bluuebunny/crossref_metadata_2025 huggingface dataset:
Dynamics of Chemical Bonding Mapped by Energy-Resolved 4D Electron Microscopy
Authors: Carbone Fabrizio , Kwon Oh-Hoon , Zewail Ahmed H.
Published: July 2009

Watching Graphite Breathe

Electron microscopy is best known for its capacity to resolve spatial features. In a variant of the technique termed electron energy loss spectroscopy (EELS), the kinetic energy dissipated as the electron probe beam penetrates a sample can be quantified to characterize the material's underlying electronic structure.

Carbone
et al.

(p.
181
) have achieved femtosecond time resolution in an EELS study of graphite, and thereby traced the correlated motion of electrons and nuclei when the sample is heated by laser irradiation. The laser pulse induces rapid compression and then expansion of the layers in graphite's sheet structure. Concurrently, EELS uncovers shifts in delocalized electronic excitations, or plasmons. Layer compression coincides with a population shift from surface to bulk (that is, interlayer) plasmons, with the reverse shift accompanying expansion.
Tofu Was Just a Start
The World of Soy

Christine M. Du Bois, Chee-Beng Tan, and Sidney W. Mintz, Eds.

University of Illinois Press, Urbana, 2008. 350 pp. $40, £30.99. ISBN 9780252033414.
Authors: Grusak Michael A.
Published: July 2009

The contributors explore the range of foods made from soybean and the other ways soy products enter our meals, highlighting how important these foods are and how important they may become.
Babylon, Newton, and All That
Science
A Four Thousand Year History

by Patricia Fara

Oxford University Press, Oxford, 2009. 424 pp. $34.95, £20. ISBN 9780199226894.
Authors: Gordin Michael D.
Published: July 2009

In this accessible history, Fara surveys the practice of science from ancient Babylon through current projects in genomics and particle physics.
Smoke and Climate Change
Authors: Quaas Johannes
Published: July 2009

Since preindustrial times, increasing soot concentrations have strongly reduced cooling by anthropogenic aerosols.
Science in the Future of India
Authors: Rao C. N. R.
Published: July 2009

India has voted for Science. In May, half a billion people cast their ballots, and they decisively favored spurring the development of the world's second most populous nation. The reelected Prime Minister Manmohan Singh and his new coalition government have made a commitment to reduce poverty and disease, create employment, and stimulate rural and industrial development. Attaining these goals will require substantial new investments in science and technology (S&T) plus much greater investments in human capital.
Sizing Up the Cell
Authors: Edgar Bruce A. , Kim Kerry J.
Published: July 2009

Control over cell division depends on coordinately functioning sensors of cell size and age.
Straight From the Pig's Mouth: Swine Research With Swine Influenzas
Authors: Cohen Jon
Published: July 2009

If the novel H1N1 virus behaves like its ancestors, humans may have a rough road ahead, especially if it takes hold on hog farms.
Subtype Analysis of
Cryptosporidium
Specimens from Sporadic Cases in Colorado, Idaho, New Mexico, and Iowa in 2007: Widespread Occurrence of One
Cryptosporidium hominis
Subtype and Case History of an Infection with the
Cryptosporidium
Horse Genotype
Authors: Xiao Lihua , Hlavsa Michele C. , Yoder Jonathan , Ewers Christina , Dearen Theresa , Yang Wenli , Nett Randall , Harris Stephanie , Brend Sarah M. , Harris Meghan , Onischuk Lisa , Valderrama Amy L. , Cosgrove Shaun , Xavier Karen , Hall Nancy , Romero Sylvia , Young Stephen , Johnston Stephanie P. , Arrowood Michael , Roy Sharon , Beach Michael J.
Published: July 2009

Subtyping was conducted in late 2007 on 57
Cryptosporidium
specimens from sporadic cases in Colorado, Idaho, New Mexico, and Iowa. One previously rare
Cryptosporidium hominis
subtype was indentified in 40 cases (70%) from all four states, and the
Cryptosporidium
horse genotype was identified in a pet shop employee with severe clinical symptoms.
Protein Kinase G Phosphorylates Mosquito-Borne Flavivirus NS5
Authors: Bhattacharya Dipankar , Mayuri  , Best S. M. , Perera R. , Kuhn R. J. , Striker Rob
Published: July 2009

Serine/threonine phosphorylation of the nonstructural protein 5 (NS5) is a conserved feature of flaviviruses, but the kinase(s) responsible and function(s) remain unknown. Mass spectrometry was used to compare the phosphorylation sites of the NS5 proteins of yellow fever virus (YFV) and dengue virus (DENV), two flaviviruses transmitted by mosquitoes. Seven DENV phosphopeptides were identified, but only one conserved phosphoacceptor site (threonine 449 in DENV) was identified in both viruses. This site is predicted to be a protein kinase G (PKG) recognition site and is a strictly conserved serine/threonine phosphoacceptor site in mosquito-borne flaviviruses. In contrast, in tick-borne flaviviruses, this residue is typically a histidine. A DENV replicon engineered to have the tick-specific histidine residue at this position is replication defective. We show that DENV NS5 purified from
Escherichia coli
is a substrate for PKG in vitro and facilitates the autophosphorylation of PKG as seen with cellular substrates. Phosphorylation in vitro by PKG also occurs at threonine 449. Activators and inhibitors of PKG modulate DENV replication in cell culture but not replication of the tick-borne langat virus. Collectively, these data argue that PKG mediates a conserved serine/threonine phosphorylation event specifically for flaviviruses spread by mosquitoes.
The Impact of Individual Human Immunodeficiency Virus Type 1 Protease Mutations on Drug Susceptibility Is Highly Influenced by Complex Interactions with the Background Protease Sequence
Authors: Van Marck H. , Dierynck I. , Kraus G. , Hallenberger S. , Pattery T. , Muyldermans G. , Geeraert L. , Borozdina L. , Bonesteel R. , Aston C. , Shaw E. , Chen Q. , Martinez C. , Koka V. , Lee J. , Chi E. , de Béthune M.-P. , Hertogs K.
Published: July 2009

The requirement for multiple mutations for protease inhibitor (PI) resistance necessitates a better understanding of the molecular basis of resistance development. The novel bioinformatics resistance determination approach presented here elaborates on genetic profiles observed in clinical human immunodeficiency virus type 1 (HIV-1) isolates. Synthetic protease sequences were cloned in a wild-type HIV-1 background to generate a large number of close variants, covering 69 mutation clusters between multi-PI-resistant viruses and their corresponding genetically closely related, but PI-susceptible, counterparts. The vast number of mutants generated facilitates a profound and broad analysis of the influence of the background on the effect of individual PI resistance-associated mutations (PI-RAMs) on PI susceptibility. Within a set of viruses, all PI-RAMs that differed between susceptible and resistant viruses were varied while maintaining the background sequence from the resistant virus. The PI darunavir was used to evaluate PI susceptibility. Single sets allowed delineation of the impact of individual mutations on PI susceptibility, as well as the influence of PI-RAMs on one another. Comparing across sets, it could be inferred how the background influenced the interaction between two mutations, in some cases even changing antagonistic relationships into synergistic ones or vice versa. The approach elaborates on patient data and demonstrates how the specific mutational background greatly influences the impact of individual mutations on PI susceptibility in clinical patterns.
Mouse Norovirus Replication Is Associated with Virus-Induced Vesicle Clusters Originating from Membranes Derived from the Secretory Pathway
Authors: Hyde Jennifer L. , Sosnovtsev Stanislav V. , Green Kim Y. , Wobus Christiane , Virgin Herbert W. , Mackenzie Jason M.
Published: July 2009

Human noroviruses (familyCaliciviridae) are the leading cause of nonbacterial gastroenteritis worldwide. Despite the prevalence of these viruses within the community, the study of human norovirus has largely been hindered due to the inability to cultivate the viruses ex vivo and the lack of a small-animal model. In 2003, the discovery of a novel murine norovirus (MNV-1) and the identification of the tropism of MNV-1 for cells of a mononuclear origin led to the establishment of the first norovirus tissue culture system. Like other positive-sense RNA viruses, MNV-1 replication is associated with host membranes, which undergo significant rearrangement during infection. We characterize here the subcellular localization of the MNV-1 open reading frame 1 proteins and viral double-stranded RNA (dsRNA). Over the course of infection, dsRNA and the MNV-1 RNA-dependent RNA polymerase (NS7) were observed to proliferate from punctate foci located in the perinuclear region. All of the MNV-1 open reading frame 1 proteins were observed to colocalize with dsRNA during the course of infection. The MNV-1 replication complex was immunolocalized to virus-induced vesicle clusters formed in the cytoplasm of infected cells. Both dsRNA and MNV-1 NS7 were observed to localize to the limiting membrane of the individual clusters by cryo-immunoelectron microscopy. We show that the MNV-1 replication complex initially associates with membranes derived from the endoplasmic reticulum,trans-Golgi apparatus, and endosomes. In addition, we show that MNV-1 replication is insensitive to the fungal metabolite brefeldin A and consistently does not appear to recruit coatomer protein complex I (COPI) or COPII component proteins during replication. These data provide preliminary insights into key aspects of replication of MNV-1, which will potentially further our understanding of the pathogenesis of noroviruses and aid in the identification of potential targets for drug development.
Disruption of LANA in Rhesus Rhadinovirus Generates a Highly Lytic Recombinant Virus
Authors: Wen Kwun Wah , Dittmer Dirk P. , Damania Blossom
Published: July 2009

Rhesus monkey rhadinovirus (RRV) is a gammaherpesvirus that is closely related to human Kaposi's sarcoma-associated herpesvirus (KSHV/HHV-8). RRV is the closest relative to KSHV that has a fully sequenced genome and serves as an in vitro and an in vivo model system for KSHV. The latency-associated nuclear antigen (LANA) protein of both KSHV and RRV plays key roles in the establishment and maintenance of these herpesviruses. We have constructed a RRV recombinant virus (RRVΔLANA/GFP) in which the RRV LANA open reading frame has been disrupted with a green fluorescent protein (GFP) expression cassette generated by homologous recombination. The integrity of the recombinant virus was confirmed by diagnostic PCR, restriction digestion, Southern blot analysis, and whole-genome sequencing. We compared the single-step and multistep replication kinetics of RRVΔLANA/GFP, RRV-GFP, wild-type (WT) RRV H26-95, and a revertant virus using traditional plaque assays, as well as real-time quantitative PCR-based genome quantification assays. The RRVΔLANA/GFP recombinant virus exhibited significantly higher lytic replicative properties compared to RRV-GFP, WT RRV, or the revertant virus. This was observed upon de novo infection and in the absence of chemical inducers such as phorbol esters. In addition, by using a quantitative real-time PCR-based viral array, we are the first to report differences in global viral gene expression between WT and recombinant viruses. The RRVΔLANA/GFP virus displayed increased lytic gene transcription at all time points postinfection compared to RRV-GFP. Moreover, we also examined several cellular genes that are known to be repressed by KSHV LANA and report that these genes are derepressed during de novo lytic infection with the RRVΔLANA/GFP virus compared to RRV-GFP. Finally, we also demonstrate that the RRVΔLANA/GFP virus fails to establish latency in B cells, as measured by the loss of GFP-positive cells and intracellular viral genomes.
Influenza Virus Directly Infects Human Natural Killer Cells and Induces Cell Apoptosis
Authors: Mao Huawei , Tu Wenwei , Qin Gang , Law Helen Ka Wai , Sia Sin Fun , Chan Ping-Lung , Liu Yinping , Lam Kwok-Tai , Zheng Jian , Peiris Malik , Lau Yu-Lung
Published: July 2009

Influenza is an acute respiratory viral disease that is transmitted in the first few days of infection. Evasion of host innate immune defenses, including natural killer (NK) cells, is important for the virus's success as a pathogen of humans and other animals. NK cells encounter influenza viruses within the microenvironment of infected cells and are important for host innate immunity during influenza virus infection. It is therefore important to investigate the direct effects of influenza virus on NK cells. In this study, we demonstrated for the first time that influenza virus directly infects and replicates in primary human NK cells. Viral entry into NK cells was mediated by both clathrin- and caveolin-dependent endocytosis rather than through macropinocytosis and was dependent on the sialic acids on cell surfaces. In addition, influenza virus infection induced a marked apoptosis of NK cells. Our findings suggest that influenza virus can directly target and kill NK cells, a potential novel strategy of influenza virus to evade the NK cell innate immune defense that is likely to facilitate viral transmission and may also contribute to virus pathogenesis.
Human Immunodeficiency Virus Type 1 Nucleocapsid Inhibitors Impede
trans
Infection in Cellular and Explant Models and Protect Nonhuman Primates from Infection
Authors: Wallace Gregory S. , Cheng-Mayer Cecilia , Schito Marco L. , Fletcher Patricia , Miller Jenkins Lisa M. , Hayashi Ryo , Neurath A. Robert , Appella Ettore , Shattock Robin J.
Published: July 2009

Here, we report that the
S
-acyl-2-mercaptobenzamide thioester (SAMT) class of human immunodeficiency virus type 1 (HIV-1) nucleocapsid protein (NCp7) inhibitors was able to prevent transmission of HIV-1 from infected cells, including primary cells. Furthermore, when SAMTs were introduced during an HIV-1 challenge of cervical explant tissue, inhibition of dissemination of infectious virus by cells emigrating from the tissue explants was observed. Preliminary studies using a rhesus macaque vaginal challenge model with mixed R5 and X4 simian-human immunodeficiency virus infection found that five of six monkeys were completely protected, with the remaining animal being partially protected, infected only by the R5 virus. These data suggest that SAMTs may be promising new drug candidates for further development in anti-HIV-1 topical microbicide applications.
The Porcine Reproductive and Respiratory Syndrome Virus nsp2 Cysteine Protease Domain Possesses bothtrans- andcis-Cleavage Activities
Authors: Han Jun , Rutherford Mark S. , Faaberg Kay S.
Published: July 2009

The N terminus of the replicase nonstructural protein 2 (nsp2) of porcine reproductive and respiratory syndrome virus (PRRSV) contains a putative cysteine protease domain (PL2). Previously, we demonstrated that deletion of either the PL2 core domain (amino acids [aa] 47 to 180) or the immediate downstream region (aa 181 to 323) is lethal to the virus. In this study, the PL2 domain was found to encode an active enzyme that mediates efficient processing of nsp2-3 in CHO cells. The PL2 protease possessed bothtrans- andcis-cleavage activities, which were distinguished by individual point mutations in the protease domain. The minimal size required to maintain these two enzymatic activities included nsp2 aa 47 to 240 (Tyr47to Cys240) and aa 47 to 323 (Tyr47to Leu323), respectively. Introduction of targeted amino acid mutations in the protease domain confirmed the importance of the putative Cys55- His124catalytic motif for nsp2/3 proteolysis in vitro, as were three additional conserved cysteine residues (Cys111, Cys142, and Cys147). The conserved aspartic acids (e.g., Asp89) were essential for the PL2 proteasetrans-cleavage activity. Reverse genetics revealed that the PL2trans-cleavage activity played an important role in the PRRSV replication cycle in that mutations that impaired the PL2 proteasetransfunction, but not thecisactivity, were detrimental to viral viability. Lastly, the potential nsp2/3 cleavage site was probed. Mutations with the largest impact on in vitro cleavage were at or near the G1196|G1197dipeptide.
Clearance of Measles Virus from Persistently Infected Cells by Short Hairpin RNA
Authors: Zinke Michael , Kendl Sabine , Singethan Katrin , Fehrholz Markus , Reuter Dajana , Rennick Linda , Herold Marco J. , Schneider-Schaulies Jürgen
Published: July 2009

Subacute sclerosing panencephalitis (SSPE) is a demyelinating central nervous system disease caused by a persistent measles virus (MV) infection of neurons and glial cells. There is still no specific therapy available, and in spite of an intact innate and adaptive immune response, SSPE leads inevitably to death. In order to select effective antiviral short interfering RNAs (siRNAs), we established a plasmid-based test system expressing the mRNA of DsRed2 fused with mRNA sequences of single viral genes, to which certain siRNAs were directed. siRNA sequences were expressed as short hairpin RNA (shRNA) from a lentiviral vector additionally expressing enhanced green fluorescent protein (EGFP) as an indicator. Evaluation by flow cytometry of the dual-color system (DsRed and EGFP) allowed us to find optimal shRNA sequences. Using the most active shRNA constructs, we transduced persistently infected human NT2 cells expressing virus-encoded HcRed (piNT2-HcRed) as an indicator of infection. shRNA against N, P, and L mRNAs of MV led to a reduction of the infection below detectable levels in a high percentage of transduced piNT2-HcRed cells within 1 week. The fraction of virus-negative cells in these cultures was constant over at least 3 weeks posttransduction in the presence of a fusion-inhibiting peptide (Z-Phe-Phe-Gly), preventing the cell fusion of potentially cured cells with persistently infected cells. Transduced piNT2 cells that lost HcRed did not fuse with underlying Vero/hSLAM cells, indicating that these cells do not express viral proteins any more and are “cured.” This demonstrates in tissue culture that NT2 cells persistently infected with MV can be cured by the transduction of lentiviral vectors mediating the long-lasting expression of anti-MV shRNA.
CXCR3 Deficiency Increases Susceptibility to Genital Herpes Simplex Virus Type 2 Infection: Uncoupling of CD8+T-Cell Effector Function but Not Migration
Authors: Thapa Manoj , Carr Daniel J. J.
Published: July 2009

CXCR3 is a G-protein-coupled receptor preferentially expressed by activated T cells, NK cells, and dendritic cells. Signaling through gamma interferon-regulated chemokines CXCL9, CXCL10, CXCL11, and CXCR3 plays a critical role in the immune response of many viral pathogens. However, the relevance of CXCR3 for optimal T-cell activation and the induction of regulatory transcription factors (i.e., T-bet and eomesodermin) relative to host immune defense against genital herpes simplex virus type 2 (HSV-2) infection have been poorly defined. In this study, we evaluated the requirement of CXCR3 expression during genital HSV-2 infection using mice deficient in CXCR3 (CXCR3−/−) along with wild-type (WT) controls, assessing the resistance of mice to viral infection and focusing on the cytokine/chemokine response, phenotypic analysis of recruited leukocytes, and functional analysis of CD8+T cells. CXCR3−/−mice showed a heightened sensitivity to infection compared to WT animals in terms of the viral burden in infected tissues as well as elevated mortality. The poor response of CXCR3−/−mice to viral infection was associated with reduced cytotoxic T-lymphocyte activity through the impairment of T-bet, perforin, and granzyme B expression by CD8+T cells. Corresponding with the defective cytolytic activity, a reduction in recruitment of plasmacytoid dendritic cells and CD80 expression in CD11c+dendritic cells in the draining lymph nodes of CXCR3−/−mice were detected. Collectively, the results provide a new perspective to CXCR3 signaling for the appropriate activation of CD8+T cells required for host defense against genital HSV-2 infection.
Nucleoside Monophosphate Complex Structures of the Endonuclease Domain from the Influenza Virus Polymerase PA Subunit Reveal the Substrate Binding Site inside the Catalytic Center
Authors: Zhao Cong , Lou Zhiyong , Guo Yu , Ma Ming , Chen Yutao , Liang Shuaiyi , Zhang Liang , Chen Shoudeng , Li Xuemei , Liu Yingfang , Bartlam Mark , Rao Zihe
Published: July 2009

Highly pathogenic influenza virus strains currently in circulation pose a significant risk of a global pandemic. Following the reported crystal structure of the endonuclease domain from the avian influenza virus polymerase PA subunit, here we report the results of a systematic X-ray crystallographic analysis of its complex with adenosine, uridine, and thymidine nucleoside monophosphates (NMPs). Electron density corresponding to the monophosphate moiety of each nucleotide was apparent in each NMP complex and bound to the catalytic metal. A hydrophobic site was found to contribute to nucleoside binding. The NMP complex structures should represent the conformation of the bound product after nuclease cleavage. Moreover, one solvent molecule was found to occupy an equivalent position to the second reported Mn
2+
ion, where it mediates the interaction between bound NMPs and the N-terminal PA domain in the presence of the Mg
2+
ion. The results presented here indicate a possible cleavage mechanism and identify a distinct nucleotide binding pocket. The identification of this binding pocket opens a new avenue for anti-influenza drug discovery, targeting the cap-dependent endonuclease, in response to the worldwide threat of influenza.
Gag Determinants of Fitness and Drug Susceptibility in Protease Inhibitor-Resistant Human Immunodeficiency Virus Type 1
Authors: Parry Chris M. , Kohli Arinder , Boinett Christine J. , Towers Greg J. , McCormick Adele L. , Pillay Deenan
Published: July 2009

Mutations can accumulate in the protease and
gag
genes of human immunodeficiency virus in patients who fail therapy with protease inhibitor drugs. Mutations within protease, the drug target, have been extensively studied. Mutations in
gag
have been less well studied, mostly concentrating on cleavage sites. A retroviral vector system has been adapted to study full-length
gag
, protease, and reverse transcriptase genes from patient-derived viruses. Patient plasma-derived mutant full-length
gag
, protease, and
gag
-protease from a multidrug-resistant virus were studied. Mutant protease alone led to a 95% drop in replication capacity that was completely rescued by coexpressing the full-length coevolved mutant
gag
gene. Cleavage site mutations have been shown to improve the replication capacity of mutated protease. Strikingly, in this study, the matrix region and part of the capsid region from the coevolved mutant
gag
gene were sufficient to achieve full recovery of replication capacity due to the mutant protease, without cleavage site mutations. The same region of
gag
from a second, unrelated, multidrug-resistant clinical isolate also rescued the replication capacity of the original mutant protease, suggesting a common mechanism that evolves with resistance to protease inhibitors. Mutant
gag
alone conferred reduced susceptibility to all protease inhibitors and acted synergistically when linked to mutant protease. The matrix region and partial capsid region of
gag
sufficient to rescue replication capacity also conferred resistance to protease inhibitors. Thus, the amino terminus of Gag has a previously unidentified and important function in protease inhibitor susceptibility and replication capacity.
Paleomagnetic evidence for late Cenozoic glaciations in the Mackenzie Mountains of the Northwest Territories, Canada
Authors: Barendregt R. W. , Enkin R. J. , Baker J. , Duk-Rodkin A.
Published: July 2009

The Mackenzie Mountains were affected by montane valley glaciers during the Pleistocene and peripherally by the Laurentide Ice Sheet during the last glaciation. In this paper we report on magnetostratigraphic dating and correlation of three sections recording Late Pliocene to Late Pleistocene glaciations: Katherine Creek, Little Bear River, and Inlin Brook (located around 65°N, 127°W). Each section consists of a colluvial unit overlying a Pliocene pediment surface cut into Proterozoic or Paleozoic bedrock, or Tertiary gravel, which is in turn overlain by a stack of five, and in places six, montane tills, usually with soils developed at their surfaces, and capped by a Laurentide till. Normal and reversed magnetizations were recognized with single-domain magnetite as a dominant remanence carrier. The Katherine Creek section has a normally magnetized colluvium at its base, which is overlain by two reversed tills, succeeded by three normal tills. We interpret the top two tills to be of Brunhes age (< 780 ka) but argue that the lowermost normal till is of probable Olduvai age (ca. 1.8 Ma). The two underlying tills are of Matuyama age (2.6 Ma to 780 ka), and the colluvial base is assigned to the Gauss (3.5–2.6 Ma). The Little Bear River section exposes a stratigraphic record similar to that found at Katherine Creek. Only four units could be assigned a paleomagnetic polarity, the others yielding incoherent results. Paleosols on the first and second till units were reversed and normal, respectively, and the top till was normal. Thus there is clear evidence of an older (reversed) Pleistocene glaciation and a magnetostratigraphic record compatible with that found at Katherine Creek. Magnetic measurements from Inlin Brook gave largely incoherent results, with the exception of the surface (Laurentide) till, which is normal. The glacial history recorded in the Mackenzie Mountains correlates well with other studies carried out in the Cordillera. The large-scale changes in climate revealed in these terrestrial records provide baseline data for paleoenvironmental reconstruction.
Early Pleistocene volcanism and glaciation in central Yukon: a new chronology from field studies and paleomagnetism
Authors: Jackson Jr L. E. , Barendregt R.W. , Baker J. , Irving E.
Published: July 2009

The paleomagnetism of the Selkirk Volcanics and nearby stratified Pleistocene sediments was investigated to resolve the chronology of Early Pleistocene glaciations in central Yukon. Radiometric dates on these low-K basalts have proven to be erroneously old. Most sampled sediments and all basalts accurately record the paleofield and true reversals. The valley-filling phase of the Selkirk Volcanics was in part coeval with the younger pre-Reid glaciation. It was erupted during the Matuyama Chron, either post-Cobb Mountain Subchron or post-Jaramillo Subchron, over a period too brief to average secular variation. The older pre-Reid glaciation occurred after ca. 1.60 Ma and prior to the eruption of the Fort Selkirk tephra (pre-Jaramillo or pre-Cobb Mountain). Sediments investigated at Revenue Creek and Braden's Canyon are normally magnetized. The assigned Brunhes age is compatible with their occurrence in valleys that were cut or deepened sometime after the pre-Reid glaciations.
Systematic sampling of discrete and continuous populations: sample selection and the choice of estimator
Authors: Valentine Harry T. , Affleck David L.R. , Gregoire Timothy G.
Published: July 2009

Systematic sampling is easy, efficient, and widely used, though it is not generally recognized that a systematic sample may be drawn from the population of interest with or without restrictions on randomization. The restrictions or the lack of them determine which estimators are unbiased, when using the sampling design as the basis for inference. We describe the selection of a systematic sample, with and without restriction, from populations of discrete elements and from linear and areal continuums (continuous populations). We also provide unbiased estimators for both restricted and unrestricted selection. When the population size is known at the outset, systematic sampling with unrestricted selection is most likely the best choice. Restricted selection affords estimation of attribute totals for a population when the population size — for example, the area of an areal continuum — is unknown. Ratio estimation, however, is most likely a more precise option when the selection is restricted and the population size becomes known at the end of the sampling. There is no difference between restricted and unrestricted selection if the sampling interval or grid tessellates the frame in such a way that all samples contain an equal number of measurements. Moreover, all the estimators are unbiased and identical in this situation.
Contribution of atmospheric nitrogen deposition to net primary productivity in a northern hardwood forest
Authors: Nave Lucas E. , Vogel Christoph S. , Gough Christopher M. , Curtis Peter S.
Published: July 2009

Net primary productivity (NPP) in northern temperate forests is an important part of the global carbon cycle. Because NPP often is limited by nitrogen (N), atmospheric N deposition (Ndep) may increase forest NPP. At a northern hardwood forest site in northern Lower Michigan, USA, we quantified rates of N supply by Ndep, canopy retention of Ndep (Ncr), and soil net N mineralization (Nmin); calculated the N requirement of NPP; and estimated the fraction of NPP that could be attributed to atmospheric N inputs. Net N mineralization supplied 42.6 kg N·ha–1·year–1 (84% of the NPP N requirement), and Ndep averaged 7.5 kg N·ha–1·year–1 (15%). The forest canopy retained 38% of Ndep (Ncr = 2.8 kg N·ha–1·year–1), primarily in the forms of organic N and NH4-N. Fine root (62%) and leaf (31%) N requirements dominated the NPP N requirement of 50.7 kg N·ha–1·year–1. Annual N supply by the processes we measured agreed very closely with the NPP N requirement, suggesting that internally cycled N and N of atmospheric origin contribute to the N nutrition of this forest. Our results indicate that up to 15% of the NPP at this site may be driven by atmospheric N inputs.
Evaluation of population-averaged and subject-specific approaches for modeling the dominant or codominant height of lodgepole pine trees
Authors: Meng Shawn X. , Huang Shongming , Yang Yuqing , Trincado Guillermo , VanderSchaaf Curtis L.
Published: July 2009

Population-averaged (PA) and subject-specific (SS) approaches for modeling the height of dominant or codominant lodgepole pine ( Pinus contorta Dougl. ex Loud.) trees were evaluated using six candidate models derived from the Chapman–Richards and logistic functions. The true PA response obtained from separate fits of the models was compared with the typical mean (TM) response computed using only the fixed-effects parameters of the mixed-effects models. Results showed that the TM response had higher prediction errors than the PA response, suggesting that a true PA response and not the TM response is needed to reflect the overall mean response of the model. The SS approach produced improved height predictions relative to the PA approach when evaluated using independent validation data. In addition, the logistic performed better than the Chapman–Richards function, regardless of whether the SS or PA approach was applied. Among the candidate models, the logistic function with the inclusion of site index gave the most accurate predictions. Three scenarios of calibrating the mixed-effects models on the validation data set were compared. The SS predictions obtained using only one premeasured observation per subject were poorer than those using all observations, but they were still generally better than PA predictions.
Soil greenhouse gas and nutrient dynamics in fertilized western Canadian plantation forests
Authors: Basiliko Nathan , Khan Amer , Prescott Cindy E. , Roy Réal , Grayston Sue J.
Published: July 2009

We explored the impacts of fertilization on soil greenhouse gas fluxes and underlying soil nutrient transformations using short-term (up to 7 months) simulated operational fertilization with urea-nitrogen or nitrogen, phosphorus, potassium, and micronutrients in lodgepole pine ( Pinus contorta Dougl. ex Loud. var. latifolia Engelm.), western hemlock ( Tsuga heterophylla (Raf.) Sarge.), and Douglas-fir ( Pseudotsuga menziesii (Mirb.) Franco) forests in British Columbia. Urea appeared to be rapidly mineralized to ammonium, and nitrification (relative to controls) was only observed at the lodgepole pine site and represented only 0.5% of added nitrogen. All sites were small net sinks for atmospheric methane, and fertilization effects, both stimulatory and inhibitory, were short-lived. Across all sites and treatments, soils were as likely to consume as emit nitrous oxide, and among treatment replicates, rates were never significantly different from 0, with the exception of one efflux rate of 1.5 µg·m–2·h–1on the warmest day in the study. We conclude from this pilot study that in acidic, unpolluted (with regard to nitrogen deposition) upland conifer forest soils in western Canada fertilized once or infrequently with urea, ammonium, or a combination of nutrients, the dynamics of soil greenhouse-gas fluxes are generally not disturbed over the short-term, with soils remaining small sinks for atmospheric methane and neutral with regard to flux of nitrous oxide.
ROUGHNESS EFFECT OF DIFFERENT GEOMETRIES ON MICRO GAS FLOWS BY LATTICE BOLTZMANN SIMULATION
Authors: LIU CHAOFENG , NI YUSHAN , RAO YONG
Published: July 2009

The roughness effects of the gas flows of nitrogen and helium in microchannels with various relative roughnesses and different geometries are studied and analyzed by a lattice Boltzmann model. The shape of surface roughness is simulated to be square, sinusoidal, triangular, and fractal. Numerical computations compared with theoretical and experimental studies show that the roughness geometry is an important factor besides the relative roughness in the study of the effects of surface roughness. The fractal boundary presents a higher influence on the velocity field and the resistance coefficient than other regular boundaries at the same Knudsen number and relative roughness. In addition, the effects of rarefaction, compressibility, and roughness are strongly coupled, and the roughness effect should not be ignored in studying rarefaction and compressibility of the microchannel as the relative roughness increases.
MORE ABOUT THE WILSONIAN ANALYSIS ON THE PIONLESS NEFT
Authors: HARADA KOJI , KUBO HIROFUMI , NINOMIYA ATSUSHI
Published: July 2009

We extend our Wilsonian renormalization group (RG) analysis on the pionless nuclear effective field theory in the two-nucleon sector in two ways; on the one hand, (1) we enlarge the space of operators up to including those of [Formula: see text] in the S waves, and, on the other hand, (2) we consider the RG flows in higher partial waves (P and D waves). In the larger space calculations, we find, in addition to nontrivial fixed points, two "fixed lines" and a "fixed surface" which are related to marginal operators. In the higher partial wave calculations, we find similar phase structures to that of the S waves, but there are two relevant directions in the P waves at the nontrivial fixed points and three in the D waves. We explain the physical meaning of the P-wave phase structure by explicitly calculating the low-energy scattering amplitude. We also discuss the relation between the Legendre flow equation which we employ and the RG equation by Birse, McGovern and Richardson, and possible implementation of power divergence subtraction in higher partial waves.
Chapter 14 Charmonium Spectroscopy
Authors: Barnes T. , Olsen S.L.
Published: July 2009

The following sections are included:

Introduction

Conventional Charmonium States

Issues for BES-III

Novel States Incorporating a [Formula: see text] Subsystem

The XYZ Mesons, Recent Experimental Developments
Chapter 16 Charmonium Leptonic and EM Decays
Authors: Barnes T. , Zhang Y.J. , Pineda A.
Published: July 2009

The following sections are included:

Leptonic and EM Decays in Potential Models

Leptonic and EM Decays in Effective Field Theories
Chapter 25 $D^0 - \overline D^0 $ Mixing
Authors: Bigi I. I. , Li H. B. , Asner D. M.
Published: July 2009

The following sections are included:

Theoretical Review

Experimental Review

Measurements at the ψ(3770) Peak
Chapter 26 CP and T Violation
Authors: Bigi Ikaros , Li Hai-Bo
Published: July 2009

The following sections are included:

Formalism and Review

CP Violation in [Formula: see text] Mixing

CP Violation in Decay

CP Violation in the Interference Between Decays With and Without Mixing

Rate of the CP Violation in the Coherent [Formula: see text] Pair

T Violation
Signaling in Adult Neurogenesis
Authors: Suh Hoonkyo , Deng Wei , Gage Fred H.
Published: July 2009

The identification of neural stem cells (NSCs) and their contribution to continuous neurogenesis has shown that the hippocampus and olfactory bulb are plastic. Brain plasticity, achieved at the level of cell genesis, has an essential role in the maintenance of brain homeostasis. Via combinatorial functions of extrinsic signals and intrinsic programs, adult neurogenesis is tightly regulated in a specialized microenvironment, a niche. Misregulated neurogenesis is detrimental to normal brain functions and, in extreme cases, pathogenic. Hence, understanding signaling in adult neurogenesis is not only important to understand the physiological roles of neurogenesis, but also to provide knowledge that is essential for developing therapeutic applications using NSCs to intervene in the progression of brain diseases.
Calcium homeostasis in human melanocytes: role of transient receptor potential melastatin 1 (TRPM1) and its regulation by ultraviolet light
Authors: Devi Sulochana , Kedlaya Rajendra , Maddodi Nityanand , Bhat Kumar M. R. , Weber Craig S. , Valdivia Hector , Setaluri Vijayasaradhi
Published: July 2009

Transient receptor potential melastatin (TRPM) is a subfamily of ion channels that are involved in sensing taste, ambient temperature, low pH, osmolarity, and chemical ligands. Melastatin 1/TRPM1, the founding member, was originally identified as melanoma metastasis suppressor based on its expression in normal pigment cells in the skin and the eye but not in aggressive, metastasis-competent melanomas. The role of TRPM1 and its regulation in normal melanocytes and in melanoma progression is not understood. Here, we studied the relationship of TRPM1 expression to growth and differentiation of human epidermal melanocytes. TRPM1 expression and intracellular Ca2+ levels are significantly lower in rapidly proliferating melanocytes compared to the slow growing, differentiated melanocytes. We show that lentiviral short hairpin RNA (shRNA)-mediated knockdown of TRPM1 results in reduced intracellular Ca2+ and decreased Ca2+ uptake suggesting a role for TRPM1 in Ca2+ homeostasis in melanocytes. TRPM1 knockdown also resulted in a decrease in tyrosinase activity and intracellular melanin pigment. Expression of the tumor suppressor p53 by transfection or induction of endogenous p53 by ultraviolet B radiation caused repression of TRPM1 expression accompanied by decrease in mobilization of intracellular Ca2+ and uptake of extracellular Ca2+. These data suggest a role for TRPM1-mediated Ca2+ homeostasis, which is also regulated by ultraviolet B, in melanogenesis.
Regulation of amino acid transporters by glucose and growth factors in cultured primary human trophoblast cells is mediated by mTOR signaling
Authors: Roos S. , Lagerlöf O. , Wennergren M. , Powell T. L. , Jansson T.
Published: July 2009

Inhibition of mammalian target of rapamycin (mTOR) signaling in cultured human primary trophoblast cells reduces the activity of key placental amino acid transporters. However, the upstream regulators of placental mTOR are unknown. We hypothesized that glucose, insulin, and IGF-I regulate placental amino acid transporters by inducing changes in mTOR signaling. Primary human trophoblast cells were cultured for 24 h with media containing various glucose concentrations, insulin, or IGF-I, with or without the mTOR inhibitor rapamycin, and, subsequently, the activity of system A, system L, and taurine (TAUT) transporters was measured. Glucose deprivation (0.5 mM glucose) did not significantly affect Thr172-AMP-activated protein kinase phosphorylation or REDD1 expression but decreased S6 kinase 1 phosphorylation at Thr389. The activity of system L decreased in a dose-dependent manner in response to decreasing glucose concentrations. This effect was abolished in the presence of rapamycin. Glucose deprivation had two opposing effects on system A activity: 1) an “adaptive” upregulation mediated by an mTOR-independent mechanism and 2) downregulation by an mTOR-dependent mechanism. TAUT activity was increased after incubating cells with glucose-deprived media, and this effect was largely independent of mTOR signaling. Insulin and IGF-I increased system A activity and insulin stimulated system L activity, effects that were abolished by rapamycin. We conclude that the mTOR pathway represents an important intracellular regulatory link between nutrient and growth factor concentrations and amino acid transport in the human placenta.
Metabolic inhibition increases activity of connexin-32 hemichannels permeable to Ca2+ in transfected HeLa cells
Authors: Sánchez Helmuth A. , Orellana Juan A. , Verselis Vytas K. , Sáez Juan C.
Published: July 2009

Numerous cell types express functional connexin (Cx) hemichannels (HCs), and membrane depolarization and/or exposure to a divalent cation-free bathing solution (DCFS) have been shown to promote HC opening. However, little is known about conditions that can promote HC opening in the absence of strong depolarization and when extracellular divalent cation concentrations remain at physiological levels. Here the effects of metabolic inhibition (MI), an in vitro model of ischemia, on the activity of mouse Cx32 HCs were examined. In HeLa cells stably transfected with mouse Cx32 (HeLa-Cx32), MI induced an increase in cellular permeability to ethidium (Etd). The increase in Etd uptake was directly related to an increase in levels of Cx32 HCs present at the cell surface. Moreover, MI increased membrane currents in HeLa-Cx32 cells. Underlying these currents were channels exhibiting a unitary conductance of ∼90 pS, consistent with Cx32 HCs. These currents and Etd uptake were blocked by HC inhibitors. The increase in Cx32 HC activity was preceded by a rapid reduction in mitochondrial membrane potential and a rise in free intracellular Ca2+ concentration ([Ca2+]i). The increase in free [Ca2+]i was prevented by HC blockade or exposure to extracellular DCFS and was virtually absent in parental HeLa cells. Moreover, inhibition of Cx32 HCs expressed by HeLa cells in low-confluence cultures drastically reduced cell death induced by oxygen-glucose deprivation, which is a more physiological model of ischemia-reperfusion. Thus HC blockade could reduce the increase in free [Ca2+]i and cell death induced by ischemia-like conditions in cells expressing Cx32 HCs.
GLUT1-induced cFLIP expression promotes proliferation and prevents apoptosis in vascular smooth muscle cells
Authors: Vesely Eileen D. , Heilig Charles W. , Brosius Frank C.
Published: July 2009

Enhanced expression of the facilitative glucose transporter, GLUT1, has been shown to inhibit apoptosis in several cell systems including vascular smooth muscle cells (VSMCs). A decrease in apoptosis could lead to increased VSMC numbers in neointimal and medial arterial layers under several pathologic conditions. The hypothesis underlying these studies is that GLUT1 induces expression of antiapoptotic and prosurvival genes that increase VSMC survival. Transcriptomic analysis of A7r5 VSMCs, in which GLUT1 was acutely overexpressed, showed a 2.14-fold increase in c-FLICE inhibitory protein (cFLIP), which promotes cellular growth and prevents apoptosis through caspase 8 binding. We confirmed that overexpression of GLUT1 induced mRNA and protein expression of both the long and short isoforms of cFLIP (cFLIPL and cFLIPS) in primary and stable immortalized VSMC lines as well as in aortas from GLUT1 transgenic mice. Increased GLUT1 reduced VSMC death by more than twofold after serum withdrawal, as evidenced by decreased caspase 3 activity and Trypan blue exclusion studies. GLUT1 overexpression resulted in a greater than twofold increase in proliferating cell nuclear antigen expression and live cell numbers, consistent with augmented VSMC proliferation. Lentiviral knockdown of cFLIPL showed that cFLIPL was necessary for the proproliferative and antiapoptotic effects of GLUT1 overexpression. Taken together, these data suggest that GLUT1 induction of cFLIPL expression augments proliferation and prevents apoptosis in VSMCs.
Focal adhesion kinase modulates activation of NF-κB by flow in endothelial cells
Authors: Petzold Tobias , Orr A. Wayne , Hahn Cornelia , Jhaveri Krishna A. , Parsons J. Thomas , Schwartz Martin Alexander
Published: July 2009

Atherogenesis involves activation of NF-κB in endothelial cells by fluid shear stress. Because this pathway involves integrins, we investigated the involvement of focal adhesion kinase (FAK). We found that FAK was not required for flow-stimulated translocation of the p65 NF-κB subunit to the nucleus but was essential for phosphorylation of p65 on serine 536 and induction of ICAM-1, an NF-κB-dependent gene. NF-κB activation by TNF-α or hydrogen peroxide was FAK independent. Events upstream of NF-κB, including integrin activation, Rac activation, reactive oxygen production, and degradation of IκB, were FAK independent. FAK therefore regulates NF-κB phosphorylation and transcriptional activity in response to flow by a novel mechanism.
Cardiovascular changes during daily torpor in the laboratory mouse
Authors: Swoap Steven J. , Gutilla Margaret J.
Published: July 2009

The laboratory mouse is a facultative daily heterotherm in that it experiences bouts of torpor under caloric restriction. Mice are the most frequently studied laboratory mammal, and often, genetically modified mice are used to investigate many physiological functions related to weight loss and caloric intake. As such, research documenting the cardiovascular changes during fasting-induced torpor in mice is warranted. In the current study, C57BL/6 mice were implanted either with EKG/temperature telemeters or blood pressure telemeters. Upon fasting and exposure to an ambient temperature (Ta) of 19°C, mice entered torpor bouts as assessed by core body temperature (Tb). Core Tbfell from 36.6 ± 0.2°C to a minimum of 25.9 ± 0.9°C during the fast, with a concomitant fall in heart rate from 607 ± 12 beats per minute (bpm) to a minimum of 158 ± 20 bpm. Below a core Tbof 31°C, heart rate fell exponentially with Tb, and the Q10was 2.61 ± 0.18. Further, mice implanted with blood pressure telemeters exhibited similar heart rate and activity profiles as those implanted with EKG/temperature telemeters, and the fall in heart rate and core Tbduring entrance into torpor was paralleled by a fall in blood pressure. The minimum systolic, mean, and diastolic blood pressures of torpid mice were 62.3 ± 10.2, 51.9 ± 9.2, 41.0 ± 7.5 mmHg, respectively. Torpid mice had a significantly lower heart rate (25–35%) than when euthermic at mean arterial pressures from 75 to 100 mmHg, suggesting that total peripheral resistance is elevated during torpor. These data provide new and significant insight into the cardiovascular adjustments that occur in torpid mice.