bluuebunny/crossref_metadata_2025 huggingface dataset:
Model tests of gliding with different hindwing configurations in the four-winged dromaeosaurid
Microraptor gui
Authors: Alexander David E. , Gong Enpu , Martin Larry D. , Burnham David A. , Falk Amanda R.
Published: January 2010

Fossils of the remarkable dromaeosaurid
Microraptor gui
and relatives clearly show well-developed flight feathers on the hind limbs as well as the front limbs. No modern vertebrate has hind limbs functioning as independent, fully developed wings; so, lacking a living example, little agreement exists on the functional morphology or likely flight configuration of the hindwing. Using a detailed reconstruction based on the actual skeleton of one individual, cast in the round, we developed light-weight, three-dimensional physical models and performed glide tests with anatomically reasonable hindwing configurations. Models were tested with hindwings abducted and extended laterally, as well as with a previously described biplane configuration. Although the hip joint requires the hindwing to have at least 20° of negative dihedral (anhedral), all configurations were quite stable gliders. Glide angles ranged from 3° to 21° with a mean estimated equilibrium angle of 13.7°, giving a lift to drag ratio of 4.1:1 and a lift coefficient of 0.64. The abducted hindwing model’s equilibrium glide speed corresponds to a glide speed in the living animal of 10.6 m·s
−1
. Although the biplane model glided almost as well as the other models, it was structurally deficient and required an unlikely weight distribution (very heavy head) for stable gliding. Our model with laterally abducted hindwings represents a biologically and aerodynamically reasonable configuration for this four-winged gliding animal.
M. gui
’s feathered hindwings, although effective for gliding, would have seriously hampered terrestrial locomotion.
A selective TrkB agonist with potent neurotrophic activities by 7,8-dihydroxyflavone
Authors: Jang Sung-Wuk , Liu Xia , Yepes Manuel , Shepherd Kennie R. , Miller Gary W. , Liu Yang , Wilson W. David , Xiao Ge , Blanchi Bruno , Sun Yi E. , Ye Keqiang
Published: January 2010

Brain-derived neurotrophic factor (BDNF), a cognate ligand for the tyrosine kinase receptor B (TrkB) receptor, mediates neuronal survival, differentiation, synaptic plasticity, and neurogenesis. However, BDNF has a poor pharmacokinetic profile that limits its therapeutic potential. Here we report the identification of 7,8-dihydroxyflavone as a bioactive high-affinity TrkB agonist that provokes receptor dimerization and autophosphorylation and activation of downstream signaling. 7,8-Dihydroxyflavone protected wild-type, but not TrkB-deficient, neurons from apoptosis. Administration of 7,8-dihydroxyflavone to mice activated TrkB in the brain, inhibited kainic acid-induced toxicity, decreased infarct volumes in stroke in a TrkB-dependent manner, and was neuroprotective in an animal model of Parkinson disease. Thus, 7,8-dihydroxyflavone imitates BDNF and acts as a robust TrkB agonist, providing a powerful therapeutic tool for the treatment of various neurological diseases.
Unexpected role of clathrin adaptor AP-1 in MHC-dependent positive selection of T cells
Authors: Arias Diana A. Alvarez , McCarty Nami , Lu Linrong , Maldonado Roberto A. , Shinohara Mari L. , Cantor Harvey
Published: January 2010

Trafficking of transmembrane receptors to a specific intracellular compartment is conducted by adaptor molecules that bind to target motifs within the cytoplasmic domains of cargo proteins. We generated mice containing a lymphoid-specific deficiency of AP-1 using RNAi knockdown technology. Inhibition of AP-1 expression in thymocytes blocks progression from double-positive immature thymocytes, resulting in complete absence of CD4+single-positive thymocytes and severe reduction of CD3+CD8+single-positive thymocytes. Analysis of the contribution of AP-1 deficiency on the interaction between mature CD4+T cells and antigen-presenting cells revealed that AP-1 is essential to efficient immune synapse formation and associated T cell activation, suggesting a possible mechanism of AP-1 function in thymocyte development.
Genome-minimized
Streptomyces
host for the heterologous expression of secondary metabolism
Authors: Komatsu Mamoru , Uchiyama Takuma , Ōmura Satoshi , Cane David E. , Ikeda Haruo
Published: January 2010

To construct a versatile model host for heterologous expression of genes encoding secondary metabolite biosynthesis, the genome of the industrial microorganism
Streptomyces avermitilis
was systematically deleted to remove nonessential genes. A region of more than 1.4 Mb was deleted stepwise from the 9.02-Mb
S. avermitilis
linear chromosome to generate a series of defined deletion mutants, corresponding to 83.12–81.46% of the wild-type chromosome, that did not produce any of the major endogenous secondary metabolites found in the parent strain. The suitability of the mutants as hosts for efficient production of foreign metabolites was shown by heterologous expression of three different exogenous biosynthetic gene clusters encoding the biosynthesis of streptomycin (from
S. griseus
Institute for Fermentation, Osaka [IFO] 13350), cephamycin C (from
S. clavuligerus
American type culture collection (ATCC) 27064), and pladienolide (from
S. platensis
Mer-11107). Both streptomycin and cephamycin C were efficiently produced by individual transformants at levels higher than those of the native-producing species. Although pladienolide was not produced by a deletion mutant transformed with the corresponding intact biosynthetic gene cluster, production of the macrolide was enabled by introduction of an extra copy of the regulatory gene
pldR
expressed under control of an alternative promoter. Another mutant optimized for terpenoid production efficiently produced the plant terpenoid intermediate, amorpha-4,11-diene, by introduction of a synthetic gene optimized for
Streptomyces
codon usage. These findings highlight the strength and flexibility of engineered
S. avermitilis
as a model host for heterologous gene expression, resulting in the production of exogenous natural and unnatural metabolites.
Bimodular auxin response controls organogenesis in
Arabidopsis
Authors: De Smet Ive , Lau Steffen , Voß Ute , Vanneste Steffen , Benjamins René , Rademacher Eike H. , Schlereth Alexandra , De Rybel Bert , Vassileva Valya , Grunewald Wim , Naudts Mirande , Levesque Mitchell P. , Ehrismann Jasmin S. , Inzé Dirk , Luschnig Christian , Benfey Philip N. , Weijers Dolf , Van Montagu Marc C. E. , Bennett Malcolm J. , Jürgens Gerd , Beeckman Tom
Published: January 2010

Like animals, the mature plant body develops via successive sets of instructions that determine cell fate, patterning, and organogenesis. In the coordination of various developmental programs, several plant hormones play decisive roles, among which auxin is the best-documented hormonal signal. Despite the broad range of processes influenced by auxin, how such a single signaling molecule can be translated into a multitude of distinct responses remains unclear. In
Arabidopsis thaliana
, lateral root development is a classic example of a developmental process that is controlled by auxin at multiple stages. Therefore, we used lateral root formation as a model system to gain insight into the multifunctionality of auxin. We were able to demonstrate the complementary and sequential action of two discrete auxin response modules, the previously described SOLITARY ROOT/INDOLE-3-ACETIC ACID (IAA)14-AUXIN REPONSE FACTOR (ARF)7-ARF19–dependent lateral root initiation module and the successive BODENLOS/IAA12-MONOPTEROS/ARF5–dependent module, both of which are required for proper organogenesis. The genetic framework in which two successive auxin response modules control early steps of a developmental process adds an extra dimension to the complexity of auxin’s action.
Differential release of chromatin-bound IL-1α discriminates between necrotic and apoptotic cell death by the ability to induce sterile inflammation
Authors: Cohen Idan , Rider Peleg , Carmi Yaron , Braiman Alex , Dotan Shahar , White Malka R. , Voronov Elena , Martin Michael U. , Dinarello Charles A. , Apte Ron N.
Published: January 2010

IL-1α, like IL-1β, possesses multiple inflammatory and immune properties. However, unlike IL-1β, the cytokine is present intracellularly in healthy tissues and is not actively secreted. Rather, IL-1α translocates to the nucleus and participates in transcription. Here we show that intracellular IL-1α is a chromatin-associated cytokine and highly dynamic in the nucleus of living cells. During apoptosis, IL-1α concentrates in dense nuclear foci, which markedly reduces its mobile nature. In apoptotic cells, IL-1α is retained within the chromatin fraction and is not released along with the cytoplasmic contents. To simulate the in vivo inflammatory response to cells undergoing different mechanisms of death, lysates of cells were embedded in Matrigel plugs and implanted into mice. Lysates from cells undergoing necrosis recruited cells of the myeloid lineage into the Matrigel, whereas lysates of necrotic cells lacking IL-1α failed to recruit an infiltrate. In contrast, lysates of cells undergoing apoptotic death were inactive. Cells infiltrating the Matrigel were due to low concentrations (20–50 pg) of the IL-1α precursor containing the receptor interacting C-terminal, whereas the N-terminal propiece containing the nuclear localization site failed to do so. When normal keratinocytes were subjected to hypoxia, the constitutive IL-1α precursor was released into the supernatant. Thus, after an ischemic event, the IL-1α precursor is released by hypoxic cells and incites an inflammatory response by recruiting myeloid cells into the area. Tissues surrounding the necrotic site also sustain damage from the myeloid cells. Nuclear trafficking and differential release during necrosis vs. apoptosis demonstrate that inflammation by IL-1α is tightly controlled.
Proteins of nucleotide and base excision repair pathways interact in mitochondria to protect from loss of subcutaneous fat, a hallmark of aging
Authors: Kamenisch York , Fousteri Maria , Knoch Jennifer , von Thaler Anna-Katharina , Fehrenbacher Birgit , Kato Hiroki , Becker Thomas , Dollé Martijn E.T. , Kuiper Raoul , Majora Marc , Schaller Martin , van der Horst Gijsbertus T.J. , van Steeg Harry , Röcken Martin , Rapaport Doron , Krutmann Jean , Mullenders Leon H. , Berneburg Mark
Published: January 2010

Defects in the DNA repair mechanism nucleotide excision repair (NER) may lead to tumors in xeroderma pigmentosum (XP) or to premature aging with loss of subcutaneous fat in Cockayne syndrome (CS). Mutations of mitochondrial (mt)DNA play a role in aging, but a link between the NER-associated CS proteins and base excision repair (BER)-associated proteins in mitochondrial aging remains enigmatic. We show functional increase of CSA and CSB inside mt and complex formation with mtDNA, mt human 8-oxoguanine glycosylase (mtOGG)-1, and mt single-stranded DNA binding protein (mtSSBP)-1 upon oxidative stress. MtDNA mutations are highly increased in cells from CS patients and in subcutaneous fat of aged Csbm/m and Csa−/− mice. Thus, the NER-proteins CSA and CSB localize to mt and directly interact with BER-associated human mitochondrial 8-oxoguanine glycosylase-1 to protect from aging- and stress-induced mtDNA mutations and apoptosis-mediated loss of subcutaneous fat, a hallmark of aging found in animal models, human progeroid syndromes like CS and in normal human aging.
A Quality Improvement Initiative to Reduce Central Line–Associated Bloodstream Infections in a Neonatal Intensive Care Unit
Authors: Bizzarro Matthew J. , Sabo Barbara , Noonan Melanie , Bonfiglio Mary-Pat , Northrup Veronika , Diefenbach Karen ,   Central Venous Catheter Initiative Committee
Published: January 2010

Objective.

To reduce the rate of late-onset sepsis in a neonatal intensive care unit (NICU) by decreasing the rate of central line–associated bloodstream infection (CLABSI).

Methods.

We conducted a quasi-experimental study of an educational intervention designed to improve the quality of clinical practice in an NICU. Participants included all NICU patients with a central venous catheter (CVC). Data were collected during the period from July 1, 2005, to June 30, 2007, to document existing CLABSI rates and CVC-related practices. A multidisciplinary quality improvement committee was established to review these and published data and to create guidelines for CVC placement and management. Educational efforts were conducted to implement these practices. Postintervention CLABSI rates were collected during the period from January 1, 2008, through March 31, 2009, and compared with preintervention data and with benchmark data from the National Healthcare Safety Network (NHSN).

Results.

The rate of CLABSI in the NICU decreased from 8.40 to 1.28 cases per 1,000 central line–days (adjusted rate ratio, 0.19 [95% confidence interval, 0.08–0.45]). This rate was lower than the NHSN benchmark rate for level III NICUs. The overall rate of late-onset sepsis was reduced from 5.84 to 1.42 cases per 1,000 patient-days (rate difference, −4.42 cases per 1,000 patient-days [95% confidence interval, −5.55 to −3.30 cases per 1,000 patient-days]).

Conclusions.

It is possible to reduce the rate of CLABSI, and therefore the rate of late-onset sepsis, by establishing and adhering to evidence-based guidelines. Sustainability depends on continued data surveillance, knowledge of medical and nursing literature, and timely feedback to the staff. The techniques established are applicable to other populations and areas of inpatient care.
Factors Associated with Time to Acquisition of Bloodstream Infection in a Pediatric Intensive Care Unit
Authors: de Mello Maria Júlia Gonçalves , de Albuquerque Maria de Fátima Pessoa Militão , Ximenes Ricardo Arraes de Alencar , Lacerda Heloísa Ramos , Ferraz Eduardo Jaime Seara , Byington Rita , Barbosa Maria Tereza Serrano
Published: January 2010

Objective.

To evaluate the risk factors that influence time to acquisition of a laboratory-confirmed bloodstream infection (LCBI).

Design.

Prospective cohort study with an 18-month follow-up.

Setting.

A 16-bed medical and/or surgical pediatric intensive care unit that cares for patients of the Brazilian Public Health System exclusively.

Patients.

We included children from 0 to 18 years old who were represented by 875 consecutive admissions to the pediatric intensive care unit from January 1, 2005, through June 30, 2006. The children from all but 5 (0.6%) of the admissions were followed up until discharge or death. The majority (506 [58.2%]) were hospitalized for surgical pathology, and 254 (29.2%) underwent heart surgery.

Methods.

We used a standardized questionnaire and data collection from daily charts. Information on risk factors was collected before the onset of first LCBI. Survival analysis was performed using the Kaplan-Meier method. The effect of the variables on the risk of LCBI each day was estimated through a Cox model fitting.

Results.

Fifty-seven children (6.6%) developed an LCBI, 54 (94.7%) of whom made use of a central venous catheter. LCBI incidence was 11.27 episodes/1,000 patient-days and 17.92 episodes/1,000 patient-days when associated with a central venous catheter. Factors associated with time to the first LCBI in the Cox model were age less than 2 years (hazard ratio [HR], 1.99; 95% confidence interval [CI], 1.02–3.89), malnutrition (HR, 1.74; 95% CI, 1.01–3.00), use of a central venous catheter (HR, 4.36; 95% CI, 1.30–14.64), use of antibiotics before admission (HR, 0.58; 95% CI, 0.33–0.98), and use of transfused blood products (HR, 0.40; 95% CI, 0.22–0.74).

Conclusion.

Factors associated with time to acquisition of LCBI were age less than 2 years, weight-for-age z score less than −2, and the use of a central venous catheter. Therefore, intensification of LCBI prevention efforts in patients with these characteristics is fundamental.
The strengths, weaknesses, opportunities and threats of using social software in higher and further education teaching and learning
Authors: Schroeder A. , Minocha S. , Schneider C.
Published: January 2010

Social software is increasingly being used in higher and further education to support teaching and learning processes. These applications provide students with social and cognitive stimulation and also add to the interaction between students and educators. However, in addition to the benefits the introduction of social software into a course environment can also have adverse implications on students, educators and the education institution as a whole, a phenomenon which has received much less attention in the literature. In this study we explore the various implications of introducing social software into a course environment in order to identify the associated benefits, but also the potential drawbacks. We draw on data from 20 social software initiatives in UK‐based higher and further education institutions to identify the diverse experiences and concerns of students and educators. The findings are presented in form of a SWOT analysis, which allows us to better understand the otherwise ambiguous implications of social software in terms of its strengths, weaknesses, opportunities and threats. From the analysis we have derived concrete recommendations for the use of social software as a teaching and learning tool.
Role of staphylococcal wall teichoic acid in targeting the major autolysin Atl
Authors: Schlag Martin , Biswas Raja , Krismer Bernhard , Kohler Thomas , Zoll Sebastian , Yu Wenqi , Schwarz Heinz , Peschel Andreas , Götz Friedrich
Published: January 2010

Staphylococcal cell separation depends largely on the bifunctional autolysin Atl that is processed to amidase‐R1,2 and R3‐glucosaminidase. These murein hydrolases are targeted via repeat domains (R) to the septal region of the cell surface, thereby allowing localized peptidoglycan hydrolysis and separation of the dividing cells. Here we show that targeting of the amidase repeats is based on an exclusion strategy mediated by wall teichoic acid (WTA). In Staphylococcus aureus wild‐type, externally applied repeats (R1,2) or endogenously expressed amidase were localized exclusively at the cross‐wall region, while in ΔtagO mutant that lacks WTA binding was evenly distributed on the cell surface, which explains the increased fragility and autolysis susceptibility of the mutant. WTA prevented binding of Atl to the old cell wall but not to the cross‐wall region suggesting a lower WTA content. In binding studies with ConcanavalinA‐fluorescein (ConA‐FITC) conjugate that binds preferentially to teichoic acids, ConA‐FITC was bound throughout the cell surface with the exception of the cross wall. ConA binding suggest that either content or polymerization of WTA gradually increases with distance from the cross‐wall. By preventing binding of Atl, WTA directs Atl to the cross‐wall to perform the last step of cell division, namely separation of the daughter cells.
Identification of neonatal deaths in a large managed care organisation
Authors: Escobar Gabriel J. , Gardner Maria N. , Chellino Marie , Fireman Bruce , Verdi Joan , Yanover Mark
Published: January 2010

Summary. The neonatal (< 28 days) mortality rate (NMR) is one of the most commonly employed maternal and child health epidemiological measures. It is also being employed in quality measures (‘report cards’) used to assess the performance of health care organisations. The objectives were to (1) develop methods for the rapid quantification of the neonatal mortality rate in a multi‐hospital system, the Kaiser Permanente Medical Care Program's Northern California Region (KPMCP NCR), (2) develop methods for generating facility‐specific rates and case lists, and (3) ascertain the capture rates of the information sources available to us. Potential neonatal deaths were identified in the KPMCP NCR for the 1990 and 1991 calendar years from 3 sources: (1) clerical searches of local facility records, (2) electronic searches of the KPMCP NCR hospitalisation database, and (3) linking KPMCP electronic birth records to death certificate tapes. The medical records of all infants identified through these methods were reviewed. The neonatal mortality rate was calculated in three ways: (1) including all livebirths, (2) excluding births weighing <500g, and (3) adjusting for prematurity by increasing the follow‐up period in preterm babies (these babies were included as neonatal deaths if they died up to 40 weeks corrected age + 27.9 days). A total of 352 records out of 64469 birth records in the KPMCP NCR were reviewed. If one includes babies <500g, the neonatal mortality rate was 3.72/1000 live‐births; if these babies are excluded, the rate was 3.05/1000. Adjusting for prematurity increased these rates to 3.91/1000 and 3.24/1000, respectively. Accurate quantification of the neonatal mortality rate in a multi‐hospital system requires the use of multiple information sources. Use of a single source can lead to varying rates of over‐ or under‐estimation. It is possible to employ our methodology for both research and operational purposes.
Behaviour problems of patients with Moebius sequence and parental stress
Authors: Briegel Wolfgang , Hofmann Christina , Schwab K Otfried
Published: January 2010

Aim:  Moebius sequence is a rare condition usually defined as congenital facial paralysis with congenital impairment of ocular abduction. At present, there is little information on behavioural problems, parental stress and possible relationships between these factors. To fill this gap, this study investigated these aspects relevant for counselling.

Methods:  Parents of 4–17 year old subjects known to the German Möbius syndrome foundation were anonymously asked to fill out several questionnaires, for example, the Child Behavior Checklist (CBCL)4–18.

Results:  The primary care givers of 41/58 subjects (70.7%) sent back filled‐out questionnaires. Ten subjects did not meet the inclusion criteria; 15 males and 16 females (4; 7–17; 0 years, median age: 10; 7 years) were included. Ten out of 31 subjects were rated as clinical on at least one CBCL scale; three had a total problem score in the clinical range. Social problems were the most important problems with rates of 12–17‐year old subjects being about five times as high as those of younger subjects.

Compared with the general population, but not with other parents of mentally and/or physically handicapped children, the primary care givers experienced higher levels of stress, which were correlated to anxious/depressed behaviour, aggressive behaviour, externalising problems and total problem score of the children. The older a child the higher the primary care giver's life satisfaction was.

Conclusions:  Social problems seem to be frequent among 4–17‐year old subjects with Moebius sequence, and primary care givers show increased strain. Therefore, families with an affected child need early and adequate support.
Proposed epidemiological case definition for serious skin infection in children
Authors: O'Sullivan Cathryn E , Baker Michael G
Published: January 2010

Aim:  Researching the rising incidence of serious skin infections in children is limited by the lack of a consistent and valid case definition. We aimed to develop and evaluate a good quality case definition, for use in future research and surveillance of these infections.

Methods:  We tested the validity of the existing case definition, and then of 11 proposed alternative definitions, by assessing their screening performance when applied to a population of paediatric skin infection cases identified by a chart review of 4 years of admissions to a New Zealand hospital.

Results:  Previous studies have largely used definitions based on the International Classification of Diseases skin infection subchapter. This definition is highly specific (100%) but poorly sensitive (61%); it fails to capture skin infections of atypical anatomical sites, those secondary to primary skin disease and trauma, and those recorded as additional diagnoses. Including these groups produced a new case definition with 98.9% sensitivity and 98.8% specificity.

Conclusion:  Previous analyses of serious skin infection in children have underestimated the true burden of disease. Using this proposed broader case definition should allow future researchers to produce more valid and comparable estimates of the true burden of these important and increasing infections.
Spinocerebellar ataxia type 6: Systematic patho‐anatomical study reveals different phylogenetically defined regions of the cerebellum and neural pathways undergo different evolutions of the degenerative process
Authors: Wang Xuejing , Wang Hui , Xia Yujun , Jiang Hong , Shen Lu , Wang Shoubiao , Shen Ruowu , Xu Qian , Luo Xuegang , Tang Beisha
Published: January 2010

Spinocerebellar ataxia type 6 is a late onset autosomal dominantly inherited ataxic disorder, and previous patho‐anatomical studies have only reported neurodegeneration in SCA6 as being confined to the cerebellar cortex, dentate nucleus and inferior olive. However, the characteristics of cerebellar symptoms and many poorly understood “extracerebellar” symptoms reveal the three cerebellar regions and the corresponding precerebellar nuclei may undergo differing evolution of the degenerative process, and a more widespread brainstem degeneration in SCA6. We carried out a detailed immunohistochemical study in two SCA6 patients who had rather early onset and short disease duration with 25 CAG repeats, which is atypical for SCA‐6. We investigated the severity of neurodegeneration in each of the cerebellar regions and the corresponding precerebellar nuclei, and further characterize the extent of brain degeneration. This study confirmed that vestibulocerebellar, spinocerebellum and pontocerebellar are consistent targets of the pathological process of SCA6, but the severity of neurodegeneration in each of them was different. Vestibulocerebellum and the inferior cerebellar peduncle undergo the most severe neurodegeneration, while neurodegeneration in the pontocerebellar is less severe. Furthermore, we observed obvious neurodegeneration in layers II and III of the primary motor cortex, vestibular nuclei, inferior olivary nucleus, nucleus proprius and posterior spinocerebellar tract. Our detailed postmortem findings confirmed that SCA6 was not a simple “pure” cerebellar disease, but a complex neurodegenerative disease in which the three cerebellar regions underwent different evolutions of neurodegeneration process, and the corresponding precerebellar nuclei and the neural pathway were all involved.
New acoustic method for detecting upper airway obstruction in patients with sleep apnoea
Authors: STOCKX Elaine M. , CAMILLERI Peter , SKUZA Elizabeth M. , CHURCHWARD Thomas , HOWES Julie M. , HO Michael , MCDONALD Timothy , FREEZER Nicholas , HAMILTON Garun , WILKINSON Malcolm H. , BERGER Philip J.
Published: January 2010

Background and objective:  OSA is a common disorder resulting in health and economic burdens. Currently identifying OSA in patients involves expensive techniques that require overnight studies in a laboratory setting with qualified staff. This paper tests a new acoustic device (AirwayClear (AC)) for assessing upper airway patency in human subjects with OSA. We hypothesize that obstructive apnoeas would be detected equally well with AC and polysomnography (PSG).

Methods:  Twenty‐three patients with severe OSA underwent an overnight CPAP titration study. We introduced pseudorandom noise (600–1200 Hz) using AC to the patient's nasal mask during 1 h of subtherapeutic CPAP. AC determined a measure of airway patency based on the level of pseudorandom noise reaching a sternal notch sensor. The ability of AC to detect obstructive respiratory events was compared with standard PSG.

Results:  Three hundred and twenty‐two obstructive events (obstructive and mixed apnoeas) were identified by PSG. AC scored 80% as complete obstructions and 16% as partial obstructions. Conversely, AC detected 281 complete obstructions. PSG recognized 84% as apnoeas and scored 11% as hypopnoeas. Of the 204 hypopnoeas identified with PSG, AC indicated the airway was partially or completely obstructed in 69% of patients. A Bland–Altman analysis for the apnoeas from the two measures showed a mean difference of 2.3 events/h and 95% confidence intervals of ±15.5 events/h.

Conclusions:  We conclude that AC is able to track airway patency and to identify airway closure in patients with OSA.
Genetic susceptibility in tuberculosis
Authors: YIM Jae‐Joon , SELVARAJ Paramasivam
Published: January 2010

The importance of host genetic factors in determining susceptibility to tuberculosis (TB) has been studied extensively using various methods, such as case‐control, candidate gene and genome‐wide linkage studies. Several important candidate genes like human leucocyte antigen/alleles and non‐human leucocyte antigen genes, such as cytokines and their receptors, chemokines and their receptors, pattern recognition receptors (including toll‐like receptors, mannose binding lectin and the dendritic cell‐specific intercellular adhesion molecule‐3 grabbing nonintegrin), solute carrier family 11A member 1 (formerly known as natural resistance‐associated macrophage protein 1) and purinergic P2X7 receptor gene polymorphisms, have been associated with differential susceptibility to TB in various ethnic populations. This heterogeneity has been explained by host–pathogen and gene–environment interactions and evolutionary selection pressures. Although the achievements of genetics studies might not yet have advanced the prevention and treatment of TB, researchers have begun to widen their scope of investigation to encompass these practical considerations.
Advances in the diagnosis of tuberculosis
Authors: LANGE Christoph , MORI Toru
Published: January 2010

Tuberculosis ranges among the leading causes of morbidity and mortality worldwide. A diagnostic approach to a patient with possible tuberculosis includes a detailed medical history and clinical examination as well as radiological, microbiological, immunological, molecular‐biological and histological investigations, where available. Recently, important advances have been achieved in these fields that have led to substantial improvements in the accuracy and the timing of the diagnosis of tuberculosis. Novel methods allow for a better identification of latently infected individuals who are at risk of developing active tuberculosis, they also offer the possibility for a rapid diagnosis of active tuberculosis in patients with negative sputum smears for acid‐fast bacilli and enable prompt identification of drug‐resistant strains of Mycobacterium tuberculosis directly from respiratory specimen with a high accuracy. In addition, promising methods that will further optimize the diagnosis of tuberculosis are under development. In the future, therapeutic interventions based on the results of novel diagnostic procedures can be made earlier leading to improvements in patient care.
High concentrations of vascular endothelial growth factor reduce stretch‐induced apoptosis of alveolar type II cells
Authors: KUHN Hartmut , KRÜGER Saskia , HAMMERSCHMIDT Stefan , WIRTZ Hubert
Published: January 2010

Background and objective:  Vascular endothelial growth factor (VEGF) is strongly expressed in the alveolar epithelium. VEGF has been shown to exhibit protective as well as injurious effects in ARDS/acute lung injury. We therefore investigated the influence of VEGF in a model of stretch‐induced apoptosis.

Methods:  Isolated rat alveolar type II (ATII) cells were subjected to high‐amplitude cyclic mechanical stretch (40 per minute, 30% change in surface area) for 24 h. VEGF gene expression was investigated by real‐time reverse transcription‐PCR. Concentrations of VEGF in culture supernatants of stretched cells were determined by ELISA. Apoptosis of cells following stretching was assessed by flow cytometry.

Results:  Vascular endothelial growth factor gene expression increased during the first 4 h of stretching and then declined to a similar level to that of static control cells. VEGF concentrations in cell supernatants increased in response to mechanical stretch, as compared with those in supernatants of static control cells. Incubation of ATII cells with higher concentrations of VEGF (50 ng/mL) during stretching inhibited apoptosis, presumably by restoring stretch‐impaired phosphatidylinositol‐3 kinase signalling. However, blocking free VEGF in the supernatant with an anti‐VEGF antibody did not influence stretch‐induced apoptosis.

Conclusions:  These findings suggest that high‐amplitude mechanical stretch induced secretion of VEGF, which in high concentrations, may prevent stretch‐induced apoptosis. In this model, however, the protective influence of VEGF was not essential for survival of ATII cells subjected to high‐amplitude mechanical stretch.
1p36 deletion syndrome associated with Prader–Willi‐like phenotype
Authors: Tsuyusaki Yu , Yoshihashi Hiroshi , Furuya Noritaka , Adachi Masanori , Osaka Hitoshi , Yamamoto Kayono , Kurosawa Kenji
Published: January 2010

Background:  1p36 deletion syndrome is one of the most common subtelomeric deletion syndromes, characterized by moderate to severe mental retardation, characteristic facial appearance, hypotonia, obesity, and seizures. The clinical features often overlap with those of Prader–Willi syndrome (PWS). To elucidate the phenotype–genotype correlation in 1p36 deletion syndrome, two cases involving a PWS‐like phenotype were analyzed on molecular cytogenetics.

Methods:  Two patients presenting with the PWS‐like phenotype but having negative results for PWS underwent fluorescence in situ hybridization (FISH). The size of the chromosome 1p36 deletions was characterized using probes of BAC clones based on the University of California, Santa Cruz (UCSC) Genome Browser.

Results:  PWS was excluded on FISH and methylation‐specific polymerase chain reaction. Subsequent FISH using the probe D1Z2 showed deletion of the 1p36.3 region, confirming the diagnosis of 1p36 deletion syndrome. Further analysis characterized the 1p36 deletions as being located between 4.17 and 4.36 Mb in patient 1 and between 4.89 and 6.09 Mb in patient 2.

Conclusion:  Patients with 1p36 deletion syndrome exhibit a PWS‐like phenotype and are therefore probably underdiagnosed. The possible involvement of the terminal 4 Mb region of chromosome 1p36 in the PWS‐like phenotype is hypothesized.
Relationship between resistin and aPAI‐1 levels with insulin resistance in Saudi children
Authors: Al‐Daghri Nasser M. , Al‐Attas Omar S. , Alokail Majed S. , Alkharfy Khalid M. , Draz Hossam M.
Published: January 2010

Background:  Association of resistin with insulin resistance (IR) in humans is still controversial and few studies have investigated the association of plasminogen activator inhibitor‐1 (PAI‐1) with IR in children. The purpose of the present study was therefore to evaluate serum levels of resistin and active PAI‐1 (aPAI‐1) in Saudi children and their association with the various obesity‐related complications.

Methods:  In this cross‐sectional study, 73 boys and 77 girls with varying body mass index (BMI) were recruited. They were assessed for anthropometric measures and fasting serum levels of glucose, insulin, lipid profile, resistin, angiotensin II (ANG II) and aPAI‐1.

Results:  Resistin was positively correlated with hips (r = 0.33, P < 0.01), waist (r = 0.23, P < 0.05) and BMI (r = 0.33, P < 0.01). The association of resistin with the markers of obesity was also significant in girls but lost significance in boys. aPAI‐1 was positively correlated with total cholesterol (r = 0.24; P < 0.01), triglycerides (r = 0.2, P < 0.05), HOMA‐IR (r = 0.26, P < 0.01) and insulin (r = 0.26, P < 0.01). The significant association of aPAI‐1 with IR was also true in girls but lost significance in boys.

Conclusion:  Resistin is not correlated with IR and further studies are needed to explore the role of resistin especially in childhood obesity. In contrast, increased levels of PAI‐1 may contribute to the risk of cardiovascular diseases related to obesity and insulin resistance in children. The observed gender‐related differences in the association between resistin, aPAI‐1 with obesity markers and IR could be attributed to sexual dimorphism in body fat distribution.
Nicotine facilitates long‐term potentiation induction in oriens‐lacunosum moleculare cells via Ca2+ entry through non‐α7 nicotinic acetylcholine receptors
Authors: Jia Yousheng , Yamazaki Yoshihiko , Nakauchi Sakura , Ito Ken‐Ichi , Sumikawa Katumi
Published: January 2010

Hippocampal inhibitory interneurons have a central role in the control of network activity, and excitatory synapses that they receive express Hebbian and anti‐Hebbian long‐term potentiation (LTP). Because many interneurons in the hippocampus express nicotinic acetylcholine receptors (nAChRs), we explored whether exposure to nicotine promotes LTP induction in these interneurons. We focussed on a subset of interneurons in the stratum oriens/alveus that were continuously activated in the presence of nicotine due to the expression of non‐desensitizing non‐α7 nAChRs. We found that, in addition to α2 subunit mRNAs, these interneurons were consistently positive for somatostatin and neuropeptide Y mRNAs, and showed morphological characteristics of oriens‐lacunosum moleculare cells. Activation of non‐α7 nAChRs increased intracellular Ca2+ levels at least in part via Ca2+ entry through their channels. Presynaptic tetanic stimulation induced N‐methyl‐d‐aspartate receptor‐independent LTP in voltage‐clamped interneurons at −70 mV when in the presence, but not absence, of nicotine. Intracellular application of a Ca2+ chelator blocked LTP induction, suggesting the requirement of Ca2+ signal for LTP induction. The induction of LTP was still observed in the presence of ryanodine, which inhibits Ca2+ ‐induced Ca2+ release from ryanodine‐sensitive intracellular stores, and the L‐type Ca2+ channel blocker nifedipine. These results suggest that Ca2+ entry through non‐α7 nAChR channels is critical for LTP induction. Thus, nicotine affects hippocampal network activity by promoting LTP induction in oriens‐lacunosum moleculare cells via continuous activation of non‐α7 nAChRs.
WELFARE IMPACT OF A BAN ON CHILD LABOR
Authors: SOARES JORGE
Published: January 2010

This article presents a new rationale for imposing restrictions on child labor. In a standard overlapping generation model where parental altruism results in transfers that children allocate to consumption and education, the Nash‐Cournot equilibrium results in suboptimal levels of parental transfers and does not maximize the average level of utility of currently living agents. A ban on child labor decreases children's income and generates an increase in parental transfers bringing their levels closer to the optimum, raising children's welfare as well as average welfare in the short run and in the long run. Moreover, the inability to work allows children to allocate more time to education, and it leads to an increase in human capital. Besides, to increase transfers, parents decrease savings and hence physical capital accumulation. When prices are flexible, these effects diminish the positive welfare impact of the ban on child labor. (JEL D91, E21)
THE IMPACT OF TRADE COSTS ON FIRM ENTRY, EXPORTING, AND SURVIVAL IN KOREA
Authors: KIM SOOIL , REIMER JEFFREY J. , GOPINATH MUNISAMY
Published: January 2010

This study examines how changes in trade costs have affected entry, exit, productivity, and exporting in the Korean manufacturing sector. We verify several predictions of heterogeneous‐firm models of international trade. For example, falling import‐trade costs are associated with less entry and lower market shares among existing domestic firms, and higher total factor productivity for Korean manufacturing as a whole. The size of firms plays an important role in many of our results. New domestic firms are more likely to be small, but large firms are less likely to exit and more likely to have an increase in total factor productivity. (JEL F10, D24)
660. NUYTSIA FLORIBUNDA
Authors: Hopper Stephen D.
Published: January 2010

Summary.
Nuytsia floribunda (Labill.) R.Br. ex G.Don, a monotypic arborescent root hemiparasite endemic to the Southwest Australian Floristic Region, sister to all other showy mistletoes, is described and illustrated. A review is provided of its mythological and practical use by Noongar Aborigines, its discovery and early documentation by Europeans, and its phylogeny, biology, ecology and systematics. Experiences with its cultivation and propagation before and after it was discovered to be parasitic are discussed. Nuytsia provides a useful case study for testing many hypotheses developed in OCBIL theory, which aims to explain the evolution and ecology of, and best conservation practices for, biota on very old, climatically buffered, infertile landscapes (i.e. OCBILs), found especially in regions such as the Southwest Australian Floristic Region, the Greater Cape of South Africa and the Pantepui of Venezuela.
663. LATHRAEA CLANDESTINA
Authors: Fay Michael F.
Published: January 2010

Lathraea clandestina L. is a desirable but challenging plant in gardens which has escaped into natural environments. Intriguing aspects of its biology are discussed, and cultivation notes, a description, a colour plate and line drawings are provided.
Wittgenstein and Ebersole
Authors: Mosedale Frederick E.
Published: January 2010

Frank B. Ebersole died recently. Here I remind philosophers of the thinking of this reclusive philosopher who brought out the value of Wittgenstein's dictum that philosophers should “bring words back from their metaphysical to their everyday use.” I illustrate Ebersole's singular thinking by focusing on his philosophical investigation of Wittgenstein's family resemblance metaphor.
Statistical inference on seemingly unrelated varying coefficient partially linear models
Authors: You Jinhong , Zhou Xian
Published: January 2010

This paper is concerned with the statistical inference on seemingly unrelated varying coefficient partially linear models. By combining the local polynomial and profile least squares techniques, and estimating the contemporaneous correlation, we propose a class of weighted profile least squares estimators (WPLSEs) for the parametric components. It is shown that the WPLSEs achieve the semiparametric efficiency bound and are asymptotically normal. For the non‐parametric components, by applying the undersmoothing technique, and taking the contemporaneous correlation into account, we propose an efficient local polynomial estimation. The resulting estimators are shown to have mean‐squared errors smaller than those estimators that neglect the contemporaneous correlation. In addition, a class of variable selection procedures is developed for simultaneously selecting significant variables and estimating unknown parameters, based on the non‐concave penalized and weighted profile least squares techniques. With a proper choice of regularization parameters and penalty functions, the proposed variable selection procedures perform as efficiently as if one knew the true submodels. The proposed methods are evaluated using wide simulation studies and applied to a set of real data.
Introducing maternal morbidity audit in the Netherlands
Authors: van Dillen J , Mesman JAJM , Zwart JJ , Bloemenkamp KWM , van Roosmalen J
Published: January 2010

Please cite this paper as: van Dillen J, Mesman J, Zwart J, Bloemenkamp K, van Roosmalen J. Introducing maternal morbidity audit in the Netherlands. BJOG 2010;117:416–421.

Objective  To describe the panel audit process and to identify substandard care in selected women from a nationwide prospective cohort study into severe acute maternal morbidity (SAMM) in the Netherlands.

Design  Prospective audit of selected women with SAMM.

Setting  Eight audit meetings held throughout the Netherlands.

Population  All pregnant women in the Netherlands.

Methods  Before each meeting, SAMM details of selected women were sent to all panel members for individual assessment by completing an audit form. During a subsequent plenary meeting, findings were discussed and substandard care factors as judged by the majority of assessors were scored.

Main outcome measures  Incidence of substandard care and recommendations for improving the quality of care.

Results  Substandard care was identified in 53 of 67 women (79%). Specific recommendations were formulated concerning the procedure of audit and concerning local as well as national management guidelines.

Conclusion  Our findings reflect SAMM in the Netherlands and substandard care is present in four out of five women. Ongoing audit of women with SAMM is promoted both at local and national level.
The Accuracy of Predicted Wages of the Non‐Employed and Implications for Policy Simulations from Structural Labour Supply Models*
Authors: BREUNIG ROBERT , MERCANTE JOSEPH
Published: January 2010

We examine the accuracy of predicted wages for the non‐employed. We argue that unemployment, marginal attachment, and not in the labour force are three distinct states. Using panel data from Australia, we test the accuracy of predicted wages for these three groups of non‐employed using sample selection models. Focusing on those individuals who subsequently enter employment, we find that predictions which incorporate the estimated sample selection correction perform poorly, particularly for the marginally attached and the not in the labour force. These results have important implications for policy simulations from structural labour supply models.
MicroRNAs: Master Regulators of Ethanol Abuse and Toxicity?
Authors: Miranda Rajesh C. , Pietrzykowski Andrzej Z. , Tang Yueming , Sathyan Pratheesh , Mayfield Dayne , Keshavarzian Ali , Sampson Wayne , Hereld Dale
Published: January 2010

Ethanol exerts complex effects on human physiology and health. Ethanol is not only addictive, but it is also a fetal teratogen, an adult neurotoxin, and an etiologic agent in hepatic and cardiovascular disease, inflammation, bone loss, and fracture susceptibility. A large number of genes and signaling mechanisms have been implicated in ethanol’s deleterious effects leading to the suggestion that ethanol is a “dirty drug.” An important question is, are there cellular “master‐switches” that can explain these pleiotropic effects of ethanol? MicroRNAs (miRNAs) have been recently identified as master regulators of the cellular transcriptome and proteome. miRNAs play an increasingly appreciated and crucial role in shaping the differentiation and function of tissues and organs in both health and disease. This critical review discusses new evidence showing that ethanol‐sensitive miRNAs are indeed regulatory master‐switches. More specifically, miRNAs control the development of tolerance, a crucial component of ethanol addiction. Other drugs of abuse also target some ethanol‐sensitive miRNAs suggesting that common biochemical mechanisms underlie addiction. This review also discusses evidence that miRNAs mediate several ethanol pathologies, including disruption of neural stem cell proliferation and differentiation in the exposed fetus, gut leakiness that contributes to endotoxemia and alcoholic liver disease, and possibly also hepatocellular carcinomas and other gastrointestinal cancers. Finally, this review provides a perspective on emerging investigations into potential roles of miRNAs as mediators of ethanol’s effects on inflammation and fracture healing, as well as the potential for miRNAs as diagnostic biomarkers and as targets for therapeutic interventions for alcohol‐related disorders.