The Korean black raspberry (Rubus coreanus Miquel, KB) on ripening is usually consumed as fresh fruit, whereas the unripe KB has been widely used as a source of traditional herbal medicine. Such a stage specific utilization of KB has been assumed due to the changing metabolite profile during fruit ripening process, but so far molecular and biochemical changes during its fruit maturation are poorly understood. To analyze biochemical changes during fruit ripening process at molecular level, firstly, we have sequenced, assembled, and annotated the transcriptome of KB fruits. Over 4.86 Gb of normalized cDNA prepared from fruits was sequenced using Illumina HiSeq™ 2000, and assembled into 43,723 unigenes. Secondly, we have reported that alterations in anthocyanins and proanthocyanidins are the major factors facilitating variations in these stages of fruits. In addition, up-regulation of F3′H1, DFR4 and LDOX1 resulted in the accumulation of cyanidin derivatives during the ripening process of KB, indicating the positive relationship between the expression of anthocyanin biosynthetic genes and the anthocyanin accumulation. Furthermore, the ability of RcMCHI2 (R. coreanus Miquel chalcone flavanone isomerase 2) gene to complement Arabidopsis transparent testa 5 mutant supported the feasibility of our transcriptome library to provide the gene resources for improving plant nutrition and pigmentation. Taken together, these datasets obtained from transcriptome library and metabolic profiling would be helpful to define the gene-metabolite relationships in this non-model plant.
To introduce a robot-assisted surgical system for spinal posterior fixation that can automatically recognize the drilling state and stop potential cortical penetration with force and image information and to further evaluate the accuracy and safety of the robot for sheep vertebra pedicle screw placement.
The Robotic Spinal Surgery System (RSSS) was composed of an optical tracking system, a navigation and planning system, and a surgical robot equipped with a 6-DOF force/torque sensor. The robot used the image message and force signals to sense the different operation states and to prevent potential cortical penetration in the pedicle screw insertion operation. To evaluate the accuracy and safety of the RSSS, 32 screw insertions were conducted. Furthermore, six trajectories were deliberately planned incorrectly to explore whether the robot could recognize the different drilling states and immediately prevent cortical penetration.
All 32 pedicle screws were placed in the pedicle without any broken pedicle walls. Compared with the preoperative planning, the average deviations of the entry points in the axial and sagittal views were 0.50±0.33 and 0.65±0.40 mm, and the average deviations of the angles in the axial and sagittal views were 1.9±0.82° and 1.48±1.2°. The robot successfully recognized the different drilling states and prevented potential cortical penetration. In the deliberately incorrectly planned trajectory experiments, the robot successfully prevented the cortical penetration.
These results verified the RSSS’s accuracy and safety, which supported its potential use for the spinal surgery.
The field of view (FOV) of a cone-beam computed tomography (CBCT) unit in single-photon emission computed tomography (SPECT)/CBCT system can be increased by offsetting CBCT detector. Analytic-based algorithms have been developed for image reconstruction from data collected at a large number of densely sampled views in offset-detector CBCT. However, the radiation dose involved in a large number of projections can be of a health concern to the imaged subject. CBCT-imaging dose can be reduced by lowering the number of projections. As analytic-based algorithms are unlikely to reconstruct accurate images from sparse-view data, we investigate and characterize in the work optimization-based algorithms, including an adaptive steepest descent-weighted projection onto convex sets (ASD-WPOCS) algorithm, for image reconstruction from sparse-view data collected in offset-detector CBCT. Using simulated data, and real data collected from a physical pelvis phantom and patient, we verify and characterize properties of the algorithms under study. Results of our study suggest that optimization-based algorithms such as ASD-WPOCS may be developed for yielding images of potential utility from a number of projections substantially smaller than those used currently in clinical SPECT/CBCT imaging, thus leading to a dose reduction in CBCT imaging.
Two-way selection is a common phenomenon in nature and society. It appears in the processes like choosing a mate between men and women, making contracts between job hunters and recruiters, and trading between buyers and sellers. In this paper, we propose a model of two-way selection system, and present its analytical solution for the expectation of successful matching total and the regular pattern that the matching rate trends toward an inverse proportion to either the ratio between the two sides or the ratio of the state total to the smaller group's people number. The proposed model is verified by empirical data of the matchmaking fairs. Results indicate that the model well predicts this typical real-world two-way selection behavior to the bounded error extent, thus it is helpful for understanding the dynamics mechanism of the real-world two-way selection system.
In recent years, several path-breaking findings on human mobility patterns point out a novel issue which is of important theoretical significance and great application prospects. The empirical analysis of the data which can reflect the real-world human mobility provides the basic cognition and verification of the theoretical models and predictive results on human mobility. One of the most noticeable findings in previous studies on human mobility is the wide-spread scaling anomalies, e.g. the power-law-like displacement distributions. Understanding the origin of these scaling anomalies is of central importance to this issue and therefore is the focus of our discussion.
In this paper, we empirically analyze the real-world human movements which are based on GPS records, and observe rich scaling properties in the temporal-spatial patterns as well as an abnormal transition in the speed-displacement patterns together with an evidence to the real-world traffic jams. In addition, we notice that the displacements at the population level show a significant positive correlation, indicating a cascading-like nature in human movements. Furthermore, our analysis at the individual level finds that the displacement distributions of users with stronger correlations usually are closer to the power law, suggesting a correlation between the positive correlation of the displacement series and the form of an individual's displacement distribution.
These empirical findings make connections between the two basic properties of human mobility, the scaling anomalies on displacement distributions and the positive correlations on displacement series, implying the cascading-like dynamics which is exhibited by the positive correlations would cause the emergence of scaling properties on human mobility patterns. Our findings would inspire further researches on mechanisms and predictions of human mobility.
This study aimed to elucidate clinical significance of anaplastic lymphoma kinase (ALK) rearrangement in selected advanced non-small cell lung cancer (NSCLC), to compare the application of different ALK detection methods, and especially evaluate a possible association between ALK expression and clinical outcomes in crizotinib-treated patients.
ALK status was assessed by fluorescent in situ hybridization (FISH), immunohistochemistry (IHC) and quantitative RT-PCR (qRT-PCR) in 173 selected advanced NSCLC patients. Clinicopathologic data, genotype status and survival outcomes were analyzed. Moreover, the association of ALK expression with clinical outcomes was evaluated in ALK FISH-positive crizotinib-treated patients including two patients with concurrent epidermal growth factor receptor (EGFR) mutation.
The positivity detection rate of ALK rearrangement by FISH, IHC and qRT-PCR was 35.5% (59/166), 35.7% (61/171), and 27.9% (34/122), respectively. ALK rearrangement was observed predominantly in young patients, never or light smokers, and adenocarcinomas, especially with signet ring cell features and poor differentiation. Median progression-free survival (PFS) of crizotinib-treated patients was 7.6 months. The overall survival (OS) of these patients was longer compared with that of crizotinib-naive or wild-type cohorts, but there was no significant difference in OS compared with patients with EGFR mutation. ALK expression did not associate with PFS; but, when ALK expression was analyzed as a dichotomous variable, moderate and strong ALK expression had a decreased risk of death (P = 0.026). The two patients with concomitant EGFR and ALK alterations showed difference in ALK expression, response to EGFR and ALK inhibitors, and overall survival.
Selective enrichment according to clinicopathologic features in NSCLC patients could highly improve the positivity detection rate of ALK rearrangement for ALK-targeted therapy. IHC could provide more clues for clinical trial design and therapeutic strategies for ALK-positive NSCLC patients including patients with double genetic aberration of ALK and EGFR.
Type 2 diabetes is characterized by defective glucose-stimulated insulin secretion (GSIS) from pancreatic β cells, which can be restored by glucagon-like peptide 1 (GLP-1), an incretin hormone commonly used for the treatment of type 2 diabetes. However, molecular mechanisms by which GLP-1 affects glucose responsiveness in islet β cells remain poorly understood. Here we investigated a role of SAD-A, an AMP-activated protein kinase (AMPK)-related kinase, in regulating GSIS in mice with conditional SAD-A deletion. We show that selective deletion of SAD-A in pancreas impaired incretin's effect on GSIS, leading to glucose intolerance. Conversely, overexpression of SAD-A significantly enhanced GSIS and further potentiated GLP-1's effect on GSIS from isolated mouse islets. In support of SAD-A as a mediator of incretin response, SAD-A is expressed exclusively in pancreas and brain, the primary targeting tissues of GLP-1 action. Additionally, SAD-A kinase is activated in response to stimulation by GLP-1 through cyclic AMP (cAMP)/Ca2+-dependent signaling pathways in islet β cells. Furthermore, we identified Thr443 as a key autoinhibitory phosphorylation site which mediates SAD-A's effect on incretin response in islet β cells. Consequently, ablation of Thr443 significantly enhanced GLP-1's effect on GSIS from isolated mouse islets. Together, these findings identified SAD-A kinase as a pancreas-specific mediator of incretin response in islet β cells.
We aim to investigate the effects of locally injected natural and recombinant hirudin on vascular endothelial growth factor (VEGF) expression and flap survival in venous congested skin flaps using a rat model. A dorsal random skin flap (10 × 3 cm) was prepared on each of 30 Wistar rats to establish a venous congested model. The rats were randomly divided into 2 treatment groups [receiving subcutaneous injection of either natural hirudin (6 U) or recombinant hirudin (6 U)] and a control group, which received subcutaneous injection of physiologic saline. After treatment, skin flap survival rates were calculated. VEGF messenger RNA levels and VEGF-positive vessel density as a marker for VEGF levels were measured in the flaps during and after treatment. The skin flap VEGF messenger RNA levels increased in the natural hirudin-treated group. The VEGF-positive vessel density was increased in all 3 groups. Statistically significant increases of VEGF levels were observed in the natural and recombinant hirudin-treated groups compared with the control group (P < 0.05). The skin flap survival rates were improved in both hirudin treated groups. Natural and recombinant hirudin can increase VEGF expression in random skin flaps, which can potentially improve random skin flap survival in rats through angio genic mechanisms. Our results showed that hirudin treatment led to an increase in VEGF expression in the congested skin flaps. Natural hirudin demonstrated more pronounced effects than recombinant hirudin. Further studies are needed to understand the specific mechanisms.
Natural hirudin; Recombinant hirudin; VEGF; Random skin flap; Flap survival rate
Flavonoids are secondary metabolites derived from phenylalanine and acetate metabolism. They fulfil a variety of functions in plants and have health benefits for humans. During the synthesis of the tricyclic flavonoid natural products in plants, oxidative modifications to the central C ring are catalyzed by four of FeII and 2-oxoglutarate dependent (2-ODD) oxygenases, namely flavone synthase I (FNS I), flavonol synthase (FLS), anthocyanidin synthase (ANS) and flavanone 3β-hydroxylase (FHT). FNS I, FLS and ANS are involved in desaturation of C2–C3 of flavonoids and FHT in hydroxylation of C3. FNS I, which is restricted to the Apiaceae species and in rice, is predicted to have evolved from FHT by duplication. Due to their sequence similarity and substrate specificity, FLS and ANS, which interact with the α surface of the substrate, belong to a group of dioxygenases having a broad substrate specificity, while FNS I and FHT are more selective, and interact with the naringenin β surface. Here, we summarize recent findings regarding the function of the four 2-ODD oxygenases and the relationship between their catalytic activity, their polypeptide sequence and their tertiary structure.
flavonoid synthesis; 2-ODD oxygenases; flavone synthase I; flavonol synthase; anthocyanidin synthase; flavanone 3β-hydroxylase
Objective: This study aimed to investigate the development of neural stem cells (NSCs) in fetal brain, which may provide experimental evidence for the clinical treatment of brain injury in children. Methods: A total of 60 fetuses were collected after labor induction and divided into 6 groups according to the gestational age (16 w, 20 w, 24 w, 28 w, 32 w and 36 w; n=10 per group). The hippocampus, striatum, subventricular zone, frontal lobe, temporal lobe, occipital lobe and parietal lobe were harvested. In situ hybridization, immunohistochemistry and light microscopy were done to determine the morphology and quantity of NSCs. Results: NSCs were identified in the brain of fetuses with different gestational age. NSCs were round, oval, spindle-shaped, starlike, triangular or polygonal. NSC colony was also observed with symmetrical or asymmetrical division. Single NSC, group-like NSCs and cluster-like NSCs were found in the different sites of fetal brain, and NCSs interacted with each other via synapses. However, the distribution, morphology, growth and quantity of NSCs were different in the brain of fetuses with different gestational age. The number of NSCs reduced with the increase in gestational age, but they were always observed. Conclusion: The morphology of NSCs in fetal brain is variable and they are widely distributed in the hippocampus, subventricular zone, striatum and cortex. The number of NSCs reduced with the increase of gestational age.
Human; fetal brain; nestin
The planarian chromatin regulator HP1, at least in part acting through increased expression of Mcm5, inhibits differentiation of adult stem cells and triggers their proliferation in response to injury.
Adult stem cells (ASCs) capable of self-renewal and differentiation confer the potential of tissues to regenerate damaged parts. Epigenetic regulation is essential for driving cell fate decisions by rapidly and reversibly modulating gene expression programs. However, it remains unclear how epigenetic factors elicit ASC-driven regeneration. In this paper, we report that an RNA interference screen against 205 chromatin regulators identified 12 proteins essential for ASC function and regeneration in planarians. Surprisingly, the HP1-like protein SMED–HP1-1 (HP1-1) specifically marked self-renewing, pluripotent ASCs, and HP1-1 depletion abrogated self-renewal and promoted differentiation. Upon injury, HP1-1 expression increased and elicited increased ASC expression of Mcm5 through functional association with the FACT (facilitates chromatin transcription) complex, which consequently triggered proliferation of ASCs and initiated blastema formation. Our observations uncover an epigenetic network underlying ASC regulation in planarians and reveal that an HP1 protein is a key chromatin factor controlling stem cell function. These results provide important insights into how epigenetic mechanisms orchestrate stem cell responses during tissue regeneration.
Aromatic essential oils extracted from fresh fruits of Litsea cubeba (Lour.) Pers., have diverse medical and economic values. The dominant components in these essential oils are monoterpenes and sesquiterpenes. Understanding the molecular mechanisms of terpenoid biosynthesis is essential for improving the yield and quality of terpenes. However, the 40 available L. cubeba nucleotide sequences in the public databases are insufficient for studying the molecular mechanisms. Thus, high-throughput transcriptome sequencing of L. cubeba is necessary to generate large quantities of transcript sequences for the purpose of gene discovery, especially terpenoid biosynthesis related genes.
Using Illumina paired-end sequencing, approximately 23.5 million high-quality reads were generated. De
novo assembly yielded 68,648 unigenes with an average length of 834 bp. A total of 38,439 (56%) unigenes were annotated for their functions, and 35,732 and 25,806 unigenes could be aligned to the GO and COG database, respectively. By searching against the Kyoto Encyclopedia of Genes and Genomes Pathway database (KEGG), 16,130 unigenes were assigned to 297 KEGG pathways, and 61 unigenes, which contained the mevalonate and 2-C-methyl-D-erythritol 4-phosphate pathways, could be related to terpenoid backbone biosynthesis. Of the 12,963 unigenes, 285 were annotated to the terpenoid pathways using the PlantCyc database. Additionally, 14 terpene synthase genes were identified from the transcriptome. The expression patterns of the 16 genes related to terpenoid biosynthesis were analyzed by RT-qPCR to explore their putative functions.
RNA sequencing was effective in identifying a large quantity of sequence information. To our knowledge, this study is the first exploration of the L. cubeba transcriptome, and the substantial amount of transcripts obtained will accelerate the understanding of the molecular mechanisms of essential oils biosynthesis. The results may help improve future genetic and genomics studies on the molecular mechanisms behind the chemical composition of essential oils in L. cubeba fruits.
Independent Component Analysis (ICA) has been introduced as one of the useful tools for gene-functional discovery in animals. However, this approach has been poorly utilized in the plant sciences. In the present study, we have exploited ICA combined with pathway enrichment analysis to address the statistical challenges associated with genome-wide analysis in plant system. To generate an Arabidopsis metabolic platform, we collected 4,373 Affymetrix ATH1 microarray datasets. Out of the 3,232 metabolic genes and transcription factors, 99.47% of these genes were identified in at least one component, indicating the coverage of most of the metabolic pathways by the components. During the metabolic pathway enrichment analysis, we found components that indicate an independent regulation between the isoprenoid biosynthesis pathways. We also utilized this analysis tool to investigate some transcription factors involved in secondary cell wall biogenesis. This approach has identified remarkably more transcription factors compared to previously reported analysis tools. A website providing user-friendly searching and downloading of the entire dataset analyzed by ICA is available at http://kimjy.gnu.ac.kr/ICA.files/slide0002.htm. ICA combined with pathway enrichment analysis might provide a powerful approach for the extraction of the components responsible for a biological process of interest in plant systems.
independent component analysis (ICA); isoprenoid biosynthesis pathway; lignin biosynthesis pathway; secondary cell wall biogenesis; transcription factor (TF)
BCG-activated macrophages (BAM) could kill the tumor cells through cell-cell contact. In this process membrane proteins play an important role. However, up to date, few membrane proteins were revealed. In this study, we selected a surface molecule named Trim59, which was specifically expressed on BAM membrane (compared with the negative control). We cloned and prokaryoticly expressed the extracellular domain of Trim59, purified the recombinant protein and generated polyclonal antibodies. Immunohistochemistry showed that Trim59 abundantly expressed in spleen, stomach and ovary; intermediately expressed in brain, lung, kidney, muscle and intestine; but not in thymus, liver, heart, uterus. Using the antibodies to block Trim59 on BAM significantly reduced BAM cytotoxicity against MCA207 cells. This demonstrated that Trim59 serves as an indispensable molecule in maintaining BAM activity. Overexpression of Trim59 in Raw264.7 cell line failed to lyse target MCA207 cells, which potentiated Trim59 per se could not enhance macrophage cytotoxicity; on another hand, overexpression of Trim59 enhance the pinocytosis and Phagocytosis activity of Raw-264.7, which imply Trim59 might mediate the cell-molecule interaction. Our results indicate Trim59 might be an essential accessory molecule in mediating BAM tumoricidal functions; and Trim59 is a phagocytosis-correlated molecule.
accessory molecule; BCG-activated macrophages; cytotoxicity; Trim59
Uncovering human mobility patterns is of fundamental importance to the understanding of epidemic spreading, urban transportation and other socioeconomic dynamics embodying spatiality and human travel. According to the direct travel diaries of volunteers, we show the absence of scaling properties in the displacement distribution at the individual level,while the aggregated displacement distribution follows a power law with an exponential cutoff. Given the constraint on total travelling cost, this aggregated scaling law can be analytically predicted by the mixture nature of human travel under the principle of maximum entropy. A direct corollary of such theory is that the displacement distribution of a single mode of transportation should follow an exponential law, which also gets supportive evidences in known data. We thus conclude that the travelling cost shapes the displacement distribution at the aggregated level.
A combination of molecular-targeted cancer imaging and therapy is an emerging strategy to improve cancer diagnosis and minimize the side effects of conventional treatments. Here, we generated a recombinant protein, EC1-GLuc-p53C, by fusing EC1 peptide, an artificial ligand of ErbB2, with Gaussia luciferase (GLuc) and a p53-activating peptide, p53C. EC1-GLuc-p53C was expressed and purified from E. coli BL21. In vitro experiments showed that EC1-GLuc-p53c was stable in luminescent activity and selectively targeted ErbB2-overexpressing BT474 cells for bioluminescence imaging. Moreover, the internalized EC1-GLuc-p53C in BT474 cells exerted its function to reactivate p53 and significantly inhibited cellular proliferation. In tumor-bearing mice, the ErbB2-targeted bioluminescence imaging and therapeutic effect of EC1-GLuc-p53C were also observed specifically in BT474 tumors but not in MCF7 tumors, which does not overexpress ErbB2. Thus, the present study demonstrates EC1-GLuc-p53C to be an effective theranostic reagent targeting ErbB2 for bioluminescence imaging and cancer therapy.
Despite earlier studies demonstrating characteristics of colon cancer stem cells (CCSCs) and the role of epithelial-mesenchymal transition (EMT) in tumor development, it remains controversial as to the relationship between CCSCs and EMT. In this study, in order to present an insight into this relationship in colon cancer, we developed HCT116 and HT29 sphere models, which are known to be the cells enriching cancer stem cells. Compared to their parental counterparts, spheroid cells displayed lower homotypic/heterotypic adhesion but higher in vitro migratory/invasive capacity, as well as higher tumorigenic and metastatic potential in vivo. The spheroid cells also demonstrated down-regulated E-cadherin and up-regulated α-SMA and Vimentin expression, which is the typical phenotype of EMT. In order to explore whether this phenomenon is associated to activation of Wnt/β-catenin pathway, we detected several key signaling molecules. Compared with their parental cells, HCT116 and HT29 spheroid cells demonstrated down-regulated expression of GSK3β, but up-regulated expression of Slug and Snail. And also, the up-regulation of nucleus β-catenin in spheroid cells indicated that the free β-catenin transferred from cytoplasm to cell nucleus. Our findings indicate that spheroid cells have the characteristics of colon cancer stem cells, and EMT may account for their stemness and malignancy. And persistent activation of Wnt/β-catenin pathway may play an important role in the EMT of CCSCs.
Water deficit is a serious environmental factor limiting the growth and productivity of plants worldwide. Improvement of drought tolerance and efficient water use are significant strategies to overcome this dilemma. In this study, a drought-responsive transcription factor, NUCLEAR FACTOR Y subunit B 7 (PdNF-YB7), induced by osmotic stress (PEG6000) and abscisic acid, was isolated from fast-growing poplar clone NE-19 [Populus nigra × (Populus deltoides × Populus nigra)]. Ectopic overexpression of PdNF-YB7 (oxPdB7) in Arabidopsis enhanced drought tolerance and whole-plant and instantaneous leaf water-use efficiency (WUE, the ratio of biomass produced to water consumed). Overexpressing lines had an increase in germination rate and root length and decrease in water loss and displayed higher photosynthetic rate, instantaneous leaf WUE, and leaf water potential to exhibit enhanced drought tolerance under water scarcity. Additionally, overexpression of PdNF-YB7 in Arabidopsis improved whole-plant WUE by increasing carbon assimilation and reducing transpiration with water abundance. These drought-tolerant, higher WUE transgenic Arabidopsis had earlier seedling establishment and higher biomass than controls under normal and drought conditions. In contrast, Arabidopsis mutant nf-yb3 was more sensitive to drought stress with lower WUE. However, complementation analysis indicated that complementary lines (nf-yb3/PdB7) had almost the same drought response and WUE as wild-type Col-0. Taken together, these results suggest that PdNF-YB7 positively confers drought tolerance and improves WUE in Arabidopsis; thus it could potentially be used in breeding drought-tolerant plants with increased production even under water deficiency.
Arabidopsis; drought tolerance; NF-YB; poplar; transcription factor; water-use efficiency.
A combined kinetic and computational study on our tryptophan-based bifunctional thiourea catalyzed asymmetric Mannich reactions reveals an apparent negative activation enthalpy. The formation of the pre-transition state complex has been unambiguously confirmed and these observations provide an experimental support for the formation of multiple hydrogen bonding network between the substrates and the catalyst. Such interactions allow the creation of a binding cavity, a key factor to install high enantioselectivity.
In this work, we investigate optimization-based image reconstruction from few-view (i.e., <10 views) projections of sparse objects such as coronary-artery specimens. Using optimization programs as a guide, we formulate constraint programs as reconstruction programs and develop algorithms to reconstruct images through solving the reconstruction programs. Characterization studies are carried out for elucidating the algorithm properties of “convergence” (relative to designed solutions) and “utility” (relative to desired solutions) by using simulated few-view data calculated from a discrete FORBILD coronary-artery phantom, and real few-view data acquired from a human coronary-artery specimen. Study results suggest that carefully designed reconstruction programs and algorithms can yield accurate reconstructions of sparse images from few-view projections.
Impaired consciousness in epileptic seizures has a major negative impact on patient quality of life. Prior work on epileptic unconsciousness has mainly used retrospective and nonstandardized methods. Our goal was to validate and to obtain initial data using a standardized prospective testing battery.
The responsiveness in epilepsy scale (RES) was used on 52 patients during continuous video/EEG monitoring. RES begins with higher-level questions and commands, and switches adaptively to more basic sensorimotor responses depending on patient performance. RES continues after seizures and includes postictal memory testing. Scoring was conducted based on video review.
Testing on standardized seizure simulations yielded good intra-rater and inter-rater reliability. We captured 59 seizures from 18 patients (35% of participants) during 1420 hours of RES monitoring. RES impairment was greatest during and after tonic-clonic seizures, less in partial seizures, and minimal in auras and subclinical seizures. In partial seizures, ictal RES impairment was significantly greater if EEG changes were present. Maximum RES impairment (lowest ictal score) was also significantly correlated with long postictal recovery time, and poor postictal memory.
We found that prospective testing of responsiveness during seizures is feasible and reliable. RES impairment was related to EEG changes during seizures, as well as to postictal memory deficits and recovery time. With a larger patient sample it is hoped that this approach can identify brain networks underlying specific components of impaired consciousness in seizures. This may allow the development of improved treatments targeted at preventing dysfunction in these networks.
Consciousness; Seizure; Behavior; Testing battery; Electroencephalography; Video/EEG monitoring
So far, no effective therapy is available for acute kidney injury (AKI), a common and serious complication with high morbidity and mortality. Interest has recently been focused on the potential therapeutic effect of mouse adult renal progenitor cells (MRPC), erythropoietin (EPO) and suramin in the recovery of ischemia-induced AKI. The aim of the present study is to compare MRPC with MRPC/EPO or MRPC/suramin concomitantly in the treatment of a mouse model of ischemia/reperfusion (I/R) AKI.
MRPC were isolated from adult C57BL/6-gfp mice. Male C57BL/6 mice (eight-weeks old, n = 72) were used for the I/R AKI model. Serum creatinine (Cr), blood urea nitrogen (BUN) and renal histology were detected in MRPC-, MRPC/EPO-, MRPC/suramin- and PBS-treated I/R AKI mice. E-cadherin, CD34 and GFP protein expression was assessed by immunohistochemical assay.
MRPC exhibited characteristics consistent with renal stem cells. The features of MRPC were manifested by Pax-2, Oct-4, vimentin, α-smooth muscle actin positive, and E-cadherin negative, distinguished from mesenchymal stem cells (MSC) by expression of CD34 and Sca-1. The plasticity of MRPC was shown by the ability to differentiate into osteoblasts and lipocytes in vitro. Injection of MRPC, especially MRPC/EPO and MRPC/suramin in I/R AKI mice attenuated renal damage with a decrease of the necrotic injury, peak plasma Cr and BUN. Furthermore, seven days after the injury, MRPC/EPO or MRPC/suramin formed more CD34+ and E-cadherin+ cells than MRPC alone.
These results suggest that MRPC, in particular MRPC/EPO or MRPC/suramin, promote renal repair after injury and may be a promising therapeutic strategy.
Adult kidney stem cell; Cell therapy; Erythropoietin; Suramin
Cisplatin is one of the most widely used chemical drugs for anticancer treatment. Recent studies have focused on the ability of cisplatin to retain the high mobility group box 1 (HMGB1) protein in cisplatin-DNA adducts, thereby preventing its release from the nucleus. Because HMGB1 is a powerful inflammatory mediator in many diseases, the aim of this study is to evaluate the therapeutic effect of cisplatin acute liver failure. In this study, low-dose cisplatin was administered to treat PMA-induced macrophage-like cells induced by PMA and rats with acute liver failure. We found that cell viability and liver injury were greatly improved by cisplatin treatment. The extracellular levels of HMGB1, TNF-α and IFN-γ were also significantly decreased by the administration of cisplatin. During inflammation, nuclear HMGB1 translocates from the nucleus to the cytoplasm. The administration of cisplatin reduced the cytoplasmic levels of HMGB1 and increased nuclear HMGB1 levels in vitro and in vivo. In conclusion, cisplatin can protect against acute liver failure by retaining HMGB1 in the nucleus and preventing its release into the extracellular milieu.
cisplatin; acute liver failure; high mobility group box-1; HMGB1 translocation; inflammation
To profile RNA expression in gastric cancer by anatomic subsites as an initial step in identifying molecular subtypes and providing targets for early detection and therapy.
We performed transcriptome analysis using the Affymetrix GeneChip U133A in gastric cardia adenocarcinomas (n = 62) and gastric noncardia adenocarcinomas (n = 72) and their matched normal tissues from patients in Shanxi Province, and validated selected dysregulated genes with additional RNA studies. Expression of dysregulated genes was also related to survival of cases.
Principal Component Analysis showed that samples clustered by tumor vs. normal, anatomic location, and histopathologic features. Paired t-tests of tumor/normal tissues identified 511 genes whose expression was dysregulated (P<4.7E-07 and at least two-fold difference in magnitude) in cardia or noncardia gastric cancers, including nearly one-half (n = 239, 47%) dysregulated in both cardia and noncardia, one-fourth dysregulated in cardia only (n = 128, 25%), and about one-fourth in noncardia only (n = 144, 28%). Additional RNA studies confirmed profiling results. Expression was associated with case survival for 20 genes in cardia and 36 genes in noncardia gastric cancers.
The dysregulated genes identified here represent a comprehensive starting point for future efforts to understand etiologic heterogeneity, develop diagnostic biomarkers for early detection, and test molecularly-targeted therapies for gastric cancer.
Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) in Thailand occur most frequently in healthcare facilities. However, reports of community-associated MRSA are limited.
We characterized 14 MRSA isolates from outpatients (O-1 to O-14) by phenotypic and genotypic methods and compared them with 5 isolates from inpatients (I-1 to I-5). Thai MRSA isolates from a healthcare worker (N-1) and a pig (P-1) were also included as ST9 MRSA strains from other sources.
All MRSA isolates from the outpatients and inpatients were multidrug-resistant (resistant to ≥3 classes of antimicrobials). All of them except strains O-2 and I-3 carried type III SCCmec and belonged to agrI, coagulase IV, spa type t037 or t233, which related to ST239. The strain O-2 (JCSC6690) carried type IX SCCmec and belonged to agrII, coagulaseXIc, spa type t337 and ST9, whereas the strain I-3 carried a type III SCCmec and belonged to ST1429. Nucleotide sequence determination revealed that the type IX SCCmec element in strain O-2 was distinct from that in a Thai ST398 strain (JCSC6943) previously identified in 2011; nucleotide identities of ccrA and ccrB were 93 and 91%, respectively and several open reading frames (ORFs) at the joining regions were different. PCR experiments suggested that strain O-2 and N-1 carried similar SCCmec element, whereas that of strain P-1 was different, suggesting that distinct ST9-MRSA–IX clones might be spreading in this province.
The SCCmecIX-ST9 MRSA clones of distinct SCCmec subtypes might have emerged in the Thai community and might also have disseminated into the hospital.
S. aureus; CA-MRSA; SCCmec; ST9; Livestock