PubMed Central (PMC3 - NLM DTD)
(2,081,148 recursos)
Archive of life sciences journal literature at the U.S. National Institutes of Health (NIH), developed and managed by NIH's National Center for Biotechnology Information (NCBI) in the National Library of Medicine (NLM).
Mostrando recursos 141 - 160 de 184,040
141.
Fire cycles in North American interior grasslands and their relation to prairie drought - Brown, K. J.; Clark, J. S.; Grimm, E. C.; Donovan, J. J.; Mueller, P. G.; Hansen, B. C. S.; Stefanova, I.
High-resolution analyses of a late Holocene core from Kettle Lake in North Dakota reveal coeval fluctuations in loss-on-ignition carbonate content, percentage of grass pollen, and charcoal flux. These oscillations are indicative of climatefuelfire cycles that have prevailed on the Northern Great Plains (NGP) for most of the late Holocene. High charcoal flux occurred during past moist intervals when grass cover was extensive and fuel loads were high, whereas reduced charcoal flux characterized the intervening droughts when grass cover, and hence fuel loads, decreased, illustrating that fire is not a universal feature of the NGP through time but oscillates with climate....
142.
Premature ovarian aging in mice deficient for Gpr3 - Ledent, Catherine; Demeestere, Isabelle; Blum, David; Petermans, Julien; Hämäläinen, Tuula; Smits, Guillaume; Vassart, Gilbert
After becoming competent for resuming meiosis, fully developed mammalian oocytes are maintained arrested in prophase I until ovulation is triggered by the luteotropin surge. Meiotic pause has been shown to depend critically on maintenance of cAMP level in the oocyte and was recently attributed to the constitutive Gs (the heterotrimeric GTP-binding protein that activates adenylyl cyclase) signaling activity of the G protein-coupled receptor GPR3. Here we show that mice deficient for Gpr3 are unexpectedly fertile but display progressive reduction in litter size despite stable age-independent alteration of meiotic pause. Detailed analysis of the phenotype confirms premature resumption of meiosis, in...
143.
Rapid plasticity of binocular connections in developing monkey visual cortex (V1) - Zhang, Bin; Bi, Hua; Sakai, Eiichi; Maruko, Ichiro; Zheng, Jianghe; Smith, Earl L.; Chino, Yuzo M.
The basic sets of cortical connections are present at birth in the primate visual system. The maintenance and refinement of these innate connections are highly dependent on normal visual experience, and prolonged exposure to binocularly uncorrelated signals early in life severely disrupts the normal development of binocular functions. However, very little is known about how rapidly these changes in the functional organization of primate visual cortex emerge or what are the sequence and the nature of the abnormal neural events that occur immediately after experiencing binocular decorrelation. In this study, we investigated how brief periods of ocular misalignment (strabismus) at...
144.
Longitudinal analysis of the group A Streptococcus transcriptome in experimental pharyngitis in cynomolgus macaques - Virtaneva, Kimmo; Porcella, Stephen F.; Graham, Morag R.; Ireland, Robin M.; Johnson, Claire A.; Ricklefs, Stacy M.; Babar, Imran; Parkins, Larye D.; Romero, Romina A.; Corn, G. Judson; Gardner, Don J.; Bailey, John R.; Parnell, Michael J.; Musser, James M.
Identification of the genetic events that contribute to hostpathogen interactions is important for understanding the natural history of infectious diseases and developing therapeutics. Transcriptome studies conducted on pathogens have been central to this goal in recent years. However, most of these investigations have focused on specific end points or disease phases, rather than analysis of the entire time course of infection. To gain a more complete understanding of how bacterial gene expression changes over time in a primate host, the transcriptome of group A Streptococcus (GAS) was analyzed during an 86-day infection protocol in 20 cynomolgus macaques with experimental pharyngitis....
145.
Atomic-scale dynamical structures of fatty acid bilayers observed by ultrafast electron crystallography - Chen, Songye; Seidel, Marco T.; Zewail, Ahmed H.
The structure and dynamics of a biological model bilayer are reported with atomic-scale resolution by using ultrafast electron crystallography. The bilayer was deposited as a Langmuir-Blodgett structure of arachidic (eicosanoic) fatty acids with the two chains containing 40 carbon atoms (?50 Å), on a hydrophobic substrate, the hydrogen terminated silicon(111) surface. We determined the structure of the 2D assembly, establishing the orientation of the chains and the subunit cell of the CH2 distances: a0 = 4.7 Å, b0 = 8.0 Å, and c0 = 2.54 Å. For structural dynamics, the diffraction frames were taken every 1 picosecond after a femtosecond...
146.
Concurrent use of transgenic plants expressing a single and two Bacillus thuringiensis genes speeds insect adaptation to pyramided plants - Zhao, Jian-Zhou; Cao, Jun; Collins, Hilda L.; Bates, Sarah L.; Roush, Richard T.; Earle, Elizabeth D.; Shelton, Anthony M.
Transgenic plants expressing insecticidal proteins from the bacterium Bacillus thuringiensis (Bt) were grown on over 13 million ha in the United States and 22.4 million ha worldwide in 2004. Preventing or slowing the evolution of resistance by insects (resistance management) is critical for the sustainable use of Bt crops. Plants containing two dissimilar Bt toxin genes in the same plant (pyramided) have the potential to delay insect resistance. However, the advantage of pyramided Bt plants for resistance management may be compromised if they share similar toxins with single-gene plants that are deployed simultaneously. We tested this hypothesis using a unique...
147.
Phenotypic and functional characterization of adult brain neuropoiesis - Scheffler, Bjorn; Walton, Noah M.; Lin, Dean D.; Goetz, A. Katrin; Enikolopov, Grigori; Roper, Steve N.; Steindler, Dennis A.
The modern concept of neurogenesis in the adult brain is predicated on the premise that multipotent glial cells give rise to new neurons throughout life. Although extensive evidence exists indicating that this is the case, the transition from glial to neuronal phenotype remains poorly understood. A unique monolayer cell-culture system was developed to induce, expose, and recapitulate the entire developmental series of events of subventricular zone (SVZ) neurogenesis. We show here, using immunophentoypic, ultrastructural, electrophysiological, and time-lapse analyses, that SVZ-derived glial fibrillary acidic proteinlow/A2B5+/nestin+ candidate founder cells undergo metamorphosis to eventually generate large numbers of fully differentiated interneuron phenotypes. A...
148.
Structure of the uncleaved ectodomain of the paramyxovirus (hPIV3) fusion protein - Yin, Hsien-Sheng; Paterson, Reay G.; Wen, Xiaolin; Lamb, Robert A.; Jardetzky, Theodore S.
Class I viral fusion proteins share common mechanistic and structural features but little sequence similarity. Structural insights into the protein conformational changes associated with membrane fusion are based largely on studies of the influenza virus hemagglutinin in pre- and postfusion conformations. Here, we present the crystal structure of the secreted, uncleaved ectodomain of the paramyxovirus, human parainfluenza virus 3 fusion (F) protein, a member of the class I viral fusion protein group. The secreted human parainfluenza virus 3 F forms a trimer with distinct head, neck, and stalk regions. Unexpectedly, the structure reveals a six-helix bundle associated with the postfusion...
149.
Genomic evolution of MHC class I region in primates - Fukami-Kobayashi, Kaoru; Shiina, Takashi; Anzai, Tatsuya; Sano, Kazumi; Yamazaki, Masaaki; Inoko, Hidetoshi; Tateno, Yoshio
To elucidate the origins of the MHC-B-MHC-C pair and the MHC class I chain-related molecule (MIC)A-MICB pair, we sequenced an MHC class I genomic region of humans, chimpanzees, and rhesus monkeys and analyzed the regions from an evolutionary stand-point, focusing first on LINE sequences that are paralogous within each of the first two species and orthologous between them. Because all the long interspersed nuclear element (LINE) sequences were fragmented and nonfunctional, they were suitable for conducting phylogenetic study and, in particular, for estimating evolutionary time. Our study has revealed that MHC-B and MHC-C duplicated 22.3 million years (Myr) ago, and...
150.
Human thiopurine S-methyltransferase pharmacogenetics: Variant allozyme misfolding and aggresome formation - Wang, Liewei; Nguyen, Tien V.; McLaughlin, Richard W.; Sikkink, Laura A.; Ramirez-Alvarado, Marina; Weinshilboum, Richard M.
Thiopurine S-methyltransferase (TPMT) catalyzes the S-methylation of thiopurine drugs. TPMT genetic polymorphisms represent a striking example of the potential clinical value of pharmacogenetics. Subjects homozygous for TPMT*3A, the most common variant allele for low activity, an allele that encodes a protein with two changes in amino acid sequence, are at greatly increased risk for life-threatening toxicity when treated with standard doses of thiopurines. These subjects have virtually undetectable levels of TPMT protein. In this study, we tested the hypothesis that TPMT*3A might result in protein misfolding and aggregation. We observed that TPMT*3A forms aggresomes in cultured cells and that it...
151.
Cell intrinsic alterations underlie hematopoietic stem cell aging - Rossi, Derrick J.; Bryder, David; Zahn, Jacob M.; Ahlenius, Henrik; Sonu, Rebecca; Wagers, Amy J.; Weissman, Irving L.
Loss of immune function and an increased incidence of myeloid leukemia are two of the most clinically significant consequences of aging of the hematopoietic system. To better understand the mechanisms underlying hematopoietic aging, we evaluated the cell intrinsic functional and molecular properties of highly purified long-term hematopoietic stem cells (LT-HSCs) from young and old mice. We found that LT-HSC aging was accompanied by cell autonomous changes, including increased stem cell self-renewal, differential capacity to generate committed myeloid and lymphoid progenitors, and diminished lymphoid potential. Expression profiling revealed that LT-HSC aging was accompanied by the systemic down-regulation of genes mediating lymphoid...
152.
Aryl hydrocarbon receptor activation by cAMP vs. dioxin: Divergent signaling pathways - Oesch-Bartlomowicz, Barbara; Huelster, Andrea; Wiss, Oliver; Antoniou-Lipfert, Patricia; Dietrich, Cornelia; Arand, Michael; Weiss, Carsten; Bockamp, Ernesto; Oesch, Franz
Even before the first vertebrates appeared on our planet, the aryl hydrocarbon receptor (AHR) gene was present to carry out one or more critical life functions. The vertebrate AHR then evolved to take on functions of detecting and responding to certain classes of environmental toxicants. These environmental pollutants include polycyclic aromatic hydrocarbons (e.g., benzo[a]pyrene), polyhalogenated hydrocarbons, dibenzofurans, and the most potent small-molecular-weight toxicant known, 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD or dioxin). After binding of these ligands, the activated AHR translocates rapidly from the cytosol to the nucleus, where it forms a heterodimer with aryl hydrocarbon nuclear translocator, causing cellular responses that lead to...
153.
Reversible single-molecule photoswitching in the GFP-like fluorescent protein Dronpa - Habuchi, Satoshi; Ando, Ryoko; Dedecker, Peter; Verheijen, Wendy; Mizuno, Hideaki; Miyawaki, Atsushi; Hofkens, Johan
Reversible photoswitching of individual molecules has been demonstrated for a number of mutants of the green fluorescent protein (GFP). To date, however, a limited number of switching events with slow response to light have been achieved at the single-molecule level. Here, we report reversible photoswitching characteristics observed in individual molecules of Dronpa, a mutant of a GFP-like fluorescent protein that was cloned from a coral Pectiniidae. Ensemble spectroscopy shows that intense irradiation at 488 nm changes Dronpa to a dim protonated form, but even weak irradiation at 405 nm restores it to the bright deprotonated form. Although Dronpa exists in...
154.
An intracellular phosphate buffer filters transient fluctuations in extracellular phosphate levels - Thomas, Melissa R.; O'Shea, Erin K.
To survive in a dynamic and unpredictable environment, cells must correctly interpret and integrate extracellular signals with internal factors. In particular, internal stores of nutrients must be managed for use during periods of nutrient limitation. To gain insight into this complex process, we combined biochemical and spectroscopic techniques to follow the dynamics of the phosphate responsive signaling pathway in both single yeast cells and populations. We demonstrate that the phosphate-responsive genes PHO5 and PHO84 exhibit different kinetics of transcriptional induction in response to phosphate starvation, and that transient phosphate limitation causes induction of PHO84 but not PHO5. This differential kinetic...
155.
Critical period for sensory experience-dependent survival of newly generated granule cells in the adult mouse olfactory bulb - Yamaguchi, Masahiro; Mori, Kensaku
Granule cells in the olfactory bulb (OB) are continually produced and added into the neuronal circuit in the adult brain. Sensory input to the OB plays a key role in the survival of newly generated granule cells. Here, we examined in the adult mice whether there is a time window after the generation of new granule cells when their survival is strongly influenced by sensory input. New granule cells were labeled by BrdUrd injection, and the mice were deprived of sensory input unilaterally by naris cauterization. During the initial 14 days after BrdUrd labeling, the number of BrdUrd-positive granule cells...
156.
Structural and biochemical basis for selective repression of the orphan nuclear receptor liver receptor homolog 1 by small heterodimer partner - Li, Yong; Choi, Mihwa; Suino, Kelly; Kovach, Amanda; Daugherty, Jennifer; Kliewer, Steven A.; Xu, H. Eric
The functional interaction between the orphan nuclear receptors small heterodimer partner (SHP) and liver receptor homolog 1 (LRH-1), where SHP binds to LRH-1 and represses its constitutive transcriptional activity, is crucial for regulating genes involved in cholesterol homeostasis. Here, we report structural and biochemical analyses of the LRH-1/SHP interaction. The crystal structure and modeling studies of the LRH-1 ligand-binding domain bound to either of the two LXXLL-related motifs of SHP show that the receptor undergoes conformational changes to accommodate the SHP docking and reveal key residues that determine the potency and selectivity of SHP binding. Through a combination of mutagenesis...
157.
The impact of HIV/AIDS on the control of tuberculosis in India - Williams, B. G.; Granich, R.; Chauhan, L. S.; Dharmshaktu, N. S.; Dye, C.
Epidemics of HIV/AIDS have increased the tuberculosis (TB) case-load by five or more times in East Africa and southern Africa. As HIV continues to spread, warnings have been issued of disastrous AIDS and TB epidemics in new-wave countries, including India, which accounts for 20% of all new TB cases arising in the world each year. Here we investigate whether, in the face of the HIV epidemic, India's Revised National TB Control Program (RNTCP) could halve TB prevalence and death rates in the period 19902015, as specified by the United Nations Millennium Development Goals. Using a mathematical model to capture the...
158.
The human brain is intrinsically organized into dynamic, anticorrelated functional networks - Fox, Michael D.; Snyder, Abraham Z.; Vincent, Justin L.; Corbetta, Maurizio; Van Essen, David C.; Raichle, Marcus E.
During performance of attention-demanding cognitive tasks, certain regions of the brain routinely increase activity, whereas others routinely decrease activity. In this study, we investigate the extent to which this task-related dichotomy is represented intrinsically in the resting human brain through examination of spontaneous fluctuations in the functional MRI blood oxygen level-dependent signal. We identify two diametrically opposed, widely distributed brain networks on the basis of both spontaneous correlations within each network and anticorrelations between networks. One network consists of regions routinely exhibiting task-related activations and the other of regions routinely exhibiting task-related deactivations. This intrinsic organization, featuring the presence of...
159.
The Rho GTP exchange factor Lfc promotes spindle assembly in early mitosis - Bakal, Christopher J.; Finan, Dina; LaRose, José; Wells, Clark D.; Gish, Gerald; Kulkarni, Sarang; DeSepulveda, Paulo; Wilde, Andrew; Rottapel, Robert
Rho GTPases regulate reorganization of actin and microtubule cytoskeletal structures during both interphase and mitosis. The timing and subcellular compartment in which Rho GTPases are activated is controlled by the large family of Rho GTP exchange factors (RhoGEFs). Here, we show that the microtubule-associated RhoGEF Lfc is required for the formation of the mitotic spindle during prophase/prometaphase. The inability of cells to assemble a functioning spindle after Lfc inhibition resulted in a delay in mitosis and an accumulation of prometaphase cells. Inhibition of Lfc's primary target Rho GTPase during prophase/prometaphase, or expression of a catalytically inactive mutant of Lfc, also...
160.
Gut mucosal T cell responses and gene expression correlate with protection against disease in long-term HIV-1-infected nonprogressors - Sankaran, Sumathi; Guadalupe, Moraima; Reay, Elizabeth; George, Michael D.; Flamm, Jason; Prindiville, Thomas; Dandekar, Satya
Limited information is available on the molecular mechanisms by which long-term HIV-1-infected nonprogressors suppress HIV-1 infection and maintain immune functions. The intestinal mucosal immune system is an early target for HIV-1 infection and severe CD4+ T cell depletion. We evaluated mucosal T lymphocyte subsets, virus-specific cellular responses, gene expression profiles, and viral loads in intestinal mucosal biopsies of long-term nonprogressor (LTNP) patients as compared to chronically HIV-1-infected patients with high viral loads (HVLs) and CD4+ T cell loss, as well as HIV-seronegative healthy individuals. This study aims to identify the mucosal correlates of HIV disease progression and to determine the...
141.
