bluuebunny/crossref_metadata_2025 huggingface dataset:
Warming-induced reductions in body size are greater in aquatic than terrestrial species
Authors: Forster Jack , Hirst Andrew G. , Atkinson David
Published: November 2012

Most ectothermic organisms mature at smaller body sizes when reared in warmer conditions. This phenotypically plastic response, known as the “temperature-size rule” (TSR), is one of the most taxonomically widespread patterns in biology. However, the TSR remains a longstanding life-history puzzle for which no dominant driver has been found. We propose that oxygen supply plays a central role in explaining the magnitude of ectothermic temperature-size responses. Given the much lower oxygen availability and greater effort required to increase uptake in water vs. air, we predict that the TSR in aquatic organisms, especially larger species with lower surface area–body mass ratios, will be stronger than in terrestrial organisms. We performed a meta-analysis of 1,890 body mass responses to temperature in controlled experiments on 169 terrestrial, freshwater, and marine species. This reveals that the strength of the temperature-size response is greater in aquatic than terrestrial species. In animal species of ∼100 mg dry mass, the temperature-size response of aquatic organisms is 10 times greater than in terrestrial organisms (−5.0% °C
−1
vs. −0.5% °C
−1
). Moreover, although the size response of small (<0.1 mg dry mass) aquatic and terrestrial species is similar, increases in species size cause the response to become increasingly negative in aquatic species, as predicted, but on average less negative in terrestrial species. These results support oxygen as a major driver of temperature-size responses in aquatic organisms. Further, the environment-dependent differences parallel latitudinal body size clines, and will influence predicted impacts of climate warming on food production, community structure, and food-web dynamics.
Early responses to adenoviral-mediated transfer of the aquaporin-1 cDNA for radiation-induced salivary hypofunction
Authors: Baum Bruce J. , Alevizos Ilias , Zheng Changyu , Cotrim Ana P. , Liu Shuying , McCullagh Linda , Goldsmith Corinne M. , Burbelo Peter D. , Citrin Deborah E. , Mitchell James B. , Nottingham Liesl K. , Rudy Susan F. , Van Waes Carter , Whatley Millie A. , Brahim Jaime S. , Chiorini John A. , Danielides Stamatina , Turner R. James , Patronas Nicholas J. , Chen Clara C. , Nikolov Nikolay P. , Illei Gabor G.
Published: November 2012

No conventional therapy exists for salivary hypofunction in surviving head and neck cancer patients with Radiation Therapy Oncology Group late grade 2–3 toxicity. We conducted a phase I clinical trial to test the safety and biologic efficacy of serotype 5, adenoviral-mediated aquaporin-1 cDNA transfer to a single previously irradiated parotid gland in 11 subjects using an open label, single-dose, dose-escalation design (AdhAQP1 vector; four dose tiers from 4.8 × 10
7
to 5.8 × 10
9
vector particles per gland). Treated subjects were followed at scheduled intervals. Multiple safety parameters were measured and biologic efficacy was evaluated with measurements of parotid salivary flow rate. Symptoms were assessed with a visual analog scale. All subjects tolerated vector delivery and study procedures well over the 42-d study period reported. No deaths, serious adverse events, or dose-limiting toxicities occurred. Generally, few adverse events occurred, and all were considered mild or moderate. No consistent changes were found in any clinical chemistry and hematology parameters measured. Objective responses were seen in six subjects, all at doses <5.8 × 10
9
vector particles per gland. Five of these six subjects also experienced subjective improvement in xerostomia. AdhAQP1 vector delivery to a single parotid gland was safe and transfer of the hAQP1 cDNA increased parotid flow and relieved symptoms in a subset of subjects.
Extraordinary genome stability in the ciliate
Paramecium tetraurelia
Authors: Sung Way , Tucker Abraham E. , Doak Thomas G. , Choi Eunjin , Thomas W. Kelley , Lynch Michael
Published: November 2012

Mutation plays a central role in all evolutionary processes and is also the basis of genetic disorders. Established base-substitution mutation rates in eukaryotes range between ∼5 × 10
−10
and 5 × 10
−8
per site per generation, but here we report a genome-wide estimate for
Paramecium tetraurelia
that is more than an order of magnitude lower than any previous eukaryotic estimate. Nevertheless, when the mutation rate per cell division is extrapolated to the length of the sexual cycle for this protist, the measure obtained is comparable to that for multicellular species with similar genome sizes. Because
Paramecium
has a transcriptionally silent germ-line nucleus, these results are consistent with the hypothesis that natural selection operates on the cumulative germ-line replication fidelity per episode of somatic gene expression, with the germ-line mutation rate per cell division evolving downward to the lower barrier imposed by random genetic drift. We observe ciliate-specific modifications of widely conserved amino acid sites in DNA polymerases as one potential explanation for unusually high levels of replication fidelity.
Complex effects of nucleotide variants in a mammalian
cis
-regulatory element
Authors: Kwasnieski Jamie C. , Mogno Ilaria , Myers Connie A. , Corbo Joseph C. , Cohen Barak A.
Published: November 2012

Cis
-regulatory elements (CREs) control gene expression by recruiting transcription factors (TFs) and other DNA binding proteins. We aim to understand how individual nucleotides contribute to the function of CREs. Here we introduce CRE analysis by sequencing (CRE-seq), a high-throughput method for producing and testing large numbers of reporter genes in mammalian cells. We used CRE-seq to assay >1,000 single and double nucleotide mutations in a 52-bp CRE in the
Rhodopsin
promoter that drives strong and specific expression in mammalian photoreceptors. We find that this particular CRE is remarkably complex. The majority (86%) of single nucleotide substitutions in this sequence exert significant effects on regulatory activity. Although changes in the affinity of known TF binding sites explain some of these expression changes, we present evidence for complex phenomena, including binding site turnover and TF competition. Analysis of double mutants revealed complex, nucleotide-specific interactions between residues in different TF binding sites. We conclude that some mammalian CREs are finely tuned by evolution and function through complex, nonadditive interactions between bound TFs. CRE-seq will be an important tool to uncover the rules that govern these interactions.
Protein tyrosine phosphatase 1B is a key regulator of IFNAR1 endocytosis and a target for antiviral therapies
Authors: Carbone Christopher J. , Zheng Hui , Bhattacharya Sabyasachi , Lewis John R. , Reiter Alexander M. , Henthorn Paula , Zhang Zhong-Yin , Baker Darren P. , Ukkiramapandian Radha , Bence Kendra K. , Fuchs Serge Y.
Published: November 2012

Type 1 interferons (IFN1) elicit antiviral defenses by activating the cognate receptor composed of IFN-α/β receptor chain 1 (IFNAR1) and IFNAR2. Down-regulation of this receptor occurs through IFN1-stimulated IFNAR1 ubiquitination, which exposes a Y466-based linear endocytic motif within IFNAR1 to recruitment of the adaptin protein-2 complex (AP2) and ensuing receptor endocytosis. Paradoxically, IFN1-induced Janus kinase-mediated phosphorylation of Y466 is expected to decrease its affinity for AP2 and to inhibit the endocytic rate. To explain how IFN1 promotes Y466 phosphorylation yet stimulates IFNAR1 internalization, we proposed that the activity of a protein tyrosine phosphatase (PTP) is required to enable both events by dephosphorylating Y466. An RNAi-based screen identified PTP1B as a specific regulator of IFNAR1 endocytosis stimulated by IFN1, but not by ligand-independent inducers of IFNAR1 ubiquitination. PTP1B is a promising target for treatment of obesity and diabetes; numerous research programs are aimed at identification and characterization of clinically relevant inhibitors of PTP1B. PTP1B is capable of binding and dephosphorylating IFNAR1. Genetic or pharmacologic modulation of PTP1B activity regulated IFN1 signaling in a manner dependent on the integrity of Y466 within IFNAR1 in human cells. These effects were less evident in mouse cells whose IFNAR1 lacks an analogous motif. PTP1B inhibitors robustly augmented the antiviral effects of IFN1 against vesicular stomatitis and hepatitis C viruses in human cells and proved beneficial in feline stomatitis patients. The clinical significance of these findings in the context of using PTP1B inhibitors to increase the therapeutic efficacy of IFN against viral infections is discussed.
Image sequence reactivation in awake V4 networks
Authors: Eagleman Sarah L. , Dragoi Valentin
Published: November 2012

In the absence of sensory input, neuronal networks are far from being silent. Whether spontaneous changes in ongoing activity reflect previous sensory experience or stochastic fluctuations in brain activity is not well understood. Here we describe reactivation of stimulus-evoked activity in awake visual cortical networks. We found that continuous exposure to randomly flashed image sequences induces reactivation in macaque V4 cortical networks in the absence of visual stimulation. This reactivation of previously evoked activity is stimulus-specific, occurs only in the same temporal order as the original response, and strengthens with increased stimulus exposures. Importantly, cells exhibiting significant reactivation carry more information about the stimulus than cells that do not reactivate. These results demonstrate a surprising degree of experience-dependent plasticity in visual cortical networks as a result of repeated exposure to unattended information. We suggest that awake reactivation in visual cortex may underlie perceptual learning by passive stimulus exposure.
Developmental stage-specific metabolic and transcriptional activity of
Chlamydia trachomatis
in an axenic medium
Authors: Omsland Anders , Sager Janet , Nair Vinod , Sturdevant Daniel E. , Hackstadt Ted
Published: November 2012

Chlamydia trachomatis
is among the most clinically significant human pathogens, yet their obligate intracellular nature places severe restrictions upon research. Chlamydiae undergo a biphasic developmental cycle characterized by an infectious cell type known as an elementary body (EB) and an intracellular replicative form called a reticulate body (RB). EBs have historically been described as metabolically dormant. A cell-free (axenic) culture system was developed, which showed high levels of metabolic and biosynthetic activity from both EBs and RBs, although the requirements differed for each. EBs preferentially used glucose-6-phosphate as an energy source, whereas RBs required ATP. Both developmental forms showed increased activity when incubated under microaerobic conditions. Incorporation of isotopically labeled amino acids into proteins from both developmental forms indicated unique expression profiles, which were confirmed by genome-wide transcriptional analysis. The described axenic culture system will greatly enhance biochemical and physiological analyses of chlamydiae.
Encounter with antigen-specific primed CD4 T cells promotes MHC class II degradation in dendritic cells
Authors: Furuta Kazuyuki , Ishido Satoshi , Roche Paul A.
Published: November 2012

Major histocompatibility complex class II molecules (MHC-II) on antigen presenting cells (APCs) engage the TCR on antigen-specific CD4 T cells, thereby providing the specificity required for T cell priming and the induction of an effective immune response. In this study, we have asked whether antigen-loaded dendritic cells (DCs) that have been in contact with antigen-specific CD4 T cells retain the ability to stimulate additional naïve T cells. We show that encounter with antigen-specific primed CD4 T cells induces the degradation of surface MHC-II in antigen-loaded DCs and inhibits the ability of these DCs to stimulate additional naïve CD4 T cells. Cross-linking with MHC-II mAb as a surrogate for T-cell engagement also inhibits APC function and induces MHC-II degradation by promoting the clustering of MHC-II present in lipid raft membrane microdomains, a process that leads to MHC-II endocytosis and degradation in lysosomes. Encounter of DCs with antigen-specific primed T cells or engagement of MHC-II with antibodies promotes the degradation of both immunologically relevant and irrelevant MHC-II molecules. These data demonstrate that engagement of MHC-II on DCs after encounter with antigen-specific primed CD4 T cells promotes the down-regulation of cell surface MHC-II in DCs, thereby attenuating additional activation of naïve CD4 T cells by these APCs.
Redundant phenazine operons in
Pseudomonas aeruginosa
exhibit environment-dependent expression and differential roles in pathogenicity
Authors: Recinos David A. , Sekedat Matthew D. , Hernandez Adriana , Cohen Taylor Sitarik , Sakhtah Hassan , Prince Alice S. , Price-Whelan Alexa , Dietrich Lars E. P.
Published: November 2012

Evolutionary biologists have postulated that several fitness advantages may be conferred by the maintenance of duplicate genes, including environmental adaptation resulting from differential regulation. We examined the expression and physiological contributions of two redundant operons in the adaptable bacterium
Pseudomonas aeruginosa
PA14. These operons,
phzA1-G1
(
phz1
) and
phzA2-G2
(
phz2
), encode nearly identical sets of proteins that catalyze the synthesis of phenazine-1-carboxylic acid, the precursor for several phenazine derivatives. Phenazines perform diverse roles in
P. aeruginosa
physiology and act as virulence factors during opportunistic infections of plant and animal hosts. Although reports have indicated that
phz1
is regulated by the
Pseudomonas
quinolone signal, factors controlling
phz2
expression have not been identified, and the relative contributions of these redundant operons to phenazine biosynthesis have not been evaluated. We found that in liquid cultures,
phz1
was expressed at higher levels than
phz2
, although
phz2
showed a greater contribution to phenazine production. In colony biofilms,
phz2
was expressed at high levels, whereas
phz1
expression was not detectable, and
phz2
was responsible for virtually all phenazine production. Analysis of mutants defective in quinolone signal synthesis revealed a critical role for 4-hydroxy-2-heptylquinoline in
phz2
induction. Finally, deletion of
phz2
, but not of
phz1
, decreased lung colonization in a murine model of infection. These results suggest that differential regulation of the redundant
phz
operons allows
P. aeruginosa
to adapt to diverse environments.
Splicing program of human MENA produces a previously undescribed isoform associated with invasive, mesenchymal-like breast tumors
Authors: Di Modugno Francesca , Iapicca Pierluigi , Boudreau Aaron , Mottolese Marcella , Terrenato Irene , Perracchio Letizia , Carstens Russ P. , Santoni Angela , Bissell Mina J. , Nisticò Paola
Published: November 2012

Human mena (hMENA), a member of the actin cytoskeleton regulators Ena/VASP, is overexpressed in high-risk preneoplastic lesions and in primary breast tumors and has been identified as playing a role in invasiveness and poor prognosis in breast cancers that express HER2. Here we identify a unique isoform, hMENAΔv6, derived from the
hMENA
alternative splicing program. In an isogenic model of human breast cancer progression, we show that hMENA
11a
is expressed in premalignant cells, whereas hMENAΔv6 expression is restricted to invasive cancer cells. “Reversion” of the malignant phenotype leads to concurrent down-regulation of all hMENA isoforms. In breast cancer cell lines, isoform-specific hMENA overexpression or knockdown revealed that in the absence of hMENA
11a
, overexpression of hMENAΔv6 increased cell invasion, whereas overexpression of hMENA
11a
reduced the migratory and invasive ability of these cells.
hMENA

11a

splicing was shown to be dependent on the epithelial regulator of splicing 1 (ESRP1), and forced expression of ESRP1 in invasive mesenchymal breast cancer cells caused a phenotypic switch reminiscent of a mesenchymal-to-epithelial transition (MET) characterized by changes in the cytoskeletal architecture, reexpression of hMENA
11a
, and a reduction in cell invasion. hMENA-positive primary breast tumors, which are hMENA
11a
-negative, are more frequently E-cadherin low in comparison with tumors expressing hMENA
11a
. These data suggest that polarized and growth-arrested cellular architecture correlates with absence of alternative hMENA isoform expression, and that the
hMENA
splicing program is relevant to malignant progression in invasive disease.
Shear-induced phase transition of nanocrystalline hexagonal boron nitride to wurtzitic structure at room temperature and lower pressure
Authors: Ji Cheng , Levitas Valery I. , Zhu Hongyang , Chaudhuri Jharna , Marathe Archis , Ma Yanzhang
Published: November 2012

Disordered structures of boron nitride (BN), graphite, boron carbide (BC), and boron carbon nitride (BCN) systems are considered important precursor materials for synthesis of superhard phases in these systems. However, phase transformation of such materials can be achieved only at extreme pressure–temperature conditions, which is irrelevant to industrial applications. Here, the phase transition from disordered nanocrystalline hexagonal (h)BN to superhard wurtzitic (w)BN was found at room temperature under a pressure of 6.7 GPa after applying large plastic shear in a rotational diamond anvil cell (RDAC) monitored by in situ synchrotron X-ray diffraction (XRD) measurements. However, under hydrostatic compression to 52.8 GPa, the same hBN sample did not transform to wBN but probably underwent a reversible transformation to a high-pressure disordered phase with closed-packed buckled layers. The current phase-transition pressure is the lowest among all reported direct-phase transitions from hBN to wBN at room temperature. Usually, large plastic straining leads to disordering and amorphization; here, in contrast, highly disordered hBN transformed to crystalline wBN. The mechanisms of strain-induced phase transformation and the reasons for such a low transformation pressure are discussed. Our results demonstrate a potential of low pressure–room temperature synthesis of superhard materials under plastic shear from disordered or amorphous precursors. They also open a pathway of phase transformation of nanocrystalline materials and materials with disordered and amorphous structures under extensive shear.
Predictive energy landscapes for protein–protein association
Authors: Zheng Weihua , Schafer Nicholas P. , Davtyan Aram , Papoian Garegin A. , Wolynes Peter G.
Published: November 2012

We investigate protein–protein association using the associative-memory, water-mediated, structure, and energy model (AWSEM), a coarse-grained protein folding model that has been optimized using energy-landscape theory. The potential was originally parameterized by enforcing a funneled nature for a database of dimeric interfaces but was later further optimized to create funneled folding landscapes for individual monomeric proteins. The ability of the model to predict interfaces was not tested previously. The present results show that simulated annealing of the model indeed is able to predict successfully the native interfaces of eight homodimers and four heterodimers, thus amounting to a flexible docking algorithm. We go on to address the relative importance of monomer geometry, flexibility, and nonnative intermonomeric contacts in the association process for the homodimers. Monomer surface geometry is found to be important in determining the binding interface, but it is insufficient. Using a uniform binding potential rather than the water-mediated potential results in sampling of misbound structures that are geometrically preferred but are nonetheless energetically disfavored by AWSEM, as well as in nature. Depending on the stability of the unbound monomers, nonnative contacts play different roles in the association process. For unstable monomers, thermodynamic states stabilized by nonnative interactions correspond to productive, on-pathway intermediates and can, therefore, catalyze binding through a fly-casting mechanism. For stable monomers, in contrast, states stabilized by nonnative interactions generally correspond to traps that impede binding.
Bioinformatic identification of genes suppressing genome instability
Authors: Putnam Christopher D. , Allen-Soltero Stephanie R. , Martinez Sandra L. , Chan Jason E. , Hayes Tikvah K. , Kolodner Richard D.
Published: November 2012

Unbiased forward genetic screens for mutations causing increased gross chromosomal rearrangement (GCR) rates in
Saccharomyces cerevisiae
are hampered by the difficulty in reliably using qualitative GCR assays to detect mutants with small but significantly increased GCR rates. We therefore developed a bioinformatic procedure using genome-wide functional genomics screens to identify and prioritize candidate GCR-suppressing genes on the basis of the shared drug sensitivity suppression and similar genetic interactions as known GCR suppressors. The number of known suppressors was increased from 75 to 110 by testing 87 predicted genes, which identified unanticipated pathways in this process. This analysis explicitly dealt with the lack of concordance among high-throughput datasets to increase the reliability of phenotypic predictions. Additionally, shared phenotypes in one assay were imperfect predictors for shared phenotypes in other assays, indicating that although genome-wide datasets can be useful in aggregate, caution and validation methods are required when deciphering biological functions via surrogate measures, including growth-based genetic interactions.
Generalized entropies and logarithms and their duality relations
Authors: Hanel Rudolf , Thurner Stefan , Gell-Mann Murray
Published: November 2012

For statistical systems that violate one of the four Shannon–Khinchin axioms, entropy takes a more general form than the Boltzmann–Gibbs entropy. The framework of superstatistics allows one to formulate a maximum entropy principle with these generalized entropies, making them useful for understanding distribution functions of non-Markovian or nonergodic complex systems. For such systems where the composability axiom is violated there exist only two ways to implement the maximum entropy principle, one using escort probabilities, the other not. The two ways are connected through a duality. Here we show that this duality fixes a unique escort probability, which allows us to derive a complete theory of the generalized logarithms that naturally arise from the violation of this axiom. We then show how the functional forms of these generalized logarithms are related to the asymptotic scaling behavior of the entropy.
Mouse mtDNA mutant model of Leber hereditary optic neuropathy
Authors: Lin Chun Shi , Sharpley Mark S. , Fan Weiwei , Waymire Katrina G. , Sadun Alfredo A. , Carelli Valerio , Ross-Cisneros Fred N. , Baciu Peter , Sung Eric , McManus Meagan J. , Pan Billy X. , Gil Daniel W. , MacGregor Grant R. , Wallace Douglas C.
Published: November 2012

An animal model of Leber hereditary optic neuropathy (LHON) was produced by introducing the human optic atrophy mtDNA
ND6
P25L mutation into the mouse. Mice with this mutation exhibited reduction in retinal function by elecroretinogram (ERG), age-related decline in central smaller caliber optic nerve fibers with sparing of larger peripheral fibers, neuronal accumulation of abnormal mitochondria, axonal swelling, and demyelination. Mitochondrial analysis revealed partial complex I and respiration defects and increased reactive oxygen species (ROS) production, whereas synaptosome analysis revealed decreased complex I activity and increased ROS but no diminution of ATP production. Thus, LHON pathophysiology may result from oxidative stress.
Most rhesus macaques infected with the CCR5-tropic SHIV
AD8
generate cross-reactive antibodies that neutralize multiple HIV-1 strains
Authors: Shingai Masashi , Donau Olivia K. , Schmidt Stephen D. , Gautam Rajeev , Plishka Ronald J. , Buckler-White Alicia , Sadjadpour Reza , Lee Wendy R. , LaBranche Celia C. , Montefiori David C. , Mascola John R. , Nishimura Yoshiaki , Martin Malcolm A.
Published: November 2012

The induction of broadly reacting neutralizing antibodies has been a major goal of HIV vaccine research. Characterization of a pathogenic CCR5 (R5)-tropic SIV/HIV chimeric virus (SHIV) molecular clone (SHIV
AD8-EO
) revealed that eight of eight infected animals developed cross-reactive neutralizing antibodies (NAbs) directed against an envelope glycoprotein derived from the heterologous HIV-1
DH12
strain. A panel of plasmas, collected from monkeys inoculated with either molecularly cloned or uncloned SHIV
AD8
stocks, exhibited cross-neutralization against multiple tier 1 and tier 2 HIV-1 clade B isolates. One SHIV
AD8
-infected animal also developed NAbs against clades A and C HIV-1 strains. In this particular infected macaque, the cross-reacting anti–HIV-1 NAbs produced between weeks 7 and 13 were directed against a neutralization-sensitive virus strain, whereas neutralizing activities emerging at weeks 41–51 targeted more neutralization-resistant HIV-1 isolates. These results indicate that the SHIV
AD8
macaque model represents a potentially valuable experimental system for investigating B-cell maturation and the induction of cross-reactive NAbs directed against multiple HIV-1 strains.
Turning self-destructing
Salmonella
into a universal DNA vaccine delivery platform
Authors: Kong Wei , Brovold Matthew , Koeneman Brian A. , Clark-Curtiss Josephine , Curtiss Roy
Published: November 2012

We previously developed a biological containment system using recombinant
Salmonella
Typhimurium strains that are attenuated yet capable of synthesizing protective antigens. The regulated delayed attenuation and programmed self-destructing features designed into these
S
. Typhimurium strains enable them to efficiently colonize host tissues and allow release of the bacterial cell contents after lysis. To turn such a recombinant attenuated
Salmonella
vaccine (RASV) strain into a universal DNA vaccine-delivery vehicle, our approach was to genetically modify RASV strains to display a hyperinvasive phenotype to maximize
Salmonella
host entry and host cell internalization, to enable
Salmonella
endosomal escape to release a DNA vaccine into the cytosol, and to decrease
Salmonella
-induced pyroptosis/apoptosis that allows the DNA vaccine time to traffic to the nucleus for efficient synthesis of encoded protective antigens. A DNA vaccine vector that encodes a domain that contributes to the arabinose-regulated lysis phenotype but has a eukaryotic promoter was constructed. The vector was then improved by insertion of multiple DNA nuclear-targeting sequences for efficient nuclear trafficking and gene expression, and by increasing nuclease resistance to protect the plasmid from host degradation. A DNA vaccine encoding influenza WSN virus HA antigen delivered by the RASV strain with the best genetic attributes induced complete protection to mice against a lethal influenza virus challenge. Adoption of these technological improvements will revolutionize means for effective delivery of DNA vaccines to stimulate mucosal, systemic, and cellular protective immunities, and lead to a paradigm shift in cost-effective control and prevention of a diversity of diseases.
The role of genre in information structuring in English
Authors: Kerz Elma
Published: November 2012

In a recent paper, Biber and Gray (2010) provide empirical evidence for the dramatic increase of compressed structures in English academic writing over the last 100 years. According to their corpus findings, the grammatical complexity of academic writing displays a phrasal rather than clausal character, the corollary of which is a compressed rather than elaborated discourse style (the latter one being typical of spoken registers). Given this finding, the question arises as to how far the traditional view that information structure should be viewed as a single partition of information within a given utterance adequately accounts for genre-specific information packaging strategies. To provide an answer to this question, the current study sets out to explore and compare information structuring within what will be referred to here as ‘compression strategies’, namely the use of adverbial subordinate clauses, -ING constructions, and complex NP constructions across two different genres: the highly compressed genre of research article abstracts, and fiction. The findings reported here suggest that in more compressed discourse styles such as academic writing, there is a higher probability of encountering information structure partition not only at the clausal but also at the phrasal level. The present paper highlights the importance of genre variation as one predictor of variation in information structuring within constructions.
Noting and evaluating contact between Japanese and Australian academic cultures
Authors: Nemoto Hiroyuki
Published: November 2012

This paper reports on a case study of Japanese exchange students that investigated the ways such students note and evaluate various types of contact between native and host academic cultures while participating in new communities of practice at an Australian university. In this study, language management theory (Jernudd & Neustupný, 1987; Neustupný, 1985, 1994, 2004) was employed in conjunction with Lave and Wenger’s (1991) concept of legitimate peripheral participation in order to investigate the sociocultural influence on cognitive processes of language management. The findings illustrate that not only norm deviations but also the phenomena relating to norm universality and compatibility generated processes of noting and evaluation. This study also provides an insight into mechanisms of self- and other-noting, as well as negative evaluations of norm deviations, and sheds light on positive evaluations of common disciplinary knowledge and cross-cultural situational similarities. Based on the findings, this paper indicates that noting and evaluation in language management processes should be considered in relation to students’ social positionings, their power relations with other community members, their perceptions of self, and the context where the management occurs.
Perceived antecedents of marital satisfaction among Turkish, Turkish‐Dutch, and Dutch couples
Authors: Celenk Ozgur , van de Vijver Fons J. R.
Published: November 2012

We studied mainstream couples in The Netherlands and Turkey as well as Turkish‐Dutch immigrant couples to address cultural factors associated with marital satisfaction. A total of 13 Turkish (mainstream couples living in Turkey), 19 Turkish‐Dutch (Turkish immigrant couples living in The Netherlands), and 17 Dutch (mainstream couples living in The Netherlands) married dyads (total of 98 individuals) were independently interviewed about positive and negative characteristics of marriages, determinants of general marital satisfaction and dissatisfaction, spousal communication, marital conflict, and marital roles. Multivariate tests revealed ethnic group differences on all marriage‐related domains except the conflict resolution strategies. However, univariate analyses showed differences in few themes within domains; main differences were assessed between the Turkish/Turkish‐Dutch (who put more emphasis on children and economical aspects) and Dutch couples (who put more emphasis on behavior, and personality of the spouse, reciprocity, emotional sharing, and psychological roles). Turkish‐Dutch couples were more similar to Turkish than to Dutch couples. Results were discussed in light of the socioeconomic development and cultural value theories, which are believed to provide a useful framework for understanding the role of culture in marital satisfaction.
Living between Worlds Ancient and Modern: The Musical Collaboration of Kathleen Schlesinger and Elsie Hamilton
Authors: Bowan Kate
Published: November 2012

Musicology has recently re-evaluated the nature, form and purpose of musical biography, reflecting a broader ‘biographical turn’ in the humanities. This article takes up recent challenges to move beyond the traditional model of the ‘life and works’ of ‘great’ composers and joins the search for new paradigms of musical biography. The lives of the Australian microtonal composer Elsie Hamilton (1880–1965) and the British music archaeologist Kathleen Schlesinger (1862–1953), and their collaboration, which spanned three decades, are offered as a case study that demonstrates the importance of international and transnational networks for comparative musicology and modern music, and reveals the role of women as critical agents of scholarship and cultural transmission. It also lays bare the considerable influence exerted by the fin de siècle occult revival upon the search for new modalities of musical expression. It is an example of how a biographical approach allows an expansive examination of a mentalité and can bring together a range of discourses to reveal unrecognized connections and relationships.
At the Intersection of Public and Private Musical Life: Brahms's Op. 51 String Quartets
Authors: Sumner Lott Marie
Published: November 2012

Brahms's dedication of his op. 51 string quartets (1873) to the surgeon Theodor Billroth provides a window into Brahms's musico-political views in the 1870s that has hitherto been unexplored by music scholars. Analysis of correspondence, performance traditions and the scores of these two quartets demonstrates that Brahms chose to align himself and his works with the learned connoisseurs of the domestic chamber-music-making tradition, represented by Billroth and his frequent musical soirées. Brahms's music also shows the influence of Joseph Joachim, his oldest and dearest friend and Europe's premier chamber musician. Brahms's compositional choices in these two works combine public and private musical styles, to offer a touching memorial to earlier composers and friends, and to provide a teachable moment for the musical public.
Bartók, Beethoven and the Sonata for Two Pianos and Percussion
Authors: Russ Michael
Published: November 2012

The first movement of Bartók's Sonata for Two Pianos and Percussion (1937) has been noted for its Beethovenian use of sonata form and shares a number of features with the ‘Waldstein’ Sonata. This article examines the relationship between these two composers and these two works, starting with an examination of Bartók's use of sonata form. It attempts to establish whether Bartók borrowed gratefully from his predecessor in an attempt to ‘synthesize’ old and new, folk and art, or whether he misread Beethoven in the anxious process of carving a place for himself in the musical canon.
The Closest Thing to Crazy: The Shocking Scarcity of Septuple Time in Western Music
Authors: Gustar Andrew James
Published: November 2012

This article considers why septuple metres are so rare in Western music, despite being common in many other cultures. The scene is set by tracing the history of the septuple-time ‘meme’ (an idea that replicates by imitation) from ancient Greece through to Western art and popular music. The following sections consider the psychological, musical and environmental factors in more detail. The scarcity of septuple time in Western music is largely attributable to the development of the time signature, as a vertical conception of music evolved during the Renaissance. Subsequent evolution of the ‘Western music memeplex’ maintained septuple time on its periphery. Analysis of this interaction permits the construction of a meme-centred narrative of aspects of the development of Western music.
Correlates of Prescription Drug Misuse among Heterosexually Active Homeless Men
Authors: Rhoades Harmony , Wenzel Suzanne L.
Published: November 2012

Objective: Prescription drug misuse (PDM) is an emerging epidemic in the United States. This study examines the prevalence and correlates of PDM among homeless men. Homeless men experience higher risk for substance misuse and associated health problems and are particularly vulnerable to PDM and its negative health consequences. Methods: Participants were a representative probability sample of 305 heterosexually active homeless men interviewed from meal programs in the Skid Row region of Los Angeles. Interviews assessed demographics, substance use, mental health, and social networks. Logistic regression examined correlates of PDM. Results: Twenty-six percent of the study population reported PDM in the past year. PDM was more likely among homeless men suffering from posttraumatic stress disorder (PTSD) (odds ratio [OR] = 2.41, 95% confidence interval [CI]: 1.03–5.61) and among those with more substance-using social network members (OR = 1.07, 95% CI: 1.01–1.14). Decreased PDM was associated with good health (OR = 0.34, 95% CI: 0.16–0.75). Conclusions: The prevalence of PDM is higher among the homeless men in this study than in the general population. Correlates of PDM included PTSD and poor health, suggesting that homeless men may use PDM to self-medicate. PDM was also associated with increased substance-using social network alters. Physical and mental health and social context are important aspects to consider in prevention efforts to reduce PDM among homeless men.
Perceptions of On-the-Job Supervision Needs of Drug Rehabilitation Center Helpers in Malaysia
Authors: Chou Chih-Chin , Bourgeois Paul , Tan Sooyin
Published: November 2012

Objective: In this study, 218 national drug rehabilitation center helpers in Malaysia were surveyed regarding perceptions of their on-the-job clinical supervision needs and preferred supervisor roles and emphasis areas in their supervision sessions. Methods: Descriptive analyses were conducted. Results: Findings suggest that drug rehabilitation center helpers in Malaysia expressed high level of on-the-job supervision needs. In addition, professional behavior skills were found to be the most desirable supervisory area followed by process, conceptualization, and personalization skills. Conclusions: Implications for providing clinical supervision for drug rehabilitation center helpers in Malaysia were discussed, along with suggestions for future research.
Pilot Implementation and Preliminary Evaluation of START:AV Assessments in Secure Juvenile Correctional Facilities
Authors: Desmarais SarahL. , Sellers BrianG. , Viljoen JodiL. , Cruise KeithR. , Nicholls ToniaL. , Dvoskin JoelA.
Published: November 2012

The Short-Term Assessment of Risk and Treatability: Adolescent Version (START:AV) is a new structured professional judgment guide for assessing short-term risks in adolescents. The scheme may be distinguished from other youth risk assessment and treatment planning instruments by its inclusion of 23 dynamic factors that are each rated for both vulnerability and strength. In addition, START:AV is also unique in that it focuses on multiple adverse outcomes—namely, violence, self-harm, suicide, unauthorized leave, substance abuse, self-neglect, victimization, and general offending—over the short-term (i.e., weeks to months) rather than long-term (i.e., years). This article describes a pilot implementation and preliminary evaluation of START:AV in three secure juvenile correctional facilities in the southern United States. Specifically, we examined the descriptive characteristics and psychometric properties of START:AV assessments completed by 21 case managers on 291 adolescent offenders (250 boys and 41 girls) at the time of admission. Results provide preliminary support for the feasibility of completing START:AV assessments as part of routine practice. Findings also highlight differences in the characteristics of START:AV assessments for boys and girls and differential associations between the eight START:AV risk domains. Though results are promising, further research is needed to establish the reliability and validity of START:AV assessments completed in the field.
Assessment of Multiple Risk Outcomes, Strengths, and Change with the START:AV: A Short-Term Prospective Study with Adolescent Offenders
Authors: Viljoen JodiL. , Beneteau JenniferL. , Gulbransen Erik , Brodersen Etta , Desmarais SarahL. , Nicholls ToniaL. , Cruise KeithR.
Published: November 2012

The Short-Term Assessment of Risk and Treatability: Adolescent Version (START:AV; Nicholls, Viljoen, Cruise, Desmarais, & Webster, 2010; Viljoen, Cruise, Nicholls, Desmarais, & Webster, in preparation) is a clinical guide designed to assist in the assessment and management of adolescents’ risk for adverse events (e.g., violence, general offending, suicide, victimization). In this initial validation study, START:AV assessments were conducted on 90 adolescent offenders (62 male, 28 female), who were prospectively followed for a three-month period. START:AV assessments had good to excellent inter-rater reliability and strong concurrent validity with Structured Assessment of Violence Risk in Youth assessments (SAVRY; Borum, Bartel, & Forth, 2006). START:AV risk estimates and Vulnerability total scores predicted multiple adverse outcomes, including violence towards others, offending, victimization, suicidal ideation, and substance abuse. In addition, Strength total scores inversely predicted violence, offending, and street drug use. During the three-month follow-up, risk estimates changed in at least one domain for 92% of youth, and 27% of youth showed reliable changes in Strength and/or Vulnerability total scores (reliable change index, 90% confidence interval; Jacobsen & Truax, 1991). While these findings are promising, a strong need exists for further research on the START:AV, the measurement of change, and on the role of strengths in risk assessment and treatment planning.
Personality Disorder and Psychopathy as Predictors of Psychosocial and Criminological Outcome in Mentally Disordered Offenders
Authors: McCarthy Lucy , Huband Nick , Patel Shireen , Banerjee Penny , Duggan Conor
Published: November 2012

Ninety-five patients discharged from a specialist Personality Disorder (PD) service were prospectively assessed for Axis II disorders and Psychopathy. Sequential regression models tested the ability of different conceptual definitions of PD and Psychopathy to predict criminological and psychosocial outcome over a mean follow-up of 4.16 years. Trait definitions of PD modestly predicted criminological outcome. After controlling for age, IQ and PD, time to first reconviction after entering the community was predicted by PCL-R Factors 1, 2, and previous convictions. Psychosocial outcome was predicted by PCL-R with high scores on the affective-interpersonal Factor 1 providing strongest prediction of poor psychosocial outcome.
The C-terminal unique region of desmoglein 2 inhibits its internalization via tail–tail interactions
Authors: Chen Jing , Nekrasova Oxana E. , Patel Dipal M. , Klessner Jodi L. , Godsel Lisa M. , Koetsier Jennifer L. , Amargo Evangeline V. , Desai Bhushan V. , Green Kathleen J.
Published: November 2012

Desmosomal cadherins, desmogleins (Dsgs) and desmocollins, make up the adhesive core of intercellular junctions called desmosomes. A critical determinant of epithelial adhesive strength is the level and organization of desmosomal cadherins on the cell surface. The Dsg subclass of desmosomal cadherins contains a C-terminal unique region (Dsg unique region [DUR]) with unknown function. In this paper, we show that the DUR of Dsg2 stabilized Dsg2 at the cell surface by inhibiting its internalization and promoted strong intercellular adhesion. DUR also facilitated Dsg tail–tail interactions. Forced dimerization of a Dsg2 tail lacking the DUR led to decreased internalization, supporting the conclusion that these two functions of the DUR are mechanistically linked. We also show that a Dsg2 mutant, V977fsX1006, identified in arrhythmogenic right ventricular cardiomyopathy patients, led to a loss of Dsg2 tail self-association and underwent rapid endocytosis in cardiac muscle cells. Our observations illustrate a new mechanism desmosomal cadherins use to control their surface levels, a key factor in determining their adhesion and signaling roles.
Crawling from soft to stiff matrix polarizes the cytoskeleton and phosphoregulates myosin-II heavy chain
Authors: Raab Matthew , Swift Joe , P. Dingal P.C. Dave , Shah Palak , Shin Jae-Won , Discher Dennis E.
Published: November 2012

On rigid surfaces, the cytoskeleton of migrating cells is polarized, but tissue matrix is normally soft. We show that nonmuscle MIIB (myosin-IIB) is unpolarized in cells on soft matrix in 2D and also within soft 3D collagen, with rearward polarization of MIIB emerging only as cells migrate from soft to stiff matrix. Durotaxis is the tendency of cells to crawl from soft to stiff matrix, and durotaxis of primary mesenchymal stem cells (MSCs) proved more sensitive to MIIB than to the more abundant and persistently unpolarized nonmuscle MIIA (myosin-IIA). However, MIIA has a key upstream role: in cells on soft matrix, MIIA appeared diffuse and mobile, whereas on stiff matrix, MIIA was strongly assembled in oriented stress fibers that MIIB then polarized. The difference was caused in part by elevated phospho-S1943–MIIA in MSCs on soft matrix, with site-specific mutants revealing the importance of phosphomoderated assembly of MIIA. Polarization is thus shown to be a highly regulated compass for mechanosensitive migration.
Drosophila PATJ supports adherens junction stability by modulating Myosin light chain activity
Authors: Sen Arnab , Nagy-Zsvér-Vadas Zsanett , Krahn Michael P.
Published: November 2012

The assembly and consolidation of the adherens junctions (AJs) are key events in the establishment of an intact epithelium. However, AJs are further modified to obtain flexibility for cell migration and morphogenetic movements. Intact AJs in turn are a prerequisite for the establishment and maintenance of apical–basal polarity in epithelial cells. In this study, we report that the conserved PDZ (PSD95, Discs large, ZO-1) domain–containing protein PATJ (Pals1-associated tight junction protein) was not per se crucial for the maintenance of apical–basal polarity in Drosophila melanogaster epithelial cells but rather regulated Myosin localization and phosphorylation. PATJ directly bound to the Myosin-binding subunit of Myosin phosphatase and decreased Myosin dephosphorylation, resulting in activated Myosin. Thereby, PATJ supports the stability of the Zonula Adherens. Notably, weakening of AJ in a PATJ mutant epithelium led first to a loss of Myosin from the AJ, subsequently to a disassembly of the AJ, and finally, to a loss of apical–basal polarity and disruption of the tissue.
Characterization of the insertase for β-barrel proteins of the outer mitochondrial membrane
Authors: Klein Astrid , Israel Lars , Lackey Sebastian W.K. , Nargang Frank E. , Imhof Axel , Baumeister Wolfgang , Neupert Walter , Thomas Dennis R.
Published: November 2012

The TOB–SAM complex is an essential component of the mitochondrial outer membrane that mediates the insertion of β-barrel precursor proteins into the membrane. We report here its isolation and determine its size, composition, and structural organization. The complex from Neurospora crassa was composed of Tob55–Sam50, Tob38–Sam35, and Tob37–Sam37 in a stoichiometry of 1:1:1 and had a molecular mass of 140 kD. A very minor fraction of the purified complex was associated with one Mdm10 protein. Using molecular homology modeling for Tob55 and cryoelectron microscopy reconstructions of the TOB complex, we present a model of the TOB–SAM complex that integrates biochemical and structural data. We discuss our results and the structural model in the context of a possible mechanism of the TOB insertase.