bluuebunny/crossref_metadata_2025 huggingface dataset:
Universal scaling laws for the disintegration of electrified drops
Authors: Collins Robert T. , Sambath Krishnaraj , Harris Michael T. , Basaran Osman A.
Published: March 2013

Drops subjected to strong electric fields emit charged jets from their pointed tips. The disintegration of such jets into a spray consisting of charged droplets is common to electrospray ionization mass spectrometry, printing and coating processes, and raindrops in thunderclouds. Currently, there exist conflicting theories and measurements on the size and charge of these small electrospray droplets. We use theory and simulation to show that conductivity can be tuned to yield three scaling regimes for droplet radius and charge, a finding missed by previous studies. The amount of charge

that electrospray droplets carry determines whether they are coulombically stable and charged below the Rayleigh limit of stability

or are unstable and hence prone to further explosions once they are formed. Previous experiments reported droplet charge values ranging from 10% to in excess of

. Simulations unequivocally show that electrospray droplets are coulombically stable at the instant they are created and that there exists a universal scaling law for droplet charge,

.
Structure and accessibility of HA trimers on intact 2009 H1N1 pandemic influenza virus to stem region-specific neutralizing antibodies
Authors: Harris Audray K. , Meyerson Joel R. , Matsuoka Yumiko , Kuybeda Oleg , Moran Amy , Bliss Donald , Das Suman R. , Yewdell Jonathan W. , Sapiro Guillermo , Subbarao Kanta , Subramaniam Sriram
Published: March 2013

Rapid antigenic variation of HA, the major virion surface protein of influenza A virus, remains the principal challenge to the development of broader and more effective vaccines. Some regions of HA, such as the stem region proximal to the viral membrane, are nevertheless highly conserved across strains and among most subtypes. A fundamental question in vaccine design is the extent to which HA stem regions on the surface of the virus are accessible to broadly neutralizing antibodies. Here we report 3D structures derived from cryoelectron tomography of HA on intact 2009 H1N1 pandemic virions in the presence and absence of the antibody C179, which neutralizes viruses expressing a broad range of HA subtypes, including H1, H2, H5, H6, and H9. By fitting previously derived crystallographic structures of trimeric HA into the density maps, we deduced the locations of the molecular surfaces of HA involved in interaction with C179. Using computational methods to distinguish individual unliganded HA trimers from those that have bound C179 antibody, we demonstrate that ∼75% of HA trimers on the surface of the virus have C179 bound to the stem domain. Thus, despite their close packing on the viral membrane, the majority of HA trimers on intact virions are available to bind anti-stem antibodies that target conserved HA epitopes, establishing the feasibility of universal influenza vaccines that elicit such antibodies.
Diradical intermediate within the context of tryptophan tryptophylquinone biosynthesis
Authors: Yukl Erik T. , Liu Fange , Krzystek J. , Shin Sooim , Jensen Lyndal M. R. , Davidson Victor L. , Wilmot Carrie M. , Liu Aimin
Published: March 2013

Despite the importance of tryptophan (Trp) radicals in biology, very few radicals have been trapped and characterized in a physiologically meaningful context. Here we demonstrate that the diheme enzyme MauG uses Trp radical chemistry to catalyze formation of a Trp-derived tryptophan tryptophylquinone cofactor on its substrate protein, premethylamine dehydrogenase. The unusual six-electron oxidation that results in tryptophan tryptophylquinone formation occurs in three discrete two-electron catalytic steps. Here the exact order of these oxidation steps in the processive six-electron biosynthetic reaction is determined, and reaction intermediates are structurally characterized. The intermediates observed in crystal structures are also verified in solution using mass spectrometry. Furthermore, an unprecedented Trp-derived diradical species on premethylamine dehydrogenase, which is an intermediate in the first two-electron step, is characterized using high-frequency and -field electron paramagnetic resonance spectroscopy and UV-visible absorbance spectroscopy. This work defines a unique mechanism for radical-mediated catalysis of a protein substrate, and has broad implications in the areas of applied biocatalysis and understanding of oxidative protein modification during oxidative stress.
Nitration of Hsp90 induces cell death
Authors: Franco Maria Clara , Ye Yaozu , Refakis Christian A. , Feldman Jessica L. , Stokes Audrey L. , Basso Manuela , Melero Fernández de Mera Raquel M. , Sparrow Nicklaus A. , Calingasan Noel Y. , Kiaei Mahmoud , Rhoads Timothy W. , Ma Thong C. , Grumet Martin , Barnes Stephen , Beal M. Flint , Beckman Joseph S. , Mehl Ryan , Estévez Alvaro G.
Published: March 2013

Oxidative stress is a widely recognized cause of cell death associated with neurodegeneration, inflammation, and aging. Tyrosine nitration in these conditions has been reported extensively, but whether tyrosine nitration is a marker or plays a role in the cell-death processes was unknown. Here, we show that nitration of a single tyrosine residue on a small proportion of 90-kDa heat-shock protein (Hsp90), is sufficient to induce motor neuron death by the P2X7 receptor-dependent activation of the Fas pathway. Nitrotyrosine at position 33 or 56 stimulates a toxic gain of function that turns Hsp90 into a toxic protein. Using an antibody that recognizes the nitrated Hsp90, we found immunoreactivity in motor neurons of patients with amyotrophic lateral sclerosis, in an animal model of amyotrophic lateral sclerosis, and after experimental spinal cord injury. Our findings reveal that cell death can be triggered by nitration of a single protein and highlight nitrated Hsp90 as a potential target for the development of effective therapies for a large number of pathologies.
Illuminating the activation mechanisms and allosteric properties of metabotropic glutamate receptors
Authors: Doumazane Etienne , Scholler Pauline , Fabre Ludovic , Zwier Jurriaan M. , Trinquet Eric , Pin Jean-Philippe , Rondard Philippe
Published: March 2013

In multimeric cell-surface receptors, the conformational changes of the extracellular ligand-binding domains (ECDs) associated with receptor activation remain largely unknown. This is the case for the dimeric metabotropic glutamate receptors even though a number of ECD structures have been solved. Here, using an innovative approach based on cell-surface labeling and FRET, we demonstrate that a reorientation of the ECDs is associated with receptor and G-protein activation. Our approach helps identify partial agonists and highlights allosteric interactions between the effector and binding domains. Any approach expected to stabilize the active conformation of the effector domain increased the agonist potency in stabilizing the active ECDs conformation. These data provide key information on the structural dynamics and drug action at metabotropic glutamate receptors and validate an approach for tackling such analysis on other receptors.
Ready-to-use food-allocation policy to reduce the effects of childhood undernutrition in developing countries
Authors: Yang Yan , Van den Broeck Jan , Wein Lawrence M.
Published: March 2013

Several aid groups have proposed strategies for allocating ready-to-use (therapeutic and supplementary) foods to children in developing countries. Analysis is needed to investigate whether there are better alternatives. We use a longitudinal dataset of 5,657 children from Bwamanda to construct a bivariate time-series model that tracks each child’s height-for-age z score (HAZ) and weight-for-height z score (WHZ) throughout the first 5 y of life. Our optimization model chooses which individual children should receive ready-to-use therapeutic or supplementary food based on a child’s sex, age, HAZ, and WHZ, to minimize the mean number of disability-adjusted life years (DALYs) per child during 6–60 mo of age [which includes childhood mortality calculated from a logistic regression and the lifelong effects of stunting (i.e., low HAZ)] subject to a budget constraint. Compared with the strategies proposed by the aid groups, which do not use HAZ information, the simple strategy arising from our analysis [which prioritizes children according to low values of a linear combination of HAZ, WHZ, and age and allocates the entire budget to therapeutic (i.e., 500 kcal/d) food for the prioritized children] reduces the number of DALYs by 9% (for the same budget) or alternatively incurs the same number of DALYs with a 61% reduction in cost. Whereas our qualitative conclusions appear to be robust, the quantitative results derived from our analysis should be treated with caution because of the lack of reliable data on the impact of supplementary food on HAZ and WHZ, the application of our model to a single cohort of children and the inclusion and exclusion errors related to imperfect food targeting.
Murine thymic selection quantified using a unique method to capture deleted T cells
Authors: Stritesky Gretta L. , Xing Yan , Erickson Jami R. , Kalekar Lokesh A. , Wang Xiaodan , Mueller Daniel L. , Jameson Stephen C. , Hogquist Kristin A.
Published: March 2013

Thymic positive and negative selection events generate a T-cell repertoire that is MHC restricted and self-tolerant. The number of T cells undergoing positive and negative selection in normal mice has never been firmly established. We generated mice that lack the proapoptotic molecule Bim
(bcl2l11)
together with a Nur77
GFP
transgene, which allowed the identification and enumeration of T cells that would normally undergo clonal deletion. Using this method, we report the striking observation that six times more cells undergo negative selection than complete positive selection. Seventy-five percent of the negatively selected cells are deleted at the double positive stage in the thymic cortex, compared with 25% at the single positive stage in the medulla. The fact that more thymocytes are highly reactive to MHC than are weakly reactive is inconsistent with a random model of recognition and suggests that T-cell recognition is MHC biased. Furthermore, Bim
−/−
mice had an increased number of GFP
hi
cells in the peripheral lymphoid tissue and a corresponding increase in antigen experienced or anergic cell phenotype. Our data also show that the CD4+ T cells that are clonally deleted experienced only slightly stronger T-cell receptor signaling than those that developed into regulatory T cells.
Membrane lipid saturation activates endoplasmic reticulum unfolded protein response transducers through their transmembrane domains
Authors: Volmer Romain , van der Ploeg Kattria , Ron David
Published: March 2013

Endoplasmic reticulum (ER) stress sensors use a related luminal domain to monitor the unfolded protein load and convey the signal to downstream effectors, signaling an unfolded protein response (UPR) that maintains compartment-specific protein folding homeostasis. Surprisingly, perturbation of cellular lipid composition also activates the UPR, with important consequences in obesity and diabetes. However, it is unclear if direct sensing of the lipid perturbation contributes to UPR activation. We found that mutant mammalian ER stress sensors, IRE1α and PERK, lacking their luminal unfolded protein stress-sensing domain, nonetheless retained responsiveness to increased lipid saturation. Lipid saturation-mediated activation in cells required an ER-spanning transmembrane domain and was positively regulated in vitro by acyl-chain saturation in reconstituted liposomes. These observations suggest that direct sensing of the lipid composition of the ER membrane contributes to the UPR.
Learning and reconsolidation implicate different synaptic mechanisms
Authors: Li Yan , Meloni Edward G. , Carlezon William A. , Milad Mohammed R. , Pitman Roger K. , Nader Karim , Bolshakov Vadim Y.
Published: March 2013

Synaptic mechanisms underlying memory reconsolidation after retrieval are largely unknown. Here we report that synapses in projections to the lateral nucleus of the amygdala implicated in auditory fear conditioning, which are potentiated by learning, enter a labile state after memory reactivation, and must be restabilized through a postsynaptic mechanism implicating the mammalian target of rapamycin kinase-dependent signaling. Fear-conditioning–induced synaptic enhancements were primarily presynaptic in origin. Reconsolidation blockade with rapamycin, inhibiting mammalian target of rapamycin kinase activity, suppressed synaptic potentiation in slices from fear-conditioned rats. Surprisingly, this reduction of synaptic efficacy was mediated by post- but not presynaptic mechanisms. These findings suggest that different plasticity rules may apply to the processes underlying the acquisition of original fear memory and postreactivational stabilization of fear-conditioning–induced synaptic enhancements mediating fear memory reconsolidation.
Pubertally born neurons and glia are functionally integrated into limbic and hypothalamic circuits of the male Syrian hamster
Authors: Mohr Margaret A. , Sisk Cheryl L.
Published: March 2013

During puberty, the brain goes through extensive remodeling, involving the addition of new neurons and glia to brain regions beyond the canonical neurogenic regions (i.e., dentate gyrus and olfactory bulb), including limbic and hypothalamic cell groups associated with sex-typical behavior. Whether these pubertally born cells become functionally integrated into neural circuits remains unknown. To address this question, we gave male Syrian hamsters daily injections of the cell birthdate marker bromodeoxyuridine throughout puberty (postnatal day 28–49). Half of the animals were housed in enriched environments with access to a running wheel to determine whether enrichment increased the survival of pubertally born cells compared with the control environment. At 4 wk after the last BrdU injection, animals were allowed to interact with a receptive female and were then killed 1 h later. Triple-label immunofluorescence for BrdU, the mature neuron marker neuronal nuclear antigen, and the astrocytic marker glial fibrillary acidic protein revealed that a proportion of pubertally born cells in the medial preoptic area, arcuate nucleus, and medial amygdala differentiate into either mature neurons or astrocytes. Double-label immunofluorescence for BrdU and the protein Fos revealed that a subset of pubertally born cells in these regions is activated during sociosexual behavior, indicative of their functional incorporation into neural circuits. Enrichment affected the survival and activation of pubertally born cells in a brain region-specific manner. These results demonstrate that pubertally born cells located outside of the traditional neurogenic regions differentiate into neurons and glia and become functionally incorporated into neural circuits that subserve sex-typical behaviors.
Genome-scale analysis of gene function in the hydrogenotrophic methanogenic archaeon
Methanococcus maripaludis
Authors: Sarmiento Felipe , Mrázek Jan , Whitman William B.
Published: March 2013

A comprehensive whole-genome analysis of gene function by transposon mutagenesis and deep sequencing methodology has been implemented successfully in a representative of the Archaea domain. Libraries of transposon mutants were generated for the hydrogenotrophic, methanogenic archaeon
Methanococcus maripaludis
S2 using a derivative of the Tn5 transposon. About 89,000 unique insertions were mapped to the genome, which allowed for the classification of 526 genes or about 30% of the genome as possibly essential or strongly advantageous for growth in rich medium. Many of these genes were homologous to eukaryotic genes that encode fundamental processes in replication, transcription, and translation, providing direct evidence for their importance in Archaea. Some genes classified as possibly essential were unique to the archaeal or methanococcal lineages, such as that encoding DNA polymerase PolD. In contrast, the archaeal homolog to the gene encoding DNA polymerase B was not essential for growth, a conclusion confirmed by construction of an independent deletion mutation. Thus PolD, and not PolB, likely plays a fundamental role in DNA replication in methanococci. Similarly, 121 hypothetical ORFs were classified as possibly essential and likely play fundamental roles in methanococcal information processing or metabolism that are not established outside this group of prokaryotes.
Monolayer curvature stabilizes nanoscale raft domains in mixed lipid bilayers
Authors: Meinhardt Sebastian , Vink Richard L. C. , Schmid Friederike
Published: March 2013

According to the lipid raft hypothesis, biological lipid membranes are laterally heterogeneous and filled with nanoscale ordered “raft” domains, which are believed to play an important role for the organization of proteins in membranes. However, the mechanisms stabilizing such small rafts are not clear, and even their existence is sometimes questioned. Here, we report the observation of raft-like structures in a coarse-grained molecular model for multicomponent lipid bilayers. On small scales, our membranes demix into a liquid ordered (
lo
) phase and a liquid disordered (
ld
) phase. On large scales, phase separation is suppressed and gives way to a microemulsion-type state that contains nanometer-sized
lo
domains in an
ld
environment. Furthermore, we introduce a mechanism that generates rafts of finite size by a coupling between monolayer curvature and local composition. We show that mismatch between the spontaneous curvatures of monolayers in the
lo
and
ld
phases induces elastic interactions, which reduce the line tension between the
lo
and
ld
phases and can stabilize raft domains with a characteristic size of the order of a few nanometers. Our findings suggest that rafts in multicomponent bilayers might be closely related to the modulated ripple phase in one-component bilayers.
Electroencephalogram signatures of loss and recovery of consciousness from propofol
Authors: Purdon Patrick L. , Pierce Eric T. , Mukamel Eran A. , Prerau Michael J. , Walsh John L. , Wong Kin Foon K. , Salazar-Gomez Andres F. , Harrell Priscilla G. , Sampson Aaron L. , Cimenser Aylin , Ching ShiNung , Kopell Nancy J. , Tavares-Stoeckel Casie , Habeeb Kathleen , Merhar Rebecca , Brown Emery N.
Published: March 2013

Significance

Anesthesiologists reversibly manipulate the brain function of nearly 60,000 patients each day, but brain-state monitoring is not an accepted practice in anesthesia care because markers that reliably track changes in level of consciousness under general anesthesia have yet to be identified. We found specific behavioral and electrophysiological changes that mark the transition between consciousness and unconsciousness induced by propofol, one of the most commonly used anesthetic drugs. Our results provide insights into the mechanisms of propofol-induced unconsciousness and establish EEG signatures of this brain state that could be used to monitor the brain activity of patients receiving general anesthesia.
Gain-of-function mutations in the mechanically activated ion channel PIEZO2 cause a subtype of Distal Arthrogryposis
Authors: Coste Bertrand , Houge Gunnar , Murray Michael F. , Stitziel Nathan , Bandell Michael , Giovanni Monica A. , Philippakis Anthony , Hoischen Alexander , Riemer Gunnar , Steen Unni , Steen Vidar Martin , Mathur Jayanti , Cox James , Lebo Matthew , Rehm Heidi , Weiss Scott T. , Wood John N. , Maas Richard L. , Sunyaev Shamil R. , Patapoutian Ardem
Published: March 2013

Mechanotransduction, the pathway by which mechanical forces are translated to biological signals, plays important but poorly characterized roles in physiology. PIEZOs are recently identified, widely expressed, mechanically activated ion channels that are hypothesized to play a role in mechanotransduction in mammals. Here, we describe two distinct
PIEZO2
mutations in patients with a subtype of Distal Arthrogryposis Type 5 characterized by generalized autosomal dominant contractures with limited eye movements, restrictive lung disease, and variable absence of cruciate knee ligaments. Electrophysiological studies reveal that the two
PIEZO2
mutations affect biophysical properties related to channel inactivation: both E2727del and I802F mutations cause the PIEZO2-dependent, mechanically activated currents to recover faster from inactivation, while E2727del also causes a slowing of inactivation. Both types of changes in kinetics result in increased channel activity in response to a given mechanical stimulus, suggesting that Distal Arthrogryposis Type 5 can be caused by gain-of-function mutations in
PIEZO2
. We further show that overexpression of mutated
PIEZO2
cDNAs does not cause constitutive activity or toxicity to cells, indicating that the observed phenotype is likely due to a mechanotransduction defect. Our studies identify a type of channelopathy and link the dysfunction of mechanically activated ion channels to developmental malformations and joint contractures.
Estrogen receptor β sustains epithelial differentiation by regulating
prolyl hydroxylase 2
transcription
Authors: Mak Paul , Chang Cheng , Pursell Bryan , Mercurio Arthur M.
Published: March 2013

Estrogen receptor β (ERβ) promotes the degradation of hypoxia inducible factor 1α (HIF-1α), which contributes to the ability of this hormone receptor to sustain the differentiation of epithelial and carcinoma cells. Although the loss of ERβ and consequent HIF-1 activation occur in prostate cancer with profound consequences, the mechanism by which ERβ promotes the degradation of HIF-1α is unknown. We report that ERβ regulates the ligand (3β-adiol)-dependent transcription of
prolyl hydroxylase 2
(
PHD2
) also known as Egl nine homolog 1 (
EGLN1
), a 2-oxoglutarate-dependent dioxygenase that hydroxylates HIF-1α and targets it for recognition by the von Hippel-Lindau tumor suppressor and consequent degradation. ERβ promotes
PHD2
transcription by interacting with a unique estrogen response element in the 5′ UTR of the
PHD2
gene that functions as an enhancer. PHD2 itself is critical for maintaining epithelial differentiation. Loss of PHD2 expression or inhibition of its function results in dedifferentiation with characteristics of an epithelial–mesenchymal transition, and exogenous PHD2 expression in dedifferentiated cells can restore an epithelial phenotype. Moreover, expression of HIF-1α in cells that express PHD2 does not induce dedifferentiation but expression of HIF-1α containing mutations in the proline residues that are hydroxylated by PHD2 induces dedifferentiation. These data describe a unique mechanism for the regulation of HIF-1α stability that involves ERβ-mediated transcriptional regulation of
PHD2
and they highlight an unexpected role for PHD2 in maintaining epithelial differentiation.
Mechanism of the modulation of BK potassium channel complexes with different auxiliary subunit compositions by the omega-3 fatty acid DHA
Authors: Hoshi Toshinori , Tian Yutao , Xu Rong , Heinemann Stefan H. , Hou Shangwei
Published: March 2013

Large-conductance Ca
2+
- and voltage-activated K
+
(BK) channels are well known for their functional versatility, which is bestowed in part by their rich modulatory repertoire. We recently showed that long-chain omega-3 polyunsaturated fatty acids such as docosahexaenoic acid (DHA) found in oily fish lower blood pressure by activating vascular BK channels made of Slo1+β1 subunits. Here we examined the action of DHA on BK channels with different auxiliary subunit compositions. Neuronal Slo1+β4 channels were just as well activated by DHA as vascular Slo1+β1 channels. In contrast, the stimulatory effect of DHA was much smaller in Slo1+β2, Slo1+LRRC26 (γ1), and Slo1 channels without auxiliary subunits. Mutagenesis of β1, β2, and β4 showed that the large effect of DHA in Slo1+β1 and Slo1+β4 is conferred by the presence of two residues, one in the N terminus and the other in the first transmembrane segment of the β1 and β4 subunits. Transfer of this amino acid pair from β1 or β4 to β2 introduces a large response to DHA in Slo1+β2. The presence of a pair of oppositely charged residues at the aforementioned positions in β subunits is associated with a large response to DHA. The Slo1 auxiliary subunits are expressed in a highly tissue-dependent fashion. Thus, the subunit composition-dependent stimulation by DHA demonstrates that BK channels are effectors of omega-3 fatty acids with marked tissue specificity.
Modeling integrated photovoltaic–electrochemical devices using steady-state equivalent circuits
Authors: Winkler Mark T. , Cox Casandra R. , Nocera Daniel G. , Buonassisi Tonio
Published: March 2013

Significance

This article extends the construction of direct solar-to-fuels devices, such as the artificial leaf based on crystalline silicon. Because a single Si junction has insufficient potential to drive water splitting, it cannot be used for direct solar-to-fuels conversion. This paper performs an equivalent circuit analysis for multiple series-connected devices. The predictive utility of the model is demonstrated in the case of water oxidation at the surface of a Si solar cell, using a cobalt–borate oxygen evolving catalyst. Considering recent cost reductions of Si solar cells, this paper offers a path to the construction of low cost solar-to-fuels devices.
Arf
tumor suppressor and miR-205 regulate cell adhesion and formation of extraembryonic endoderm from pluripotent stem cells
Authors: Li Chunliang , Finkelstein David , Sherr Charles J.
Published: March 2013

Significance

The
Arf
tumor suppressor gene is not expressed in most normal tissues but when activated by oncogenic stress signals engages a p53-dependent transcriptional program that prevents tumor formation. Surprisingly, expression of the p19
Arf
protein in mouse embryoid bodies is required for the timely formation of extraembryonic endoderm (ExEn). Inactivation of
Arf
down-regulates a single microRNA, miR-205, which can “rescue” ExEn formation in
Arf
-null embryonic or induced pluripotent stem cells. During ExEn formation, miR-205 regulates a suite of genes that govern cell migration and adhesion, suggesting a conceptual basis for linking the roles of
Arf
in ExEn differentiation and tumor metastasis.
Organization of lampreyvariable lymphocyte receptor Clocus and repertoire development
Authors: Das Sabyasachi , Hirano Masayuki , Aghaallaei Narges , Bajoghli Baubak , Boehm Thomas , Cooper Max D.
Published: March 2013

Jawless vertebrates are pivotal representatives for studies of the evolution of adaptive immunity due to their unique position in chordate phylogeny. Lamprey and hagfish, the extant jawless vertebrates, have an alternative lymphocyte-based adaptive immune system that is based on somatically diversifying leucine-rich repeat (LRR)-based antigen receptors, termed variable lymphocyte receptors (VLRs). Lamprey T-like and B-like lymphocyte lineages have been shown to express VLRA and VLRB types of anticipatory receptors, respectively. An additional VLR type, termed VLRC, has recently been identified in arctic lamprey (Lethenteron camtschaticum), and our analysis indicates that VLRC sequences are well conserved in sea lamprey (Petromyzon marinus),L. camtschaticum, and European brook lamprey (Lampetra planeri). Genome sequences ofP. marinuswere analyzed to determine the organization of the VLRC-encoding locus. In addition to the incomplete germ-lineVLRCgene, we have identified 182 flanking donor genomic sequences that could be used to complete the assembly of matureVLRCgenes. DonorLRRcassettes were classifiable into five basic structural groups, the composition of which determines their order of use duringVLRCassembly by virtue of sequence similarities to the incomplete germ-line gene and to one another. BidirectionalVLRCassembly was predicted by comparisons of matureVLRCgenes with the sequences of donorLRRcassettes and verified by analysis of partially assembled intermediates. Biased and repetitive use of certain donorLRRcassettes was demonstrable in matureVLRCs. Our analysis provides insight into the unique molecular strategies used forVLRCgene assembly and repertoire diversification.
Extended Translation
Authors: Risku Hanna , Windhager Florian
Published: March 2013

Consideration of current developments in cognitive science is indispensable when defining research agendas addressing cognitive aspects of translation. One such development is the recognition of the extended nature of human cognition: Cognition is not just an information manipulation process in the brain, it is contextualised action embedded in a body and increasingly mediated by technologies and situated in its socio-cultural environment. Parallel developments are found in neighbouring disciplines, such as sociology with its actor-network and activity theories. This paper examines these approaches, their shared methodological tenets (i.e., ethnographic field studies) and the implications of the situated cognition approach for describing the cognitive aspects of translation, using a translation management case study to discuss conceptual and methodological issues.
Applying a newswriting research approach to translation
Authors: Ehrensberger-Dow Maureen , Perrin Daniel
Published: March 2013

Translation is a situated activity that involves more than simply producing target texts from source texts. In order to understand what translators actually do when they translate, their psycho-biographies as well as the social setting of the workplace and the contextual resources must be considered. In this paper, we outline how a mixed-method approach originally developed to study the newswriting processes of journalists at their workplaces can be applied in translation process research. We argue that progression analysis, which combines keystroke logging, screen recordings, eye-tracking, and cue-based retrospective verbalization, can be profitably used along with version analysis to gain insights into cognitive aspects of the translation process.
Promoting the Advancement of Women: Baha'i Schools for Girls in Iran, 1909–35
Authors: Zabihi-Moghaddam Siyamak
Published: March 2013

In the early twentieth century, Iranian Baha'is were at the forefront of efforts to promote modern schooling for girls in Iran. Using previously untapped published primary sources and archival records, this article examines the history of the Baha'i schools for girls in the context of modern schooling of Iranian girls and assesses their contribution to female education in Iran. This contribution was significant and all the more remarkable considering the Iranian Baha'is’ numbers and resources and the restrictions under which they operated. Most notably, in the spring of 1933, less than two years before the forced closure of Baha'i schools by the Pahlavi state, 4 percent of all females in Iran's accredited schools were enrolled in Baha'i schools. The Baha'i community's most prestigious school, Tarbīyat-i banāt in Tehran, was by this time Iran's largest girls’ school. Outside Tehran, in some localities, the only girls’ schools were run by Baha'is, and in others a significant portion of all female pupils were enrolled in Baha'i schools.
Iskandar's Bibulous Business: Wine, Drunkenness and the Calls to theSāqīin Nizāmī Ganjavī'sSharaf-nāma
Authors: van Ruymbeke Christine
Published: March 2013

The twelfth-century poet Nizāmī Ganjavī has produced his version of the adventures of Alexander as a unique composition mingling known Persian historiography and Qur'anic legends with unusual non-Islamic, especially Greek, elements in order to create hisIskandar-nāma(containing two parts, theSharaf-nāmaand theIqbāl-nāma) as a synthesis of eastern and western cultures. A first point is the examination of the reasons behind the importance given to wine and drunkenness within the narrative. The poet has stressed this further by heading each chapter with a call to thesāqī. The essay examines the appositeness of the invocations with the episodes in the narrative, it analyses examples of wine imagery (containing references to medicine, to the mirror and to religion) and questions the relation between authorial persona, narrator and characters, examining in particular the famous teetotaler claim in one of the introductory chapters of the first part of theIskandar-nāma.
Is Turkey coming to terms with its past? Politics of memory and majoritarian conservatism
Authors: Bakiner Onur
Published: March 2013

There is unprecedented domestic and international interest in Turkey's political past, accompanied by a societal demand for truth and justice in addressing past human rights violations. This article poses the question: Is Turkey coming to terms with its past? Drawing upon the literature on nationalism, identity, and collective memory, I argue that the Turkish state has recently taken steps to acknowledge and redress some of the past human rights violations. However, these limited and strategic acts of acknowledgment fall short of initiating a more comprehensive process of addressing past wrongs. The emergence of the Justice and Development Party as a dominant political force brings along the possibility that the discarded Kemalist memory framework will be replaced by what I callmajoritarian conservatism, a new government-sanctioned shared memory that promotes uncritical and conservative-nationalist interpretations of the past that have popular appeal, while enforcing silence on critical historiographies that challenge this hegemonic memory and identity project. Nonetheless, majoritarian conservatism will probably fail to assert state control over memory and history, even under a dominant government, as unofficial memory initiatives unsettle the hegemonic appropriation of the past.
The birth of corruption and the politics of anti-corruption in Albania, 1991–2005
Authors: Kajsiu Blendi
Published: March 2013

This paper analyzes the transformation of the signifier “corruption” in the Albanian public sphere during the period 1991–2005 from a discourse analysis approach. The aim is not to trace corruption in its presence and consequences, but to show how different articulations of corruption supported different agendas. More specifically, this paper aims to show how the corruption discourse that dominated Albanian public discussion during the period 1998–2005 served to legitimize a neoliberal order by articulating corruption as inherent to the public sector and to state intervention in the economy. This meant that corruption could be eliminated through neoliberal policies such as privatization and deregulation. Through a discourse analysis of corruption it is possible to politicize the concept of corruption instead of reducing it to a static and inherent feature of Albanian culture and society.
Safety of Feed Treated with 17α-Methyltestosterone (17MT) to Larval Nile Tilapia
Authors: Straus David L , Bowker James D , Bowman Molly P , Carty Daniel G , Mitchell Andrew J , Farmer Bradley D , Ledbetter Cynthia K
Published: March 2013

As a synthetic androgen, 17α-methyltestosterone (17MT) is frequently used to redirect the course of sex differentiation by exposing the undifferentiated gonad to a sufficient dosage. This hormone has been widely accepted as a safe and effective treatment for sex reversal in many fish species, and it is administered to larval tilapia (3–12 d old) for ∼28 consecutive days to produce populations of >90% males. This study assessed the safety of 17MT-treated feed when administered to larval Nile Tilapia Oreochromis niloticus at one, three, and five times (i.e., 1×, 3×, and 5×) the proposed dosage of 9 mg 17MT/kg fish daily for 28 consecutive days. Despite elevated total ammonia nitrogen levels measured during the last 5 d of the study, environmental conditions were acceptable for rearing tilapia. Fish fed aggressively regardless of the concentration of 17MT in the feed, behavior was considered normal with no dose-related differences detected, and no mortality was observed in the 3× treatment group. Fish that were treated with five times the proposed therapeutic dosage had significant pathological changes. Based on the results of this study, the 17MT margin of safety extends to at least 3× (27 mg 17MT/kg fish daily) the proposed dosage of 9 mg 17MT/kg fish daily when administered in feed for 28 d to Nile Tilapia.
Smokers Discount Their Drug of Abuse in the Same Way as Other Consumable Rewards
Authors: Jiga-Boy Gabriela M. , Storey Kayleigh , Buehner Marc J.
Published: March 2013

Recent research shows that drug abusers discount delayed monetary rewards more than nonabusers do, and they discount delayed substances of abuse (e.g., drugs) more than delayed money. Furthermore, non-drug-abusers discount food and substances of abuse (e.g., alcohol), more than money. Here, we compare the delay and probability discounting of money with that of a directly consumable reward (chocolate) and with that of a substance of abuse (cigarettes), in a drug-using population (smokers). In line with previous research, we found in two experiments that delay discounting differentiated between smokers and nonsmokers, and between money and a nonabused directly consumable reward (chocolate). In addition, our results show that there appears to be no difference in the extent to which smokers discount their abused substance compared to another directly consumable reward. These findings support the contention that drugs and food are part of the same category of primary reinforcers, whereas money is discounted differently, as a conditioned reinforcer.
IL-27 inhibits HIV-1 infection in human macrophages by down-regulating host factor SPTBN1 during monocyte to macrophage differentiation
Authors: Dai Lue , Lidie Kristy B. , Chen Qian , Adelsberger Joseph W. , Zheng Xin , Huang DaWei , Yang Jun , Lempicki Richard A. , Rehman Tauseef , Dewar Robin L. , Wang Yanmei , Hornung Ronald L. , Canizales Kelsey A. , Lockett Stephen J. , Lane H. Clifford , Imamichi Tomozumi
Published: March 2013

The susceptibility of macrophages to HIV-1 infection is modulated during monocyte differentiation. IL-27 is an anti-HIV cytokine that also modulates monocyte activation. In this study, we present new evidence that IL-27 promotes monocyte differentiation into macrophages that are nonpermissive for HIV-1 infection. Although IL-27 treatment does not affect expression of macrophage differentiation markers or macrophage biological functions, it confers HIV resistance by down-regulating spectrin β nonerythrocyte 1 (SPTBN1), a required host factor for HIV-1 infection. IL-27 down-regulates SPTBN1 through a TAK-1–mediated MAPK signaling pathway. Knockdown of SPTBN1 strongly inhibits HIV-1 infection of macrophages; conversely, overexpression of SPTBN1 markedly increases HIV susceptibility of IL-27–treated macrophages. Moreover, we demonstrate that SPTBN1 associates with HIV-1 gag proteins. Collectively, our results underscore the ability of IL-27 to protect macrophages from HIV-1 infection by down-regulating SPTBN1, thus indicating that SPTBN1 is an important host target to reduce HIV-1 replication in one major element of the viral reservoir.
IL-1R1 is required for dendritic cell–mediated T cell reactivation within the CNS during West Nile virus encephalitis
Authors: Durrant Douglas M. , Robinette Michelle L. , Klein Robyn S.
Published: March 2013

Infections of the central nervous system (CNS) with cytopathic viruses require efficient T cell responses to promote viral clearance, limit immunopathology, and enhance survival. We found that IL-1R1 is critical for effector T cell reactivation and limits inflammation within the CNS during murine West Nile virus (WNV) encephalitis. WNV-infected IL-1R1−/− mice display intact adaptive immunity in the periphery but succumb to WNV infection caused by loss of virologic control in the CNS with depressed local Th1 cytokine responses, despite parenchymal entry of virus-specific CD8+ T cells. Ex vivo analysis of CD4+ T cells from WNV-infected CNS of IL-1R1−/− mice revealed impaired effector responses, whereas CD8+ T cells revealed no cell intrinsic defects in response to WNV antigen. WNV-infected, IL-1R1−/− mice also exhibited decreased activation of CNS CD11c+CD11b−CD103+ and CD11c+CD11b−CD8α+Dec-205+ cells with reduced up-regulation of the co-stimulatory molecules CD80, CD86, and CD68. Adoptive transfer of wild-type CD11c-EYFP+ cells from WNV-infected CNS into WNV-infected IL-1R1−/− mice trafficked into the CNS restored T cell functions and improved survival from otherwise lethal infection. These data indicate that IL-1R1 signaling promotes virologic control during WNV infection specifically within the CNS via modulation of CD11c+ cell–mediated T cell reactivation at this site.
IL-1 enhances expansion, effector function, tissue localization, and memory response of antigen-specific CD8 T cells
Authors: Ben-Sasson Shlomo Z. , Hogg Alison , Hu-Li Jane , Wingfield Paul , Chen Xi , Crank Michelle , Caucheteux Stephane , Ratner-Hurevich Maya , Berzofsky Jay A. , Nir-Paz Ran , Paul William E.
Published: March 2013

Here, we show that interleukin-1 (IL-1) enhances antigen-driven CD8 T cell responses. When administered to recipients of OT-I T cell receptor transgenic CD8 T cells specific for an ovalbumin (OVA) peptide, IL-1 results in an increase in the numbers of wild-type but not IL1R1−/− OT-I cells, particularly in spleen, liver, and lung, upon immunization with OVA and lipopolysaccharide. IL-1 administration also results in an enhancement in the frequency of antigen-specific cells that are granzyme B+, have cytotoxic activity, and/ or produce interferon γ (IFN-γ). Cells primed in the presence of IL-1 display enhanced expression of granzyme B and increased capacity to produce IFN-γ when rechallenged 2 mo after priming. In three in vivo models, IL-1 enhances the protective value of weak immunogens. Thus, IL-1 has a marked enhancing effect on antigen-specific CD8 T cell expansion, differentiation, migration to the periphery, and memory.
Risk following hospitalization in stable chronic systolic heart failure
Authors: Abrahamsson Putte , Swedberg Karl , Borer Jeffrey S. , Böhm Michael , Kober Lars , Komajda Michel , Lloyd Suzanne M. , Metra Marco , Tavazzi Luigi , Ford Ian
Published: March 2013

Aims

We explored the impact of being hospitalized due to worsening heart failure (WHF) or a myocardial infarction (MI) on subsequent mortality in a large contemporary data set of patients with stable chronic systolic heart failure (HF).

Methods and results

A total of 6558 patients with stable systolic HF, 6505 with analysable data, with an EF of ≤35%, who were included in the Systolic Heart failure treatment with the If inhibitor ivabradine Trial (SHIFT), were followed for a median of 22.9 months with respect to hospitalizations and vital status. Among the 1288 patients who had at least one hospitalization due to WHF or MI, 455 (35.3%) died during follow‐up compared with 600 (11.5%) among patients not hospitalized for these reasons. The risk for death was highest in the early phase after hospitalization. The risk declined rapidly during the first month but remained 3.5‐fold (95% confidence interval 2.3–5.1) increased at 18 months after a first WHF hospitalization and 8.8‐fold (95% confidence interval 3.6–21.6) increased at 18 months after a first MI hospitalization.

Conclusion

The present study confirms previous findings that in patients with stable chronic systolic HF, a hospitalization for WHF or MI is associated with substantially increased risk for subsequent death even with contemporary extensive background pharmacological therapy. The risk is most pronounced in the early phase of hospitalization but remains elevated even after 18 months. Preventing HF hospitalization appears as an important therapeutic objective in such patients, and a hospitalization for WHF or MI should lead to a careful therapeutic reassessment.
Magnetic field control of the ordering of two-component suspension of hard rods
Authors: Slyusarenko K. , Reshetnyak V. , Reznikov Yu.
Published: March 2013

The Onsager theory of hard rod dispersion in a neutral solvent is extended to a case of two-component dispersion consisting of both non-magnetic and magnetic rods. It was found that the alignment of magneto-sensitive dispersion component by a magnetic field leads to the alignment of non-magnetic component in the dispersion and to an elimination of the isotropic phase. This effect is significant even at low relative concentrations of magnetic rods and leads to a magnetically induced anisotropy in a non-magnetic dispersion of rods mixed with the magnetic ones.
Tuning the defect configurations in nematic and smectic liquid crystalline shells
Authors: Liang Hsin-Ling , Noh JungHyun , Zentel Rudolf , Rudquist Per , Lagerwall Jan P.F.
Published: March 2013

Thin liquid crystalline shells surrounding and surrounded by aqueous phases can be conveniently produced using a nested capillary microfluidic system, as was first demonstrated by Fernandez-Nieveset al.in 2007. By choosing particular combinations of stabilizers in the internal and external phases, different types of alignment, uniform or hybrid, can be ensured within the shell. Here, we investigate shells in the nematic and smectic phases under varying boundary conditions, focusing in particular on textural transformations during phase transitions, on the interaction between topological defects in the director field and inclusions in the liquid crystal (LC), and on the possibility to relocate defects within the shell by rotating the shell in the gravitational field. We demonstrate that inclusions in a shell can seed defects that cannot form in a pristine shell, adding a further means of tuning the defect configuration, and that shells in which the internal aqueous phase is not density matched with the LC will gently rearrange the internal structure upon a rotation that changes the influence of gravity. Because the defects can act as anchor points for added linker molecules, allowing self-assembly of adjacent shells, the various arrangements of defects developing in these shells and the possibility of tuning the result by modifying boundary conditions, LC phase, thickness and diameter of the shell or applying external forces make this new LC configuration very attractive.
On the effect of carbon nanotubes on properties of liquid crystals
Authors: Schymura Stefan , Scalia Giusy
Published: March 2013

Liquid crystals (LCs), with their fluidity and self-organization, are attractive hosts for the dispersion and manipulation of macro- and nanoparticles, allowing the realization of their ordered assemblies. In addition, new functional materials can be created owing to the particle properties. Among the nanoparticles, carbon nanotubes (CNTs) stand out for their exceptional electrical, thermal and mechanical properties. While LCs can be used for manipulating CNTs, the nanotube properties are attractive also for influencing and tuning LC properties. In this paper, we discuss different aspects of the CNT–LC combination, briefly introducing their dispersion and interaction and then, more extensively, evaluating the CNT effect on selected properties of LCs relevant to display-related applications. We show that some previously reported improvements cannot be considered an intrinsic feature of CNT-doped LCs. In addition, we are also able to follow locally the Frederiks transition of CNT-doped LCs by Raman spectroscopy, revealing the direct effect of bundles of CNTs on LC reorientation.
Pushing, pulling and twisting liquid crystal systems: exploring new directions with laser manipulation
Authors: Sanders Jennifer L. , Yang Yiming , Dickinson Mark R. , Gleeson Helen F.
Published: March 2013

Optical tweezers are exciting tools with which to explore liquid crystal (LC) systems; the motion of particles held in laser traps through LCs is perhaps the only approach that allows a low Ericksen number regime to be accessed. This offers a new method of studying the microrheology associated with micrometre-sized particles suspended in LC media—and such hybrid systems are of increasing importance as novel soft-matter systems. This paper describes the microrheology experiments that are possible in nematic materials and discusses the sometimes unexpected results that ensue. It also presents observations made in the inverse system; micrometre-sized droplets of LC suspended in an isotropic medium.