bluuebunny/crossref_metadata_2025 huggingface dataset:
93 PRODUCTION OF LIVE PIGLETS BY CRYOPRESERVATION OF IN VITRO-PRODUCED PORCINE ZYGOTES
Authors: Somfai T. , Kashiwazaki N. , Ozawa M. , Noguchi J. , Kaneko H. , Nakai M. , Maedomari N. , Nagai T. , Kikuchi K.
Published: January 2008

Successful cryopreservation of in vitro-produced porcine zygotes is reported in the present study. Follicular oocytes were collected from prepubertal gilts. They were matured (IVM), fertilized (IVF), and cultured (IVC) in vitro (Kikuchi et al. 2002 Biol. Reprod. 66, 1033–1041). Ten or 23 h after IVF, the oocytes were centrifuged at 10 000g at 37�C for 20 min to permit visualization of pronuclei. Zygotes with two or three pronuclei were selected under stereomicroscope and used for solid surface vitrification (SSV). Briefly, after equilibration in 4% ethylene glycol (EG) for 15 min, zygotes were washed in vitrification solution (35% EG, 5% polyvinyl pyrrolidone, and 0.3 m trehalose), and then dropped with about 2 µL vitrification solution onto the dry surface of aluminum foil floating on the surface of liquid nitrogen (LN2). Microdroplets were transferred into cryotubes and stored in LN2. During warming, vitrified droplets were transferred in warming solution (0.4 m trehalose) at 37�C for 1 min, and then consecutively transferred for 1-min periods into 0.2 m, 0.1 m, or 0.05 m trehalose solutions. Survival of vitrified/warmed zygotes was determined by their morphology. To assess their developmental competence, vitrified (SSV), cryoprotectant-treated (CT), and untreated (control) zygotes were cultured in vitro for 6 days. There was no difference in developmental competence between control and CT zygotes in terms of cleavage rates (88.1% and 86.1%, respectively), blastocyst rates (23.2% and 20.8%, respectively), and blastocyst cell numbers (38.0 � 2.0 and 41.2 � 1.7, respectively). The rate of live zygotes after SSV and warming was similar to that of the control (93.4% and 100%, respectively). Cleavage rates (71.7% and 86.3%, respectively) and blastocyst rates (15.8% and 24.5%, respectively) of SSV were significantly reduced after vitrification compared to control (P < 0.05, ANOVA). Blastocyst cell numbers of SSV and control embryos were similar (41.2 � 3.4 and 41.6 � 3.3, respectively). There was no difference in developmental ability between zygotes cryopreserved at an early (10 h after IVF) or late (23 h after IVF) pronuclear stage. When embryo culture medium was supplemented with 1 µm of the antioxidant glutathione, development of cryopreserved zygotes to the blastocyst stage did not differ significantly from that of the control zygotes (18.6% and 22.1%, respectively). To test their ability to develop to term, 150 vitrified zygotes were transferred into a recipient, resulting in pregnancy and the production of five live piglets. These data demonstrate that a high rate of porcine zygotes could be successfully cryopreserved at the pronuclear stage, preserving their full developmental competence.
99 EFFECT OF VASCULAR ENDOTHELIAL GROWTH FACTOR ON IN VITRO-PRODUCED PORCINE OOCYTES AND THEIR SUBSEQUENT DEVELOPMENT: A PARTHENOGENETIC STUDY
Authors: Biswas D. , Lee J. H. , Jeung E. B. , Lee E. S. , Hyun S. H.
Published: January 2008

The addition of vascular endothelial growth factor (VEGF) to maturation media has beneficial effects on oocyte maturation and blastocyst formation (Einspanier et al. 2002 Mol. Reprod. Dev. 62, 29–36). The present study was conducted to examine the effect of parthenogenesis on in vitro-matured porcine oocytes with VEGF along with porcine follicular fluid in the maturation media. Porcine ovaries were collected from a local slaughter house in physiological saline. After aspiration, COC were matured in vitro in TCM-199 supplemented with 10 ng mL–1 of epidermal growth factor and (1) Group A: 10% pFF; (2) Group B: 10% pFF and 5 ng mL–1 of VEGF; (3) Group C: 10% polyvinyl alcohol; or (4) Group D: 5 ng mL–1 of VEGF plus 10% polyvinyl alcohol. Fifty COC were cultured for the first 22 h at 390�C in a humidified atmosphere of 5% CO2 in 95% air with 4 IU mL–1 of eCG and 4 IU mL–1 of hCG. They were then transferred to hormone-free medium and cultured for an additional 20 h. After culture, COC were denuded with hyaluronidase, and a proportion were stained with Hoechst 33342 for evaluating the metaphase II stage. The remaining oocytes were subjected to electrical parthenogenesis by using a 1-mm fusion chamber and were activated by applying 2 direct current pulses of 110V for 60 µs. Cleavage and blastocyst formation rate were evaluated under a stereomicroscope at 48 and 168 h after activation, respectively. Blastocyst quality was assessed by differential staining of inner cell mass and trophectoderm cells according to a modified staining procedure (Thouas et al. 2001 Reprod. Biomed. Online 3, 25–29). All data are presented as mean � SD and were analyzed by ANOVA followed by Duncan's multiple range test using SPSS 12.0 (SPSS Inc., Chicago, IL, USA). The maturation rate was significantly higher (P < 0.05) in Groups A and B than Groups C and D (76.1 � 9.6, 78.9 � 6.0 v. 60. � 14.2 and 58.3 � 14.3, respectively). The cleavage rate was significantly higher (P < 0.05) in Groups A and B (73.2 � 1.8 and 64.6 � 1.1, respectively) than Groups C and D (47.9 � 1.8 and 48.3 � 1.7, respectively). The blastocyst formation rate was significantly higher (P < 0.05) in Group B (32.6 � 2.4) compared to other groups. There was no significant difference in blastocyst cell number (inner cell mass or trophectoderm) among these groups. These data indicate that the exogenous VEGF along with pFF in the maturation media helps to increase the blastocyst formation rate in vitro, and it might be due to presence of some ligand/protein kinase in the pFF that plays an important role during the cyclic growth of oocytes.
Regulation of
Escherichia coli
SOS mutagenesis by dimeric intrinsically disordered
umuD
gene products
Authors: Simon S. M. , Sousa F. J. R. , Mohana-Borges R. , Walker G. C.
Published: January 2008

Products of the
umuD
gene in
Escherichia coli
play key roles in coordinating the switch from accurate DNA repair to mutagenic translesion DNA synthesis (TLS) during the SOS response to DNA damage. Homodimeric UmuD
2
is up-regulated 10-fold immediately after damage, after which slow autocleavage removes the N-terminal 24 amino acids of each UmuD. The remaining fragment, UmuD′
2
, is required for mutagenic TLS. The small proteins UmuD
2
and UmuD′
2
make a large number of specific protein–protein contacts, including three of the five known
E. coli
DNA polymerases, parts of the replication machinery, and RecA recombinase. We show that, despite forming stable homodimers, UmuD
2
and UmuD′
2
have circular dichroism (CD) spectra with almost no α-helix or β-sheet signal at physiological concentrations
in vitro
. High protein concentrations, osmolytic crowding agents, and specific interactions with a partner protein can produce CD spectra that resemble the expected β-sheet signature. A lack of secondary structure
in vitro
is characteristic of intrinsically disordered proteins (IDPs), many of which act as regulators. A stable homodimer that lacks significant secondary structure is unusual but not unprecedented. Furthermore, previous single-cysteine cross-linking studies of UmuD
2
and UmuD′
2
show that they have a nonrandom structure at physiologically relevant concentrations
in vitro
. Our results offer insights into structural characteristics of relatively poorly understood IDPs and provide a model for how the
umuD
gene products can regulate diverse aspects of the bacterial SOS response.
Knockin mice expressing a chimeric p53 protein reveal mechanistic differences in how p53 triggers apoptosis and senescence
Authors: Johnson Thomas M. , Meade Kristin , Pathak Navneeta , Marques Michelle R. , Attardi Laura D.
Published: January 2008

The contribution of transcriptional activation to the p53 effector functions critical for tumor suppression, apoptosis and cellular senescence, remains unclear because of p53's ability to regulate diverse cellular processes in a transactivation-independent manner. Dissociating the importance of transactivation from other p53 functions, including regulating transcriptional repression, DNA replication, homologous recombination, centrosome duplication, and mitochondrial function, has been difficult because of overlapping motifs for these functions in the amino terminus. To determine the relative contribution of these activities and transactivation to p53 function, we generated knockin mice expressing a p53 mutant lacking domains involved in these transactivation-independent functions, while remaining competent for transactivation through fusion to the Herpes Simplex Virus VP16 transactivation domain. This chimeric mutant, termed p53
VP16
, robustly activates the transcription of a range of p53 targets involved in both apoptosis and senescence. Intriguingly, despite being transactivation-competent, this chimeric protein shows selectivity in p53 effector function in mouse fibroblasts, with a capacity to trigger senescence but not apoptosis under a variety of conditions. Our study highlights the central role of p53 transactivation for senescence while suggesting that transactivation is insufficient for apoptosis, and provides insight into the mechanisms by which p53 serves as a tumor suppressor.
Maps of random walks on complex networks reveal community structure
Authors: Rosvall Martin , Bergstrom Carl T.
Published: January 2008

To comprehend the multipartite organization of large-scale biological and social systems, we introduce an information theoretic approach that reveals community structure in weighted and directed networks. We use the probability flow of random walks on a network as a proxy for information flows in the real system and decompose the network into modules by compressing a description of the probability flow. The result is a map that both simplifies and highlights the regularities in the structure and their relationships. We illustrate the method by making a map of scientific communication as captured in the citation patterns of >6,000 journals. We discover a multicentric organization with fields that vary dramatically in size and degree of integration into the network of science. Along the backbone of the network—including physics, chemistry, molecular biology, and medicine—information flows bidirectionally, but the map reveals a directional pattern of citation from the applied fields to the basic sciences.
Booster vaccination of cancer patients with MAGE-A3 protein reveals long-term immunological memory or tolerance depending on priming
Authors: Atanackovic Djordje , Altorki Nasser K. , Cao Yanran , Ritter Erika , Ferrara Cathy A. , Ritter Gerd , Hoffman Eric W. , Bokemeyer Carsten , Old Lloyd J. , Gnjatic Sacha
Published: January 2008

We previously reported results of a phase II trial in which recombinant MAGE-A3 protein was administered with or without adjuvant AS02B to 18 non-small-cell lung cancer (NSCLC) patients after tumor resection. We found that the presence of adjuvant was essential for the development of humoral and cellular responses against selected MAGE-A3 epitopes. In our current study, 14 patients that still had no evidence of disease up to 3 years after vaccination with MAGE-A3 protein with or without adjuvant received an additional four doses of MAGE-A3 protein with adjuvant AS02B. After just one boost injection, six of seven patients originally vaccinated with MAGE-A3 protein plus adjuvant reached again their peak antibody titers against MAGE-A3 attained during the first vaccination. All seven patients subsequently developed even stronger antibody responses. Furthermore, booster vaccination widened the spectrum of CD4+and CD8+T cells against various new and known MAGE-A3 epitopes. In contrast, only two of seven patients originally vaccinated with MAGE-A3 protein alone developed high-titer antibodies to MAGE-A3, and all these patients showed very limited CD4+and no CD8+T cell reactivity, despite now receiving antigen in the presence of adjuvant. Our results underscore the importance of appropriate antigen priming using an adjuvant for generating persistent B and T cell memory and allowing typical booster responses with reimmunization. In contrast, absence of adjuvant at priming compromises further immunization attempts. These data provide an immunological rationale for vaccine design in light of recently reported favorable clinical responses in NSCLC patients after vaccination with MAGE-A3 protein plus adjuvant AS02B.
Hepatic NF-κB essential modulator deficiency prevents obesity-induced insulin resistance but synergizes with high-fat feeding in tumorigenesis
Authors: Wunderlich F. Thomas , Luedde Tom , Singer Stephan , Schmidt-Supprian Marc , Baumgartl Julia , Schirmacher Peter , Pasparakis Manolis , Brüning Jens C.
Published: January 2008

Development of obesity-associated insulin resistance and diabetes mellitus type 2 has been linked to activation of proinflammatory pathways in the liver, leading to impaired insulin signal transduction. To further define the role of hepatic NF-κB activation in this process, we have analyzed glucose metabolism in mice with liver-specific inactivation of the NF-κB essential modulator gene (NEMO
L-KO
mice) exposed to a high-fat diet (HFD). These animals are protected from the development of obesity-associated insulin resistance, highlighting the importance of hepatic NF-κB activation in this context. However, hepatic NEMO deficiency synergizes with HFD in the development of liver steatosis as a consequence of decreased peroxisome proliferator-activated receptor (PPAR-α) and increased PPAR-γ expression. Steatosis interacts with increased inflammation, causing elevated apoptosis in the livers of these mice under HFD. These changes result in liver tumorigenesis of NEMO
L-KO
mice under normal diet, a process that is largely aggravated when these mice are exposed to HFD. These data directly demonstrate the interaction of hepatic inflammation, dietary composition, and metabolism in the development of liver tumorigenesis.
The molecular basis of chloroquine block of the inward rectifier Kir2.1 channel
Authors: Rodríguez-Menchaca Aldo A. , Navarro-Polanco Ricardo A. , Ferrer-Villada Tania , Rupp Jason , Sachse Frank B. , Tristani-Firouzi Martin , Sánchez-Chapula José A.
Published: January 2008

Although chloroquine remains an important therapeutic agent for treatment of malaria in many parts of the world, its safety margin is very narrow. Chloroquine inhibits the cardiac inward rectifier K+currentIK1and can induce lethal ventricular arrhythmias. In this study, we characterized the biophysical and molecular basis of chloroquine block of Kir2.1 channels that underlie cardiacIK1. The voltage- and K+-dependence of chloroquine block implied that the binding site was located within the ion-conduction pathway. Site-directed mutagenesis revealed the location of the chloroquine-binding site within the cytoplasmic pore domain rather than within the transmembrane pore. Molecular modeling suggested that chloroquine blocks Kir2.1 channels by plugging the cytoplasmic conduction pathway, stabilized by negatively charged and aromatic amino acids within a central pocket. Unlike most ion-channel blockers, chloroquine does not bind within the transmembrane pore and thus can reach its binding site, even while polyamines remain deeper within the channel vestibule. These findings explain how a relatively low-affinity blocker like chloroquine can effectively blockIK1even in the presence of high-affinity endogenous blockers. Moreover, our findings provide the structural framework for the design of safer, alternative compounds that are devoid of Kir2.1-blocking properties.
Molecular switch for CLC-K Cl
−
channel block/activation: Optimal pharmacophoric requirements towards high-affinity ligands
Authors: Liantonio Antonella , Picollo Alessandra , Carbonara Giuseppe , Fracchiolla Giuseppe , Tortorella Paolo , Loiodice Fulvio , Laghezza Antonio , Babini Elena , Zifarelli Giovanni , Pusch Michael , Camerino Diana Conte
Published: January 2008

ClC-Ka and ClC-Kb Cl
−
channels are pivotal for renal salt reabsorption and water balance. There is growing interest in identifying ligands that allow pharmacological interventions aimed to modulate their activity. Starting from available ligands, we followed a rational chemical strategy, accompanied by computational modeling and electrophysiological techniques, to identify the molecular requisites for binding to a blocking or to an activating binding site on ClC-Ka. The major molecular determinant that distinguishes activators from blockers is the level of planarity of the aromatic portions of the molecules: only molecules with perfectly coplanar aromatic groups display potentiating activity. Combining several molecular features of various CLC-K ligands, we discovered that phenyl-benzofuran carboxylic acid derivatives yield the most potent ClC-Ka inhibitors so far described (affinity <10 μM). The increase in affinity compared with 3-phenyl-2-
p
-chlorophenoxy-propionic acid (3-phenyl-CPP) stems primarily from the conformational constraint provided by the phenyl-benzofuran ring. Several other key structural elements for high blocking potency were identified through a detailed structure–activity relationship study. Surprisingly, some benzofuran-based drugs inhibit ClC-Kb with a similar affinity of <10 μM, thus representing the first inhibitors for this CLC-K isoform identified so far. Based on our data, we established a pharmacophore model that will be useful for the development of drugs targeting CLC-K channels.
The integrin Mac-1 (CR3) mediates internalization and directsBacillus anthracisspores into professional phagocytes
Authors: Oliva Claudia R. , Swiecki Melissa K. , Griguer Corinne E. , Lisanby Mark W. , Bullard Daniel C. , Turnbough Charles L. , Kearney John F.
Published: January 2008

Anthrax, a disease caused byBacillus anthracis, affects animals and humans. Because the inert spore is the infectious form of the organism that first contacts the potential host, the interaction between the host and spore exosporium is vital to the initiation of disease. Here, we demonstrate that the integrin Mac-1 is essential for the recognition of the major exosporium protein BclA by phagocytic cells. Expression of Mac-1, but not p150/95, in CHO cells markedly enhanced infection with Sterne strain ofB. anthracisspores (WT spores). Conversely, CD11b−/−macrophages demonstrated a significant decrease in spore uptake when compared with macrophages from normal C57BL/6 mice. However, when CD11b−/−macrophages were infected with ΔbclAspores, spore ingestion was no different from their C57BL/6 counterparts. ΔbclAspores were also efficiently internalized by all CHO cell lines tested, independently of Mac-1 expression. Taken together, these results show that there is an alternative Mac-1-independent pathway involved in spore uptake that is unmasked only in the absence of BclA. Survival studies, using C57BL/6 and CD11b−/−mice, revealed that CD11b−/−mice are more resistant to infection with WT but not ΔbclAspores. Our experiments also show that ΔbclAspores are more virulent than WT spores in C57BL/6 and A/J mice. Overall, our data indicate that the Mac-1/BclA interaction may play a major role inB. anthracispathogenesis by promoting spore uptake by professional phagocytes and subsequent access to a favorable niche for transport, germination, and outgrowth in lymphoid tissues.
The globular tail domain puts on the brake to stop the ATPase cycle of myosin Va
Authors: Li Xiang-dong , Jung Hyun Suk , Wang Qizhi , Ikebe Reiko , Craig Roger , Ikebe Mitsuo
Published: January 2008

Myosin Va is a well known processive motor involved in transport of organelles. A tail-inhibition model is generally accepted for the regulation of myosin Va: inhibited myosin Va is in a folded conformation such that the tail domain interacts with and inhibits myosin Va motor activity. Recent studies indicate that it is the C-terminal globular tail domain (GTD) that directly inhibits the motor activity of myosin Va. In the present study, we identified a conserved acidic residue in the motor domain (Asp-136) and two conserved basic residues in the GTD (Lys-1706 and Lys-1779) as critical residues for this regulation. Alanine mutations of these conserved charged residues not only abolished the inhibition of motor activity by the GTD but also prevented myosin Va from forming a folded conformation. We propose that Asp-136 forms ionic interactions with Lys-1706 and Lys-1779. This assignment locates the GTD-binding site in a pocket of the motor domain, formed by the N-terminal domain, converter, and the calmodulin in the first IQ motif. We propose that binding of the GTD to the motor domain prevents the movement of the converter/lever arm during ATP hydrolysis cycle, thus inhibiting the chemical cycle of the motor domain.
Epidemic community-associated methicillin-resistant
Staphylococcus aureus
: Recent clonal expansion and diversification
Authors: Kennedy Adam D. , Otto Michael , Braughton Kevin R. , Whitney Adeline R. , Chen Liang , Mathema Barun , Mediavilla Jose R. , Byrne Kelly A. , Parkins Larye D. , Tenover Fred C. , Kreiswirth Barry N. , Musser James M. , DeLeo Frank R.
Published: January 2008

Emerging and re-emerging infectious diseases, especially those caused by drug-resistant bacteria, are a major problem worldwide. Community-associated methicillin-resistant
Staphylococcus aureus
(CA-MRSA) appeared rapidly and unexpectedly in the United States, resulting in an epidemic caused primarily by isolates classified as USA300. The evolutionary and molecular underpinnings of this epidemic are poorly understood. Specifically, it is unclear whether there has been clonal emergence of USA300 isolates or evolutionary convergence toward a hypervirulent phenotype resulting in the independent appearance of similar organisms. To definitively resolve this issue and understand the phylogeny of USA300 isolates, we used comparative whole-genome sequencing to analyze 10 USA300 patient isolates from eight states in diverse geographic regions of the United States and multiple types of human infection. Eight of 10 isolates analyzed had very few single nucleotide polymorphisms (SNPs) and thus were closely related, indicating recent diversification rather than convergence. Unexpectedly, 2 of the clonal isolates had significantly reduced mortality in a mouse sepsis model compared with the reference isolate (
P
= 0.0002), providing strong support to the idea that minimal genetic change in the bacterial genome can have profound effects on virulence. Taken together, our results demonstrate that there has been recent clonal expansion and diversification of a subset of isolates classified as USA300. The findings add an evolutionary dimension to the epidemiology and emergence of USA300 and suggest a similar mechanism for the pandemic occurrence and spread of penicillin-resistant
S. aureus
(known as phage-type 80/81
S. aureus
) in the 1950s.
Enzyme structure and dynamics affect hydrogen tunneling: The impact of a remote side chain (I553) in soybean lipoxygenase-1
Authors: Meyer Matthew P. , Tomchick Diana R. , Klinman Judith P.
Published: January 2008

This study examines the impact of a series of mutations at position 553 on the kinetic and structural properties of soybean lipoxygenase-1 (SLO-1). The previously uncharacterized mutants reported herein are I553L, I553V, and I553G. High-resolution x-ray studies of these mutants, together with the earlier studied I553A, show almost no structural change in relation to the WT-enzyme. By contrast, a progression in kinetic behavior occurs in which the decrease in the size of the side chain at position 553 leads to an increased importance of donor–acceptor distance sampling in the course of the hydrogen transfer process. These dynamical changes in behavior are interpreted in the context of two general classes of protein motions, preorganization and reorganization, with the latter including the distance sampling modes [Klinman JP (2006)
Philos Trans R Soc London Ser B
361:1323–1331; Nagel Z, Klinman JP (2006)
Chem Rev
106:3095–3118]. The aggregate data for SLO-1 show how judicious placement of hydrophobic side chains can influence enzyme catalysis via enhanced donor–acceptor hydrogenic wave function overlap.
The insulin-like growth factor pathway is altered in spinocerebellar ataxia type 1 and type 7
Authors: Gatchel Jennifer R. , Watase Kei , Thaller Christina , Carson James P. , Jafar-Nejad Paymaan , Shaw Chad , Zu Tao , Orr Harry T. , Zoghbi Huda Y.
Published: January 2008

Polyglutamine diseases are inherited neurodegenerative disorders caused by expansion of CAG repeats encoding a glutamine tract in the disease-causing proteins. There are nine disorders, each having distinct features but also clinical and pathological similarities. In particular, spinocerebellar ataxia type 1 and 7 (SCA1 and SCA7) patients manifest cerebellar ataxia with degeneration of Purkinje cells. To determine whether the disorders share molecular pathogenic events, we studied two mouse models of SCA1 and SCA7 that express the glutamine-expanded protein from the respective endogenous loci. We found common transcriptional changes, with down-regulation of insulin-like growth factor binding protein 5 (
Igfbp5
) representing one of the most robust changes.
Igfbp5
down-regulation occurred in granule neurons through a non-cell-autonomous mechanism and was concomitant with activation of the insulin-like growth factor (IGF) pathway and the type I IGF receptor on Purkinje cells. These data define one common pathogenic response in SCA1 and SCA7 and reveal the importance of intercellular mechanisms in their pathogenesis.
Maternal traces of deep common ancestry and asymmetric gene flow between Pygmy hunter–gatherers and Bantu-speaking farmers
Authors: Quintana-Murci Lluís , Quach Hélène , Harmant Christine , Luca Francesca , Massonnet Blandine , Patin Etienne , Sica Lucas , Mouguiama-Daouda Patrick , Comas David , Tzur Shay , Balanovsky Oleg , Kidd Kenneth K. , Kidd Judith R. , van der Veen Lolke , Hombert Jean-Marie , Gessain Antoine , Verdu Paul , Froment Alain , Bahuchet Serge , Heyer Evelyne , Dausset Jean , Salas Antonio , Behar Doron M.
Published: January 2008

Two groups of populations with completely different lifestyles—the Pygmy hunter–gatherers and the Bantu-speaking farmers—coexist in Central Africa. We investigated the origins of these two groups and the interactions between them, by analyzing mtDNA variation in 1,404 individuals from 20 farming populations and 9 Pygmy populations from Central Africa, with the aim of shedding light on one of the most fascinating cultural transitions in human evolution (the transition from hunting and gathering to agriculture). Our data indicate that this region was colonized gradually, with an initial L1c-rich ancestral population ultimately giving rise to current-day farmers, who display various L1c clades, and to Pygmies, in whom L1c1a is the only surviving clade. Detailed phylogenetic analysis of complete mtDNA sequences for L1c1a showed this clade to be autochthonous to Central Africa, with its most recent branches shared between farmers and Pygmies. Coalescence analyses revealed that these two groups arose through a complex evolutionary process characterized by (
i
) initial divergence of the ancestors of contemporary Pygmies from an ancestral Central African population no more than ≈70,000 years ago, (
ii
) a period of isolation between the two groups, accounting for their phenotypic differences, (
iii
) long-standing asymmetric maternal gene flow from Pygmies to the ancestors of the farming populations, beginning no more than ≈40,000 years ago and persisting until a few thousand years ago, and (
iv
) enrichment of the maternal gene pool of the ancestors of the farming populations by the arrival and/or subsequent demographic expansion of L0a, L2, and L3 carriers.
Structure of the transmembrane regions of a bacterial cyclic nucleotide-regulated channel
Authors: Clayton Gina M. , Altieri Steve , Heginbotham Lise , Unger Vinzenz M. , Morais-Cabral João H.
Published: January 2008

The six-transmembrane helix (6 TM) tetrameric cation channels form the largest ion channel family, some members of which are voltage-gated and others are not. There are no reported channel structures to match the wealth of functional data on the non-voltage-gated members. We determined the structure of the transmembrane regions of the bacterial cyclic nucleotide-regulated channel MlotiK1, a non-voltage-gated 6 TM channel. The structure showed how the S1–S4 domain and its associated linker can serve as a clamp to constrain the gate of the pore and possibly function in concert with ligand-binding domains to regulate the opening of the pore. The structure also led us to hypothesize a new mechanism by which motions of the S6 inner helices can gate the ion conduction pathway at a position along the pore closer to the selectivity filter than the canonical helix bundle crossing.
Mood and Attention Variability in Women with Alcohol Dependence: A Preliminary Investigation
Authors: Bowen Rudy , Block Gerald , Baetz Marilyn
Published: January 2008

We compared women (n = 22) with alcohol dependence in an in‐patient rehabilitation program at three weeks abstinence with student controls on mood scales and affect variability measured with a visual analogue scale. Patients also completed a measure of attention variability using a Continuous Performance Test. Fourteen of the patients met criteria for a bipolar spectrum disorder. Patients scored higher on mood scales and affect variability measures than controls. High and scared affect variability correlated with attention variability. This suggests that mood/cognitive dysregulation may be a component of alcohol dependence in women.
The Association between Attention Deficit Hyperactivity Disorder in Adolescence and Smoking in Adulthood
Authors: Brook Judith S. , Duan Tao , Zhang Chenshu , Cohen Patricia R. , Brook David W.
Published: January 2008

This longitudinal study examined the interrelationships between early and/or middle adolescent attention deficit hyperactivity disorder (ADHD), middle adolescent conduct disorder (CD), and later adult smoking behavior. This is a prospective longitudinal study. Data were collected via structured interviews of representative families in the northeastern United States (N = 641). The mean ages of the offspring were as follows: 14 years (T2, 1983), 17 years (T3, 1985–1986), and 32 years (T6, 2002). The dependent variable was the participants' daily cigarette smoking in their early thirties. Logistic regression analyses indicated that the relationship between ADHD and daily smoking behavior was mediated by CD with control on gender, age, SES, and adolescent smoking. CD had a direct effect on daily smoking in adulthood. Our findings suggest that ADHD is related to CD, which in turn is associated with daily smoking. Therefore, interventions with ADHD adolescents who have ADHD at an early age might lead to some reduction in later smoking provided that the intervention has a positive effect on CD. For those adolescents who never had ADHD, our findings suggest that prevention or treatment aimed at reducing CD may be most successful in reducing daily smoking later in adulthood.
Cigarette Smoking in Opioid‐Using Patients Presenting for Hospital‐Based Medical Services
Authors: Haas Amie L. , Sorensen James L. , Hall Sharon M. , Lin Christine , Delucchi Kevin , Sporer Karl , Chen TeChieh
Published: January 2008

Little is known about cigarette smoking among opioid users who are not in substance abuse treatment. The study examined cigarette smoking in out‐of‐treatment opioid users presenting at a hospital who participated in drug abuse research. Participants exhibited a high rate of smoking (92%) at baseline that remained unchanged at one year and were moderately nicotine‐dependent. Nineteen percent preferred unfiltered cigarettes. Women were more likely to smoke menthol cigarettes; men were more likely to smoke unfiltered cigarettes. Caucasians tended to smoke more than other ethnicities and exhibited greater dependence. Out‐of‐treatment drug users continue to be at high risk for continued smoking.
Do Alcoholics Anonymous Groups Really Work? Factors of Adherence in a Brazilian Sample of Hospitalized Alcohol Dependents
Authors: Terra Mauro Barbosa , Tannhauser Barros Helena Maria , Stein Airton Tetelbom , Figueira Ivan , Palermo Luiz Henrique , Athayde Luciana Dias , De Souza Gonçalves Marcelo , Da Silveira Dartiu Xavier
Published: January 2008

This study was designed to determine factors affecting adherence to Alcoholics Anonymous (AA) groups. This cohort involved 300 alcoholics committed to three hospitals in Porto Alegre, Brazil. They were interviewed again in their homes after six months. The SCID‐I and a questionnaire focusing on patient relationship with AA groups were used. The responses obtained through the questionnaire were independently evaluated by two researchers. AA adherence was below 20%. The main factors reported by patients as reasons for non‐adherence to AA were relapse, lack of identification with the method, lack of need, and lack of credibility. The factors reported by patients as reasons for adherence were identification with the method and a way to avoid relapse. Although AA is considered an effective intervention for alcoholism, its adherence rate was excessively low. The identification of these nonadherence factors could help health professionals in referring certain alcoholic patients to therapeutic interventions other than AA.
Fascinating futurism: The historiographical politics of an historical avant-garde
Authors: Adamson Walter L.
Published: January 2008

The Italian futurist movement and its founder, F.T. Marinetti, have stimulated a vast historiography. Why has futurism fascinated so many and how, in particular, have the futurism-fascism and Marinetti-futurism relationships been conceived? To answer such questions, this article surveys nearly five decades of scholarship on futurism. It shows how futurism's fascist trajectory has polarised it and led scholars to a wide variety of positions. Some scholars limit themselves to the ‘heroic years’ up to 1916; others focus on ‘second futurism’ after 1915 without much reference to Marinetti; and still others treat futurism's ‘multiplicity’ using a centre-periphery model with Marinetti at the centre. Similarly, some insist on futurism's continuously ‘revolutionary’ character, others limit that claim, and still others deny it altogether. It is argued that recent biographical work on Marinetti has helped to clarify how one ought to approach and resolve these differences, but that scholarship on futurism nonetheless remains intensely politicised.
Study of in-vessel nonaxisymmetric ELM suppression coil concepts for ITER
Authors: Schaffer M.J. , Menard J.E. , Aldan M.P. , Bialek J.M. , Evans T.E. , Moyer R.A.
Published: January 2008

Large Type-I edge-localized mode (ELM) heat pulses may limit the life of divertor targets in a burning plasma. Recent experiments show that pitch-resonant nonaxisymmetric magnetic perturbations of the plasma edge of 0.0005 or less of the main magnetic field offer a useful solution, but there is little room in the presently designed ITER for even small perturbation coils. We present proposed coil requirements for ITER ELM suppression, derived primarily from DIII-D ELM suppression experiments. We show by calculated examples that large arrays of coils (e.g. four toroidal rows of nine coils each) on the outboard wall near the plasma (at the radius of the blanket-vacuum vessel interfaceR∼ 8 m) can meet the known requirements, expressed in terms of the toroidal helical Fourier harmonic spectrum, for both low- and high-qITER plasmas, when coil currents are distributed to concentrate the magnetic perturbation into a single dominant Fourier spectral peak. Fields from arrays of less than four rows of nine coils (a) penetrate relatively more strongly into the core plasma, and (b) generate more and larger nonresonant spectral peaks. Both features are expected to brake desirable plasma rotation. We found that the Moiré effect from approximating sinusoidal perturbations by a limited discrete coil set can be used to control nonfundamental harmonics in large arrays. We show that a judicious choice of current distribution among the coils ameliorates effects of an 80° toroidal gap where no coils are allowed in the ITER midplane.
New method for inductively forming an oblate field reversed configuration from a spheromak
Authors: Gerhardt S.P. , Belova E.V. , Yamada M. , Ji H. , Inomoto M. , Ren Y. , McGeehan B.
Published: January 2008

A new method for inductively forming a field reversed configuration is demonstrated, based on the inductively driven transformation of a spheromak. The driven transition can be achieved in argon and krypton plasmas, in which MHD modes are suppressed; simulations indicate that stability through the transition is explained by magnetic diffusion. Spheromaks with lighter working gas, such as neon and helium, either display a tilt mode or ann= 2 kink instability, both resulting in discharge termination.
Overview of TCV results*
Authors: Fasoli A.
Published: January 2008

This overview highlights the progress accomplished on tokamak à configuration variable (TCV) during the past two years, along five research avenues: particle, energy and momentum transport, edge physics, H-mode physics under strong electron heating, electron cyclotron (EC) heating and electron cyclotron current drive physics, scenarios with internal transport barriers and large non-inductive current fractions. Peaked density profiles are measured in the absence of a Ware pinch or a core particle source. Decreasing the plasma triangularity leads to a significant reduction in χe. Measurements of the plasma toroidal rotation in the absence of external torque are inconsistent with diffusion of toroidal momentum from the edge. Scrape-off layer fluctuation measurements and the relevant modelling using a fluid turbulence code indicate radial interchange motion of plasma filaments as the cause of cross-field transport. Third harmonic EC heating (1.5 MW) applied to ELMy H-modes leads to βN∼ 2, large ELMs and peaked density profiles, significant ion heating (Ti∼ 1 keV, withTi/Te∼ 0.4) and to quasi-stationary ELM-free H-modes lasting for many energy confinement times. Supra-thermal electrons produced during strong EC heating and following sawtooth crashes are shown to undergo rapid cross-field transport. Electron Bernstein wave heating is demonstrated in the O–X–B conversion scheme. Electron internal transport barriers are generated in a variety of scenarios, leading to significant confinement improvement and bootstrap current fractions in excess of 70%.
Study of ion viscosity by spontaneous L–H transitions under marginal hot cathode biasing in the Tohoku University Heliac
Authors: Kitajima S. , Takahashi H. , Tanaka Y. , Utoh H. , Takenaga M. , Yokoyama M. , Inagaki S. , Suzuki Y. , Nishimura K. , Ogawa H. , Takayama M. , Shinde J. , Ogawa M. , Aoyama H. , Iwazaki K. , Okamoto A. , Shinto K. , Sasao M.
Published: January 2008

Using the spontaneous transition condition under marginal hot cathode biasing, the ion viscosity at the L–H transition was estimated in various magnetic configurations in the Tohoku University Heliac. The critical viscosity, which is the viscosity at the transition point, was experimentally estimated from theJ×Bdriving force. The critical viscosities in different magnetic configurations were in agreement with the neoclassical predictions within a factor of 2 and were compared with the viscosities obtained in the externally forced biasing experiments. Although the transition points were spread over a wide range, poloidal Mach numbers at the transition point were concentrated near the viscosity maxima predicted by the theory.
Two dimensionally steep structure of the electric field in tokamak H-mode
Authors: Kasuya N , Itoh K
Published: January 2008

The formation of a poloidal shock structure is predicted in H-mode transport barriers, which must be taken into account for transport analyses to clarify the rapid formation mechanism of the H-mode pedestal. The analyses are carried out with edge plasmas in tokamak H-modes, which are induced either spontaneously or by electrode biasing. Two-dimensional structures of the potential, density and flow velocity are calculated with the momentum conservation equation. The validity of one-dimensional L/H transition theory and the iterative process to obtain the two-dimensional structure are confirmed by our analysis. A steep electric field structure both in the radial and poloidal directions induces radial ion fluxes, which increase in the H-mode transport barrier. If the Boltzmann relation is violated, radial electron fluxes are induced. A transport model is constructed, including generation of particle fluxes associated with the two-dimensional structure and reduction of anomalous transport by the steep gradient of the radial electric field. A self-consistent evolution of the density profile is calculated in the L/H transition, which clarifies that the generation of particle fluxes accelerates the density pedestal formation.
Neutronics investigation of advanced self-cooled liquid blanket systems in the helical reactor
Authors: Tanaka T. , Sagara A. , Muroga T. , Youssef M.Z.
Published: January 2008

Neutronics investigations have been conducted in the design activity of the helical-type reactor Force Free Helical Reactor (FFHR2) adopting Flibe-cooled and Li-cooled advanced liquid blanket systems. In this study, comprehensive investigations and geometry modifications related to the tritium breeding ratios (TBRs), neutron shielding performance and neutron wall loading on the first walls in FFHR2 have been performed by improving the three-dimensional (3D) neutronics calculation system developed for non-axisymmetric helical designs. The total TBRs obtained after modifying the blanket dimensions indicated that all the advanced blanket systems proposed for FFHR2 would achieve adequate tritium self-sufficiency by dimension adjustment and optimization of structures in the breeder layers. However, it appeared that the most important neutronics issue in the present helical blanket configuration was suppression of neutron streaming through the divertor pumping areas and reflection from support structures for protection of poloidal and helical coils. Evaluation of neutron wall loading on the first walls indicated that the peaking factor would be moderated as low as 1.2 by the toroidal and helical effect of the helical-shaped plasma distribution in the helical reactor.
Thermonuclear microdetonation macron accelerator for impact ignition
Authors: Winterberg F
Published: January 2008

It is proposed to replace the expensive ∼150 kJ petawatt laser as a means for the fast ignition of a highly compressed dense DT target by a small flyer plate propelled to high velocities by a thermonuclear microdetonation ignited at one end of a super-pinch. It appears that this can most efficiently be done with the previously proposed modification of the dense plasma focus device, adding a high voltage relativistic electron beam emitting diode inside the coaxial plasma focus discharge tube, igniting at the end of the plasma focus pinch column a thermonuclear detonation wave, propagating in the axial direction and accelerating at the end of the pinch a flyer plate to a velocity of 103 km s−1.
Luminescence Property and Synthesis of Sulfur-doped ZnO Nanowires by Electrochemical Deposition
Authors: Wang Xiu-hua , Liu Su , Chang Peng , Tang Ying
Published: January 2008

Sulfur-doped zinc oxide (ZnO) nanowires were successfully synthesized by an electric field-assisted electrochemical deposition in porous anodized aluminum oxide template at room temperature. The structure, morphology, chemical composition and photoluminescence properties of the as-synthesized ZnO:S nanostructures were investigated. X-ray diffraction and the selected area electron diffraction results reveal that the as-synthesized products are single phase with hexagonal wurtzite structure with a highly preferential orientation in the (101) direction. Transmission electron microscopy observations indicate that the nanowires are uniform with an average diameter of 70 nm and length up to several tens of micrometers. X-ray photoelectron spectroscopy further reveals the presence of S in the ZnO nanowires. Room-temperature photoluminescence is observed in the sulfur-doped ZnO nanowires which exhibits strong near-band-edge ultraviolet peaks at 378 and 392 nm and weak green emissions at 533 and 507 nm. A blue emission at 456 nm and violet emissions at around 406, 420, and 434 nm were also observed in the PL spectrum for the as-synthesized ZnO:S nanowires. The PL spectrum shows that S-doping had an obvious effect on the luminescence property of typical ZnO nanowires.
Preparation and Characterization of Poly(methyl methacrylate)-functionalized Carboxyl Multi-walled Carbon Nanotubes
Authors: Meng Qing-jie , Zhang Xing-xiang , Bai Shi-he , Wang Xue-chen
Published: January 2008

An in situ polymerization process was used to prepare poly (methyl methacrylate) (PMMA)-functionalized carboxyl multi-walled carbon nanotubes using carboxylate carbon nanotubes and methyl methacrylate as reactants and benzoyl peroxide as an initiator agent. The functionalized multi-walled carbon nanotubes were characterized using transmission electron microscope, scanning electron microscope, nuclear magnetic resonance, Fourier transform infrared spectroscopy, thermogravimetric analysis and Raman. The results indicate that the PMMA chains are covalently linked with the surface of carboxylate carbon nanotubes. The surface morphology is controlled by the content of carboxylate carbon nanotubes in the reactants. The PMMA functionalized multi-walled carbon nanotubes are soluble in deuterated chloroform. The storage modulus and tan magnitude increase as the content of CCNTs increases up to 0.3%.
Silica Coating of Water-Soluble CdTe/CdS Core-Shell Nanocrystals by Microemulsion Method
Authors: Wang Yong , Niu Shu-hua , Zhang Zhi-juan , Wang Hai-tao , Yuan Chun-wei , Fu De-gang
Published: January 2008

Using Te powder as a tellurium source and Na2S as a sulfur source, core-shell CdTe/CdS NPs were synthesized at 50C. UV-visible and photoluminescence (PL) spectra were used to probe the effect of CdS passivation on the CdTe quantum dots. As the thickness of CdS shell increases, there is a red-shift in the optical absorption spectra, as well as the PL spectra. The broadening absorption peaks and PL spectra indicate that the size distributions of CdTe/CdS NPs widen increasingly with the increase of CdS coverage. The PL spectra also show that the fluorescence intensity of CdTe QDs will increase when the particles are covered with CdS shell with ratio of S/Te less than 1.0, otherwise it will decrease if the ratio of S/Te is larger than 1.0. Furthermore, the (CdTe/CdS)@SiO2 particles were prepared using a water-in-oil microemulsion method at room temperature in which hydrolysis of tetraethyl orthosilicate leads to the formation of monodispersed silica nanospheres. The obtained (CdTe/CdS)@SiO2 particles show bright photoluminescence with their fluorescence intensity being enhanced 18.5% compared with that of CdTe NPs. TEM imaging shows that the diameter of these composite particles is 50 nm. These nanoparticles are suitable for biomarker applications since they are much smaller than cellular dimensions.