bluuebunny/crossref_metadata_2025 huggingface dataset:
Resistive switching behavior of Pt/Mg0.2Zn0.8O/Pt devices for nonvolatile memory applications
Authors: Chen Xinman , Wu Guangheng , Bao Dinghua
Published: September 2008

Highly c-axis oriented Mg0.2Zn0.8O thin films with hexagonal structure were prepared on Pt/TiO2/SiO2/Si substrates by sol-gel spin coating technique. The Pt/Mg0.2Zn0.8O/Pt devices showed a reversible and steady resistance switching characteristic. The resistance switching from low resistance state (LRS) to high resistance state (HRS) with a resistance ratio of HRS to LRS of about 25 was achieved at a voltage of as low as 0.65 V. The dominant conduction mechanisms of LRS and HRS were explained by Ohmic behavior and trap-controlled space charge limited current, respectively. Furthermore, formation of conducting filaments in LRS was suggested. This study indicates that the Pt/Mg0.2Zn0.8O/Pt device may be a promising candidate for memristor applications.
A study of capacitance-voltage curve narrowing effect in capacitive microelectromechanical switches
Authors: Olszewski Zbigniew , Duane Russell , O’Mahony Conor
Published: September 2008

In this letter, we report on the capacitance-voltage (C-V) curve narrowing effect, which occurs in the oxide-based microelectromechanical switches that are subjected to dc bias stress for a prolonged period of time. The narrowing effect for the noncontact dc bias stress condition is shown, which proves that membrane-to-dielectric contact is not needed for narrowing to occur. It is also shown that neither mechanical degradation nor charge trapping due to dielectric conduction or air ionization is solely responsible for the C-V instabilities reported in the literature.
Piezoelectric K0.5Na0.5NbO3 thick films derived from polyvinylpyrrolidone-modified chemical solution deposition
Authors: Wang Lingyan , Yao Kui , Ren Wei
Published: September 2008

Lead-free K0.5Na0.5NbO3 (KNN) ferroelectric films with enhanced thickness of 3.5 μm were prepared by a polyvinylpyrrolidone-modified chemical solution deposition method. A single perovskite phase with a dense morphology and (100) orientation was obtained at relatively low annealing temperature of 600 °C. A large effective piezoelectric coefficient d33, of 61 pm/V was demonstrated at 100 kHz without considering the substrate clamping effect. A well-saturated polarization hysteresis loop was obtained with a high remnant polarization Pr of 16.4 μC/cm2. These results showed that KNN is a promising lead-free piezoelectric film candidate, and that crystallizing the film at low processing temperature to obtain (100) orientation and dense morphology is critical to achieving excellent ferroelectric and piezoelectric properties.
High-resolution x-ray structure of human aquaporin 5
Authors: Horsefield Rob , Nordén Kristina , Fellert Maria , Backmark Anna , Törnroth-Horsefield Susanna , Terwisscha van Scheltinga Anke C. , Kvassman Jan , Kjellbom Per , Johanson Urban , Neutze Richard
Published: September 2008

Human aquaporin 5 (HsAQP5) facilitates the transport of water across plasma membranes and has been identified within cells of the stomach, duodenum, pancreas, airways, lungs, salivary glands, sweat glands, eyes, lacrimal glands, and the inner ear. AQP5, like AQP2, is subject to posttranslational regulation by phosphorylation, at which point it is trafficked between intracellular storage compartments and the plasma membrane. Details concerning the molecular mechanism of membrane trafficking are unknown. Here we report the x-ray structure of HsAQP5 to 2.0-Å resolution and highlight structural similarities and differences relative to other eukaryotic aquaporins. A lipid occludes the putative central pore, preventing the passage of gas or ions through the center of the tetramer. Multiple consensus phosphorylation sites are observed in the structure and their potential regulatory role is discussed. We postulate that a change in the conformation of the C terminus may arise from the phosphorylation of AQP5 and thereby signal trafficking.
Dopamine transporter/syntaxin 1A interactions regulate transporter channel activity and dopaminergic synaptic transmission
Authors: Carvelli Lucia , Blakely Randy D. , DeFelice Louis J.
Published: September 2008

The
Caenorhabditis elegans (C. elegans)
dopamine (DA) transporter (DAT-1) regulates DA signaling through efficient DA reuptake following synaptic release. In addition to its DA transport function, DAT-1 generates detectible DA-gated currents that may influence neuronal excitability. Previously, we provided evidence that single Cl-channel events underlie DAT-1 currents. In these studies, we identified a distinct population of altered DAT-1 currents arising from DAT-1 transgenic constructs bearing an N-terminal GFP fusion. The presence of these channels suggested disruption of an endogenous regulatory mechanism that modulates occupancy of DAT-1 channel states. A leading candidate for such a regulator is the SNARE protein syntaxin 1A (Syn1A), previously found to interact with homologous transporters through N-terminal interactions. Here we establish that UNC-64 (
C. elegans
Syn1A homologue) associates with DAT-1 and suppresses transporter channel properties. In contrast, GFP::DAT-1 is unable to form stable transporter/UNC-64 complexes that limit channel states. Although DAT-1 and GFP::DAT-1 expressing DA neurons exhibit comparable DA uptake, GFP::DAT-1 animals exhibit swimming-induced paralysis (SWIP), a phenotype associated with excess synaptic DA release and spillover. We propose that loss of UNC-64/DAT-1 interactions leads to enhanced synaptic DA release, providing a novel mechanism for DA neuron sensitization that may be relevant to mechanisms of DA-associated disorders.
Elucidation of phenotypic adaptations: Molecular analyses of dim-light vision proteins in vertebrates
Authors: Yokoyama Shozo , Tada Takashi , Zhang Huan , Britt Lyle
Published: September 2008

Vertebrate ancestors appeared in a uniform, shallow water environment, but modern species flourish in highly variable niches. A striking array of phenotypes exhibited by contemporary animals is assumed to have evolved by accumulating a series of selectively advantageous mutations. However, the experimental test of such adaptive events at the molecular level is remarkably difficult. One testable phenotype, dim-light vision, is mediated by rhodopsins. Here, we engineered 11 ancestral rhodopsins and show that those in early ancestors absorbed light maximally (λ
max
) at 500 nm, from which contemporary rhodopsins with variable λ
max
s of 480–525 nm evolved on at least 18 separate occasions. These highly environment-specific adaptations seem to have occurred largely by amino acid replacements at 12 sites, and most of those at the remaining 191 (≈94%) sites have undergone neutral evolution. The comparison between these results and those inferred by commonly-used parsimony and Bayesian methods demonstrates that statistical tests of positive selection can be misleading without experimental support and that the molecular basis of spectral tuning in rhodopsins should be elucidated by mutagenesis analyses using ancestral pigments.
A microRNA DNA methylation signature for human cancer metastasis
Authors: Lujambio Amaia , Calin George A. , Villanueva Alberto , Ropero Santiago , Sánchez-Céspedes Montserrat , Blanco David , Montuenga Luis M. , Rossi Simona , Nicoloso Milena S. , Faller William J. , Gallagher William M. , Eccles Suzanne A. , Croce Carlo M. , Esteller Manel
Published: September 2008

MicroRNAs (miRNAs) are small, noncoding RNAs that can contribute to cancer development and progression by acting as oncogenes or tumor suppressor genes. Recent studies have also linked different sets of miRNAs to metastasis through either the promotion or suppression of this malignant process. Interestingly, epigenetic silencing of miRNAs with tumor suppressor features by CpG island hypermethylation is also emerging as a common hallmark of human tumors. Thus, we wondered whether there was a miRNA hypermethylation profile characteristic of human metastasis. We used a pharmacological and genomic approach to reveal this aberrant epigenetic silencing program by treating lymph node metastatic cancer cells with a DNA demethylating agent followed by hybridization to an expression microarray. Among the miRNAs that were reactivated upon drug treatment, miR-148a, miR-34b/c, and miR-9 were found to undergo specific hypermethylation-associated silencing in cancer cells compared with normal tissues. The reintroduction of miR-148a and miR-34b/c in cancer cells with epigenetic inactivation inhibited their motility, reduced tumor growth, and inhibited metastasis formation in xenograft models, with an associated down-regulation of the miRNA oncogenic target genes, such as C-MYC, E2F3, CDK6, and TGIF2. Most important, the involvement of miR-148a, miR-34b/c, and miR-9 hypermethylation in metastasis formation was also suggested in human primary malignancies (
n
= 207) because it was significantly associated with the appearance of lymph node metastasis. Our findings indicate that DNA methylation-associated silencing of tumor suppressor miRNAs contributes to the development of human cancer metastasis.
Antagonism of dopamine D2 receptor/β-arrestin 2 interaction is a common property of clinically effective antipsychotics
Authors: Masri Bernard , Salahpour Ali , Didriksen Michael , Ghisi Valentina , Beaulieu Jean-Martin , Gainetdinov Raul R. , Caron Marc G.
Published: September 2008

Since the unexpected discovery of the antipsychotic activity of chlorpromazine, a variety of therapeutic agents have been developed for the treatment of schizophrenia. Despite differences in their activities at various neurotransmitter systems, all clinically effective antipsychotics share the ability to interact with D2 class dopamine receptors (D2R). D2R mediate their physiological effects via both G protein-dependent and independent (β-arrestin 2-dependent) signaling, but the role of these D2R-mediated signaling events in the actions of antipsychotics remains unclear. We demonstrate here that while different classes of antipsychotics have complex pharmacological profiles at G protein-dependent D2R long isoform (D2
L
R) signaling, they share the common property of antagonizing dopamine-mediated interaction of D2
L
R with β-arrestin 2. Using two cellular assays based on a bioluminescence resonance energy transfer (BRET) approach, we demonstrate that a series of antipsychotics including haloperidol, clozapine, aripiprazole, chlorpromazine, quetiapine, olanzapine, risperidone, and ziprasidone all potently antagonize the β-arrestin 2 recruitment to D2
L
R induced by quinpirole. However, these antipsychotics have various effects on D2
L
R mediated G
i/o
protein activation ranging from inverse to partial agonists and antagonists with highly variable efficacies and potencies at quinpirole-induced cAMP inhibition. These results suggest that the different classes of clinically effective antipsychotics share a common molecular mechanism involving inhibition of D2
L
R/β-arrestin 2 mediated signaling. Thus, selective targeting of D2
L
R/β-arrestin 2 interaction and related signaling pathways may provide new opportunities for antipsychotic development.
The genetic expectations of a protracted model for the origins of domesticated crops
Authors: Allaby Robin G. , Fuller Dorian Q. , Brown Terence A.
Published: September 2008

Until recently, domestication has been interpreted as a rapid process with little predomestication cultivation and a relatively rapid rise of the domestication syndrome. This interpretation has had a profound effect on the biological framework within which investigations into crop origins have been carried out. A major underlying assumption has been that artificial selection pressures were substantially stronger than natural selection pressures, resulting in genetic patterns of diversity that reflect genetic independence of geographic localities. Recent archaeobotanical evidence has overturned the notion of a rapid transition, resulting in a protracted model that undermines these assumptions. Conclusions of genome-wide multilocus studies remain problematic in their support of a rapid-transition model by indicating that domesticated crops appear to be associated by monophyly with only a single geographic locality. Simulations presented here resolve this conflict, indicating that the results observed in such studies are inevitable over time at a rate that is largely influenced by the long-term population size. Counterintuitively, multiple origin crops are shown to be more likely to produce monophyletic clades than crops of a single origin. Under the protracted transition, the importance of the rise of the domestication syndrome becomes paramount in producing the patterns of genetic diversity from which crop origins may be deduced. We identify four different interacting levels of organization that now need to be considered to track crop origins from modern genetic diversity, making crop origins a problem that could be addressed through system-based approaches.
Green chemistry for chemical synthesis
Authors: Li Chao-Jun , Trost Barry M.
Published: September 2008

Green chemistry for chemical synthesis addresses our future challenges in working with chemical processes and products by inventing novel reactions that can maximize the desired products and minimize by-products, designing new synthetic schemes and apparati that can simplify operations in chemical productions, and seeking greener solvents that are inherently environmentally and ecologically benign.
Transplantation of a myelodysplastic syndrome by a long-term repopulating hematopoietic cell
Authors: Chung Yang Jo , Choi Chul Won , Slape Christopher , Fry Terry , Aplan Peter D.
Published: September 2008

The myelodysplastic syndromes (MDS) comprise a group of premalignant hematologic disorders characterized by ineffective hematopoiesis, dysplasia, and transformation to acute myeloid leukemia (AML). Although it is well established that many malignancies can be transplanted, there is little evidence to demonstrate that a premalignant disease entity, such as MDS or colonic polyps, can be transplanted and subsequently undergo malignant transformation
in vivo
. Using mice that express a
NUP98-HOXD13
(
NHD13
) transgene in hematopoietic tissues, we show that a MDS can be transplanted to WT recipients. Recipients of the MDS bone marrow displayed all of the critical features of MDS, including peripheral blood cytopenias, dysplasia, and transformation to AML. Even when transplanted with a 10-fold excess of WT cells, the NHD13 cells outcompeted the WT cells over a 38-week period. Limiting-dilution experiments demonstrated that the frequency of the cell that could transmit the disease was ≈1/6,000–1/16,000 and that the MDS was also transferable to secondary recipients as a premalignant condition. Transformation to AML in primary transplant recipients was generally delayed (46–49 weeks after transplant); however, 6 of 10 secondary transplant recipients developed AML. These findings demonstrate that MDS originates in a transplantable, premalignant, long-term repopulating, MDS-initiating cell.
Thermostability of model protocell membranes
Authors: Mansy Sheref S. , Szostak Jack W.
Published: September 2008

The earliest cells may have consisted of a self-replicating genetic polymer encapsulated within a self-replicating membrane vesicle. Here, we show that vesicles composed of simple single-chain amphiphiles such as fatty acids, fatty alcohols, and fatty-acid glycerol esters are extremely thermostable and retain internal RNA and DNA oligonucleotides at temperatures ranging from 0°C to 100°C. The strands of encapsulated double-stranded DNA can be separated by denaturation at high temperature while being retained within vesicles, implying that strand separation in primitive protocells could have been mediated by thermal fluctuations without the loss of genetic material from the protocell. At elevated temperatures, complex charged molecules such as nucleotides cross fatty-acid-based membranes very rapidly, suggesting that high temperature excursions may have facilitated nutrient uptake before the evolution of advanced membrane transporters. The thermostability of these membranes is consistent with the spontaneous replication of encapsulated nucleic acids by the alternation of template-copying chemistry at low temperature with strand-separation and nutrient uptake at high temperature.
Crystal structure of bovine mitochondrial factor B at 0.96-Å resolution
Authors: Lee John K. , Belogrudov Grigory I. , Stroud Robert M.
Published: September 2008

Coupling factor B (FB) is a mitochondrial inner membrane polypeptide that facilitates the energy-driven catalysis of ATP synthesis in animal mitochondria by blocking a proton leak across the membrane. Here, we report the crystal structure of the bovine mitochondrial FB mutant with Gly-3–Glu substitution determined at a resolution of 0.96 Å and that of the WT polypeptide at a resolution of 2.9 Å. The structure reveals an oblong, oval-shaped molecule with a unique globular N-terminal domain that is proposed to be the membrane anchor domain and the capping region to the C-terminal leucine-rich repeats domain. A short N-terminal α-helix, which extends away from the molecule's body, is suggestive of functioning as an anchor for FB to the matrix side of the mitochondrial inner membrane. Identification of a bound Mg
2+
ion reveals that FB is a metalloprotein. We also report the cocrystal structures of FB bound with phenylarsine oxide and Cd
2+
, two known inhibitors of the FB coupling activity.
Characterization of reconnecting vortices in superfluid helium
Authors: Bewley Gregory P. , Paoletti Matthew S. , Sreenivasan Katepalli R. , Lathrop Daniel P.
Published: September 2008

When two vortices cross, each of them breaks into two parts and exchanges part of itself for part of the other. This process, called vortex reconnection, occurs in classical and superfluids, and in magnetized plasmas and superconductors. We present the first experimental observations of reconnection between quantized vortices in superfluid helium. We do so by imaging micrometer-sized solid hydrogen particles trapped on quantized vortex cores and by inferring the occurrence of reconnection from the motions of groups of recoiling particles. We show that the distance separating particles on the just-reconnected vortex lines grows as a power law in time. The average value of the scaling exponent is approximately ½, consistent with the self-similar evolution of the vortices.
Dynamics of static friction between steel and silicon
Authors: Yang Zhiping , Zhang H. P. , Marder M.
Published: September 2008

We conducted experiments in which steel and silicon or quartz are clamped together. Even with the smallest tangential forces we could apply, we always found reproducible sliding motions on the nanometer scale. The velocities we study are thousands of times smaller than in previous investigations. The samples first slide and then lock up even when external forces hold steady. One might call the result “slip-stick” friction. We account for the results with a phenomenological theory that results from considering the rate and state theory of dynamic friction at low velocities. Our measurements lead us to set the instantaneous coefficient of static friction that normally enters rate and state theories to zero.
Dynamic charge interactions create surprising rigidity in the ER/K α-helical protein motif
Authors: Sivaramakrishnan Sivaraj , Spink Benjamin J. , Sim Adelene Y. L. , Doniach Sebastian , Spudich James A.
Published: September 2008

Protein α-helices are ubiquitous secondary structural elements, seldom considered to be stable without tertiary contacts. However, amino acid sequences in proteins that are based on alternating repeats of four glutamic acid (E) residues and four positively charged residues, a combination of arginine (R) and lysine (K), have been shown to form stable α-helices in a few proteins, in the absence of tertiary interactions. Here, we find that this ER/K motif is more prevalent than previously reported, being represented in proteins of diverse function from archaea to humans. By using molecular dynamics (MD) simulations, we characterize a dynamic pattern of side-chain interactions that extends along the backbone of ER/K α-helices. A simplified model predicts that side-chain interactions alone contribute substantial bending rigidity (0.5 pN/nm) to ER/K α-helices. Results of small-angle x-ray scattering (SAXS) and single-molecule optical-trap analyses are consistent with the high bending rigidity predicted by our model. Thus, the ER/K α-helix is an isolated secondary structural element that can efficiently span long distances in proteins, making it a promising tool in designing synthetic proteins. We propose that the significant rigidity of the ER/K α-helix can help regulate protein function, as a force transducer between protein subdomains.
Apoptotic function of human PMS2 compromised by the nonsynonymous single-nucleotide polymorphic variant R20Q
Authors: Marinovic-Terzic Ivana , Yoshioka-Yamashita Atsuko , Shimodaira Hideki , Avdievich Elena , Hunton Irina C. , Kolodner Richard D. , Edelmann Winfried , Wang Jean Y. J.
Published: September 2008

Mismatch repair (MMR) corrects replication errors during DNA synthesis. The mammalian MMR proteins also activate cell cycle checkpoints and apoptosis in response to persistent DNA damage. MMR-deficient cells are resistant to cisplatin, a DNA cross-linking agent used in chemotherapy, because of impaired activation of apoptotic pathways. It is shown that postmeiotic segregation 2 (PMS2), an MMR protein, is required for cisplatin-induced activation of p73, a member of the p53 family of transcription factors with proapoptotic activity. The human
PMS2
is highly polymorphic, with at least 12 known nonsynonymous codon changes identified. We show here that the PMS2(R20Q) variant is defective in activating p73-dependent apoptotic response to cisplatin. When expressed in
Pms2
-deficient mouse fibroblasts, human PMS2(R20Q) but not PMS2 interfered with the apoptotic response to cisplatin. Correspondingly, PMS2 but not PMS2(R20Q) enhanced the cytotoxic effect of cisplatin measured by clonogenic survival. Because PMS2(R20Q) lacks proapoptotic activity, this polymorphic allele may modulate tumor responses to cisplatin among cancer patients.
The neonate brain detects speech structure
Authors: Gervain Judit , Macagno Francesco , Cogoi Silvia , Peña Marcela , Mehler Jacques
Published: September 2008

What are the origins of the efficient language learning abilities that allow humans to acquire their mother tongue in just a few years very early in life? Although previous studies have identified different mechanisms underlying the acquisition of auditory and speech patterns in older infants and adults, the earliest sensitivities remain unexplored. To address this issue, we investigated the ability of newborns to learn simple repetition-based structures in two optical brain-imaging experiments. In the first experiment, 22 neonates listened to syllable sequences containing immediate repetitions (ABB; e.g., “mubaba,” “penana”), intermixed with random control sequences (ABC; e.g., “mubage,” “penaku”). We found increased responses to the repetition sequences in the temporal and left frontal areas, indicating that the newborn brain differentiated the two patterns. The repetition sequences evoked greater activation than the random sequences during the first few trials, suggesting the presence of an automatic perceptual mechanism to detect repetitions. In addition, over the subsequent trials, activation increased further in response to the repetition sequences but not in response to the random sequences, indicating that recognition of the ABB pattern was enhanced by repeated exposure. In the second experiment, in which nonadjacent repetitions (ABA; e.g., “bamuba,” “napena”) were contrasted with the same random controls, no discrimination was observed. These findings suggest that newborns are sensitive to certain input configurations in the auditory domain, a perceptual ability that might facilitate later language development.
Anomalous high-pressure behavior of amorphous selenium from synchrotron x-ray diffraction and microtomography
Authors: Liu Haozhe , Wang Luhong , Xiao Xianghui , De Carlo Francesco , Feng Ji , Mao Ho-kwang , Hemley Russell J.
Published: September 2008

The high-pressure behavior of amorphous selenium has been investigated with time-resolved diamond anvil cell synchrotron x-ray diffraction and computed microtomography techniques. A two-step dynamic crystallization process is observed in which the monoclinic phase crystallized from the amorphous selenium and gradually converted to the trigonal phase, thereby explaining previously observed anomalous changes in electrical conductivity of the material under pressure. The crystallization of this elemental system involves local topological fluctuations and results in an unusual pressure-induced volume expansion. The metastability of the phases involved in the transition accounts for this phenomenon. The results demonstrate the use of pressure to control and directly monitor the relative densities and energetics of phases to create new phases from highly metastable states. The microtomographic technique developed here represents a method for determination of the equations of state of amorphous materials at extreme pressures and temperatures.
Highly efficient transient gene expression and gene targeting in primate embryonic stem cells with helper-dependent adenoviral vectors
Authors: Suzuki Keiichiro , Mitsui Kaoru , Aizawa Emi , Hasegawa Kouichi , Kawase Eihachiro , Yamagishi Toshiyuki , Shimizu Yoshihiko , Suemori Hirofumi , Nakatsuji Norio , Mitani Kohnosuke
Published: September 2008

Human embryonic stem (hES) cells are regarded as a potentially unlimited source of cellular materials for regenerative medicine. For biological studies and clinical applications using primate ES cells, the development of a general strategy to obtain efficient gene delivery and genetic manipulation, especially gene targeting via homologous recombination (HR), would be of paramount importance. However, unlike mouse ES (mES) cells, efficient strategies for transient gene delivery and HR in hES cells have not been established. Here, we report that helper-dependent adenoviral vectors (HDAdVs) were able to transfer genes in hES and cynomolgus monkey (
Macaca fasicularis
) ES (cES) cells efficiently. Without losing the undifferentiated state of the ES cells, transient gene transfer efficiency was ≈100%. Using HDAdVs with homology arms, approximately one out of 10 chromosomal integrations of the vector was via HR, whereas the rate was only ≈1% with other gene delivery methods. Furthermore, in combination with negative selection, ≈45% of chromosomal integrations of the vector were targeted integrations, indicating that HDAdVs would be a powerful tool for genetic manipulation in hES cells and potentially in other types of human stem cells, such as induced pluripotent stem (iPS) cells.
Periplasmic orientation of nascent lipid A in the inner membrane of an
Escherichia coli
LptA mutant
Authors: Ma Bing , Reynolds C. Michael , Raetz Christian R. H.
Published: September 2008

The core-lipid A domain of
Escherichia coli
lipopolysaccharide (LPS) is synthesized on the inner surface of the inner membrane (IM) and flipped to its outer surface by the ABC transporter MsbA. Recent studies with deletion mutants implicate the periplasmic protein LptA, the cytosolic protein LptB, and the IM proteins LptC, LptF, and LptG in the subsequent transport of nascent LPS to the outer membrane (OM), where the LptD/LptE complex flips LPS to the outer surface. We have isolated a temperature-sensitive mutant (MB1) harboring the S22C and Q111P substitutions in LptA. MB1 stops growing after 30 min at 42°C.
32
P
i
and [
35
S]methionine labeling show that export of newly synthesized phospholipids and proteins is not severely impaired, but export of LPS is defective. Using the lipid A 1-phosphatase LpxE as a periplasmic IM marker and the lipid A 3-
O
-deacylase PagL as an OM marker, we show that core-lipid A reaches the periplasmic side of the IM at 42°C in MB1 but not the outer surface of the OM. Electron microscopy of MB1 reveals dense periplasmic material and a smooth OM at 42°C, consistent with a role for LptA in shuttling LPS across the periplasm.
Liberalisation of the Gold Mining Sector in Burkina Faso
Authors: Luning Sabine
Published: September 2008

Since the liberalisation of the gold mining sector in the 1990s, the state of Burkina Faso has the task of allotting exploration and exploitation permits to private companies. International junior companies are exploring vast concessions in Burkina, and publish promising prospects on the internet. Scrutinising the presence of (inter)national companies both on the web and on the ground, the article shows how a set of concessions constitutes a ‘field’, defined as a system of social positions structured in terms of power relations. Concessions bring together a wide range of professionals in mining: potential investors, international companies, Burkinabe entrepreneurs and artisanal miners. The article describes how legal distinctions affect the power structure of working arrangements on one particular group of exploration permits in the central part of Burkina, currently held by the Canadian company High River Gold: the Bissa permit Group. It examines what happens on the ground when companies are allotted formal titles, whereas artisanal miners can at best aspire to obtain marginal places for their informal practices.
Complex Surgical Site Infections and the Devilish Details of Risk Adjustment: Important Implications for Public Reporting
Authors: Anderson Deverick J. , Chen Luke F. , Sexton Daniel J. , Kaye Keith S.
Published: September 2008

Objective.

To validate the National Nosocomial Infection Surveillance (NNIS) risk index as a tool to account for differences in case mix when reporting rates of complex surgical site infection (SSI).

Design.

Prospective cohort study.

Setting.

Twenty-four community hospitals in the southeastern United States.

Methods.

We identified surgical procedures performed between January 1, 2005, and June 30, 2007. The Goodman-Kruskal gamma or G statistic was used to determine the correlation between the NNIS risk index score and the rates of complex SSI (not including superficial incisional SSI). Procedure-specific analyses were performed for SSI after abdominal hysterectomy, cardiothoracic procedures, colon procedures, insertion of a hip prosthesis, insertion of a knee prosthesis, and vascular procedures.

Results.

A total of 2,257 SSIs were identified during the study period (overall rate, 1.19 SSIs per 100 procedures), of which 1,093 (48.4%) were complex (0.58 complex SSIs per 100 procedures). There were 45 complex SSIs identified following 7,032 abdominal hysterectomies (rate, 0.64 SSIs per 100 procedures); 63 following 5,318 cardiothoracic procedures (1.18 SSIs per 100 procedures); 139 following 5,144 colon procedures (2.70 SSIs per 100 procedures); 63 following 6,639 hip prosthesis insertions (0.94 SSIs per 100 procedures); 73 following 9,658 knee prosthesis insertions (0.76 SSIs per 100 procedures); and 55 following 6,575 vascular procedures (0.84 SSIs per 100 procedures). All 6 procedure-specific rates of complex SSI were significantly correlated with increasing NNIS risk index score (P< .05).

Conclusions.

Some experts recommend reporting rates of complex SSI to overcome the widely acknowledged detection bias associated with superficial incisional infection. Furthermore, it is necessary to compensate for case-mix differences in patient populations, to ensure that intrahospital comparisons are meaningful. Our results indicate that the NNIS risk index is a reasonable method for the risk stratification of complex SSIs for several commonly performed procedures.
The Membrane Dynamics of Pexophagy Are Influenced by Sar1p inPichia pastoris
Authors: Schroder Laura A. , Ortiz Michael V. , Dunn William A.
Published: September 2008

Several Sec proteins including a guanosine diphosphate/guanosine triphosphate exchange factor for Sar1p have been implicated in autophagy. In this study, we investigated the role of Sar1p in pexophagy by expressing dominant-negative mutant forms of Sar1p in Pichia pastoris. When expressing sar1pT34N or sar1pH79G, starvation-induced autophagy, glucose-induced micropexophagy, and ethanol-induced macropexophagy are dramatically suppressed. These Sar1p mutants did not affect the initiation or expansion of the sequestering membranes nor the trafficking of Atg11p and Atg9p to these membranes during micropexophagy. However, the lipidation of Atg8p and assembly of the micropexophagic membrane apparatus, which are essential to complete the incorporation of the peroxisomes into the degradative vacuole, were inhibited when either Sar1p mutant protein was expressed. During macropexophagy, the expression of sar1pT34N inhibited the formation of the pexophagosome, whereas sar1pH79G suppressed the delivery of the peroxisome from the pexophagosome to the vacuole. The pexophagosome contained Atg8p in wild-type cells, but in cells expressing sar1pH79G these organelles contain both Atg8p and endoplasmic reticulum components as visualized by DsRFP-HDEL. Our results demonstrate key roles for Sar1p in both micro- and macropexophagy.
Membrane Ruffles Capture C3bi-opsonized Particles in Activated Macrophages
Authors: Patel Prerna C. , Harrison Rene E.
Published: September 2008

A widespread belief in phagocyte biology is that FcγR-mediated phagocytosis utilizes membrane pseudopods, whereas Mac-1–mediated phagocytosis does not involve elaborate plasma membrane extensions. Here we report that dynamic membrane ruffles in activated macrophages promote binding of C3bi-opsonized particles. We identify these ruffles as components of the macropinocytosis machinery in both PMA- and LPS-stimulated macrophages. C3bi-particle capture is facilitated by enrichment of high-affinity Mac-1 and the integrin-regulating protein talin in membrane ruffles. Membrane ruffle formation and C3bi-particle binding are cytoskeleton dependent events, having a strong requirement for F-actin and microtubules (MTs). MT disruption blunts ruffle formation and PMA- and LPS-induced up-regulation of surface Mac-1 expression. Furthermore, the MT motor, kinesin participates in ruffle formation implicating a requirement for intracellular membrane delivery to active membrane regions during Mac-1–mediated phagocytosis. We observed colocalization of Rab11-positive vesicles with CLIP-170, a MT plus-end binding protein, at sites of particle adherence using TIRF imaging. Rab11 has been implicated in recycling endosome dynamics and mutant Rab11 expression inhibits both membrane ruffle formation and C3bi-sRBC adherence to macrophages. Collectively these findings represent a novel membrane ruffle “capture” mechanism for C3bi-particle binding during Mac-1–mediated phagocytosis. Importantly, this work also demonstrates a strong functional link between integrin activation, macropinocytosis and phagocytosis in macrophages.
Opposing Activities of the Snx3-Retromer Complex and ESCRT Proteins Mediate Regulated Cargo Sorting at a Common Endosome
Authors: Strochlic Todd I. , Schmiedekamp Briana C. , Lee Jacqueline , Katzmann David J. , Burd Christopher G.
Published: September 2008

Endocytosed proteins are either delivered to the lysosome to be degraded or are exported from the endosomal system and delivered to other organelles. Sorting of the Saccharomyces cerevisiae reductive iron transporter, composed of the Fet3 and Ftr1 proteins, in the endosomal system is regulated by available iron; in iron-starved cells, Fet3-Ftr1 is sorted by Snx3/Grd19 and retromer into a recycling pathway that delivers it back to the plasma membrane, but when starved cells are exposed to iron, Fet3-Ftr1 is targeted to the lysosome-like vacuole and is degraded. We report that iron-induced endocytosis of Fet3-Ftr1 is independent of Fet3-Ftr1 ubiquitylation, and after endocytosis, degradation of Fet3-Ftr1 is mediated by the multivesicular body (MVB) sorting pathway. In mutant cells lacking any component of the ESCRT protein-dependent MVB sorting machinery, the Rsp5 ubiquitin ligase, or in wild-type cells expressing Fet3-Ftr1 lacking cytosolic lysyl ubiquitin acceptor sites, Fet3-Ftr1 is constitutively sorted into the recycling pathway independent of iron status. In the presence and absence of iron, Fet3-Ftr1 transits an endosomal compartment where a subunit of the MVB sorting receptor (Vps27), Snx3/Grd19, and retromer proteins colocalize. We propose that this endosome is where Rsp5 ubiquitylates Fet3-Ftr1 and where the recycling and degradative pathways diverge.
The Atg8 Conjugation System Is Indispensable for Proper Development of Autophagic Isolation Membranes in Mice
Authors: Sou Yu-shin , Waguri Satoshi , Iwata Jun-ichi , Ueno Takashi , Fujimura Tsutomu , Hara Taichi , Sawada Naoki , Yamada Akane , Mizushima Noboru , Uchiyama Yasuo , Kominami Eiki , Tanaka Keiji , Komatsu Masaaki
Published: September 2008

Autophagy is an evolutionarily conserved bulk-protein degradation pathway in which isolation membranes engulf the cytoplasmic constituents, and the resulting autophagosomes transport them to lysosomes. Two ubiquitin-like conjugation systems, termed Atg12 and Atg8 systems, are essential for autophagosomal formation. In addition to the pathophysiological roles of autophagy in mammals, recent mouse genetic studies have shown that the Atg8 system is predominantly under the control of the Atg12 system. To clarify the roles of the Atg8 system in mammalian autophagosome formation, we generated mice deficient in Atg3 gene encoding specific E2 enzyme for Atg8. Atg3-deficient mice were born but died within 1 d after birth. Conjugate formation of mammalian Atg8 homologues was completely defective in the mutant mice. Intriguingly, Atg12–Atg5 conjugation was markedly decreased in Atg3-deficient mice, and its dissociation from isolation membranes was significantly delayed. Furthermore, loss of Atg3 was associated with defective process of autophagosome formation, including the elongation and complete closure of the isolation membranes, resulting in malformation of the autophagosomes. The results indicate the essential role of the Atg8 system in the proper development of autophagic isolation membranes in mice.
An Atg4B Mutant Hampers the Lipidation of LC3 Paralogues and Causes Defects in Autophagosome Closure
Authors: Fujita Naonobu , Hayashi-Nishino Mitsuko , Fukumoto Hiromi , Omori Hiroko , Yamamoto Akitsugu , Noda Takeshi , Yoshimori Tamotsu
Published: September 2008

In the process of autophagy, a ubiquitin-like molecule, LC3/Atg8, is conjugated to phosphatidylethanolamine (PE) and associates with forming autophagosomes. In mammalian cells, the existence of multiple Atg8 homologues (referred to as LC3 paralogues) has hampered genetic analysis of the lipidation of LC3 paralogues. Here, we show that overexpression of an inactive mutant of Atg4B, a protease that processes pro-LC3 paralogues, inhibits autophagic degradation and lipidation of LC3 paralogues. Inhibition was caused by sequestration of free LC3 paralogues in stable complexes with the Atg4B mutant. In mutant overexpressing cells, Atg5- and ULK1-positive intermediate autophagic structures accumulated. The length of these membrane structures was comparable to that in control cells; however, a significant number were not closed. These results show that the lipidation of LC3 paralogues is involved in the completion of autophagosome formation in mammalian cells. This study also provides a powerful tool for a wide variety of studies of autophagy in the future.
Loss of Occludin Affects Tricellular Localization of Tricellulin
Authors: Ikenouchi Junichi , Sasaki Hiroyuki , Tsukita Sachiko , Furuse Mikio , Tsukita Shoichiro
Published: September 2008

The tricellular tight junction (tTJ) forms at the convergence of bicellular tight junctions (bTJs) where three epithelial cells meet in polarized epithelia, and it is required for the maintenance of the transepithelial barrier. Tricellulin is a four transmembrane domain protein recently identified as the first marker of tTJ, but little is known about how tricellulin is localized at tTJs. As for the molecular mechanism of association of tricellulin with tight junctions (TJs), we found that tricellulin was incorporated into claudin-based TJs independently of binding to zona occludens-1. Unexpectedly, exogenous expression of tricellulin increased cross-links of TJ strands in the plasma membrane. As for the molecular mechanisms for localization of tricellulin at tricellular junctions, we found that knockdown of occludin caused mislocalization of tricellulin to bTJs, implying that occludin supports tricellular localization of tricellulin by excluding tricellulin from bTJs.
Cdc7-Dbf4 RegulatesNDT80Transcription as Well as Reductional Segregation during Budding Yeast Meiosis
Authors: Lo Hsiao-Chi , Wan Lihong , Rosebrock Adam , Futcher Bruce , Hollingsworth Nancy M.
Published: September 2008

In budding yeast, as in other eukaryotes, the Cdc7 protein kinase is important for initiation of DNA synthesis in vegetative cells. In addition, Cdc7 has crucial meiotic functions: it facilitates premeiotic DNA replication, and it is essential for the initiation of recombination. This work uses a chemical genetic approach to demonstrate that Cdc7 kinase has additional roles in meiosis. First, Cdc7 allows expression of NDT80, a meiosis-specific transcriptional activator required for the induction of genes involved in exit from pachytene, meiotic progression, and spore formation. Second, Cdc7 is necessary for recruitment of monopolin to sister kinetochores, and it is necessary for the reductional segregation occurring at meiosis I. The use of the same kinase to regulate several distinct meiosis-specific processes may be important for the coordination of these processes during meiosis.
Structure and dynamics of odonate communities: accessing habitat, responding to risk, and enabling reproduction
Authors: Crumrine Patrick W. , Switzer Paul V. , Crowley Philip H.
Published: September 2008

This chapter highlights the key abiotic and community-level interactions that influence odonate community structure. Three important life-history based issues central to odonate communities are developed: habitat access, response to risk during the larval stage, and emergence and reproduction. Each issue is addressed by considering relevant ecological theory and identifying and reviewing empirical studies with odonates that address hypotheses raised by theoretical studies. Although numerous short-term studies at relatively small spatial scales have been conducted with odonate larvae, very little is known about the relative impacts of competition, cannibalism, predation, intraguild predation and size structure on odonate population dynamics, and community structure in natural systems. Long-term studies at multiple life history stages and levels of organization are required to generate a more complete understanding of odonate communities, and ecological communities in general.
Life-history plasticity under time stress in damselfly larvae
Authors: Stoks Robby , Johansson Frank , De Block Marjan
Published: September 2008

Animals often face time stress because they have to reach a certain stage before a certain time horizon (e.g., the onset of winter or pond drying). Damselflies react to time stress with a shortening of their development time, and often show compensatory growth to avoid a smaller size at metamorphosis. Behaviour (increased foraging) and digestive physiology (increased growth efficiency) underlie this life history plasticity. Both ecological and physiological costs of this accelerated life history have been shown: time-stressed larvae are less responsive to predators and hence suffer higher mortality by predation, and show larger mass loss during starvation and reduced investment in immune function and in energy storage. These costs may explain why time-stressed larvae suffer a reduced lifetime mating success in the adult stage.
Ecological factors limiting the distributions and abundances of Odonata
Authors: McPeek Mark A.
Published: September 2008

This chapter reviews the ecological processes that define and limit the distributions and abundances of many odonate species across ecological environments. Distributions of species among standing bodies of water seem to be limited mainly by the distributions of their predators in the larval stage (e.g., larger dragonflies and fish). Although species also show restricted distributions among flowing water habitats, much less is known about the ecological processes that constrain their distributions. Many different types of species interactions (e.g., resource abundances, competitors, predators, parasites) contribute to the limitation of local abundances. Directions for potential future research are suggested.
Migration in Odonata: a case study ofAnax junius
Authors: May Michael L. , Matthews John H.
Published: September 2008

Migration by Odonata may illuminate patterns and evolution of insect migration in general. As aquatic/aerial carnivores dragonflies differ from most migratory insects, and because they are large and diurnal, observational techniques are available that are impossible in most other insects. Geographic analysis of genetic structure and stable and radiogenic isotope composition and use of newly developed radio-tracking techniques has been applied to migration in the North American dragonfly, Anax junius. Southbound migrants move up to 2,800 km. Developmental phenology suggests early (‘resident’) and late (‘migrant’) cohorts at most sites, but these groups appear genetically identical, and the species is essentially panmictic in eastern North America. Apparently environmental cues and physiological responses to photoperiod and temperature engender migratory behaviour. Successful radio-tracking of individual A. junius has revealed alternating periods of migration and energy replenishment, and responses to wind and temperature similar to avian migration.
The use of dragonflies in the assessment and monitoring of aquatic habitats
Authors: Oertli Beat
Published: September 2008

Odonata constitute a valuable tool for various types of bioassessment and biomonitoring of aquatic habitats, such as the measure of biodiversity, the appraisal of waterbody health or integrity (including water quality and ecosystem function), the monitoring of management or restoration practices, and the detection and prediction of biological impacts of climate warming. Furthermore, they have already provided excellent data sets for hypothesis testing in ecology or evolution. An efficient sampling method for Odonata should account for the three live stages, i.e., larvae, exuviae, and adults. However, as this approach may be too expensive, most existing methods only focus on one stage. In applied issues, the adult stage is surveyed at a low cost, and is therefore useful for rapid assessments; it can serve for preliminary screening, for example when identifying local hotspots of diversity or, on the contrary, to mark degraded sites.
Interspecific interactions and premating reproductive isolation
Authors: Tynkkynen Katja , Kotiaho Janne S. , Svensson Erik I.
Published: September 2008

Two species can interact in several ways: there may occur interspecific competition or aggression, the two species may hybridize or they may interact indirectly through different predator-prey interactions. One consequence of these interactions is the evolution of premating reproductive isolation between the two species. For example, there may be divergent selection on male secondary sexual characters, which results in enhancement of premating reproductive isolation of two closely related species. This chapter focuses on two questions: firstly, how do interspecific hybridization, aggression and predation, affect premating reproductive isolation? Secondly, is reproductive isolation a direct target of selection or does it evolve as a correlated response to selection on other traits? This chapter uses Calopteryx damselflies as model organisms in this discussion, which have been under intensive study concerning these topics.