bluuebunny/crossref_metadata_2025 huggingface dataset:
Analytic projections, Corona problem and geometry of holomorphic vector bundles
Authors: Treil Sergei , Wick Brett
Published: October 2008

The main result of the paper is a theorem giving a sufficient condition for the existence of a bounded analytic projection onto a holomorphic family of generally infinite dimensional subspaces (a holomorphic sub-bundle of a trivial bundle). This sufficient condition is also necessary in the case of finite dimension or codimension of the bundle. A simple lemma of N. Nikolski connects the existence of a bounded analytic projection with the Operator Corona Problem (existence of a bounded analytic left inverse for an operator-valued function), so as corollaries of the main result we obtain new results about the Operator Corona Problem. In particular, we find a new sufficient condition, a complete solution in the case of finite codimension, and a solution of the generalized Corona Problem.
Constructible sheaves and the Fukaya category
Authors: Nadler David , Zaslow Eric
Published: October 2008

Let

X
X

be a compact real analytic manifold, and let

T
∗

X

T^*X

be its cotangent bundle. Let

S
h
(
X
)

Sh(X)

be the triangulated dg category of bounded, constructible complexes of sheaves on

X
X

. In this paper, we develop a Fukaya

A
∞

A_\infty

-category

F
u
k
(

T
∗

X
)

Fuk(T^*X)

whose objects are exact, not necessarily compact Lagrangian branes in the cotangent bundle. We write

T
w
F
u
k
(

T
∗

X
)

Tw Fuk(T^*X)

for the

A
∞

A_\infty

-triangulated envelope of

F
u
k
(

T
∗

X
)

Fuk(T^*X)

consisting of twisted complexes of Lagrangian branes. Our main result is that

S
h
(
X
)

Sh(X)

quasi-embeds into

T
w
F
u
k
(

T
∗

X
)

Tw Fuk(T^*X)

as an

A
∞

A_\infty

-category. Taking cohomology gives an embedding of the corresponding derived categories.
Manifolds with 1/4-pinched curvature are space forms
Authors: Brendle Simon , Schoen Richard
Published: October 2008

Let

(
M
,

g
0

)

(M,g_0)

be a compact Riemannian manifold with pointwise

1

/

4

1/4

-pinched sectional curvatures. We show that the Ricci flow deforms

g
0

g_0

to a constant curvature metric. The proof uses the fact, also established in this paper, that positive isotropic curvature is preserved by the Ricci flow in all dimensions. We also rely on earlier work of Hamilton and of Böhm and Wilking.
Farnesylation of Ydj1 Is Required for In Vivo Interaction with Hsp90 Client Proteins
Authors: Flom Gary A. , Lemieszek Marta , Fortunato Elizabeth A. , Johnson Jill L.
Published: October 2008

Ydj1 of Saccharomyces cerevisiae is an abundant cytosolic Hsp40, or J-type, molecular chaperone. Ydj1 cooperates with Hsp70 of the Ssa family in the translocation of preproteins to the ER and mitochondria and in the maturation of Hsp90 client proteins. The substrate-binding domain of Ydj1 directly interacts with steroid receptors and is required for the activity of diverse Hsp90-dependent client proteins. However, the effect of Ydj1 alteration on client interaction was unknown. We analyzed the in vivo interaction of Ydj1 with the protein kinase Ste11 and the glucocorticoid receptor. Amino acid alterations in the proposed client-binding domain or zinc-binding domain had minor effects on the physical interaction of Ydj1 with both clients. However, alteration of the carboxy-terminal farnesylation signal disrupted the functional and physical interaction of Ydj1 and Hsp90 with both clients. Similar effects were observed upon deletion of RAM1, which encodes one of the subunits of yeast farnesyltransferase. Our results indicate that farnesylation is a major factor contributing to the specific requirement for Ydj1 in promoting proper regulation and activation of diverse Hsp90 clients.
Munc18a Scaffolds SNARE Assembly to Promote Membrane Fusion
Authors: Rodkey Travis L. , Liu Song , Barry Meagan , McNew James A.
Published: October 2008

Munc18a is an SM protein required for SNARE-mediated fusion. The molecular details of how Munc18a acts to enhance neurosecretion have remained elusive. Here, we use in vitro fusion assays to characterize how specific interactions between Munc18a and the neuronal SNAREs enhance the rate and extent of fusion. We show that Munc18a interacts directly and functionally with the preassembled t-SNARE complex. Analysis of Munc18a point mutations indicates that Munc18a interacts with helix C of the Syntaxin1a NRD in the t-SNARE complex. Replacement of the t-SNARE SNAP25b with yeast Sec9c had little effect, suggesting that Munc18a has minimal contact with SNAP25b within the t-SNARE complex. A chimeric Syntaxin built of the Syntaxin1a NRD and the H3 domain of yeast Sso1p and paired with Sec9c eliminated stimulation of fusion, suggesting that Munc18a/Syntaxin1a H3 domain contacts are important. Additionally, a Syntaxin1A mutant lacking a flexible linker region that allows NRD movement abolished stimulation of fusion. These experiments suggest that Munc18a binds to the Syntaxin1a NRD and H3 domain within the assembled t-SNARE complex, positioning them for productive VAMP2 binding. In this capacity, Munc18a serves as a platform for trans-SNARE complex assembly that facilitates efficient SNARE-mediated membrane fusion.
Self-Interaction Is Critical for Atg9 Transport and Function at the Phagophore Assembly Site during Autophagy
Authors: He Congcong , Baba Misuzu , Cao Yang , Klionsky Daniel J.
Published: October 2008

Autophagy is the degradation of a cell's own components within lysosomes (or the analogous yeast vacuole), and its malfunction contributes to a variety of human diseases. Atg9 is the sole integral membrane protein required in formation of the initial sequestering compartment, the phagophore, and is proposed to play a key role in membrane transport; the phagophore presumably expands by vesicular addition to form a complete autophagosome. It is not clear through what mechanism Atg9 functions at the phagophore assembly site (PAS). Here we report that Atg9 molecules self-associate independently of other known autophagy proteins in both nutrient-rich and starvation conditions. Mutational analyses reveal that self-interaction is critical for anterograde transport of Atg9 to the PAS. The ability of Atg9 to self-interact is required for both selective and nonselective autophagy at the step of phagophore expansion at the PAS. Our results support a model in which Atg9 multimerization facilitates membrane flow to the PAS for phagophore formation.
Physical protein–protein interactions predicted from microarrays
Authors: Soong Ta-tsen , Wrzeszczynski Kazimierz O. , Rost Burkhard
Published: October 2008

Motivation: Microarray expression data reveal functionally associated proteins. However, most proteins that are associated are not actually in direct physical contact. Predicting physical interactions directly from microarrays is both a challenging and important task that we addressed by developing a novel machine learning method optimized for this task.

Results: We validated our support vector machine-based method on several independent datasets. At the same levels of accuracy, our method recovered more experimentally observed physical interactions than a conventional correlation-based approach. Pairs predicted by our method to very likely interact were close in the overall network of interaction, suggesting our method as an aid for functional annotation. We applied the method to predict interactions in yeast (Saccharomyces cerevisiae). A Gene Ontology function annotation analysis and literature search revealed several probable and novel predictions worthy of future experimental validation. We therefore hope our new method will improve the annotation of interactions as one component of multi-source integrated systems.

Contact:  ts2186@columbia.edu

Supplementary information:  Supplementary data are available at Bioinformatics online.
Some recent advances in understanding the mineralogy of Earth's deep mantle
Authors: Duffy Thomas S
Published: October 2008

Understanding planetary structure and evolution requires a detailed knowledge of the properties of geological materials under the conditions of deep planetary interiors. Experiments under the extreme pressure–temperature conditions of the deep mantle are challenging, and many fundamental properties remain poorly constrained or are inferred only through uncertain extrapolations from lower pressure–temperature states. Nevertheless, the last several years have witnessed a number of new developments in this area, and a broad overview of the current understanding of the Earth's lower mantle is presented here. Some recent experimental and theoretical advances related to the lowermost mantle are highlighted. Measurements of the equation of state and deformation behaviour of (Mg,Fe)SiO3in the CaIrO3-type (post-perovskite) structure yield insights into the nature of the core–mantle boundary region. Theoretical studies of the behaviour of MgSiO3liquids under high pressure–temperature conditions provide constraints on melt volumes, diffusivities and viscosities that are relevant to understanding both the early Earth (e.g. deep magma oceans) and seismic structure observed in the present Earth (e.g. ultra-low-velocity zones).
Explicit neural signals reflecting reward uncertainty
Authors: Schultz Wolfram , Preuschoff Kerstin , Camerer Colin , Hsu Ming , Fiorillo Christopher D , Tobler Philippe N , Bossaerts Peter
Published: October 2008

The acknowledged importance of uncertainty in economic decision making has stimulated the search for neural signals that could influence learning and inform decision mechanisms. Current views distinguish two forms of uncertainty, namely risk and ambiguity, depending on whether the probability distributions of outcomes are known or unknown. Behavioural neurophysiological studies on dopamine neurons revealed a risk signal, which covaried with the standard deviation or variance of the magnitude of juice rewards and occurred separately from reward value coding. Human imaging studies identified similarly distinct risk signals for monetary rewards in the striatum and orbitofrontal cortex (OFC), thus fulfilling a requirement for the mean variance approach of economic decision theory. The orbitofrontal risk signal covaried with individual risk attitudes, possibly explaining individual differences in risk perception and risky decision making. Ambiguous gambles with incomplete probabilistic information induced stronger brain signals than risky gambles in OFC and amygdala, suggesting that the brain's reward system signals the partial lack of information. The brain can use the uncertainty signals to assess the uncertainty of rewards, influence learning, modulate the value of uncertain rewards and make appropriate behavioural choices between only partly known options.
Introduction. Neuroeconomics: the promise and the profit
Authors: Schultz Wolfram
Published: October 2008

Neuroeconomics investigates the neural mechanisms underlying decisions about rewarding or punishing outcomes (‘economic’ decisions). It combines the knowledge about the behavioural phenomena of economic decisions with the mechanistic explanatory power of neuroscience. Thus, it is about the neurobiological foundations of economic decision making. It is hoped that by ‘opening the box’ we can understand how decisions about gains and losses are directed by the brain of the individual decision maker. Perhaps we can even learn why some decisions are apparently paradoxical or pathological. The knowledge could be used to create situations that avoid suboptimal decisions and harm.
Neural correlates of economic game playing
Authors: Krueger Frank , Grafman Jordan , McCabe Kevin
Published: October 2008

The theory of games provides a mathematical formalization of strategic choices, which have been studied in both economics and neuroscience, and more recently has become the focus of neuroeconomics experiments with human and non-human actors. This paper reviews the results from a number of game experiments that establish a unitary system for forming subjective expected utility maps in the brain, and acting on these maps to produce choices. Social situations require the brain to build an understanding of the other person using neuronal mechanisms that share affective and intentional mental states. These systems allow subjects to better predict other players' choices, and allow them to modify their subjective utility maps to value pro-social strategies. New results for a trust game are presented, which show that the trust relationship includes systems common to both trusting and trustworthy behaviour, but they also show that the relative temporal positions of first and second players require computations unique to that role.
Pristionchus pacificus: A Genetic Model System for the Study of Evolutionary Developmental Biology and the Evolution of Complex Life-History Traits
Authors: Rae Robbie , Schlager Benjamin , Sommer Ralf J.
Published: October 2008

INTRODUCTION

Pristionchus pacificus is a nematode that has been established as a model system for evolutionary developmental biology. Initially, P. pacificus was used as a convenient nematode with which to compare the processes of vulva and gonad development as well as sex determination to Caenorhabditis elegans, one of the best-studied animal models. P. pacificus shares many features with C. elegans, including a short generation time, its ability to be easily cultured in the laboratory, and self-fertilization as a mode of reproduction. These features allowed forward and reverse genetic tools to be developed for this species. The application of these tools for genetic and molecular analysis of vulva formation revealed substantial differences between P. pacificus and C. elegans. The genome of P. pacificus has recently been sequenced and showed an expansion of protein-coding genes compared with C. elegans. Interestingly, the P. pacificus genome encodes some genes, such as cellulases, that are known to be present only in plant-parasitic nematodes. Many of the putative functions of the predicted genes in the genome are related to the ecology of P. pacificus and other Pristionchus species. Pristionchus nematodes can be isolated from beetles and soil, indicating that the ecology of P. pacificus is strikingly different from that of C. elegans. Generally, Pristionchus species show an unexpected level of species specificity in their beetle associations, providing a unique opportunity to study the genetic and molecular mechanisms underlying the interactions of organisms in the environment. Thus, P. pacificus is not only an established model system for evolutionary developmental biology, but also an emerging model system for the evolution of complex life-history traits.
Isolation of RNA and DNA from Biofilm Samples Obtained by Laser Capture Microdissection Microscopy: Figure 1.
Authors: Pérez-Osorio Ailyn C. , Franklin Michael J.
Published: October 2008

INTRODUCTION

The metabolic activities of bacteria growing in biofilms result in spatial gradients of oxygen, nutrients, and waste products. Because bacteria respond to local environmental conditions through changes in gene expression, mRNA levels of individual genes may vary spatially among bacteria within the biofilm. This article describes an approach to isolate RNA for quantification from cells at localized sites within biofilms. Biofilm thin sections are generated by embedding biofilms in cryoembedding resin, freezing the embedded biofilms on dry ice, and cutting with a cryomicrotome. The sections are placed on membrane-coated microscope slides and maintained on dry ice. Laser capture microdissection microscopy (LCMM) is used to dissect small subsets of cells at different regions within the biofilms, and RNA is extracted from the samples using either hot phenol or TRI reagent. A TRI reagent-based DNA extraction method is also presented.
Whole-Mount In Situ Hybridization of Spider Embryos
Authors: Prpic Nikola-Michael , Schoppmeier Michael , Damen Wim G.M.
Published: October 2008

INTRODUCTION

The spider Cupiennius salei, commonly known as the American wandering spider, is a particularly useful laboratory model for embryological studies because of the availability of tools to study and manipulate its embryonic development. Cupiennius is used to study axis formation, segmentation, appendage development, neurogenesis, and silk production. These studies contribute to our understanding of the evolution of these processes, but they also help us to understand the origin and diversification of evolutionary novelties. Comparisons between spiders and insects can show the degree of conservation and divergence of developmental mechanisms during arthropod evolution. Any embryological feature conserved between spiders and insects is likely to represent an ancestral feature for arthropods. Comparative molecular embryological work in insects and spiders should eventually allow us to define a molecular archetype for the phylum Arthropoda. This in itself will be a necessary cornerstone for comparing the different metazoan phyla, including chordates. This protocol describes the detection of transcripts in fixed C. salei embryos using whole-mount in situ hybridization.
Detection of Cell Death in Spider Embryos Using TUNEL
Authors: Prpic Nikola-Michael , Schoppmeier Michael , Damen Wim G.M.
Published: October 2008

INTRODUCTION

The spider Cupiennius salei, commonly known as the American Wandering Spider, is a particularly useful laboratory model for embryological studies because of the availability of tools to study and manipulate its embryonic development. Cupiennius is used to study axis formation, segmentation, appendage development, neurogenesis, and silk production. These studies contribute to our understanding of the evolution of these processes, but they also help us to understand the origin and diversification of evolutionary novelties. Comparisons between spiders and insects can show the degree of conservation and divergence of developmental mechanisms during arthropod evolution. Any embryological feature conserved between spiders and insects is likely to represent an ancestral feature for arthropods. Comparative molecular embryological work in insects and spiders should eventually allow us to define a molecular archetype for the phylum Arthropoda. This in itself will be a necessary cornerstone for comparing the different metazoan phyla, including chordates. A feature of apoptosis (i.e., cell death) is the cleavage or fragmentation of DNA that occurs in dead or dying cells. This protocol describes the detection of fragmented DNA in whole-mount Cupiennius embryos. The 3′-OH ends of these DNA fragments can be labeled with the terminal deoxynucleotidyl-transferase-mediated dUTP-digoxigenin nick-end labeling (TUNEL) technique. This protocol uses a terminal deoxynucleotidyl transferase to add labeled dUTP to the fragmented DNA, and this label is then detected by immunocytochemistry. The TUNEL technique is a relatively easy way to obtain a reliable picture of the cell death pattern during normal and abnormal development.
Basic Maintenance and Breeding of the Opossum Monodelphis domestica
Authors: Keyte Anna L. , Smith Kathleen K.
Published: October 2008

INTRODUCTION

Monodelphis domestica, the gray, short-tailed, or laboratory opossum, is the most commonly used laboratory marsupial. In addition to the factors that make it a convenient laboratory animal (small size, ease of care, nonseasonal breeding), it is the first marsupial whose genome has been sequenced. Monodelphis has proven useful as a model organism for studies on spinal cord regeneration, ultraviolet (UV)-induced melanoma, and genetic influences on cholesterol, as well as comparative studies of the immune system. In addition, Monodelphis has been used to understand the basic functions of the olfactory system and the role of various olfactory chemicals in social and reproductive behavior. Recently, Monodelphis has been used to understand fundamental aspects of marsupial development, anatomy, evolution, and evolutionary consequences of the derived marsupial mode of development and reproduction. Monodelphis are easily maintained and bred in the lab. To do extensive embryonic work, a reasonably large breeding colony must be maintained. A colony of ~100 animals (~3:1 female:male ratio) allows for sacrifice of up to 12 pregnant females per month for experimental purposes, as well as for replenishment of the colony. However, because adults will fight and often kill one another if kept in the same cage for prolonged periods, we have developed a special breeding protocol that provides high rates of breeding success (75%-90%), with minimal injury due to fighting. Here, we outline this breeding strategy and describe how to successfully maintain a colony of Monodelphis in a laboratory setting.
Cell Membrane Surface Potential (ψ
0) Plays a Dominant Role in the Phytotoxicity of Copper and Arsenate
Authors: Wang Peng , Zhou Dongmei , Kinraide Thomas B. , Luo Xiaosan , Li Lianzhen , Li Dandan , Zhang Hailin
Published: October 2008

Negative charges at cell membrane surfaces (CMS) create a surface electrical potential (ψ  0) that affects ion concentrations at the CMS and consequently affects the phytotoxicity of metallic cations and metalloid anions in different ways. The ζ potentials of root protoplasts of wheat (Triticum aestivum), as affected by the ionic environment of the solution, were measured and compared with the values of ψ  0 calculated with a Gouy-Chapman-Stern model. The mechanisms for the effects of cations (H+, Ca2+, Mg2+, Na+, and K+) on the acute toxicity of Cu2+ and As(V) to wheat were studied in terms of ψ  0. The order of effectiveness of the ions in reducing the negativity of ψ  0 was H+ > Ca2+ ≈ Mg2+ > Na+ ≈ K+. The calculated values of ψ  0 were proportional to the measured ζ potentials (r  2 = 0.93). Increasing Ca2+ or Mg2+ activities in bulk-phase media resulted in decreased CMS activities of Cu2+ ({Cu2+}0) and increased CMS activities of As(V) ({As(V)}0). The 48-h EA50{Cu2+}b ({Cu2+} in bulk-phase media accounting for 50% inhibition of root elongation over 48 h) increased initially and then declined, whereas the 48-h EA50{As(V)}b decreased linearly. However, the intrinsic toxicity of Cu2+ (toxicity expressed in terms of {Cu2+}0) appeared to be enhanced as ψ  0 became less negative and the intrinsic toxicity of As(V) appeared to be reduced. The ψ  0 effects, rather than site-specific competitions among ions at the CMS (invoked by the biotic ligand model), may play the dominant role in the phytotoxicities of Cu2+ and As(V) to wheat.
Arabidopsis Transcriptome Reveals Control Circuits Regulating Redox Homeostasis and the Role of an AP2 Transcription Factor
Authors: Khandelwal Abha , Elvitigala Thanura , Ghosh Bijoy , Quatrano Ralph S.
Published: October 2008

Sensors and regulatory circuits that maintain redox homeostasis play a central role in adjusting plant metabolism and development to changing environmental conditions. We report here control networks in Arabidopsis (Arabidopsis thaliana) that respond to photosynthetic stress. We independently subjected Arabidopsis leaves to two commonly used photosystem II inhibitors: high light (HL) and 3-(3,4-dichlorophenyl)-1,1-dimethylurea (DCMU). Microarray analysis of expression patterns during the period of redox adjustment to these inhibitors reveals that 20% and 8% of the transcriptome are under HL and DCMU regulation, respectively. Approximately 6% comprise a subset of genes common to both perturbations, the redox responsive genes (RRGs). A redox network was generated in an attempt to identify genes whose expression is tightly coordinated during adjustment to homeostasis, using expression of these RRGs under HL conditions. Ten subnetworks were identified from the network. Hierarchal subclustering of subnetworks responding to the DCMU stress identified novel groups of genes that were tightly controlled while adjusting to homeostasis. Upstream analysis of the promoters of the genes in these clusters revealed different motifs for each subnetwork, including motifs that were previously identified with responses to other stresses, such as light, dehydration, or abscisic acid. Functional categorization of RRGs demonstrated involvement of genes in many metabolic pathways, including several families of transcription factors, especially those in the AP2 family. Using a T-DNA insertion in one AP2 transcription factor (redox-responsive transcription factor 1 [RRTF1]) from the RRGs, we showed that the genes predicted to be within the subnetwork containing RRTF1 were changed in this insertion line (Δrrtf1). Furthermore, Δrrtf1 showed greater sensitivity to photosynthetic stress compared to the wild type.
Proteolysis-Independent Downregulation of DELLA Repression inArabidopsisby the Gibberellin Receptor GIBBERELLIN INSENSITIVE DWARF1
Authors: Ariizumi Tohru , Murase Kohji , Sun Tai-ping , Steber Camille M.
Published: October 2008

This article presents evidence that DELLA repression of gibberellin (GA) signaling is relieved both by proteolysis-dependent and -independent pathways in Arabidopsis thaliana. DELLA proteins are negative regulators of GA responses, including seed germination, stem elongation, and fertility. GA stimulates GA responses by causing DELLA repressor degradation via the ubiquitin-proteasome pathway. DELLA degradation requires GA biosynthesis, three functionally redundant GA receptors GIBBERELLIN INSENSITIVE DWARF1 (GID1a, b, and c), and the SLEEPY1 (SLY1) F-box subunit of an SCF E3 ubiquitin ligase. The sly1 mutants accumulate more DELLA proteins but display less severe dwarf and germination phenotypes than the GA biosynthesis mutant ga1-3 or the gid1abc triple mutant. Interestingly, GID1 overexpression rescued the sly1 dwarf and infertility phenotypes without decreasing the accumulation of the DELLA protein REPRESSOR OF ga1-3. GID1 rescue of sly1 mutants was dependent on the level of GID1 protein, GA, and the presence of a functional DELLA motif. Since DELLA shows increasing interaction with GID1 with increasing GA levels, it appears that GA-bound GID1 can block DELLA repressor activity by direct protein–protein interaction with the DELLA domain. Thus, a SLY1-independent mechanism for GA signaling may function without DELLA degradation.
Record of sea‐level fall in tropical carbonates
Authors: Schlager Wolfgang , Warrlich Georg
Published: October 2008

Stratigraphic forward modeling and comparison with published case studies have been used to determine the controls and stability domains of two conceptual models concerning relative sea‐level fall in carbonate sequence stratigraphy. In the standard model, deposition occurs principally during rise and stillstands of relative sea level; a continuous erosional unconformity develops during sea‐level fall. The falling‐stage systems tract model (FST) postulates significant deposition during sea‐level fall. Sedimentological principles, numerical models and published case studies of tropical carbonate sequences indicate that presence or absence of FST is not simply a function of the rate of sea‐level fall but depends on the balance of the rates of erosion, sea‐level fall and carbonate production, whereby the FST is favoured by high production, slow erosion and slow sea‐level fall. Case studies plotted in the parameter space spanned by these variables support the modeling results. The ranges of rates required for the FST in the modeling runs are common in the geologic record. Consequently, the FST can be expected to be more common in tropical carbonate rocks than published records, particularly seismic data, currently indicate.
ADAMTS13 cleavage efficiency is altered by mutagenic and, to a lesser extent, polymorphic sequence changes in the A1 and A2 domains of von Willebrand factor
Authors: Pruss Cynthia M. , Notley Colleen R. P. , Hegadorn Carol A. , O’Brien Lee A. , Lillicrap David
Published: October 2008

The multimeric plasma protein von Willebrand factor (VWF) is regulated in size by its protease, ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motif, member 13). Y1605‐M1606 cleavage site mutations and single nucleotide polymorphisms (SNPs) in the VWF A1 and A2 domains were examined for alteration in ADAMTS13‐mediated cleavage of VWF. Recombinant human full‐length VWF (rVWF) was digested with recombinant human ADAMTS13 (rADAMTS13) using a dialysis membrane method with 1·5 mol/l urea, and analyzed via multimer migration distance. The glutathione‐S‐transferase (GST) and histidine‐tagged construct, E1554‐R1668 of VWF (VWF115) was assayed via enzyme‐linked immunosorbent assay: VWF115 was bound to anti‐GST coated plates, digested with rADAMTS13, and intact VWF115 detected via horseradish peroxidase‐labelled anti‐histidine tag antibody. All alterations examined in the Y1605‐M1606 cleavage site greatly reduced the cleavability of VWF by ADAMTS13 in the rVWF assay. Greatest cleavage resistance in both assays was observed in Y1605A/M1606A. In contrast, Y1605H and M1606L show a loss of cleavability only in the rVWF assay, suggesting that an aromatic ring at 1605 is critical for ADAMTS13 recognition. Additionally, under our rVWF assay conditions, the G1643S polymorphism showed increased cleavage, suggesting a Type 2A VWD phenotype, while D1472H, Q1571H and P1601T showed slightly decreased ADAMTS13 cleavage. Our two complementary assay conditions show that A‐domain changes in VWF alter ADAMTS13‐mediated proteolysis.
Bortezomib is associated with better health‐related quality of life than high‐dose dexamethasone in patients with relapsed multiple myeloma: results from the APEX study
Authors: Lee Stephanie J. , Richardson Paul G. , Sonneveld Pieter , Schuster Michael W. , Irwin David , San Miguel Jesús‐F. , Crawford Bruce , Massaro Joseph , Dhawan Ravinder , Gupta Sanjay , Anderson Kenneth C.
Published: October 2008

Health‐related quality of life (HRQL) was prospectively measured during the phase III APEX trial of bortezomib versus dexamethasone in relapsed multiple myeloma patients. The European Organisation for Research and Treatment of Cancer (EORTC) Quality of Life Questionnaire – Core (QLQ‐C30) and Functional Assessment of Cancer Therapy/Gynecologic Oncology Group–Neurotoxicity (NTX) side‐effects questionnaires were administered at baseline and every 6 weeks up to 42 weeks. Patients receiving bortezomib (1·3 mg/m2, days 1, 4, 8 and 11 for eight 3‐week cycles, then days 1, 8, 15 and 22 for three 5‐week cycles; n = 296) demonstrated significantly better mean Global Health Status over the study versus patients receiving dexamethasone (40 mg/d, days 1–4, 9–12, and 17–20 for four 5‐week cycles, then days 1–4 only for five 4‐week cycles; n = 302), plus significantly better physical health, role, cognitive, and emotional functioning scores, lower dyspnoea and sleep symptom scores, and better NTX questionnaire score, using multiple imputation to account for missing data. Results were similar using available‐data analyses. Sensitivity analyses suggested that improved HRQL with bortezomib is at least partially explained by improved survival. These results show that bortezomib was associated with significantly better multidimensional HRQL compared with dexamethasone, consistent with the better clinical outcomes seen with bortezomib.
Differential clot stabilising effects of rFVIIa and rFXIII‐A2 in whole blood from thrombocytopenic patients and healthy volunteers
Authors: Johansson Pär I. , Jacobsen Niels , Viuff Dorthe , Olsen Eva H. N. , Rojkjaer Rasmus , Andersen Søren , Petersen Lars C. , Kjalke Marianne
Published: October 2008

The haemostatic effect of recombinant activated factor VII (rFVIIa; NovoSeven®) in thrombocytopenic patients has been a matter of controversy. Haemostasis by rFVIIa occurs via FVIIa‐mediated thrombin generation in a platelet‐dependent manner and may therefore be suboptimal in patients without functional platelets. Under such conditions, a clot‐stabilizing agent, such as factor XIII (FXIII), may supplement the effect of rFVIIa and improve haemostasis. Recombinant factor XIII (rFXIII‐A2) is produced as an A2 homodimer of the FXIII A subunit and is equivalent to cellular FXIII normally found in platelets. The combined effects of rFVIIa and rFXIII‐A2 were evaluated in clot lysis assays using factor XIII‐deficient plasma and by whole blood thrombelastography (TEG) analysis from normal donors and thrombocytopenic stem cell transplantation patients. Clotting time was shortened by rFVIIa (0·6–10 μg/ml). rFVIIa only modestly improved anti‐fibrinolysis, whereas rFXIII‐A2 (0–20 μg/ml) enhanced anti‐fibrinolysis without effect on clotting time. TEG analysis showed rFVIIa shortened the clotting time, and enhanced clot development, maximal mechanical strength and resistance to fibrinolysis, whereas, rFXIII‐A2 enhanced clot development, maximal mechanical strength and markedly enhanced resistance to fibrinolysis. These data illustrate that rFVIIa and rFXIII‐A2 contribute to clot formation and stability by different mechanisms suggesting enhanced haemostatic efficacy by combining these agents.
MicroRNA 155 modulates megakaryopoiesis at progenitor and precursor level by targeting Ets‐1 and Meis1 transcription factors
Authors: Romania Paolo , Lulli Valentina , Pelosi Elvira , Biffoni Mauro , Peschle Cesare , Marziali Giovanna
Published: October 2008

MicroRNAs (miRNAs) control basic biological functions and are emerging as key regulators of haematopoiesis. This study focused on the functional role of MIRN155 on megakaryocytic (MK) differentiation of human cord blood CD34+ haematopoietic progenitor cells (HPCs). MIRN155, abundantly expressed in early HPCs, decreases sharply during MK differentiation. Functional studies showed that enforced expression of MIRN155 impairs proliferation and differentiation of MK cells. Furthermore, HPCs transfected with MIRN155 showed a significant reduction of their MK clonogenic capacity, suggesting that down‐modulation of this miRNA favours MK progenitor differentiation. Consistent with this observation, MIRN155 down‐regulates, by directly binding to their 3′‐UTR, the expression of Ets‐1 and Meis1, two transcription factors with well‐known functions in MK cells. These results show that the decline of MIRN155 is required for MK proliferation and differentiation at progenitors and precursors level and indicate that sustained expression of MIRN155 inhibits megakaryopoiesis.
Thrombin activatable fibrinolysis inhibitor gene polymorphisms are associated with antigenic levels in the Asian‐Indian population but may not be a risk for stroke
Authors: Biswas Arijit , Tiwari Arun K. , Ranjan Ravi , Meena Arvind , Akhter Mohammad S. , Yadav Birendra K. , Behari Madhuri , Saxena Renu
Published: October 2008

Thrombin activatable fibrinolysis inhibitor [carboxypeptidase B2 (plasma), CPB2] is a basic carboxypeptidase, which inhibits fibrinolysis by cleaving the C‐terminal lysine residues on plasmin‐modified partially degraded fibrin. Plasma CPB2 concentrations have been reported to be under the control of numerous single nucleotide polymorphisms located in the regulatory and coding regions of the gene encoding CPB2 (CPB2). High functional CPB2 levels have been found to be associated with an increased risk for ischemic stroke. The present study investigated CPB2 antigen levels and associated CPB2 polymorphisms in an acute onset non‐cardioembolic stroke population compared with an age‐ and sex‐matched healthy control population. This is, to the best of our knowledge, the first such study done in an Asian Indian population. CPB2 antigen levels were significantly associated with the disease phenotype (P < 0·001) and with CPB2 polymorphisms (P < 0·001). The haplotypes generated on analysis of the genotypic data accounted for 21% of the natural variation in the CPB2 antigenic levels. However none of the haplotype combinations generated showed any association with disease phenotype and therefore could not explain for the difference in CPB2 antigen levels between cases and controls.
Treosulfan‐based conditioning regimen for allogeneic haematopoietic stem cell transplantation in patients with thalassaemia major
Authors: Bernardo Maria Ester , Zecca Marco , Piras Eugenia , Vacca Adriana , Giorgiani Giovanna , Cugno Chiara , Caocci Giovanni , Comoli Patrizia , Mastronuzzi Angela , Merli Pietro , La Nasa Giorgio , Locatelli Franco
Published: October 2008

The safety and efficacy of a preparation with treosulfan/thiotepa/fludarabine were explored in 20 thalassaemia patients given allogeneic marrow transplantation. Seventeen patients were transplanted from unrelated donors after receiving anti‐thymocyte globulin. The regimen was well tolerated. Two patients experienced secondary graft failure; one died of acute graft‐versus‐host disease. Cumulative incidence (95% confidence interval, CI) of transplantation‐related mortality and graft failure was 5% (95% CI, 0–34%) and 11% (95% CI, 3–43%), respectively. Two‐year probability of survival and thalassaemia‐free survival was 95% (95% CI, 85–100%) and 85% (95% CI, 66–100%), respectively. This regimen might find elective application in patients at high risk of developing life‐threatening complications.
Understanding haemophilic arthropathy: an exploration of current open issues
Authors: Jansen Nathalie W. D. , Roosendaal Goris , Lafeber Floris P. J. G.
Published: October 2008

Haemophilic arthropathy is joint damage evolving from recurrent joint bleeds that occur in patients suffering from the clotting disorder haemophilia. Insight into the pathogenetic mechanism of this blood‐induced arthropathy yields possible treatment targets and modalities useful to reduce this invalidating co‐morbidity of haemophilia. Joint bleeding leads to initially independent adverse changes in both the synovial tissue and the articular cartilage. These subsequently influence each other: the synovial inflammatory changes enhancing cartilage damage and vice versa. Consequently, effective treatment strategies will have to affect both pathways.
Salinity tolerance of Great Lakes invaders
Authors: ELLIS SANDRA , MACISAAC HUGH J.
Published: October 2008

1. The Laurentian Great Lakes are among the most invaded freshwater ecosystems in the world. Historically, the major vector for the introduction of non‐indigenous species (NIS) has been the release of contaminated ballast water via transoceanic ships. Despite regulations implemented in 1993, requiring vessels carrying fresh ballast water to exchange this water with saline ocean water, new reports of invasions have continued.

2. NIS often have a wide environmental tolerance allowing them to adapt to and invade a variety of habitats. It has been hypothesized that NIS with broad salinity tolerance may be able to survive ballast water exchange (BWE) and continue to pose an invasion risk to the Great Lakes.

3. We tested the short‐term salinity tolerance of eight recent invaders to the Great Lakes, specifically three cladocera (Bosmina coregoni, Bythotrephes longimanus, Cercopagis pengoi), two molluscs (Dreissena polymorpha, Dreissena rostriformis bugensis), and one species each of the families Gammaridae, Mysidae and Gobidae (Echinogammarus ischnus, Hemimysis anomala, Neogobius melanostomus) to determine if they could have survived salinities associated with BWE.

4. Overall, short‐term exposure to highly saline water dramatically reduced survival of all species. Two different methods of BWE tested, simultaneous and sequential, were equally effective in reducing survival. Species that survived the longest in highly saline water either possess behavioural characteristics that reduce exposure to adverse environments (valve closure; both Dreissena species) or are reported to have some degree of salinity tolerance in their native region (Echinogammarus). Given that exposure in our trials lasted a maximum of 48 h, and that species in ballast tanks would typically be exposed to saline water for c. 5 days, it appears that BWE is an effective method to reduce the survival of these NIS. These results provide impetus for tightening policy and monitoring of BWE, in particular for ships entering the Great Lakes from freshwater ports.
Information technology‐based standardized patient education in psychiatric inpatient care
Authors: Anttila Minna , Koivunen Marita , Välimäki Maritta
Published: October 2008

Title.  Information technology‐based standardized patient education in psychiatric inpatient care

Aim.  This paper is a report of a study to describe nurses’ experiences of information technology‐based standardized patient education in inpatient psychiatric care.

Background.  Serious mental health problems are an increasing global concern. Emerging evidence supports the implementation of practices that are conducive to patient self‐management and improved patient outcomes among chronically ill patients with mental health problems. In contrast, the attitude of staff towards information technology has been reported to be contradictory in mental health care.

Method.  After 1 year of using an Internet‐based portal (Mieli.Net) developed for patients with schizophrenia spectrum psychosis, all 89 participating nurses were asked to complete questionnaires about their experiences. The data were collected in 2006. Fifty‐six participants (63%) returned completed questionnaires and the data were analysed using content analysis.

Findings.  Nurses’ experiences of the information technology‐based standardized patient education were categorized into two major categories describing the advantages and obstacles in using information technology. Nurses thought that it brought the patients and nurses closer to each other and helped nurses to provide individual support for their patients. However, the education was time‐consuming.

Conclusion.  Systematic patient education using information technology is a promising method of patient‐centred care which supports nurses in their daily work. However, it must fit in with clinical activities, and nurses need some guidance in understanding its benefits. The study data can be used in policy‐making when developing methods to improve the transparency of information provision in psychiatric nursing.
How people live with or get over being suicidal: a review of qualitative studies
Authors: Lakeman Richard , FitzGerald Mary
Published: October 2008

Title. How people live with or get over being suicidal: a review of qualitative studies

Aim. To systematically review qualitative research which addresses how people live with suicidality or recover a desire to live.

Background. Suicide is a pressing social and public health problem. Much emphasis in suicide research has been on the epidemiology of suicide and the identification of risk and protective factors. Relatively little emphasis has been given to the subjective experiences of suicidal people, but this is necessary to inform the care and help provided to individuals.

Data sources. Electronic searches of CINAHL Plus with full text, Medline and PsychArticles (included PsycINFO, Social Services Abstracts and Sociological abstracts) were undertaken for the period from 1997 to April 2007. In addition, the following journals were hand searched (1997–2007): ‘Mortality’, ‘Death Studies’, ‘Archives of Suicide Research’ and ‘Crisis: The Journal of Crisis Intervention and Suicide Prevention’.

Method. A systematic review of the literature and thematic content analysis of findings. The findings were extracted from selected papers and synthesized by way of content analysis in narrative and tabular form.

Findings. Twelve studies were identified. Analysis revealed a number of interconnected themes: the experience of suffering, struggle, connection, turning points and coping.

Conclusions. Living with or overcoming suicidality involves various struggles, often existential in nature. Suicide may be seen as both a failure and a means of coping. People may turn away from suicide quite abruptly through experiencing, gaining or regaining the right kind of connection with others. Nurses working with suicidal individuals should aspire to be identified as people who can turn people’s lives around.
Development and psychometric testing of the Nursing Workplace Relational Environment Scale (NWRES)
Authors: Duddle Maree , Boughton Maureen
Published: October 2008

Aims and objectives.  The aim of this study was to develop and test the psychometric properties of the Nursing Workplace Relational Environment Scale (NWRES).

Background.  A positive relational environment in the workplace is characterised by a sense of connectedness and belonging, support and cooperation among colleagues, open communication and effectively managed conflict. A poor relational environment in the workplace may contribute to job dissatisfaction and early turnover of staff.

Design.  Quantitative survey.

Method.  A three‐stage process was used to design and test the NWRES. In Stage 1, an extensive literature review was conducted on professional working relationships and the nursing work environment. Three key concepts; collegiality, workplace conflict and job satisfaction were identified and defined. In Stage 2, a pool of items was developed from the dimensions of each concept and formulated into a 35‐item scale which was piloted on a convenience sample of 31 nurses. In Stage 3, the newly refined 28‐item scale was administered randomly to a convenience sample of 150 nurses. Psychometric testing was conducted to establish the construct validity and reliability of the scale.

Results.  Exploratory factor analysis resulted in a 22‐item scale. The factor analysis indicated a four‐factor structure: collegial behaviours, relational atmosphere, outcomes of conflict and job satisfaction which explained 68·12% of the total variance. Cronbach’s alpha coefficient for the NWRES was 0·872 and the subscales ranged from 0·781–0·927.

Conclusion.  The results of the study confirm the reliability and validity of the NWRES. Replication of this study with a larger sample is indicated to determine relationships among the subscales.

Relevance to clinical practice.  The results of this study have implications for health managers in terms of understanding the impact of the relational environment of the workplace on job satisfaction and retention.
Patient participation in emergency care – a phenomenographic analysis of caregivers’ conceptions
Authors: Frank Catharina , Asp Margareta , Dahlberg Karin
Published: October 2008

Aims and objectives.  The aim of this study was to describe caregivers’ conceptions of patient participation in an emergency care unit.

Background.  Patient participation is an important goal in health care. Patients who are given the opportunity to participate in care situations are able to influence care in a way that is more beneficial to them. Patients’ participation in caring has been studied in different contexts, but little health care research has been conducted into patient participation in the emergency care unit. Patients treated in emergency care units sometimes express dissatisfaction with their care situation and it would therefore be important to find out how caregivers in emergency care experience patient participation.

Design.  A phenomenographic research method based on life world theory was used in the study.

Method.  Data were collected from 11 caregivers with experience of working in an emergency department. The caregivers were from different professions: three physicians, four nurses and four auxiliary nurses.

Results.  The caregivers’ conceptions of patient participation can be divided into three different descriptive categories: caregivers offer the opportunity for participation, patients demand participation and mutual participation.

Conclusions.  The study adds knowledge that caregivers’ different qualitative conceptions of patient participation are mainly conditional from caregivers.

Relevance to clinical practice.  Mutual participation is perceived occasionally and often unexpectedly, when the right circumstances occur, despite international and national guidelines that lay down the need for patient participation.