bluuebunny/crossref_metadata_2025 huggingface dataset:
Genetic and Epidemiological Analysis of Influenza Virus Epidemics in Taiwan during 2003 to 2006
Authors: Jian Jhih-Wei , Chen Guang-Wu , Lai Cheng-Tsung , Hsu Li-Ching , Chen Pei-Jer , Kuo Steve Hsu-Sung , Wu Ho-Sheng , Shih Shin-Ru
Published: February 2008

The genetic characterization of Taiwanese influenza A and B viruses on the basis of analyses of pairwise amino acid variations, genetic clustering, and phylogenetics was performed. A total of 548, 2,123, and 1,336 sequences of the HA1 genes of influenza A virus subtypes H1 and H3 and influenza B virus, respectively, collected during 2003 to 2006 from an island-wide surveillance network were determined. Influenza A virus H3 showed activity during all periods, although it was dominant only in the winters of 2002-2003 and 2003-2004. Instead, influenza B virus and influenza A virus H1 were dominant in the winters of 2004-2005 and 2005-2006, respectively. Additionally, two influenza A virus H3 peaks were found in the summers of 2004 and 2005. From clustering analysis, similar characteristics of high sequence diversity and short life spans for the influenza A virus H1 and H3 clusters were observed, despite their distinct seasonal patterns. In contrast, clusters with longer life spans and fewer but larger clusters were found among the influenza B viruses. We also noticed that more amino acid changes at antigenic sites, especially at sites B and D in the H3 viruses, were found in 2003 and 2004 than in the following 2 years. The only epidemic of the H1 viruses, which occurred in the winter of 2005-2006, was caused by two genetically distinct lineages, and neither of them showed apparent antigenic changes compared with the antigens of the vaccine strain. For the influenza B viruses, the multiple dominant lineages of Yamagata-like strains with large genetic variations observed reflected the evolutionary pressure caused by the Yamagata-like vaccine strain. On the other hand, only one dominant lineage of Victoria-like strains circulated from 2004 to 2006.
GeneXpert Enterovirus Assay: One-Year Experience in a Routine Laboratory Setting and Evaluation on Three Proficiency Panels
Authors: Seme Katja , Močilnik Tina , Komloš Kristina Fujs , Doplihar Ana , Persing David H. , Poljak Mario
Published: February 2008

A prospective unblinded comparative evaluation of three assays for the detection of enteroviral RNA performed on 83 positive and 79 negative cerebrospinal fluid samples showed initial and resolved sensitivities of 90.4% and 98.8%, respectively, for the Cepheid GeneXpert enterovirus assay; 94.0% and 97.6%, respectively, for the Argene enterovirus consensus kit; and 100% and 100%, respectively, for an in-house real-time PCR. The initial and resolved specificities were 100% for all three assays.
Human Fulminant Gas Gangrene Caused by
Clostridium chauvoei
Authors: Nagano Noriyuki , Isomine Shinji , Kato Haru , Sasaki Yoshimasa , Takahashi Motohide , Sakaida Koji , Nagano Yukiko , Arakawa Yoshichika
Published: February 2008

The first human case of fulminant gas gangrene caused by
Clostridium chauvoei
, a pathogen causing ruminant blackleg, was confirmed for a 58-year-old man suffering from diabetes mellitus. The patient developed conspicuous emphysematous gangrene in the right chest wall as well as intravascular gas entrapments and died 2 h after hospital arrival.
Is a Two-Step Glutamate Dehyrogenase Antigen-Cytotoxicity Neutralization Assay Algorithm Superior to the Premier Toxin A and B Enzyme Immunoassay for Laboratory Detection of
Clostridium difficile
?
Authors: Gilligan Peter H.
Published: February 2008

A two-step algorithm for the detection of
Clostridium difficile
by the use of C. Diff Quik Chek (TechLab, Blacksburg, VA) and a tissue culture cytotoxicity neutralization assay was found to be more sensitive than the widely used solid-phase enzyme immunoassay (EIA), the Premier toxin A and B EIA (Meridian Bioscience, Cincinnati, OH), and a newly developed, rapid single-test EIA for
C. difficile
toxins A and B (Tox A/B Quik Chek; TechLab).
Prevalence and Genetic Diversity of Aichi Virus Strains in Stool Samples from Community and Hospitalized Patients
Authors: Ambert-Balay K. , Lorrot M. , Bon F. , Giraudon H. , Kaplon J. , Wolfer M. , Lebon P. , Gendrel D. , Pothier P.
Published: February 2008

Aichi virus has been proposed as a causative agent of gastroenteritis. A total of 457 stool specimens from children hospitalized with acute diarrhea and 566 stool specimens from adults and children involved in 110 gastroenteritis outbreaks were screened for the presence of Aichi virus by reverse transcription-PCR (RT-PCR) amplification of the genomic region of the 3C and 3D (3CD) nonstructural proteins. Our results show a low incidence of Aichi virus in pediatric samples and the existence of mixed infections with other microbiological agents in some cases. From the outbreak survey, it appears that the presence of Aichi virus is an indicator of mixed infections causing gastroenteritis outbreaks and that it could be involved in half of the oyster-associated outbreaks. A second RT-PCR was developed to amplify a part of the VP1 gene. The phylogenetic analysis showed a good correlation between the two classifications based on 3CD and VP1 gene sequences and revealed the prevalence of genotype A in France. It also allowed us to partially describe an Aichi virus strain that could represent a new genotype, thus suggesting the existence of a certain diversity.
The E6 Oncoproteins from Human Betapapillomaviruses Differentially Activate Telomerase through an E6AP-Dependent Mechanism and Prolong the Lifespan of Primary Keratinocytes
Authors: Bedard Kristin M. , Underbrink Michael P. , Howie Heather L. , Galloway Denise A.
Published: February 2008

Human papillomaviruses (HPVs) belonging to the
Betapapillomavirus
genus have recently been implicated in squamous cell carcinomas of the skin, though the mechanisms by which they initiate carcinogenesis are unclear. We show that human foreskin keratinocytes (HFKs) expressing several betapapillomavirus E6 (beta-E6) proteins display life span extension, but not to the extent seen in HFKs expressing HPV type 16 E6 (16E6). Additionally, we demonstrate that beta-E6 proteins can differentially activate telomerase. HFKs expressing 38E6 exhibit significant telomerase activity but to a lesser degree than that observed with 16E6; however, other beta-E6 proteins, including 5E6, 8E6, 20E6, and 22E6, exhibit low or background levels of telomerase activity. Utilizing glutathione
S
-transferase pull-down and coimmunoprecipitation experiments, the beta-E6 proteins were shown to interact with the cellular proteins E6-associated protein (E6AP) and NFX1-91, two proteins known to be important for telomerase activation by 16E6. Interestingly, the relative strength of the interaction between E6 and E6AP or NFX1-91 was proportionate to the activation of telomerase by each beta-E6 protein. To address the requirement for E6AP in telomerase activation by beta-E6 proteins, we utilized a shRNA to knock down endogenous levels of E6AP. Lysates with decreased levels of E6AP showed a reduced ability to activate telomerase, suggesting that E6AP is a necessary component. These data suggest that complex formation between E6, E6AP, and NFX1-91 is a critical step in mediating telomerase activation, which may be one contributing factor to cellular life span extension during human betapapillomavirus infection.
Evaluation of relative density, diameter growth, and stem form in a red spruce (Picearubens) stand 15 years after precommercial thinning
Authors: Barbour R. James , Bailey R.E. , Cook Jean A.
Published: February 2008

Thirty red spruce (Picearubens Sarg.) trees were harvested from a precommercial thinning trial near St. Margaret's Bay, Nova Scotia. Total height was measured, and samples were removed from the following five stem heights: stump height, breast height, 25, 50, and 75% of total height. Relative density and growth rate were measured using X-ray densitometry, and taper was calculated for log and tree lengths. Growth rates were significantly greater on the treatment plot than on the control plot. No significant differences in relative density were found between trees from the treatment plot (2.4 × 2.4 m spacing) and trees from the unthinned control. The relative density of the treatment and control trees was also compared with the species average relative density for red spruce. No significant differences were found, except for the relative density at stump height in the after-treatment portion of the trees from the thinned plot. The difference was not considered great enough to cause a deterioration of the mechanical properties of lumber or the yield of pulp produced from this material. The taper factor was significantly different between the treatment and control plots, but the taper factor for the treatment trees was similar to that for the spruce resource currently being processed in eastern Canada.
Decoding of Light Signals by Plant Phytochromes and Their Interacting Proteins
Authors: Bae Gabyong , Choi Giltsu
Published: February 2008

Phytochromes are red/far-red light photoreceptors that convert the information contained in external light into biological signals. The decoding process starts with the perception of red light, which occurs through photoisomerization of a chromophore located within the phytochrome, leading to structural changes that include the disruption of intramolecular interactions between the N- and C-terminal domains of the phytochrome. This disruption exposes surfaces required for interactions with other proteins. In contrast, the perception of far-red light reverses the photoisomerization, restores the intramolecular interaction, and closes the interacting surfaces. Light information represented by the concentration of opened interacting surfaces is converted into biological signals through the modulating activity of interacting proteins. This review summarizes plant phytochromes, phytochrome-interacting proteins, and signal transmission from phytochromes to their interacting proteins.
Structure-Based View of Epidermal Growth Factor Receptor Regulation
Authors: Ferguson Kathryn M.
Published: February 2008

High-resolution X-ray crystal structures determined in the past six years dramatically influence our view of ligand-induced activation of the epidermal growth factor receptor (EGFR) family of receptor tyrosine kinases. Ligand binding to the extracellular region of EGFR promotes a major domain reorganization, plus local conformational changes, that are required to generate an entirely receptor-mediated dimer. In this activated complex the intracellular kinase domains associate to form an asymmetric dimer that supports the allosteric activation of one kinase. These models are discussed with emphasis on recent studies that add details or bolster the generality of this view of activation of this family of receptors. The EGFR family is implicated in several disease states, perhaps most notably in cancers. Activating tumor mutations have been identified in the intracellular and extracellular regions of EGFR. The impact of these tumor mutations on the understanding of EGFR activation and of its inhibition is discussed.
Structure of Eukaryotic RNA Polymerases
Authors: Cramer P. , Armache K.-J. , Baumli S. , Benkert S. , Brueckner F. , Buchen C. , Damsma G.E. , Dengl S. , Geiger S.R. , Jasiak A.J. , Jawhari A. , Jennebach S. , Kamenski T. , Kettenberger H. , Kuhn C.-D. , Lehmann E. , Leike K. , Sydow J.F. , Vannini A.
Published: February 2008

The eukaryotic RNA polymerases Pol I, Pol II, and Pol III are the central multiprotein machines that synthesize ribosomal, messenger, and transfer RNA, respectively. Here we provide a catalog of available structural information for these three enzymes. Most structural data have been accumulated for Pol II and its functional complexes. These studies have provided insights into many aspects of the transcription mechanism, including initiation at promoter DNA, elongation of the mRNA chain, tunability of the polymerase active site, which supports RNA synthesis and cleavage, and the response of Pol II to DNA lesions. Detailed structural studies of Pol I and Pol III were reported recently and showed that the active center region and core enzymes are similar to Pol II and that strong structural differences on the surfaces account for gene class-specific functions.
Mechanoregulation of intracellular Ca2+ in human autosomal recessive polycystic kidney disease cyst-lining renal epithelial cells
Authors: Rohatgi Rajeev , Battini Lorenzo , Kim Paul , Israeli Sharon , Wilson Patricia D. , Gusella G. Luca , Satlin Lisa M.
Published: February 2008

Mutations of cilia-expressed proteins are associated with an attenuated shear-induced increase in intracellular Ca2+ concentration ([Ca2+]i) in renal epithelial cell lines derived from murine models of autosomal recessive polycystic kidney disease (ARPKD). We hypothesized that human ARPKD cyst-lining renal epithelial cells also exhibited dysregulated mechanosensation. To test this, conditionally immortalized cell lines derived from human fetal ARPKD cyst-lining (pool and clone 5E) cell lines with low levels of fibrocystin/polyductin expression and age-matched normal collecting tubule [human fetal collecting tubule (HFCT) pool and clone 2C] cell lines were grown in culture, loaded with a Ca2+ indicator dye, and subjected to laminar shear. Clonal cell lines were derived from single cells present in pools of cells from cyst-lining and collecting tubules, microdissected from human kidney. Resting and peak [Ca2+]i were similar between ARPKD 5E and pool, and HFCT 2C and pool; however, the flow-induced peak [Ca2+]i was greater in ARPKD 5E (700 ± 87 nM, n = 21) than in HFCT 2C (315 ± 58 nM, n = 12; P < 0.01) cells. ARPKD 5E cells treated with Gd3+, an inhibitor of nonselective cation channels, inhibited but did not abolish the shear-induced [Ca2+]i transient. Cilia were ∼20% shorter in ARPKD than HFCT cells, but no difference in ciliary localization or total cellular expression of polycystin-2, a mechanosenory Gd3+-sensitive cation channel, was detected between ARPKD and HFCT cells. The intracellular Ca2+ stores were similar between cells. In summary, human ARPKD cells exhibit an exaggerated Gd3+-sensitive mechano-induced Ca2+ response compared with controls; whether this represents dysregulated polycystin-2 activity in ARPKD cells remains to be explored.
Control of glycogen synthase through ADIPOR1-AMPK pathway in renal distal tubules of normal and diabetic rats
Authors: Cammisotto Philippe G. , Londono Irene , Gingras Diane , Bendayan Moïse
Published: February 2008

Diabetic nephropathies are characterized by glycogen accumulation in distal tubular cells, which eventually leads to their apoptosis. The present study aims to determine whether adiponectin and AMPK are involved in the regulation of glycogen synthase (GS) in these structures. Western blots of isolated distal tubules revealed the presence of adiponectin receptor ADIPOR1, catalytic AMPK subunits α1 and α2, their phosphorylated active forms, and the glycogen-binding AMPK subunit β2. ADIPOR2 was not detected. Expression levels of ADIPOR1, AMPKα1, AMPKα2, and AMPKβ2 were increased in streptozotocin-treated diabetic rats, whereas phosphorylated active AMPK levels were strongly decreased. Immunohistochemistry revealed the presence of ADIPOR1 on the luminal portion of distal tubules and thick ascending limb cells. Catalytic subunits α1 and α2, their phosphorylated active forms, and the glycogen-binding subunit β2 were also found in the same cells, confirming immunoblot results. In vitro, 5-aminoimidazole-4-carboxamide-1-β-d-ribofuranoside (AICAR; 2 mM) and globular adiponectin (10 μg/ml) activated catalytic AMPK in distal tubules isolated from kidneys of normal rats but much more weakly in those from diabetic rats. GS inhibition paralleled AMPK activation in both groups of animals: active GS levels were low in control animals and elevated in diabetic ones. Finally, glucose-6-phosphate, an allosteric activator of GS, was also increased in diabetic rats. These results demonstrate that in distal tubular cells, adiponectin through luminal ADIPOR1 activates AMPK, leading to the inhibition of GS. During hyperglycemia, this regulation is altered, which may explain, at least in part, the accumulation of large glycogen deposits.
Population Coding by Electrosensory Neurons
Authors: Chacron Maurice J. , Bastian Joseph
Published: February 2008

Sensory stimuli typically activate many receptors at once and therefore should lead to increases in correlated activity among central neurons. Such correlated activity could be a critical feature in the encoding and decoding of information in central circuits. Here we characterize correlated activity in response to two biologically relevant classes of sensory stimuli in the primary electrosensory nuclei, the electrosensory lateral line lobe, of the weakly electric fish Apteronotus leptorhynchus. Our results show that these neurons can display significant correlations in their baseline activities that depend on the amount of receptive field overlap. A detailed analysis of spike trains revealed that correlated activity resulted predominantly from a tendency to fire synchronous or anti-synchronous bursts of spikes. We also explored how different stimulation protocols affected correlated activity: while prey-like stimuli increased correlated activity, conspecific-like stimuli decreased correlated activity. We also computed the correlations between the variabilities of each neuron to repeated presentations of the same stimulus (noise correlations) and found lower amounts of noise correlation for communication stimuli. Therefore the decrease in correlated activity seen with communication stimuli is caused at least in part by reduced noise correlations. This differential modulation in correlated activity occurred because of changes in burst firing at the individual neuron level. Our results show that different categories of behaviorally relevant input will differentially affect correlated activity. In particular, we show that the number of correlated bursts within a given time window could be used by postsynaptic neurons to distinguish between both stimulus categories.
Tracking for Underweight, Overweight and Obesity from Childhood to Adolescence: A 5-Year Follow-Up Study in Urban Indonesian Children
Authors: Julia M. , van Weissenbruch M.M. , Prawirohartono E.P. , Surjono A. , Delemarre-van de Waal H.A.
Published: February 2008

Aims: To assess tracking of body mass index (BMI) of urban Indonesian children from childhood to adolescence and to compare the prevalence of underweight, overweight and obesity in 6- to 8-year-old children from two surveys: years 1999 and 2004. Methods: A longitudinal study assessing BMI tracking of 308 urban children followed from age 6–8 to 11–13 years and two cross-sectional surveys comparing the prevalence of underweight, overweight and obesity in 6- to 8-year-old children: year 1999 (n = 1,524) and 2004 (n = 510). Results: Childhood BMI determined 52.3% variation of later BMI. After 5.1 (0.6) years the prevalence of overweight and obesity increased from 4.2 and 1.9% in childhood to 8.8 and 3.2% in adolescence. The prevalence of underweight decreased from 27.3 to 18.8%. All obese children remained obese, 84.6% overweight children stayed overweight, 56.0% underweight children remained underweight. In cross-sectional comparison the prevalence of overweight and obesity raised from 5.3 to 8.6% and from 2.7 to 3.7%, respectively. The prevalence of underweight remained constant. Conclusions: The prevalence of overweight and obesity increases as children grow into adolescence. Overweight or obese children are more likely to remain overweight or obese. Cross-sectional comparison shows, while the prevalence of underweight stays constant, the prevalence of overweight and obesity increases.
Temporal Changes in Insulin-Like Growth Factors I and II and in Insulin-Like Growth Factor Binding Proteins 1, 2, and 3 in Human Milk
Authors: Milsom Stella R. , Blum Werner F. , Gunn Alistair J.
Published: February 2008

Aim: To evaluate the postpartum time course of changes in insulin-like growth factors (IGFs) and their binding proteins (IGFBPs). Methods: Breast milk IGF-I and IGF-II and IGFBP-1, IGFBP-2, and IGFBP-3 levels were determined in 23 women with babies born at term, from day 4 until up to 9 months after birth. Results: The IGFBP-3 levels were highest from day 4 to day 6 and then decreased by days 10–12. In contrast, IGF-I and IGF-II and IGFBP-1 and IGFBP-2 showed little change over the first 2 weeks after birth. Subsequently, all the IGF components showed a moderate decline over approximately the first 1–3 months and then stable levels up to 9 months after birth. Conclusion: Although the possibility cannot be excluded that these changes in levels of IGFs and their binding proteins in human milk represent passive loss from the mammary gland, we speculate that higher early levels of the human milk IGF system contribute to maturation of the infant gut.
McCune-Albright Syndrome with Male Premature Pubarche of Unusual Origin
Authors: von Puttkamer J. , Karges B. , Wudy S. , Wabitsch M.
Published: February 2008

Premature pubarche in boys is a rare manifestation of McCune-Albright syndrome (MAS). In all cases published so far, it has always been attributed to an excessive testosterone production in the testicles. For the first time we describe a boy with MAS and evidence of premature pubarche of extragonadal origin. Apart from fibrous dysplasia of the forehead and a growth hormone- and prolactin-producing pituitary adenoma, the boy presented with premature pubarche at the age of 6 years and 11 months. The size of his testicles was only 2 ml at that time and remained thus despite a progression of his pubic hair to Tanner stage IV at the age of 10 years. In the basal blood analysis testosterone was not significantly elevated. However, androstenedione and DHEAS were elevated in the serum, and in repetitive 24-hour urine samples DHEAS metabolites were markedly elevated. We therefore concluded that the patient’s premature pubarche might have originated in an increased production of DHEAS. This increased production might be due to an activating mutation of a hormone receptor in the zona reticularis of his adrenal glands leading to an increase in sulfotransferase activity and excessive DHEAS production.
TMC1 but Not TMC2 Is Responsible for Autosomal Recessive Nonsyndromic Hearing Impairment in Tunisian Families
Authors: Tlili Abdelaziz , Rebeh Imen Ben , Aifa-Hmani Mounira , Dhouib Houria , Moalla Jihen , Tlili-Chouchène Jihen , Said Mariem Ben , Lahmar Imed , Benzina Zeineb , Charfedine Ilhem , Driss Nabil , Ghorbel Abdelmonem , Ayadi Hammadi , Masmoudi Saber
Published: February 2008

Hereditary nonsyndromic hearing impairment (HI) is extremely heterogeneous. Mutations of the transmembrane channel-like gene 1 (TMC1) have been shown to cause autosomal dominant and recessive forms of nonsyndromic HI linked to the loci DFNA36 and DFNB7/B11, respectively. TMC1 is 1 member of a family of 8 genes encoding transmembrane proteins. In the mouse, MmTmc1 and MmTmc2 are both members of Tmc subfamily A and are highly and almost exclusively expressed in the cochlea. The restricted expression of Tmc2 in the cochlea and its close phylogenetic relationship to Tmc1 makes it a candidate gene for nonsyndromic HI. We analyzed 3 microsatellite markers linked to the TMC1 and TMC2 genes in 85 Tunisian families with autosomal recessive nonsyndromic HI and without mutations in the protein-coding region of the GJB2 gene. Autozygosity by descent analysis of 2 markers bordering the TMC2 gene allowed us to rule out its association with deafness within these families. However, 5 families were found to segregate deafness with 3 different alleles of marker D9S1837, located within the first intron of the TMC1 gene. By DNA sequencing of coding exons of TMC1 in affected individuals, we identified 3 homozygous mutations, c.100C→T (p.R34X), c.1165C→T (p.R389X) and the novel mutation c.1764G→A (p.W588X). We additionally tested 60 unrelated deaf Tunisian individuals for the c.100C→T mutation. We detected this mutation in a homozygous state in 2 cases. This study confirms that mutations in the TMC1 gene may be a common cause for autosomal recessive nonsyndromic HI.
A Novel Implantable Hearing System with Direct Acoustic Cochlear Stimulation
Authors: Häusler Rudolf , Stieger Christof , Bernhard Hans , Kompis Martin
Published: February 2008

A new implantable hearing system, the direct acoustic cochlear stimulator (DACS) is presented. This system is based on the principle of a power-driven stapes prosthesis and intended for the treatment of severe mixed hearing loss due to advanced otosclerosis. It consists of an implantable electromagnetic transducer, which transfers acoustic energy directly to the inner ear, and an audio processor worn externally behind the implanted ear. The device is implanted using a specially developed retromeatal microsurgical approach. After removal of the stapes, a conventional stapes prosthesis is attached to the transducer and placed in the oval window to allow direct acoustical coupling to the perilymph of the inner ear. In order to restore the natural sound transmission of the ossicular chain, a second stapes prosthesis is placed in parallel to the first one into the oval window and attached to the patient’s own incus, as in a conventional stapedectomy. Four patients were implanted with an investigational DACS device. The hearing threshold of the implanted ears before implantation ranged from 78 to 101 dB (air conduction, pure tone average, 0.5–4 kHz) with air-bone gaps of 33–44 dB in the same frequency range. Postoperatively, substantial improvements in sound field thresholds, speech intelligibility as well as in the subjective assessment of everyday situations were found in all patients. Two years after the implantations, monosyllabic word recognition scores in quiet at 75 dB improved by 45–100 percent points when using the DACS. Furthermore, hearing thresholds were already improved by the second stapes prosthesis alone by 14–28 dB (pure tone average 0.5–4 kHz, DACS switched off). No device-related serious medical complications occurred and all patients have continued to use their device on a daily basis for over 2 years.
Selection of School Leaders: A Critical Component for Change
Authors: Schlueter Keri , Walker Jan
Published: February 2008

This study was designed to analyze the hiring criteria of principals in Iowa to determine whether districts were seeking the characteristics of second-order change in their principals. Using content analysis, hiring criteria provided by districts were coded to identify those that described second-order change responsibilities per Mid-continent Research for Education and Learning's Balanced Leadership Framework. There was little congruence between the hiring criteria and the characteristics of second-order change. The results revealed that only 21% of the criteria were coded as second-order change, 46% of the districts did not use written criteria, and those hiring secondary principals were half as likely to include second-order change characteristics as those seeking elementary principals. The authors provide recommendations for districts and higher education as they seek school leaders who can initiate significant change.
Selecting and Developing an A+ Staff
Authors: Smith Vernon G.
Published: February 2008

Because the demand for excellence in public education is ever present, this article explores the development of a professional enhancement program designed to select and develop a qualified, competent faculty and staff. The basis for the program is a strong educational philosophy, which leads to a vision of what schools can be. It stresses the need for leadership on the part of administrators and the awareness that good administrators are change agents. It points out that good recruitment and selection lessens the demands on a staff development program. Even so, it concludes that staff development must be a continuous process. The cornerstone of this article is a desire for excellence. Recognizing that there is no place for mediocrity in education, this information is offered for those who recognize the same.
Interactions of GABAA Receptor Activation and Light on Period mRNA Expression in the Suprachiasmatic Nucleus
Authors: Ehlen J. Christopher , Novak Colleen M. , Karom Mary C. , Gamble Karen L. , Albers H. Elliott
Published: February 2008

Activation of γ-aminobutyric acid (GABA)A receptors in the suprachiasmatic nucleus (SCN) resets the circadian clock during the day and inhibits the ability of light to reset the clock at night. Light in turn acts during the day to inhibit the phase-resetting effects of GABA. Some evidence suggests that Period mRNA changes in the SCN are responsible for these interactions between light and GABA. Here, the hypothesis that light and the GABAA receptor interact by altering the expression of Period 1 and/or Period 2 mRNA in the SCN is tested. The GABAA agonist muscimol was injected near the SCN just prior to a light pulse, during the mid-subjective day and the early and late subjective night. Changes in Period 1 and Period 2 mRNA were measured in the SCN by in situ hybridization. Light-induced Period 1 mRNA was inhibited by GABAA receptor activation in the early and late subjective night, while Period 2 mRNA was only inhibited during the late night. During the subjective day, light had no effect on the ability of muscimol to suppress Period 1 mRNA hybridization signal. Thus, light and GABA A receptor activation inhibit each other's ability to induce behavioral phase shifts throughout the subjective day and night. However, only in the late night are these behavioral effects correlated with changes in Period gene expression. Together, our data support the hypothesis that the interacting effects of light and GABA are the result of the opposing actions of these stimuli on Period mRNA, but only during the subjective night.
Positive Response Distortion by Police Officer Applicants
Authors: Detrick Paul , Chibnall John T.
Published: February 2008

Interpretation of positive response distortion (socially desirable responding) in employment evaluations is an important validity issue. This study of police officer applicants examined the construct validity of the Paulhus Deception Scales (PDS)—Moralistic Bias (MB; exaggerated adjustment/agreeableness) and Egoistic Bias (EB; exaggerated power/ status)—in relation to validity scales of the Minnesota Multiphasic Personality Inventory—2 (MMPI-2; L, K, and S) and Inwald Personality Inventory (IPI; Guardedness). In regression analyses, MB was significantly associated with each validity scale (particularly L and Guardedness), whereas EB was significantly, but weakly, associated with L only. MB is consistent with response distortion as reflected in L (“perfect” adjustment/personality) and Guardedness (denial of shortcomings/faults). EB is a unique form of response distortion that is not reflected in MMPI-2 or IPI validity scales. The relevance of EB to self-assessment among police officer applicants is an important practical concern in personnel selection and an important theoretical question for future response distortion research.
Factorial Validity and Measurement Invariance of the 20-Item Toronto Alexithymia Scale in Clinical and Nonclinical Samples
Authors: Meganck Reitske , Vanheule Stijn , Desmet Mattias
Published: February 2008

The most widely used instrument to measure alexithymia is the 20-item Toronto Alexithymia Scale (TAS-20). However, different factor structures have been found in different languages. This study tests six published factor models and metric invariance across clinical and nonclinical samples. It also investigated whether there is a method effect of the negatively keyed items. Second-order models with alexithymia as a higher order factor are tested. Confirmatory factor analyses showed that the original factor model with three factors—difficulty identifying feelings (DIF); difficulty describing feelings (DDF) and externally oriented thinking (EOT)—is the best fitting model. Partial measurement invariance across samples was illustrated but requires further study. A weakness of the model is the low internal consistency of the third factor. Because models with a method factor had a better fit, future reconsideration of the negatively formulated items seems necessary. No evidence was found for the second-order models.
CCL8 is a potential molecular candidate for the diagnosis of graft-versus-host disease
Authors: Hori Tsukasa , Naishiro Yasuyoshi , Sohma Hitoshi , Suzuki Nobuhiro , Hatakeyama Naoki , Yamamoto Masaki , Sonoda Tomoko , Mizue Yuka , Imai Kohzoh , Tsutsumi Hiroyuki , Kokai Yasuo
Published: February 2008

Although graft-versus-host disease (GVHD) is a life-threatening complication of hematopoietic stem-cell transplantation (HSCT), its current diagnosis depends mainly on clinical manifestations and invasive biopsies. Specific biomarkers for GVHD would facilitate early and accurate recognition of this grave condition. Using proteomics, we screened for plasma proteins specific for GVHD in a mouse model. One peak with 8972-Da molecular mass (m/z) retained a discriminatory value in 2 diagnostic groups (GVHD and normal controls) with increased expression in the disease and decreased expression during cyclosporin A treatment, and was barely detectable in syngeneic transplantation. Purification and mass analysis identified this molecule as CCL8, a member of a large chemokine family. In human samples, the serum concentration of CCL8 correlated closely with GVHD severity. All non-GVHD samples contained less than 48 pg/mL (mean ± SE: 22.5 ± 5.5 pg/mL, range: 12.6-48.0 pg/mL, n = 7). In sharp contrast, CCL8 was highly up-regulated in GVHD sera ranging from 52.0 to 333.6 pg/mL (mean ± SE: 165.0 ± 39.8 pg/mL, n = 7). Strikingly, 2 patients with severe fatal GVHD had extremely high levels of CCL8 (333.6 and 290.4 pg/mL. CCL8 is a promising specific serum marker for the early and accurate diagnosis of GVHD.
Efficacy of infliximab in extrapulmonary sarcoidosis: results from a randomised trial
Authors: Judson M. A. , Baughman R. P. , Costabel U. , Flavin S. , Lo K. H. , Kavuru M. S. , Drent M. ,   the Centocor T48 Sarcoidosis investigators
Published: February 2008

The aim of the present study was to investigate the efficacy of infliximab for the treatment of extrapulmonary sarcoidosis.

A prospective, randomised, double-blind, placebo-controlled trial was conducted, with infliximab at 3 and 5 mg·kg−1body weight administered over 24 weeks. Extrapulmonary organ severity was determined by a novel severity tool (extrapulmonary physician organ severity tool; ePOST) with an adjustment for the number of organs involved (ePOSTadj). In total, 138 patients enrolled in the trial of infliximabversusplacebo for the treatment of chronic corticosteroid-dependent pulmonary sarcoidosis.

The baseline severity of extrapulmonary organ involvement, as measured by ePOST, was similar across treatment groups. After 24 weeks of drug-therapy study, the change from baseline to week 24 in ePOST was greater for the combined infliximab group compared with the placebo group. After adjustment for the number of extrapulmonary organs involved, the improvement in ePOSTadj observed in the combined infliximab group was also greater than that observed in placebo-treated patients, after 24 weeks of therapy. The improvements in ePOST and ePOSTadj were not maintained during a subsequent 24-week washout period.

Infliximab may be beneficial compared with placebo in the treatment of extrapulmonary sarcoidosis in patients already receiving corticosteroids, as assessed by the severity tool described in the present study.
Trazodone increases arousal threshold in obstructive sleep apnoea
Authors: Heinzer R. C. , White D. P. , Jordan A. S. , Lo Y. L. , Dover L. , Stevenson K. , Malhotra A.
Published: February 2008

A low arousal threshold is believed to predispose to breathing instability during sleep. The present authors hypothesised that trazodone, a nonmyorelaxant sleep-promoting agent, would increase the effort-related arousal threshold in obstructive sleep apnoea (OSA) patients.

In total, nine OSA patients, mean±sdage 49±9 yrs, apnoea/hypopnoea index 52±32 events·h−1, were studied on 2 nights, one with trazodone at 100 mg and one with a placebo, in a double blind randomised fashion. While receiving continuous positive airway pressure (CPAP), repeated arousals were induced: 1) by increasing inspired CO2and 2) by stepwise decreases in CPAP level. Respiratory effort was measured with an oesophageal balloon. End-tidal CO2tension (PET,CO2) was monitored with a nasal catheter.

During trazodone nights, compared with placebo nights, the arousals occurred at a higherPET,CO2level (mean±sd7.30±0.57versus6.62±0.64 kPa (54.9±4.3versus49.8±4.8 mmHg), respectively). When arousals were triggered by increasing inspired CO2level, the maximal oesophageal pressure swing was greater (19.4±4.0versus13.1±4.9 cmH2O) and the oesophageal pressure nadir before the arousals was lower (-5.1±4.7versus-0.38±4.2 cmH2O) with trazodone. When arousals were induced by stepwise CPAP drops, the maximal oesophageal pressure swings before the arousals did not differ.

Trazodone at 100 mg increased the effort-related arousal threshold in response to hypercapnia in obstructive sleep apnoea patients and allowed them to tolerate higher CO2levels.
Dog ownership and contact during childhood and later allergy development
Authors: Chen C-M. , Morgenstern V. , Bischof W. , Herbarth O. , Borte M. , Behrendt H. , Krämer U. , von Berg A. , Berdel D. , Bauer C. P. , Koletzko S. , Wichmann H-E. , Heinrich J. ,   the Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA) Study Group and the German Infant Nutrition Intervention Programme (GINI) Study Group
Published: February 2008

The effect of dog ownership during childhood on the development of allergy has been investigated in few studies with conflicting results. The association between dog contact and indoor endotoxin exposure during infancy and the development of allergic sensitisation and atopic disease up to age 6 yrs was investigated.

Two ongoing birth cohorts, the German Infant Nutrition Intervention Programme (GINI; n = 1,962) and the Influences of Lifestyle Related Factors on the Human Immune System and Development of Allergies in Children (LISA; n = 1,193), were analysed. In both studies, information on children's contact with dogs and their allergic symptoms and doctor-diagnosed allergic disease were collected during follow-up using questionnaires. Specific immunoglobulin E to common aeroallergens was measured at age 6 yrs. House dust samples were collected at age 3 months and the amount of endotoxin was determined.

Dog ownership in early childhood was associated with a significantly lower rate of mixed pollen and inhalant sensitisation but not with dog sensitisation or allergic symptoms and diseases up to age 6 yrs. Regular contact with dogs, without ownership, during childhood was not associated with those health outcomes. No associations were found between house dust endotoxin exposure during infancy and sensitisation outcomes.

In conclusion, dog ownership in early childhood protects against the development of inhalant sensitisation and this effect cannot be attributed to the simultaneous exposure to endotoxin.
CTLA-4-mediated regulatory phenotype of T-cells in tolerant lung recipients
Authors: Botturi K. , Lacoeuille Y. , Thomas P. , Boniface S. , Reynaud-Gaubert M. , Magnan A.
Published: February 2008

Obliterative bronchiolitis (OB) is the major cause of long-term lung allograft loss resulting from an unclear immune process occurring in the absence of the donor's immune cells. The present authors hypothesised that interactions of autologous dendritic cells (DCs) with T-cells could differ in OB patients compared with healthy lung transplant recipients (LTRs).

Monocyte-derived DCs from 14 OB and 35 non-OB LTRs were cultured with autologous T-cells. T-regulatory (Treg) cells, co-receptors, cytokine production, DC phenotype and indoleamine 2,3-dioxygenase (IDO) expression were assessed by flow cytometry. Experiments were repeated in the presence ofPseudomonas aeruginosaor anti-co-receptor antibodies.

DCs from non-OB LTR upregulated Tregcells, cytotoxic T-lymphocyte antigen (CTLA)-4 and interleukin (IL)-10. By contrast CD28 and inducible T-cell co-stimulator were downregulated concomitantly to IL-13 and IL-4. Compared to OB, non-OB DCs displayed an immature phenotype with lower CD80 and CD83 and higher IDO levels of expression. Stimulation byP. aeruginosadid not abolish the tolerogenic effects of DCs on non-OB T-cells. Finally, decreased Tregcells and IL-10 production were detected when adding anti-CTLA-4 antibodies in non-OB LTR.

The present study demonstrates that dendritic cells from nonobliterative bronchiolitis lung transplant recipients induce a tolerant T-cell phenotype which is dependent on cytotoxic T-lymphocyte antigen-4 engagement.
Preoperative Chemotherapy: Updates of National Surgical Adjuvant Breast and Bowel Project Protocols B-18 and B-27
Authors: Rastogi Priya , Anderson Stewart J. , Bear Harry D. , Geyer Charles E. , Kahlenberg Morton S. , Robidoux André , Margolese Richard G. , Hoehn James L. , Vogel Victor G. , Dakhil Shaker R. , Tamkus Deimante , King Karen M. , Pajon Eduardo R. , Wright Mary Johanna , Robert Jean , Paik Soonmyung , Mamounas Eleftherios P. , Wolmark Norman
Published: February 2008

Purpose

National Surgical Adjuvant Breast and Bowel Project (NSABP) Protocol B-18 was designed to determine whether four cycles of doxorubicin and cyclophosphamide (AC) administered preoperatively improved breast cancer disease-free survival (DFS) and overall survival (OS) compared with AC administered postoperatively. Protocol B-27 was designed to determine the effect of adding docetaxel (T) to preoperative AC on tumor response rates, DFS, and OS.

Patients and Methods

Analyses were limited to eligible patients. In B-18, 751 patients were assigned to receive preoperative AC, and 742 patients were assigned to receive postoperative AC. In B-27, 784 patients were assigned to receive preoperative AC followed by surgery, 783 patients were assigned to AC followed by T and surgery, and 777 patients were assigned to AC followed by surgery and then T.

Results

Results from B-18 show no statistically significant differences in DFS and OS between the two groups. However, there were trends in favor of preoperative chemotherapy for DFS and OS in women less than 50 years old (hazard ratio [HR] = 0.85, P = .09 for DFS; HR = 0.81, P = .06 for OS). DFS conditional on being event free for 5 years also demonstrated a strong trend in favor of the preoperative group (HR = 0.81, P = .053). Protocol B-27 results demonstrated that the addition of T to AC did not significantly impact DFS or OS. Preoperative T added to AC significantly increased the proportion of patients having pathologic complete responses (pCRs) compared with preoperative AC alone (26% v 13%, respectively; P < .0001). In both studies, patients who achieved a pCR continue to have significantly superior DFS and OS outcomes compared with patients who did not.

Conclusion

B-18 and B-27 demonstrate that preoperative therapy is equivalent to adjuvant therapy. B-27 also showed that the addition of preoperative taxanes to AC improves response.
In vivo regulation of Yorkie phosphorylation and localization
Authors: Oh Hyangyee , Irvine Kenneth D.
Published: February 2008

Yorkie (Yki), a transcription factor of the Fat and Hippo signaling pathways, is negatively regulated by the Warts kinase. Here, we use Phos-tag gels to characterize Warts-dependent phosphorylation of Yki in vivo, and show that Warts promotes phosphorylation of Yki at multiple sites. We also show that Warts inhibits Yki nuclear localization in vivo, and can promote binding of Yki to 14-3-3 proteins in cultured cells. In vivo assessment of the influence of individual upstream regulators of Warts reveals that some mutants(e.g. fat) have only partial effects on Yki phosphorylation, and weak effects on Yki localization, whereas other genotypes (e.g. ex fatdouble mutants) have stronger effects on both Yki phosphorylation and localization. We also identify serine 168 as a critical site through which negative regulation of Yki by Warts-mediated phosphorylation occurs, but find that this site is not sufficient to explain effects of Hippo signaling on Yki in vivo. These results identify modulation of subcellular localization as a mechanism of Yki regulation, and establish that this regulation occurs in vivo through multiple sites of Warts-dependent phosphorylation on Yki.
C. elegansRab GTPase 2 is required for the degradation of apoptotic cells
Authors: Lu Qun , Zhang Yan , Hu Tianjing , Guo Pengfei , Li Weida , Wang Xiaochen
Published: February 2008

During apoptosis, the dying cell activates an intrinsic mechanism that quickly dismantles itself. The apoptotic cell corpses are then recognized and removed by neighboring cells or professional phagocytes. How dying cells are degraded after internalization is poorly understood. Here, we report the identification and characterization of unc-108, the Caenorhabditis elegans homolog of the human Rab GTPase 2, as a novel component involved in the degradation of apoptotic cells. unc-108 is expressed and functions in the engulfing cells and is likely to affect the degradation rather than the internalization of cell corpses. Similar to other Rab GTPases, unc-108 also affects endocytosis, acting in the endosomal trafficking from early to late endosome and late endosome to lysosome. UNC-108 co-localizes with RAB-5, RAB-7 and LMP-1 to the phagosome and promotes cell corpse degradation, possibly by mediating phagosome maturation.
Colloidal-gold Immunocytochemical Localization of Osteopontin in Avian Eggshell Gland and Eggshell
Authors: Hincke Maxwell T. , Chien Yung-Ching , Gerstenfeld Louis C. , McKee Marc D.
Published: February 2008

During mineralization of the avian eggshell, there is a sequential and orderly deposition of both matrix and mineral phases. Therefore, the eggshell is an excellent model for studying matrix–mineral relationships and the regulation of mineralization. Osteopontin, as an inhibitor of crystal growth, potently influences the formation of calcium phosphate and calcium carbonate biominerals. The purpose of this study was to characterize matrix–mineral relationships, specifically for osteopontin, in the avian eggshell using high-resolution transmission (TEM) and scanning (SEM) electron microscopy to gain insight into how calcite crystal growth is structured and compartmentalized during eggshell mineralization. Osteopontin was localized at the ultrastructural level by colloidal-gold immunocytochemistry. In EDTA-decalcified eggshell, an extensive matrix network was observed by TEM and SEM throughout all regions and included interconnected fibrous sheets, irregularly shaped aggregates, vesicular structures, protein films, and isolated protein fibers. Osteopontin was associated with protein sheets in the highly mineralized palisades region; some of these features defined boundaries that compartmentalized different eggshell structural units. In fractured and un-decalcified eggshell, osteopontin was immunolocalized on the [104] crystallographic faces of calcite—its natural cleavage plane. The specific occlusion of osteopontin into calcite during mineralization may influence eggshell structure to modify its fracture resistance.
Die Byzanzreise des Erzbischofs Gebhard von Salzburg
Authors: Bayer Axel
Published: February 2008

Für die beiden ersten Jahrzehnte der Regierungszeit des Saliers Heinrich IV. stellen die Nachrichten über die Byzanzreise des Erzbischofs Gebhard von Salzburg eines der wenigen Zeugnisse dar, die über die politischen Beziehungen zwischen dem Reich und Byzanz Auskunft zu geben vermögen. Die Reise Gebhards ist in der Forschung bislang auffallend selten behandelt worden, lediglich Wilhelm Erben und Werner Ohnsorge widmeten ihr eine eigene Untersuchung.