bluuebunny/crossref_metadata_2025 huggingface dataset:
Transport and retention of colloidal particles in partially saturated porous media: Effect of ionic strength
Authors: Zevi Yuniati , Dathe Annette , Gao Bin , Zhang Wei , Richards Brian K. , Steenhuis Tammo S.
Published: December 2009

We directly observed pore‐scale attachment of fluorescent synthetic polystyrene colloids (1.0 μm diameter) in a partially saturated sand pack (pore space saturation ranging from 0.7 to 0.9) at four solution ionic strengths (0, 1, 100, 200 mmol NaCl). Sequential confocal laser microscope images were analyzed to quantify colloid retention, particularly at air‐water meniscus‐solid (AWmS) interfaces. We concurrently measured effluent colloid concentrations to determine overall matrix retention. Ionic strength had no effect on meniscus contact angles (26.7 ± 3.7 degrees) or surface tension (63–67 mN/m), both important components of the capillary forces thought to play the primary role in retention at the AWmS interfaces. AWmS interfaces attachment was greatest at 1 mmol, with the 0 mmol ionic strength reducing attachment by half. Increasing ionic strength to 100 and 200 mmol markedly decreased colloid retention at the AWmS interfaces due to observed increased competing attachment at grain surfaces (solid/water interface) that reduced the number of colloids available for AWmS interface attachment.
Measurement of crack‐face friction in collapsed weak snow layers
Authors: van Herwijnen A. , Heierli J.
Published: December 2009

In this letter we analyze the frictional contact forces during and immediately after the collapse of a weak snowpack layer, when the sliding plane consists of the freshly collapsed and crushed, but not yet eroded granular debris of the weak layer. The results from thirty‐four field experiments show that frictional contact forces per unit area are on the order of 0.6 times the normal stress, equivalent to a friction angle close to 30 degrees. The measurements show that there is a transient, sharp drop in the coefficient of friction during the collapse of the weak layer and relatively constant values afterwards. One implication of our findings is that the minimum angle for avalanche release does not depend on shear strength, as commonly thought, but results from crack‐face friction which comes into play only as the fracture through the weak layer is already propagating.
Kelvin‐Helmholtz waves at the Earth's magnetopause: Multiscale development and associated reconnection
Authors: Hasegawa H. , Retinò A. , Vaivads A. , Khotyaintsev Y. , André M. , Nakamura T. K. M. , Teh W.‐L. , Sonnerup B. U. Ö. , Schwartz S. J. , Seki Y. , Fujimoto M. , Saito Y. , Rème H. , Canu P.
Published: December 2009

We examine traversals on 20 November 2001 of the equatorial magnetopause boundary layer simultaneously at ∼1500 magnetic local time (MLT) by the Geotail spacecraft and at ∼1900 MLT by the Cluster spacecraft, which detected rolled‐up MHD‐scale vortices generated by the Kelvin‐Helmholtz instability (KHI) under prolonged northward interplanetary magnetic field conditions. Our purpose is to address the excitation process of the KHI, MHD‐scale and ion‐scale structures of the vortices, and the formation mechanism of the low‐latitude boundary layer (LLBL). The observed KH wavelength (>4 × 104 km) is considerably longer than predicted by the linear theory from the thickness (∼1000 km) of the dayside velocity shear layer. Our analyses suggest that the KHI excitation is facilitated by combined effects of the formation of the LLBL presumably through high‐latitude magnetopause reconnection and compressional magnetosheath fluctuations on the dayside, and that breakup and/or coalescence of the vortices are beginning around 1900 MLT. Current layers of thickness a few times ion inertia length ∼100 km and of magnetic shear ∼60° existed at the trailing edges of the vortices. Identified in one such current sheet were signatures of local reconnection: Alfvénic outflow jet within a bifurcated current sheet, nonzero magnetic field component normal to the sheet, and field‐aligned beam of accelerated electrons. Because of its incipient nature, however, this reconnection process is unlikely to lead to the observed dusk‐flank LLBL. It is thus inferred that the flank LLBL resulted from other mechanisms, namely, diffusion and/or remote reconnection unidentified by Cluster.
Dependence of premidnight field‐aligned currents and particle precipitation on solar illumination
Authors: Ohtani S. , Wing S. , Ueno G. , Higuchi T.
Published: December 2009

The present study statistically addresses the dependence of large‐scale field‐aligned currents (R1/R2) and particle precipitation in the premidnight sector on solar illumination at the ionosphere. The energy flux and average energy of precipitating electrons and ions are examined for downward R2 and upward R1 currents. Results are summarized as follows: (1) The R1 current density is larger in the dark hemisphere, whereas the dependence of R2 density on solar illumination is unclear. (2) For R1 currents the electron energy flux is larger and the average electron energy is higher in the dark hemisphere. (3) For R2 currents, a similar preference for the dark hemisphere is found for the electron energy flux, which, however, is significantly lower than for R1 currents. The average electron energy is similar between the two hemispheres. (4) For both R1 and R2 currents, ion precipitation is more intense and energetic in the dark hemisphere. (5) For a given field‐aligned current density, whether R1 or R2 currents, both electron and ion precipitation is more intense and energetic in the dark hemisphere. The Pedersen conductivity is estimated from electron precipitation and solar illumination. The result suggests that in the dark hemisphere the absence of solar illumination is often overcompensated by more intense and energetic electron precipitation. The interhemispheric difference in electron acceleration may be interpreted in terms of plasma density in the acceleration region, which is known to be significantly lower in the dark hemisphere, and therefore electrons need to be more accelerated along the field line to carry imposed currents.
Statistical study of substorm timing sequence
Authors: Lin Naiguo , Frey H. U. , Mende S. B. , Mozer F. S. , Lysak R. L. , Song Y. , Angelopoulos V.
Published: December 2009

Observations of timing sequences of substorms expected in various onset mechanisms are examined by using a space‐time diagram, which correlates observed space signatures and auroral signatures on the ground during substorm onset. Results from a statistical study of 11 substorms show that signatures in the midtail (x ∼ 15–25 RE) typically occur before the ground signatures and those in the near‐Earth tail (x ∼ 10 RE) and that signatures in the midtail region observed prior to the substorm onset often occur at a time which was shorter than that expected from MHD wave propagation between the different regions. This suggests that the disturbance onsets in different active regions do not seem to have a simple causal relationship between them as described by the reconnection or current disruption models of substorms. The activation of perturbed fields and plasma flows in space including the signatures of reconnection and current disruption may occur in multiple localized regions throughout the stressed tail current sheet. The activation seems to be continuously observed well after the substorm onset. These results to some extent are consistent with suggested global Alfvénic interaction considerations, in which the substorm onset is the result of Alfvénic interaction in the global current systems.
Atmospheric and upper ocean environments of Southern Ocean polar mesocyclones in the transition season months and associations with teleconnections
Authors: Claud Chantal , Carleton Andrew M. , Duchiron Bertrand , Terray Pascal
Published: December 2009

Over middle and higher latitudes of the Southern Hemisphere, intense mesoscale cyclonic vortices that develop in cold‐air outbreaks (cold‐air mesocyclones) occur frequently during transition season months. In this study, previously published mesocyclone inventories for March–April and October–November are compared to atmospheric and upper ocean variables pertinent to mesocyclogenesis, as provided by reanalyses. This procedure allows the determination of the large‐scale environments favorable for mesocyclone occurrence: low midtropospheric temperatures, greater sea ice extent, and large positive differences in the sea surface temperature minus low‐altitude air temperature, the latter coinciding with enhanced low‐level winds having a southerly component. We then evaluate the associations between polar mesocyclone formation and dominant patterns of low‐frequency variability in the atmospheric circulation: the El Niño–Southern Oscillation (ENSO), the Southern Annular Mode (SAM), and the Trans‐Polar Index (TPI). Our results suggest that in spring, the intrahemispheric variability in mesocyclogenesis is dominated by ENSO. In autumn, the influences of ENSO, SAM, and TPI on mesocyclone activity are about equal, although the response differs regionally. Moreover, teleconnections' effects on mesocyclone activity are somewhat reduced compared to that in spring. In both seasons, the phase of the semiannual oscillation modulates the associations with mesocyclones by influencing the latitude of the circumpolar trough and the amount of cyclonic activity over the Southern Ocean. These associations likely result from the displacement of the storm track between opposite phases of a given teleconnection and its position relative to the sea ice edge.
Water vapor measurements in the mesosphere from Mauna Loa over solar cycle 23
Authors: Nedoluha Gerald E. , Gomez R. Michael , Hicks Brian C. , Wrotny Jonathan E. , Boone Chris , Lambert Alyn
Published: December 2009

The Water Vapor Millimeter‐wave Spectrometer (WVMS) system has been making measurements from the Network for the Detection of Atmospheric Composition Change site at Mauna Loa, Hawaii (19.5°N, 204.4°E), since 1996, covering nearly the complete period of solar cycle 23. The WVMS measurements are compared with Halogen Occultation Experiment (HALOE) (1992–2005), Microwave Limb Sounder (MLS) (2004 to present), and Atmospheric Chemistry Experiment (ACE) Fourier transform spectrometer (2004 to present) measurements in the mesosphere. In the upper mesosphere Lyman α radiation photodissociates water vapor; hence, water vapor in the upper mesosphere varies with the solar cycle. We calculate fits to the WVMS and HALOE water vapor data in this region using the Lasp Interactive Solar Irradiance Datacenter Lyman α data set. This is, to our knowledge, the only published validation of the sensitivity of HALOE water vapor measurements to the solar cycle, and the HALOE and WVMS water vapor measurements show a very similar sensitivity to the solar cycle. Once the solar cycle variations are taken into account, the primary water vapor variations at all of these altitudes from 1992 to the present are an increase from 1992 to 1996, a maximum in water vapor in 1996, and small changes from 1997 to the present. Measurements from 2004 to 2008, which are available from WVMS, MLS, and ACE, show not only good agreement in interannual variations but also excellent agreement in their absolute measurements (to within better than 3%) of the water vapor mixing ratio from 50 to 80 km.
Exposure of different bacterial inocula to newborn chicken affects gut microbiota development and ileum gene expression
Authors: Yin Yeshi , Lei Fang , Zhu Liying , Li Sujuan , Wu Zuowei , Zhang Ruifen , Gao George F , Zhu Baoli , Wang Xin
Published: December 2009

The transition from a sterile gut environment to the development of microbiota in the newborns is not fully understood. The objective of this study was to investigate the impact of exposure to bacterial communities on the development of gut microbiota in the newly hatched chicken. A total of 90 as-hatched chicks were divided into three groups. Groups A and B were treated with inocula of the cecal origin, whereas group C was fed with sterile water. The major bacteria in Inoculum-I to treat group A included Bacteroides (20.7%), Lachnospiraceae (17.2%) and unclassified Ruminococcaceae (16.1%), whereas group B was introduced with Inoculum-II composed of Prevotella (37.9%), Acidaminococcus (16.1%) and Dorea (12.6%). Analyses of the ileal and cecal contents over a period of 15 days showed that Inoculum-I resulted in a higher rate of colonization than Inoculum-II, but the colonization was predominantly in the cecum. The influence of Inoculum-II on group B was similar to that of water on group C, showing only a marginal effect on colonization. Microarray analysis showed that each group presented a distinct pattern of gene expression in the ileum. In group A, the most obvious changes were noted in genes controlling the function of ion transport, cell cycle and chromosome maintenance, suggesting that the inocula influenced gene expression. Our findings indicate that initial exposure to different bacterial communities could lead to the development of distinct microbiota and gene expression in the gut. It is possible to manipulate the gut microbiota by feeding to a proper bacterial composition at an early age.
Effect of Alginate on Satiation, Appetite, Gastric Function, and Selected Gut Satiety Hormones in Overweight and Obesity
Authors: Odunsi Suwebatu T. , Vázquez‐Roque María I. , Camilleri Michael , Papathanasopoulos Athanasios , Clark Matthew M. , Wodrich Lynne , Lempke Mary , McKinzie Sanna , Ryks Michael , Burton Duane , Zinsmeister Alan R.
Published: December 2009

Lack of control of food intake, excess size, and frequency of meals are critical to the development of obesity. The stomach signals satiation postprandially and may play an important role in control of calorie intake. Sodium alginate (based on brown seaweed Laminaria digitata) is currently marketed as a weight loss supplement, but its effects on gastric motor functions and satiation are unknown. We evaluated effects of 10 days treatment with alginate or placebo on gastric functions, satiation, appetite, and gut hormones associated with satiety in overweight or obese adults. We conducted a randomized, 1:1, placebo‐controlled, allocation‐concealed study in 48 overweight or obese participants with excluded psychiatric comorbidity and binge eating disorder. All underwent measurements of gastric emptying (GE), fasting, and postprandial gastric volumes (GVs), postprandial satiation, calorie intake at a free choice meal and selected gut hormones after 1 week of alginate (three capsules vs. matching placebo per day, ingested 30 min before the main meal). Six capsules were ingested with water 30 min before the GE, GV, and satiation tests on days 8–10. There were no treatment group effects on GE or volumes, gut hormones (ghrelin, cholecystokinin (CCK), glucagon‐like peptide‐1 (GLP‐1), peptide YY (PYY)), satiation, total and macronutrient calorie intake at a free choice meal. There was no difference detected in results between obese and overweight patients. Alginate treatment for a period of 10 days showed no effect on gastric motor functions, satiation, appetite, or gut hormones. These results question the use of short‐term alginate treatment for weight loss.
Muscular Strength Is Inversely Related to Prevalence and Incidence of Obesity in Adult Men
Authors: Jackson Allen W. , Lee Duck‐Chul , Sui Xuemei , Morrow James R. , Church Timothy S. , Maslow Andrea L. , Blair Steven N.
Published: December 2009

The purpose of the study was to determine the relation between quintiles of muscular strength after adjustment for age and body weight, and excessive body fat (EBF) and excessive abdominal fat (EAF) when controlling for cardiorespiratory fitness (CRF) and other potential confounders. A two‐phased cross‐sectional and longitudinal study was conducted assessing the prevalence and incidence of EBF and EAF across quintiles of muscular strength. The sample included 3,258 men (mean age = 42.2 ± 8.9; weight (kg) = 81.2 ± 11.0; BMI = 25.3 ± 2.9; %fat = 19.4 ± 5.8; waist girth (cm) = 91.2 ± 9.0) who completed at least two clinical examinations as part of the Aerobics Center Longitudinal Study (ACLS). Muscular strength was assessed with tests of upper and lower body muscular strength using rack‐mounted weights with participants placed into strength quintiles. CRF was measured by a modified Balke treadmill test, %fat via underwater weighing or seven‐site skinfold measurements, and waist girth measured at the level of the umbilicus. EBF was defined as ≥25% and EAF was defined as >102 cm. There was a strong inverse gradient across quintiles of muscular strength for prevalence and incidence of EBF and EAF (P trend <0.01, each). With the lowest quintile serving as the referent, reductions in risk of EBF and EAF exceeded 70% for the highest strength quintile. Evidence suggests muscular strength may provide protection from EBF and EAF and their related comorbidities.
Adiponectin Multimers and ADIPOQ T45G in Coronary Artery Disease in Caribbean Type 2 Diabetic Subjects of African Descent
Authors: Foucan Lydia , Ezourhi Nabila , Maimaitiming Suliya , Hedreville Segho , Inamo Jocelyn , Atallah Andre , Bangou‐Bredent Jacqueline , Aubert Roberte , Chout Roger , Fumeron Frederic , Donnet Jean‐Paul , Marre Michel
Published: December 2009

Ethnic differences may affect the association of adiponectin (Ad) multimers with coronary artery disease (CAD). We analyzed the associations of total Ad, Ad multimers, and T45G polymorphism of ADIPOQ gene with pre‐existing CAD. We carried out a cross‐sectional study of 216 Afro‐Caribbean type 2 diabetic (T2D) subjects. Levels of total Ad, high molecular weight (HMW), middle molecular weight (MMW), and low molecular weight (LMW) isoforms were measured. Subjects were genotyped. Of the subjects studied, 57 had pre‐existing CAD, 77% of whom have had myocardial infarction. Subjects with CAD had lower Ad levels (total and multimers) and a higher frequency carried the minor allele 45G, GG/TG, (18% vs. 8%, P = 0.03) than subjects without CAD. In logistic regression analysis, the models used evaluate Ad in the context of adjustment for metabolic syndrome characteristics. The adjusted odds ratio (OR) of CAD was increased significantly (by factors of 1.05–3.27) for males, older subjects, low high‐density lipoprotein cholesterol (HDL‐C), high triglycerides (TGs), and carriers of the 45 G allele. For Ad, in model 1 (including only total Ad) the adjusted OR was 2.30; P = 0.03 and, in model 2 (including the three multimers, but not total Ad), the adjusted ORs were 0.73; P = 0.52 (HMW), 2.90; P = 0.01 (MMW), and 2.08; P = 0.09 (LMW). The T45G polymorphism in the ADIPOQ gene and hypoadiponectinemia were associated with CAD in our T2D subjects of predominantly African background. This effect of Ad level was mainly related to the MMW Ad form.
New Approach to the Visualization of International Scientific Collaboration
Authors: Chinchilla-Rodríguez Zaida , Vargas-Quesada Benjamin , Hassan-Montero Yusef , González-Molina Antonio , Moya-Anegóna Félix
Published: December 2009

In this study, visual representations are created in order to analyze different aspects of scientific collaboration at the international level. The main objective is to identify the international facet of research by following the flow of knowledge as expressed by the number of scientific publications, and then establishes the main geographical axes of output, showing the interrelationships of the domain, the intensity of these relations, and how the different types of collaboration are reflected in terms of visibility. Thus, the methodology has a twofold application, allowing us to detect significant differences that help characterize patterns of behaviour of a geographical system of output, along with the generation of representations that serve as interfaces for domain analysis and information retrieval.
Characterization of a
Bacillus subtilis
transporter for petrobactin, an anthrax stealth siderophore
Authors: Zawadzka Anna M. , Kim Youngchang , Maltseva Natalia , Nichiporuk Rita , Fan Yao , Joachimiak Andrzej , Raymond Kenneth N.
Published: December 2009

Iron deprivation activates the expression of components of the siderophore-mediated iron acquisition systems in
Bacillus subtilis
, including not only the synthesis and uptake of its siderophore bacillibactin but also expression of multiple ABC transporters for iron scavenging using xenosiderophores. The
yclNOPQ
operon is shown to encode the complete transporter for petrobactin (PB), a photoreactive 3,4-catecholate siderophore produced by many members of the
B. cereus
group, including
B. anthracis
. Isogenic disruption mutants in the
yclNOPQ
transporter, including permease YclN, ATPase YclP, and a substrate-binding protein YclQ, are unable to use either PB or the photoproduct of FePB (FePB
ν
) for iron delivery and growth, in contrast to the wild-type
B. subtilis
. Complementation of the mutations with the copies of the respective genes restores this capability. The YclQ receptor binds selectively iron-free and ferric PB, the PB precursor, 3,4-dihydroxybenzoic acid (3,4-DHB), and FePB
ν
with high affinity; the ferric complexes are seen in ESI-MS, implying strong electrostatic interaction between the protein-binding pocket and siderophore. The first structure of a Gram-positive siderophore receptor is presented. The 1.75-Å crystal structure of YclQ reveals a bilobal periplasmic binding protein (PBP) fold consisting of two α/β/α sandwich domains connected by a long α-helix with the binding pocket containing conserved positively charged and aromatic residues and large enough to accommodate FePB. Orthologs of the
B. subtilis
PB-transporter YclNOPQ in PB-producing
Bacilli
are likely contributors to the pathogenicity of these species and provide a potential target for antibacterial strategies.
Human cancers converge at the HIF-2α oncogenic axis
Authors: Franovic Aleksandra , Holterman Chet E. , Payette Josianne , Lee Stephen
Published: December 2009

Cancer development is a multistep process, driven by a series of genetic and environmental alterations, that endows cells with a set of hallmark traits required for tumorigenesis. It is broadly accepted that growth signal autonomy, the first hallmark of malignancies, can be acquired through multiple genetic mutations that activate an array of complex, cancer-specific growth circuits [Hanahan D, Weinberg RA (2000) The hallmarks of cancer.Cell100:57–70; Vogelstein B, Kinzler KW (2004) Cancer genes and the pathways they control.Nat Med10:789–799]. The superfluous nature of these pathways is thought to severely limit therapeutic approaches targeting tumor proliferation, and it has been suggested that this strategy be abandoned in favor of inhibiting more systemic hallmarks, including angiogenesis (Ellis LM, Hicklin DJ (2008) VEGF-targeted therapy: Mechanisms of anti-tumor activity.Nat Rev Cancer8:579–591; Stommel JM, et al. (2007) Coactivation of receptor tyrosine kinases affects the response of tumor cells to targeted therapies.Science318:287–290; Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors.Nat Rev Cancer2:727–739; Kaiser J (2008) Cancer genetics: A detailed genetic portrait of the deadliest human cancers.Science321:1280–1281]. Here, we report the unexpected observation that genetically diverse cancers converge at a common and obligatory growth axis instigated by HIF-2α, an element of the oxygen-sensing machinery. Inhibition of HIF-2α prevents the in vivo growth and tumorigenesis of highly aggressive glioblastoma, colorectal, and non–small-cell lung carcinomas and the in vitro autonomous proliferation of several others, regardless of their mutational status and tissue of origin. The concomitant deactivation of select receptor tyrosine kinases, including the EGFR and IGF1R, as well as downstream ERK/Akt signaling, suggests that HIF-2α exerts its proliferative effects by endorsing these major pathways. Consistently, silencing these receptors phenocopies the loss of HIF-2α oncogenic activity, abrogating the serum-independent growth of human cancer cells in culture. Based on these data, we propose an alternative to the predominant view that cancers exploit independent autonomous growth pathways and reveal HIF-2α as a potentially universal culprit in promoting the persistent proliferation of neoplastic cells.
Conditional c-
myb
knockout in adult hematopoietic stem cells leads to loss of self-renewal due to impaired proliferation and accelerated differentiation
Authors: Lieu Yen K. , Reddy E. Premkumar
Published: December 2009

Hematopoietic stem cells (HSCs) have a unique capacity to undergo self-renewal and multi-lineage differentiation to provide a lifetime supply of mature blood cells. By using conditional knockout technology, we disrupted the c-
myb
proto-oncogene specifically in adult bone marrow (BM) to demonstrate that this transcription factor is a regulator of self-renewal and multi-lineage differentiation of adult HSCs. Targeted disruption of the c-
myb
gene resulted in a critical depletion of the HSC pool. In addition, BM hematopoiesis in adult mice was impaired, resulting in profound reductions of various hematopoietic lineages including neutrophilic, monocytic, B lymphoid, erythroid, and, unexpectedly, megakaryocytic cells. Serial BM transplantation into lethally irradiated recipient mice indicated an essential role for c-
myb
in the self-renewal process. Furthermore, in vitro functional assays demonstrated that deletion of the c-
myb
gene leads to a slightly reduced proliferative capacity and an aberrant and accelerated differentiation of HSCs. In addition to long-term HSCs, functional studies also show that c-
myb
plays a critical role in short-term HSCs and multi-potential progenitors. Collectively, our data indicate a critical role for c-
myb
in adult BM hematopoiesis and in self-renewal and multi-lineage differentiation of adult HSCs.
Mitochondrial genome evidence reveals successful Late Paleolithic settlement on the Tibetan Plateau
Authors: Zhao Mian , Kong Qing-Peng , Wang Hua-Wei , Peng Min-Sheng , Xie Xiao-Dong , Wang Wen-Zhi , Jiayang  , Duan Jian-Guo , Cai Ming-Cui , Zhao Shi-Neng , Cidanpingcuo  , Tu Yuan-Quan , Wu Shi-Fang , Yao Yong-Gang , Bandelt Hans-Jürgen , Zhang Ya-Ping
Published: December 2009

Due to its numerous environmental extremes, the Tibetan Plateau—the world's highest plateau—is one of the most challenging areas of modern human settlement. Archaeological evidence dates the earliest settlement on the plateau to the Late Paleolithic, while previous genetic studies have traced the colonization event(s) to no earlier than the Neolithic. To explore whether the genetic continuity on the plateau has an exclusively Neolithic time depth, we studied mitochondrial DNA (mtDNA) genome variation within 6 regional Tibetan populations sampled from Tibet and neighboring areas. Our results confirm that the vast majority of Tibetan matrilineal components can trace their ancestry to Epipaleolithic and Neolithic immigrants from northern China during the mid-Holocene. Significantly, we also identified an infrequent novel haplogroup, M16, that branched off directly from the Eurasian M founder type. Its nearly exclusive distribution in Tibetan populations and ancient age (>21 kya) suggest that M16 may represent the genetic relics of the Late Paleolithic inhabitants on the plateau. This partial genetic continuity between the Paleolithic inhabitants and the contemporary Tibetan populations bridges the results and inferences from archaeology, history, and genetics.
Hydrogen sulfide is an endogenous stimulator of angiogenesis
Authors: Papapetropoulos Andreas , Pyriochou Anastasia , Altaany Zaid , Yang Guangdong , Marazioti Antonia , Zhou Zongmin , Jeschke Mark G. , Branski Ludwik K. , Herndon David N. , Wang Rui , Szabó Csaba
Published: December 2009

The goal of the current study was to investigate the role of exogenous and endogenous hydrogen sulfide (H
2
S) on neovascularization and wound healing in vitro and in vivo. Incubation of endothelial cells (ECs) with H
2
S enhanced their angiogenic potential, evidenced by accelerated cell growth, migration, and capillary morphogenesis on Matrigel. Treatment of chicken chorioallantoic membranes (CAMS) with H
2
S increased vascular length. Exposure of ECs to H
2
S resulted in increased phosphorylation of Akt, ERK, and p38. The K
ATP
channel blocker glibenclamide or the p38 inhibitor SB203580 abolished H
2
S-induced EC motility. Since glibenclamide inhibited H
2
S-triggered p38 phosphorylation, we propose that K
ATP
channels lay upstream of p38 in this process. When CAMs were treated with H
2
S biosynthesis inhibitors dl-propylargylglycine or beta-cyano-L-alanine, a reduction in vessel length and branching was observed, indicating that H
2
S serves as an endogenous stimulator of the angiogenic response. Stimulation of ECs with vascular endothelial growth factor (VEGF) increased H
2
S release, while pharmacological inhibition of H
2
S production or K
ATP
channels or silencing of cystathionine gamma-lyase (CSE) attenuated VEGF signaling and migration of ECs. These results implicate endothelial H
2
S synthesis in the pro-angiogenic action of VEGF. Aortic rings isolated from CSE knockout mice exhibited markedly reduced microvessel formation in response to VEGF when compared to wild-type littermates. Finally, in vivo, topical administration of H
2
S enhanced wound healing in a rat model, while wound healing was delayed in CSE
−/−
mice. We conclude that endogenous and exogenous H
2
S stimulates EC-related angiogenic properties through a K
ATP
channel/MAPK pathway.
A G-protein editor gates coenzyme B
12
loading and is corrupted in methylmalonic aciduria
Authors: Padovani Dominique , Banerjee Ruma
Published: December 2009

The mechanism by which docking fidelity is achieved for the multitude of cofactor-dependent enzymes is poorly understood. In this study, we demonstrate that delivery of coenzyme B
12
or 5′-deoxyadenosylcobalamin by adenosyltransferase to methylmalonyl-CoA mutase is gated by a small G protein, MeaB. While the GTP-binding energy is needed for the editing function; that is, to discriminate between active and inactive cofactor forms, the chemical energy of GTP hydrolysis is required for gating cofactor transfer. The G protein chaperone also exerts its editing function during turnover by using the binding energy of GTP to elicit release of inactive cofactor that is occasionally formed during the catalytic cycle of MCM. The physiological relevance of this mechanism is demonstrated by a patient mutation in methylmalonyl-CoA mutase that does not impair the activity of this enzyme per se but corrupts both the fidelity of the cofactor-loading process and the ejection of inactive cofactor that forms occasionally during catalysis. Consequently, cofactor in the incorrect oxidation state gains access to the mutase active site and is not released if generated during catalysis, leading, respectively, to assembly and accumulation of inactive enzyme and resulting in methylmalonic aciduria.
A protein kinase-phosphatase pair interacts with an ion channel to regulate ABA signaling in plant guard cells
Authors: Lee Sung Chul , Lan Wenzhi , Buchanan Bob B. , Luan Sheng
Published: December 2009

The plant hormone abscisic acid (ABA) serves as a physiological monitor to assess the water status of plants and, under drought conditions, induces stomatal pore closure by activating specific ion channels, such as a slow-anion channel (SLAC1) that, in turn, mediate ion efflux from the guard cells. Earlier genetic analyses uncovered a protein kinase (OST1) and several 2C-type phosphatases, as respective positive and negative regulators of ABA-induced stomatal closure. Here we show that the OST1 kinase interacts with the SLAC1 anion channel, leading to its activation via phosphorylation. PP2CA, one of the PP2C phosphatase family members acts in an opposing manner and inhibits the activity of SLAC1 by two mechanisms: (1) direct interaction with SLAC1 itself, and (2) physical interaction with OSTI leading to inhibition of the kinase independently of phosphatase activity. The results suggest that ABA signaling is mediated by a physical interaction chain consisting of several components, including a PP2C member, SnRK2-type kinase (OST1), and an ion channel, SLAC1, to regulate stomatal movements. The findings are in keeping with a paradigm in which a protein kinase-phosphatase pair interacts physically with a target protein to couple a signal with a specific response.
The crystal structure of
apo
-FtsH reveals domain movements necessary for substrate unfolding and translocation
Authors: Bieniossek Christoph , Niederhauser Barbara , Baumann Ulrich M.
Published: December 2009

The hexameric membrane-spanning ATP-dependent metalloprotease FtsH is universally conserved in eubacteria, mitochondria, and chloroplasts, where it fulfills key functions in quality control and signaling. As a member of the self-compartmentalizing ATPases associated with various cellular activities (AAA+ proteases), FtsH converts the chemical energy stored in ATP via conformational rearrangements into a mechanical force that is used for substrate unfolding and translocation into the proteolytic chamber. The crystal structure of the ADP state of
Thermotoga maritima
FtsH showed a hexameric assembly consisting of a 6-fold symmetric protease disk and a 2-fold symmetric AAA ring. The 2.6 Å resolution structure of the cytosolic region of apo-FtsH presented here reveals a new arrangement where the ATPase ring shows perfect 6-fold symmetry with the crucial pore residues lining an open circular entrance. Triggered by this conformational change, a substrate-binding edge beta strand appears within the proteolytic domain. Comparison of the apo- and ADP-bound structure visualizes an inward movement of the aromatic pore residues and generates a model of substrate translocation by AAA+ proteases. Furthermore, we demonstrate that mutation of a conserved glycine in the linker region inactivates FtsH.
Multiple Ser/Thr-rich degrons mediate the degradation of Ci/Gli by the Cul3-HIB/SPOP E3 ubiquitin ligase
Authors: Zhang Qing , Shi Qing , Chen Yongbin , Yue Tao , Li Shuang , Wang Bing , Jiang Jin
Published: December 2009

The Cul3-based E3 ubiquitin ligases regulate many cellular processes using a large family of BTB domain–containing proteins as their target recognition components, but how they recognize targets remains unknown. Here we identify and characterize degrons that mediate the degradation of the Hedgehog pathway transcription factor cubitus interruptus (Ci)/Gli by Cul3-Hedghog–induced MATH and BTB domain–containing protein (HIB)/SPOP. Ci uses multiple Ser/Thr (S/T)-rich motifs that bind HIB cooperatively to mediate its degradation. We provide evidence that both HIB and Ci form dimers/oligomers and engage in multivalent interactions, which underlies the in vivo cooperativity among individual HIB-binding sites. We find that similar S/T-rich motifs are present in Gli proteins as well as in numerous HIB-interacting proteins and mediate Gli degradation by SPOP. Our results provide a mechanistic insight into how HIB/SPOP recognizes its substrates and have important implications for the genome-wide prediction of substrates for Cul3-based E3 ligases.
Activity of guard cell anion channel SLAC1 is controlled by drought-stress signaling kinase-phosphatase pair
Authors: Geiger Dietmar , Scherzer Sönke , Mumm Patrick , Stange Annette , Marten Irene , Bauer Hubert , Ache Peter , Matschi Susanne , Liese Anja , Al-Rasheid Khaled A. S. , Romeis Tina , Hedrich Rainer
Published: December 2009

In response to drought stress the phytohormone ABA (abscisic acid) induces stomatal closure and, therein, activates guard cell anion channels in a calcium-dependent as well as-independent manner. Two key components of the ABA signaling pathway are the protein kinase OST1 (open stomata 1) and the protein phosphatase ABI1 (ABA insensitive 1). The recently identified guard cell anion channel SLAC1 appeared to be the key ion channel in this signaling pathway but remained electrically silent when expressed heterologously. Using split YFP assays, we identified OST1 as an interaction partner of SLAC1 and ABI1. Upon coexpression of SLAC1 with OST1 in
Xenopus
oocytes, SLAC1-related anion currents appeared similar to those observed in guard cells. Integration of ABI1 into the SLAC1/OST1 complex, however, prevented SLAC1 activation. Our studies demonstrate that SLAC1 represents the slow, deactivating, weak voltage-dependent anion channel of guard cells controlled by phosphorylation/dephosphorylation.
IL-17-producing T cells can augment autoantibody-induced arthritis
Authors: Jacobs Jonathan P. , Wu Hsin-Jung , Benoist Christophe , Mathis Diane
Published: December 2009

Rheumatoid arthritis is a T lymphocyte-mediated disorder, but the precise nature of T cell involvement remains unclear. In the K/BxN mouse model of inflammatory arthritis, T cells initiate disease by providing help to B cells to produce arthritogenic autoantibodies. Here, we have characterized an additional, nonhumoral role for T cells in promoting autoantibody-induced arthritis. Autoreactive KRN T cells introduced either by direct transfer or bone marrow transplantation into B-cell-deficient hosts enhanced K/BxN serum-transferred arthritis, an effect that was dependent on expression of the cognate MHC-molecule/peptide complex. The T cell influence was dependent on interleukin (IL)-17; in contrast, standard serum-transferred arthritis, unenhanced by the addition of T cells, was unaffected by IL-17 neutralization. An IL-17-producing population of transferred KRN T cells was identified and found to be supported by the cotransfer of arthritogenic autoantibodies. IL-17-producing KRN T cells were enriched in inflamed joints of K/BxN mice, suggesting either selective recruitment or preferential differentiation. These results demonstrate the potential for autoreactive T cells to play two roles in the development of arthritis, both driving the production of pathogenic autoantibodies and bolstering the subsequent inflammatory cascade dependent on the innate immune system.
Impairment of developmental stem cell-mediated striatal neurogenesis and pluripotency genes in a knock-in model of Huntington's disease
Authors: Molero Aldrin E. , Gokhan Solen , Gonzalez Sara , Feig Jessica L. , Alexandre Lucien C. , Mehler Mark F.
Published: December 2009

The pathogenesis of Huntington's disease (HD) remains elusive. The identification of increasingly early pathophysiological abnormalities in HD suggests the possibility that impairments of striatal medium spiny neuron (MSN) specification and maturation may underlie the etiology of HD. In fact, we demonstrate that HD knock-in (Hdh-Q111) mice exhibited delayed acquisition of early striatal cytoarchitecture with aberrant expression of progressive markers of MSN neurogenesis (Islet1, DARPP-32, mGluR1, and NeuN). Hdh-Q111 striatal progenitors also displayed delayed cell cycle exit between E13.5–15.5 (BrdU birth-dating) and an enhanced fraction of abnormal cycling cells in association with expansion of the pool of intermediate progenitors and over expression of the core pluripotency (PP) factor, Sox2. Clonal analysis further revealed that Hdh-Q111 neural stem cells (NSCs) displayed: impaired lineage restriction, reduced proliferative potential, enhanced late-stage self-renewal, and deregulated MSN subtype specification. Further, our analysis revealed that in addition to Sox2, the core PP factor, Nanog is expressed within the striatal generative and mantle regions, and in Hdh-Q111 embryos the fraction of Nanog-expressing MSN precursors was substantially increased. Moreover, compared to Hdh-Q18 embryos, the Hdh-Q111 striatal anlagen exhibited significantly higher levels of the essential PP cofactor, Stat3. These findings suggest that Sox2 and Nanog may play roles during a selective window of embryonic brain maturation, and alterations of these factors may, in part, be responsible for mediating the aberrant program of Hdh-Q111 striatal MSN specification and maturation. We propose that these HD-associated developmental abnormalities might compromise neuronal homeostasis and subsequently render MSNs more vulnerable to late life stressors.
Deletion of phospholipase C β4 in thalamocortical relay nucleus leads to absence seizures
Authors: Cheong Eunji , Zheng Yihong , Lee Kyoobin , Lee Jungryun , Kim Seongwook , Sanati Maryam , Lee Sukyung , Kim Yeon-Soo , Shin Hee-Sup
Published: December 2009

Absence seizures are characterized by cortical spike-wave discharges (SWDs) on electroencephalography, often accompanied by a shift in the firing pattern of thalamocortical (TC) neurons from tonic to burst firing driven by T-type Ca2+currents. We recently demonstrated that the phospholipase C β4 (PLCβ4) pathway tunes the firing mode of TC neurons via the simultaneous regulation of T- and L-type Ca2+currents, which prompted us to investigate the contribution of TC firing modes to absence seizures. PLCβ4-deficient TC neurons were readily shifted to the oscillatory burst firing mode after a slight hyperpolarization of membrane potential. TC-limited knockdown as well as whole-animal knockout of PLCβ4 induced spontaneous SWDs with simultaneous behavioral arrests and increased the susceptibility to drug-induced SWDs, indicating that the deletion of thalamic PLCβ4 leads to the genesis of absence seizures. The SWDs were effectively suppressed by thalamic infusion of a T-type, but not an L-type, Ca2+channel blocker. These results reveal a primary role of TC neurons in the genesis of absence seizures and provide strong evidence that an alteration of the firing property of TC neurons is sufficient to generate absence seizures. Our study presents PLCβ4-deficient mice as a potential animal model for absence seizures.
CRM1 mediates nuclear-cytoplasmic shuttling of mature microRNAs
Authors: Castanotto Daniela , Lingeman Robert , Riggs Arthur D. , Rossi John J.
Published: December 2009

Drosha-processed microRNAs (miRNAs) have been shown to be exported from the nucleus to the cytoplasm by Exportin 5, where they are processed a second time to generate mature miRNAs. In this work we show that miRNAs also use CRM1 for nuclear-cytoplasmic shuttling. Inhibition of CRM1 by Leptomycin B results in nuclear accumulation of miRNA guide sequences. Nuclear to cytoplasmic transport can be actively competed by synthetic small interfering RNAs, indicating that this pathway is shared by different classes of processed small RNAs. We also find that CRM1 coimmunoprecipitates with Ago-1, Ago-2, Topo2α, EzH2, and Mta, consistent with a role of Argonautes and small RNAs in chromatin remodeling.
Love Gone Wrong, Then Right Again: Male/Female Dynamics in the Bahrām Gūr–Slave Girl Story
Authors: Gabbay Alyssa
Published: December 2009

This article examines male/female dynamics in three versions of the classical story of the Sassanian prince Bahrām Gūr and his lyre-playing slave girl: that of the Shāhnāma of Firdawsī, the Haft Paykar of Nizāmī Ganjavī, and the Hasht Bihisht of Amīr Khusraw. It argues that each version provides progressively more positive depictions of intergender dynamics, ones that are contingent upon more egalitarian understandings of the male/female dichotomy. The later authors destabilize the categories of “male” and “female,” equalizing and even uniting the dichotomous pairs, so that men and women draw nearer to each other in qualities rather than remaining in their usual polarized positions. In the Hasht Bihisht, moreover, we witness a reversal of hierarchies in which traditionally feminine qualities receive preference over masculine virtues—an act that suggests fresh possibilities for harmonious interactions between the sexes.
Poetics and Eros in Early Modern Persia:The Lovers’ ConfectionandThe Glorious Epistleby Muhtasham Kāshānī
Authors: Losensky Paul
Published: December 2009

The poet Muhtasham Kāshānī (d. 1588) is today known primarily for his strophic elegy on the martyrdom of Imam Husayn at Karbalā, but such devotional poems make up only a tiny fraction of large oeuvre. Far more substantial are two works of a very different tenor,Nuql-i ‘Ushshāq (The Lover's Confection)andRisāla-yi Jalāliyya (The Glorious Epistle). Using an innovative combination of prose and poetry, these works tell the story of the poet-narrator's stormy affairs with, respectively, an upper-class courtesan and a footman attached to a nobleman's house. As part of the larger literary movement known as themaktab-i vuqū‘or “realist school,” these purported autobiographical accounts of Muhtasham's amorous adventures reveal a sophisticated culture of eros and desire that differs strikingly from the usual representations of the state of literature and the arts under Shah Tahmāsp. After situating these works in their historical, literary, and cultural contexts, the article turns to a close analysis of an extended passage from each work to show how Muhtasham integrates lyric poetry, narrative, and setting to depict the pursuit of desire in the urbane world of early modern Persia.
Forbidden Love, Persianate Style: Re-reading Tales of Iranian Poets and Mughal Patrons
Authors: Sharma Sunil
Published: December 2009

The patronage system at the Mughal court drew many Safavid poets and men of learning to India who interacted with Indians at various levels. In an unusual case, the young Iranian poet ‘Urfī's attachment to his patron, Prince Salīm (later Emperor Jahāngīr), was interpreted by some as more than merely professional and the poet's death at a young age gave rise to speculations of intrigue. Mughal princesses were also actively involved in the literary scene of the time. In another instance, the association of Princess Zībunnisa, daughter of the Emperor Awrangzīb, with Persian poets was sometimes personal, leading to gossip and scandal about her. It turns out that in both cases stories about the sexual aspects of the relationships between Mughal patrons and Iranian poets arose in the eighteenth century and are more reflective of the concerns of the literary culture of that period. This paper explores the power and gender dynamics of these poet–patron relationships in the context of the general Iranian–Indian tension at the Mughal court and a highly developed and creative tradition of crafting biographical accounts.
Out‐of‐school learning: The uneven distribution of school provision and local authority support
Authors: Taylor Chris , Power Sally , Rees Gareth
Published: December 2009

A significant volume of research demonstrates that out‐of‐school learning activities enhance student development in terms of cognitive, affective and social outcomes. However, there is also evidence that the opportunity to engage in these activities has been severely reduced in recent years. This paper explores the extent to which the provision of such opportunities is unevenly distributed—spatially and institutionally. The paper draws on research from two recently completed projects: one charting the distribution, attributes and vulnerability of local authority outdoor education centres across England and the other exploring variations in provision and participation in out‐of‐school learning within secondary schools throughout the UK. The paper highlights the uneven, precarious and uncertain nature of such activities and demonstrates that important regional and structural variations in the support and provision of opportunities for such activities by local authorities appear to have an important role in determining the provision of activities at the level of the schools.