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891.
Travis J. Mitchell Camila Zugarramurdi J. Fernando Olivera Craig Gatto Pablo Artigas 《Biophysical journal》2014
The Na/K pump hydrolyzes ATP to export three intracellular Na (Nai) as it imports two extracellular K (Ko) across animal plasma membranes. Within the protein, two ion-binding sites (sites I and II) can reciprocally bind Na or K, but a third site (site III) exclusively binds Na in a voltage-dependent fashion. In the absence of Nao and Ko, the pump passively imports protons, generating an inward current (IH). To elucidate the mechanisms of IH, we used voltage-clamp techniques to investigate the [H]o, [Na]o, and voltage dependence of IH in Na/K pumps from ventricular myocytes and in ouabain-resistant pumps expressed in Xenopus oocytes. Lowering pHo revealed that Ho both activates IH (in a voltage-dependent manner) and inhibits it (in a voltage-independent manner) by binding to different sites. Nao effects depend on pHo; at pHo where no Ho inhibition is observed, Nao inhibits IH at all concentrations, but when applied at pHo that inhibits pump-mediated current, low [Na]o activates IH and high [Na]o inhibits it. Our results demonstrate that IH is a property inherent to Na/K pumps, not linked to the oocyte expression environment, explains differences in the characteristics of IH previously reported in the literature, and supports a model in which 1), protons leak through site III; 2), binding of two Na or two protons to sites I and II inhibits proton transport; and 3), pumps with mixed Na/proton occupancy of sites I and II remain permeable to protons. 相似文献
892.
Jill T. Anderson Cheng‐Ruei Lee Thomas Mitchell‐Olds 《Evolution; international journal of organic evolution》2014,68(1):16-31
Fitness trade‐offs across episodes of selection and environments influence life‐history evolution and adaptive population divergence. Documenting these trade‐offs remains challenging as selection can vary in magnitude and direction through time and space. Here, we evaluate fitness trade‐offs at the levels of the whole organism and the quantitative trait locus (QTL) in a multiyear field study of Boechera stricta (Brassicaceae), a genetically tractable mustard native to the Rocky Mountains. Reciprocal local adaptation was pronounced for viability, but not for reproductive components of fitness. Instead, local genomes had a fecundity advantage only in the high latitude garden. By estimating realized selection coefficients from individual‐level data on viability and reproductive success and permuting the data to infer significance, we examined the genetic basis of fitness trade‐offs. This analytical approach (Conditional Neutrality‐Antagonistic Pleiotropy, CNAP) identified genetic trade‐offs at a flowering phenology QTL (costs of adaptation) and revealed genetic trade‐offs across fitness components (costs of reproduction). These patterns would not have emerged from traditional ANOVA‐based QTL mapping. Our analytical framework can be applied to other systems to investigate fitness trade‐offs. This task is becoming increasingly important as climate change may alter fitness landscapes, potentially disrupting fitness trade‐offs that took many generations to evolve. 相似文献
893.
Mitchell Lawrence Jones Jorge Gabriel Ganopolsky Alain Labbé Christopher Wahl Satya Prakash 《Applied microbiology and biotechnology》2010,88(2):401-407
This review describes the antimicrobial properties of nitric oxide (NO) and its application as an antimicrobial agent in different
formulations and medical devices. We depict the eukaryotic biosynthesis of NO and its physiologic functions as a cell messenger
and as an antimicrobial agent of the cell-mediated immune response. We analyze the antimicrobial activity of NO and the eukaryotic
protective mechanisms against NO for the purpose of delineating the therapeutic NO dosage range required for an efficacious
and safe antimicrobial activity. We also examine the role of NO produced by virulent bacteria in lessening the efficacy of
traditional antimicrobials. In addition, we discuss the efficacy of NO in the healing of infected wounds, describing different
NO-producing devices by category, analyzing therapeutic levels, duration of NO production, as well as commercial considerations.
Finally, we provide current and future prospects for the design and use of NO-producing devices. 相似文献
894.
Lee JH Agacinski G Williams JH Wilcock GK Esiri MM Francis PT Wong PT Chen CP Lai MK 《Neurochemistry international》2010,57(8):985-989
The cannabinoid CB1 receptor has gained much attention as a potential pharmacotherapeutic target in various neurodegenerative diseases including Alzheimer's disease (AD). However, the relation of CB1 receptors to cognitive function in AD is at present unclear. In this study, postmortem brain tissues from a cohort of prospectively assessed, neuropathologically confirmed AD patients and aged controls were used to measure CB1 receptors by immunoblotting, and a subset of subjects also had [(3)H]SR141716A binding. Correlational analyses were then performed for the neurochemical and cognitive data. We found that CB1 receptor levels in were unchanged AD in the brain regions assessed (frontal cortex, anterior cingulate gyrus, hippocampus, caudate nucleus). Within the AD group, frontal cortical CB1 immunoreactivity correlated with cognitive scores assessed within a year of death. Our study suggests that CB1 receptors are intact in AD and may play a role in preserving cognitive function. Therefore, CB1 receptors should be further assessed as a potential therapeutic target in AD. 相似文献
895.
Alexandra Magro Christine Ducamp Felipe Ramon-Portugal Emilie Lecompte Brigitte Crouau-Roy Anthony Frederick George Dixon Jean-Louis Hemptinne 《Evolutionary ecology》2010,24(1):251-271
Faced with an ephemeral prey, aphidophagous ladybirds rely on the hydrocarbons present in the tracks of their larvae to choose
an unoccupied patch for egg laying. Although both conspecific and heterospecific larval tracks might deter females from oviposition,
the response to the later is often less striking. Several explanations have been suggested to account for this. In this paper
we tested the phylogeny hypothesis, which predicts that the chemical composition of the tracks of closely related species
of ladybirds will be more similar to one another than to those of more distantly related species. Qualitative and quantitative
information on the chemical nature of the larval tracks and a molecular phylogeny of seven species belonging to three different
genera are provided, and the congruence between these two sets of results assessed. The results confirm the phylogeny hypothesis
and infer a gradual mode of evolution of these infochemicals. 相似文献
896.
Mumford Cove, a 48 ha Connecticut embayment on Long Island Sound, has a history of excessive nutrient inputs and corresponding eutrophic conditions with concomitant eelgrass (Zostera marina L.) loss. From 1945 to 1987, a municipal wastewater treatment facility discharged into the cove. In 1987, when the wastewater outfall was diverted to another location, the cove supported a near monoculture of the green algae Ulva lactuca L., covering 74% of the bottom. By 1988, macroalgal areal cover in Mumford Cove had declined to 9%. When we first sampled the cove in 1992, Z. marina and Ruppia maritima L. were present. By 1999, areal distribution of Z. marina and R. maritima had expanded to cover a third of the bottom. Periodic summertime surveys from 2002 through 2004 indicated that Z. marina was present in approximately half of the cove; R. maritima was sparse. Fifteen years after termination of nutrient enrichment, this cove had recovered from 40 years of point source anthropogenic nutrient input, returning from an Ulva-dominated to a Zostera-dominated state. 相似文献
897.
898.
Evan M. Kroh Rachael K. Parkin Patrick S. Mitchell Muneesh Tewari 《Methods (San Diego, Calif.)》2010,50(4):298-301
MicroRNAs (miRNAs) are small (~22 nt) RNAs that play important roles in gene regulatory networks by binding to and repressing the activity of specific target mRNAs. Recent studies have indicated that miRNAs circulate in a stable, cell-free form in the bloodstream and that the abundance of specific miRNAs in plasma or serum can serve as biomarkers of cancer and other diseases. Measurement of circulating miRNAs as biomarkers is associated with some special challenges, including those related to pre-analytic variation and data normalization. We describe here our procedure for qRT-PCR analysis of circulating miRNAs as biomarkers, and discuss relevant issues of sample preparation, experimental design and data analysis. 相似文献
899.
Cheol-Min Ghim Taesung Kim Robert J. Mitchell Sung Kuk Lee 《Biotechnology and Bioprocess Engineering》2010,15(1):11-21
The ultimate goal in the production of biofuels is to produce fuels identical or similar to petroleum-derived transportation
fuels more efficiently and in commercial quantities. Synthetic biologists have been engineering microbes to synthesize biofuels,
such as butanol and fatty acid- or isoprenoid-based fuels, which are nearly identical to gasoline and diesel. One of the most
urgent demands along this direction is to attain a solid framework for characterizing and standardizing the biological parts
and devices. It seems quite promising because biotechnologies specially based on miniaturizations have been making a big contribution
to this work. Therefore, in this review, recent advances and difficulties in the biofuel field are discussed, along with the
advances of synthetic biology, which will make it possible to create designer microorganisms that produce economically viable
next generation biofuels, aside from bioethanol, from corn or sugar cane, and biodiesel from plant or animal oils. 相似文献
900.