bluuebunny/crossref_metadata_2025 huggingface dataset:
Functionalized Nanoporous Membranes from Reactive Triblock Polymers
Authors: Amendt Mark A. , Roerdink Monique , Moench Sarah , Phillip William A. , Cussler Edward L. , Hillmyer Marc A.
Published: August 2011

Hydrophilic and stimuli responsive nanoporous poly(dicyclopentadiene) membranes are prepared using reactive ABC triblock polymers consisting of a chemically etchable ‘A’ block, poly(lactide), various functionalized ‘B’ blocks, and a metathesis-reactive ‘C’ block, poly(styrene-stat-norbornenylethylstyrene).A membrane with a bicontinuous structure is formed by reaction-induced phase separation during the metathesis crosslinking of dicyclopentadiene in the presence of the ABC triblock polymers. Selective etching of the poly(lactide) block exposed the functionality contained in the B block. Hydrophilic membranes are prepared from a triblock polymer with a poly(N,N-dimethylacrylamide) B midblock as evidenced by static contact angle measurements in comparison to AC diblock templated membranes. Temperature responsive membranes are prepared from a triblock polymer with a poly(N-isopropylacrylamide) B block.
End Group Reactions of RAFT-Prepared (Co)Polymers
Authors: Harvison M. Alyse , Roth Peter J. , Davis Thomas P. , Lowe Andrew B.
Published: August 2011

This review highlights the chemistry of thiocarbonylthio groups with an emphasis on chemistry conducted at ω or α and ω chain-ends in copolymers prepared by reversible addition–fragmentation chain-transfer (RAFT) radical polymerization. We begin by giving a general overview of reactions associated with the thiocarbonylthio groups, followed by examples associated with macromolecular thiols.
Enabling the Development of N-Heterocyclic Carbene (NHC) Catalyzed Reactions: Practical Methods for the Preparation of 1-Acyl-2-Alkylcycloalkenes from Cycloalkanones
Authors: Ryan Sarah J. , Candish Lisa , Martínez Iván , Lupton David W.
Published: August 2011

The synthesis of 1-acyl-2-alkylcycloalkenes from a variety of cycloalkanones has been achieved via either β-keto enol phosphates or β-bromoenones. Both methods exploit simple and readily scalable transformations allowing the preparation of the desired compounds to be achieved in three, or four steps, respectively. The utility of these strategies has been examined, resulting in the preparation of 17 disubstituted cycloalkenes.
Metal Complexes of an Ionic Liquid-Derived Carbene
Authors: Cole Marcus L. , Gyton Matthew R. , Harper Jason B.
Published: August 2011

A range of metal carbene complexes containing the ionic liquid-derived N-heterocyclic carbene (NHC) 1-nbutyl-3-methylimidazol-2-ylidene (IBuMe, 1) have been prepared by (i) direct ligand substitution using the free NHC ([Mo(CO)5(IBuMe)] 2), (ii) transmetallation using the silver salt [AgCl(IBuMe)] (3) ([RhCl(NBD)(IBuMe)] (4) and [IrCl(COD)(IBuMe)] (5), NBD = 2,5-norbornadiene, COD = 1,5-cyclooctadiene) and (iii) direct reaction of a metal acetate with the hydrochloride salt of 1 (trans-[PdCl2(IBuMe)] (6)). The dicarbonyl cis-[RhCl(CO)2(IBuMe)] (7) has been prepared by diene substitution under a carbon monoxide atmosphere. The molecular structures of 2, 4, 5 and 6 are reported and the sigma donation and steric properties of 1 are discussed relative to those of common imidazol-2-ylidene ligands.
Yes They Can: Small-molecule Activation with Stable Diaminocarbenes
Authors: Siemeling Ulrich
Published: August 2011

Although small-molecule activation has long been the exclusive domain of transition metal chemistry, it has been increasingly realized that subvalent heavier main-group element compounds, too, are capable of activating H2, NH3, CO, etc. In a remarkable breakthrough, it was recently discovered that this is even possible with certain selected carbon(ii) compounds, viz. (alkyl)(amino)carbenes. However, N-heterocyclic carbenes and related diaminocarbenes, which represent the largest and most widely applied class of singlet carbenes, have been judged to be incapable of exhibiting similar reactivity. It now turns out that this is not quite true and that their reactivity needs to be reassessed.
A review of financial instruments to pay for predator conservation and encourage human–carnivore coexistence
Authors: Dickman Amy J. , Macdonald Ewan A. , Macdonald David W.
Published: August 2011

One of the greatest challenges in biodiversity conservation today is how to facilitate protection of species that are highly valued at a global scale but have little or even negative value at a local scale. Imperiled species such as large predators can impose significant economic costs at a local level, often in poverty-stricken rural areas where households are least able to tolerate such costs, and impede efforts of local people, especially traditional pastoralists, to escape from poverty. Furthermore, the costs and benefits involved in predator conservation often include diverse dimensions, which are hard to quantify and nearly impossible to reconcile with one another. The best chance of effective conservation relies upon translating the global value of carnivores into tangible local benefits large enough to drive conservation “on the ground.” Although human–carnivore coexistence involves significant noneconomic values, providing financial incentives to those affected negatively by carnivore presence is a common strategy for encouraging such coexistence, and this can also have important benefits in terms of reducing poverty. Here, we provide a critical overview of such financial instruments, which we term “payments to encourage coexistence”; assess the pitfalls and potentials of these methods, particularly compensation and insurance, revenue-sharing, and conservation payments; and discuss how existing strategies of payment to encourage coexistence could be combined to facilitate carnivore conservation and alleviate local poverty.
Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment
Authors: Roblyer Darren , Ueda Shigeto , Cerussi Albert , Tanamai Wendy , Durkin Amanda , Mehta Rita , Hsiang David , Butler John A. , McLaren Christine , Chen Wen-Pin , Tromberg Bruce
Published: August 2011

Approximately 8–20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (
n
= 11) and pathologic complete responding tumors (
n
= 8) on day 1, whereas nonresponders (
n
= 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.
Crystal structure of Toll-like receptor adaptor MAL/TIRAP reveals the molecular basis for signal transduction and disease protection
Authors: Valkov Eugene , Stamp Anna , DiMaio Frank , Baker David , Verstak Brett , Roversi Pietro , Kellie Stuart , Sweet Matthew J. , Mansell Ashley , Gay Nicholas J. , Martin Jennifer L. , Kobe Bostjan
Published: August 2011

Initiation of the innate immune response requires agonist recognition by pathogen-recognition receptors such as the Toll-like receptors (TLRs). Toll/interleukin-1 receptor (TIR) domain-containing adaptors are critical in orchestrating the signal transduction pathways after TLR and interleukin-1 receptor activation. Myeloid differentiation primary response gene 88 (MyD88) adaptor-like (MAL)/TIR domain-containing adaptor protein (TIRAP) is involved in bridging MyD88 to TLR2 and TLR4 in response to bacterial infection. Genetic studies have associated a number of unique single-nucleotide polymorphisms in MAL with protection against invasive microbial infection, but a molecular understanding has been hampered by a lack of structural information. The present study describes the crystal structure of MAL TIR domain. Significant structural differences exist in the overall fold of MAL compared with other TIR domain structures: A sequence motif comprising a β-strand in other TIR domains instead corresponds to a long loop, placing the functionally important “BB loop” proline motif in a unique surface position in MAL. The structure suggests possible dimerization and MyD88-interacting interfaces, and we confirm the key interface residues by coimmunoprecipitation using site-directed mutants. Jointly, our results provide a molecular and structural basis for the role of MAL in TLR signaling and disease protection.
A stable hippocampal representation of a space requires its direct experience
Authors: Rowland David C. , Yanovich Yelizaveta , Kentros Clifford G.
Published: August 2011

In humans and other mammals, the hippocampus is critical for episodic memory, the autobiographical record of events, including where and when they happen. When one records from hippocampal pyramidal neurons in awake, behaving rodents, their most obvious firing correlate is the animal's position within a particular environment, earning them the name “place cells.” When an animal explores a novel environment, its pyramidal neurons form their spatial receptive fields over a matter of minutes and are generally stable thereafter. This experience-dependent stabilization of place fields is therefore an attractive candidate neural correlate of the formation of hippocampal memory. However, precisely how the animal's experience of a context translates into stable place fields remains largely unclear. For instance, we still do not know whether observation of a space is sufficient to generate a stable hippocampal representation of that space because the animal must physically visit a spot to demonstrate which cells fire there. We circumvented this problem by comparing the relative stability of place fields of directly experienced space from merely observed space following blockade of NMDA receptors, which preferentially destabilizes newly generated place fields. This allowed us to determine whether place cells stably represent parts of the environment the animal sees, but does not actually occupy. We found that the formation of stable place fields clearly requires direct experience with a space. This suggests that place cells are part of an autobiographical record of events and their spatial context, consistent with providing the “where” information in episodic memory.
Multilevel autoregulation of λ repressor protein CI by DNA looping in vitro
Authors: Lewis Dale , Le Phuoc , Zurla Chiara , Finzi Laura , Adhya Sankar
Published: August 2011

The prophage state of bacteriophage λ is extremely stable and is maintained by a highly regulated level of λ repressor protein, CI, which represses lytic functions. CI regulates its own synthesis in a lysogen by activating and repressing its promoter,
P
RM
. CI participates in long-range interactions involving two regions of widely separated operator sites by generating a loop in the intervening DNA. We investigated the roles of each individual site under conditions that permitted DNA loop formation by using in vitro transcription assays for the first time on supercoiled DNA that mimics in vivo situation. We confirmed that DNA loops generated by oligomerization of CI bound to its operators influence the autoactivation and autorepression of
P
RM
regulation. We additionally report that different configurations of DNA loops are central to this regulation—one configuration further enhances autoactivation and another is essential for autorepression of
P
RM
.
Chemical genetic strategy for targeting protein kinases based on covalent complementarity
Authors: Garske Adam L. , Peters Ulf , Cortesi Arianna T. , Perez Jenny L. , Shokat Kevan M.
Published: August 2011

The conserved nature of the ATP-binding site of the > 500 human kinases renders the development of specific inhibitors a challenging task. A widely used chemical genetic strategy to overcome the specificity challenge exploits a large-to-small mutation of the gatekeeper residue (a conserved hydrophobic amino acid) and the use of a bulky inhibitor to achieve specificity via shape complementarity. However, in a number of cases, introduction of a glycine or alanine gatekeeper results in diminished kinase activity and ATP affinity. A new chemical genetic approach based on covalent complementarity between an engineered gatekeeper cysteine and an electrophilic inhibitor was developed to address these challenges. This strategy was evaluated with Src, a proto-oncogenic tyrosine kinase known to lose some enzymatic activity using the shape complementarity chemical genetic strategy. We found that Src with a cysteine gatekeeper recapitulates wild type activity and can be irreversibly inhibited both in vitro and in cells. A cocrystal structure of T338C c-Src with a vinylsulfonamide-derivatized pyrazolopyrimidine inhibitor was solved to elucidate the inhibitor binding mode. A panel of electrophilic inhibitors was analyzed against 307 kinases and MOK (MAPK/MAK/MRK overlapping kinase), one of only two human kinases known to have an endogenous cysteine gatekeeper. This analysis revealed remarkably few off-targets, making these compounds the most selective chemical genetic inhibitors reported to date. Protein engineering studies demonstrated that it is possible to increase inhibitor potency through secondary-site mutations. These results suggest that chemical genetic strategies based on covalent complementarity should be widely applicable to the study of protein kinases.
Howard N. Rose’sThesaurus of Slang(1934)
Authors: Coleman Julie
Published: August 2011

This paper is a re-examination of Howard N. Rose’sThesaurus of Slang(1934): of its purpose, structure, contents, reliability, and sources. Contemporary reviewers were largely unimpressed, and their criticisms are also considered. Despite its undoubtedly poor quality, Rose’s work provides some interesting insights into attitudes towards American English, the power of the word “thesaurus”, and the partiality of the reviewing process.
Prosodic and multimodal markers of humor in conversation
Authors: Attardo Salvatore , Pickering Lucy , Baker Amanda
Published: August 2011

This case study extends the findings of Pickering et al. 2009 to the domain of conversational humor. We find that, as was the case in humorous narratives, conversational humor is not marked by higher pitch or volume, increased speech rate, or significant pauses. Unlike narrative humor, conversational humor is not produced at a lower pitch and slower rate than non-humorous parts of the text. We find that smiling and laughter tend to occur with humor.
Rich pitch
Authors: Wennerstrom Ann
Published: August 2011

This paper argues that intonation contributes to the humorous meaning of a certain class of jokes. Examples of both canned and spontaneous jokes show that two intonation patterns, the intonation of contrast, or “L+H* pitch accent”, and the intonation of given information, or “deaccent”, can contribute to a humorous effect. Both of these patterns act as cohesive devises in discourse: they trigger a mental search in the mind of a hearer for a cohesive tie that may not be obvious from the lexicogrammatical structure alone. A punch line effect is created if this search yields an unexpected incongruity between the hearer’s initial mental model of the joke discourse and a humorous alternative. The hearer must shift his “script” (Raskin 1984) of the discourse in an unexpected way. To the extent that intonation facilitates processing by directing attention to particular elements in the information structure of the discourse (Chafe 1994), the processing of jokes depends in part on their intonation. The implications of this premise for the processing of humorous texts will be discussed for the two intonation patterns in question. It is argued that intonation analysis can lead to a broader understanding of cognitive processes and structures.
Evaluating the Potential for Stock Size to Limit Recruitment in Largemouth Bass
Authors: Allen Micheal S. , Rogers Mark W. , Catalano Matthew J. , Gwinn Daniel G. , Walsh Stephen J.
Published: August 2011

Compensatory changes in juvenile survival allow fish stocks to maintain relatively constant recruitment across a wide range of stock sizes (and levels of fishing), but few studies have experimentally explored recruitment compensation in fish populations. We evaluated the potential for recruitment compensation in largemouth bass Micropterus salmoides by stocking six 0.4‐ha hatchery ponds with adult densities ranging from 6 to 40 fish over 2 years. Ponds were drained in October each year, and the age‐0 fish densities were used as a measure of recruitment. We found no relationship between stock abundance and recruitment; ponds with low adult densities produced nearly as many recruits as the higher‐density ponds in some cases. Both prey abundance and the growth of age‐0 largemouth bass declined with age‐0 fish density. Recruit abundance was highly variable both within and among the adult density groups, and thus we were unable to identify a clear stock–recruit relationship for largemouth bass. Our results indicate that reducing the number of effective spawners via angling practices would not reduce recruitment over a relatively large range in stock size.
CLASS IN THE SOUTH CAUCASUS
Authors: Roberts Ken , Pollock Gary
Published: August 2011

This paper identifies classes using evidence from surveys taken in 2009 among nationally representative samples of approximately 2000 households from each of the three South Caucasus countries –Armenia, Azerbaijan and Georgia. Information on employment, education and income is used to identify clusters of both individuals and households, in each case a middle class, a working class and a lower class. Using individual classification, the lower classes are the largest classes in each country, which therefore appear to have pyramid-shaped class structures. However, classifying households gives the class structures a diamond shape, with larger working classes than either middle classes or lower classes. The evidence shows that the main differences between classes of households lie in their standards of living, and are driven by differences in income levels. The main differences between classes of individuals are driven primarily by education, which result in differences in attitudes and (to some extent) individual lifestyles. It is argued that in economic and socio-political terms there are as yet just two real classes among actual and potential employees in the South Caucasus –middle classes and lower classes –and that although these classes differ in their standards of living and political dispositions, these are unlikely to become bases for conflict between them.
The Use of Participatory Action Research to Create a Positive Youth Development Program
Authors: Hamby Anne , Pierce Meghan , Daniloski Kim , Brinberg David
Published: August 2011

A positive youth development program focusing on HIV prevention, alcohol abuse prevention, conflict resolution skills, and managing peer pressure was developed and implemented in the Eastern Cape of South Africa. Participatory action research methods were combined with a social marketing approach to generate and implement a narrative-based curriculum. A posttest-only control group field experiment was used to evaluate the impact of a classroom intervention on adolescents' knowledge and attitudes related to the topics covered. The narrative-based curriculum was more effective than the standard, government-endorsed curriculum in increasing knowledge and changing attitudes toward sexual behavior and conflict resolution. The implications of implementing a narrative-based curriculum using a social marketing approach are discussed.
“Act on Climate Change”: An Application of Protection Motivation Theory
Authors: Cismaru Magdalena , Cismaru Romulus , Ono Takaya , Nelson Kristina
Published: August 2011

Our planet's climate is changing (U.S. Environmental Protection Agency, 2010), and current scientific evidence proves that global climate change is induced by humans (Intergovernmental Panel on Climate Change, 2007). Many scientists agree that climate change is one of the greatest threats faced by our planet. The climate change literature demonstrates that fear appeals can be used to encourage behavioral changes that will mitigate climate change (Nisbet, 2009; Patchen, 2006; Pike, Doppelt, & Herr, 2010). This article proposes Protection Motivation Theory (PMT; Rogers, 1983) as a suitable model to guide communication campaigns in the area of climate change. It also analyzes the extent to which a series of communication campaigns that are designed to persuade individuals to adopt behaviors that prevent climate change conform to PMT. Recommendations to improve the campaigns are presented.
Electrical properties of nematic liquid crystals doped with anatase TiO2nanoparticles
Authors: Tang Chen-Yu , Huang Sheng-Miao , Lee Wei
Published: August 2011

This study focuses on the electrical characteristics of nematic liquid crystals doped with anatase titania nanoparticles (NPs). Low-frequency dielectric spectroscopy between 10−2and 103 Hz is used to investigate the space-charge polarization. The results indicate that the doped samples have lower ionic concentration, diffusion constant and activation energy due to the effect of the dopant on ion transport. Temperature-dependent data provide an insight into the feasibility of using these NPs as a dopant to promote the device performance in a real environment. Verified by the voltage holding ratio, it is clear that doping anatase NPs into liquid crystals is a potentially cost-effective and easy way to improve the device performance.
Laws, causation and dynamics at different levels
Authors: Butterfield Jeremy
Published: August 2011

I have two main aims. The first is general, and more philosophical (§2). The second is specific, and more closely related to physics (§§3 and 4). The first aim is to state my general views about laws and causation at different ‘levels’. The main task is to understand how the higher levels sustain notions of law and causation that ‘ride free’ of reductions to the lower level or levels. I endeavour to relate my views to those of other symposiasts. The second aim is to give a framework for describing dynamics at different levels, emphasizing how the various levels' dynamics can mesh or fail to mesh. This framework is essentially that of elementary dynamical systems theory. The main idea will be, for simplicity, to work with just two levels, dubbed ‘micro’ and ‘macro’, which are related by coarse-graining. I use this framework to describe, in part, the first four of Ellis' five types of top-down causation.
Variability of neuD transcription levels and capsular sialic acid expression among serotype III group B Streptococcus strains
Authors: Lartigue Marie-Frédérique , Poulard Agnès Fribourg , Al Safadi Rim , Pailhories Hélène , Domelier-Valentin Anne-Sophie , van der Mee-Marquet Nathalie , Rosenau Agnès , Quentin Roland
Published: August 2011

Serotype III group B Streptococcus (GBS) is the major cause of neonatal meningitis, but the risk of infection in the colonized neonates is variable. Capsular sialic acid (Sia), whose synthesis is encoded by neu genes, appears to be a major virulence factor in several bacterial species able to reach the cerebrospinal fluid. Therefore, variations of Sia expression related to the genetic diversity of strains may have an impact on the risk of meningitis in colonized neonates. We characterized by MLST the phylogenetic diversity of 64 serotype III GBS strains isolated from vaginal flora and randomly selected. These strains mostly belonged to three major sequence types (STs): ST1 (11 %), ST17 (39 %) and ST19 (31 %). The genetic diversity of strains of these lineages, characterized by PFGE, allowed the selection of 17 representative strains, three ST1, six ST17 and eight ST19, with NEM316 as reference, in order to evaluate (i) by quantitative RT-PCR, the level of transcription of the neuD gene as a marker for the transcription of neu genes and (ii) by enzymological analysis, the expression of Sia. The mean transcription level of neuD was higher for ST17 strains than for ST1 and ST19 strains in the early, mid- and late exponential growth phases, and was maximum in the early exponential growth phase for ST17 strains and in the mid-exponential growth phase for ST1 and ST19 strains. Mean Sia concentration was higher for ST17 than for ST1 and ST9 strains in all three growth phases. For the total population, Sia concentration varied notably in the stationary phase, from 0.38 to 9.30 nmol per 108 viable bacteria, with a median value of 2.99 nmol per 108 bacteria. All ST17 strains, only one-third of the ST19 strains and none of the ST1 strains had Sia concentrations higher than the median Sia concentration. Therefore, differences in the level of expression of Sia by strains of the major serotype III GBS phylogenetic lineages might be one of the factors that explain the leading role of ST17 strains in neonatal meningitis.
Atomic force microscopy of a ctpA mutant in Rhizobium leguminosarum reveals surface defects linking CtpA function to biofilm formation
Authors: Dong Jun , Signo Karla S. L. , Vanderlinde Elizabeth M. , Yost Christopher K. , Dahms Tanya E. S.
Published: August 2011

Atomic force microscopy was used to investigate the surface ultrastructure, adhesive properties and biofilm formation ofRhizobium leguminosarumand actpAmutant strain. The surface ultrastructure of wild-typeR. leguminosarumconsists of tightly packed surface subunits, whereas thectpAmutant has much larger subunits with loose lateral packing. ThectpAmutant strain is not capable of developing fully mature biofilms, consistent with its altered surface ultrastructure, greater roughness and stronger adhesion to hydrophilic surfaces. For both strains, surface roughness and adhesive forces increased as a function of calcium ion concentration, and for each, biofilms were thicker at higher calcium concentrations.
Single nucleotide polypmorphisms of fimH associated with adherence and biofilm formation by serovars of Salmonella enterica
Authors: Dwyer Brett E. , Newton Karly L. , Kisiela Dagmara , Sokurenko Evgeni V. , Clegg Steven
Published: August 2011

Type 1 fimbriae produced by serovars of Salmonella are characterized by their ability to agglutinate guinea pig erythrocytes in the absence of d-mannose but not in its presence. The FimH protein is the adhesin that mediates this reaction; it is distinct from the major fimbrial protei.n (FimA) that composes the fimbrial shaft. Avian-adapted serovars of Salmonella produce non-haemagglutinating fimbriae that have been reported to mediate adherence to avian cells. A single amino acid substitution is present in the FimH adhesin of these strains compared to that of a Typhimurium isolate. Also, previous studies have shown that single nucleotide polymorphisms in two strains of the Typhimurium fimH alter the binding specificity. We therefore investigated the allelic variation of fimH from a range of serotypes (both host-adapted and non-host-adapted) and isolates of Salmonella. Most FimH adhesins mediated the mannose-sensitive haemagglutination of guinea pig erythrocytes, but many did not facilitate adherence to HEp-2 cells. A small number of isolates also produced fimbriae but did not mediate adherence to either cell type. Transformants possessing cloned fimH genes exhibited a number of different substitutions within the predicted amino acid sequence of the FimH polypeptide. No identical FimH amino sequence was found between strains that adhere to erythrocytes and/or HEp-2 cells and those produced by non-adherent strains. FimH-mediated adherence to HEp-2 cells was invariably associated with the ability to form biofilms on mannosylated bovine serum albumin.
High-throughput semiquantitative analysis of insertional mutations in heterogeneous tumors
Authors: Koudijs Marco J. , Klijn Christiaan , van der Weyden Louise , Kool Jaap , ten Hoeve Jelle , Sie Daoud , Prasetyanti Pramudita R. , Schut Eva , Kas Sjors , Whipp Theodore , Cuppen Edwin , Wessels Lodewyk , Adams David J. , Jonkers Jos
Published: August 2011

Retroviral and transposon-based insertional mutagenesis (IM) screens are widely used for cancer gene discovery in mice. Exploiting the full potential of IM screens requires methods for high-throughput sequencing and mapping of transposon and retroviral insertion sites. Current protocols are based on ligation-mediated PCR amplification of junction fragments from restriction endonuclease-digested genomic DNA, resulting in amplification biases due to uneven genomic distribution of restriction enzyme recognition sites. Consequently, sequence coverage cannot be used to assess the clonality of individual insertions. We have developed a novel method, called shear-splink, for the semiquantitative high-throughput analysis of insertional mutations. Shear-splink employs random fragmentation of genomic DNA, which reduces unwanted amplification biases. Additionally, shear-splink enables us to assess clonality of individual insertions by determining the number of unique ligation points (LPs) between the adapter and genomic DNA. This parameter serves as a semiquantitative measure of the relative clonality of individual insertions within heterogeneous tumors. Mixing experiments with clonal cell lines derived from mouse mammary tumor virus (MMTV)-induced tumors showed that shear-splink enables the semiquantitative assessment of the clonality of MMTV insertions. Further, shear-splink analysis of 16 MMTV- and 127 Sleeping Beauty (SB)–induced tumors showed enrichment for cancer-relevant insertions by exclusion of irrelevant background insertions marked by single LPs, thereby facilitating the discovery of candidate cancer genes. To fully exploit the use of the shear-splink method, we set up the Insertional Mutagenesis Database (iMDB), offering a publicly available web-based application to analyze both retroviral- and transposon-based insertional mutagenesis data.
Reelin supplementation enhances cognitive ability, synaptic plasticity, and dendritic spine density
Authors: Rogers Justin T. , Rusiana Ian , Trotter Justin , Zhao Lisa , Donaldson Erika , Pak Daniel T.S. , Babus Lenard W. , Peters Melinda , Banko Jessica L. , Chavis Pascale , Rebeck G. William , Hoe Hyang-Sook , Weeber Edwin J.
Published: August 2011

Apolipoprotein receptors belong to an evolutionarily conserved surface receptor family that has intimate roles in the modulation of synaptic plasticity and is necessary for proper hippocampal-dependent memory formation. The known lipoprotein receptor ligand Reelin is important for normal synaptic plasticity, dendritic morphology, and cognitive function; however, the in vivo effect of enhanced Reelin signaling on cognitive function and synaptic plasticity in wild-type mice is unknown. The present studies test the hypothesis that in vivo enhancement of Reelin signaling can alter synaptic plasticity and ultimately influence processes of learning and memory. Purified recombinant Reelin was injected bilaterally into the ventricles of wild-type mice. We demonstrate that a single in vivo injection of Reelin increased activation of adaptor protein Disabled-1 and cAMP-response element binding protein after 15 min. These changes correlated with increased dendritic spine density, increased hippocampal CA1 long-term potentiation (LTP), and enhanced performance in associative and spatial learning and memory. The present study suggests that an acute elevation of in vivo Reelin can have long-term effects on synaptic function and cognitive ability in wild-type mice.
RSK2 signaling in brain habenula contributes to place aversion learning
Authors: Darcq Emmanuel , Koebel Pascale , Del Boca Carolina , Pannetier Solange , Kirstetter Anne-Sophie , Garnier Jean-Marie , Hanauer André , Befort Katia , Kieffer Brigitte L.
Published: August 2011

RSK2 is a Ser/Thr kinase acting in the Ras/MAPK pathway. Rsk2 gene deficiency leads to the Coffin-Lowry Syndrome, notably characterized by cognitive deficits. We found that mrsk2 knockout mice are unable to associate an aversive stimulus with context in a lithium-induced conditioned place aversion task requiring both high-order cognition and emotional processing. Virally mediated shRNA-RSK2 knockdown in the habenula, whose involvement in cognition is receiving increasing attention, also ablated contextual conditioning. RSK2 signaling in the habenula, therefore, is essential for this task. Our study reveals a novel role for RSK2 in cognitive processes and uncovers the critical implication of an intriguing brain structure in place aversion learning.
The ZmASR1 Protein Influences Branched-Chain Amino Acid Biosynthesis and Maintains Kernel Yield in Maize under Water-Limited Conditions
Authors: Virlouvet Laetitia , Jacquemot Marie-Pierre , Gerentes Denise , Corti Hélène , Bouton Sophie , Gilard Françoise , Valot Benoît , Trouverie Jacques , Tcherkez Guillaume , Falque Matthieu , Damerval Catherine , Rogowsky Peter , Perez Pascual , Noctor Graham , Zivy Michel , Coursol Sylvie
Published: August 2011

Abscisic acid-, stress-, and ripening-induced (ASR) proteins were first described about 15 years ago as accumulating to high levels during plant developmental processes and in response to diverse stresses. Currently, the effects of ASRs on water deficit tolerance and the ways in which their physiological and biochemical functions lead to this stress tolerance remain poorly understood. Here, we characterized the ASR gene family from maize (Zea mays), which contains nine paralogous genes, and showed that maize ASR1 (ZmASR1) was encoded by one of the most highly expressed paralogs. Ectopic expression of ZmASR1 had a large overall impact on maize yield that was maintained under water-limited stress conditions in the field. Comparative transcriptomic and proteomic analyses of wild-type and ZmASR1-overexpressing leaves led to the identification of three transcripts and 16 proteins up- or down-regulated by ZmASR1. The majority of them were involved in primary and/or cellular metabolic processes, including branched-chain amino acid (BCAA) biosynthesis. Metabolomic and transcript analyses further indicated that ZmASR1-overexpressing plants showed a decrease in BCAA compounds and changes in BCAA-related gene expression in comparison with wild-type plants. Interestingly, within-group correlation matrix analysis revealed a close link between 13 decreased metabolites in ZmASR1-overexpressing leaves, including two BCAAs. Among these 13 metabolites, six were previously shown to be negatively correlated to biomass, suggesting that ZmASR1-dependent regulation of these 13 metabolites might contribute to regulate leaf growth, resulting in improvement in kernel yield.
Arabidopsis Cys2/His2 Zinc-Finger Proteins AZF1 and AZF2 Negatively Regulate Abscisic Acid-Repressive and Auxin-Inducible Genes under Abiotic Stress Conditions
Authors: Kodaira Ken-Suke , Qin Feng , Tran Lam-Son Phan , Maruyama Kyonoshin , Kidokoro Satoshi , Fujita Yasunari , Shinozaki Kazuo , Yamaguchi-Shinozaki Kazuko
Published: August 2011

In plants, abiotic stresses induce various physiological changes and growth inhibition that result in adaptive responses to these stresses. However, little is known about how such stresses cause plant growth inhibition. Many genes have been reported to be repressed in plants under abiotic stress conditions. ZPT2 (for petunia [Petunia hybrida] zinc-finger protein 2)-related proteins with two Cys2/His2-type zinc-finger motifs and an ethylene-responsive element binding factor-associated amphiphilic repression motif are thought to function as transcriptional repressors. To characterize the roles of this type of transcriptional repressor under abiotic stress conditions, we analyzed the functions of two Arabidopsis (Arabidopsis thaliana) ZPT2-related genes that were induced by osmotic stress and abscisic acid: AZF1 (for Arabidopsis zinc-finger protein 1) and AZF2. The nuclear localization of these two proteins was observed in the roots under control conditions, and the accumulation of AZF2 was clearly detected in the nuclei of leaf cells under stress conditions. Transgenic plants overexpressing AZF1 and AZF2 were generated using stress-responsive promoters or the GVG chemical induction system. The overexpression of these genes caused severe damage to plant growth and viability. Transcriptome analyses of the transgenic plants demonstrated that AZF1 and AZF2 repressed various genes that were down-regulated by osmotic stress and abscisic acid treatment. Moreover, many auxin-responsive genes were found to be commonly down-regulated in the transgenic plants. Gel mobility shift assays revealed that both the AZF1 and AZF2 proteins bound to the promoter regions of these down-regulated genes. These results indicate that AZF1 and AZF2 function as transcriptional repressors involved in the inhibition of plant growth under abiotic stress conditions.
The effects of a single nucleotide polymorphism in SLCO1B1 on the pharmacodynamics of pravastatin
Authors: Martin Nicholas G. , Li Ka Wah , Murray Heather , Putt Wendy , Packard Chris J. , Humphries Steve E.
Published: August 2011

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT

• The SNP rs4149056 is associated with altered statin pharmacokinetics and increased risk of statin intolerance. LDL‐cholesterol lowering by simvastatin is also affected by rs4149056 but differences between the genotypes are small. Studies of the effect of rs4149056 on pravastatin pharmacodynamics have been inconclusive.

WHAT THIS PAPER ADDS

• rs4149056 was not associated with an altered lipid or CRP response to 40 mg day−1 pravastatin in more than 600 high risk men from Scotland, suggesting that the rs4149056 genotype does not significantly affect pravastatin efficacy.

AIM To determine whether the SNP rs4149056 in SLCO1B1 alters the pharmacodynamics of pravastatin.

METHODS rs4149056 was genotyped in 626 pravastatin‐treated participants in the WOSCOPS trial and the response after 1 year of treatment was compared between the different genotypes.

RESULTS Pravastatin reduced serum LDL cholesterol by 22.2% in TT homozygotes, by 22.2% in TC heterozygotes and by 17.7% in CC homozygotes (TT + TC vs. CC P value 0.33). There were no significant differences in the response of total cholesterol, LDL, HDL, triglycerides or CRP to pravastatin between the genotypes.

CONCLUSION The rs4149056 SNP did not significantly affect the pharmacodynamics of pravastatin.
Efficacy of prophylaxis and genotype‐phenotype correlation in patients with severe Factor X deficiency in Iran
Authors: KARIMI M. , VAFAFAR A. , HAGHPANAH S. , PAYANDEH M. , ESHGHI P. , HOOFAR H. , AFRASIABI A. , GERDABI J. , ARDESHIRI R. , MENEGATTI M. , PEYVANDI F.
Published: August 2011

Summary.  We aimed to evaluate the effect of regular prophylaxis with a Factor X (FX) concentrate for patients with severe FXD in Iran and to assess the correlation of the genotype and phenotype in these patients. Ten patients with severe FXD (FX activity <1%) were enrolled and characterized during 2010–2011. Prophylaxis with 20 IU FX P Behring per kg body weight was administered once a week. FX levels, were monitored at baseline, 15 and 30 min, 1, 3, 6, 12, 24, 48, 72 and 96 h after starting prophylaxis. All patients were followed for 1 year. The mean age of the patients was 15 ± 7.8 years (age range of: 6–27 years). One patient had anaphylactic reaction after the first infusion, and the treatment was stopped. During one‐year follow‐up after starting prophylaxis, no bleeding symptoms occurred in any patient who tolerated and remained on the prophylaxis programme and all of them had a FX level of 1% or above. The maximum level of FX activity has been observed at 15 min after starting prophylaxis. A level of 1.5–3.5% was detected after 96 h. Homozygous mutations p.Arg40Thr (Arg‐1Thr), p.Gly51Arg and p.Glu69Lys were detected in patients with intracranial haemorrhage. In our patients, significant decrease in symptoms without any complication after administration of FX, was demonstrated in all except one patient who had an anaphylactic reaction. It seems that the dose of 20 IU kg−1 could be probably the best choice for patients with severe FXD, who require regular prophylaxis.
The impact of foreign caregiving on depression among older people in Taiwan: model testing
Authors: Chiao Chia‐Yi , Schepp Karen G.
Published: August 2011

chiao c.‐y. & schepp k.g. (2011) The impact of foreign caregiving on depression among older people in Taiwan: model testing. Journal of Advanced Nursing 68(5), 1090–1099.

Aim.  This article is a report of a study of predicting the factors that influence depression in the older people in Taiwan.

Background.  In 1991, Taiwan opened the labour market to foreign caregivers for the older people who needed long‐term care. With the differences in language, culture and lifestyle between foreign caregivers and older people in Taiwan, it was hypothesized that the older people would not be able to relate to them, and therefore become depressed.

Methods.  The data were collected from 116 Taiwanese older people from July to September, 2005. Path analysis using multiple regression analyses was conducted to estimate the direct and indirect effects of caregiving communication, activities of daily living, income and social support on depression among older people in Taiwan. To evaluate the hypotheses for this research, bi‐variate linear regression and multiple regression analyses were used.

Results/findings.  The results indicated that the level of activities of daily living (β = −0·201, P = 0·010), care‐giving communication (β = −0·272, P = 0·002) income (β = −0·305, P = 0·000) and social support (β = −0·276, P = 0·002) were the predictors of depression in older people in Taiwan. Social support was a mediating factor for caregiving communication and depression. Furthermore, foreign caregiver care was not correlated with depression among older people in Taiwan.

Conclusions.  The findings influence the public awareness of depression in older people, and provide the foundational information to influence the policy makers of Taiwan to evaluate the foreign caregiver policy.
Literature review: using pictographs in discharge instructions for older adults with low‐literacy skills
Authors: Choi Jeungok
Published: August 2011

Aims.  To evaluate current visual aids used in health education; to explore evidence regarding the use of pictographs (simple line drawings showing explicit health care actions); and to provide suggestions for uses of pictographs in discharge instructions for older adults with low‐literacy skills.

Background.  Discharge instructions consist of recommended homecare actions. However, these healthcare actions are provided in text‐based discharge instructions, which are often difficult for patients with low‐literacy skills to follow precisely at home. Various forms of visual aids are currently used to improve health education; however, the appropriateness of these visual aids for educating discharge instructions for older adults with low‐literacy skills is unknown.

Design.  A narrative literature review.

Methods.  Eligible articles were identified via electronic searches of databases. In total, 44 articles were reviewed and analysed.

Results.  Among various visual aids, pictographs using simple line drawings combined with simplified text are the most efficient and effective tool to improve discharge education. Indeed, pictographs are well suited to show a step‐by‐step procedure of complex and lengthy discharge instructions consisting of multiple actions, thus making an entire action sequence easier to learn.

Conclusion.  By using pictographs with simplified text, healthcare educators can improve discharge instructions for low‐literate older adults. Further research is needed to develop pictographs representing explicit healthcare actions themselves rather than concepts associated with healthcare actions; and to examine the effects of pictographs on adherence and health outcomes.

Relevance to clinical practice.  Healthcare education materials using pictographs provide effective strategies in improving discharge education for low‐literate older adults in acute healthcare settings where nurses have primary responsibility as a first line of healthcare providers. It can also serve as an efficient tool to improve health education for immigrants speaking English as a second language.
A national survey of GP and nurse attitudes and beliefs towards depression after myocardial infarction
Authors: Haws Joanne , Ramjeet Janet , Gray Richard
Published: August 2011

Aim.  To investigate primary care practitioner’s attitudes to depression after myocardial infarction.

Background.  Depression after myocardial infarction affects almost half of all patients and has a considerable negative effect on recovery. Despite the increased prevalence of depression in this population, it is often not recognised or treated.

Design.  Survey.

Method.  A total of 813 (106 general practitioners and 707 nurses) practitioners responded. Our questionnaire developed for this project by the authors in collaboration with a group of ten cardiovascular nurse specialists contained 27 items that were summated into five subscales.

Results.  Primary care practitioners underestimated the prevalence of depression in the post‐myocardial infarction population. General acknowledgement of the negative impact that depression can have was reported by the majority of participants. Diagnosing depression was perceived as complex by both groups but significantly more so by nurses. General practitioners were significantly more positive about their understanding of the signs and symptoms of depression and in using depression‐screening tools. We observed that training seems to have a significant effect on reported practice. Practitioners who reported that they had recent training in the management of depression were significantly more accurate in their estimate of how common depression was in this population.

Conclusion.  Depression may be underdiagnosed in this population because primary care practitioners, especially nurses, are not aware of how common the disorder is and lack competence in diagnosis. There is merit in developing and testing a brief training intervention to ensure competence in depression screening and treatment in post‐myocardial infarction patients.

Relevance to clinical practice.  Diagnosing depression in post‐myocardial infarction patients is perceived by nurses as complex but training in the management of depression is seen as helping practice.