Given their recent worldwide declines and extinctions, characterization of species-level diversity is of critical importance for large-scale biodiversity assessments and conservation of amphibians. This task is made difficult by the existence of cryptic species complexes, species groups comprising closely related and morphologically analogous species. The combination of morphology, genetic, and bioacoustic analyses permits robust and accurate species identification. Using these methods, we discovered two undescribed Xenophrys species, namely Xenophrys lini
sp. nov. and Xenophrys cheni
sp. nov. from the middle range of Luoxiao Mountains, southeast China. These two new species can be reliably distinguished from other known congeners by morphological and morphometric differences, distinctness in male advertisement calls, and substantial genetic distances (>3.6%) based on the mitochondrial 16s and 12s rRNA genes. The two new species, together with X. jinggangensis, are sympatric in the middle range of Luoxiao Mountains but may be isolated altitudinally and ecologically. Our study provides a first step to help resolve previously unrecognized cryptic biodiversity and provides insights into the understanding of Xenophrys diversification in the mountain complexes of southeast China.
MicroRNA (miRNA)-related single nucleotide polymorphisms (miR-SNPs) can affect cancer development, treatment efficacy and patients prognosis. We examined 6 miR-SNPs in miRNA processing machinery genes including exportin 5 (XPO5) (rs11077), Ran-GTPase (RAN) (rs14035), Dicer (rs3742330), Trinucleotide Repeat Containing 6B (TNRC6B) (rs9623117), GEMIN3 (rs197412), GEMIN4 (rs2740348) in 108 surgically resected HCC patients and evaluated the impact of these miR-SNPs on HCC outcome. Among the 6 SNPs, only the A/A genotype of rs11077 located in XPO5 3′UTR was identified to associated independently with worse survival in HCC patients by multivariate analysis with relative risk, 0.395; 95% CI, 0.167–0.933; p = 0.034. This is the first study reporting that polymorphisms related to miRSNPs have prognostic value in hepatocellular carcinoma and identify the A/A genotype of rs11077 SNP site located in XPO5 3′UTR can help to predict worse prognosis in patients.
Alkaline polygalacturonate lyase (PGL, EC 220.127.116.11) is an enzyme used in many industries. We developed a fed-batch fermentation process that combines the enzymatic pretreatment of the carbon source with controlling the pH of the fermentative broth to enhance the PGL production from Bacillus subtilis 7-3-3 to decrease the production cost. Maintaining the fermentation broth at pH 6.5 prior to feeding with ammonia and at pH 6.0 after feeding significantly improved PGL activity (743.5 U mL−1) compared with the control (202.5 U mL−1). The average PGL productivity reached 19.6 U mL−1 h−1 after 38 h of fermentation. The crude PGL was suitable for environmentally friendly ramie enzymatic degumming.
Biometrics plays an important role in authentication applications since they are strongly linked to holders. With an increasing growth of e-commerce and e-government, one can expect that biometric-based authentication systems are possibly deployed over the open networks in the near future. However, due to its openness, the Internet poses a great challenge to the security and privacy of biometric authentication. Biometric data cannot be revoked, so it is of paramount importance that biometric data should be handled in a secure way. In this paper we present a scheme achieving privacy-preserving fingerprint authentication between two parties, in which fingerprint minutiae matching algorithm is completed in the encrypted domain. To improve the efficiency, we exploit homomorphic encryption as well as garbled circuits to design the protocol. Our goal is to provide protection for the security of template in storage and data privacy of two parties in transaction. The experimental results show that the proposed authentication protocol runs efficiently. Therefore, the protocol can run over open networks and help to alleviate the concerns on security and privacy of biometric applications over the open networks.
TECTA-related deafness can be inherited as autosomal-dominant nonsyndromic deafness (designated DFNA) or as the autosomal-recessive version. The α-tectorin protein, which is encoded by the TECTA gene, is one of the major components of the tectorial membrane in the inner ear. Using targeted DNA capture and massively parallel sequencing (MPS), we screened 42 genes known to be responsible for human deafness in a Chinese family (Family 3187) in which common deafness mutations had been ruled out as the cause, and identified a novel mutation, c.257–262CCTTTC>GCT (p. Ser86Cys; p. Pro88del) in exon 3 of the TECTA gene in the proband and his extended family. All affected individuals in this family had moderate down-sloping hearing loss across all frequencies. To our knowledge, this is the second TECTA mutation identified in Chinese population. This study demonstrates that targeted genomic capture, MPS, and barcode technology might broaden the availability of genetic testing for individuals with undiagnosed DFNA.
AIM: To evaluate transjugular intrahepatic portosystemic shunt (TIPS) with covered stents for hepatocellular carcinoma (HCC) with main portal vein tumor thrombus (PVTT).
METHODS: Eleven advanced HCC patients (all male, aged 37-78 years, mean: 54.3 ± 12.7 years) presented with acute massive upper gastrointestinal bleeding (n = 9) or refractory ascites (n = 2) due to tumor thrombus in the main portal vein. The diagnosis of PVTT was based on contrast-enhanced computed tomography and color Doppler sonography. The patients underwent TIPS with covered stents. Clinical characteristics and average survival time of 11 patients were analyzed. Portal vein pressure was assessed before and after TIPS. The follow-up period was 2-18 mo.
RESULTS: TIPS with covered stents was successfully completed in all 11 patients. The mean portal vein pressure was reduced from 32.0 to 11.8 mmHg (t = 10.756, P = 0.000). Gastrointestinal bleeding was stopped in nine patients. Refractory ascites completely disappeared in one patient and was alleviated in another. Hepatic encephalopathy was observed in six patients and was resolved with drug therapy. During the follow-up, ultrasound indicated the patency of the shunt and there was no recurrence of symptoms. Death occurred 2-14 mo (mean: 5.67 mo) after TIPS in nine cases, which were all due to multiple organ failure. In the remaining two cases, the patients were still alive at the 16- and 18-mo follow-up, respectively.
CONCLUSION: TIPS with covered stents for HCC patients with tumor thrombus in the main portal vein is technically feasible, and short-term efficacy is favorable.
Transjugular intrahepatic portosystemic shunt; Covered stent; Portal hypertension; Main portal vein tumor thrombus; Hepatocellular carcinoma
Genome-wide association studies on components of the one-carbon metabolic pathway revealed that human vitamin B12 levels could be significantly influenced by variationsinthefucosyltransferase 2 (FUT2), cubilin (CUBN), and transcobalamin-I (TCN1) genes. An altered vitamin B12 level is an important factor that disturbs the homeostasis of the folate metabolism pathway, which in turn can potentially lead to the development of congenital heart disease (CHD). Therefore, we investigated the association between the variants of vitamin B12-related genes and CHD in Han Chinese populations.
Methods and Results
Six variants of the vitamin B12-related genes were selected for analysis in two independent case-control studies, with a total of 868 CHD patients and 931 controls. The variant rs11254363 of the CUBN gene was associated with a decreased risk of developing CHD in both the separate and combined case-control studies. Combined samples from the two cohorts had a significant decrease in CHD risk for the G allele (OR = 0.48, P = 1.7×10−5) and AG+GG genotypes (OR = 0.49, P = 4×10−5), compared with the wild-type A allele and AA genotype, respectively.
Considering the G allele of variant rs11254363 of the CUBN gene was associated with an increased level of circulating vitamin B12. This result suggested that the carriers of the G allele would benefit from the protection offered by the high vitamin B12 concentration during critical heart development stages. This finding shed light on the unexpected role of CUBN in CHD development and highlighted the interplay of diet, genetics, and human birth defects.
Homocysteine is an independent risk factor for various cardiovascular diseases. There are
two ways to remove homocysteine from embryonic cardiac cells: remethylation to form
methionine or transsulfuration to form cysteine. Cystathionine β-synthase (CBS)
catalyzes the first step of homocysteine transsulfuration as a rate-limiting enzyme. In
this study, we identified a functional variant −4673C>G (rs2850144) in the
CBS gene promoter region that significantly reduces the susceptibility to
congenital heart disease (CHD) in a Han Chinese population consisting of 2 340 CHD
patients and 2 270 controls. Individuals carrying the heterozygous CG and homozygous GG
genotypes had a 15% (odds ratio (OR) = 0.85, 95% confidence interval (CI) = 0.75-0.96,
P = 0.011) and 40% (OR = 0.60, 95% CI = 0.49-0.73, P = 1.78 ×
10−7) reduced risk to develop CHD than the wild-type CC genotype
carriers in the combined samples, respectively. Additional stratified analyses
demonstrated that CBS −4673C>G is significantly related to septation
defects and conotruncal defects. In vivo detection of CBS mRNA levels in
human cardiac tissues and in vitro luciferase assays consistently showed that the
minor G allele significantly increased CBS transcription. A functional analysis
revealed that both the attenuated transcription suppressor SP1 binding affinity and the
CBS promoter hypomethylation specifically linked with the minor G allele
contributed to the remarkably upregulated CBS expression. Consequently, the
carriers with genetically increased CBS expression would benefit from the
protection due to the low homocysteine levels maintained by CBS in certain cells during
the critical heart development stages. These results shed light on unexpected role of CBS
and highlight the importance of homocysteine removal in cardiac development.
congenital heart disease; cystathionine β-synthase; non-coding variant; homocysteine
Neuropathic pain is a refractory disease characterized by maladaptive changes in gene transcription and translation within the sensory pathway. Long noncoding RNAs (lncRNAs) are emerging as new players in gene regulation, but how lncRNAs operate in the development of neuropathic pain is unclear. Here we identify a conserved lncRNA for Kcna2 (named Kcna2 antisense RNA) in first-order sensory neurons of rat dorsal root ganglion (DRG). Peripheral nerve injury increases Kcna2 antisense RNA expression in injured DRG through activation of myeloid zinc finger protein 1, a transcription factor that binds to Kcna2 antisense RNA gene promoter. Mimicking this increase downregulates Kcna2, reduces total Kv current, increases excitability in DRG neurons, and produces neuropathic pain symptoms. Blocking this increase reverses nerve injury-induced downregulation of DRG Kcna2 and attenuates development and maintenance of neuropathic pain. These findings suggest native Kcna2 antisense RNA as a new therapeutic target for the treatment of neuropathic pain.
Voltage-gated potassium (Kv) channels are critical in controlling neuronal excitability and are involved in the induction of neuropathic pain. Therefore, Kv channels might be potential targets for prevention and/or treatment of this disorder. We reported here that a majority of dorsal root ganglion (DRG) neurons were positive for Kv channel alpha subunit Kv1.2. Most of them were large and medium, although there was a variety of sizes. Peripheral nerve injury caused by lumbar (L)5 spinal nerve ligation (SNL) produced a time-dependent reduction in the number of Kv1.2-positive neurons in the ipsilateral L5 DRG, but not in the contralateral L5 DRG. Such reduction was also observed in the ipsilateral L5 DRG on day 7 after sciatic nerve axotomy. Rescuing nerve injury-induced reduction of Kv1.2 in the injured L5 DRG attenuated the development and maintenance of SNL-induced pain hypersensitivity without affecting acute pain and locomotor function. This effect might be attributed to the prevention of SNL-induced upregulation of endogenous Kv1.2 antisense RNA, in addition to the increase in Kv1.2 protein expression, in the injured DRG. Our findings suggest that Kv1.2 may be a novel potential target for preventing and/or treating neuropathic pain.
Potassium channels; Kv1.2; Distribution; Dorsal root ganglion; Neuropathic pain
The Pacific Decadal Oscillation (PDO) is a large-scale climatic phenomenon modulating ocean-atmosphere variability on decadal time scales. While precipitation and river flow variability in the Great Barrier Reef (GBR) catchments are sensitive to PDO phases, the extent to which the PDO influences coral reefs is poorly understood. Here, six Porites coral cores were used to produce a composite record of coral luminescence variability (runoff proxy) and identify drivers of terrestrial influence on the Keppel reefs, southern GBR. We found that coral skeletal luminescence effectively captured seasonal, inter-annual and decadal variability of river discharge and rainfall from the Fitzroy River catchment. Most importantly, although the influence of El Niño-Southern Oscillation (ENSO) events was evident in the luminescence records, the variability in the coral luminescence composite record was significantly explained by the PDO. Negative luminescence anomalies (reduced runoff) were associated with El Niño years during positive PDO phases while positive luminescence anomalies (increased runoff) coincided with strong/moderate La Niña years during negative PDO phases. This study provides clear evidence that not only ENSO but also the PDO have significantly affected runoff regimes at the Keppel reefs for at least a century, and suggests that upcoming hydrological disturbances and ecological responses in the southern GBR region will be mediated by the future evolution of these sources of climate variability.
The inshore reefs of the Great Barrier Reef (GBR) have undergone significant declines in water quality following European settlement (approx. 1870 AD). However, direct evidence of impacts on coral assemblages is limited by a lack of historical baselines prior to the onset of modern monitoring programmes in the early 1980s. Through palaeoecological reconstructions, we report a previously undocumented historical collapse of Acropora assemblages at Pelorus Island (central GBR). High-precision U-series dating of dead Acropora fragments indicates that this collapse occurred between 1920 and 1955, with few dates obtained after 1980. Prior to this event, our results indicate remarkable long-term stability in coral community structure over centennial scales. We suggest that chronic increases in sediment flux and nutrient loading following European settlement acted as the ultimate cause for the lack of recovery of Acropora assemblages following a series of acute disturbance events (SST anomalies, cyclones and flood events). Evidence for major degradation in reef condition owing to human impacts prior to modern ecological surveys indicates that current monitoring of inshore reefs on the GBR may be predicated on a significantly shifted baseline.
coral; Acropora; palaeoecology; historical mortality; Great Barrier Reef; European settlement
The development of opioid-induced analgesic tolerance and hyperalgesia is a clinical challenge for managing chronic pain. Adaptive changes in protein translation in the nervous system are thought to promote opioid tolerance and hyperalgesia; however, how opioids drive such changes remains elusive. Here, we report that mammalian target of rapamycin (mTOR), which governs most protein translation, was activated in rat spinal dorsal horn neurons after repeated intrathecal morphine injections. Activation was triggered through μ opioid receptor and mediated by intracellular PI3K/Akt. Spinal mTOR inhibition blocked both induction and maintenance of morphine tolerance and hyperalgesia, without affecting basal pain perception or locomotor functions. These effects were attributed to the attenuation of morphine-induced increases in translation initiation activity, nascent protein synthesis, and expression of some known key tolerance-associated proteins, including neuronal NOS (nNOS), in dorsal horn. Moreover, elevating spinal mTOR activity by knocking down the mTOR-negative regulator TSC2 reduced morphine analgesia, produced pain hypersensitivity, and increased spinal nNOS expression. Our findings implicate the μ opioid receptor–triggered PI3K/Akt/mTOR pathway in promoting morphine-induced spinal protein translation changes and associated morphine tolerance and hyperalgesia. These data suggest that mTOR inhibitors could be explored for prevention and/or reduction of opioid tolerance in chronic pain management.
The increased risk of thrombosis in systemic lupus erythematosus (SLE) may be partially explained by interrelated genetic pathways for thrombosis and SLE. In a case-control analysis, we investigated whether 33 established and novel single nucleotide polymorphisms (SNP) in 20 genes involved in hemostasis pathways that have been associated with deep venous thrombosis in the general population were risk factors for SLE development among Asians.
Patients in the discovery cohort were enrolled in one of two North American SLE cohorts. Patients in the replication cohort were enrolled in one of four Asian or two North American cohorts. SLE cases met American College of Rheumatology classification criteria. We first genotyped 263 Asian SLE and 357 healthy Asian control individuals for 33 SNPs using Luminex multiplex technology in the discovery phase, and then used Taqman and Immunochip assays to examine 5 SNPs in up to an additional 1496 cases and 993 controls in the Replication phase. SLE patients were compared to healthy controls for association with minor alleles in allelic models. Principal components analysis was used to control for intra-Asian ancestry in an analysis of the replication cohort.
Two genetic variants in the gene VKORC1, rs9934438 and rs9923231, were highly significant in both the discovery and replication cohorts: OR(disc) = 2.45 (p=2×10−9), OR(rep) = 1.53 (p=5×10−6) and OR(disc) = 2.40 (p=6×10−9), OR(rep) = 1.53 (p=5×10−6), respectively. These associations were significant in the replication cohort after adjustment for intra-Asian ancestry: rs9934438 OR(adj) = 1.34 (p=0.0029) and rs9923231 OR(adj) = 1.34 (p=0.0032).
Genetic variants in VKORC1, involved in vitamin K reduction and associated with DVT, are associated with SLE development in Asians. These results suggest intersecting genetic pathways for the development of SLE and thrombosis.
systemic lupus erythematosus; single nucleotide polymorphisms; genetic risk factors
Novel small molecule antagonists of NPBWR1 (GPR7) are herein reported. A high-throughput screening (HTS) of the Molecular Libraries-Small Molecule Repository library identified 5-chloro-4-(4-methoxyphenoxy)-2-(p-tolyl)pyridazin-3(2H)-one as a NPBWR1 hit antagonist with micromolar activity. Design, synthesis and structure–activity relationships study of the HTS-derived hit led to the identification of 5-chloro-2-(3,5-dimethylphenyl)-4-(4-methoxyphenoxy)pyridazin-3(2H)-one lead molecule with submicromolar antagonist activity at the target receptor and high selectivity against a panel of therapeutically relevant off-target proteins. This lead molecule may provide a pharmacological tool to clarify the molecular basis of the in vivo physiological function and therapeutic utility of NPBWR1 in diverse disease areas including inflammatory pain and eating disorders.
NPBWR1 (GPR7); Selective small molecule antagonists; Feeding behavior and energy homeostasis; Inflammatory pain
An alkaline polygalacturonate lyase (PGL) from Bacillus subtilis 7-3-3, PelC, with diverse depolymerization abilities for different pectin substrates was found. The PGL activity of PelC decreased with increasing degree of methyl esterification of the substrate. PelA and PelC displayed notable synergistic effects in the enzymatic degumming of ramie fibers. Gum loss rates increased by 62% when PelC was used to replace up to three-eighths of the PelA dose (PelC, 60 U g−1 ramie fibers). To the best of our knowledge, this study is the first to report the synergistic action of members of polysaccharide lyase families 1 and 3, represented by PelA and PelC, respectively. The present paper provides new insights into the improvement and production of enzymes used in enzymatic degumming.
The symmetric title molecule, [Hf(C26H40N4Si)Cl4], lies about a twofold rotation axis. The HfIV and Si atoms lie on the rotation axis with all other atoms being in general positions. The HfIV atom is six-coordinated by two N atoms from the N
2′-(dimethylsilanediyl)bis(N-tert-butyl-3-methylbenzimidamidate) ligand and four Cl− ions in a slightly distorted octahedral geometry. The two amidinate moieties are connected through the central Si atom with Si—N bond length of 1.762 (3) Å, generating the characteristic N—C—N—Si—N—C—N skeleton of a silyl-linked ansa-bis(amidine) species.
Accumulating evidence implicates the relationship between neuroinflammation and pathogenesis in idiopathic Parkinson's disease (iPD). The nose has recently been considered a gate way to the brain which facilitates entry of environmental neurotoxin into the brain. Our study aims to build a PD model by a natural exposure route. In this report, we establish a new endotoxin-based PD model in mice by unilateral intranasal (i.n.) instillation of the lipopolysaccharides (LPS) every other day for 5 months. These mice display a progressive hypokinesia, selective loss of dopaminergic neurons, and reduction in striatal dopamine (DA) content, as well as α-synuclein aggregation in the SN, without systemic inflammatory and immune responses. This new PD model provides a tool for studying the inflammation-mediated chronic pathogenesis and searching for therapeutic intervention in glia-neuron pathway that will slow or halt neurodegeneration in PD.
Objectives: A number of studies conducted to assess the association between Clara cell 10-kDa protein (CC10) +38A/G polymorphism and susceptibility to asthma have yielded inconsistent and inconclusive results. In the present study, the possible association was assessed by a meta-analysis.
Methods: Relevant articles were identified for the period ranging from Jan 1998 up to March 2013. Pooled odds ratios (OR) with 95% confidence intervals (CI) were appropriately derived from fixed effects or random-effects models.
Results: Ten case-control studies with a total of 1529 asthma cases and 2399 controls were included in this meta-analysis. The association between CC10 +38A/G polymorphism and asthma risk was determined in dominant model, recessive model, additive model, and codominant model. In dominant model, CC10 +38A/G polymorphism seemed to be associated with elevated asthma risk (OR = 1.62; 95% CI, 1.23-2.12; P = 0.0005). Subgroup analyses by ethnicity also found significant associations between this polymorphism and asthma risk in Asians and Caucasians. Results from other genetic models further identified this possible association.
Conclusion: This meta-analysis suggests that CC10 +38A/G polymorphism confers asthma risk.
Asthma; CC10; Meta-analysis; Polymorphism
Immunoregulatory cytokine interleukin-10 (IL-10) is elevated in sera from patients with systemic lupus erythematosus (SLE) correlating with disease activity. The established association of IL10 with SLE and other autoimmune diseases led us to fine map causal variant(s) and to explore underlying mechanisms. We assessed 19 tag SNPs, covering the IL10 gene cluster including IL19, IL20 and IL24, for association with SLE in 15,533 case and control subjects from four ancestries. The previously reported IL10 variant, rs3024505 located at 1 kb downstream of IL10, exhibited the strongest association signal and was confirmed for association with SLE in European American (EA) (P = 2.7×10−8, OR = 1.30), but not in non-EA ancestries. SNP imputation conducted in EA dataset identified three additional SLE-associated SNPs tagged by rs3024505 (rs3122605, rs3024493 and rs3024495 located at 9.2 kb upstream, intron 3 and 4 of IL10, respectively), and SLE-risk alleles of these SNPs were dose-dependently associated with elevated levels of IL10 mRNA in PBMCs and circulating IL-10 protein in SLE patients and controls. Using nuclear extracts of peripheral blood cells from SLE patients for electrophoretic mobility shift assays, we identified specific binding of transcription factor Elk-1 to oligodeoxynucleotides containing the risk (G) allele of rs3122605, suggesting rs3122605 as the most likely causal variant regulating IL10 expression. Elk-1 is known to be activated by phosphorylation and nuclear localization to induce transcription. Of interest, phosphorylated Elk-1 (p-Elk-1) detected only in nuclear extracts of SLE PBMCs appeared to increase with disease activity. Co-expression levels of p-Elk-1 and IL-10 were elevated in SLE T, B cells and monocytes, associated with increased disease activity in SLE B cells, and were best downregulated by ERK inhibitor. Taken together, our data suggest that preferential binding of activated Elk-1 to the IL10 rs3122605-G allele upregulates IL10 expression and confers increased risk for SLE in European Americans.
Systemic lupus erythematosus (SLE), a debilitating autoimmune disease characterized by the production of pathogenic autoantibodies, has a strong genetic basis. Variants of the IL10 gene, which encodes cytokine interleukin-10 (IL-10) with known function of promoting B cell hyperactivity and autoantibody production, are associated with SLE and other autoimmune diseases, and serum IL-10 levels are elevated in SLE patients correlating with increased disease activity. In this study, to discover SLE-predisposing causal variant(s), we assessed variants within the genomic region containing IL10 and its gene family member IL19, IL20 and IL24 for association with SLE in case and control subjects from diverse ancestries. We identified SLE-associated SNP rs3122605 located at 9.2 kb upstream of IL10 as the most likely causal variant in subjects of European ancestry. The SLE-risk allele of rs3122605 was dose-dependently associated with elevated IL10 expression at both mRNA and protein levels in peripheral blood samples from SLE patients and controls, which could be explained, at least in part, by its preferential binding to Elk-1, a transcription factor activated in B cells during active disease of SLE patients. Elk-1-mediated IL-10 overexpression could be downregulated by inhibiting activation of mitogen-activated protein kinases, suggesting a potential therapeutic target for SLE.
The role of many genes and interactions among genes involved in flowering time have been studied extensively in Arabidopsis, and the purpose of this study was to investigate how effectively results obtained with the model species Arabidopsis can be applied to the Brassicacea with often larger and more complex genomes. Brassica rapa represents a very close relative, with its triplicated genome, with subgenomes having evolved by genome fractionation. The question of whether this genome fractionation is a random process, or whether specific genes are preferentially retained, such as flowering time (Ft) genes that play a role in the extreme morphological variation within the B. rapa species (displayed by the diverse morphotypes), is addressed. Data are presented showing that indeed Ft genes are preferentially retained, so the next intriguing question is whether these different orthologues of Arabidopsis Ft genes play similar roles compared with Arabidopsis, and what is the role of these different orthologues in B. rapa. Using a genetical–genomics approach, co-location of flowering quantitative trait loci (QTLs) and expression QTLs (eQTLs) resulted in identification of candidate genes for flowering QTLs and visualization of co-expression networks of Ft genes and flowering time. A major flowering QTL on A02 at the BrFLC2 locus co-localized with cis eQTLs for BrFLC2, BrSSR1, and BrTCP11, and trans eQTLs for the photoperiod gene BrCO and two paralogues of the floral integrator genes BrSOC1 and BrFT. It is concluded that the BrFLC2 Ft gene is a major regulator of flowering time in the studied doubled haploid population.
Brassica rapa; candidate gene mapping; expression quantitative trait loci (eQTL); FLOWERING LOCUS C (FLC).; flowering time; gene expression networks; genome triplication.
Cancer treatment-related bone loss has become growing problematic, especially in breast and prostate cancer treated with hormone/endocrine therapy, chemotherapy and radiotherapy. However, bone loss caused by targeted therapy in cancer patients is largely unknown yet. In present study, a kinase inhibitors screen was applied for MC3T3-E1, a murine osteoprogenitor cell line, and seven kinase inhibitors (GSK1838705A, PF-04691502, Dasatinib, Masitinib, GDC-0941, XL880 and Everolimus) were found to suppress the cell viability with dose- and time-dependent manner. The most interesting is that many kinase inhibitors (such as lapatinib, erlotinib and sunitinib) can promote MC3T3-E1 cell proliferation at 0.01 μM. 4 out of 7 inhibitors were selected to perform the functional study and found that they lead to cell cycle dysregulation, treatments of PF-04691502 (AKT inhibitor), Dasatinib (Src inhibitor) and Everolimus (mTOR inhibitor) lead to G1 arrest of MC3T3-E1 cells via downregulation of cyclin D1 and p-AKT, whereas XL880 (MET and VEGFR inhibitor) treatment results in increase of sub-G1 and G2/M phase by upregulation of p53 protein. Our work provides important indications for the comprehensive care of cancer patients treated with some targeted drugs.
Cancer treatment-related bone loss; kinases inhibitors screening; osteoprogenitor cells
The aim of this study was to evaluate the effects of recombinant human adenovirus p53 (rAd-p53; Gendicine) transfection and radiation at various time points following transfection. Cytotoxic effects and p53 protein expression levels were analyzed. rAd-p53 containing the human wild-type p53 gene was introduced into the human lung adenocarcinoma cell line A549, and cells were irradiated with a single dose of 6 MeV 4 Gy β rays. According to the time interval between rAd-p53 transfection and radiotherapy (RT), A549-transfected rAd-p53 cells were divided into 5 groups: radiation administered immediately after transfection (0 h-RT) group, after 3 h group (3 h-RT), after 6 h group (6 h-RT), after 24 h group (24 h-RT) and after 48 h group (48 h-RT). Cells with rAd-p53 transfection alone (Ad-p53) and with empty adenovirus (Ad) were included as the two control groups. Following 72 h of transfection, cell viability and growth were analyzed using MTT assays and flow cytometry, and p53 protein expression was analyzed using western blot analysis. From 0 h-RT to 48 h-RT, cell viability gradually decreased, while percentage of apoptotic cells and p53 protein expression gradually increased. The cell viability suppression rates in the 6 h-RT, 24 h-RT and 48 h-RT groups were 56.7±5.4, 60.8±6.0 and 68.9±6.6, respectively, which were significantly greater compared to that of the Ad-p53 (40.8±4.7), 0 h-RT (45.0±3.5) and 3 h-RT groups (47.0±4.3). No statistically significant differences were observed in the cell viability suppression rates among the 6 h-RT, 24 h-RT and 48 h-RT groups (P>0.05). Similar changes were observed in the percentage of apoptotic cells. The p53 protein expression level in the 6 h-RT group (0.856±0.092) was higher compared to that in the 3 h-RT group (0.643±0.089) (t=2.882; P=0.045), but not significantly different from that of the 24 h-RT group (1.193±0.202). The cell viability suppression rate and percentage of apoptotic cells was positively correlated with p53 protein expression in the A549 cells (P<0.05). Radiation may inhibit or damage p53 protein expression at the early stage of rAd-p53 transfection. To sensitize tumor cells to irradiation and achieve maximal cytotoxic effects, it is recommended to conduct RT at least 6 h following transfection with rAd-p53.
adenovirus p53; radiation therapy; gene therapy
To analyze the clinicopathologic characteristics and prognostic factors of small gastrointestinal stromal tumor (GIST) of the stomach.
A total of 31 small gastric GIST patients, including 10 males and 21 females, with a median age of 58 years (37-81 years), who underwent surgery at any time from 1999 to 2012 were included in this study. The clinical records of the patients were analyzed retrospectively.
Abdominal discomfort and pain (10 cases, 32.3%, respectively) were the two most common complaints among the patients. All patients received surgery, 11 received gastric wedge resection, 11 received subtotal gastrectomy, 5 received laparoscopic gastric wedge resection, and 4 received endoscopic submucosal dissection. No severe adverse complication was observed. A total of 29 patients (93.5%) were followed up. During the follow-up, 2 patients were found to exhibit tumor recurrence, and 1 patient had liver metastases. One patient died of tumor progression, while another died of another malignant tumor. Median progression free survival (PFS) time was 120.3 months, and median overall survival (OS) time was 130.4 months.
Small gastric GIST has better prognosis. Surgery is the best choice for therapy. Micro-invasive procedures are safe and effective for elective patients. Tumor necrosis, tumor bleeding, and muscle invasion are potential prognostic factors of small gastric GIST.
Gastrointestinal stromal tumors; endoscopy; prognosis