bluuebunny/crossref_metadata_2025 huggingface dataset:
Biophysical ocean observation in the southeastern Bering Sea
Authors: Stafford Kathleen M. , Moore Sue E. , Stabeno Phyllis J. , Holliday D. V. , Napp Jeffrey M. , Mellinger David K.
Published: January 2010

Integrated ocean observation, from physical and atmospheric forcing mechanisms to the distribution and abundance of top‐level predators, is critical to the investigation of marine ecosystems and the impact of climate change on them. We integrated data from a biophysical mooring in the southeast Bering Sea to create a one‐year snapshot of ocean dynamics in this remote large marine ecosystem. Distinct patterns in production (chlorophyll), zooplankton biovolume (copepods and euphausiids) and the occurrence of zooplankton predators (fin and right whales) were defined and related to discrete features in the annual physical cycle. Peaks in prey and predator cycles were linked to spikes in fluorescence that occurred at the onset of water column stratification in late spring 2006 and the appearance of sea ice in late winter 2007. These data illustrate the capability and potential of integrated ocean observing systems (IOOS) to describe seasonal variability and linkages in a remote marine ecosystem.
Impact of atmosphere and sub‐surface ocean data on decadal climate prediction
Authors: Dunstone N. J. , Smith D. M.
Published: January 2010

We present a set of idealised model experiments that investigate the impact of assimilating different amounts of ocean and atmosphere data on decadal climate prediction skill. Assimilating monthly average sub‐surface temperature and salinity data successfully initialises the meridional overturning circulation and produces skillful predictions of global ocean heat content. However, when sea surface temperature data is assimilated alone the predictions have much less skill, particularly in the extra‐tropics. The upper 2000m temperature and salinity observations currently provided by the Argo array of floats are therefore potentially well suited to initialising decadal climate predictions. We note however that we do not attempt to simulate the actual distribution of Argo floats. Assimilating data beneath 2000m always reduces the RMSE, with the most significant improvements in the Southern Ocean. Furthermore, assimilating six hourly atmospheric observations significantly improves the forecast skill within the first year, but has little impact thereafter.
Phase reversal of the diurnal cycle in the midlatitude ionosphere
Authors: Liu Huixin , Thampi Smitha V. , Yamamoto Mamoru
Published: January 2010

The typical diurnal cycle of the midlatitude F region electron density consists of a midday maximum and a midnight minimum. However, a phase reversal of this diurnal cycle has been found to occur in three distinct regions on the globe. They are the East Asian (EA) region centered around (53°N, 150°E), the Northern Atlantic (NA) region centered around (45°N, 50°W) and the South Pacific (SP) region centered around (60°S, 110°W). The intensively reported Weddell Sea Anomaly falls inside the SP region. The phase reversal occurs during March–August in EA and NA regions, and between August and March in SP region, being most prominent in local summer. Furthermore, this diurnal anomaly is more pronounced at solar minimum than at solar maximum, and more pronounced in SP region than in NA and EA regions, in terms of larger diurnal magnitude and more months it lasts in a year. It is emphasized that the diurnal anomaly consists of not only a nighttime enhancement, but also a concurrent noontime depletion. Hence, midlatitude summer nighttime enhancements reported in previous studies are just part of this reversed diurnal cycle. The cause for the phase reversal involves several interplaying physical processes. Among these, the neutral wind combined with the geomagnetic field configuration plays a pivotal role. It generates a one‐wave longitudinal pattern at southern middle latitudes and a two‐wave pattern at northern middle latitudes, whose wave peaks correspond to the center of the SP, EA, and NA regions, respectively. The seasonal variation of neutral winds and downward motion of the ionization induced by thermal contraction of the ionosphere at sunset may largely control the occurring local time of the nighttime density enhancement and how long it persists in different months. The phase reversal occurs as a result of close ion‐neutral coupling. It is further noted that winter anomaly in the EA, NA, and SP regions is very weak or missing.
HIRDLS and CALIPSO observations of tropical cirrus
Authors: Massie Steven T. , Gille John , Craig Cheryl , Khosravi Rashid , Barnett John , Read William , Winker David
Published: January 2010

High Resolution Dynamics Limb Sounder (HIRDLS) and Cloud‐Aerosol Lidar and Infrared Pathfinder Satellite Observation (CALIPSO) measurements of cirrus frequency of occurrence in the upper tropical troposphere are quantified for September 2006 to August 2007. Monthly geospatial averages of cloud frequency of occurrence between 90 and 177 hPa are similar and correlate well with Microwave Limb Sounder (MLS) relative humidity with respect to ice (RHI) data, though clouds are present at individual RHI values less than 100%, due to the 5, 1, and sub‐1 km vertical resolutions of the MLS, HIRDLS, and CALIPSO experiments. Seasonal variations in cloud frequency of occurrence are similar, with largest frequencies during winter (December–February). Though the CALIPSO and HIRDLS experiments employ nadir‐ and limb‐viewing observational geometries, respectively, CALIPSO horizontal scales of cirrus are frequently larger than 100 km, and therefore similarities are present in the geospatial distributions of cloud occurrence. Isolated laminar cirrus is most prevalent away from the equator. The monthly patterns of HIRDLS and CALIPSO cloud occurrence are archived for useful comparisons to climate models.
Compatibility between modes of low‐frequency variability and circulation types: A case study of the northwest Iberian Peninsula
Authors: Ramos A. M. , Lorenzo M. N. , Gimeno L.
Published: January 2010

Modes of low‐frequency variability have a major influence on the variability of the climate system at different temporal and spatial scales. Although the North Atlantic Oscillation explains a substantial portion of the climate variability in Europe, it is also necessary to consider other modes of low‐frequency variability, such as the Scandinavian index, the eastern Atlantic or the eastern Atlantic/western Russia indices. Furthermore, the relationship between the modes of low‐frequency variability and the climate in Europe cannot be considered to be stable over time. The aim of this paper is to assess the compatibility between the modes of low‐frequency variability in Europe (computed using a principal component analysis (PCA)) and local circulation regimes (using an automated version of the Lamb weather‐type classification), thus to observe how shifts in the positions of the modes of low‐frequency variability in Europe, could affect local circulation. Our study area (NW Iberian Peninsula) was chosen because it is characterized by the passage of cold fronts associated with the storm track in the North Atlantic Ocean and is sensitive to any variability in precipitation and temperature that is linked to the main North Atlantic modes of low‐frequency variability. The results show that there is a high degree of correlation between regional modes of low‐frequency variability derived from a statistical approach (using PCA) and real physical circulations (as represented by circulation types). Furthermore, changes in the position of modes of low‐frequency variability tend to favor some circulation types over others.
Mdm10 as a dynamic constituent of the TOB/SAM complex directs coordinated assembly of Tom40
Authors: Yamano Koji , Tanaka‐Yamano Sachiko , Endo Toshiya
Published: January 2010

The mitochondrial outer membrane contains two protein translocators: the TOM40 and TOB/SAM complexes. Mdm10 is distributed in the TOB complex for β‐barrel protein assembly and in the MMM1 complex for tethering of the endoplasmic reticulum and mitochondria. Here, we establish a system in which the Mdm10 level in the TOB complex—but not in the MMM1 complex—is altered to analyse its part in β‐barrel protein assembly. A decrease in the Mdm10 level results in accumulation of in vitro imported Tom40, which is a β‐barrel protein, at the level of the TOB complex. An increase in the Mdm10 level inhibits association not only of Tom40 but also of other β‐barrel proteins with the TOB complex. These results show that Mdm10 regulates the timing of release of unassembled Tom40 from the TOB complex, to facilitate its coordinated assembly into the TOM40 complex.
Ionotropic and metabotropic mechanisms in chemoreception: 'chance or design'?
Authors: Silbering Ana Florencia , Benton Richard
Published: January 2010

Chemosensory receptors convert an enormous diversity of chemical signals from the external world into a common language of electrical activity in the brain. Mammals and insects use several families of transmembrane receptor proteins to recognize distinct classes of volatile and non‐volatile chemicals that are produced by conspecifics or other environmental sources. A comparison of the signalling mechanisms of mammalian and insect receptors has revealed an unexpected functional distinction: mammals rely almost exclusively on metabotropic ligand‐binding receptors, which use second messenger signalling cascades to indirectly activate ion channels, whereas insects use ionotropic receptors, which are gated directly by chemical stimuli, thereby leading to neuronal depolarization. In this review, we consider possible reasons for this dichotomy, taking into account biophysical, cell biological, ecological and evolutionary influences on how information is extracted from chemosensory cues by these animal classes.
Inhibition of Akt/GSK3β signalling pathway byLegionella pneumophilais involved in induction of T-cell apoptosis
Authors: Takamatsu Reika , Takeshima Eriko , Ishikawa Chie , Yamamoto Kei , Teruya Hiromitsu , Heuner Klaus , Higa Futoshi , Fujita Jiro , Mori Naoki
Published: January 2010

Legionella pneumophila is the causative agent of human Legionnaires' disease. L. pneumophila has been shown to induce apoptosis of T-cells and this may be important pathologically and clinically. The present study has determined the molecular mechanisms underlying L. pneumophila-induced apoptosis, which were unclear. Wild-type L. pneumophila and flagellin-deficient Legionella, but not L. pneumophila lacking a functional type IV secretion system Dot/Icm, replicated in T-cells. However, apoptosis was efficiently induced in T-cells only by wild-type L. pneumophila, and not flagellin-deficient or Dot/Icm-deficient Legionella. Induction of apoptosis involved activation of the initiator caspase 9 and effector caspase 3. Infection with L. pneumophila inhibited phosphorylation of Akt (also known as protein kinase B) and the Akt substrate GSK3β (glycogen synthase kinase 3β), and reduced the levels of β-catenin, a transcriptional activator regulated by GSK3β. It also caused the activation of the pro-apoptotic protein Bax and inhibited the expression of the anti-apoptotic protein XIAP (X-linked inhibitor of apoptosis) via inhibition of the Akt pathway. In conclusion, L. pneumophila induces mitochondria-mediated T-cell apoptosis through inhibition of the Akt/GSK3β signalling pathway.
Biotic and abiotic determinants of intermediate-consumer trophic diversity in the Florida everglades
Authors: Sargeant Brooke L. , Gaiser Evelyn E. , Trexler Joel C.
Published: January 2010

Food-web structure can shape population dynamics and ecosystem functioning and stability. We investigated the structure of a food-web fragment consisting of dominant intermediate consumers (fishes and crayfishes) in the Florida Everglades, using stable isotope analysis to quantify trophic diversity along gradients of primary production (periphyton), disturbance (marsh drying) and intermediate-consumer density (a possible indicator of competition). We predicted that trophic diversity would increase with resource availability and decrease after disturbance, and that competition could result in greater trophic diversity by favouring resource partitioning. Total trophic diversity, measured by niche area, decreased with periphyton biomass and an ordination axis representing several bluegreen algae species. Consumers’ basal resource diversity, estimated by δ13C values, was similarly related to algal community structure. The range of trophic levels (δ15N range) increased with time since the most recent drying and reflooding event, but decreased with intermediate-consumer density, and was positively related to the ordination axis reflecting increases in green algae and decreases in filamentous bluegreen algae. Our findings suggest that algal quality, independent of quantity, influences food-web structure and demonstrate an indirect role of nutrient enrichment mediated by its effects on periphyton palatability and biomass. These results reveal potential mechanisms for anthropogenic effects on Everglades communities.
Too close for comfort: a fishway exit and a hydro-power station inlet
Authors: Stuart Ivor G. , Koehn John D. , O'Brien Tim A. , McKenzie John A. , Quinn Gerry P.
Published: January 2010

A major environmental issue for hydro-electric power generation is passage of fish through turbines, or entrainment onto trash racks. At Yarrawonga Weir, on the upper Murray River in south-eastern Australia, the positioning of a fish lock resulted in the potential for upstream migrating fish to be swept back into the adjacent power station by cross flows. In 2004, a 4.5-m long steel extension flume was attached to the exit to alleviate this problem. To determine the fate of native fish after exiting the extension flume, 72 individuals (305–1015 mm long) were implanted with radio-transmitters and released into the fish lock exit channel. In 2004 (power station inflows 10 300 ML day–1), the majority of fish exited successfully (44 of 45) and only a single fish (2%) was entrained into the power station. In 2005 (power station inflows 12 000 ML day–1), fish again exited successfully (26 of 27) but with a higher proportion entrained (5 of 27; 18%). This reduced success appeared to be related to strong transverse flows with high water velocities adjacent to the fish lock exit. The efficiency of fish passage at this site might be improved by altering water management strategies, integrating engineering and fish biology, and through field-testing of proposed solutions.
A novel push trap element to manage carp (Cyprinus carpio L.): a laboratory trial
Authors: Thwaites L. A. , Smith B. B. , Decelis M. , Fleer D. , Conallin A.
Published: January 2010

Common carp (Cyprinus carpio L.) cause detrimental changes to aquatic ecosystems and are a declared pest fish in several countries. Despite existing management options, the development of new technologies is desirable as the range of the common carp is predicted to expand and their eventual control will rely on an integrated approach. The present paper describes a laboratory trial of a novel ‘finger style’ push trap element designed to catch carp ≥250 mm total length (TL). Forty-five adult carp (mean length: 603.0 ± 74.9 mm s.d. TL) were placed into the downstream section of a 7.25-m flume and exposed to three stimuli (water level manipulation, flow and light) to encourage upstream movement towards the push trap element. Forty-one carp (91.1%) pushed through the trap element over 16 h and none escaped. Only an average of ~5% of carp’s known pushing capacity was needed to push through the ‘fingers’ and enter the trap, and modelling suggested that a 250-mm TL carp would need to exert ~22% of its pushing capacity. The results confirm that the push trap element design is matched to the morphology and ecology of carp and, pending field validation trials, promises success as a novel management option.
Dietary variation and food selection by an algivorous loach (Pseudogastromyzon myersi: Balitoridae) in Hong Kong streams
Authors: Yang Grace Y. , Dudgeon David
Published: January 2010

The algivorous balitorid loach Pseudogastromyzon myersi is abundant in Hong Kong streams where it may exert top-down control on benthic algal assemblages as reported for grazing fish in temperate and neotropical streams. Dietary selectivity by P. myersi was investigated in two shaded and two unshaded streams during the wet and dry seasons, thereby allowing for variation in the potential bottom-up influences of light and flow on algae. Fish stomach contents were compared with the benthic algal assemblages to assess selectivity and to test whether algal growth form influenced susceptibility to grazing. Diatoms and filamentous cyanobacteria dominated the diets of the fish, regardless of stream or season; most of the remainder of the stomach contents comprised fine particulate organic matter (FPOM). Stalked diatoms (Gomphonema) and filamentous cyanobacteria (Homeothrix) were the most important dietary items, with the former selected during the dry season and the latter in the wet season. Adherent diatoms (Achnanthes) were underrepresented in the diet, and filamentous chlorophytes were rarely eaten. Seasonal changes in diet were minor. Interstream variations reflected differences in the proportions of Gomphonema, Homeothrix and FPOM ingested, and were unrelated to shading. Grazing by P. myersi may influence algal composition and productivity by removing loosely attached diatoms and facilitating growth of filamentous cyanobacteria.
Making short-term climate forecasts useful: Linking science and action
Authors: Buizer James , Jacobs Katharine , Cash David
Published: January 2010

This paper discusses the evolution of scientific and social understanding that has led to the development of knowledge systems supporting the application of El Niñ
o
-Southern Oscillation (ENSO) forecasts, including the development of successful efforts to connect climate predictions with sectoral applications and actions “on the ground”. The evolution of “boundary-spanning” activities to connect science and decisionmaking is then discussed, setting the stage for a report of outcomes from an international workshop comprised of producers, translators, and users of climate predictions. The workshop, which focused on identifying critical boundary-spanning features of successful boundary organizations, included participants from Australia, Hawaii, and the Pacific Islands, the US Pacific Northwest, and the state of Ceará in northwestern Brazil. Workshop participants agreed that boundary organizations have multiple roles including those of information broker, convenor of forums for engagement, translator of scientific information, arbiter of access to knowledge, and exemplar of adaptive behavior. Through these roles, boundary organizations will ensure the stability of the knowledge system in a changing political, economic, and climatic context. The international examples reviewed in this workshop demonstrated an interesting case of convergent evolution, where organizations that were very different in origin evolved toward similar structures and individuals engaged in them had similar experiences to share. These examples provide evidence that boundary organizations and boundary-spanners fill some social/institutional roles that are independent of culture.
Mammalian Pumilio 2 regulates dendrite morphogenesis and synaptic function
Authors: Vessey John P. , Schoderboeck Lucia , Gingl Ewald , Luzi Ettore , Riefler Julia , Di Leva Francesca , Karra Daniela , Thomas Sabine , Kiebler Michael A. , Macchi Paolo
Published: January 2010

In
Drosophila
, Pumilio (Pum) is important for neuronal homeostasis as well as learning and memory. We have recently characterized a mammalian homolog of Pum, Pum2, which is found in discrete RNA-containing particles in the somatodendritic compartment of polarized neurons. In this study, we investigated the role of Pum2 in developing and mature neurons by RNA interference. In immature neurons, loss of Pum2 led to enhanced dendritic outgrowth and arborization. In mature neurons, Pum2 down-regulation resulted in a significant reduction in dendritic spines and an increase in elongated dendritic filopodia. Furthermore, we observed an increase in excitatory synapse markers along dendritic shafts. Electrophysiological analysis of synaptic function of neurons lacking Pum2 revealed an increased miniature excitatory postsynaptic current frequency. We then identified two specific mRNAs coding for a known translational regulator, eIF4E, and for a voltage-gated sodium channel, Scn1a, which interacts with Pum2 in immunoprecipitations from brain lysates. Finally, we show that Pum2 regulates translation of the
eIF4E
mRNA. Taken together, our data reveal a previously undescribed role for Pum2 in dendrite morphogenesis, synapse function, and translational control.
Importance of antibody and complement for oxidative burst and killing of invasive nontyphoidalSalmonellaby blood cells in Africans
Authors: Gondwe Esther N. , Molyneux Malcolm E. , Goodall Margaret , Graham Stephen M. , Mastroeni Pietro , Drayson Mark T. , MacLennan Calman A.
Published: January 2010

Bacteremia caused by nontyphoidal strains ofSalmonellais endemic among African children. Case-fatality rates are high and antibiotic resistance increasing, but no vaccine is currently available. T cells are important for clearance ofSalmonellainfection within macrophages, but in Africa, invasiveSalmonelladisease usually manifests in the blood and affects children between 4 months and 2 y of age, when anti-Salmonellaantibody is absent. We have previously found a role for complement-fixing bactericidal antibody in protecting these children. Here we show that opsonic activity of antibody and complement is required for oxidative burst and killing ofSalmonellaby blood cells in Africans. Induction of neutrophil oxidative burst correlated with anti-SalmonellaIgG and IgM titers and C3 deposition on bacteria and was significantly lower in African children younger than 2 y compared with older children. PreopsonizingSalmonellawith immune serum overcame this deficit, indicating a requirement for antibody and/or complement. Using different opsonization procedures, both antibody and complement were found to be necessary for optimal oxidative burst, phagocytosis and killing of nontyphoidalSalmonellaby peripheral blood cells in Africans. Although most strains of African nontyphoidalSalmonellacan be killed with antibody and complement alone, phagocytes in the presence of specific antibody and complement can kill strains resistant to killing by immune serum. These findings increase the likelihood that an antibody-inducing vaccine will protect against invasive nontyphoidalSalmonelladisease in African children.
Evidence for widespread adaptive evolution of gene expression in budding yeast
Authors: Fraser Hunter B. , Moses Alan M. , Schadt Eric E.
Published: January 2010

Changes in gene expression have been proposed to underlie many, or even most, adaptive differences between species. Despite the increasing acceptance of this view, only a handful of cases of adaptive gene expression evolution have been demonstrated. To address this discrepancy, we introduce a simple test for lineage-specific selection on gene expression. Applying the test to genome-wide gene expression data from the budding yeast
Saccharomyces cerevisiae
, we find that hundreds of gene expression levels have been subject to lineage-specific selection. Comparing these findings with independent population genetic evidence of selective sweeps suggests that this lineage-specific selection has resulted in recent sweeps at over a hundred genes, most of which led to increased transcript levels. Examination of the implicated genes revealed a specific biochemical pathway—ergosterol biosynthesis—where the expression of multiple genes has been subject to selection for reduced levels. In sum, these results suggest that adaptive evolution of gene expression is common in yeast, that regulatory adaptation can occur at the level of entire pathways, and that similar genome-wide scans may be possible in other species, including humans.
Blimp1-mediated repression of negative regulators is required for osteoclast differentiation
Authors: Nishikawa Keizo , Nakashima Tomoki , Hayashi Mikihito , Fukunaga Takanobu , Kato Shigeaki , Kodama Tatsuhiko , Takahashi Satoru , Calame Kathryn , Takayanagi Hiroshi
Published: January 2010

Regulation of irreversible cell lineage commitment depends on a delicate balance between positive and negative regulators, which comprise a sophisticated network of transcription factors. Receptor activator of NF-κB ligand (RANKL) stimulates the differentiation of bone-resorbing osteoclasts through the induction of nuclear factor of activated T cells c1 (NFATc1), the essential transcription factor for osteoclastogenesis. Osteoclast-specific robust induction of NFATc1 is achieved through an autoamplification mechanism, in which NFATc1 is constantly activated by calcium signaling while the negative regulators of NFATc1 are suppressed. However, it has been unclear how such negative regulators are repressed during osteoclastogenesis. Here we show that B lymphocyte-induced maturation protein-1 (Blimp1; encoded by
Prdm1
), which is induced by RANKL through NFATc1 during osteoclastogenesis, functions as a transcriptional repressor of anti-osteoclastogenic genes such as
Irf8
and
Mafb
. Overexpression of Blimp1 leads to an increase in osteoclast formation, and
Prdm1
-deficient osteoclast precursor cells do not undergo osteoclast differentiation efficiently. The importance of Blimp1 in bone homeostasis is underscored by the observation that mice with an osteoclast-specific deficiency in the
Prdm1
gene exhibit a high bone mass phenotype caused by a decreased number of osteoclasts. Thus, NFATc1 choreographs the determination of cell fate in the osteoclast lineage by inducing the repression of negative regulators as well as through its effect on positive regulators.
Capillarity theory for the fly-casting mechanism
Authors: Trizac Emmanuel , Levy Yaakov , Wolynes Peter G.
Published: January 2010

Biomolecular folding and function are often coupled. During molecular recognition events, one of the binding partners may transiently or partially unfold, allowing more rapid access to a binding site. We describe a simple model for this fly-casting mechanism based on the capillarity approximation and polymer chain statistics. The model shows that fly casting is most effective when the protein unfolding barrier is small and the part of the chain which extends toward the target is relatively rigid. These features are often seen in known examples of fly casting in protein–DNA binding. Simulations of protein–DNA binding based on well-funneled native-topology models with electrostatic forces confirm the trends of the analytical theory.
Lipid signaling in cytosolic phospholipase A2α–cyclooxygenase-2 cascade mediates cerebellar long-term depression and motor learning
Authors: Le Tung Dinh , Shirai Yoshinori , Okamoto Takehito , Tatsukawa Tetsuya , Nagao Soichi , Shimizu Takao , Ito Masao
Published: January 2010

In this study, we show the crucial roles of lipid signaling in long-term depression (LTD), that is, synaptic plasticity prevailing in cerebellar Purkinje cells. In mouse brain slices, we found that cPLA2α knockout blocked LTD induction, which was rescued by replenishing arachidonic acid (AA) or prostaglandin (PG) D2or E2. Moreover, cyclooxygenase (COX)–2 inhibitors block LTD, which is rescued by supplementing PGD2/E2. The blockade or rescue occurs when these reagents are applied within a time window of 5–15 min following the onset of LTD-inducing stimulation. Furthermore, PGD2/E2facilitates the chemical induction of LTD by a PKC activator but is unable to rescue the LTD blocked by a PKC inhibitor. We conclude that PGD2/E2mediates LTD jointly with PKC, and suggest possible pathways for their interaction. Finally, we demonstrate in awake mice that cPLA2α deficiency or COX-2 inhibition attenuates short-term adaptation of optokinetic eye movements, supporting the view that LTD underlies motor learning.
Histone H3 lysine 36 methyltransferase Hypb/Setd2 is required for embryonic vascular remodeling
Authors: Hu Ming , Sun Xiao-Jian , Zhang Yuan-Liang , Kuang Ying , Hu Chao-Quan , Wu Wei-Li , Shen Shu-Hong , Du Ting-Ting , Li Hong , He Fei , Xiao Hua-Sheng , Wang Zhu-Gang , Liu Ting-Xi , Lu He , Huang Qiu-Hua , Chen Sai-Juan , Chen Zhu
Published: January 2010

HYPB is a human histone H3 lysine 36 (H3K36)–specific methyltransferase and acts as the ortholog of yeast Set2. This study explored the physiological function of mammalian HYPB using knockout mice. Homozygous disruption of
Hypb
impaired H3K36 trimethylation but not mono- or dimethylation, and resulted in embryonic lethality at E10.5-E11.5. Severe vascular defects were observed in the
Hypb
−/−
embryo, yolk sac, and placenta. The abnormally dilated capillaries in mutant embryos and yolk sacs could not be remodeled into large blood vessels or intricate networks, and the aberrantly rounded mesodermal cells exhibited weakened interaction with endothelial cells. The embryonic vessels failed to invade the labyrinthine layer of placenta, which impaired the embryonic–maternal vascular connection. These defects could not be rescued by wild-type tetraploid blastocysts, excluding the possibility that they were caused by the extraembryonic tissues. Consistent with these phenotypes, gene expression profiling in wild-type and
Hypb
−/−
yolk sacs revealed that the
Hypb
disruption altered the expression of some genes involved in vascular remodeling. At the cellular level,
Hypb
−/−
embryonic stem cell–derived embryonic bodies, as well as in vitro–cultured human endothelial cells with siRNA-mediated suppression of
HYPB
, showed obvious defects in cell migration and invasion during vessel formation, suggesting an intrinsic role of
Hypb
in vascular development. Taken together, these results indicate that Hypb is required for embryonic vascular remodeling and provide a tool to study the function of H3K36 methylation in vasculogenesis/angiogenesis.
Activation state and intracellular trafficking contribute to the repertoire of endogenous glycosphingolipids presented by CD1d
Authors: Muindi Karen , Cernadas Manuela , Watts Gerald F. M. , Royle Louise , Neville David C. A. , Dwek Raymond A. , Besra Gurdyal S. , Rudd Pauline M. , Butters Terry D. , Brenner Michael B.
Published: January 2010

Myeloid antigen-presenting cells (APC) express CD1d molecules that present exogenous and endogenous lipid antigens that activate CD1d-restricted T cells, natural killer T (NKT) cells. NKT cell activation has been shown to mediate the potent downstream activation of other immune cells through cell–cell interactions and rapid, prolific cytokine production. Foreign antigens are not required for NKT cell activation. The endogenous lipids bound to CD1d are sufficient for activation of NKT cells in the setting of Toll-like receptor-induced cytokines. The most potent NKT cell antigens identified are glycosphingolipids (GSL). The GSL repertoire of endogenous ligands bound to CD1d molecules that are expressed in myeloid APC at steady state and in the setting of activation has not been delineated. This report identifies the range of GSL bound to soluble murine CD1d (mCD1d) molecules that sample the endoplasmic reticulum/secretory routes and cell surface-cleaved mCD1d that also samples the endocytic system. Specific GSL species are preferentially bound by mCD1d and do not solely reflect cellular GSL. GM1a and GD1a are prominent CD1d ligands for molecules following both the ER/secretory and lysosomal trafficking routes, whereas GM2 was eluted from soluble CD1d but not lysosomal trafficking CD1d. Further, after LPS activation, the quantities of soluble CD1d-bound GM3 and GM1a markedly increased. A unique α-galactose-terminating GSL was also found to be preferentially bound to mCD1d at steady state, and it increased with APC activation. Together, these studies identify the range of GSL presented by CD1d and how presentation varies based on CD1d intracellular trafficking and microbial activation.
Two distinct mechanisms underlie progesterone-induced proliferation in the mammary gland
Authors: Beleut Manfred , Rajaram Renuga Devi , Caikovski Marian , Ayyanan Ayyakkannu , Germano Davide , Choi Yongwon , Schneider Pascal , Brisken Cathrin
Published: January 2010

The mouse mammary gland develops postnatally under the control of female reproductive hormones. Estrogens and progesterone trigger morphogenesis by poorly understood mechanisms acting on a subset of mammary epithelial cells (MECs) that express their cognate receptors, estrogen receptor α (ERα) and progesterone receptor (PR). Here, we show that in the adult female, progesterone drives proliferation of MECs in two waves. The first, small wave, encompasses PR(+) cells and requires cyclin D1, the second, large wave, comprises mostly PR(−) cells and relies on the tumor necrosis factor (TNF) family member, receptor activator of NF-κB-ligand (RANKL). RANKL elicits proliferation by a paracrine mechanism. Ablation of RANKL in the mammary epithelium blocks progesterone-induced morphogenesis, and ectopic expression of RANKL in MECs completely rescues the PR
−/−
phenotype. Systemic administration of RANKL triggers proliferation in the absence of PR signaling, and injection of a RANK signaling inhibitor interferes with progesterone-induced proliferation. Thus, progesterone elicits proliferation by a cell-intrinsic and a, more important, paracrine mechanism.
Assembly of the AAA ATPase Vps4 on ESCRT-III
Authors: Shestakova Anna , Hanono Abraham , Drosner Stacey , Curtiss Matt , Davies Brian A. , Katzmann David J. , Babst Markus
Published: January 2010

Vps4 is a key enzyme that functions in endosomal protein trafficking, cytokinesis, and retroviral budding. Vps4 activity is regulated by its recruitment from the cytoplasm to ESCRT-III, where the protein oligomerizes into an active ATPase. The recruitment and oligomerization steps are mediated by a complex network of at least 12 distinct interactions between Vps4, ESCRT-III, Ist1, Vta1, and Did2. The order of events leading to active, ESCRT-III–associated Vps4 is poorly understood. In this study we present a systematic in vivo analysis of the Vps4 interaction network. The data demonstrated a high degree of redundancy in the network. Although no single interaction was found to be essential for the localization or activity of Vps4, certain interactions proved more important than others. The most significant among these were the binding of Vps4 to Vta1 and to the ESCRT-III subunits Vps2 and Snf7. In our model we propose the formation of a recruitment complex in the cytoplasm that is composed of Did2-Ist1-Vps4, which upon binding to ESCRT-III recruits Vta1. Vta1 in turn is predicted to cause a rearrangement of the Vps4 interactions that initiates the assembly of the active Vps4 oligomer.
The Endoplasmic Reticulum–associated Degradation of the Epithelial Sodium Channel Requires a Unique Complement of Molecular Chaperones
Authors: Buck Teresa M. , Kolb Alexander R. , Boyd Cary R. , Kleyman Thomas R. , Brodsky Jeffrey L.
Published: January 2010

The epithelial sodium channel (ENaC) is composed of a single copy of an α-, β-, and γ-subunit and plays an essential role in water and salt balance. Because ENaC assembles inefficiently after its insertion into the ER, a substantial percentage of each subunit is targeted for ER-associated degradation (ERAD). To define how the ENaC subunits are selected for degradation, we developed novel yeast expression systems for each ENaC subunit. Data from this analysis suggested that ENaC subunits display folding defects in more than one compartment and that subunit turnover might require a unique group of factors. Consistent with this hypothesis, yeast lacking the lumenal Hsp40s, Jem1 and Scj1, exhibited defects in ENaC degradation, whereas BiP function was dispensable. We also discovered that Jem1 and Scj1 assist in ENaC ubiquitination, and overexpression of ERdj3 and ERdj4, two lumenal mammalian Hsp40s, increased the proteasome-mediated degradation of ENaC in vertebrate cells. Our data indicate that Hsp40s can act independently of Hsp70 to select substrates for ERAD.
Rad17 Plays a Central Role in Establishment of the Interaction between TopBP1 and the Rad9-Hus1-Rad1 Complex at Stalled Replication Forks
Authors: Lee Joon , Dunphy William G.
Published: January 2010

Rad17 is critical for the ATR-dependent activation of Chk1 during checkpoint responses. It is known that Rad17 loads the Rad9-Hus1-Rad1 (9-1-1) complex onto DNA. We show that Rad17 also mediates the interaction of 9-1-1 with the ATR-activating protein TopBP1 in Xenopus egg extracts. Studies with Rad17 mutants indicate that binding of ATP to Rad17 is essential for the association of 9-1-1 and TopBP1. Furthermore, hydrolysis of ATP by Rad17 is necessary for the loading of 9-1-1 onto DNA and the elevated, checkpoint-dependent accumulation of TopBP1 on chromatin. Significantly, a mutant 9-1-1 complex that cannot bind TopBP1 has a normal capacity to promote elevated accumulation of TopBP1 on chromatin. Taken together, we propose the following mechanism. First, Rad17 loads 9-1-1 onto DNA. Second, TopBP1 accumulates on chromatin in a manner that depends on both Rad17 and 9-1-1. Finally, 9-1-1 and TopBP1 dock in a Rad17-dependent manner before activation of Chk1.
Decoupled Farm Payments and the Role of Base Acreage and Yield Updating Under Uncertainty
Authors: Bhaskar Arathi , Beghin John C.
Published: January 2010

We analyze the coupling effect of expectations about base acreage and yield updating in future farm policy on production decisions in the presence of price, yield, and policy uncertainty for a risk‐averse farmer producing a single crop. The farmer receives market revenue and government payments. Using stochastic dynamic programming, optimum decisions under present value calculations positively link current acreage and fertilizer decisions to future government payments through expected updates of base acreage and yield in the future regime. Moving from a zero probability of updating to a probability of one increases optimum acreage and yield by 6.25% and 0.134%, respectively.
Bayesian inference for finite mixtures of univariate and multivariate skew-normal and skew-t distributions
Authors: Frühwirth-Schnatter Sylvia , Pyne Saumyadipta
Published: January 2010

Skew-normal and skew-t distributions have proved to be useful for capturing skewness and kurtosis in data directly without transformation. Recently, finite mixtures of such distributions have been considered as a more general tool for handling heterogeneous data involving asymmetric behaviors across subpopulations. We consider such mixture models for both univariate as well as multivariate data. This allows robust modeling of high-dimensional multimodal and asymmetric data generated by popular biotechnological platforms such as flow cytometry.

We develop Bayesian inference based on data augmentation and Markov chain Monte Carlo (MCMC) sampling. In addition to the latent allocations, data augmentation is based on a stochastic representation of the skew-normal distribution in terms of a random-effects model with truncated normal random effects. For finite mixtures of skew normals, this leads to a Gibbs sampling scheme that draws from standard densities only. This MCMC scheme is extended to mixtures of skew-t distributions based on representing the skew-t distribution as a scale mixture of skew normals.

As an important application of our new method, we demonstrate how it provides a new computational framework for automated analysis of high-dimensional flow cytometric data. Using multivariate skew-normal and skew-t mixture models, we could model non-Gaussian cell populations rigorously and directly without transformation or projection to lower dimensions.
Action Mechanisms of Du‐Huo‐Ji‐Sheng‐Tang on Cartilage Degradation in a Rabbit Model of Osteoarthritis
Authors: Chen Chao-Wei , Sun Jian , Li Yu-Mei , Shen Pi-An , Chen Yong-Qiang
Published: January 2010

Du‐Huo‐Ji‐Sheng‐Tang (DHJST) is a traditional Chinese herbal medicine used to treat osteoarthritis. In the present study, the therapeutic effect of DHJST on cartilage degradation in a rabbit model of osteoarthritis was investigated. In the knee joints of rabbits, anterior cruciate ligament transection (ACLT) was performed to induce experimental osteoarthritis. At the end of the sixth week, 30 rabbits with ACLT were divided into six groups, control group, DHJST group and Osaminethacine (OSA) group, which were followed for another 4 weeks. The other three groups of rabbits with ACLT were untreated with DHJST or OSA, which were sacrificed after 6 weeks, and served as 6‐week time point controls. Results indicated that at the end of the sixth week after surgery, there was a significantly histological degeneration in the control group compared with the normal group. In the control group, the mean score for histological degeneration were further increases at 10th week, and there was a significantly lower mean score for histological degeneration in the DHJST group compared with the control group. To research the potential mechanism, the expression level of VEGF and HIF‐1α were detected. The expression of VEGF mRNA and HIF‐1α mRNA are low in normal group, while the activities increase gradually in the control group. However, compared to that of the same time point model group, activity of VEGF and HIF‐1α decreased significantly in DHJST group. In conclusion, DHJST exerts significant therapeutic effect on osteoarthritis rabbits, and mechanisms are associated with inhibition of VEGF and HIF‐1α expression.
Probiotic Escherichia coli strain Nissle 1917 outcompetes intestinalpathogens during biofilm formation
Authors: Hancock Viktoria , Dahl Malin , Klemm Per
Published: January 2010

Many bacterial infections are associated with biofilm formation. Bacterialbiofilms can develop on essentially all kinds of surfaces, producing chronicand often intractable infections.Escherichia coliis an importantpathogen causing a wide range of gastrointestinal infections.E. colistrain Nissle 1917 has been used for many decades as a probiotic againsta variety of intestinal disorders and is probably the best field-testedE. colistrain in the world. Here we have investigated the biofilm-formingcapacity of Nissle 1917. We found that the strain was a good biofilm former.Not only was it significantly better at biofilm formation than enteropathogenic,enterotoxigenic and enterohaemorrhagicE. colistrains, it was alsoable to outcompete such strains during biofilm formation. The results supportthe notion of bacterial prophylaxis employing Nissle 1917 and may partiallyexplain why the strain has a beneficial effect on many intestinal disorders.
Inhibitory effects of Lactobacillus casei subsp. rhamnosus on Salmonella lipopolysaccharide-induced inflammation and epithelial barrier dysfunction in a co-culture model using Caco-2/peripheral blood mononuclear cells
Authors: Fang Hsu-Wei , Fang Shiuh-Bin , Chiang Chiau Jen-Shiu , Yeung Chun-Yan , Chan Wai-Tao , Jiang Chuen-Bin , Cheng Mei-Lien , Lee Hung-Chang
Published: January 2010

In this study, we investigated the anti-inflammatory and reinforcing barrier effects of Lactobacillus casei subsp. rhamnosus (Lcr35) on Caco-2 intestinal epithelial cells already exposed to Salmonella LPS. Using the Transwell co-culture model, Salmonella LPS was apically added to polarized Caco-2 cells co-cultured with peripheral blood mononuclear cells (PBMCs) in the basolateral compartment. LPS-stimulated Caco-2 cells were incubated with Lcr35 for 1, 6, 24 or 48 h. Apical inoculation of Lcr35 after 48 h significantly inhibited the basolateral secretion of interleukin-8 (IL-8) in the Caco-2/PBMC co-culture. The PCR analysis showed that Lcr35 significantly downregulated mRNA expression of monocyte chemoattractant protein 1 (MCP-1) (P<0.05) and had a trend of decreasing mRNA expression of IL-8 (P=0.05), but did not alter mRNA expression of transforming growth factor-β1 in LPS-stimulated Caco-2 cells at 48 h after addition of Lcr35. Compared to non-LPS-pretreated controls, transepithelial electrical resistance (TEER) of the polarized Caco-2 cell monolayers pretreated with LPS for 48 h was decreased by 9.9 % (P<0.05). Additionally, compared to those cells only treated with LPS, apical co-incubation with Lcr35 showed biphasic TEER levels increased by 12.1 % (P<0.001), 5.7 % (P<0.05) and 86.8 % (P<0.001) in the Caco-2 cell monolayers compared to those without Lcr35 treatment after 1, 6 and 48 h, respectively. In conclusion, Lcr35 can exert anti-inflammatory effects and ameliorate barrier dysfunction in the Salmonella LPS-pretreated inflamed intestinal epithelium in vitro.
Reversible hearing impairment: delayed complication of murine typhus or adverse reaction to azithromycin?
Authors: Lin Shang-Yi , Wang Ya-Ling , Lin Hsiu-Fen , Chen Tun-Chieh , Chen Yen-Hsu , Lu Po-Liang
Published: January 2010

Delayed and reversible hearing loss occurred in a 55-year-old male patient with murine typhus infection. The patient had the initial symptoms of headache, fever and chills, followed by the occurrence of bilateral hearing loss on day 9 from fever onset. Murine typhus was diagnosed with a high IgM titre by indirect immunofluorescence assay. After treatment with azithromycin and prednisolone, the fever and other symptoms subsided gradually and bilateral hearing loss improved 3 weeks later. Though an adverse reaction to azithromycin could not be ruled out, delayed onset of hearing loss was more likely a complication of murine typhus, mainly because the hearing loss did not occur during the azithromycin usage period. Although hearing loss due to murine typhus is rare, clinicians should be alert to the existence of such a delayed complication.
Enhanced production of exopolysaccharide matrix and biofilm by a menadione-auxotrophic Staphylococcus aureus small-colony variant
Authors: Singh Rachna , Ray Pallab , Das Anindita , Sharma Meera
Published: January 2010

The role ofStaphylococcus aureussmall-colony variants (SCVs) in the pathogenesis of biofilm-associated infections remains unclear. This study investigated the mechanism behind increased biofilm-forming potential of a menadione-auxotrophicStaphylococcus aureusSCV compared with the wild-type parental strain, as recently reported by our laboratory. SCVs displayed an autoaggregative phenotype, with a greater amount of polysaccharide intercellular adhesin (PIA), significantly reduced tricarboxylic acid cycle activity and a decreased susceptibility to aminoglycosides and cell-wall inhibitors compared with wild-type. The biofilms formed by the SCV were highly structured, consisting of large microcolonies separated by channels, and contained more biomass as well as significantly more PIA than wild-type biofilms. The surface hydrophobicity of the two phenotypes was similar. Thus, the autoaggregation and increased biofilm-forming capacity of menadione-auxotrophicStaphylococcus aureusSCVs in this study was related to the enhanced production of PIA in these variants.