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41.
Tomoaki Hishida Eric Vazquez-Ferrer Yuriko Hishida-Nozaki Ignacio Sancho-Martinez Yuta Takahashi Fumiyuki Hatanaka Jun Wu Alejandro Ocampo Pradeep Reddy Min-Zu Wu Laurie Gerken Reuben J. Shaw Concepcion Rodriguez Esteban Christopher Benner Hiroshi Nakagawa Pedro Guillen Garcia Estrella Nu ez Delicado Antoni Castells Josep M. Campistol Guang-Hui Liu Juan Carlos Izpisua Belmonte 《蛋白质与细胞》2019,10(7):485
Identification of the precise molecular pathways involved in oncogene-induced transformation may help us gain a better understanding of tumor initiation and promotion. Here, we demonstrate that SOX2+ foregut epithelial cells are prone to oncogenic transformation upon mutagenic insults, such as KrasG12D and p53 deletion. GFP-based lineage-tracing experiments indicate that SOX2+ cells are the cells-of-origin of esophagus and stomach hyperplasia. Our observations indicate distinct roles for oncogenic KRAS mutation and P53 deletion. p53 homozygous deletion is required for the acquisition of an invasive potential, and KrasG12D expression, but not p53 deletion, suffices for tumor formation. Global gene expression analysis reveals secreting factors upregulated in the hyperplasia induced by oncogenic KRAS and highlights a crucial role for the CXCR2 pathway in driving hyperplasia. Collectively, the array of genetic models presented here demonstrate that stratified epithelial cells are susceptible to oncogenic insults, which may lead to a better understanding of tumor initiation and aid in the design of new cancer therapeutics. 相似文献
42.
Cluster Computing - This paper proposes a new version of the power of two choices, SQ(d), load balancing algorithm. This new algorithm improves the performance of the classical model based on the... 相似文献
43.
Starlings' preferences for constant versus variable food sourceswere studied in the laboratory. The constant alternative gavea fixed amount of food after a fixed delay. The variable alternativeoffered either a varying amount of food after a fixed delay(treatment A) or a fixed amount of food after a variable delay(treatment B). In both treatments the ratio of amount of foodover trial length (the sum of intertrial interval plus delayand handling times) of the constant alternative equaled theaverage of the two ratios of the variable alternative. The variableratios were 30% higher and 30% smaller than the fixed ratio.In free-choice trials (both options available in each trial),the subjects were risk-averse or indifferent in treatment Aand indifferent or riskprone in treatment B. In no-choice trials(only one source available per trial), the latency to respondwas longer in the variable than in the constant source in treatmentA and the opposite in treatment B. The greater preference forvariability in time than for variability in reward amount isnot consistent with either maximizing the ratio of expectedenergy over expected time or the expected ratio of energy overtime for individual trials. There was a negative correlationbetween individual intake rate and degree of risk pronenessfor both kinds of variability. We present a model of choicebased on an information-processing theory for temporal memorythat accounts for the different effects of variability in delayand in amount but cannot explain the effects of intake rate.[Behav Ecol 1991;2:301308] 相似文献
44.
Romero A Galbany J De Juan J Pérez-Pérez A 《American journal of physical anthropology》2012,148(3):467-472
Buccal-dental microwear depends on the abrasive content of chewed foodstuffs and can reveal long-term dietary trends in human populations. However, in vivo experimental analyses of buccal microwear formation processes are scarce. Here, we report the effects of an abrasive diet on microwear rates in two adult volunteers at intervals of 8 days over a period of 1 month and document long-term turnover over 5 consecutive years in the same subjects under an ad libitum Mediterranean diet. Buccal microwear was analyzed on mandibular first molars using high-resolution replicas and scanning electron microscopy. Microwear turnover was assessed by recording the scratches lost and gained at each time point. Our results indicate that scratch formation on enamel surfaces increased with a highly abrasive diet compared to both pre-test and post-test ad libitum dietary controls. In the long-term analysis, scratch turnover was higher than expected, but no significant long-term trends in microwear density or length were observed, because microwear formation was compensated by scratch disappearance. Our results confirm that buccal microwear patterns on mandibular molars show a dynamic formation process directly related to the chewing of abrasive particles along with ingested food. In addition, the observed long-term stability of buccal microwear patterns makes them a reliable indicator of overall dietary habits. 相似文献
45.
A Lamana A Balsa B Rueda AM Ortiz L Nuño ME Miranda-Carus MF Gonzalez-Escribano MA Lopez-Nevot D Pascual-Salcedo J Martin I González-Álvaro 《PloS one》2012,7(8):e43661
Background
The number of copies of the HLA-DRB1 shared epitope, and the minor alleles of the STAT4 rs7574865 and the PTPN22 rs2476601 polymorphisms have all been linked with an increased risk of developing rheumatoid arthritis. In the present study, we investigated the effects of these genetic variants on disease activity and disability in patients with early arthritis.Methodology and Results
We studied 640 patients with early arthritis (76% women; median age, 52 years), recording disease-related variables every 6 months during a 2-year follow-up. HLA-DRB1 alleles were determined by PCR-SSO, while rs7574865 and rs2476601 were genotyped with the Taqman 5′ allelic discrimination assay. Multivariate analysis was performed using generalized estimating equations for repeated measures. After adjusting for confounding variables such as gender, age and ACPA, the TT genotype of rs7574865 in STAT4 was associated with increased disease activity (DAS28) as compared with the GG genotype (β coefficient [95% confidence interval] = 0.42 [0.01–0.83], p = 0.044). Conversely, the presence of the T allele of rs2476601 in PTPN22 was associated with diminished disease activity during follow-up in a dose-dependent manner (CT genotype = −0.27 [−0.56– −0.01], p = 0.042; TT genotype = −0.68 [−1.64– −0.27], p = 0.162). After adjustment for gender, age and disease activity, homozygosity for the T allele of rs7574865 in STAT4 was associated with greater disability as compared with the GG genotype.Conclusions
Our data suggest that patients with early arthritis who are homozygous for the T allele of rs7574865 in STAT4 may develop a more severe form of the disease with increased disease activity and disability. 相似文献46.
Relevance of forage fish in the diet of Magellanic penguins breeding in northern Patagonia,Argentina
Pablo Yorio Diego González-Zevallos Alejandro Gatto Oscar Biagioni Joanna Castillo 《Marine Biology Research》2017,13(6):603-617
We quantified the trophic niche of Magellanic penguins (Spheniscus magellanicus) breeding and moulting in Golfo San Jorge, Argentina, through conventional stomach content and stable isotope analysis. A total of 112 adults were flushed during the early and late chick stages of 2011 and 2012 at Isla Vernacci Norte, and at least 15 prey taxa were found, including fishes, cephalopods, crustaceans and polychaetes. Overall, Argentine anchovy (Engraulis anchoita) showed the highest contribution in terms of importance by mass (68.1–85.3%, depending on chick stage and year), except for the old chick stage in 2011 when the shortfin squid (Illex argentinus) was the main prey consumed (56.0%). Based on carbon and nitrogen isotopic values from a total of 256 blood samples, corresponding to young and old chicks and to adults of both sexes sampled throughout the incubation, chick and moult stages at the above mentioned colony and years, Bayesian mixing model outputs showed that Argentine anchovy was always the main prey (48–86%). Bayesian mixing model outputs obtained from adults of both sexes and their chicks during the late chick stage of 2013 at Isla Vernacci Norte, Isla Tova and Isla Leones also showed that Argentine anchovy was the main prey consumed. This is the first comprehensive assessment of Magellanic penguin diet composition in northern Patagonia, quantifying the relative contribution of prey in the diet of adults and chicks at different stages of the annual cycle and years, and confirms the relevance of a forage fish such as the Argentine anchovy in its trophic ecology. 相似文献
47.
Gene delivery to embryonic stem cells 总被引:1,自引:0,他引:1
Kobayashi N Rivas-Carrillo JD Soto-Gutierrez A Fukazawa T Chen Y Navarro-Alvarez N Tanaka N 《Birth defects research. Part C, Embryo today : reviews》2005,75(1):10-18
Since the establishment of embryonic stem (ES) cells and the identification of tissue-specific stem cells, researchers have made great strides in the analysis of the natural biology of such stem cells for the development of therapeutic applications. Specifically, ES cells are capable of differentiating into all of the cell types that constitute the whole body. Thus, ES cell research promises new type of treatments and possible cures for a variety of debilitating diseases and injuries. The potential medical benefits obtained from stem cell technology are compelling and stem cell research sees a bright future. Control of the growth and differentiation of stem cells is a critical tool in the fields of regenerative medicine, tissue engineering, drug discovery, and toxicity testing. Toward such a goal, we present here an overview of gene delivery in ES cells, covering the following topics: significance of gene delivery in ES cells, stable versus transient gene delivery, cytotoxicity, suspension versus adherent cells, expertise, time, cost, viral vectors for gene transduction (lentiviruses, adenoviruses, and adeno-associated viruses, chemical methods for gene delivery, and mechanical or physical gene delivery methods (electroporation, nucleofection, microinjection, and nuclear transfer). 相似文献
48.
Marti MA Crespo A Capece L Boechi L Bikiel DE Scherlis DA Estrin DA 《Journal of inorganic biochemistry》2006,100(4):761-770
We present an investigation of the molecular basis of the modulation of oxygen affinity in heme proteins using computer simulation. QM-MM calculations are applied to explore distal and proximal effects on O(2) binding to the heme, while classical molecular dynamics simulations are employed to investigate ligand migration across the polypeptide to the active site. Trends in binding energies and in the kinetic constants are illustrated through a number of selected examples highlighting the virtues and the limitations of the applied methodologies. These examples cover a wide range of O(2)-affinities, and include: the truncated-N and truncated-O hemoglobins from Mycobacterium tuberculosis, the mammalian muscular O(2) storage protein: myoglobin, the hemoglobin from the parasitic nematode Ascaris lumbricoides, the oxygen transporter in the root of leguminous plants: leghemoglobin, the Cerebratulus lacteus nerve tissue hemoglobin, and the Alcaligenes xyloxidans cytochrome c'. 相似文献
49.
Alejandro R. Giraudo Silvia D. Matteucci Julián Alonso Justo Herrera Raúl R. Abramson 《Biodiversity and Conservation》2008,17(5):1251-1265
The Atlantic Forest (AF) is one of the five most threatened and megadiverse world hotspots. It is arguably the most devastated
and highly threatened ecosystem on the planet. The vast scope of habitat loss and extreme fragmentation in the AF hotspots
has left intact very few extensive and continuous forested fragments. We compared bird assemblages between small (<100 ha)
and large (>6,000 ha) forest remnants, in one of the largest AF remnants in Argentina. We performed 84 point-counts of birds
in four large fragments (LF) and 67 points in 25 small fragments (SF). We recorded 4,527 bird individuals belonging to 173
species; 2,632 belonging to 153 species in LF and 1,897 in 124 species in SF. Small fragments suffered a significant loss
of bird richness, mainly forest dependent species, but the birds abundance did not decrease, due to an increase in abundance
of forest independent and semi-dependent bird species (edge and non forest species) that benefit from forest fragmentation.
The bird guilds of frugivores, undestory, terrestrial and midstory insectivores, nectarivores and raptors, and the endemic
species of AF were area sensitive, decreasing significantly in richness and abundance in the SF. Terrestrial granivores were
the only guild positively affected by forest fragmentation, containing mainly edge species, which forage in open areas or
borders including crops. Our first observations on fragmentation effects on bird assemblages in the southernmost Argentinean
Atlantic Forests did not validate the hypothesis on pre-adaptation to human disturbances in the bird communities of AF. On
the contrary, we observed that forest dependent, endemic and several sensitive bird guilds were strongly affected by fragmentation,
putting in evidence the vulnerability to the fragmentation process and the necessity to conserve large remnants to avoid reduction
of the high biodiversity of AF birds. 相似文献
50.
Michelini FM Berra A Alché LE 《The Journal of steroid biochemistry and molecular biology》2008,108(1-2):164-170
Herpes simplex virus type 1 (HSV-1) induces an ocular chronic immunoinflammatory syndrome named herpetic stromal keratitis that can lead to vision impairment and blindness. We have reported that the synthetic brassinosteroid (22S,23S)-3beta-bromo-5alpha,22,23-trihydroxystigmastan-6-one, designated as 2, is a potent antiviral in vitro and reduces the incidence of murine herpetic stromal keratitis, although it does not exert an antiviral effect in vivo. In the present report, we investigated whether brassinosteroid 2 may play a role in the modulation of the response of epithelial and immune cells to HSV-1 infection. Compound 2 blocked HSV-1-induced activation of NF-kappaB by inhibiting its translocation to the nucleus of infected corneal and conjunctival cells in vitro, as well as significantly reduced the secretion of TNF-alpha in infected NHC cells. Conversely, IL-6 production was enhanced by compound 2 after HSV-1 infection in both cell types. The production of these cytokines was considerably reduced in a LPS-stimulated macrophage cell line after treatment with compound 2. In conclusion, brassinosteroid 2 would be playing a modulating effect as an inductor or inhibitor, depending on the cell type involved. The improvement of disease observed in mice could be a balance between both, the immunostimulating and immunosuppressive effects of brassinosteroid 2 in vivo. 相似文献