Página 8 dos resultados de 60878 itens digitais encontrados em 0.039 segundos
Resultados filtrados por Publicador: National Academy of Sciences

‣ Flickering fusion pores comparable with initial exocytotic pores occur in protein-free phospholipid bilayers

Chanturiya, Alexandr; Chernomordik, Leonid V.; Zimmerberg, Joshua
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Publicado em 23/12/1997 Português
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For the act of membrane fusion, there are two competing, mutually exclusive molecular models that differ in the structure of the initial pore, the pathway for ionic continuity between formerly separated volumes. Because biological “fusion pores” can be as small as ionic channels or gap junctions, one model posits a proteinaceous initial fusion pore. Because biological fusion pore conductance varies widely, another model proposes a lipidic initial pore. We have found pore opening and flickering during the fusion of protein-free phospholipid vesicles with planar phospholipid bilayers. Fusion pore formation appears to follow the coalescence of contacting monolayers to create a zone of hemifusion where continuity between the two adherent membranes is lipidic, but not aqueous. Hypotonic stress, causing tension in the vesicle membrane, promotes complete fusion. Pores closed soon after opening (flickering), and the distribution of fusion pore conductance appears similar to the distribution of initial fusion pores in biological fusion. Because small flickering pores can form in the absence of protein, the existence of small pores in biological fusion cannot be an argument in support of models based on proteinaceous pores. Rather, these results support the model of a lipidic fusion pore developing within a hemifused contact site.

‣ Comparing the continuous representation of time-series expression profiles to identify differentially expressed genes

Bar-Joseph, Ziv; Gerber, Georg; Simon, Itamar; Gifford, David K.; Jaakkola, Tommi S.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.72014%
We present a general algorithm to detect genes differentially expressed between two nonhomogeneous time-series data sets. As increasing amounts of high-throughput biological data become available, a major challenge in genomic and computational biology is to develop methods for comparing data from different experimental sources. Time-series whole-genome expression data are a particularly valuable source of information because they can describe an unfolding biological process such as the cell cycle or immune response. However, comparisons of time-series expression data sets are hindered by biological and experimental inconsistencies such as differences in sampling rate, variations in the timing of biological processes, and the lack of repeats. Our algorithm overcomes these difficulties by using a continuous representation for time-series data and combining a noise model for individual samples with a global difference measure. We introduce a corresponding statistical method for computing the significance of this differential expression measure. We used our algorithm to compare cell-cycle-dependent gene expression in wild-type and knockout yeast strains. Our algorithm identified a set of 56 differentially expressed genes...

‣ Light-switching excimer probes for rapid protein monitoring in complex biological fluids

Yang, Chaoyong James; Jockusch, Steffen; Vicens, Marie; Turro, Nicholas J.; Tan, Weihong
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.72014%
Quantitative protein bioanalysis in complex biological fluids presents considerable challenges in biological studies and disease diagnosis. The major obstacles are the background signals from both the probe and the biological fluids where the proteins reside. We have molecularly engineered light-switching excimer aptamer probes for rapid and sensitive detection of a biomarker protein, platelet-derived growth factor (PDGF). Labeled with one pyrene at each end, the aptamer switches its fluorescence emission from ≈400 nm (pyrene monomer) to 485 nm (pyrene excimer) upon PDGF binding. This fluorescence wavelength change from monomer to excimer emission is a result of aptamer conformation rearrangement induced by target binding. The excimer probe is able to effectively detect picomolar PDGF in homogeneous solutions. Because the excimer has a much longer fluorescence lifetime (≈40 ns) than that of the background (≈5 ns), time-resolved measurements were used to eliminate the biological background. We thus were able to detect PDGF in a cell sample quantitatively without any sample pretreatment. This molecular engineering strategy can be used to develop other aptamer probes for protein monitoring. Combined with lifetime-based measurements and molecular engineering...

‣ DNA energy landscapes via calorimetric detection of microstate ensembles of metastable macrostates and triplet repeat diseases

Völker, Jens; Klump, Horst H.; Breslauer, Kenneth J.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.72014%
Biopolymers exhibit rough energy landscapes, thereby allowing biological processes to access a broad range of kinetic and thermodynamic states. In contrast to proteins, the energy landscapes of nucleic acids have been the subject of relatively few experimental investigations. In this study, we use calorimetric and spectroscopic observables to detect, resolve, and selectively enrich energetically discrete ensembles of microstates within metastable DNA structures. Our results are consistent with metastable, “native” DNA states being composed of an ensemble of discrete and kinetically stable microstates of differential stabilities, rather than exclusively being a single, discrete thermodynamic species. This conceptual construct is important for understanding the linkage between biopolymer conformational/configurational space and biological function, such as in protein folding, allosteric control of enzyme activity, RNA and DNA folding and function, DNA structure and biological regulation, etc. For the specific DNA sequences and structures studied here, the demonstration of discrete, kinetically stable microstates potentially has biological consequences for understanding the development and onset of DNA expansion and triplet repeat diseases.

‣ Geographic, seasonal, and precipitation chemistry influence on the abundance and activity of biological ice nucleators in rain and snow

Christner, Brent C.; Cai, Rongman; Morris, Cindy E.; McCarter, Kevin S.; Foreman, Christine M.; Skidmore, Mark L.; Montross, Scott N.; Sands, David C.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.72014%
Biological ice nucleators (IN) function as catalysts for freezing at relatively warm temperatures (warmer than −10 °C). We examined the concentration (per volume of liquid) and nature of IN in precipitation collected from Montana and Louisiana, the Alps and Pyrenees (France), Ross Island (Antarctica), and Yukon (Canada). The temperature of detectable ice-nucleating activity for more than half of the samples was ≥ −5 °C based on immersion freezing testing. Digestion of the samples with lysozyme (i.e., to hydrolyze bacterial cell walls) led to reductions in the frequency of freezing (0–100%); heat treatment greatly reduced (95% average) or completely eliminated ice nucleation at the measured conditions in every sample. These behaviors were consistent with the activity being bacterial and/or proteinaceous in origin. Statistical analysis revealed seasonal similarities between warm-temperature ice-nucleating activities in snow samples collected over 7 months in Montana. Multiple regression was used to construct models with biogeochemical data [major ions, total organic carbon (TOC), particle, and cell concentration] that were accurate in predicting the concentration of microbial cells and biological IN in precipitation based on the concentration of TOC...

‣ Systematic variation in the temperature dependence of physiological and ecological traits

Dell, Anthony I.; Pawar, Samraat; Savage, Van M.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.72014%
To understand the effects of temperature on biological systems, we compile, organize, and analyze a database of 1,072 thermal responses for microbes, plants, and animals. The unprecedented diversity of traits (n = 112), species (n = 309), body sizes (15 orders of magnitude), and habitats (all major biomes) in our database allows us to quantify novel features of the temperature response of biological traits. In particular, analysis of the rising component of within-species (intraspecific) responses reveals that 87% are fit well by the Boltzmann–Arrhenius model. The mean activation energy for these rises is 0.66 ± 0.05 eV, similar to the reported across-species (interspecific) value of 0.65 eV. However, systematic variation in the distribution of rise activation energies is evident, including previously unrecognized right skewness around a median of 0.55 eV. This skewness exists across levels of organization, taxa, trophic groups, and habitats, and it is partially explained by prey having increased trait performance at lower temperatures relative to predators, suggesting a thermal version of the life-dinner principle—stronger selection on running for your life than running for your dinner. For unimodal responses, habitat (marine...

‣ Co-occurrence of linguistic and biological diversity in biodiversity hotspots and high biodiversity wilderness areas

Gorenflo, L. J.; Romaine, Suzanne; Mittermeier, Russell A.; Walker-Painemilla, Kristen
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
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As the world grows less biologically diverse, it is becoming less linguistically and culturally diverse as well. Biologists estimate annual loss of species at 1,000 times or more greater than historic rates, and linguists predict that 50–90% of the world’s languages will disappear by the end of this century. Prior studies indicate similarities in the geographic arrangement of biological and linguistic diversity, although conclusions have often been constrained by use of data with limited spatial precision. Here we use greatly improved datasets to explore the co-occurrence of linguistic and biological diversity in regions containing many of the Earth’s remaining species: biodiversity hotspots and high biodiversity wilderness areas. Results indicate that these regions often contain considerable linguistic diversity, accounting for 70% of all languages on Earth. Moreover, the languages involved are frequently unique (endemic) to particular regions, with many facing extinction. Likely reasons for co-occurrence of linguistic and biological diversity are complex and appear to vary among localities, although strong geographic concordance between biological and linguistic diversity in many areas argues for some form of functional connection. Languages in high biodiversity regions also often co-occur with one or more specific conservation priorities...

‣ Childhood maltreatment is associated with distinct genomic and epigenetic profiles in posttraumatic stress disorder

Mehta, Divya; Klengel, Torsten; Conneely, Karen N.; Smith, Alicia K.; Altmann, André; Pace, Thaddeus W.; Rex-Haffner, Monika; Loeschner, Anne; Gonik, Mariya; Mercer, Kristina B.; Bradley, Bekh; Müller-Myhsok, Bertram; Ressler, Kerry J.; Binder, Elisabet
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.72014%
Childhood maltreatment is likely to influence fundamental biological processes and engrave long-lasting epigenetic marks, leading to adverse health outcomes in adulthood. We aimed to elucidate the impact of different early environment on disease-related genome-wide gene expression and DNA methylation in peripheral blood cells in patients with posttraumatic stress disorder (PTSD). Compared with the same trauma-exposed controls (n = 108), gene-expression profiles of PTSD patients with similar clinical symptoms and matched adult trauma exposure but different childhood adverse events (n = 32 and 29) were almost completely nonoverlapping (98%). These differences on the level of individual transcripts were paralleled by the enrichment of several distinct biological networks between the groups. Moreover, these gene-expression changes were accompanied and likely mediated by changes in DNA methylation in the same loci to a much larger proportion in the childhood abuse (69%) vs. the non-child abuse-only group (34%). This study is unique in providing genome-wide evidence of distinct biological modifications in PTSD in the presence or absence of exposure to childhood abuse. The findings that nonoverlapping biological pathways seem to be affected in the two PTSD groups and that changes in DNA methylation appear to have a much greater impact in the childhood-abuse group might reflect differences in the pathophysiology of PTSD...

‣ Effects of biological explanations for mental disorders on clinicians’ empathy

Lebowitz, Matthew S.; Ahn, Woo-kyoung
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
46.72014%
Mental disorders are increasingly understood biologically. We tested the effects of biological explanations among mental health clinicians, specifically examining their empathy toward patients. Conventional wisdom suggests that biological explanations reduce perceived blameworthiness against those with mental disorders, which could increase empathy. Yet, conceptualizing mental disorders biologically can cast patients as physiologically different from “normal” people and as governed by genetic or neurochemical abnormalities instead of their own human agency, which can engender negative social attitudes and dehumanization. This suggests that biological explanations might actually decrease empathy. Indeed, we find that biological explanations significantly reduce clinicians’ empathy. This is alarming because clinicians’ empathy is important for the therapeutic alliance between mental health providers and patients and significantly predicts positive clinical outcomes.

‣ Biological spectra analysis: Linking biological activity profiles to molecular structure

Fliri, Anton F.; Loging, William T.; Thadeio, Peter F.; Volkmann, Robert A.
Fonte: National Academy of Sciences Publicador: National Academy of Sciences
Tipo: Artigo de Revista Científica
Português
Relevância na Pesquisa
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Establishing quantitative relationships between molecular structure and broad biological effects has been a longstanding challenge in science. Currently, no method exists for forecasting broad biological activity profiles of medicinal agents even within narrow boundaries of structurally similar molecules. Starting from the premise that biological activity results from the capacity of small organic molecules to modulate the activity of the proteome, we set out to investigate whether descriptor sets could be developed for measuring and quantifying this molecular property. Using a 1,567-compound database, we show that percent inhibition values, determined at single high drug concentration in a battery of in vitro assays representing a cross section of the proteome, provide precise molecular property descriptors that identify the structure of molecules. When broad biological activity of molecules is represented in spectra form, organic molecules can be sorted by quantifying differences between biological spectra. Unlike traditional structure–activity relationship methods, sorting of molecules by using biospectra comparisons does not require knowledge of a molecule's putative drug targets. To illustrate this finding, we selected as starting point the biological activity spectra of clotrimazole and tioconazole because their putative target...