bluuebunny/crossref_metadata_2025 huggingface dataset:
AKT signalling in the failing heart
Authors: Chaanine Antoine H. , Hajjar Roger J.
Published: July 2011

AKT is a serine/threonine protein kinase, also known as protein kinase B, which regulates cardiac growth, myocardial angiogenesis, glucose metabolism, and cell death in cardiac myocytes. AKT is activated by its phosphorylation at Thr 308 and ser 473 by PDK1 and mTORC2, respectively, in response to trophic stimuli such as insulin and insulin growth factor. c‐Jun N‐Terminal Kinases (JNKs) phosphorylate AKT at Thr 450 and potentiate its interaction with its downstream effectors. The short‐term activation of AKT promotes physiological hypertrophy and protection from myocardial injury; whereas, its long‐term activation causes pathological hypertrophy and heart failure. In this review we will discuss the role of AKT in regulating signalling pathways in the heart with special emphasis on the role of AKT in modulating stress induced autophagic cell death in cardiomyocytes in vitro.
Tunnel magnetoresistance effect and magnetic damping in half-metallic Heusler alloys
Authors: Oogane M. , Mizukami S.
Published: July 2011

Some full-Heusler alloys, such as Co
2
MnSi and Co
2
MnGe, are expected to be half-metallic ferromagnetic material, which has complete spin polarization. They are the most promising materials for realizing half-metallicity at room temperature owing to their high Curie temperature. We demonstrate a huge tunnel magnetoresistance effect in a magnetic tunnel junction using a Co
2
MnSi Heusler alloy electrode. This result proves high spin polarization of the Heusler alloy. We also demonstrate a small magnetic damping constant in Co
2
FeAl epitaxial film. The very high spin polarization and small magnetic constant of Heusler alloys will be a great advantage for future spintronic device applications.
Mapping the networks for pluripotency
Authors: Xue Kun , Ng Jia-Hui , Ng Huck-Hui
Published: July 2011

There has been an immense interest in embryonic stem cells owing to their pluripotent property, which refers to the ability to differentiate into all cell types of an embryo. In the maintenance of this pluripotent nature, transcription factors play essential roles, and signalling pathways also act to sustain the undifferentiated state. Recent studies have unravelled multiple forms of interconnection and crosstalk between these two regulatory aspects of pluripotency. With the discovery of epiblast stem cells, there is an emerging concept that different pluripotent states could exist, and knowledge of both transcriptional networks and signalling pathways has been vital in dissecting the properties of these different states. Similar to classical reprogramming methodologies, various combinations of transcription factor transduction and the modulation of intracellular signalling have enabled the interconversion between pluripotent states. These studies provide an insight into the defining characteristics as well as the plasticity of pluripotent cells.
The evolving biology of small molecules: controlling cell fate and identity
Authors: Efe Jem A. , Ding Sheng
Published: July 2011

Small molecules have been playing important roles in elucidating basic biology and treatment of a vast number of diseases for nearly a century, making their use in the field of stem cell biology a comparatively recent phenomenon. Nonetheless, the power of biology-oriented chemical design and synthesis, coupled with significant advances in screening technology, has enabled the discovery of a growing number of small molecules that have improved our understanding of stem cell biology and allowed us to manipulate stem cells in unprecedented ways. This review focuses on recent small molecule studies of (i) the key pathways governing stem cell homeostasis, (ii) the pluripotent stem cell niche, (iii) the directed differentiation of stem cells, (iv) the biology of adult stem cells, and (v) somatic cell reprogramming. In a very short period of time, small molecules have defined a perhaps universally attainable naive ground state of pluripotency, and are facilitating the precise, rapid and efficient differentiation of stem cells into somatic cell populations relevant to the clinic. Finally, following the publication of numerous groundbreaking studies at a pace and consistency unusual for a young field, we are closer than ever to completely eliminating the need for genetic modification in reprogramming.
Induced pluripotent stem cells for modelling human diseases
Authors: Unternaehrer Juli J. , Daley George Q.
Published: July 2011

Research into the pathophysiological mechanisms of human disease and the development of targeted therapies have been hindered by a lack of predictive disease models that can be experimentally manipulated
in vitro
. This review describes the current state of modelling human diseases with the use of human induced pluripotent stem (iPS) cell lines. To date, a variety of neurodegenerative diseases, haematopoietic disorders, metabolic conditions and cardiovascular pathologies have been captured in a Petri dish through reprogramming of patient cells into iPS cells followed by directed differentiation of disease-relevant cells and tissues. However, realizing the true promise of iPS cells for advancing our basic understanding of disease and ultimately providing novel cell-based therapies will require more refined protocols for generating the highly specialized cells affected by disease, coupled with strategies for drug discovery and cell transplantation.
Stem cells for skeletal muscle repair
Authors: Shadrach Jennifer L. , Wagers Amy J.
Published: July 2011

Skeletal muscle is a highly specialized tissue composed of non-dividing, multi-nucleated muscle fibres that contract to generate force in a controlled and directed manner. Skeletal muscle is formed during embryogenesis from a subset of muscle precursor cells, which generate both differentiated muscle fibres and specialized muscle-forming stem cells known as satellite cells. Satellite cells remain associated with muscle fibres after birth and are responsible for muscle growth and repair throughout life. Failure in satellite cell function can lead to delayed, impaired or failed recovery after muscle injury, and such failures become increasingly prominent in cases of progressive muscle disease and in old age. Recent progress in the isolation of muscle satellite cells and elucidation of the cellular and molecular mediators controlling their activity indicate that these cells represent promising therapeutic targets. Such satellite cell-based therapies may involve either direct cell replacement or development of drugs that enhance endogenous muscle repair mechanisms. Here, we discuss recent breakthroughs in understanding both the cell intrinsic and extrinsic regulators that determine the formation and function of muscle satellite cells, as well as promising paths forward to realizing their full therapeutic potential.
The business of exploiting induced pluripotent stem cells
Authors: Prescott Catherine
Published: July 2011

Induced pluripotent stem cells (iPS cells) can be exploited for both research and clinical applications. The first part of this review seeks to provide an understanding of the financial drivers and key elements of a successful business strategy that underpin a company focused on developing iPS-related products and services targeted at the research market. The latter part of the review highlights some of the reasons as to why the reprogramming of somatic cells is currently being used to develop cell-based models to screen for small molecules with drug-like properties rather than to develop cell-based regenerative medicines
per se
. The latter may be used to repair or replace a patient's damaged cells and thereby have the potential to ‘cure’ a disease and, in doing so, prevent or delay the onset of associated medical conditions. However, the cost of an expensive regenerative medicine and time to accrue any benefit linked to a decrease in co-morbidity expenditure may not outweigh the benefit for a healthcare community that has finite resources. The implications of this are discussed together with evidence that the UK National Institute for Health and Clinical Excellence (NICE) and the National Health Service (NHS) have established a precedent for a cost-sharing strategy with the pharmaceutical industry.
Immunohistochemical distinction of haematogones from B lymphoblastic leukaemia/lymphoma or B‐cell acute lymphoblastic leukaemia (B‐ALL) on bone marrow trephine biopsies: a study on 62 patients
Authors: Al‐Shieban Saeed , Byrne Elizabeth , Trivedi Pritesh , Morilla Ricardo , Matutes Estella , Naresh Kikkeri N.
Published: July 2011

Haematogones are normal, maturing B‐cell precursors. They can be confused with neoplastic immature lymphoid cells of B lymphoblastic leukaemia/lymphoma or B‐cell acute lymphoblastic leukaemia (B‐ALL). Though multi‐colour flow‐cytometry strategies for distinguishing haematogones from cells of B‐ALL are well‐described, similar strategies have not been determined for bone marrow trephine biopsies (BMTB). We revisited the morphological and immunohistochemical features (CD20, CD34, TdT and PAX5 expression) in 69 BMTB from 62 patients – 27 with excess haematogones; seven with residual B‐ALL after therapy; 18 with no reported excess of haematogones or residual acute leukaemia on BMTB; and 17 diagnostic samples of B‐ALL. The distinctive immunophenotypic pattern of BMTB with excess haematogones was of CD34, TdT, CD20 and PAX5 accounting for increasing proportions of cells in the order mentioned, whereas among B‐ALL, the immunohistochemical pattern was of CD20, PAX5 and TdT accounting for an equal proportion of cells. Furthermore, among haematogones, the intensity of CD20 expression was extremely heterogeneous as compared to the neoplastic cells in CD20‐positive B‐ALL. The TdT‐positive haematogones were generally small and uniform, while a certain degree of heterogeneity was noticed among neoplastic B‐ALL cells. This study provides a practical strategy to distinguish haematogones from B‐ALL cells in BMTB.
An examination of how adolescent–caregiver dyad illness representations relate to adolescents' reported diabetes self‐management
Authors: Gaston A. M. , Cottrell D. J. , Fullen T.
Published: July 2011

Background  Adolescence is a period associated with poor glycaemic control. The key developmental concerns of young people are in conflict with the requirements of diabetes self‐management. This study explores the relative influence of adolescents' and caregivers' illness representations and how any difference/similarity in their representations may be related to adolescents' diabetes self‐management.

Methods  Fifty‐five adolescents between 12 and 16 years of age were asked to complete the Diabetes Illness Representation Questionnaire and Summary of Diabetes Self‐Care Activities Questionnaire. Their primary caregivers were asked to complete a caregivers' version of the Diabetes Illness Representation Questionnaire.

Results  Caregivers believed diabetes to be more chronic, to have a more negative impact, pose more of a threat to adolescents' health and believed more strongly in the effectiveness of treatment than did adolescents. Caregivers' representations about the impact of diabetes and the ability of treatment to prevent future complications were related to adolescents' dietary self‐management.

Conclusions  This study emphasizes the important role of significant others illness representations in adolescent self‐management of diabetes.
The views of mental health nurses on continuing professional development
Authors: Cleary Michelle , Horsfall Jan , O’Hara‐Aarons Maureen , Jackson Debra , Hunt Glenn E
Published: July 2011

Aims and objectives.  To determine clinical mental health nurses’ views and preferences about continuing professional development.

Background.  Participation in continuing professional development is now expected for nurse and midwifery registration. However, it is unclear how clinically based mental health nurses view continuing professional development and its relevance to career intentions.

Design.  Qualitative.

Method.  Semi‐structured face‐to‐face interviews with mental health nurses (n = 50) drawn from inpatient mental health units.

Results.  The most prominent factor identified through this research is that the majority of the fifty participants valued continuing professional development and sought more opportunities to participate. They particularly favoured in‐house locally based sessions targeting patient‐related clinical skills enhancement. Importantly, this interest in continuing professional development was not confined to new graduates needing to consolidate their skills. Work‐based flexibility, the types of courses available and opportunities for study leave were also identified as important factors. Of the 50 nurses interviewed, 40% expressed a desire for continuing professional development vis‐à‐vis remaining in the service; 30% of nurses responded to the same question with an emphasis on the importance of collegial support amongst peers and management; and 30% of the nurses indicated their primary focus for continuing professional development was to further their tertiary studies.

Conclusions.  These results are not only timely given the requirements around continuing professional development, but are also important to drive improvements in quality continuing professional development where needs are prioritised, discussed and agreed on.

Relevance to clinical practice.  Findings from this study highlight the value clinical nurses place on having access to work‐based and clinically focussed education and development. Relevant on‐the‐job professional education has the potential to improve job satisfaction and retention of clinical nurses, thus ultimately directly and positively influence patient care.
The evolution of the role of the Emergency Nurse Practitioner in Scotland: a longitudinal study
Authors: Fotheringham Diane , Dickie Sarah , Cooper Mark
Published: July 2011

Aims and objectives.  To examine how the role of the Emergency Nurse Practitioner has evolved in Scotland.

Background.  In 2001, Cooper and colleagues published a report on their survey (carried out in 1998) which described the extent and nature of Emergency Nurse Practitioner services in Scotland. They described a nascent nursing role and service that existed in almost half of Emergency Departments and that concentrated its activity on the management of minor distal limb trauma and wound management. Since that date, several relevant and important political, professional and local issues have combined to accelerate the development of this role.

Design.  Longitudinal survey of Scottish Emergency Departments (n = 97 in 1998, n = 93 in 2009).

Method.  Census survey of all Scottish Emergency Departments identified by NHS National Services Scotland’s Information and Statistics Division Accident and Emergency Waiting Times dataset 2006‐07.

Results.  Emergency Nurse Practitioners are now practising in the majority (89%) of Emergency Departments and Minor Injury Units compared with 47% in 1998. Most departments (78%) use Emergency Nurse Practitioners in dual roles, and most departments (67%) differentiate their Emergency Nurse Practitioners from other nursing staff by use of a title. Wide variations in pay, role and scope of practice still exist.

Conclusions.  The role of the Emergency Nurse Practitioner has increasingly become part of mainstream health care delivery in Emergency Departments across Scotland and can now be considered to be common place. This study demonstrates that ‘Advanced Nursing Practitioners’ and ‘Nurse Practitioners’ cannot necessarily be considered to be synonymous, and nursing roles that are allowed to evolve naturally adopt a non‐uniform level of practice.

Relevance to clinical practice.  This paper is of interest to Nurse Practitioners and workforce planners.
Safety and efficacy of two‐step peginterferon α‐2a treatment in patients of chronic hepatitis B with acute exacerbation
Authors: Chen C.‐C. , Wang P.‐C. , Chang H.‐W. , Chen C.‐F.
Published: July 2011

Summary.  The focus of this study was to evaluate the safety and efficacy of sequential peginterferon α‐2a (Pegasys) therapy for chronic hepatitis B with acute exacerbation [ALT > 10 × upper limit of normal (ULN), bilirubin <2.0 mg/dL]. Four groups of patients categorized by HBeAg status and treatment regimens were studied since May 2007. Nineteen HBeAg‐positive patients (Group 1) had received entecavir  pretreatment  (when ALT > 10 × ULN) plus Pegasys (180 μg/kg/week, when ALT was 5–10 × ULN) for 24 weeks. Thirteen HBeAg‐negative patients (Group 2) had the same protocol for 48 weeks. In both groups, entecavir was then discontinued 14 days after the initiation of Pegasys. The results were compared, respectively, to 35 HBeAg‐positive patients (Group 3) and 24 HBeAg‐negative patients (Group 4), all with ALT > 5 × ULN, under continual entecavir monotherapy. The ALT levels of patients in Group 1 and 2 who had received entecavir pretreatment for a duration of 19.63 ± 3.34 days were below four times of ULN following 4 weeks of Pegasys treatment. At week 96, the rates of sustained virological response were 69.2% (9/13) and 80% (8/10), and the relapse rates were 23.1% (3/13) and 11.2% (1/9) for HBeAg‐positive and HBeAg‐negative patients with two‐step Pegasys treatment, respectively. The HBeAg seroconversion rates were 46.2% in Group 1, and 42.1% in Group 3; HBsAg loss rates were 15.4% (2/13) in Group 1, and 30% (3/10) in Group 2, whereas none achieved HBsAg loss with entecavir monotherapy (Group 3 and 4). The two‐step Pegasys treatment offers an alternative, other than the nucleos(t)ides, for treating chronic hepatitis B with acute exacerbation and provides a safe, efficacious, short‐term and finite strategy.
Temporal distribution and pathogenicity of the predominant tomato‐infecting begomoviruses in Taiwan
Authors: Tsai W. S. , Shih S. L. , Kenyon L. , Green S. K. , Jan F.‐J.
Published: July 2011

Between 1998 and 2009, the four tomato‐infecting begomovirus species detected in Taiwan were Ageratum yellow vein Hualien virus (AYVHuV), Tomato leaf curl Taiwan virus (ToLCTWV), Tomato yellow leaf curl Thailand virus (TYLCTHV) and a newly defined species Tomato leaf curl Hsinchu virus (ToLCHsV). AYVHuV was detected occasionally in 2003 and ToLCHsV only in 2000–2001, whilst ToLCTWV was detected throughout the period. TYLCTHV was first detected in 2005. Between 1998 and 2005, >99% of the begomovirus‐positive samples were infected with ToLCTWV. In 2007 in western Taiwan, 16% of the positive samples were infected with ToLCTWV, 35% with TYLCTHV and 49% with mixed infection (ToLCTWV/TYLCTHV). In contrast, in eastern Taiwan the proportions were 84% ToLCTWV, 2% TYLCTHV and 14% mixed infection. However, throughout Taiwan in 2008–2009, most positive samples were either identified as TYLCTHV (51%) or mixed infection (ToLCTWV/TYLCTHV; 41%), and only 8% were ToLCTWV. This shows a clear trend of shifting from ToLCTWV to TYLCTHV and mixed infection over a short time period in Taiwan. Sequence analyses indicated that tomato‐infecting AYVHuV, an apparent recombinant between ToLCTWV and AYVHuV from Ageratum, represents a new strain Hsinchu. TYLCTHV Taiwan isolates were highly similar to each other, whereas ToLCTWV isolates had greater diversity and were classified into three strains which had one country‐wide and two local distributions. ToLCTWV and TYLCTHV were confirmed as monopartite and bipartite begomoviruses, respectively, by agroinfection followed by transmission with Bemisia tabaci biotype B. In addition, TYLCTHV was found to be mechanically transmissible together with viral DNA‐B.
Grapevine virus A variants of group II associated with Shiraz disease in South Africa are present in plants affected by Australian Shiraz disease, and have also been detected in the USA
Authors: Goszczynski D. E. , Habili N.
Published: July 2011

Primers were designed for RT‐nested PCR amplification of the highly variable 293‐nt fragment from the 5′ terminal part of the Grapevine virus A (GVA) replicase gene, specific to South African variants of molecular groups I and II. This new technique, along with RT‐PCR for simultaneous amplification of variants of groups I, II and III, as well as cloning of amplicons, single‐strand conformation polymorphism (SSCP) analysis of clones and sequencing, were used to investigate the populations of variants infecting 16 local Shiraz grapevines with different Shiraz disease (SD) status. The techniques were also used to study variants in GVA‐infected grapevines from Australia and the USA. The Australian grapevines included seven plants of cvs Shiraz and Merlot affected by Australian Shiraz disease (AuSD), and one plant of cv. Crimson Seedless with unknown AuSD status. Grapevines from the USA included plants of cvs Chardonnay, Thompson Seedless and an unknown cultivar. The results confirmed the association of certain genetic variants of group II with SD and showed the common presence of these variants in AuSD‐affected grapevines from Australia. Interestingly, a variant of this group was also detected in grapevine cv. Chardonnay from the USA, although the disease has not yet been reported from that country. The study also supports an earlier observation that members of group II, closely related to variant GTR1‐2, are not associated with the disease. The variants were found only in SD‐free grapevines. Results show that variants of the most divergent group III, which are common in South Africa, are also present in Australia and the USA. These variants are not associated with SD, but frequently occur in mixed infections with members of group II in plants affected by this disease in South Africa.
Weed seedbanks in arable fields: effects of management practices and surrounding landscape
Authors: JOSÉ‐MARÍA L , SANS F X
Published: July 2011

José‐María L & Sans FX (2011). Weed seedbanks in arable fields: effects of management practices and surrounding landscape. Weed Research51, 631–640.

Weed seedbanks are a reserve of weed diversity and can contribute to the prediction of future weed problems in arable fields. Managing seedbanks should therefore help in optimising biodiversity and controlling weed infestations. This study assessed the effects of management system (organic vs. conventional) and landscape complexity on seedbank size and species richness at the edges and centres of Mediterranean dryland cereal fields and examines the relationship between specific management practices and seedbanks. Field edges and organic fields had more species‐rich, denser seedbanks than field centres and conventional fields, and landscape complexity had a limited effect on arable seedbanks. Accordingly, the promotion of low‐intensity farming practices regardless of landscape complexity, especially at field edges, would be an effective measure for conservation purposes in Mediterranean agroecosystems. Nevertheless, the high seed density of organic seedbanks reveals the need for more effective seedbank management. The analysis of the effects of specific management practices highlights the importance of cleaning crop seeds properly to reduce seedbank size and using complex rotations, especially as this tends to conserve species richness while reducing seed abundance.
Expression characteristics of ARF1 and SAR1 during development and the de‐etiolation process
Authors: Keskin B. Cevher , Yuca E. , Ertekin Ö. , Yüksel B. , Memon A. R.
Published: July 2011

ARF1 (ADP‐ribosylation factor 1) and SAR1 (secretion‐associated RAS super family) are involved in the formation and budding of vesicles throughout plant endomembrane systems. The molecular mechanisms of this transport have been studied extensively in mammalian and yeast cells. However, very little is known about the mechanisms of coat protein complex (COP) formation and recruitment of COP‐vesicle cargoes in plants. To provide insights into vesicular trafficking in Pisum sativum L., we investigated mRNA and protein expression patterns of ARF1 and SAR1 in roots and shoots at early growth stages and in the de‐etiolation process. We showed that ARF1 was concentrated mostly in the crude Golgi fractions, and SAR1 was concentrated predominantly in the crude ER fractions of de‐etiolated shoots. ARF1 and SAR1 proteins were several times more abundant in shoots relative to roots. In total protein homogenates, the expression level of SAR1 and ARF1 was higher in shoots of dark‐grown pea plants than light‐grown plants. In contrast, ARF1 was higher in roots of light‐grown pea relative to roots of dark‐grown pea. With ageing, the ARF1 mRNA in roots was reduced, while SAR1 expression increased. Unlike ARF1 transcripts, ARF1 protein levels did not fluctuate significantly in root and shoot tissue during early development. The relative abundance of SAR1 protein in root tissues may suggest a high level of vesicular transport from the ER to the Golgi. Experimental results suggested that white light probably affects the regulation of ARF1 and SAR1 protein levels. On the other hand, short‐term white light affects SAR1 but not ARF1.
Evaluation of dietary stevioside supplementation on anti‐human serum albumin immunoglobulin G, Alpha‐1‐glycoprotein, body weight and thyroid hormones in broiler chickens
Authors: Daneshyar M. , Geuns J. M. C. , Willemsen H. , Ansari Z. , Darras V. M. , Buyse J. G. , Everaert N.
Published: July 2011

Sixty male broiler chickens fed a diet supplemented with 130 mg/kg stevioside (S group) or an unsupplemented diet (C group) from day 1 of age onwards. On day 21 of age, ten birds from either the S (SH) or C (CH) group were injected subcutaneously with 100 μg human serum albumin (HSA) and ten others from either S (SP) or C (CP) group injected with 100 μl phosphate‐buffered saline (PBS) in the same way. There were no significant effect of supplementation nor interaction with age on average body weights, T3 and T4 concentrations of non‐injected chickens. After the primary immunization, α1‐glycoprotein concentrations increased in all treatment groups except the CP group, and were significantly higher in the CH group in relation to the other groups. Fourteen and 18 days after the primary immunization, HSA injected chickens of both dietary treatments had significantly higher anti‐HSA immunoglobulin G (IgG) levels than their PBS injected controls. No effect of stevioside supplementation was observed for IgG level. In conclusion, dietary stevioside inclusion can attenuate the pro‐inflammatory response after stimulation of the innate immune response in broiler chickens.
The antidepressant fluoxetine but not citalopram suppresses synapse formation and synaptic transmission between Lymnaea neurons by perturbing presynaptic and postsynaptic machinery
Authors: Getz Angela , Xu Fenglian , Zaidi Wali , Syed Naweed I.
Published: July 2011

Depression is a debilitating mental disorder, and selective serotonin reuptake inhibitors (SSRIs) constitute the first‐line antidepressant treatment choice for the clinical management of this illness; however, the mechanisms underlying their therapeutic actions and side effects remain poorly understood. Here, we compared the effects of two SSRIs, fluoxetine and citalopram, on synaptic connectivity and the efficacy of cholinergic synaptic transmission between identified presynaptic and postsynaptic neurons from the mollusc Lymnaea. The in vitro paired cells were exposed to clinically relevant concentrations of the two SSRIs under chronic and acute experimental conditions, and the incidence of synapse formation and the efficacy of synaptic transmission were tested electrophysiologically and with fluorescent Ca2+ imaging. We demonstrate that chronic exposure to fluoxetine, but not to citalopram, inhibits synapse formation and reduces synaptic strength, and that these effects are reversible following prolonged drug washout. At the structural level, we demonstrate that fluoxetine, but not citalopram, prevents the expression and localization of the presynaptic protein synaptophysin. Acute exposure to fluoxetine substantially reduced synaptic transmission and synaptic plasticity (post‐tetanic potentiation) in established synapses, whereas citalopram reduced synaptic transmission, but not short‐term synaptic plasticity. We further demonstrate that fluoxetine, but not citalopram, directly inhibits voltage‐gated Ca2+ currents in the presynaptic neuron, as well as postsynaptic responsiveness to exogenously applied neurotransmitter. This study provides the first direct evidence that fluoxetine and citalopram exert characteristic, non‐specific side effects that are unrelated to their function as SSRIs, and that fluoxetine is more detrimental to synaptic physiology and structure than citalopram.
Effects of divalent cations on slow unblock of native NMDA receptors in mouse neocortical pyramidal neurons
Authors: Kim Nam‐Kyung , Robinson Hugh P. C.
Published: July 2011

The N‐methyl‐d‐aspartate receptor (NMDAR) exhibits strong voltage‐dependent block by extracellular Mg2+, which is relieved by sustained depolarization and glutamate binding, and which is central to the function of the NMDAR in synaptic plasticity. Rapid membrane depolarization during agonist application reveals a slow unblock of NMDARs, which has important functional implications, for example in the generation of NMDAR spikes, and in determining the narrow time window for spike‐timing‐dependent plasticity. However, its mechanism is still unclear. Here, we study unblock of divalent cations in native NMDARs in nucleated patches isolated from mouse cortical layer 2/3 pyramidal neurons. Comparing unblock kinetics of NMDARs in the presence of extracellular Mg2+or in nominally zero Mg2+, and with Mn2+or Co2+substituting for Mg2+, we found that the properties of slow unblock were determined by the identity of the blocking metal ion at the binding site, presumably by affecting the operation of a structural link to channel gating. The time course of slow unblock was not affected by zinc, or the zinc chelator TPEN [N,N,N′,N′‐tetrakis‐(2‐pyridylmethyl)‐ethylenediamine], while the slower fraction of unblock was reduced by ifenprodil, an NR2B‐selective antagonist. Slow unblock was only weakly temperature dependent, speeding up with rise in temperature with a Q10 of ≈1.5. Finally, using action potential waveform voltage‐clamp, we show that this slow relief from divalent cation block is a prominent feature in physiologically realistic patterns of changing membrane potential.
Excess comorbidities associated with malignant hyperthermia diagnosis in pediatric hospital discharge records
Authors: Li Guohua , Brady Joanne E. , Rosenberg Henry , Sun Lena S.
Published: July 2011

Background:  Case reports have linked malignant hyperthermia (MH) to several genetic diseases.

Objective/aim:  The objective of this study was to quantitatively assess excess comorbidities associated with MH diagnosis in pediatric hospital discharge records.

Patients and methods:  Data for this study came from the Kids’ Inpatient Database (KID) for the years 2000, 2003, and 2006. The KID contains an 80% random sample of patients under the age of 21 discharged from short‐term, non‐Federal hospitals in the United States, with up to 19 diagnoses recorded for each patient. Using all pediatric inpatients as the reference, we calculated the standardized morbidity ratios (SMRs) and 95% confidence intervals (CIs) for children with MH diagnosis according to major disease groups and specific medical conditions.

Results:  Of the 5 916 989 nonbirth‐related hospital discharges studied, 175 had a recorded diagnosis of MH. Compared with the general pediatric inpatient population, children with MH diagnosis were significantly more likely to be diagnosed with diseases of the musculoskeletal system and connective tissue (SMR 5.7; 95% CI: 3.9–7.9), diseases of the circulatory system (SMR 3.3; 95% CI: 2.1–4.8), and congenital anomalies (SMR 3.2; 95% CI: 2.3–4.4). The specific diagnosis that was most strongly associated with MH was muscular dystrophies (SMR 31.3; 95% CI 12.6–64.6).

Conclusions:  Diseases of the musculoskeletal system and connective tissue are significantly associated with MH diagnosis in children. Further research is warranted to determine the clinical utility of these comorbidities in assessing MH susceptibility in children.
THE REAL EXCHANGE RATE AND REAL INTEREST DIFFERENTIALS: THE ROLE OF THE TREND‐CYCLE DECOMPOSITION
Authors: WADA TATSUMA
Published: July 2011

We propose an alternative model and method to reconcile the puzzling feature in the relationship between the real exchange rate and real interest rate differentials. Our simple two‐country model with preset prices, along with firms' misperception about the future exchange rate, implies that the real exchange rate follows an ARIMA(0,1,p) process. This allows us to compute the exact Beveridge‐Nelson decomposition, which is a model‐consistent decomposition. In accordance with our model, unit roots in the real exchange rates are found; and statistical inference is partially found to be affirmative regarding the link between the real exchange rate detrended by the Beveridge‐Nelson decomposition and corresponding real interest differentials. (JEL F31, F41)
Asymptotic comparison at optimal levels of reduced‐bias extreme value index estimators
Authors: Caeiro Frederico , Gomes M. Ivette
Published: July 2011

In this article we are interested in the asymptotic comparison, at optimal levels, of a set of semi‐parametric reduced‐bias extreme value (EV) index estimators, valid for a wide class of heavy‐tailed models, underlying the available data. Again, as in the classical case, there is not any estimator that can always dominate the alternatives, but interesting clear‐cut patterns are found. Consequently, and in practice, a suitable choice of a set of EV index estimators will jointly enable us to better estimate the EV index γ, the primary parameter of extreme events.
SOME NORMATIVE IMPLICATIONS OF KORSGAARD'S THEORY OF THE INTERSUBJECTIVITY OF REASON
Authors: BIRD‐POLLAN STEFAN
Published: July 2011

Abstract: This article argues that Christine Korsgaard's conception of self‐constitution can be historicized by considering the impact of actual humans on our reflective activity. Because Korsgaard bases her argument on a philosophy of action rather than of intention (as Kant does), and our actions must always be concrete, the article argues that the principles for action which we develop in reflection are likewise responses to concrete human demands. It further interprets the types of demands humans make on each other as the expression of historical circumstance rather than as transcendentally anchored. The notion of universal respect that reflection seeks to achieve is thus seen as developing by a self‐correcting process of concrete human interaction. Finally, the article concludes that there can be no metaphysical proof of morality, since morality develops through human interaction that seeks to approximate the idea of respect for persons.
AGENCY AND PRACTICAL IDENTITY: A HEGELIAN RESPONSE TO KORSGAARD
Authors: MOLAND LYDIA
Published: July 2011

Abstract: This article argues that Christine Korsgaard's stimulating claim that practical identity is at the foundation of agency is weakened by her reliance on a Kantian conception of freedom. The commitments that make up our practical identity are, the article suggests, better described through a system like Hegel's that attends to the nature of and connection among different kinds of commitments. Beginning with such an analysis allows us better to describe human agency; it also enables us to reflect the place commitments have in our lives more accurately. Hegel offers a description of ethical life in which commitments are central but still subject to norms that themselves better allow humans to achieve concrete freedom.
PHILOSOPHY AND DEFAULT DESCRIPTIVISM: THE FUNCTIONS DEBATE
Authors: BRUNNANDER BJÖRN
Published: July 2011

Abstract: By focusing on contributions to the literature on function ascription, this article seeks to illustrate two problems with philosophical accounts that are presented as having descriptive aims. There is a motivational problem in that there is frequently no good reason why descriptive aims should be important, and there is a methodological problem in that the methods employed frequently fail to match the task description. This suggests that the task description as such may be the result of “default descriptivism,” a tendency to take considerations that make sense of a practice to be the very considerations that generate it. Although such hypotheses are frequently quite plausible, the fact of the matter may not be very important for the pursuits of philosophers.
ON THE DISTINCTION BETWEEN REDUCTIVE AND NONREDUCTIVE PHYSICALISM
Authors: HAUG MATTHEW C.
Published: July 2011

Abtract: This article argues that the debate between reductive and nonreductive physicalists is best characterized as a disagreement about which properties are natural. Among other things, natural properties are those that characterize the world completely. All physicalists accept the “completeness of physics,” but this claim contains a subtle ambiguity, which results in two conceptions of natural properties. Reductive physicalists should assert, while nonreductive physicalists should deny, that a single set of low‐level physical properties is natural in both of these senses. This way of drawing the distinction succeeds where previous approaches have failed and illuminates why the debate about reductionism is important.
AN ARCHIMEDEAN POINT FOR PHILOSOPHY
Authors: RANGANATHAN SHYAM
Published: July 2011

Abstract: According to an orthodox account of meaning and translation, meaning is a property of expressions of a language, and translation is a matching of synonymous expressions across languages. This linguistic account of translation gives rise to well‐known skeptical conclusions about translation, objectivity, meaning, and truth, but it does not conform to our best translational practices. In contrast, I argue for a textual account of meaning based on the concept of a text‐type that does conform to our best translational practices. With their semantic function in view, text‐types are Archimedean points for their respective disciplines. The text‐type of philosophy is no exception. Culture‐transcendent conceptual analysis can proceed on firm footing without having to deny the reality of radical cultural and linguistic difference by treating components of text‐types as the concepts to be analyzed. Analyses of central philosophical concepts are provided as a means of adjudicating philosophical controversy.
Raz on the Right to Autonomy
Authors: Hassoun Nicole
Published: July 2011

Abstract: In The Morality of Freedom, Joseph Raz argues against a right to autonomy. This argument helps to distinguish his theory from his competitors'. For, many liberal theories ground such a right. Some even defend entirely autonomy‐based accounts of rights. This paper suggests that Raz's argument against a right to autonomy raises an important dilemma for his larger theory. Unless his account of rights is limited in some way, Raz's argument applies against almost all (purported) rights, not just a right to autonomy. But, on the traditional way of limiting accounts like his, Raz's account actually supports the conclusion that people have a right to autonomy. So, unless there is another way of limiting his account that does not have this consequence, Raz's argument against a right to autonomy does not go through.
Impaired antibody memory to varicella zoster virus in HIV‐infected children: low antibody levels and avidity*
Authors: L'Huillier AG , Ferry T , Courvoisier DS , Aebi C , Cheseaux J‐J , Kind C , Rudin C , Nadal D , Hirschel B , Sottas C , Siegrist C‐A , Posfay‐Barbe KM ,   the Pediatric Infectious Diseases,   Group of Switzerland (PIGS),   the Swiss HIV Cohort Study (SHCS) and the Swiss Mother & Child HIV Cohort Study (MoCHiV)
Published: July 2011

Objective

HIV‐infected children have impaired antibody responses after exposure to certain antigens. Our aim was to determine whether HIV‐infected children had lower varicella zoster virus (VZV) antibody levels compared with HIV‐infected adults or healthy children and, if so, whether this was attributable to an impaired primary response, accelerated antibody loss, or failure to reactivate the memory VZV response.

Methods

In a prospective, cross‐sectional and retrospective longitudinal study, we compared antibody responses, measured by enzyme‐linked immunosorbent assay (ELISA), elicited by VZV infection in 97 HIV‐infected children and 78 HIV‐infected adults treated with antiretroviral therapy, followed over 10 years, and 97 age‐matched healthy children. We also tested antibody avidity in HIV‐infected and healthy children.

Results

Median anti‐VZV immunoglobulin G (IgG) levels were lower in HIV‐infected children than in adults (264 vs. 1535 IU/L; P<0.001) and levels became more frequently unprotective over time in the children [odds ratio (OR) 17.74; 95% confidence interval (CI) 4.36–72.25; P<0.001]. High HIV viral load was predictive of VZV antibody waning in HIV‐infected children. Anti‐VZV antibodies did not decline more rapidly in HIV‐infected children than in adults. Antibody levels increased with age in healthy (P=0.004) but not in HIV‐infected children. Thus, antibody levels were lower in HIV‐infected than in healthy children (median 1151 IU/L; P<0.001). Antibody avidity was lower in HIV‐infected than healthy children (P<0.001). A direct correlation between anti‐VZV IgG level and avidity was present in HIV‐infected children (P=0.001), but not in healthy children.

Conclusion

Failure to maintain anti‐VZV IgG levels in HIV‐infected children results from failure to reactivate memory responses. Further studies are required to investigate long‐term protection and the potential benefits of immunization.
The Death of Socio‐Economic Rights
Authors: O'Connell Paul
Published: July 2011

Over the last decade, apex courts in Canada, India, and South Africa – which have traditionally been viewed as socio‐economic rights friendly – have issued judgments fundamentally at variance with the meaningful protection of socio‐economic rights. This jurisprudential turn can be understood as part of a de facto harmonisation of constitutional rights protection in the era of neo‐liberal globalisation. These national courts, although dealing with idiosyncratic domestic constitutional systems, have nonetheless begun to articulate analogous conceptions of fundamental rights which are atomistic, ‘market friendly’ and, more broadly, congruent with the narrow neo‐liberal conception of rights, and consequently antithetical to the protection of socio‐economic rights. This view of rights is becoming, well established as the hegemonic view and the pre‐eminence of this view, taken with the entrenchment of neo‐liberal policy prescriptions – and tacit judicial approval of such policies – signals the end, in substantive terms, for the prospect of meaningful protection of socio‐economic rights.
Does the Emperor Have Financial Crisis Clothes? Reflections on the Legal Basis of the European Banking Authority
Authors: Fahey Elaine
Published: July 2011

The European Union institutional package launched in response to the financial crisis used Article 114 TFEU as its legal basis. The author explores the legal basis for one of the European Supervisory Authorities recently established – the European Banking Authority (EBA). The use of Article 114 TFEU, the main Treaty basis used to harmonise laws in order to further the internal market, as the foundation for the EBA, is considered in detail. A paradox of contemporary EU institutional law is assessed here, considering whether on the one hand, the EBA is functionally both too narrow and too broad as a matter of law, while on the other hand, it may prove to be central to restoring confidence in EU regulatory powers, rendering it ‘too big to fail,’ despite its slender foundations in Article 114 TFEU.
Job creation and labour market flexibility: miracle or mirage on the Polish labour market?
Authors: Ingham Hilary , Ingham Mike
Published: July 2011

Poland's post‐communist economic performance has been generally good. However, for many years, its growth was jobless; it exhibited very high unemployment rates and made little progress towards the targets set for EU Member States and accession countries. Unexpectedly, in 2003, the country's labour market began to exhibit a new dynamism, with employment growing strongly and unemployment tumbling. This apparent improvement coincided with a liberalisation of its Labour Code. Unfortunately, the measures introduced to increase flexibility are at variance with the EU's Fixed‐term Work Directive and will likely need to be modified, which may conceivably reverse the recent developments that form the focus of this article.
Population dynamics of three songbird species in a nestbox population in Central Europe show effects of density, climate and competitive interactions
Authors: SMALLEGANGE ISABEL M. , VAN DER MEER JAAP , FIEDLER WOLFGANG
Published: July 2011

Unravelling the contributions of density‐dependent and density‐independent factors in determining species population dynamics is a challenge, especially if the two factors interact. One approach is to apply stochastic population models to long‐term data, yet few studies have included interactions between density‐dependent and density‐independent factors, or explored more than one type of stochastic population model. However, both are important because model choice critically affects inference on population dynamics and stability. Here, we used a multiple models approach and applied log‐linear and non‐linear stochastic population models to time series (spanning 29 years) on the population growth rates of Blue Tits Cyanistes caeruleus, Great Tits Parus major and Pied Flycatchers Ficedula hypoleuca breeding in two nestbox populations in southern Germany. We focused on the roles of climate conditions and intra‐ and interspecific competition in determining population growth rates. Density dependence was evident in all populations. For Blue Tits in one population and for Great Tits in both populations, addition of a density‐independent factor improved model fit. At one location, Blue Tit population growth rate increased following warmer winters, whereas Great Tit population growth rates decreased following warmer springs. Importantly, Great Tit population growth rate also decreased following years of high Blue Tit abundance, but not vice versa. This finding is consistent with asymmetric interspecific competition and implies that competition could carry over to influence population dynamics. At the other location, Great Tit population growth rate decreased following years of high Pied Flycatcher abundance but only when Great Tit population numbers were low, illustrating that the roles of density‐dependent and density‐independent factors are not necessarily mutually exclusive. The dynamics of this Great Tit population, in contrast to the other populations, were unstable and chaotic, raising the question of whether interactions between density‐dependent and density‐independent factors play a role in determining the (in) stability of the dynamics of species populations.