast, the protein expression level of COX2 and cyclin-D1 increased as the tumor malignancy progressed, suggesting that SOX7 may function through the Wnt/β-catenin signaling pathway as a tumor suppressor. In comparison between the protein expression levels of SOX7 with pathological features of the cancer, we found that SOX7 was down-regulated mainly in serous cystadenocarcinoma and advanced stages of the cancers.
The expression of SOX7 correlates with tumor progression as a tumor suppressor, possibly through the Wnt/β-catenin signaling pathway in ovarian cancers, suggesting that SOX7 may be a promising prognostic marker.
Electronic supplementary material
The online version of this article (doi:10.1186/s13048-014-0087-1) contains supplementary material, which is available to authorized users.
SOX7; Tumor suppressor; Ovarian cancer; Wnt/β-catenin signaling pathway
The band offsets of non-polar A-plane GaN/AlN and AlN/GaN heterojunctions are measured by X-ray photoemission spectroscopy. A large forward-backward asymmetry is observed in the non-polar GaN/AlN and AlN/GaN heterojunctions. The valence-band offsets in the non-polar A-plane GaN/AlN and AlN/GaN heterojunctions are determined to be 1.33 ± 0.16 and 0.73 ± 0.16 eV, respectively. The large valence-band offset difference of 0.6 eV between the non-polar GaN/AlN and AlN/GaN heterojunctions is considered to be due to piezoelectric strain effect in the non-polar heterojunction overlayers.
GaN/AlN; Heterostructure; X-ray photoemission spectroscopy; Non-polar
Caveolin-1 and flotillin-1 are considered as markers of lipid rafts which can be regarded as sorting platforms for targeted transport of transmembrane proteins and are involved in fundamental cellular events such as signal transduction, cell adhesion, lipid/protein sorting, and human cancer. We addressed caveolin-1 and flotillin-1 expression in 90 human hepatocellular carcinoma (HCC) and adjacent noncancerous tissues (ANT) samples by SDS-PAGE and immunoblotting with specific antibodies. Significant caveolin-1 and flotillin-1 overexpression was found in HCC tissues compared to ANT and was confirmed by immunohistochemistry. Raft-associated Akt signaling pathway components involved in the regulation of cell survival were altered by western blotting in HCC microdomain-enriched subcellular fractions purified from paired HCC and ANT samples. Our results demonstrated that the activity of raft-associated but not total membrane Akt determines its cellular functions. Lipid rafts differ in different types of tissues, which allows for the possibility of tissue-type-specific targeting for cell survival.
The bacterial genus Salmonella contains thousands of serotypes that infect humans or other hosts, causing mild gastroenteritis to potentially fatal systemic infections in humans. Pathogenically distinct Salmonella serotypes have been classified as individual species or as serological variants of merely one or two species, causing considerable confusion in both research and clinical settings. This situation reflects a long unanswered question regarding whether the Salmonella serotypes exist as discrete genetic clusters (natural species) of organisms or as phenotypic (e.g. pathogenic) variants of a single (or two) natural species with a continuous spectrum of genetic divergence among them. Our recent work, based on genomic sequence divergence analysis, has demonstrated that genetic boundaries exist among Salmonella serotypes, circumscribing them into clear-cut genetic clusters of bacteria.
To further test the genetic boundary concept for delineating Salmonella into clearly defined natural lineages (e.g., species), we sampled a small subset of conserved genomic DNA sequences, i.e., the endonuclease cleavage sites that contain the highly conserved CTAG sequence such as TCTAGA for XbaI. We found that the CTAG-containing cleavage sequence profiles could be used to resolve the genetic boundaries as reliably and efficiently as whole genome sequence comparisons but with enormously reduced requirements for time and resources.
Profiling of CTAG sequence subsets reflects genetic boundaries among Salmonella lineages and can delineate these bacteria into discrete natural clusters.
Nodal/TGF-Lefty signaling pathway has important effects at early stages of differentiation of human embryonic stem cells in directing them to differentiate into different embryonic lineages. LEFTY, one of transforming growth factors in the Nodal/TGF-Lefty signaling pathway, plays an important role in the development of heart. The aim of this work was to find evidence on whether Lefty variations are associated with congenital heart diseases (CHD).
We sequenced the Lefty gene for 230 Chinese Han CHD patients and evaluated SNPs rs2295418, rs360057 and g.G169A, which are located within the translated regions of the genes. The statistical analyses were conducted using Chi-Square Tests as implemented in SPSS (version 13.0). The Hardy-Weinberg equilibrium test of the population was carried out using online software OEGE, and multiple-sequence alignments of LEFTY proteins were carried out using the Vector NTI software.
Two heterozygous variants in Lefty1 gene, g.G169A and g.A1035C, and one heterozygous variant in Lefty2 gene, g.C925A, were identified. Statistical analyses showed that the rs2295418 (g.C925A) variant in Lefty2 gene was obviously associated with the risk of CHD (P value = 0.016<0.05). The genotype frequency of rs360057 (g.A1035C) variant in Lefty1 gene was associated with the risk of CHD (P value = 0.007<0.05), but the allele frequency was not (P value = 0.317>0.05).
The SNP rs2295418 in the Lefty2 gene is associated with CHD in Chinese Han populations.
Aims: The potential receptor for hydrogen sulfide (H2S) remains unknown. Results: H2S could directly activate vascular endothelial growth factor receptor 2 (VEGFR2) and that a small interfering RNA (siRNA)-mediated knockdown of VEGFR2 inhibited H2S-induced migration of human vascular endothelial cells. H2S promoted angiogenesis in Matrigel plug assay in mice and this effect was attenuated by a VEGF receptor inhibitor. Using tandem mass spectrometry (MS), we identified a new disulfide complex located between Cys1045 and Cys1024 within VEGFR2 that was labile to H2S-mediated modification. Kinase activity of the mutant VEGFR2 (C1045A) devoid of the Cys1045–Cys1024 disulfide bond was significantly higher than wild-type VEGFR2. Transfection with vectors expressing VEGFR2 (C1045A) caused a significant increase in cell migration, while the migration-promoting effect of H2S disappeared in the cells transfected with VEGFR2 (C1045A). Therefore, the Cys1045–Cys1024 disulfide bond serves as an intrinsic inhibitory motif and functions as a molecular switch for H2S. The formation of the Cys1045–Cys1024 disulfide bond disrupted the integrity of the active conformation of VEGFR2. Breaking the Cys1045–Cys1024 disulfide bond recovered the active conformation of VEGFR2. This motif was prone to a nucleophilic attack by H2S via an interaction of their frontier molecular orbitals. siRNA-mediated knockdown of cystathionine γ-lyase attenuated migration of vascular endothelial cells induced by VEGF or moderate hypoxia. Innovation and Conclusion: The study provides the first piece of evidence of a molecular switch in H2S-targeting receptor protein kinase in H2S-induced angiogenesis and that may be applicable to additional kinases containing functionally important disulfide bonds in mediating various H2S actions. Antioxid. Redox Signal. 19, 448–464.