Mesenchymal stem cells (MSCs) have immunoregulatory and proangiogenic effects and are suggested to be involved in the pathological processes of immune-related diseases, including psoriasis. Biological characteristics of bone marrow MSCs (BMSCs) from patients with autoimmune diseases, such as systemic lupus erythematosus or rheumatoid arthritis, but not psoriasis, have been characterized. We compared the gene expression profile and biological characteristics of BMSCs from patients with psoriasis and healthy controls. Although the phenotype, differentiation potential and ability to support CD34(+) cell proliferation were similar to those of normal BMSCs, psoriatic BMSCs showed aberrant proliferative activity, increased apoptosis rate and a characteristic gene expression profile. These aberrations may develop after the abnormal immune response in psoriasis and result in BMSC dysfunction. The functionally deficient BMSCs may then fail to suppress overactive immune cells, thereby contributing to the pathogenesis of psoriasis.
In this paper, a special gradient-index electromagnetically induced transparency medium is induced with a Gaussian control field, which can be realized in a four-level ??Rb cold atomic cloud. Special directional self-imaging and imaging transforming properties are studied in this work. Simulated results show that a complex object can be imaged in the cold atoms, as the control field substituted with the elliptical Gaussian beam, then the self-imaging is directional, which has potental application in encryption.
The aim of this study was to investigate incidence trend of childhood type 1 diabetes in Shanghai, a megalopolis in east China. We established a population-based retrospective registry for the disease in the city's registered population during 1997-2011 and collected 622 incident type 1 diabetes in children aged 0-14 years. Standardized incidence rates and 95 % CI were estimated by applying the capture-recapture method and assuming Poisson distribution. Incidence trend was analyzed using the Poisson regression model. The mean annual incidence of childhood type 1 diabetes was 3.1 per 100,000 person-years. We did not observe significant difference in incidence between boys and girls. The incidence is unstable and had a mean annual increase 14.2 % per year during the studied period. A faster annual increase was observed in boys, warmer seasons, and in the outer regions of the city. If present trends continue, the number of new type 1 diabetes cases will double from 2016 to 2020, and prevalent cases will sextuple by 2025. Our results showed the incidence of childhood type 1 diabetes was rising rapidly in Shanghai. More studies are needed to analyze incidence changes in other regions of China for appropriate allocation of healthcare resources.
Ageing is associated with an increased incidence of constipation in humans. The contribution that the ageing process makes to this condition is unclear. The aim of this study was to determine the effects of age on faecal output and colonic motility in male C57BL/6J mice and to determine the role that altered tachykinin signalling plays in this process. Total faecal output recorded over a 24h period decreased with age due to a reduction in the number of pellets produced and their water content. These changes occurred in the absence of any significant change in food and water intake. There was an increase in the amount of faecal matter stored in the isolated colon with age which caused a proportional increase in colonic length. Analysis of colonic motility using an artificial pellet demonstrated that pellets moved in a stepwise fashion through the colon. There was an age-related increase in pellet transit time due to decreases in the step distance, velocity, and frequency of stepwise movements. These changes were reversed using the neurokinin 2 (NK2) receptor agonist neurokinin A. Addition of the NK2receptor antagonist GR159897 significantly increased transit time in the young animals by decreasing step distance, velocity and frequency, but was without effect in the aged colon. In summary, the ageing C57BL/6J mouse shows an impaired motility phenotype. These effects appear, at least in part, to be due to an attenuation of tachykinin signalling via NK2 receptors.
A growth trial was conducted to detect the effects of different diets on the growth performance and hypoxia adaptation capacity of Mississippi Paddlefish (Polyodon spathula) larvae. The larvae were fed with live food, formulated diets, and 1/2 live food with 1/2 formulated diets. After a 15-d growth trial, final body weight and total body length were measured, and five larvae from each dietary group were subjected to 1 h of hypoxia treatment. Serum total antioxidant capacity (T-AOC), serum superoxide dismutase (SOD), and liver malondialdehyde (MDA) were measured. Final body weight and weight gain of the fish fed live food were significantly higher than the values for the other two groups. Total body length of the fish fed live food and 1/2 live food with 1/2 formulated diets exhibited no significant difference. After hypoxia treatment, serum T-AOC and SOD activities of the fish fed formulated diets were significantly lower than those of the other two groups. Liver MDA content of the fish fed with live food was significantly higher than that of the other two groups. In conclusion, larval paddlefish fed with an appropriate proportion of live food and formulated diets exhibit improved adaptive capacity to hypoxia.
Green foxtail (Setaria viridis) is a new model plant for the genomic investigation of C4 photosynthesis biology. As the ancestor of foxtail millet (Setaria italica), an ancient cereal of great importance in arid regions of the world, green foxtail is crucial for the study of domestication and evolution of this ancient crop. In the present study, 288 green foxtail accessions, which were collected from all geographical regions of China, were analysed using 77 simple sequence repeats (SSRs) that cover the whole genome. A high degree of molecular diversity was detected in these accessions, with an average of 33.5 alleles per locus. Two clusters, which were inconsistent with the distribution of eco-geographical regions in China, were inferred from STRUCTURE, Neighbor-Joining, and principal component analysis, indicating a partially mixed distribution of Chinese green foxtails. The higher subpopulation diversity was from accessions mainly collected from North China. A low level of linkage disequilibrium was observed in the green foxtail genome. Furthermore, a combined analysis of green foxtail and foxtail millet landraces was conducted, and the origin and domestication of foxtail millet was inferred in North China.
Inconsistent results have been found on the association between air pollution and stroke mortality. Additionally, evidence on people who are potentially sensitive to air pollution-associated stroke mortality is limited.
The human cerebral microvascular endothelial cell line, hCMEC/D3, has been used extensively to model the blood-brain barrier (BBB) in vitro. Recently, we reported that cytokine-treatment induced loss of brain endothelial barrier properties. In this study, we further determined the gene expression pattern of hCMEC/D3 cells in response to activation with TNF? and IFN?.
Mesenchymal stem cells (MSCs) are likely involved in pathological processes of immune-related diseases, including psoriasis, because of their immunoregulatory and pro-angiogenic effects. DNA methylation plays an essential role in regulating gene expression and maintaining cell function.
A method to reproduce colored images with a guided-mode resonance filter (GMRF) array is presented in this Letter. Because of their excellent characteristics, monochromatic light of the three primary colors with high purity can be achieved by using GMRF structures. Moreover, the primary colors are obtained without changing other GMRF parameters except the period, which could be realized easily with laser direct writing technology. The result shows that a colored image with high resolution and verisimilitude can be reproduced.
Intrahepatic cholestasis of pregnancy (ICP) is a pregnancy-associated liver disease of unknown etiology. The aim of this study was to investigate the change in maternal and fetal adrenal function in clinical and experimental ICP.
Dietary restriction (DR) extends the lifespan of a wide variety of species and reduces the incidence of major age-related diseases. Cell senescence has been proposed as one causal mechanism for tissue and organism ageing. We show for the first time that adult-onset, short-term DR reduced frequencies of senescent cells in the small intestinal epithelium and liver of mice, which are tissues known to accumulate increased numbers of senescent cells with advancing age. This reduction was associated with improved telomere maintenance without increased telomerase activity. We also found a decrease in cumulative oxidative stress markers in the same compartments despite absence of significant changes in steady-state oxidative stress markers at the whole tissue level. The data suggest the possibility that reduction of cell senescence may be a primary consequence of DR which in turn may explain known effects of DR such as improved mitochondrial function and reduced production of reactive oxygen species.
Foxtail millet (Setaria italica (L.) P. Beauv.), one of the most ancient domesticated crops, is becoming a model system for studying biofuel crops and comparative genomics in the grasses. However, knowledge on the level of genetic diversity and linkage disequilibrium (LD) is very limited in this crop and its wild ancestor, green foxtail (Setaria viridis (L.) P. Beauv.). Such information would help us to understand the domestication process of cultivated species and will allow further research in these species, including association mapping and identification of agricultural significant genes involved in domestication.
Recent advances in molecular biology of hearing and deafness have made genetic testing an option for deaf individuals and their families. In China, DNA microarray and other genetic testing method has been applied to rapid genetic diagnosis of non-syndromic hearing loss. However, there is no information about the interests in such testing in China. The purpose of this study is to document the attitudes of parents with normal hearing who have one or more deaf children toward diagnostic, carrier, and prenatal genetic testing for deafness.
Neural stem cells transplantation has been proposed as a future therapy for spinal cord injury. The challenge is how to make proportionally more neural stem cells differentiate into spinal motor neurons. Recent reports reveal that microRNAs play an important role in regulating stem cell self-renewal and differentiation. The aim of this study was to compare the profiling of microRNA expression between neural stem cells and motor neurons and to find candidate targets that direct differentiation of neural stem cells into motor neurons. We performed a parallel isolation and purification of motor neurons and neural stem cells from the same rat embryonic spinal cord sample. With the high-throughput TaqMan low-density array platform, 44 differentially expressed microRNAs were identified (22 specially expressed microRNAs in motor neurons and neural stem cells, respectively). Using bioinformatic methods, clustering, transcriptional regulation and target genes of differential microRNAs were analyzed. Furthermore, miR-126 specially expressed in cultured motor neurons identified by TaqMan low-density array was significantly elevated in choline acetyltransferase-positive neurons differentiated from the neural stem cells. These findings suggest that specially expressed microRNAs may contribute to the directed differentiation of neural stem cells into motor neurons and are potential targets for therapeutic interventions following spinal cord injury.
Cellular senescence--the permanent arrest of cycling in normally proliferating cells such as fibroblasts--contributes both to age-related loss of mammalian tissue homeostasis and acts as a tumour suppressor mechanism. The pathways leading to establishment of senescence are proving to be more complex than was previously envisaged. Combining in-silico interactome analysis and functional target gene inhibition, stochastic modelling and live cell microscopy, we show here that there exists a dynamic feedback loop that is triggered by a DNA damage response (DDR) and, which after a delay of several days, locks the cell into an actively maintained state of deep cellular senescence. The essential feature of the loop is that long-term activation of the checkpoint gene CDKN1A (p21) induces mitochondrial dysfunction and production of reactive oxygen species (ROS) through serial signalling through GADD45-MAPK14(p38MAPK)-GRB2-TGFBR2-TGFbeta. These ROS in turn replenish short-lived DNA damage foci and maintain an ongoing DDR. We show that this loop is both necessary and sufficient for the stability of growth arrest during the establishment of the senescent phenotype.
Cellular senescence, the irreversible loss of replicative capacity, might be a tumour suppressor and a contributor to age-related loss of tissue function. The absence of quantitative tests for reliability of candidate markers for senescent cells is a major drawback in cell population studies. Fibroblasts in culture constitute mixed populations of proliferation-competent and senescent cells, with transition between these with increasing population doublings (PD). We estimated senescent fraction in human and mouse fibroblasts with high precision from easily observed growth curves using a dynamic simulation model. We also determined senescent fractions, at various PD (over a wide range of senescent cell frequencies) using candidate senescence markers: Ki67, p21 (CDKN1A), ?H2AX, SAHF and Sen-?-Gal either alone or in combination, and compared with those derived from growth curves. This comparison allowed ranking of candidate markers. High rankings were obtained for Sen-?-Gal, SAHFs and the combination of Ki67 negativity with high (>5 per nucleus) ?H2A.X foci density in MRC5 fibroblasts. We demonstrate that this latter marker combination, which can easily be performed in paraffin-embedded tissue, gives quantitative senescent cell frequency estimates in mouse embryonic fibroblast cultures and in mouse intestinal sections. The technique presented is a framework for quantitative assessment of markers for senescence.
Telomeres of most somatic cells progressively shorten, compromising the regenerative capacity of human tissues during aging and chronic diseases and after acute injury. Whether telomere shortening reduces renal regeneration after acute injury is unknown. Here, renal ischemia-reperfusion injury led to greater impairment of renal function and increased acute and chronic histopathologic damage in fourth-generation telomerase-deficient mice compared with both wild-type and first-generation telomerase-deficient mice. Critically short telomeres, increased expression of the cell-cycle inhibitor p21, and more apoptotic renal cells accompanied the pronounced damage in fourth-generation telomerase-deficient mice. These mice also demonstrated significantly reduced proliferative capacity in tubular, glomerular, and interstitial cells. These data suggest that critical telomere shortening in the kidney leads to increased senescence and apoptosis, thereby limiting regenerative capacity in response to injury.
The impact of cellular senescence onto aging of organisms is not fully clear, not at least because of the scarcity of reliable data on the mere frequency of senescent cells in aging tissues. Activation of a DNA damage response including formation of DNA damage foci containing activated H2A.X (gamma-H2A.X) at either uncapped telomeres or persistent DNA strand breaks is the major trigger of cell senescence. Therefore, gamma-H2A.X immunohistochemistry (IHC) was established by us as a reliable quantitative indicator of senescence in fibroblasts in vitro and in hepatocytes in vivo and the age dependency of DNA damage foci accumulation in ten organs of C57Bl6 mice was analysed over an age range from 12 to 42 months. There were significant increases with age in the frequency of foci-containing cells in lung, spleen, dermis, liver and gut epithelium. In liver, foci-positive cells were preferentially found in the centrilobular area, which is exposed to higher levels of oxidative stress. Foci formation in the intestine was restricted to the crypts. It was not associated with either apoptosis or hyperproliferation. That telomeres shortened with age in both crypt and villus enterocytes, but telomeres in the crypt epithelium were longer than those in villi at all ages were confirmed by us. Still, there was no more than random co-localization between gamma-H2A.X foci and telomeres even in crypts from very old mice, indicating that senescence in the crypt enterocytes is telomere independent. The results suggest that stress-dependent cell senescence could play a causal role for aging of mice.
Walleye (Sander vitreus) is an important sport fish throughout much of North America, and walleye populations support valuable commercial fisheries in certain lakes as well. Using a corrected algorithm for balancing the energy budget, we reevaluated the performance of the Wisconsin bioenergetics model for walleye in the laboratory. Walleyes were fed rainbow smelt (Osmerus mordax) in four laboratory tanks each day during a 126-day experiment. Feeding rates ranged from 1.4 to 1.7% of walleye body weight per day. Based on a statistical comparison of bioenergetics model predictions of monthly consumption with observed monthly consumption, we concluded that the bioenergetics model estimated food consumption by walleye without any significant bias. Similarly, based on a statistical comparison of bioenergetics model predictions of weight at the end of the monthly test period with observed weight, we concluded that the bioenergetics model predicted walleye growth without any detectable bias. In addition, the bioenergetics model predictions of cumulative consumption over the 126-day experiment differed from observed cumulative consumption by less than 10%. Although additional laboratory and field testing will be needed to fully evaluate model performance, based on our laboratory results, the Wisconsin bioenergetics model for walleye appears to be providing unbiased predictions of food consumption.
Generalized Additive Model (GAM) provides a flexible and effective technique for modelling nonlinear time-series in studies of the health effects of environmental factors. However, GAM assumes that errors are mutually independent, while time series can be correlated in adjacent time points. Here, a GAM with Autoregressive terms (GAMAR) is introduced to fill this gap.
An 8-week feeding trial was carried out with juvenile yellow catfish to study the effects of dietary available phosphorus (P) on growth performance, body composition, and hepatic antioxidant property. Six pellet diets were formulated to contain graded available P levels at 0.33, 0.56, 0.81, 1.15, 1.31, and 1.57% of dry matter, respectively. Triplicate tanks with each tank containing 60 juveniles (3.09 ± 0.03 g) were fed one of the six experimental diets for 8 weeks. Specific growth rate, feeding rate, and protein efficiency ratio were significantly higher at 0.81% dietary available P. Efficiency of P utilization distinctly decreased with increasing P level. Body lipid content significantly decreased while body ash and feces P content significantly increased with increasing P level. Quadratic regression analysis indicated that vertebrae P content was maximized at 1.21% dietary available P. Fish fed 1.57% dietary available P had highest activity of hepatic superoxide dismutase and catalase and malonaldehyde content. In conclusion, decreasing dietary available P increased P utilization efficiency and body lipid content while decreased vertebrae P content. Juvenile yellow catfish were subjected to oxidative damage under the condition of high dietary P content (1.57%), and the damage could not be eradicated by their own antioxidant defense system.
In senescent cells, a DNA damage response drives not only irreversible loss of replicative capacity but also production and secretion of reactive oxygen species (ROS) and bioactive peptides including pro-inflammatory cytokines. This makes senescent cells a potential cause of tissue functional decline in aging. To our knowledge, we show here for the first time evidence suggesting that DNA damage induces a senescence-like state in mature postmitotic neurons in vivo. About 40-80% of Purkinje neurons and 20-40% of cortical, hippocampal and peripheral neurons in the myenteric plexus from old C57Bl/6 mice showed severe DNA damage, activated p38MAPkinase, high ROS production and oxidative damage, interleukin IL-6 production, heterochromatinization and senescence-associated ?-galactosidase activity. Frequencies of these senescence-like neurons increased with age. Short-term caloric restriction tended to decrease frequencies of positive cells. The phenotype was aggravated in brains of late-generation TERC-/- mice with dysfunctional telomeres. It was fully rescued by loss of p21(CDKN1A) function in late-generation TERC-/-CDKN1A-/- mice, indicating p21 as the necessary signal transducer between DNA damage response and senescence-like phenotype in neurons, as in senescing fibroblasts and other proliferation-competent cells. We conclude that a senescence-like phenotype is possibly not restricted to proliferation-competent cells. Rather, dysfunctional telomeres and/or accumulated DNA damage can induce a DNA damage response leading to a phenotype in postmitotic neurons that resembles cell senescence in multiple features. Senescence-like neurons might be a source of oxidative and inflammatory stress and a contributor to brain aging.
As an ancient cereal of great importance for dryland agriculture even today, foxtail millet (Setaria italica) is fast becoming a new plant genomic model crop. A genotypic analysis of 250 foxtail millet landraces, which represent 1% of foxtail millet germplasm kept in the Chinese National Gene Bank (CNGB), was conducted with 77 SSRs covering the foxtail millet genome. A high degree of molecular diversity among the landraces was found, with an average of 20.9 alleles per locus detected. STRUCTURE, neighbor-jointing, and principal components analyses classify the accessions into three clusters (topmost hierarchy) and, ultimately, four conservative subgroups (substructuring within the topmost clusters) in total, which are in good accordance with eco-geographical distribution in China. The highest subpopulation diversity was identified in the accessions of Pop3 from the middle regions of the Yellow River, followed by accessions in Pop1 from the downstream regions of the Yellow River, suggesting that foxtail millet was domesticated in the Yellow River drainage area first and then spread to other parts of the country. Linkage disequilibrium (LD) decay of less than 20 cM of genetic distance in the foxtail millet landrace genome was observed, which suggests that it could be possible to achieve resolution down to the 20 cM level for association mapping.
Senescent cells produce and secrete various bioactive molecules including interleukins, growth factors, matrix-degrading enzymes and reactive oxygen species (ROS). Thus, it has been proposed that senescent cells can damage their local environment, and a stimulatory effect on tumour cell growth and invasiveness has been documented. However, it was unknown what effect, if any, senescent cells have on their normal, proliferation-competent counterparts. We show here that senescent cells induce a DNA damage response, characteristic for senescence, in neighbouring cells via gap junction-mediated cell-cell contact and processes involving ROS. Continuous exposure to senescent cells induced cell senescence in intact bystander fibroblasts. Hepatocytes bearing senescence markers clustered together in mice livers. Thus, senescent cells can induce a bystander effect, spreading senescence towards their neighbours in vitro and, possibly, in vivo.
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