Understanding the causal relation between neural inputs and movements is very important for the success of brain-machine interfaces (BMIs). In this study, we analyze 104 neurons’ firings using statistical, information theoretic, and fractal analysis. The latter include Fano factor analysis, multifractal adaptive fractal analysis (MF-AFA), and wavelet multifractal analysis. We find neuronal firings are highly non-stationary, and Fano factor analysis always indicates long-range correlations in neuronal firings, irrespective of whether those firings are correlated with movement trajectory or not, and thus does not reveal any actual correlations between neural inputs and movements. On the other hand, MF-AFA and wavelet multifractal analysis clearly indicate that when neuronal firings are not well correlated with movement trajectory, they do not have or only have weak temporal correlations. When neuronal firings are well correlated with movements, they are characterized by very strong temporal correlations, up to a time scale comparable to the average time between two successive reaching tasks. This suggests that neurons well correlated with hand trajectory experienced a “re-setting” effect at the start of each reaching task, in the sense that within the movement correlated neurons the spike trains’ long-range dependences persisted about the length of time the monkey used to switch between task executions. A new task execution re-sets their activity, making them only weakly correlated with their prior activities on longer time scales. We further discuss the significance of the coalition of those important neurons in executing cortical control of prostheses.
brain-machine interface; Fano factor; adaptive fluctuation analysis; wavelet; neuronal firings
The filamentous fungus Magnaporthe oryzae is the causal agent of rice blast disease. Here we show that glycogen metabolic genes play an important role in plant infection by M. oryzae. Targeted deletion of AGL1 and GPH1, which encode amyloglucosidase and glycogen phosphorylase, respectively, prevented mobilisation of glycogen stores during appressorium development and caused a significant reduction in the ability of M. oryzae to cause rice blast disease. By contrast, targeted mutation of GSN1, which encodes glycogen synthase, significantly reduced the synthesis of intracellular glycogen, but had no effect on fungal pathogenicity. We found that loss of AGL1 and GPH1 led to a reduction in expression of TPS1 and TPS3, which encode components of the trehalose-6-phosphate synthase complex, that acts as a genetic switch in M. oryzae. Tps1 responds to glucose-6-phosphate levels and the balance of NADP/NADPH to regulate virulence-associated gene expression, in association with Nmr transcriptional inhibitors. We show that deletion of the NMR3 transcriptional inhibitor gene partially restores virulence to a Δagl1Δgph1 mutant, suggesting that glycogen metabolic genes are necessary for operation of the NADPH-dependent genetic switch in M. oryzae.
The fungus Magnaporthe oryzae causes a devastating disease of rice called blast. Each year, rice blast disease destroys almost a quarter of the potential global rice harvest. The fungus infects rice plants by elaborating a special infection structure called an appressorium, which physically breaks the tough outer cuticle of a rice leaf. Magnaporthe can develop appressoria in the absence of a nutrient source. We are therefore studying how the fungus utilizes energy stores in its spores to fuel its initial growth and development. Glycogen is a key storage compound in fungi and in this study we have investigated how glycogen breakdown occurs in the rice blast fungus. We have shown that the two major enzymes that degrade cellular stores of glycogen are important in rice blast disease. However, we also found that a strain of the fungus which is severely impaired in its ability to synthesize its own glycogen can still infect plants normally. To explain these apparently contradictory findings we explored the regulatory role of glycogen breakdown and provide evidence that glycogen metabolism is a key regulator of a recently described, virulence-associated genetic switch in Magnaporthe that is operated by an enzyme called trehalose-6-phosphate synthase.
Sequential adsorption of poly(styrene sulfonate) (PSS) and proteases in porous nylon yields enzymatic membrane reactors for limited protein digestion. Although a high local enzyme density (~30 mg/cm3) and small pore diameters in the membrane lead to digestion in < 1 s, the low membrane thickness (170 μm) affords control over residence times at the ms level to limit digestion. Apomyoglobin digestion demonstrates that peptide lengths increase as the residence time in the membrane decreases. Moreover, electron transfer dissociation (ETD) tandem mass spectrometry (MS/MS) on a large myoglobin proteolytic peptide (8 kD) provides a resolution of 1–2 amino acids. Under denaturing conditions, limited membrane digestion of bovine serum albumin (BSA) and subsequent ESI-Orbitrap MS analysis reveal large peptides (3 kD–10 kD) that increase the sequence coverage from 53 % (2-s digestion) to 82 % (0.05-s digestion). With this approach we also performed membrane-based limited proteolysis of a large Arabidopsis GTPase, ROOT HAIR DEFECTIVE 3 (RHD3), and showed suitable probing for labile regions near the C-terminus to suggest what protein reconstruction might make RHD3 more suitable for crystallization.
Cryptococcus neoformans (C. neoformans) penetration into the central nervous system (CNS) requires traversal of the blood-brain barrier that is composed of a single layer of human brain microvascular endothelial cells (HBMEC), but the underlying mechanisms of C. neoformans traversal remain incompletely understood. C. neoformans transcytosis of HBMEC monolayer involves rearrangements of the host cell actin cytoskeleton and small GTP-binding Rho family proteins such as Rac1 are shown to regulate host cell actin cytoskeleton. We, therefore, examined whether C. neoformans traversal of the blood-brain barrier involves host Rac1. While the levels of activated Rac1 (GTP-Rac1) in HBMEC increased significantly upon incubation with C. neoformans strains, pharmacological inhibition and down-modulation of Rac1 significantly decreased C. neoformans transcytosis of HBMEC monolayer. Also, Rac1 inhibition was efficient in preventing C. neoformans penetration into the brain. In addition, C. neoformans phospholipase B1 (Plb1) was shown to contribute to activating host cell Rac1, and STAT3 was observed to associate with GTP-Rac1 in HBMEC that were incubated with C. neoformans strain but not with its Δplb1 mutant. These findings demonstrate for the first time that C. neoformans Plb1 aids fungal traversal across the blood-brain barrier by activating host cell Rac1 and its association with STAT3, and suggest that pharmacological intervention of host-microbial interaction contributing to traversal of the blood-brain barrier may prevent C. neoformans penetration into the brain.
In some cross-sectional studies, hypertriglyceridemic waist (HTGW) has been recommended as an alternative to metabolic syndrome (MetS) for screening individuals at high risk for diabetes mellitus (DM). However, little information is about the predictive power of HTGW for future DM. The aims of the study were to assess the DM predictive power of HTGW compared with MetS based on the follow-up data over 15 years collected from a general Chinese population.
And Findings: The data were collected in 1992 and then again in 2007 from the same group of 687 individuals without DM in 1992. For the whole population (n =687), multivariate analysis showed presence of HTGW was associated with a 4.1-fold (95%CI: 2.4-7.0, p < 0.001) increased risk and presence of MetS was associated with a 3.7-fold (95%CI: 2.2-6.2, p < 0.001) increased risk for future DM. For the population without elevated fasting plasma glucose (n = 650), multivariate analysis showed presence of HTGW was associated with a 3.9-fold (95%CI: 2.2-7.0, p < 0.001) increased risk and presence of MetS was associated with a 3.7-fold (95%CI: 2.1-6.6, p < 0.001) increased risk for future DM.
HTGW could predict future DM independently, and the predictive power was similar to MetS. HTGW might be an alternative to MetS for predicting future DM. For simpler and fewer components, HTGW might be more practical than MetS, and it might be recommended in most clinical practices. This finding might be more useful for the individuals who only have elevated WC and TG. Although these individuals are without MetS, they are still at high risk for future DM, similarly to the individuals with MetS.
Infectious spleen and kidney necrosis virus (ISKNV) is the type species of the genus Megalocytivirus from the family Iridoviridae. ISKNV is one of the major agents that cause mortality and economic losses to the freshwater fish culture industry in Asian countries, particularly for mandarin fish (Siniperca chuatsi). In the present study, we report that the interaction of mandarin fish caveolin 1 (mCav-1) with the ISKNV major capsid protein (MCP) was detected by using a virus overlay assay and confirmed by pulldown assay and coimmunoprecipitation. This interaction was independent of the classic caveolin 1 scaffolding domain (CSD), which is responsible for interacting with several signaling proteins and receptors. Confocal immunofluorescence microscopy showed that ISKNV MCP colocalized with mCav-1 in the perinuclear region of virus-infected mandarin fish fry (MFF-1) cells, which appeared as soon as 4 h postinfection. Subcellular fractionation analysis showed that ISKNV MCP was associated with caveolae in the early stages of viral infection. RNA interference silencing of mCav-1 did not change virus-cell binding but efficiently inhibited the entry of virions into the cell. Taken together, these results suggested that mCav-1 plays an important role in the early stages of ISKNV infection.
Aspartic proteases (APs) are a large family of proteolytic enzymes found in almost all organisms. In plants, they are involved in many biological processes, such as senescence, stress responses, programmed cell death, and reproduction. Prior to the present study, no grape AP gene(s) had been reported, and their research on woody species was very limited.
In this study, a total of 50 AP genes (VvAP) were identified in the grape genome, among which 30 contained the complete ASP domain. Synteny analysis within grape indicated that segmental and tandem duplication events contributed to the expansion of the grape AP family. Additional analysis between grape and Arabidopsis demonstrated that several grape AP genes were found in the corresponding syntenic blocks of Arabidopsis, suggesting that these genes arose before the divergence of grape and Arabidopsis. Phylogenetic relationships of the 30 VvAPs with the complete ASP domain and their Arabidopsis orthologs, as well as their gene and protein features were analyzed and their cellular localization was predicted. Moreover, expression profiles of VvAP genes in six different tissues were determined, and their transcript abundance under various stresses and hormone treatments were measured. Twenty-seven VvAP genes were expressed in at least one of the six tissues examined; nineteen VvAPs responded to at least one abiotic stress, 12 VvAPs responded to powdery mildew infection, and most of the VvAPs responded to SA and ABA treatments. Furthermore, integrated synteny and phylogenetic analysis identified orthologous AP genes between grape and Arabidopsis, providing a unique starting point for investigating the function of grape AP genes.
The genome-wide identification, evolutionary and expression analyses of grape AP genes provide a framework for future analysis of AP genes in defining their roles during stress response. Integrated synteny and phylogenetic analyses provide novel insight into the functions of less well-studied genes using information from their better understood orthologs.
Synteny analysis; Phylogenetic analysis; Gene expression; Orthologous genes; Grape
The association between Human Leukocyte Antigen (HLA) class II and rheumatoid arthritis (RA) has been extensively studied, but few reported DR-DQ haplotype. Here we investigated the association of HLA-DRB1, DQA1, DQB1, and DR-DQ haplotypes with RA susceptibility and with anti-CCP antibodies in 281 RA patients and 297 control in Han population. High-resolution genotyping were performed. The HLA-DRB1 shared epitope (SE)-encoding allele *0405 displayed the most significant RA association (P = 1.35×10−6). The grouped DRB1 SE alleles showed great association with RA (P = 3.88×10−13). The DRB1 DRRAA alleles displayed significant protective effects (P = 0.021). The SE-dependent DR-DQ haplotype SE-DQ3/4/5 remained strong association with both anti-CCP -positive (P = 3.71×10−13) and -negative RA (P = 3.89×10−5). Our study revealed that SE alleles and its haplotypes SE-DQ3/4/5 were highly associated with RA susceptibility in Han population. The SE-DQ3/4/5 haplotypes were associated with both anti-CCP positive RA and -negative RA.
Exposure to arsenic is associated with an increased risk of lung disease. Novel strategies are needed to reduce the adverse health effects associated with arsenic exposure in the lung. Nrf2, a transcription factor that mediates an adaptive cellular defense response, is effective in detoxifying environmental insults and prevents a broad spectrum of diseases induced by environmental exposure to harmful substances. In this report, we tested whether Nrf2 activation protects mice from arsenic-induced toxicity. We used an in vivo arsenic inhalation model that is highly relevant to low environmental human exposure to arsenic-containing dusts. Two-week exposure to arsenic-containing dust resulted in pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung; all of which were blocked by sulforaphane (SF) in an Nrf2-dependent manner. Mechanistically, SF-mediated activation of Nrf2 alleviated inflammatory responses by modulating cytokine production. This study provides strong evidence that dietary intervention targeting Nrf2 activation is a feasible approach to reduce adverse health effects associated with arsenic exposure.
Nrf2; Keap1; Arsenic; Antioxidant response
AIM: To investigate the potential roles of Delta-like ligand 4 (DLL4) on the biological behavior of gastric cancer cells and its molecular mechanisms.
METHODS: A recombinant eukaryotic expression vector containing human DLL4 gene was constructed and transfected into the human gastric cancer cell line SGC7901. Clones with up-regulated DLL4 were selected and amplified. The effect of DLL4 up-regulation on gastric cancer cell growth was assessed using cell growth assay. The migration and invasion were assessed using a transwell migration assay and matrigel invasion assay. Matrix metalloproteinases were detected using the zymogram technique. Cells were implanted subcutaneously into male BALB/c nu/nu mice. Tumor volumes were then calculated and compared. DLL4 staining in the implanted tumor was performed using immunohistochemistry technique.
RESULTS: Growth curves over a six-day time course showed significantly promoted cell proliferation of SGC7901 cells with up-regulated DLL4. DLL4 up-regulation in SGC7901 cells promoted the migration (205.4 ± 15.2 vs 22.3 ± 12.1, P < 0.05) and invasion (68.8 ± 5.3 vs 18.2 ± 6.0, P < 0.05) in vitro and tumorigenicity in vivo (2640.5 ± 923.6 mm3
vs 1115.1 ± 223.8 mm3, P < 0.05). Furthermore, significantly increased mRNA level and increased secretion of matrix metalloproteinase-2 (MMP-2) proenzyme were observed in SGC7901 cells with up-regulated DLL4. However, increased MMP-9 mRNA level but decreased extracellular MMP-9 proenzyme level was observed.
CONCLUSION: Our observations indicated a mechanism by which activation of DLL4-mediated Notch signaling promotes the expression and secretion of MMP-2 proenzyme and influences the progress of gastric cancer.
Gastric cancer; Delta-like ligand 4/Notch; Matrix metalloproteinase; Migration; Invasion
To date, most studies of Rho GTPase regulation have focused on the classic GTPase cycle – GTP binding and hydrolysis – controlled by guanine nucleotide exchange factors (GEFs), GTPase-activating proteins (GAPs) and GDP-dissociation inhibitors (GDIs). Recent investigations have unveiled important additional regulatory mechanisms: microRNA (miRNA) regulating post-transcriptional processing of Rho GTPase-encoding mRNAs; palmitoylation and nuclear targeting affecting intracellular distribution; post-translational phosphorylation, transglutamination and AMPylation impacting Rho GTPase signaling; and ubiquitination controlling Rho GTPase protein stability and turnover. These modes of regulation add to the complexity of the Rho GTPase signaling network and allow precise spatiotemporal control of individual Rho GTPases. This review will discuss these ‘unconventional’ modes of regulation and their contribution to cellular function, focusing on post-transcriptional and post-translational events beyond the classic GTPase cycle regulatory model.
small GTPases; microRNAs; ubiquitination; phosphorylation; transglutamination
Rho GTPases have been implicated in diverse cellular functions and are potential therapeutic targets. By virtual screening, we have identified a Rho specific inhibitor, Rhosin. Rhosin contains two-aromatic rings tethered by a linker, and it binds to the surface area sandwiching Trp58 of RhoA with a submicromolar Kd and effectively inhibits GEF-catalyzed RhoA activation. In cells Rhosin specifically inhibited RhoA activity and RhoA-mediated cellular function without affecting Cdc42 or Rac1 signaling activities. By suppressing RhoA or RhoC activity Rhosin could inhibit mammary sphere formation by breast cancer cells, suppress invasion of mammary epithelial cells, and induce neurite outgrowth of PC12 cells in synergy with NGF. Thus, the rational designed RhoA subfamily specific small molecule inhibitor is useful for studying the physiological and pathologic roles of Rho GTPase.
Rho GTPases; RhoA; signaling; small molecule; inhibitor; rational drug design; targeting
Metabolic risk factors and abnormalities such as obesity and hypertension are rapidly rising among the Chinese population following China’s tremendous economic growth and widespread westernization of lifestyle in recent decades. Limited information is available about the current burden of metabolic syndrome (MetS) in China.
We analyzed data on metabolic risk factors among 22,457 adults aged ≥ 32 years participating in the “Zhabei Health 2020” survey (2009–2010), a cross-sectional study of a representative sample of community residents in Zhabei District. We defined MetS using Chinese-specific cut-off points for central obesity according to consensus criteria recently endorsed by several international and national organizations in defining MetS in different populations worldwide. We used a multiple logistic regression model to assess the associations of potential risk factors with MetS.
The unadjusted prevalence of the MetS was 35.1% for men and 32.5% for women according to the consensus criteria for Chinese. The prevalence increased progressively from 12.1% among participants aged 32–45 years to 45.4% among those aged ≥ 75 years. Age, smoking, family history of diabetes, and education are significantly associated with risk of MetS.
The MetS is highly prevalent and has reached epidemic proportion in Chinese urban adult community residents.
Metabolic syndrome; Prevalence; Population-based survey; China
To evaluate bone marrow stem cell treatment (BMSC) in patients with ischemic heart disease (IHD) and no option of revascularization.
Autologous BMSC therapy has emerged as a novel approach to treat patients with acute myocardial infarction or chronic ischemia and heart failure following percutaneous or surgical revascularization, respectively. However, the effect of the treatment has not been systematic evaluated in patients who are not eligible for revascularization.
MEDLINE (1950–2012), EMBASE (1980–2012), CENTRAL (The Cochrane Library 2012, Issue 8) and ongoing trial databases were searched for relevant randomized controlled trials. Trials where participants were diagnosed with IHD, with no option for revascularization and who received any dose of stem cells by any delivery route were selected for inclusion. Study and participant characteristics, details of the intervention and comparator, and outcomes measured were recorded by two reviewers independently. Primary outcome measures were defined as mortality and measures of angina; secondary outcomes were heart failure, quality of life measures, exercise/performance and left ventricular ejection fraction (LVEF).
Nine trials were eligible for inclusion. BMSC treatment significantly reduced the risk of mortality (Relative Risk 0.33; 95% Confidence Interval 0.17 to 0.65; P = 0.001). Patients who received BMSC showed a significantly greater improvement in CCS angina class (Mean Difference −0.55; 95% Confidence Interval −1.00 to −0.10; P = 0.02) and significantly fewer angina episodes per week at the end of the trial (Mean Difference −5.21; 95% Confidence Interval −7.35 to −3.07; P<0.00001) than those who received no BMSC. In addition, the treatment significantly improved quality of life, exercise/performance and LVEF in these patients.
BMSC treatment has significant clinical benefit as stand-alone treatment in patients with IHD and no other treatment option. These results require confirmation in large well-powered trials with long-term follow-up to fully evaluate the clinical efficacy of this treatment.
We report a case of pancreatic hemolymphangioma. Hemolymphangioma is a malformation of both lymphatic vessels and blood vessels. The incidence of this disease in the pancreas is extremely rare. To the best of our knowledge, only seven cases have been reported worldwide (PubMed). A 39-year-old woman with a one-day history of abdominal pain was admitted to our hospital. There was no obvious precipitating factor. The preoperative examination, including ultrasonography and computed tomography, showed a cystic-solid tumor in the pancreas, and it was considered to be a mucinous cystadenoma or cystadenocarcinoma. Pancreatic body-tail resection combined with splenectomy was performed. After the operation, the tumor was pathologically demonstrated to be a pancreatic hemolymphangioma. Although pancreatic hemolymphangioma is rare, we believe that it should be considered in the differential diagnosis of cystic-solid tumors of the pancreas, particularly when there is no sufficient evidence for diagnosing cystadenoma, cystadenocarcinoma or some other relatively common disease of the pancreas.
Pancreatic neoplasm; Hemolymphangioma; Differential diagnosis; Computed tomography; Ultrasonography
Objective: The study compared laparoscopy-assisted gastrectomy (LAG) with open gastrectomy (OG) in the management of advanced gastric cancer (AGC). Methods: Literature search was performed in the Medline, Embase, and Cochrane Library databases to identify control studies that compared LAG and OG for AGC. A meta-analysis was conducted to examine the surgical safety and oncologic adequacy, using the random-effect model. Results: Seven eligible studies including 815 patients were analyzed. LAG was associated with less blood loss, less use of analgesics, shorter time of flatus and periods of hospital stay, but longer time of operation. The incidence of most complications was similar between the two groups. However, LAG was associated with a lower rate of pulmonary infection (odds ratio (OR) 0.19; 95% confidence interval (CI) 0.05 to 0.68; P<0.05). No significant differences were noted in terms of the number of harvested lymph nodes (weighted mean difference (WMD) 1.165; 95% CI −2.000 to 4.311; P>0.05), overall mortality (OR 0.65; 95% CI 0.39 to 1.10; P>0.05), cancer-related mortality (OR 0.64; 95% CI 0.32 to 1.25; P>0.05), or recurrence (OR 0.62; 95% CI 0.33 to 1.16; P>0.05). Conclusions: LAG could be performed safely for AGC with adequate lymphadenectomy and has several short-term advantages compared with conventional OG. No differences were found in long-term outcomes. However, these results should be validated in large randomized controlled studies (RCTs) with sufficient follow-up.
Gastric cancer; Laparoscopic gastrectomy; Meta-analysis; Mortality; Recurrence
To evaluate the application of immediate breast reconstruction (IBR) with silicon prosthetic implantation following bilateral nipple-preserving subcutaneous mammary gland excision in the treatment of young patients with early breast cancer.
We retrospectively analyzed the clinical data of 21 patients with breast cancer who were performed on IBR following bilateral nipple-preserving subcutaneous mammary gland excision in our hospital from January 2006 to March 2011.
The operations were successful in all the 21 patients. Also, the treatment provided a good cosmetic effect. No local recurrence or distant metastasis was found in these 21 patients during the 6-66-month follow-up.
For the young patients with early breast cancer, mammary gland excision on the affected side along with prophylactic excision of the contralateral side, namely IBR following bilateral nipple-preserving subcutaneous mammary gland excision, provides good clinical effectiveness and cosmetological effects.
Breast cancer; prophylactic mastectomy; immediate breast reconstruction
During peripheral nervous system development, Schwann cells (SCs) surrounding single large axons differentiate into myelinating SCs. Previous studies implicate RhoGTPases in SC myelination, but the mechanisms involved in RhoGTPase regulation of SC myelination are unknown. Here, we show that SC myelination is arrested in Rac1 conditional knockout (Rac1-CKO) mice. Rac1 knockout abrogated phosphorylation of the effector p21-activated kinase (PAK) and decreased NF2/merlin phosphorylation. Mutation of NF2/merlin rescued the myelin deficit in Rac1-CKO mice in vivo, and the shortened processes in cultured Rac1-CKO SCs in vitro. Mechanistically, cyclic adenosine monophosphate (cAMP) levels and E-cadherin expression were decreased in the absence of Rac1, and both were restored by mutation of NF2/merlin. Reduced cAMP is a cause of the myelin deficiency in Rac1-CKO mice, as elevation of cAMP by rolipram in Rac1-CKO mice in vivo allowed myelin formation. Thus NF2/merlin and cAMP function downstream of Rac1 signaling in SC myelination, and cAMP levels control Rac1-regulated SC myelination.
MicroRNAs play an important role in plant development and plant responses to various biotic and abiotic stimuli. As one of the most important ornamental crops, rose (Rosa hybrida) possesses several specific morphological and physiological features, including recurrent flowering, highly divergent flower shapes, colors and volatiles. Ethylene plays an important role in regulating petal cell expansion during rose flower opening. Here, we report the population and expression profiles of miRNAs in rose petals during flower opening and in response to ethylene based on high throughput sequencing. We identified a total of 33 conserved miRNAs, as well as 47 putative novel miRNAs were identified from rose petals. The conserved and novel targets to those miRNAs were predicted using the rose floral transcriptome database. Expression profiling revealed that expression of 28 known (84.8% of known miRNAs) and 39 novel (83.0% of novel miRNAs) miRNAs was substantially changed in rose petals during the earlier opening period. We also found that 28 known and 22 novel miRNAs showed expression changes in response to ethylene treatment. Furthermore, we performed integrative analysis of expression profiles of miRNAs and their targets. We found that ethylene-caused expression changes of five miRNAs (miR156, miR164, miR166, miR5139 and rhy-miRC1) were inversely correlated to those of their seven target genes. These results indicate that these miRNA/target modules might be regulated by ethylene and were involved in ethylene-regulated petal growth.
There currently lacks of a way to directly write out electronics, just like printing pictures on paper by an office printer. Here we show a desktop printing of flexible circuits on paper via developing liquid metal ink and related working mechanisms. Through modifying adhesion of the ink, overcoming its high surface tension by dispensing machine and designing a brush like porous pinhead for printing alloy and identifying matched substrate materials among different papers, the slightly oxidized alloy ink was demonstrated to be flexibly printed on coated paper, which could compose various functional electronics and the concept of Printed-Circuits-on-Paper was thus presented. Further, RTV silicone rubber was adopted as isolating inks and packaging material to guarantee the functional stability of the circuit, which suggests an approach for printing 3D hybrid electro-mechanical device. The present work paved the way for a low cost and easygoing method in directly printing paper electronics.
The functional decline in hematopoietic function seen during aging involves a progressive reduction in the immune response and an increased incidence of myeloid malignancy, and has been linked to aging of hematopoietic stem cells (HSCs). The molecular mechanisms underlying HSC aging remain unclear. Here we demonstrate that elevated activity of the small RhoGTPase Cdc42 in aged HSCs is causally linked to HSC aging and correlates with a loss of polarity in aged HSCs. Pharmacological inhibition of Cdc42 activity functionally rejuvenates aged HSCs, increases the percentage of polarized cells in an aged HSC population, and restores the level and spatial distribution of histone H4 lysine 16 acetylation to a similar status as seen in young HSCs. Our data therefore suggest a mechanistic role for Cdc42 activity in HSC biology and epigenetic regulation, and identify Cdc42 activity as a pharmacological target for ameliorating stem cell aging.
Highly active horseradish peroxidase functionalized magnetic nanoparticles were prepared and packed into a microfluidic channel, producing an in-line bioreactor that enabled a sensitive chemiluminescence assay of H2O2. The proposed magnetically active microfluidic device proved useful for chemiluminescence assays of biomedically interesting compounds.
Accurate and timely glucose monitoring is essential in intensive care units. Real-time continuous glucose monitoring system (CGMS) has been advocated for many years to improve glycemic management in critically ill patients. In order to determine the effect of calibration time on the accuracy of CGMS, real-time subcutaneous CGMS was used in 18 critically ill patients. CGMS sensor was calibrated with blood glucose measurements by blood gas/glucose analyzer every 12 hours. Venous blood was sampled every 2 to 4 hours, and glucose concentration was measured by standard central laboratory device (CLD) and by blood gas/glucose analyzer. With CLD measurement as reference, relative absolute difference (mean±SD) in CGMS and blood gas/glucose analyzer were 14.4%±12.2% and 6.5%±6.2%, respectively. The percentage of matched points in Clarke error grid zone A was 74.8% in CGMS, and 98.4% in blood gas/glucose analyzer. The relative absolute difference of CGMS obtained within 6 hours after sensor calibration (8.8%±7.2%) was significantly less than that between 6 to 12 hours after calibration (20.1%±13.5%, p<0.0001). The percentage of matched points in Clarke error grid zone A was also significantly higher in data sets within 6 hours after calibration (92.4% versus 57.1%, p<0.0001). In conclusion, real-time subcutaneous CGMS is accurate in glucose monitoring in critically ill patients. CGMS sensor should be calibrated less than 6 hours, no matter what time interval recommended by manufacturer.
Trauma and sepsis can cause acute lung injury (ALI) and Acute Respiratory Distress Syndrome (ARDS) in part by triggering neutrophil (PMN)-mediated increases in endothelial cell (EC) permeability. We had shown that mitochondrial (mt) damage-associated molecular patterns (DAMPs) appear in the blood after injury or shock and activate human PMN. So we now hypothesized that mitochondrial DAMPs (MTD) like mitochondrial DNA (mtDNA) and peptides might play a role in increased EC permeability during systemic inflammation and proceeded to evaluate the underlying mechanisms. MtDNA induced changes in EC permeability occurred in two phases: a brief, PMN-independent ‘spike’ in permeability was followed by a prolonged PMN-dependent increase in permeability. Fragmented mitochondria (MTD) caused PMN-independent increase in EC permeability that were abolished with protease treatment. Exposure to mtDNA caused PMN-EC adherence by activating expression of adherence molecule expression in both cell types. Cellular activation was manifested as an increase in PMN calcium flux and EC MAPK phosphorylation. Permeability and PMN adherence were attenuated by endosomal TLR inhibitors. EC lacked formyl peptide receptors but were nonetheless activated by mt-proteins, showing that non-formylated mt-protein DAMPs can activate EC. Mitochondrial DAMPs can be released into the circulation by many processes that cause cell injury and lead to pathologic endothelial permeability. We show here that mitochondria contain multiple DAMP motifs that can act on EC and/or PMN via multiple pathways. This can enhance PMN adherence to EC, activate PMN-EC interactions and subsequently increase systemic endothelial permeability. Mitochondrial DAMPs may be important therapeutic targets in conditions where inflammation pathologically increases endothelial permeability.
Objective: Weed pollens are common sources of allergens worldwide. The prevalence of weed pollen sensitization is not yet fully known in China. The purpose of this study was to investigate the prevalence of sensitization to weed allergens from Artemisia, Ambrosia, and Humulus in northern China. Methods: A total of 1 144 subjects (aged from 5 to 68 years) visiting our clinic from June to October 2011 underwent intradermal testing using a panel of 25 allergen sources. Subjects with positive skin responses to any pollen were further tested for their serum concentrations of IgE antibodies against Artemisia vulgaris, Ambrosia artemisiifolia, and Humulus scandens, and against the purified allergens, Art v 1 and Amb a 1. Results: Of 1 144 subjects, 170 had positive intradermal reactions to pollen and 144 donated serum for IgE testing. The prevalence of positive intradermal responses to pollens of Artemisia sieversiana, Artemisia annua, A. artemisiifolia, and H. scandens was 11.0%, 10.2%, 3.7%, and 6.6%, respectively. Among the intradermal positive subjects, the prevalence of specific IgE antigens to A. vulgaris was 58.3%, to A. artemisiifolia 14.7%, and to H. scandens 41.0%. The prevalence of specific IgE antigens to the allergen Art v 1 was 46.9%, and to Amb a 1 was 11.2%. The correlation between the presence of IgE antibodies specific to A. vulgaris and to the Art v 1 antigen was very high. Subjects with A. artemisiifolia specific IgE also had A. vulgaris specific IgE, but with relatively high levels of A. vulgaris IgE antibodies. There were no correlations between the presence of IgE antibodies to H. scandens and A. vulgaris or to H. scandens and A. artemisiifolia. Conclusions: The intradermal prevalence of weed pollen sensitization among allergic subjects in northern China is about 13.5%. Correlations of specific IgE antibodies suggest that pollen allergens from Artemisia and Humulus are independent sources for primary sensitization.
Humulus scandens; Artemisia vulgaris; Ambrosia artemisiifolia; Intradermal test; Specific IgE; Sensitization