N-methyl-D-aspartic acid (NMDA) receptors are critical for both normal brain functions and the pathogenesis of schizophrenia. We investigated the functional changes of glutamatergic receptors in the pyramidal cells and fast-spiking (FS) interneurons in the adolescent rat prefrontal cortex in MK-801 model of schizophrenia. We found that although both pyramidal cells and FS interneurons were affected by in vivo subchronic blockade of NMDA receptors, MK-801 induced distinct changes in αamino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) and NMDA receptors in the FS interneurons compared with pyramidal cells. Specifically, the amplitude, but not the frequency, of AMPA-mediated miniature excitatory postsynaptic currents (mEPSCs) in FS interneurons was significantly decreased whereas both the frequency and amplitude in pyramidal neurons were increased. In addition, MK-801-induced new presynaptic NMDA receptors were detected in the glutamatergic terminals targeting pyramidal neurons but not FS interneurons. MK-801 also induced distinct alterations in FS interneurons but not in pyramidal neurons, including significantly decreased rectification index and increased calcium permeability. These data suggest a distinct cell-type specific and homeostatic synaptic scaling and redistribution of AMPA and NMDA receptors in response to the subchronic blockade of NMDA receptors and thus provide a direct mechanistic explanation for the NMDA hypofunction hypothesis that have long been proposed for the schizophrenia pathophysiology.
MK-801; AMPA receptors; fast-spiking interneurons; NMDA receptor hypofunction; schizophrenia
As a proinflammatory cytokine, interleukin-17 (IL-17) contributes to the inflammation of many autoimmune diseases. We examined IL-17 levels in serum and tissues from patients with chronic hepatitis B virus infection (HBV), and especially evaluated the role of IL-17 in the pathogenesis and progression of liver fibrosis.
Materials and methods
Whole venous blood was obtained from four patient groups: chronic hepatitis B (CHB, n = 47), liver cirrhosis (LC, n = 49), primary hepatocellular carcinoma (PHC, n = 44), chronic liver failure (CLF, n = 33), and a normal control group (n = 20). HBsAg was positive in all patients. Liver biopsy samples were acquired from asymptomatic HBsAg carriers (ASC, n = 35), CHB (n = 57), and LC (n = 31) patients. We performed ELISA to measure IL-17 levels in serum samples, and used reverse RT-PCR to measure IL-17 mRNA levels in peripheral blood mononuclear cells (PBMC). IL-17 protein expression was detected in liver biopsy tissues by immunohistochemistry.
Compared to normal controls, serum IL-17 protein and mRNA levels were significantly higher in the four infection groups. LC patients exhibited the highest serum IL-17 and PBMC mRNA levels. No significant differences were found between the other three groups. High levels of IL-17 were also observed in tissues from CHB and LC patients, compared to ASC. IL-17 expression was mainly located in the portal area and was positively correlated with inflammation grade and fibrosis stage.
IL-17 expression was found to be increased with increasing degrees of liver fibrosis. This suggests that IL-17 may not only induce the inflammation, but also contribute to disease progression and chronicity.
The virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/5306959258322482
Asymptomatic; Hepatitis B surface antigen Carriers; Interleukin-17; Hepatitis B virus; Chronic hepatitis B; Liver cirrhosis; Primary hepatitis carcinoma; Chronic liver failure; Fibrosis
Rs2910164, a Single nucleotide polymorphism (SNP) located in the precursor microRNA sequence of miR-146a, is the only MicroRNA sequence SNP studied in papillary thyroid cancer (PTC). Association studies had been performed in US and UK-Northern European populations, but results were inconsistence. This study evaluated the association between rs2910164 and the risk of PTC as well as benign thyroid tumor (BN), and examined the clinicopathological characteristics of PTC and BN for different genotypes.
This case-control study genotyped rs2910164 in 753 PTCs, 484 BNs and 760 controls in a Chinese Han population. Clinicopathological and genetic data were collected and compared. Multivariate logistic regression was performed to calculate adjusted odds ratios (ORs).
There were no differences in rs2910164 genotype distributions between the three groups. PTC cases with three genotypes (CC, CG, GG) had similar clinicopathological characteristics except the existence of “para-cancer” BN (PTC/BN, P = 0.006). PTC/BN patients were older (P = 0.009), and had smaller cancer lesions (P<0.001), lower serum thyrotropin levels (1.82±1.42 vs. 2.21±1.74, P = 0.04), and lower rates of level VI lymph node metastasis (20.8% vs. 52.7%, P<0.001) and lateral neck lymph node metastasis (11.5% vs. 23.0%, P = 0.011) compared with PTC only. Then we supposed a possible progression from BN to PTC which may involve rs2910164 in and performed a multivariate logistic regression analysis of PTC/BN and BN cases to determine risk factors of this progression. Results showed that the rs2910164 GG homozygote (OR = 2.25, 95% CI 1.22–4.14, P = 0.01) was the only risk factor in this study.
Rs2910164 was not associated with increased risk of PTC and BN in Chinese patients, but may play a latent role in the transformation from BN to PTC.
A two-year study (2009 ∼ 2010) was carried out to investigate the dynamics of different carbon (C) forms, and the role of stream export in the C balance of a 23.4-ha headwater catchment in a tropical seasonal rainforest at Xishuangbanna (XSBN), southwest China. The seasonal volumetric weighted mean (VWM) concentrations of total inorganic C (TIC) and dissolved inorganic C (DIC) were higher, and particulate inorganic C (PIC) and organic C (POC) were lower, in the dry season than the rainy season, while the VWM concentrations of total organic C (TOC) and dissolved organic C (DOC) were similar between seasons. With increased monthly stream discharge and stream water temperature (SWT), only TIC and DIC concentrations decreased significantly. The most important C form in stream export was DIC, accounting for 51.8% of the total C (TC) export; DOC, POC, and PIC accounted for 21.8%, 14.9%, and 11.5% of the TC export, respectively. Dynamics of C flux were closely related to stream discharge, with the greatest export during the rainy season. C export in the headwater stream was 47.1 kg C ha−1 yr−1, about 2.85% of the annual net ecosystem exchange. This finding indicates that stream export represented a minor contribution to the C balance in this tropical seasonal rainforest.
The scavenger receptor, class B, type I (SR-BI) binds high-density lipoprotein (HDL) and mediates selective delivery of cholesteryl esters (CEs) to the liver and steroidogenic cells of the adrenal and gonads. Although it is clear that the large extracellular domain (ECD) of SR-BI binds HDL, the role of ECD in the selective HDL-CE transport remains poorly understood. In this study, we used a combination of mutational and chemical approaches to systematically evaluate the contribution of cysteine residues, especially six cysteine residues of ECD, in SR-BI-mediated selective HDL-CE uptake, intracellular trafficking and SR-BI dimerization. Pretreatment of SR-BI overexpressing COS-7 cells with disulfide (S-S) bond reducing agent, β-mercaptoethanol (100 mM) or dithiothreitol (DTT) (10 mM) modestly, but significantly impaired the SR-BI mediated selective HDL-CE uptake. Treatment of SR-BI overexpressing COS-7 cells with the optimum doses of membrane permeant alkyl methanethiosulfonate (MTS) reagents, positively charged MTSEA or neutral MMTS that specifically react with the free sulfhydryl group of cysteine reduced the SR-BI-mediated selective HDL-CE uptake, indicating that certain intracellular free cysteine residues may also be critically involved in the selective cholesterol transport process. In contrast, use of membrane impermeant MTS reagent, positively charged MTSET and negatively charged MTSES showed no such effect. Next, the importance of eight cysteine residues in SR-BI expression, cell surface expression, dimer formation and selective HDL-derived CE transport was evaluated. These cysteine residues were replaced either singly or in pairs with serine and the mutant SR-BIs expressed in either COS-7 or CHO cells. Four mutations, C280S, C321S, C323S or C334S of the ECD, either singly or in various pair combinations, resulted in significant decreases in SR-BI (HDL) binding activity, selective-CE uptake, and trafficking to cell surface. Surprisingly, we found that mutation of the two remaining cysteine residues, C251 and C384 of the ECD, had no effect on either SR-BI expression or function. Other cysteine mutations and substitutions were also without any effect. Western blot data indicated that single and double mutants of C280, C321, C323 and C334 residues strongly favor dimer formation. However, they are rendered non-functional presumably due to mutation-induced formation of aberrant disulfide linkages resulting in inhibition of optimal HDL binding and, thus, selective HDL-CE uptake. These results provide novel insights about the functional role of four cysteine residues, C280, C321, C323 and C334 of SR-BI ECD domain in SR-BI expression and trafficking to cell surface, its dimerization, and associated selective CE transport function.
Endophytic actinobacteria colonize internal tissues of their host plants and are considered as a rich and reliable source of diverse species and functional microorganisms. In this study, endophytic actinobacterial strain YIM 63111 was isolated from surface-sterilized tissue of the medicinal plant Artemisia annua. We identified strain YIM 63111 as a member of the genus Pseudonocardia. A. annua seedlings grown under both sterile and greenhouse conditions were inoculated with strain YIM 63111. The growth of A. annua seedlings was strongly reduced when YIM 63111 was inoculated at higher concentrations under sterile conditions. However, no growth inhibition was observed when A. annua was grown under greenhouse conditions. Using an enhanced green fluorescent protein (EGFP) expressing YIM 63111 strain, we also observed the endophytic colonization of A. annua seedling using confocal laser-scanning microscopy. The transcription levels of the key genes involved in artemisinin biosynthesis were investigated using real time RT-PCR, revealing that cytochrome P450 monooxygenase (CYP71AV1) and cytochrome P450 oxidoreductase (CPR) expression were up-regulated in A. annua upon inoculation with strain YIM 63111 under certain conditions. The up-regulation of these genes was associated with the increased accumulation of artemisinin. These results suggest that endophytic actinobacteria effectively stimulate certain plant defense responses. Our data also demonstrate the use of Pseudonocardia sp. strain YIM 63111 as a promising means to enhance artemisinin production in plants.
It is recognized that endogenous cannabinoids, which signal through CB1 receptors in hepatic stellate cells (HSCs), exert a profibrotic effect on chronic liver diseases. In this study, we suppressed CB1 expression by lentivirus mediated small interfering RNA (CB1-RNAi-LV) and investigated its effect on hepatic fibrosis in vitro and in vivo. Our results demonstrated that CB1-RNAi-LV significantly inhibited CB1 expression, and suppressed proliferation and extracellular matrix production in HSCs. Furthermore, CB1-RNAi-LV ameliorated dimethylnitrosamine induced hepatic fibrosis markedly, which was associated with the decreased expression of mesenchymal cell markers smooth muscle α-actin, vimentin and snail, and the increased expression of epithelial cell marker E-cadherin. The mechanism lies on the blockage of Smad signaling transduction induced by transforming growth factor β1 and its receptor TGF-β RII. Our study firstly provides the evidence that CB1-RNAi-LV might ameliorate hepatic fibrosis through the reversal of epithelial-to-mesenchymal transition (EMT), while the CB1 antagonists AM251 had no effect on epithelial-mesenchymal transitions of HSCs. This suggests that CB1 is implicated in hepatic fibrosis and selective suppression of CB1 by small interfering RNA may present a powerful tool for hepatic fibrosis treatment.
AIM: To investigate the clinicopathological features and prognostic value of lysine specific demethylase 1 (LSD1) in hepatocellular carcinoma (HCC).
METHODS: We examined LSD1 expression in 60 paired liver cancer tissues and adjacent noncancerous tissues by quantitative real time polymerase chain reaction (qRT-PCR) and Western blotting. In addition, we analyzed LSD1 expression in 198 HCC samples by immunohistochemistry. The relationship between LSD1 expression, clinicopathological features and patient survival was investigated.
RESULTS: Immunohistochemistry, Western blotting, and qRT-PCR consistently confirmed LSD1 overexpression in HCC tissues compared to adjacent non-neoplastic tissues (P < 0.01). Additionally, immunostaining showed more LSD1-positive cells in the higher tumor stage (T3-4) and tumor grade (G3) than in the lower tumor stage (T1-2, P < 0.001) and tumor grade (G1-2, P < 0.001), respectively. Moreover, HCC patients with high LSD1 expression had significantly lower 5-year overall survival rates (P < 0.001) and lower 5-year disease-free survival rates (P < 0.001), respectively. A Cox proportional hazards model further demonstrated that LSD1 over-expression was an independent predictor of poor prognosis for both 5-year disease-free survival [hazards ratio (HR) = 1.426, 95%CI: 0.672-2.146, P < 0.001] and 5-year overall survival (HR = 2.456, 95%CI: 1.234-3.932, P < 0.001) in HCC.
CONCLUSION: Our data suggest for the first time that the overexpression of LSD1 protein in HCC tissues indicates tumor progression and predicts poor prognosis.
Hepatocellular carcinoma; Lysine specific demethylase 1; Tumor progression; Prognosis
Classical swine fever virus (CSFV) is the cause of CSF which is a severe disease of pigs, leading to heavy economic losses in many regions of the world. Nuclear factor-kappa B (NF-κB) is a critical regulator of innate and adaptive immunity, and commonly activated upon viral infection. In our previous study, we found that CSFV could suppress the maturation and modulate the functions of monocyte-derived dendritic cells (Mo-DCs) without activating NF-κB pathway. To further prove the effects of CSFV on the NF-κB signaling pathway, we investigated the activity of NF-κB after CSFV infection in vivo and in vitro.
Attenuated Thiverval strain and virulent wild-type GXW-07 strain were used as challenge viruses in this study. Porcine kidney 15 (PK-15) cells were cultured in vitro and peripheral blood mononuclear cells (PBMCs) were isolated from the blood of CSFV-infected pigs. DNA binding of NF-κB was measured by electrophoretic mobility shift assays (EMSA), NF-κB p65 translocation was detected using immunofluorescent staining, and p65/RelA and IκBα expression was measured by Western Blotting.
Infection of cells with CSFV in vitro and in vivo showed that compared with tumor necrosis factor alpha (TNF-α) stimulated cells, there was no distinct DNA binding band of NF-κB, and no significant translocation of p65/RelA from the cytoplasm to the nucleus was observed, which might have been due to the apparent lack of IkBa degradation.
CSFV infection had no effect on the NF-κB signaling pathway, indicating that CSFV could evade host activation of NF-κB during infection.
CSFV; NF-κB; PK-15; PBMC; p65; IκBα
Background and Aims Eleusine
(Poaceae) is a small genus of the subfamily Chloridoideae exhibiting considerable morphological and ecological diversity in East Africa and the Americas. The interspecific phylogenetic relationships of Eleusine are investigated in order to identify its allotetraploid origin, and a chronogram is estimated to infer temporal relationships between palaeoenvironment changes and divergence of Eleusine in East Africa.
Two low-copy nuclear (LCN) markers, Pepc4 and EF-1α, were analysed using parsimony, likelihood and Bayesian approaches. A chronogram of Eleusine was inferred from a combined data set of six plastid DNA markers (ndhA intron, ndhF, rps16-trnK, rps16 intron, rps3, and rpl32-trnL) using the Bayesian dating method.
The monophyly of Eleusine is strongly supported by sequence data from two LCN markers. In the cpDNA phylogeny, three tetraploid species (E. africana, E. coracana and E. kigeziensis) share a common ancestor with the E. indica–E. tristachya clade, which is considered a source of maternal parents for allotetraploids. Two homoeologous loci are isolated from three tetraploid species in the Pepc4 phylogeny, and the maternal parents receive further support. The A-type EF-1α sequences possess three characters, i.e. a large number of variations of intron 2; clade E-A distantly diverged from clade E-B and other diploid species; and seven deletions in intron 2, implying a possible derivation through a gene duplication event. The crown age of Eleusine and the allotetraploid lineage are 3·89 million years ago (mya) and 1·40 mya, respectively.
The molecular data support independent allotetraploid origins for E. kigeziensis and the E. africana–E. coracana clade. Both events may have involved diploids E. indica and E. tristachya as the maternal parents, but the paternal parents remain unidentified. The habitat-specific hypothesis is proposed to explain the divergence of Eleusine and its allotetraploid lineage.
Allotetraploid origin; chloroplast markers; East Africa; Eleusine; low-copy nuclear markers; phylogeny; Poaceae
Elevated blood glucose is generally regarded as one of the risk factors that lead to coronary heart disease in patients with type 2 diabetes. However, our studies show that after inducing short-term damage, high blood glucose subsequently provides paradoxical protection for vessel function of animals with high blood pressure. Vessels can adapt to sustained high blood glucose and produce different stress proteins to counteract, to some extent, the damage brought about by hypertension. The results help us understand part of the basis for vessel adaptation in diabetes. The implication for treatment of diabetes is that if the patients have long-standing diabetes and established cardiovascular disease, the target of blood glucose lowering should be less stringent and reached gradually to avoid abrupt cancellation of the pre-existing adaptations.
Although both diabetes and hypertension are risk factors for cardiovascular disease, the role of hyperglycaemia per se in endothelial dysfunction is controversial. This study was designed to examine whether hyperglycaemia, or streptozotocin-induced diabetes, could aggravate endothelial dysfunction in stroke-prone spontaneously hypertensive rats (SHRSP). Hyperglycaemia was induced by streptozotocin in 2-month-old SHRSP and age-matched normotensive Wistar–Kyoto (WKY) rats. The aorta was isolated 8 weeks after induction of hyperglycaemia to record its function and to examine its morphology with transmission electron microscopy. Endothelial/inducible nitric oxide synthase (eNOS/iNOS) and inducible/constitutive haem oxygenase (HO-1/HO-2) levels were determined with Western blotting. Aortic endothelial function and production of reactive oxygen species and nitric oxide were assayed after incubation in vitro in hyperglycaemic, hyperosmolar solution. Streptozotocin-induced diabetes of 8 weeks duration did not result in endothelial dysfunction in normotensive WKY rats. In contrast, hyperglycaemic WKY rats showed significantly enhanced endothelium-dependent vasodilatation, which was abrogated by simultaneous blocking of NOS and HO. The enhanced vasodilatation was associated with elevation of vascular eNOS and HO-1. Significant endothelial dysfunction and massive macrophage–monocyte infiltration were found in SHRSP aorta (the ratio of the number of macrophages to endothelial cells in the intima, expressed as a percentage, was 20.9 ± 2.8% in SHRSP versus 1.9 ± 0.5% in WKY rats, P < 0.01), which was attenuated significantly in hyperglycaemic SHRSP (11.3 ± 1.6%, P < 0.01 versus SHRSP). Acute hyperglycaemia (10 min) aggravated endothelial dysfunction in SHRSP, with a marked increase in intracellular reactive oxygen species and NO production. Sustained in vitro incubation in hyperglycaemic/hyperosmolar conditions (addition of an extra 50 mmol L−1 of glucose or mannitol to the usual buffer, to produce a final osmolarity of 350 mosmol L−1) for 5 h enhanced endothelium-dependent vasodilatation, with elevated vessel NO production and upregulation of eNOS/HO-1 proteins. Sustained hyperglycaemia does not aggravate endothelial dysfunction and macrophage infiltration in SHRSP. Hyperglycaemia/hyperosmolarity-induced upregulation of eNOS and HO-1 may play a role in this paradoxical adaptation of endothelial function.
autism; Chinese; amino Acids profiles; liquid chromatography-tandem mass spectrometry
Sarcandra glabra, as a type of “antipyretic-detoxicate drugs”, has always been widely used in traditional Chinese medicine (TCM). The Sarcandra glabra extract (SGE) is applied frequently as anti-inflammatory and anti-infectious drug in folk medicine. However, relative experiment data supporting this effective clinical consequence was limited. In order to mimic the physiological conditions of the susceptible population, we employed restraint stress mouse model to investigate the effect of SGE against influenza. Mice were infected with influenza virus three days after restraint, while SGE was orally administrated for 10 consecutive days. Body weight, morbidity, and mortality were recorded daily. Histopathologic changes, susceptibility genes expressions and inflammatory markers in lungs were determined. Our results showed that restraint stress significantly increased susceptibility and severity of influenza virus. However, oral administration of SGE could reduce morbidity, mortality and significantly prolonged survival time. The results further showed that SGE had a crucial effect on improving susceptibility markers levels to recover the balance of host defense system and inhibiting inflammatory cytokines levels through down-regulation of NF-κB protein expression to ameliorate the lung injury. These data showed that SGE reduced the susceptibility and severity of influenza.
The objective of this study was to detect cerebral potentials elicited by proximal stimulation of the first sacral (S1) nerve root at the S1 dorsal foramen and to investigate latency and amplitude of the first cerebral potential. Tibial nerve SEP and S1 nerve root SEP were obtained from 20 healthy subjects and 5 patients with unilateral sciatic nerve or tibial nerve injury. Stimulation of the S1 nerve root was performed by a needle electrode via the S1 dorsal foramen. Cerebral potentials were recorded twice to document reproducibility. Latencies and amplitudes of the first cerebral potentials were recorded. Reproducible cerebral evoked potentials were recorded and P20s were identified in 36 of 40 limbs in the healthy subjects. The mean latency of P20 was 19.8 ± 1.6 ms. The mean amplitude of P20–N30 was 1.2 ± 0.9 μV. In the five patients, P40 of tibial nerve SEP was absent, while well-defined cerebral potentials of S1 nerve root SEP were recorded and P20 was identified from the involved side. This method may be useful in detecting S1 nerve root lesion and other disorders affecting the proximal portions of somatosensory pathway. Combined with tibial nerve SEP, it may provide useful information for diagnosis of lesions affecting the peripheral nerve versus the central portion of somatosensory pathway.
Somatosensory evoked potentials; Intra-operative monitoring; S1 nerve root; Nerve root stimulation
To study the prevalence rate of tuberous sclerosis complex in autistic disorder.
We studied one cohort of children followed up since 2005 until 2009, with autistic disorder, to determine the incidence of tuberous sclerosis complex. We established an autistic disorder registry in 2005 at China Rehabilitation Research Center. During the 4-year period (2005–2009), we collected a database of 429 children (390 boys and 39 girls; male to female ratio 10:1) with autistic disorder and pervasive developmental disorders. We routinely examined all children with autistic disorder for any features of tuberous sclerosis complex by looking for neurocutaneous markers such as depigmented spots. In those with infantile spasm or epilepsy, the clinical features of tuberous sclerosis complex were monitored regularly during follow-up.
Of these, five had tuberous sclerosis complex. Thus, the prevalence rate of tuberous sclerosis complex in autistic disorder is 1.17%. All of these children were mentally retarded with moderate to severe grades. Their IQ or developmental quotient was less than 70.
The prevalence rate of tuberous sclerosis complex in autistic disorder was 1.17% in our region; autism spectrum disorder is a condition that might be associated with development of tuberous sclerosis complex.
Tuberous Sclerosis Complex; Autism; Autistic Disorder; Neurocutaneous Syndromes
AIM: To investigate the expression of chondroitin sulphate proteoglycans (CSPGs) in rat liver tissues of hepatocellular carcinoma (HCC).
METHODS: Thirty male Sprague Dawley rats were randomly divided into two groups: control group (n = 10) and HCC model group (n = 20). Rats in the HCC model groups were intragastrically administrated with 0.2% (w/v) N-diethylnitrosamine (DEN) every 5 d for 16 wk, whereas 0.9% (w/v) normal saline was administered to rats in the control group. After 16 wk from the initiation of experiment, all rats were killed and livers were collected and fixed in 4% (w/v) paraformaldehyde. All tissues were embedded in paraffin and sectioned. Histological staining (hematoxylin and eosin and Toluidine blue) was performed to demonstrate the onset of HCC and the content of sulphated glycosaminoglycan (sGAG). Immunohistochemical staining was performed to investigate the expression of chondroitin sulphate (CS)/dermatan sulphate (DS)-GAG, heparan sulphate (HS)-GAG, keratan sulphate (KS)-GAG in liver tissues. Furthermore, expression and distribution of CSPG family members, including aggrecan, versican, biglycan and decorin in liver tissues, were also immunohistochemically determined.
RESULTS: After 16 wk administration of DEN, malignant nodules were observed on the surface of livers from the HCC model group, and their hepatic lobule structures appeared largely disrupted under microscope. Toluidine blue staining demonstrated that there was an significant increase in sGAG content in HCC tissues when compared with that in the normal liver tissues from the control group [0.37 ± 0.05 integrated optical density per stained area (IOD/area) and 0.21 ± 0.01 IOD/area, P < 0.05]. Immunohistochemical studies demonstrated that this increased sGAG in HCC tissues was induced by an elevated expression of CS/DS (0.28 ± 0.02 IOD/area and 0.18 ± 0.02 IOD/area, P < 0.05) and HS (0.30 ± 0.03 IOD/area and 0.17 ± 0.02 IOD/area, P < 0.01) but not KS GAGs in HCC tissues. Further studies thereby were performed to investigate the expression and distribution of several CSPG components in HCC tissues, including aggrecan, versican, biglycan and decorin. Interestingly, there was a distinct distribution pattern for these CSPG components between HCC tissues and the normal tissues. Positive staining of aggrecan, biglycan and decorin was localized in hepatic membrane and/or pericellular matrix in normal liver tissues; however, their expression was mainly observed in the cytoplasm, cell membranes in hepatoma cells and/or pericellular matrix within HCC tissues. Semi-quantitative analysis indicated that there was a higher level of expression of aggrecan (0.43 ± 0.01 and 0.35 ± 0.03, P < 0.05), biglycan (0.32 ± 0.01 and 0.25 ± 0.01, P < 0.001) and decorin (0.29 ± 0.01 and 0.26 ± 0.01, P < 0.05) in HCC tissues compared with that in the normal liver tissues. Very weak versican positive staining was observed in hepatocytes near central vein in normal liver tissues; however there was an intensive versican distribution in fibrosis septa between the hepatoma nodules. Semi-quantitative analysis indicated that the positive rate of versican in hepatoma tissues from the HCC model group was much higher than that in the control group (33.61% and 21.28%, P < 0.05). There was no positive staining in lumican and keratocan, two major KSPGs, in either normal or HCC liver tissues.
CONCLUSION: CSPGs play important roles in the onset and progression of HCC, and may provide potential therapeutic targets and clinical biomarkers for this prevalent tumor in humans.
Hepatocellular carcinoma; Proteoglycan; Chondroitin sulphate; Heparan sulphate; Keratan sulphate
Two new species, Olecryptotendipes exilis
sp. n. and Olecryptotendipes melasmus
sp. n. are described and illustrated as males and Chinese males of Olecryptotendipes lenzi are re-examined. A key to all known males of Olecryptotendipes is provided.
Chironomidae; Olecryptotendipes; new species; key; China
In a single proteomic project, tandem mass spectrometers can produce hundreds of millions of tandem mass spectra. However, majority of tandem mass spectra are of poor quality, it wastes time to search them for peptides. Therefore, the quality assessment (before database search) is very useful in the pipeline of protein identification via tandem mass spectra, especially on the reduction of searching time and the decrease of false identifications. Most existing methods for quality assessment are supervised machine learning methods based on a number of features which describe the quality of tandem mass spectra. These methods need the training datasets with knowing the quality of all spectra, which are usually unavailable for the new datasets.
This study proposes an unsupervised machine learning method for quality assessment of tandem mass spectra without any training dataset. This proposed method estimates the conditional probabilities of spectra being high quality from the quality assessments based on individual features. The probabilities are estimated through a constraint optimization problem. An efficient algorithm is developed to solve the constraint optimization problem and is proved to be convergent. Experimental results on two datasets illustrate that if we search only tandem spectra with the high quality determined by the proposed method, we can save about 56 % and 62% of database searching time while losing only a small amount of high-quality spectra.
Results indicate that the proposed method has a good performance for the quality assessment of tandem mass spectra and the way we estimate the conditional probabilities is effective.
Abnormal posture and spinal mobility have been demonstrated to cause functional impairment in the quality of life, especially in the postmenopausal osteoporotic population. Most of the literature studies focus on either thoracic kyphosis or lumbar lordosis, but not on the change of the entire spinal alignment. Very few articles reported the spinal alignment of Chinese people. The purpose of this study was threefold: to classify the spinal curvature based on the classification system defined by Satoh consisting of the entire spine alignment; to identify the change of trunk mobility; and to relate spinal curvature to balance disorder in a Chinese population.
450 osteoporotic volunteers were recruited for this study. Spinal range of motion and global curvature were evaluated noninvasively using the Spinal-Mouse® system and sagittal postural deformities were characterized.
We found a new spine postural alignment consisting of an increased thoracic kyphosis and decreased lumbar lordosis which we classified as our modified round back. We did not find any of Satoh’s type 5 classification in our population. Type 2 sagittal alignment was the most common spinal deformity (38.44%). In standing, thoracic kyphosis angles in types 2 (58.34°) and 3 (58.03°) were the largest and lumbar lordosis angles in types 4 (13.95°) and 5 (−8.61°) were the smallest. The range of flexion (ROF) and range of flexion-extension (ROFE) of types 2 and 3 were usually greater than types 4 and 5, with type 1 being the largest.
The present study classified and compared for the first time the mobility, curvature and balance in a Chinese population based on the entire spine alignment and found types 4 and 5 to present the worst balance and mobility. This study included a new spine postural alignment classification that should be considered in future population studies.
The American Diabetes Association and World Health Organization have recently adopted the HbA1c measurement as one method of diagnostic criteria for diabetes. The change in diagnostic criteria has important implications for diabetes treatment and prevention. We therefore investigate diabetes using HbA1c and glucose criteria together, and assess the prevalent trend in a developing southern Chinese population with 85 million residents.
A stratified multistage random sampling method was applied and a representative sample of 3590 residents 18 years of age or above was obtained in 2010. Each participant received a full medical check-up, including measurement of fasting plasma glucose, 2-hour post-load plasma glucose, and HbA1c. Information on history of diagnosis and treatment of diabetes was collected. The prevalence of diabetes obtained from the present survey was compared with the data from the survey in 2002.
The prevalence of diabetes based on both glucose and HbA1c measurements was 21.7% (95% CI: 17.4%–26.1%) in 2010, which suggests that more than 1 in 5 adult residents were suffering from diabetes in this developing population. Only 12.9% (95% CI: 8.3%–17.6%) of diabetic residents were aware of their condition. The prevalence of pre-diabetes was 66.3% (95% CI: 62.7%–69.8%). The prevalence of diabetes and pre-diabetes which met all the three diagnostic thresholds (fast plasma glucose, 2 hour post-load plasma glucose, and HbA1c) was 3.1% and 5.2%, respectively. Diabetes and pre-diabetes as determined by HbA1c measurement had higher vascular risk than those determined by glucose levels. The prevalence of diabetes increased from 2.9% (95% CI: 2.0%–3.7%) in 2002 to 13.8% (95% CI: 10.2%–17.3%) in 2010 based on the same glucose criteria.
Our results show that the diabetes epidemic is accelerating in China. The awareness of diabetes is extremely low. The glucose test and HbA1c measurement should be used together to increase detection of diabetes and pre-diabetes.
Saccharomonospora marina Liu et al. 2010 is a member of the genus Saccharomonospora, in the family Pseudonocardiaceae that is poorly characterized at the genome level thus far. Members of the genus Saccharomonospora are of interest because they originate from diverse habitats, such as leaf litter, manure, compost, surface of peat, moist, over-heated grain, and ocean sediment, where they might play a role in the primary degradation of plant material by attacking hemicellulose. Organisms belonging to the genus are usually Gram-positive staining, non-acid fast, and classify among the actinomycetes. Here we describe the features of this organism, together with the complete genome sequence (permanent draft status), and annotation. The 5,965,593 bp long chromosome with its 5,727 protein-coding and 57 RNA genes was sequenced as part of the DOE funded Community Sequencing Program (CSP) 2010 at the Joint Genome Institute (JGI).
aerobic; chemoheterotrophic; Gram-positive; vegetative and aerial mycelia; spore-forming; non-motile; marine bacterium; Pseudonocardiaceae; CSP 2010
Poly(4-hydroxybutyrate) [poly(4HB)] is a strong thermoplastic biomaterial with remarkable mechanical properties, biocompatibility and biodegradability. However, it is generally synthesized when 4-hydroxybutyrate (4HB) structurally related substrates such as γ-butyrolactone, 4-hydroxybutyrate or 1,4-butanediol (1,4-BD) are provided as precursor which are much more expensive than glucose. At present, high production cost is a big obstacle for large scale production of poly(4HB).
Recombinant Escherichia coli strain was constructed to achieve hyperproduction of poly(4-hydroxybutyrate) [poly(4HB)] using glucose as a sole carbon source. An engineering pathway was established in E. coli containing genes encoding succinate degradation of Clostridium kluyveri and PHB synthase of Ralstonia eutropha. Native succinate semialdehyde dehydrogenase genes sad and gabD in E. coli were both inactivated to enhance the carbon flux to poly(4HB) biosynthesis. Four PHA binding proteins (PhaP or phasins) including PhaP1, PhaP2, PhaP3 and PhaP4 from R. eutropha were heterologously expressed in the recombinant E. coli, respectively, leading to different levels of improvement in poly(4HB) production. Among them PhaP1 exhibited the highest capability for enhanced polymer synthesis. The recombinant E. coli produced 5.5 g L-1 cell dry weight containing 35.4% poly(4HB) using glucose as a sole carbon source in a 48 h shake flask growth. In a 6-L fermentor study, 11.5 g L-1 cell dry weight containing 68.2% poly(4HB) was obtained after 52 h of cultivation. This was the highest poly(4HB) yield using glucose as a sole carbon source reported so far. Poly(4HB) was structurally confirmed by gas chromatographic (GC) as well as 1H and 13C NMR studies.
Significant level of poly(4HB) biosynthesis from glucose can be achieved in sad and gabD genes deficient strain of E. coli JM109 harboring an engineering pathway encoding succinate degradation genes and PHB synthase gene, together with expression of four PHA binding proteins PhaP or phasins, respectively. Over 68% poly(4HB) was produced in a fed-batch fermentation process, demonstrating the feasibility for enhanced poly(4HB) production using the recombinant strain for future cost effective commercial development.
Poly(4HB); PHB; Polyhydroxyalkanoates; PhaP; 4-hydroxybutyrate; Escherichia coli; Metabolic engineering; Synthetic biology
Pharmacological intervention targeting mGluRs has emerged as a potential treatment for schizophrenia, whereas the mechanisms involved remain elusive. We explored the antipsychotic effects of an mGluR2/3 agonist in the MK-801 model of schizophrenia in the rat prefrontal cortex. We found that the mGluR2/3 agonist LY379268 effectively recovered the disrupted expression of NMDA receptors induced by MK-801 administration. This effect was attributable to the direct regulatory action of LY379268 on NMDA receptors via activation of the Akt/GSK-3β signaling pathway. As occurs with the antipsychotic drug clozapine, acute treatment with LY379268 significantly increased the expression and phosphorylation of NMDA receptors, as well as Akt and GSK-3β. Physiologically, LY379268 significantly enhanced NMDA-induced current in prefrontal neurons and a GSK-3β inhibitor occluded this effect. In contrast to the widely proposed mechanism of modulating presynaptic glutamate release, our results strongly argue that mGluR2/3 agonists modulate the function of NMDA receptors through postsynaptic actions and reverse the MK-801-induced NMDA dysfunction via the Akt/GSK-3β pathway. This study provides novel evidence for postsynaptic mechanisms of mGluR2/3 in regulation of NMDA receptors and presents useful insights into the mechanistic actions of mGluR2/3 agonists as potential antipsychotic agents for treating schizophrenia.
Antipsychotics; metabolic glutamate receptors; NMDA receptors; NMDA antagonism; signaling pathway; schizophrenia; schizophrenia; antipsychotics; glutamate; signal transduction; animal models; mGluR agonist; NMDA receptor
As more families participate expanded newborn screening for metabolic disorders in China, the overall number of false positives increases. Our goal was to assess the potential impact on parental stress, perceptions of the child's health, and family relationships.
Parents of 49 infants with false-positive screening results for metabolic disorders in the expanded newborn screening panel were compared with parents of 42 children with normal screening results. Parents first completed structured interview using likert scales, closed and open questions. Parents also completed the parenting stress index.
A total of 88 mothers and 41 fathers were interviewed. More mothers in the false-positive group reported that their children required extra parental care (21%), compared with 5% of mothers in the normal-screened group (P<0.001). 39% of mothers in the false-positive group reported that they worry about their child's future development, compared with 10% of mothers in the normal-screened group (P<0.001). Fathers in the false-positive group did not differ from fathers in the normal-screened group in reporting worry about their child's extra care requirements, and their child's future development. Children with false-positive results compared with children with normal results were triple as likely to experience hospitalization (27%vs 9%, respectively; P<0.001).
The results showing false-positive screening results may affect parental stress and the parent-child relationship. Parental stress and anxiety can be reduced with improved education and communication to parents about false-positive results.
The Maddenia clade of Prunus L. is monographed based on herbarium and field studies. Four species are currently accepted in this group: Prunus himalayana J.Wen, Prunus hypoleuca (Koehne) J.Wen, Prunus hypoxantha (Koehne) J.Wen, and Prunus gongshanensis J.Wen, with the last described herein as a new species. Maddenia fujianensis Y.T.Chang and Maddenia incisoserrata T.T.Yü & T.C.Ku are treated as synonyms of Prunus hypoleuca.
Maddenia; Prunus; Prunus gongshanensis; revision; Rosaceae