bluuebunny/crossref_metadata_2025 huggingface dataset:
Utility of the Clostridial Site-Specific Recombinase TnpX To Clone Toxic-Product-Encoding Genes and Selectively Remove Genomic DNA Fragments
Authors: Adams Vicki , Bantwal Radhika , Stevenson Lauren , Cheung Jackie K. , Awad Milena M. , Nicholson Joel , Carter Glen P. , Mackin Kate E. , Rood Julian I. , Lyras Dena
Published: March 2014

TnpX is a site-specific recombinase responsible for the excision and insertion of the transposons Tn
4451
and Tn
4453
in
Clostridium perfringens
and
Clostridium difficile
, respectively. Here, we exploit phenotypic features of TnpX to facilitate genetic mutagenesis and complementation studies. Genetic manipulation of bacteria often relies on the use of antibiotic resistance genes; however, a limited number are available for use in the clostridia. The ability of TnpX to recognize and excise specific DNA fragments was exploited here as the basis of an antibiotic resistance marker recycling system, specifically to remove antibiotic resistance genes from plasmids in
Escherichia coli
and from marked chromosomal
C. perfringens
mutants. This methodology enabled the construction of a
C. perfringens
plc virR
double mutant by allowing the removal and subsequent reuse of the same resistance gene to construct a second mutation. Genetic complementation can be challenging when the gene of interest encodes a product toxic to
E. coli
. We show that TnpX represses expression from its own promoter, P

attCI

, which can be exploited to facilitate the cloning of recalcitrant genes in
E. coli
for subsequent expression in the heterologous host
C. perfringens
. Importantly, this technology expands the repertoire of tools available for the genetic manipulation of the clostridia.
Depletion of the Trypanosome Pumilio Domain Protein PUF2 or of Some Other Essential Proteins Causes Transcriptome Changes Related to Coding Region Length
Authors: Jha Bhaskar Anand , Fadda Abeer , Merce Clementine , Mugo Elisha , Droll Dorothea , Clayton Christine
Published: March 2014

Pumilio domain RNA-binding proteins are known mainly as posttranscriptional repressors of gene expression that reduce mRNA translation and stability.
Trypanosoma brucei
has 11 PUF proteins. We show here that PUF2 is in the cytosol, with roughly the same number of molecules per cell as there are mRNAs. Although PUF2 exhibits a low level of
in vivo
RNA binding, it is not associated with polysomes. PUF2 also decreased reporter mRNA levels in a tethering assay, consistent with a repressive role. Depletion of PUF2 inhibited growth of bloodstream-form trypanosomes, causing selective loss of mRNAs with long open reading frames and increases in mRNAs with shorter open reading frames. Reexamination of published RNASeq data revealed the same trend in cells depleted of some other proteins. We speculate that these length effects could be caused by inhibition of the elongation phase of transcription or by an influence of translation status or polysomal conformation on mRNA decay.
Calcineurin-Crz1 Signaling in Lower Eukaryotes
Authors: Thewes S.
Published: March 2014

Calcium ions are ubiquitous intracellular messengers. An increase in the cytosolic Ca
2+
concentration activates many proteins, including calmodulin and the Ca
2+
/calmodulin-dependent protein phosphatase calcineurin. The phosphatase is conserved from yeast to humans (except in plants), and many target proteins of calcineurin have been identified. The most prominent and best-investigated targets, however, are the transcription factors NFAT (nuclear factor of activated T cells) in mammals and Crz1 (calcineurin-responsive zinc finger 1) in yeast. In recent years, many orthologues of Crz1 have been identified and characterized in various species of fungi, amoebae, and other lower eukaryotes. It has been shown that the functions of calcineurin-Crz1 signaling, ranging from ion homeostasis through cell wall biogenesis to the building of filamentous structures, are conserved in the different organisms. Furthermore, frequency-modulated gene expression through Crz1 has been discovered as a striking new mechanism by which cells can coordinate their response to a signal. In this review, I focus on the latest findings concerning calcineurin-Crz1 signaling in fungi, amoebae and other lower eukaryotes. I discuss the potential of Crz1 and its orthologues as putative drug targets, and I also discuss possible parallels with calcineurin-NFAT signaling in mammals.
Role of Force-Sensitive Amyloid-Like Interactions in Fungal Catch Bonding and Biofilms
Authors: Chan Cho X. J. , Lipke Peter N.
Published: March 2014

The
Candida albicans
Als adhesin Als5p has an amyloid-forming sequence that is required for aggregation and formation of model biofilms on polystyrene. Because amyloid formation can be triggered by force, we investigated whether laminar flow could activate amyloid formation and increase binding to surfaces. Shearing
Saccharomyces cerevisiae
cells expressing Als5p or
C. albicans
at 0.8 dyne/cm
2
increased the quantity and strength of cell-to-surface and cell-to-cell binding compared to that at 0.02 dyne/cm
2
. Thioflavin T fluorescence showed that the laminar flow also induced adhesin aggregation into surface amyloid nanodomains in Als5p-expressing cells. Inhibitory concentrations of the amyloid dyes thioflavin S and Congo red or a sequence-specific anti-amyloid peptide decreased binding and biofilm formation under flow. Shear-induced binding also led to formation of robust biofilms. There was less shear-activated increase in adhesion, thioflavin fluorescence, and biofilm formation in cells expressing the amyloid-impaired V326N-substituted Als5p. Similarly,
S. cerevisiae
cells expressing Flo1p or Flo11p flocculins also showed shear-dependent binding, amyloid formation, biofilm formation, and inhibition by anti-amyloid compounds. Together, these results show that laminar flow activated amyloid formation and led to enhanced adhesion of yeast cells to surfaces and to biofilm formation.
Heterologous Expression of Bartonella Adhesin A in Escherichia coli by Exchange of Trimeric Autotransporter Adhesin Domains Results in Enhanced Adhesion Properties and a Pathogenic Phenotype
Authors: Schmidgen Thomas , Kaiser Patrick O. , Ballhorn Wibke , Franz Bettina , Göttig Stephan , Linke Dirk , Kempf Volkhard A. J.
Published: March 2014

Human-pathogenic
Bartonella henselae
causes cat scratch disease and vasculoproliferative disorders. An important pathogenicity factor of
B. henselae
is the trimeric autotransporter adhesin (TAA)
Bartonella
adhesin A (BadA), which is modularly constructed, consisting of a head, a long and repetitive neck-stalk module, and a membrane anchor. BadA is involved in bacterial autoagglutination, binding to extracellular matrix proteins and host cells, and in proangiogenic reprogramming. The slow growth of
B. henselae
and limited tools for genetic manipulation are obstacles for detailed examination of BadA and its domains. Here, we established a recombinant expression system for BadA mutants in
Escherichia coli
allowing functional analysis of particular BadA domains. Using a BadA mutant lacking 21 neck-stalk repeats (BadA HN23), the BadA HN23 signal sequence was exchanged with that of
E. coli
OmpA, and the BadA membrane anchor was additionally replaced with that of
Yersinia
adhesin A (YadA). Constructs were cloned in
E. coli
, and hybrid protein expression was detected by immunoblotting, fluorescence microscopy, and flow cytometry. Functional analysis revealed that BadA hybrid proteins mediate autoagglutination and binding to collagen and endothelial cells.
In vivo
, expression of this BadA construct correlated with higher pathogenicity of
E. coli
in a
Galleria mellonella
infection model.
Mental health admissions in paediatric populations in North Wales: two cohorts compared 1875–1924 and 1994–2008
Authors: Basa Fouad B , Harris Margret , Syed Mujahid Ali , Le Noury Joanna , Healy David
Published: March 2014

Objectives

To investigate frequency of under-18s admitted to mental health services (MHS) in North West Wales (NWW) between 1875 and 2008. There are claims that 1 in 10 children have a mental illness, but there are little data on their inpatient MHS utilisation.

Setting

Looking at admissions at the secondary care level, three data samples were included; the first comprises historical asylum admissions, the second comprises contemporary admissions to acute psychiatric beds, and the third comprises admissions to district general hospital (DGH) beds that resulted in a mental health coding.

Participants

All were under 18. There were 65 historical patients, 41 contemporary mental illness admissions and 943 DGH admissions.

Primary and secondary outcome measures

The primary outcome measures were diagnoses based on case notes of the historical cohort between 1875 and 1924, as well as details of paediatric admissions to MHS from 1994 to 2008 and paediatric admissions with a mental health component to the DGH in NWW.

Results

The incidence of admission to a mental health bed was 1.55 per year in the historical cohort compared with 2.9 in the contemporary. The overall incidence of admission to any bed in the contemporary cohort was 129 patients per year. There has been a twofold increase in the incidence of admissions for schizophrenia and related psychosis, but this most likely stems from an earlier age of admission rather than a true increase.

Conclusions

There is a greater frequency of hospital admissions for youth under the age of 18 in NWW for mental health today than previously. The rates reported in the DGH sample are consistent with data from community surveys of patients meeting criteria for mental disorders and complement such data when it comes to planning for paediatric MHS. However, they also raise questions about the boundaries between disease and distress.
Acute hospital-based services utilisation during the last year of life in New South Wales, Australia: methods for a population-based study
Authors: O'Connell Dianne L , Goldsbury David E , Davidson Patricia , Girgis Afaf , Phillips Jane L , Piza Michael , Wilkinson Anne , Ingham Jane M
Published: March 2014

Objectives

The aim of this study is to describe healthcare utilisation in the last year of life for people in Australia, to help inform health services planning. The methods and datasets that are being used are described in this paper.

Design/Setting

Linked, routinely collected administrative health data are being analysed for all people who died in New South Wales (NSW), Australia's most populous state, in 2007. The data comprised linked death records (2007), hospital admissions and emergency department presentations (2006–2007) and cancer registrations (1994–2007).

Participants

There were 46 341 deaths in NSW in 2007. The initial analyses include 45 760 decedents aged 18 years and over.

Outcome measures

The primary measures address the utilisation of hospital-based services at the end of life, including number and length of hospital admissions, emergency department presentations, intensive care admissions, palliative-related admissions and place of death.

Results

The median age at death was 80 years. Cause of death was available for 95% of decedents and 85% were linked to a hospital admission record. In the greater metropolitan area, where data capture was complete, 83% of decedents were linked to an emergency department presentation. 38% of decedents were linked to a cancer diagnosis in 1994–2007. The most common causes of death were diseases of the circulatory system (34%) and neoplasms (29%).

Conclusions

This study is among the first in Australia to give an information-rich census of end-of-life hospital-based experiences. While the administrative datasets have some limitations, these population-wide data can provide a foundation to enable further exploration of needs and barriers in relation to care. They also serve to inform the development of a relatively inexpensive, timely and reliable approach to the ongoing monitoring of acute hospital-based care utilisation near the end of life and inform whether service access and care are optimised.
Caring for those who die at home: the use and validation of ‘Care Of the Dying Evaluation’ (CODE) with bereaved relatives
Authors: Mayland Catriona R , Lees Carolyn , Germain Alison , Jack Barbara A , Cox Trevor F , Mason Stephen R , West Angela , Ellershaw John E
Published: March 2014

Background

As well as facilitating patients’ wish to die at home, evaluating quality of care in this setting is essential. Postbereavement surveys with family members represent one assessment method. ‘Care Of the Dying Evaluation’ (CODE) is a 40-item self-completion postbereavement questionnaire, based on the key components of best practice for care of the dying.

Aim

To assess the validity and reliability of CODE by conducting: cognitive ‘think aloud’ interviews; test–retest analysis; and assessing internal consistency and construct validity of three key composite scales.

Design

Postbereavement survey to next-of-kin (NOK).

Setting/participants

291 NOK to patients who died at home in Northwest England from an advanced incurable illness were invited to complete the CODE questionnaire. Additionally, potential participants were asked to undertake a cognitive interview and/or complete CODE for a second time a month later.

Results

72 bereaved relatives (24.7% response rate) returned the completed CODE questionnaire, and 25 completed CODE for a second time. 15 cognitive interviews were undertaken. All interviewees found CODE sensitively worded and easy to understand. Minor revisions were suggested to provide additional clarity. Test–retest analysis showed all except one question had moderate or good stability. Although the ENVIRONMENT scale was not as relevant within the home setting, all three key composite scales showed good internal consistency and construct validity.

Conclusions

‘CODE’ represents a user-friendly, comprehensive outcome measure for care of the dying and has been found to be valid and reliable. CODE could potentially be used to benchmark individual organisations and identify areas for improvement.
Potential triggers for the holistic assessment of people with severe chronic obstructive pulmonary disease: analysis of multiperspective, serial qualitative interviews
Authors: Cawley D , Billings J , Oliver D , Kendall M , Pinnock H
Published: March 2014

Objectives

This study explores the narrative accounts of chronic obstructive pulmonary disease (COPD) to identify events that potentially could act as triggers for provision of supportive and palliative care. Trigger events must have meaning for the patient/carer, be visible to professionals, and have value in provoking useful actions.

Methods

A purposive sample of people with severe COPD, and their informal and professional carers, was recruited from primary/secondary care in Scotland. Indepth participant-led interviews allowed people to tell their illness story. Events occurring throughout the individual's account of the COPD journey were identified, and analysed thematically with regard to the meaning, visibility and use as potential triggers.

Results

Events identified from 92 transcripts (21 patients, 13 family carers, 18 professionals) punctuated the disease trajectory and crossed multiprofessional boundaries of care. These reflected advancing disease (increasing carer burden, becoming housebound, appointment frequency, increasing burden of disease, shifting priorities of care) or were an intervention addressing the consequences of advancing disease (requesting disabled parking, home adaptations, hospital admissions). Despite being meaningful in terms of increasing disability, many were invisible to professionals. Others were isolated events symptomatic of wider, ongoing disability which could potentially have use as triggers.

Conclusions

Meaningful events can be identified within the story of COPD which reflect wider needs, are clearly visible to alert professionals, and be of use in terms of potentially guiding supportive interventions. To achieve this level of usefulness, services will need to promote health and social care integration with clear processes to facilitate holistic assessment when a trigger is detected.
Global educational disparities in the associations between body mass index and diabetes mellitus in 49 low-income and middle-income countries
Authors: Wang Aolin , Stronks Karien , Arah Onyebuchi A
Published: March 2014

Background

Despite the well-established link between body mass index (BMI) and diabetes mellitus (DM), it remains unclear whether this association is more pronounced at certain levels of education. This study assessed the modifying effect of educational attainment on the associations between BMI and DM—as well as the joint associations of BMI and education with DM—in low-income countries (LICs) and middle-income countries (MICs).

Methods

The authors used cross-sectional data from 160 381 participants among 49 LICs and MICs in the World Health Survey. Overweight and obesity levels were defined using WHO's classification. Educational attainment was classified in four categories: ‘no formal education’, ‘some/completed primary school’, ‘secondary/high school completed’ and ‘college and beyond’. We used random-intercept multilevel logistic regressions to investigate the modifying influence of educational attainment on the associations of different BMI levels—as well as their joint associations—with DM.

Results

We found positive associations between excessive BMI and DM at each education level in both LICs and MICs. We found that the joint associations of BMI and education with DM were larger than the product of their separate single associations among females in LICs. With joint increases in BMI and education, males and females in LICs had similar increased odds of DM, but males had higher such odds than females in MICs.

Conclusions

BMI and education are associated with the DM, but the associations seem to differ in complex ways between LICs and MICs and by gender.
J-shapedness: an often missed, often miscalculated relation: the example of weight and mortality
Authors: Cao Sissi , Moineddin Rahim , Urquia Marcelo L , Razak Fahad , Ray Joel G
Published: March 2014

We present three considerations in analysing the association between weight and mortality, as well as other relations that might be non-linear in nature. First, authors must graphically plot their independent and dependent variables in a continuous manner. Second, authors should assess the shape of that relation, and note its shape. If it is non-linear, and specifically, J-shaped or U-shaped, careful consideration should be given to using the ‘best’ statistical model, of which multivariate fractional polynomial regression is a reasonable choice. Authors should also refrain from truncating their data to avoid dealing with non-linear relations.
Viscous behaviour of clays in one-dimensional compression
Authors: Wong Ron C.K. , Varatharajan Sivarajan
Published: March 2014

Oedometer tests were conducted on dry and saturated kaolinite clay samples to investigate the effects of stress level, stress history, pore fluid type, and drainage path on time-dependent deformation under one-dimensional (1D) constant stress. Different deformation modes involved in the creep compression were identified and quantified: creep deformation of individual particles and creep shear displacement at particle contacts. It was found that the creep compression is a coupled process involving the above creep deformations and induced viscous flow resulting in pore compression. The rate of 1D creep compression is controlled by the drainage path along which the viscous flow occurs. It was also observed that mechanically induced consolidation has an accelerating effect on the creep compression of the test samples existing within the limit time zone. This observation confirms that 1D creep compression is a continuation of 1D consolidation in which the largest existing interaggregate pores collapse under a given effective stress. No creep compression was observed when the test samples were mechanically overconsolidated to a state beyond the limit time zone because the interaggregates were compressed to a stable structure. Reduced creep compression was detected in chemically induced consolidated samples though their states were beyond the limit time line.
Combined effects of rising [CO2] and temperature on boreal forests: growth, physiology and limitations
Authors: Stinziano Joseph R. , Way Danielle A.
Published: March 2014

Climate change is expected to be most pronounced at high latitudes, but we have little data on how dominant boreal tree species will respond to rising temperatures and CO2 concentrations ([CO2]). We review the mechanisms through which elevated growth temperatures and atmospheric CO2 alter tree physiology and growth, focusing on the dominant species in northern forests. Water and nutrient availability, as well as day length, are likely to constrain the ability of these forests to respond positively to warmer, potentially longer growing seasons and higher CO2 levels. We also analyze published tree responses to future climate scenarios for key boreal tree species and show that (i) high [CO2] increases biomass and net photosynthetic rates compared with ambient [CO2], under both current temperatures and warmer climates; (ii) increases in temperature above current levels have little effect on growth or carbon gain; and (iii) the combination of elevated [CO2] and elevated temperatures increases plant biomass, but this effect appears to have a threshold above a 5 °C increase in growth temperatures. While rising temperatures and [CO2], therefore, have the potential to increase the productivity of northern forest species (based on experiments that supply ample water and fertilizer), this response is likely to be limited by these soil resources and the photoperiod in the field, and may not occur under the more extreme warming conditions predicted for the future in this region.
Muonic–electronic quasi molecules based on a fully stripped multicharged ion
Authors: Kryukov N. , Oks E.
Published: March 2014

In our previous paper (Can. J. Phys. 91, 715 (2013) doi: 10.1139/cjp-2013-0077 ) we studied a system consisting of a proton, a muon, and an electron; the muon and the electron being in circular states. The study was motivated by numerous applications of muonic atoms and molecules, where one of the electrons is substituted by the heavier lepton μ–. We demonstrated that in such a μpe quasi molecule, the muonic motion can represent a rapid subsystem while the electronic motion can represent a slow subsystem — a result that may seem counterintuitive. In other words, the muon rapidly revolves in a circular orbit about the axis connecting the proton and electron while this axis slowly rotates following a relatively slow electronic motion. We showed that the spectral lines, emitted by the muon in the quasi molecule, μpe, experience a red shift compared to the corresponding spectral lines that would have been emitted by the muon in a muonic hydrogen atom. In the present paper we generalize this study by replacing the proton in the μpe quasi molecule by a fully stripped ion of nuclear charge Z > 1. We show that in this case, just as in the previously studied case of Z = 1, the muonic motion can represent a rapid subsystem while the electronic motion can represent a slow subsystem. For this to be valid, the ratio of the muonic and electronic angular momenta should be slightly greater than in the case of Z = 1. We demonstrate that the binding energies of the muon for Z > 1 are much greater than for Z = 1 at any finite value of the nucleus–electron distance. Finally we show that the red shift of the spectral lines emitted by the muon (compared to the spectral lines of the corresponding muonic hydrogen-like ion of nuclear charge Z) decreases as Z increases. However, the relative red shift remains within the spectral resolution of available spectrometers at least up to Z = 5. Observing this red shift should be one of the ways to detect the formation of the quasi molecules, μZe.
Testing predictions of optimal diving theory using animal-borne video from harbour seals (Phoca vitulina concolor)
Authors: Heaslip Susan G. , Bowen W. Don , Iverson Sara J.
Published: March 2014

Optimal diving theory predicts that animals make decisions that maximize their foraging profitability subject to the constraint of oxygen stores. We examined the temporal pattern of prey encounters within a dive from concurrently collected dive data and animal-borne video from a free-ranging pinniped to test predictions of optimal diving theory. Crittercams were deployed on 32 adult male harbour seals (Phoca vitulina concolor De Kay, 1842) at Sable Island, Nova Scotia, Canada, for 3 days each. Deployments resulted in approximately 3 h of video per seal and a total of 2275 capture attempts for 1474 prey encounter events recorded. We found support for seven of the nine selected predictions of optimal diving theory. As predicted, prey encounters increased with bottom duration; dive duration increased with dive depth; and travel duration, bottom duration, and percent bottom duration decreased over a wide range of travel durations. Descent duration did increase with dive depth, and seals terminated dives earlier when no prey were encountered and when prey were encountered later in a dive. Contrary to prediction, bottom duration did not increase and then decrease for short travel durations and dives were not terminated earlier when travel durations were short and prey encounter rate was low.
Diel patterns of baseline glucocorticoids and stress responsiveness in a teleost fish (bluegill, Lepomis macrochirus)
Authors: Cousineau A. , Midwood J.D. , Stamplecoskie K. , King G. , Suski C.D. , Cooke S.J.
Published: March 2014

Little is known about whether glucocorticoids (GC) and GC responsiveness vary on a diel basis in the wild, especially for fish. Using bluegill (Lepomis macrochirus Rafinesque, 1819) as a model freshwater teleost fish, we tested whether baseline concentration and stress responsiveness of GCs (i.e., plasma glucose and cortisol) varied over a 24 h period. Blood samples from lake-dwelling wild bluegill were obtained across six periods representing a complete circadian cycle to determine GC levels in newly captured fish (i.e., within 3 min of capture; baseline), the maximum value (maximum) 45 min following exposure to a standardized aerial exposure stressor, and determining responsiveness (by subtracting minimum from maximum). Our results revealed that baseline glucose concentration did not vary on a diel basis, whereas baseline cortisol concentration did. Maximum and stress-induced glucose responsiveness varied significantly among several time periods with lowest values recorded at midnight and higher values at mid-day. Maximum and stress-induced cortisol responsiveness were consistent across time periods. Collectively, these data suggest that baseline concentrations and stress-induced values of GCs in a freshwater temperate teleost fish tend to be consistent across diel periods such that there is apparently an absence of strong GC diel patterns.
The Cycle of Classification: DSM-I Through DSM-5
Authors: Blashfield Roger K. , Keeley Jared W. , Flanagan Elizabeth H. , Miles Shannon R.
Published: March 2014

The Diagnostic and Statistical Manual of Mental Disorders (DSM) was created in 1952 by the American Psychiatric Association so that mental health professionals in the United States would have a common language to use when diagnosing individuals with mental disorders. Since the initial publication of the DSM, there have been five subsequent editions of this manual published (including the DSM-III-R). This review discusses the structural changes in the six editions and the research that influenced those changes. Research is classified into three domains: (a) issues related to the DSMs as measurement systems, (b) studies of clinicians and how clinicians form diagnoses, and (c) taxonomic issues involving the philosophy of science and metatheoretical ideas about how classification systems function. The review ends with recommendations about future efforts to revise the DSMs.
Development of Clinical Practice Guidelines
Authors: Hollon Steven D. , Areán Patricia A. , Craske Michelle G. , Crawford Kermit A. , Kivlahan Daniel R. , Magnavita Jeffrey J. , Ollendick Thomas H. , Sexton Thomas L. , Spring Bonnie , Bufka Lynn F. , Galper Daniel I. , Kurtzman Howard
Published: March 2014

Clinical practice guidelines (CPGs) are intended to improve mental, behavioral, and physical health by promoting clinical practices that are based on the best available evidence. The American Psychological Association (APA) is committed to generating patient-focused CPGs that are scientifically sound, clinically useful, and informative for psychologists, other health professionals, training programs, policy makers, and the public. The Institute of Medicine (IOM) 2011 standards for generating CPGs represent current best practices in the field. These standards involve multidisciplinary guideline development panels charged with generating recommendations based on comprehensive systematic reviews of the evidence. The IOM standards will guide the APA as it generates CPGs that can be used to inform the general public and the practice community regarding the benefits and harms of various treatment options. CPG recommendations are advisory rather than compulsory. When used appropriately, high-quality guidelines can facilitate shared decision making and identify gaps in knowledge.
Matrix elasticity regulates the optimal cardiac myocyte shape for contractility
Authors: McCain Megan L. , Yuan Hongyan , Pasqualini Francesco S. , Campbell Patrick H. , Parker Kevin Kit
Published: March 2014

Concentric hypertrophy is characterized by ventricular wall thickening, fibrosis, and decreased myocyte length-to-width aspect ratio. Ventricular thickening is considered compensatory because it reduces wall stress, but the functional consequences of cell shape remodeling in this pathological setting are unknown. We hypothesized that decreases in myocyte aspect ratio allow myocytes to maximize contractility when the extracellular matrix becomes stiffer due to conditions such as fibrosis. To test this, we engineered neonatal rat ventricular myocytes into rectangles mimicking the 2-D profiles of healthy and hypertrophied myocytes on hydrogels with moderate (13 kPa) and high (90 kPa) elastic moduli. Actin alignment was unaffected by matrix elasticity, but sarcomere content was typically higher on stiff gels. Microtubule polymerization was higher on stiff gels, implying increased intracellular elastic modulus. On moderate gels, myocytes with moderate aspect ratios (∼7:1) generated the most peak systolic work compared with other cell shapes. However, on stiffer gels, low aspect ratios (∼2:1) generated the most peak systolic work. To compare the relative contributions of intracellular vs. extracellular elasticity to contractility, we developed an analytical model and used our experimental data to fit unknown parameters. Our model predicted that matrix elasticity dominates over intracellular elasticity, suggesting that the extracellular matrix may potentially be a more effective therapeutic target than microtubules. Our data and model suggest that myocytes with lower aspect ratios have a functional advantage when the elasticity of the extracellular matrix decreases due to conditions such as fibrosis, highlighting the role of the extracellular matrix in cardiac disease.
Conditioned media from mesenchymal stromal cells restore sodium transport and preserve epithelial permeability in an in vitro model of acute alveolar injury
Authors: Goolaerts Arnaud , Pellan-Randrianarison Nadia , Larghero Jérôme , Vanneaux Valérie , Uzunhan Yurdagül , Gille Thomas , Dard Nicolas , Planès Carole , Matthay Michael A. , Clerici Christine
Published: March 2014

Mesenchymal stromal cells (MSCs) or their media (MSC-M) were reported to reverse acute lung injury (ALI)-induced decrease of alveolar fluid clearance. To determine the mechanisms by which MSC-M exert their beneficial effects, an in vitro model of alveolar epithelial injury was created by exposing primary rat alveolar epithelial cells (AECs) to hypoxia (3% O2) plus cytomix, a combination of IL-1β, TNF-α, and IFN-γ. MSC-M were collected from human MSCs exposed for 12 h to either normoxia (MSC-M) or to hypoxia plus cytomix (HCYT-MSC-M). This latter condition was used to model the effect of alveolar inflammation and hypoxia on paracrine secretion of MSCs in the injured lung. Comparison of paracrine soluble factors in MSC media showed that the IL-1 receptor antagonist and prostaglandin E2were markedly increased while keratinocyte growth factor (KGF) was twofold lower in HCYT-MSC-M compared with MSC-M. In AECs, hypoxia plus cytomix increased protein permeability, reduced amiloride-sensitive short-circuit current (AS- Isc), and also decreased the number of α-epithelial sodium channel (α-ENaC) subunits in the apical membrane. To test the effects of MSC media, MSC-M and HCYT-MSC-M were added for an additional 12 h to AECs exposed to hypoxia plus cytomix. MSC-M and HCYT-MSC-M completely restored epithelial permeability to normal. MSC-M, but not HCYT-MSC-M, significantly prevented the hypoxia plus cytomix-induced decrease of ENaC activity and restored apical α-ENaC channels. Interestingly, KGF-deprived MSC-M were unable to restore amiloride-sensitive sodium transport, indicating a possible role for KGF in the beneficial effect of MSC-M. These results indicate that MSC-M may be a preferable therapeutic option for ALI.
Alveolar type II cells maintain bioenergetic homeostasis in hypoxia through metabolic and molecular adaptation
Authors: Lottes Robyn G. , Newton Danforth A. , Spyropoulos Demetri D. , Baatz John E.
Published: March 2014

Although many lung diseases are associated with hypoxia, alveolar type II epithelial (ATII) cell impairment, and pulmonary surfactant dysfunction, the effects of O2limitation on metabolic pathways necessary to maintain cellular energy in ATII cells have not been studied extensively. This report presents results of targeted assays aimed at identifying specific metabolic processes that contribute to energy homeostasis using primary ATII cells and a model ATII cell line, mouse lung epithelial 15 (MLE-15), cultured in normoxic and hypoxic conditions. MLEs cultured in normoxia demonstrated a robust O2consumption rate (OCR) coupled to ATP generation and limited extracellular lactate production, indicating reliance on oxidative phosphorylation for ATP production. Pharmacological uncoupling of respiration increased OCR in normoxic cultures to 175% of basal levels, indicating significant spare respiratory capacity. However, when exposed to hypoxia for 20 h, basal O2consumption fell to 60% of normoxic rates, and cells maintained only ∼50% of normoxic spare respiratory capacity, indicating suppression of mitochondrial function, although intracellular ATP levels remained at near normoxic levels. Moreover, while hypoxic exposure stimulated glycogen synthesis and storage in MLE-15, glycolytic rate (as measured by lactate generation) was not significantly increased in the cells, despite enhanced expression of several enzymes related to glycolysis. These results were largely recapitulated in murine primary ATII, demonstrating MLE-15 suitability for modeling ATII metabolism. The ability of ATII cells to maintain ATP levels in hypoxia without enhancing glycolysis suggests that these cells are exceptionally efficient at conserving ATP to maintain bioenergetic homeostasis under O2limitation.
On the Paranormed Nörlund Sequence Space of Nonabsolute Type
Authors: Yeşilkayagil Medine , Başar Feyzi
Published: March 2014

Maddox defined the spaceℓ(p)of the sequencesx=(xk)such that∑k=0∞‍|xk|pk<∞, in Maddox, 1967. In the present paper, the Nörlund sequence spaceNt(p)of nonabsolute type is introduced and proved that the spacesNt(p)andℓ(p)are linearly isomorphic. Besides this, the alpha-, beta-, and gamma-duals of the spaceNt(p)are computed and the basis of the spaceNt(p)is constructed. The classes(Nt(p):μ)and(μ:Nt(p))of infinite matrices are characterized. Finally, some geometric properties of the spaceNt(p)are investigated.
Impairment in Preattentive Processing among Patients with Hypertension Revealed by Visual Mismatch Negativity
Authors: Si Cuiping , Ren Changjie , Wang Peng , Bian Hetao , Wang Haiming , Yan Zhongrui
Published: March 2014

Objective.Patients with hypertension show deficits in cognitive function. However, the neural mechanisms underlying the preattentive information processing in hypertensive patients are poorly understood. We seek to investigate whether hypertensive patients have impairments in preattentive information processing.Methods.We compared visual mismatch negativity (vMMN) between 15 hypertensive patients and 15 age-matched healthy controls, which was elicited by the change of visual duration randomly presented in both peripheral visual fields. In addition, the global cognitive function for all participants was assessed with Mini-Mental State Examination (MMSE).Results.The vMMN in deviant-standard comparison was observed at occipital-temporal regions. Compared with normal healthy controls, the amplitude of vMMN was significantly decreased in hypertensive patients (P<0.05). Meanwhile, the vMMN peak latency was delayed in the hypertensive group (P<0.05). However, the MMSE scores of patients with hypertension were not significantly different from those of controls (P>0.05), and there was no significant correlation between the mean amplitude of vMMN and SBP, DBP, and MMSE in hypertensive individuals, respectively.Conclusions.These data indicate dysfunction of automatically change detection processing in patients with hypertension. Moreover, the changes of vMMN provide a more objective and reliable assessment for cognitive impairment in hypertensive patients.
Determination of Location, Size, and Transmurality of Chronic Myocardial Infarction Without Exogenous Contrast Media by Using Cardiac Magnetic Resonance Imaging at 3 T
Authors: Kali Avinash , Cokic Ivan , Tang Richard L.Q. , Yang Hsin-Jung , Sharif Behzad , Marbán Eduardo , Li Debiao , Berman Daniel S. , Dharmakumar Rohan
Published: March 2014

Background—

Late-gadolinium–enhanced (LGE) cardiac MRI (CMR) is a powerful method for characterizing myocardial infarction (MI), but the requisite gadolinium infusion is estimated to be contraindicated in ≈20% of patients with MI because of end-stage chronic kidney disease. The purpose of this study is to investigate whether T
1
CMR obtained without contrast agents at 3 T could be an alternative to LGE CMR for characterizing chronic MIs using a canine model of MI.

Methods and Results—

Canines (n=29) underwent CMR at 7 days (acute MI [AMI]) and 4 months (chronic MI [CMI]) after MI. Infarct location, size, and transmurality measured by using native T
1
maps and LGE images at 1.5 T and 3 T were compared. Resolution of edema between AMI and CMI was examined with T
2
maps. T
1
maps overestimated infarct size and transmurality relative to LGE images in AMI (
P
=0.016 and
P
=0.007, respectively), which was not observed in CMI (
P
=0.49 and
P
=0.81, respectively) at 3 T. T
1
maps underestimated infarct size and transmurality relative to LGE images in AMI and CMI (
P
<0.001) at 1.5 T. Relative to the remote territories, T
1
of the infarcted myocardium was increased in CMI and AMI (
P
<0.05), and T
2
of the infarcted myocardium was increased in AMI (
P
<0.001) but not in CMI (
P
>0.20) at both field strengths. Histology showed extensive replacement fibrosis within the CMI territories. CMI detection sensitivity and specificity of T
1
CMR at 3 T were 95% and 97%, respectively.

Conclusions—

Native T
1
maps at 3 T can determine the location, size, and transmurality of CMI with high diagnostic accuracy. Patient studies are necessary for clinical translation.
Globalization and the Quality of Asian and Non-Asian Jobs
Authors: Flanagan Robert J. , Khor Niny
Published: March 2014

This paper assesses the impact of international trade and investment flows on the evolution of working conditions and labor rights in Asian and non-Asian countries in the late 20th and early 21st centuries. Labor conditions improved as globalization increased during this period. We find that real per capita income growth remains a powerful source of improved labor conditions, and the effect of trade on working conditions is mainly indirect through its impact on per capita gross domestic product (GDP). We find no evidence that eliminating trade barriers degrades labor conditions. We do find evidence that persistent differences in labor conditions between Asia and the rest of the world can be explained by differences in growth and international trade. Finally, we find no evidence that countries with poor labor conditions attract disproportionate flows of foreign direct investment (FDI). Instead, FDI flows seem mainly influenced by considerations of market size, investment risks, and the share of trade in GDP. After holding those influences constant, Asia receives a comparatively small share of world FDI inflows.
A Comprehensive Analysis of Poverty in India
Authors: Panagariya Arvind , Mukim Megha
Published: March 2014

This paper offers a comprehensive analysis of poverty in India. It shows that regardless of which of the two official poverty lines we use, we see a steady decline in poverty in all states and for all social and religious groups. Accelerated growth between fiscal years 2004–2005 and 2009–2010 also led to an accelerated decline in poverty rates. Moreover, the decline in poverty rates during these years has been sharper for the socially disadvantaged groups relative to upper caste groups so that we now observe a narrowing of the gap in the poverty rates between the two sets of social groups. The paper also provides a discussion of the recent controversies in India regarding the choice of poverty lines.
Effects of Monetary Policy Shocks on the Exchange Rate in the Republic of Korea: Capital Flows in Stock and Bond Markets
Authors: Kim Soyoung
Published: March 2014

Several studies have suggested that the prediction of standard theory on the effects of monetary policy on the exchange rate might not be applicable to or in the case of the Republic of Korea because participation of foreign investors is weak in the bond market but strong in the stock market. The current study examines the effects of monetary policy shocks on the exchange rate in the Republic of Korea by using structural vector autoregression models with sign restrictions. To determine the channels by which monetary policy shocks affect the exchange rate, I investigate the effects on various components of capital flows. The main empirical findings are as follows. First, a contractionary monetary policy shock, which increases the interest rate, appreciates the Korean won significantly in the short run as predicted by most theories. Second, contractionary monetary policy shocks increase capital inflows into the bond market consistent with the prediction of the uncovered interest parity condition. This seems to be the main channel by which contractionary monetary shocks appreciate the won. Finally, foreign investors tend to withdraw money from the domestic stock market in response to a monetary tightening, resulting in a decrease in capital inflows.
Spatial Price Differences and Inequality in the People's Republic of China: Housing Market Evidence
Authors: Li Chao , Gibson John
Published: March 2014

The large literature on regional inequality in the People's Republic of China (PRC) is hampered by incomplete evidence on price dispersion across space, making it hard to distinguish real and nominal inequality. The two main methods used to calculate spatial deflators have been to price a national basket of goods and services across different regions in the country or else to estimate a food Engel curve and define the deflator as that needed for nominally similar households to have the same food budget shares in all regions. Neither approach is convincing with the data available. Moreover, a focus on tradable goods such as food may be misplaced because of the emerging literature on the rapid convergence of traded goods prices within the PRC that contrasts with earlier claims of fragmented internal markets. In a setting where traded goods prices converge rapidly, the main source of price dispersion across space should come from nontraded items, and especially from housing given the fixity of land. In this paper we use newly available data on dwelling sales in urban PRC to develop spatially-disaggregated indices of house prices which are then used as spatial deflators for both provinces and core urban districts. These new deflators complement existing approaches that have relied more on traded goods prices and are used to re-examine the evidence on the level of regional inequality. Around one-quarter of the apparent spatial inequality disappears once account is taken of cost-of-living differences.
Foreign Direct Investment and the Survival of Domestic Private Firms in Viet Nam
Authors: Kokko Ari , Thang Tran Toan
Published: March 2014

Foreign direct investment (FDI) may benefit local firms in the host country through various kinds of spillovers, but it may also raise competition and result in the crowding out of domestic firms. Using detailed firm-level data for the period 2001–2008, this paper examines the aggregate effect of FDI on the survival of domestic private firms in Viet Nam. We estimate the impact of both horizontal and vertical FDI and explore how the presence of state-owned enterprises (SOEs) influences the exit hazard for private firms. The results suggest that horizontal and upstream FDI raise the exit hazard significantly, while downstream FDI may reduce the hazard. The presence of SOEs has a direct negative effect on the survival odds of local private firms in the same industry, but there is also an indirect impact on the exit hazard from FDI. Local firms are more vulnerable to foreign entry in sectors with high SOE shares. Looking at the net effects of FDI during the period 2001–2008, we find that results vary between sectors and over time but that the overall impact has been surprising small. The paper also discusses policy conclusions and implications for empirical analyses of spillovers from FDI.
Conscious and Unconscious Representations of Observed Actions in the Human Motor System
Authors: Mattiassi Alan D. A. , Mele Sonia , Ticini Luca F. , Urgesi Cosimo
Published: March 2014

Action observation activates the observer's motor system. These motor resonance responses are automatic and triggered even when the action is only implied in static snapshots. However, it is largely unknown whether an action needs to be consciously perceived to trigger motor resonance. In this study, we used single-pulse TMS to study the facilitation of corticospinal excitability (a measure of motor resonance) during supraliminal and subliminal presentations of implied action images. We used a forward and backward dynamic masking procedure that successfully prevented the conscious perception of prime stimuli depicting a still hand or an implied abduction movement of the index or little finger. The prime was followed by the supraliminal presentation of a still or implied action probe hand. Our results revealed a muscle-specific increase of motor facilitation following observation of the probe hand actions that were consciously perceived as compared with observation of a still hand. Crucially, unconscious perception of prime hand actions presented before probe still hands did not increase motor facilitation as compared with observation of a still hand, suggesting that motor resonance requires perceptual awareness. However, the presentation of a masked prime depicting an action that was incongruent with the probe hand action suppressed motor resonance to the probe action such that comparable motor facilitation was recorded during observation of implied action and still hand probes. This suppression of motor resonance may reflect the processing of action conflicts in areas upstream of the motor cortex and may subserve a basic mechanism for dealing with the multiple and possibly incongruent actions of other individuals.