bluuebunny/crossref_metadata_2025 huggingface dataset:
Novel molecular defect in the platelet ADP receptor P2Y12 of a patient with haemorrhagic diathesis
Authors: Remijn Jasper A. , IJsseldijk Martin J.W. , Strunk Annuska L.M. , Abbes Andre P. , Engel Henk , Dikkeschei Bert , Dompeling Ellen C. , Groot Philip G. de , Slingerland Robbert J.
Published: February 2007

Clin Chem Lab Med 2007;45:187–9.
Plasma homocysteine cutoff values for venous thrombosis
Authors: Castañon María Mercedes , Lauricella Ana María , Kordich Lucía , Quintana Irene
Published: February 2007

: Hyperhomocysteinemia is considered an independent risk factor for vascular occlusive diseases. To date, there is no general agreement on hyperhomocysteinemia cutoff values.

: To establish a homocysteine cutoff value, we performed a case-control study in 118 patients suffering from venous thrombosis and in 115 healthy subjects. We calculated odds ratios at different cutoff points and considered hyperhomocysteinemia as homocysteine levels above which the risk of venous thrombosis was increased.

: Initially we used the 97.5th percentiles for fasting homocysteine levels in the control group to calculate odds ratios (95% CI) of 9.5 (2.6–35.3), 3.7 (0.8–17.9) and 4.5 (1.7–123.8) for the total population, women and men, respectively. When individuals with well-known thrombotic risk factors were excluded (selected population), odds ratios were 10.5 (2.7– 41.1), 6.5 (1.3–32.1) and 11.2 (1.2–103.1), respectively, confirming hyperhomocysteinemia as an independent risk factor for venous thrombosis. We did not find any association of venous thrombosis with the homozygous methylenetetrahydrofolate reductase C677T mutation. When the hyperhomocysteinemia cutoff was set at other arbitrary points, odds ratios for the selected population were statistically significant only at >12 μmol/L.

: Based on our results, we propose 12 μmol/L as the hyperhomocysteinemia cutoff value.

Clin Chem Lab Med 2007;45:232–6.
Predicted influence of sample hematocrit on injected mass of internal standard in mass spectrometry assays utilizing simple protein precipitation for sample preparation
Authors: Cushman-Vokoun Allison M. , Plath Kim B. , Landmark James D. , Stickle Douglas F.
Published: February 2007

The injected mass of internal standard is often monitored in mass spectrometry assays to flag aberrant specimen processing. When simple protein precipitation is used for sample preparation, the protein volume (solids fraction) of the specimen is in principle a variable affecting the final concentration of the internal standard in the liquid phase. We examined the predicted extent of this variation for an example of protein precipitation for sample preparation used in a mass spectrometry assay for immunosuppressants in whole blood.

Liquid and solid mass fractions of samples with hematocrit ranging from 15% to 60% were measured after protein precipitation of samples using a whole blood/precipitating reagent ratio of 1:4. Relative supernatant volumes as a function of hematocrit were determined.

Liquid volume variation was consistent with a predicted variation in the internal standard concentration of only approximately ±1% across this hematocrit range. Data were in close agreement with calculations based simply on protein density and concentration.

Hematocrit affects the injected mass of internal standard in assays that utilize protein precipitation for sample preparation, due to predictable variation in solids and liquid fractions. The effect is small, however, compared to the typical variation observed for injected mass of internal standard.

Clin Chem Lab Med 2007;45:215–9.
Evaluation of cardiovascular risk factors and related clinical markers in healthy young Japanese adults
Authors: Yagura Chiaki , Takamura Noboru , Kadota Koichiro , Nagazumi Tatsuki , Morishita Yukiko , Nakazato Mio , Maeda Takahiro , Kusano Yosuke , Abe Yasuyo , Aoyagi Kiyoshi
Published: February 2007

: Since atherosclerosis is a slowly progressive process at a young age, effective preventive measures should be taken early in life to prevent future events associated with cardiovascular disease.

: The study population comprised 132 young Japanese adults (mean age 21.4 years, range 18–31 years). We screened plasma total homocysteine and serum folate levels and evaluated mean carotid intima-media thickness and cardio-ankle vascular index.

: Multiple regression analysis after adjustment for age and sex revealed that only folate levels were significantly correlated with plasma total homocysteine levels (β=–0.37, p=0.028). Carotid intima-media thickness adjusted for age and sex and compared between quintiles of total homocysteine levels was significantly increased in the highest quintile compared with other quintiles. Cardio-ankle vascular index increased with age in both women and men, but no additional determinants were identified in young adults.

: Serum folate is an independent determinant of plasma total homocysteine levels, and mild hyperhomocysteinemia may represent a risk factor for increased carotid intima-media thickness, even in young adults. Comprehensive health education from the early period of life, including the suggestion of appropriate dietary measures, is important for effective prevention of future atherosclerosis.

Clin Chem Lab Med 2007;45:220–5.
The Italian External Quality Control Programme for cystic fibrosis molecular diagnosis: 4 years of activity
Authors: Salvatore Marco , Falbo Vincenzo , Floridia Giovanna , Censi Federica , Tosto Fabrizio , Bombieri Cristina , Castaldo Giuseppe , Franco Pignatti Pier , Cristina Rosatelli Maria , Taruscio Domenica
Published: February 2007

: The Italian External Quality Control Programme for cystic fibrosis molecular diagnosis started in 2001; public laboratories distributed throughout Italy participated on a voluntary basis.

: The Italian Public Health Institute (Istituto Superiore di Sanità) sent six validated DNA samples to participating laboratories: technical and clinical information was provided for each sample. Laboratories were required to analyse all six samples. For each sample the laboratories had to provide the results (including raw data) and a report of molecular analysis within 2 months using current methods and nomenclature. Raw data and reports were evaluated by a Steering Committee and their comments were sent to each laboratory.

: Genotyping results indicated a general good level of quality for all laboratories, i.e., ∼1% of alleles were incorrectly assigned each year due to analytical (45%) and misinterpretation (45%) errors. During the first 2 years, more than 70% of laboratories did not test for some regional Italian mutations. Commercial kits for reverse dot-blot and oligonucleotide ligation assay PCR were used to detect mutations by 52.8% and 29.5%, respectively, of the participating laboratories. Reporting of results was still inadequate; in 2004 a model for the written report was introduced, but not all laboratories used it.

: Our data show that few genotyping errors were made by laboratories and were principally due to misinterpretation and analytical reasons. However, reports are still inadequate and it will be interesting to evaluate the introduction of the reporting model in future years.

Clin Chem Lab Med 2007;45:254–60.
Association of vitamin B12, folate and homocysteine with functional and pathological characteristics of the elderly in a mountainous village in Sicily
Authors: Spada Rosario Sebastiano , Stella Giuseppe , Calabrese Santa , Bosco Paolo , Anello Guido , Guéant-Rodriguez Rosa-Maria , Romano Antonino , Benamghar Lahoucine , Fontaine Thierry , Guéant Jean-Louis
Published: February 2007

Homocysteine is associated with age, folate and vitamin B

Subjects (n=280) were examined after door-to-door recruitment using interview, physician examination and laboratory tests.

A total of 19.3% of the population had a low blood level of folate (<7 nmol/L) and 3.2% had low vitamin B

The prevalence of deficits in folate and vitamin B

Clin Chem Lab Med 2007;45:136–42.
Die „Task Force on Pediatric Laboratory Medicine“ der International Federation of Clinical Chemistry and Laboratory Medicine (IFCC): Laboratoriumsdiagnostik-Management von Patienten von der Geburt bis zur Adoleszenz / The International Federation of Clinical Chemistry and Laboratory Medicine's “Task Force on Pediatric Laboratory Medicine”: improving diagnosis and management of patients from birth to adolescence
Authors: Kohse Klaus P.
Published: February 2007

Die im Jahre 2006 gegründete „Task Force für Pädiatrische Laboratoriumsmedizin“ der IFCC ist aus der seit 1995 bestehenden „Internationalen Assoziation für Pädiatrische Laboratoriumsmedizin“ (IAPLM) hervorgegangen. Folgende drei Bereiche stellen die Tätigkeitsschwerpunkte dar: Weltweit sollen lokale oder regionale Aktivitäten koordiniert werden, die darauf gerichtet sind, ein Rahmenwerk von Referenzbereichen für die Ergebnisse laboratoriumsdiagnostischer Untersuchungen bei Kindern aller Altersgruppen zu erstellen; eine tragfähige Basis für die langfristige Fortführung der Internationalen Kongresse für Pädiatrische Laboratoriumsmedizin soll geschaffen werden, die in den vergangenen 25 Jahren sehr erfolgreich waren; ein weltweites Netzwerk für die Kommunikation und den Informationsaustausch von Wissenschaftlern soll geknüpft werden, die in Laboratorien tätig sind, in denen Proben von pädiatrischen Patienten bearbeitet werden.
Therapeutisches Drug Monitoring in der Pädiatrie / Therapeutic drug management in pediatric patients
Authors: Vinks Alexander A. , Walson Philip D.
Published: February 2007

Theoretische Überlegungen und praktische Erfahrungen belegen, dass korrekt bestimmte und richtig interpretierte Bestimmungen von Medikamenten-Konzentrationen im Blut von Patienten (Therapeutisches Drug Monitoring – TDM) die Patientenversorgung bei gleichzeitiger Kostenreduktion verbessern können.

Viele Publikationen belegen die Notwendigkeit einer individuellen Medikamenten-Dosierung bei Kindern und Erwachsenen; wenige, jedoch überzeugende Studien sprechen für die Kosteneffizienz. Verschiedene Patientengruppen profitieren von einer individualisierten Dosierung unter Einsatz des TDM: Frühgeborene, Kritisch kranke Patienten, Epileptiker, Transplantat-Empfänger, HIV-Patienten, Patienten mit Nierenerkrankungen und Mukoviszidose-Patienten. Dennoch wird TDM aus verschiedenen Gründen nicht immer adäquat durchgeführt: Mangel an ausgebildeten Fachkräften, mangelndes Verständnis bei an der Patientenversorgung Beteiligten, Pharma-Firmen oder Laboratorien sowie fehlende Daten zur Kosteneffizienz. Darüber hinaus ist ein effizienter TDM-Service nur interdisziplinär zu bewerkstelligen, was oft auf Schwierigkeiten stößt.

In dieser Übersicht werden derzeitige Strategien zu Zielkonzentrationen von Medikamenten und aktuelle Vorgehensweisen bei TDM, unter Verwendung aller erhältlichen Daten für verschiedene Medikamentenklassen wie Antibiotika, Antikonvulsiva, Immunsuppressiva und antiretrovirale Wirkstoffe, diskutiert. Ein korrekt angewendetes TDM besitzt insbesondere bei pädiatrischen Patienten einen hohen Nutzen. Damit das volle Potenzial ausgeschöpft wird, müssen jedoch viele Defizite im Wissensstand und in der Anwendung des TDM beseitigt werden. Ein einfaches „reaktionäres“ TDM kann nutzlos, ja sogar gefährlich sein. Moderne Verfahren unter Verwendung adaptiver Techniken, die auf einer Bayesschen adaptiven Technologie beruhen, sind dagegen in der Lage, richtige Vorhersagen und damit die Kontrolle über das Verhalten von Medikamenten im individuellen Patienten zu liefern. Dadurch wird eine bessere und kosteneffizientere Patientenversorgung erreicht. Darüber hinaus verspricht die Kombination von analytischen Techniken, pharmakokinetischen und pharmakodynamischen Modellen sowie genetischen Methoden eine wirkliche Optimierung der individuellen Therapie, beginnend mit der initialen Gabe des Medikamentes und darüber hinaus.
Synchronization of Electrically Coupled Pairs of Inhibitory Interneurons in Neocortex
Authors: Mancilla Jaime G. , Lewis Timothy J. , Pinto David J. , Rinzel John , Connors Barry W.
Published: February 2007

We performed a systematic analysis of phase locking in pairs of electrically coupled neocortical fast-spiking (FS) and low-threshold-spiking (LTS) interneurons and in a conductance-based model of a pair of FS cells. Phase–response curves (PRCs) were obtained for real interneurons and the model cells. We used PRCs and the theory of weakly coupled oscillators to make predictions about phase-locking characteristics of cell pairs. Phase locking and the robustness of phase-locked states to differences in intrinsic frequencies of cells were directly examined by driving interneuron pairs through a wide range of firing frequencies.

Calculations using PRCs accurately predicted that electrical coupling robustly synchronized the firing of interneurons over all frequencies studied (FS, ∼25–80 Hz; LTS, ∼10–30 Hz). The synchronizing ability of electrical coupling and the robustness of the phase-locked states were directly dependent on the strength of coupling but not on firing frequency. The FS cell model also predicted the existence of stable antiphase firing at frequencies below ∼30 Hz, but no evidence for stable antiphase firing was found using the experimentally determined PRCs or in direct measures of phase locking in pairs of interneurons.

Despite significant differences in biophysical properties of FS and LTS cells, their phase-locking behavior was remarkably similar. The wide spikes and shallow action potential afterhyperpolarizations of interneurons, compared with the model, prohibited antiphase behavior. Electrical coupling between cortical interneurons of the same type maintained robust synchronous firing of cell pairs for up to ∼10% heterogeneity in their intrinsic frequencies.
Long-Term Upregulation of Protein Kinase A and Adenylate Cyclase Levels in Human Smokers
Authors: Hope Bruce T. , Nagarkar Deepti , Leonard Sherry , Wise Roy A.
Published: February 2007

Repeated injections of cocaine and morphine in laboratory rats cause a variety of molecular neuroadaptations in the cAMP signaling pathway in nucleus accumbens and ventral tegmental area. Here we report similar neuroadaptations in postmortem tissue from the brains of human smokers and former smokers. Activity levels of two major components of cAMP signaling, cAMP-dependent protein kinase A (PKA) and adenylate cyclase, were abnormally elevated in nucleus accumbens of smokers and in ventral midbrain dopaminergic region of both smokers and former smokers. Protein levels of the catalytic subunit of PKA were correspondingly higher in the ventral midbrain dopaminergic region of both smokers and former smokers. Protein levels of other candidate neuroadaptations, including glutamate receptor subunits, tyrosine hydroxylase, and other protein kinases, were within normal range. These findings extend our understanding of addiction-related neuroadaptations of cAMP signaling to tobacco smoking in human subjects and suggest that smoking-induced brain neuroadaptations can persist for significant periods in former smokers.
Sparse and Selective Odor Coding by Mitral/Tufted Neurons in the Main Olfactory Bulb
Authors: Davison Ian G. , Katz Lawrence C.
Published: February 2007

The mammalian olfactory system recognizes an enormous variety of odorants carrying a wide range of important behavioral cues. In the main olfactory bulb (MOB), odorants are ultimately represented through the action potential activity of mitral/tufted cells (M/Ts), whose selectivity and tuning to odorant molecules are therefore fundamental determinants of MOB sensory coding. However, the sheer number and diversity of discrete olfactory stimuli has been a major barrier to comprehensively evaluating M/T selectivity. To address this issue, we assessed M/T odorant responses in anesthetized mice to a 348-odorant panel widely and systematically distributed throughout chemical space, presented both individually and in mixtures at behaviorally relevant concentrations. We found that M/T activation by odorants was markedly selective, with neurons responding robustly, sensitively, and reliably to only a highly restricted subset of stimuli. Multiple odorants activating a single neuron commonly shared clear structural similarity, but M/T tuning also frequently extended beyond obviously defined chemical categories. Cells typically responded to effective compounds presented both individually and in mixtures, although firing rates evoked by mixtures typically showed partial suppression. Response selectivity was further confirmed in awake animals by chronic recordings of M/Ts. These data indicate that individual M/Ts encode specific odorant attributes shared by only a small fraction of compounds and imply that the MOB relays the collective molecular features of an odorant stimulus through a restricted set of M/Ts, each narrowly tuned to a particular stimulus characteristic.
M-Channels (Kv7/KCNQ Channels) That Regulate Synaptic Integration, Excitability, and Spike Pattern of CA1 Pyramidal Cells Are Located in the Perisomatic Region
Authors: Hu Hua , Vervaeke Koen , Storm Johan F.
Published: February 2007

To understand how electrical signal processing in cortical pyramidal neurons is executed by ion channels, it is essential to know their subcellular distribution. M-channels (encoded by Kv7.2–Kv7.5/KCNQ2–KCNQ5 genes) have multiple important functions in neurons, including control of excitability, spike afterpotentials, adaptation, and theta resonance. Nevertheless, the subcellular distribution of these channels has remained elusive. To determine the M-channel distribution within CA1 pyramidal neurons, we combined whole-cell patch-clamp recording from the soma and apical dendrite with focal drug application, in rat hippocampal slices. Both a M-channel opener (retigabine [N-(2-amino-4-(4-fluorobenzylamino)-phenyl) carbamic acid ethyl ester]) and a blocker (XE991 [10,10-bis(4-pyridinylmethyl)-9(10H)-antracenone]) changed the somatic subthreshold voltage response but had no observable effect on local dendritic responses. Under conditions promoting dendritic Ca2+spikes, local somatic but not dendritic application of M-channel blockers (linopirdine and XE991) enhanced the Ca2+spikes. Simultaneous dendritic and somatic whole-cell recordings showed that the medium afterhyperpolarization after a burst of spikes underwent strong attenuation along the apical dendrite and was fully blocked by somatic XE991 application. Finally, by combining patch-clamp and extracellular recordings with computer simulations, we found that perisomatic M-channels reduce the summation of EPSPs. We conclude that functional M-channels appear to be concentrated in the perisomatic region of CA1 pyramidal neurons, with no detectable M-channel activity in the distal apical dendrites.
Functional Imaging Reveals Visual Modulation of Specific Fields in Auditory Cortex
Authors: Kayser Christoph , Petkov Christopher I. , Augath Mark , Logothetis Nikos K.
Published: February 2007

Merging the information from different senses is essential for successful interaction with real-life situations. Indeed, sensory integration can reduce perceptual ambiguity, speed reactions, or change the qualitative sensory experience. It is widely held that integration occurs at later processing stages and mostly in higher association cortices; however, recent studies suggest that sensory convergence can occur in primary sensory cortex. A good model for early convergence proved to be the auditory cortex, which can be modulated by visual and tactile stimulation; however, given the large number and small size of auditory fields, neither human imaging nor microelectrode recordings have systematically identified which fields are susceptible to multisensory influences. To reconcile findings from human imaging with anatomical knowledge from nonhuman primates, we exploited high-resolution imaging (functional magnetic resonance imaging) of the macaque monkey to study the modulation of auditory processing by visual stimulation. Using a functional parcellation of auditory cortex, we localized modulations to individual fields. Our results demonstrate that both primary (core) and nonprimary (belt) auditory fields can be activated by the mere presentation of visual scenes. Audiovisual convergence was restricted to caudal fields [prominently the core field (primary auditory cortex) and belt fields (caudomedial field, caudolateral field, and mediomedial field)] and continued in the auditory parabelt and the superior temporal sulcus. The same fields exhibited enhancement of auditory activation by visual stimulation and showed stronger enhancement for less effective stimuli, two characteristics of sensory integration. Together, these findings reveal multisensory modulation of auditory processing prominently in caudal fields but also at the lowest stages of auditory cortical processing.
Estradiol Induces Diurnal Shifts in GABA Transmission to Gonadotropin-Releasing Hormone Neurons to Provide a Neural Signal for Ovulation
Authors: Christian Catherine A. , Moenter Suzanne M.
Published: February 2007

Ovulation is initiated by a surge of gonadotropin-releasing hormone (GnRH) secretion by the brain. GnRH is normally under negative feedback control by ovarian steroids. During sustained exposure to estradiol in the late follicular phase of the reproductive cycle, however, the feedback action of this steroid switches to positive, inducing the surge. Here, we used an established ovariectomized, estradiol-treated (OVX+E) mouse model exhibiting daily surges to investigate the neurobiological mechanisms underlying this switch. Specifically, we examined changes in GABA transmission to GnRH neurons, which can be excited by GABAAreceptor activation. Spontaneous GABAergic postsynaptic currents (PSCs) were recorded in GnRH neurons from OVX+E and OVX mice in coronal and sagittal slices. There were no diurnal changes in PSC frequency in cells from OVX mice in either slice orientation. In OVX+E cells in both orientations, PSC frequency was low during negative feedback but increased at surge onset. During the surge peak, this increase subsided in coronal slices but persisted in sagittal slices. Comparison of PSCs before and during tetrodotoxin (TTX) treatment showed TTX decreased PSC frequency in OVX+E cells in sagittal slices, but not coronal slices. This indicates estradiol acts on multiple GABAergic afferent populations to increase transmission through both activity-dependent and -independent mechanisms. Estradiol also increased PSC amplitude during the surge. Estradiol and the diurnal cycle thus interact to induce shifts in both GABA transmission and postsynaptic response that would produce appropriate changes in GnRH neuron firing activity and hormone release.
Antibody-Mediated Clearance of Amyloid-β Peptide from Cerebral Amyloid Angiopathy Revealed by QuantitativeIn VivoImaging
Authors: Prada Claudia M. , Garcia-Alloza Monica , Betensky Rebecca A. , Zhang-Nunes Sandy X. , Greenberg Steven M. , Bacskai Brian J. , Frosch Matthew P.
Published: February 2007

Cerebral amyloid angiopathy (CAA) is the accumulation of amyloid-β peptide (Aβ) in the vessel wall of arteries in the brain. Because CAA is commonly associated with Alzheimer's disease (AD), characterized by parenchymal deposition of the same peptide in the form of senile plaques, there is considerable interest in the relationship of the two deposits in generating human disease. The study of CAA is of particular importance for immunotherapeutic approaches to AD, because reports of anti-Aβ immunotherapy in mice and humans have suggested that, whereas CAA appeared resistant to clearance, its response to this treatment promoted potential adverse effects, including meningoencephalitis. We used multiphoton microscopy and longitudinal imaging to monitor CAA in a mouse model of amyloid deposition to evaluate the effects of anti-Aβ passive immunotherapy. We found detectable clearance of CAA deposits within 1 week after a single administration of antibody directly to the brain, an effect that was short-lived. Chronic administration of antibody over 2 weeks led to more robust clearance without evidence of hemorrhage or other destructive changes. We found that the progressive clearance of Aβ from vessels follows distinct kinetics from what has been previously reported for clearance of plaques (parenchymal deposits of Aβ). This quantitativein vivoimaging approach directly demonstrates that CAA in a transgenic mouse model can be cleared with an optimized immunotherapy.
Apolipoprotein E-Containing Lipoproteins Protect Neurons from Apoptosis via a Signaling Pathway Involving Low-Density Lipoprotein Receptor-Related Protein-1
Authors: Hayashi Hideki , Campenot Robert B. , Vance Dennis E. , Vance Jean E.
Published: February 2007

Apolipoprotein E (apoE)-containing lipoproteins (LPs) are secreted by glia and play important roles in lipid homeostasis in the CNS. Glia-derived LPs also promote synaptogenesis and stimulate axon growth of CNS neurons. Here, we provide evidence that glia-derived LPs protect CNS neurons from apoptosis by a receptor-mediated signaling pathway. The protective effect was greater for apolipoprotein E3 than for apolipoprotein E4, the expression of which is a risk factor for Alzheimer's disease. The anti-apoptotic effect of LPs required the association of apolipoprotein E with lipids but did not require cholesterol. Apoptosis was not prevented by lipids alone or by apoA1- or apoJ-containing lipoproteins. The prevention of neuronal apoptosis was initiated after the binding of LPs to the low-density lipoprotein receptor-related protein (LRP), a multifunctional receptor of the low-density lipoprotein receptor family. We showed that inhibition of LRP activation, by treatment of neurons with receptor-associated protein or anti-LRP antibodies, or by LRP gene-silencing experiments, reduced the protective effect of LPs. Furthermore, another LRP ligand, α2-macroglobulin, also protected the neurons from apoptosis. After binding to LRP, LPs initiate a signaling pathway that involves activation of protein kinase Cδ and inactivation of glycogen synthase kinase-3β. These findings indicate the potential for using glial lipoproteins or an activator of the LRP signaling pathway for treatment for neurodegenerative disorders such as Alzheimer's disease.
Parkin Mediates Neuroprotection through Activation of IκB Kinase/Nuclear Factor-κB Signaling
Authors: Henn Iris H. , Bouman Lena , Schlehe Julia S. , Schlierf Anita , Schramm Julia E. , Wegener Elmar , Nakaso Kazuhiro , Culmsee Carsten , Berninger Benedikt , Krappmann Daniel , Tatzelt Jörg , Winklhofer Konstanze F.
Published: February 2007

Mutations in the parkin gene are a major cause of autosomal recessive Parkinson's disease. Here we show that the E3 ubiquitin ligase parkin activates signaling through the IκB kinase (IKK)/nuclear factor κB (NF-κB) pathway. Our analysis revealed that activation of this signaling cascade is causally linked to the neuroprotective potential of parkin. Inhibition of NF-κB activation by an IκB super-repressor or a kinase-inactive IKKβ interferes with the neuroprotective activity of parkin. Furthermore, pathogenic parkin mutants with an impaired neuroprotective capacity show a reduced ability to stimulate NF-κB-dependent transcription. Finally, we present evidence that parkin interacts with and promotes degradation-independent ubiquitylation of IKKγ/NEMO (NF-κB essential modifier) and TRAF2 [TNF (tumor necrosis factor) receptor-associated factor 2], two critical components of the NF-κB pathway. Thus, our results support a direct link between the neuroprotective activity of parkin and ubiquitin signaling in the IKK/NF-κB pathway.
As Seen on TV or was That My Phone? New Media Literacy
Authors: Luke Carmen
Published: February 2007

Media literacy studies traditionally have been the domain of the English and Language Arts classrooms. Cultural studies has not made significant inroads into school-based media studies although, like media studies, it too is concerned with the politics of image/text representations. Information literacy, which also passes as computer or technology literacy, has focused principally on the teaching of operational ‘how-to’ skills. In the last decade, consumers have abandoned newspapers, magazines and network television en masse in favour of cable and Internet news and entertainment sources. Fast news and 24/7 coverage – of 9/11, the US presidential 2004 campaign, world soccer, the 2003 Bali bombings, or the Boxing Day 2004 tsunami in South-east Asia – are global spectacles watched by billions. Given the rapid drift towards media convergence, and consumer shifts from ‘old’ to ‘new’ media, it is argued that media literacy studies, cultural studies, information or technology studies can no longer be taught independently of each other.
Critical Media Literacy: Crucial Policy Choices for a Twenty-First-Century Democracy
Authors: Kellner Douglas , Share Jeff
Published: February 2007

The concept of critical media literacy expands the notion of literacy to include different forms of mass communication and popular culture, as well as deepens the potential of literacy education to critically analyze relationships between media and audiences, information and power. The authors argue that critical media literacy is crucial for participatory democracy in the twenty-first century, and that the only progressive option that exists is how to teach it, not whether to teach it. The article, first, explores the theoretical underpinnings of critical media literacy and demonstrates examples from community-based after school programs and an inner-city elementary school that received a federal grant to integrate media literacy and the arts into the curriculum. A multiperspectival approach addressing issues of gender, race, class and power is used to explore the interconnections of media literacy with cultural studies and critical pedagogy. It is argued that alternative media production must engage students to challenge the master narratives and the systems that make them appear natural. The article then explores the public policy options open to implementing a critical media literacy program. Focusing on media literacy policy in the USA, different approaches commonly used for teaching media literacy are explored and a hybrid critical media literacy framework is proposed. In this day and age of standardized high-stakes testing and corporate solicitations in public education, radical democracy depends on a Deweyan reconceptualization of literacy and the role of education in society. The authors conclude that on the public policy level critical media literacy must reframe our understanding of literacy so that these ideas become integrated across the curriculum at all levels from pre-school to university.
‘Read All about it!’ UK News Media Coverage of A-Level Results
Authors: Warmington Paul , Murphy Roger
Published: February 2007

News coverage of public examination results in the United Kingdom has escalated in recent years. The years 2002 and 2003, in particular, witnessed a bitter media debate over A-level results. Yet, while educationalists often deride the quality of the annual examination debate, there has been minimal research into the specific ways in which exam news issues are constructed by news media. This article discusses the critical findings of an interdisciplinary study, conducted by education and media specialists, of print and broadcast news coverage of the publication of A-level results in August 2002 and 2003. The article focuses upon three particular elements: the distribution of different headline categories and themes; the structural, narrative and presentation templates in which A-level news items were embedded, and the discursive features that have characterised the dominant template for A-level news coverage: the claim that examination standards are ‘falling’. The article concludes by briefly considering some of the broader questions about the relationship between the education sector and news media in the United Kingdom, reflecting upon the ritualistic and polarised nature of coverage, the subtext of anxieties over the ‘massification’ of post-compulsory education and the readiness (or not) of educationalists to engage in a debate being played out for increasingly high stakes.
Literacy is Just Reading and Writing, isn't it? The Ontario Secondary School Literacy Test and its Press Coverage
Authors: Pinto Laura , Boler Megan , Norris Trevor
Published: February 2007

This article examines how the public discourse of print news media defines and shapes the representation of the Ontario Secondary School Literacy Test (OSSLT) based on coverage in three primary newspapers between 1998 and 2004. The data were analysed using qualitative and quantitative measures to identify types of coverage, themes, and inclusion/exclusion of voices. The analysis, which is framed by discourse about conceptions of literacy relating to Dewey's democratic vision for the press, suggests some disappointments on the measure of democratic representation and participation. The article concludes that, if the media is to represent the diversity of voices and provide a wide range of views so as to fulfil its democratic responsibility as envisioned by Dewey, a wider debate over representations of literacy must occur and more perspectives and voices must be included in newspaper coverage.
Bringing features of human dialogue to web surveys
Authors: Conrad Frederick G. , Schober Michael F. , Coiner Tania
Published: February 2007

When web survey respondents self‐administer a questionnaire, what they are doing is in many ways similar to what goes on in human–human interviews. The studies presented here demonstrate that enabling web survey respondents to engage in the equivalent of clarification dialogue can improve respondents' comprehension of questions and thus the accuracy of their answers, much as it can in human–human interviews. In two laboratory experiments, web survey respondents (1) answered more accurately when they could obtain clarification, that is, ground their understanding of survey questions, than when no clarification was available, and (2) answered particularly accurately with mixed‐initiative clarification, where respondents could initiate clarification or the system could provide unsolicited clarification when respondents took too long to answer. Diagnosing the need for clarification based on respondent characteristics—in particular, age—proved more effective than relying on a generic model of all respondents' need for clarification. Although clarification dialogue increased response times, respondents preferred being able to request clarification than not. The current results suggest that bringing features of human dialogue to web surveys can exploit the advantages of both interviewer‐ and self‐administration of questionnaires. Copyright © 2007 John Wiley & Sons, Ltd.
What is sexual harassment? It depends on who asks! Framing effects on survey responses
Authors: Galesic Mirta , Tourangeau Roger
Published: February 2007

We examine the impact of the framing of the survey request––the description of the survey's sponsor and topic––on respondents' answers and describe three mechanisms that may underline such effects. Respondents can try to be relevant and cooperative and provide answers they see as the most useful; they can use the sponsorship and other elements of the survey presentation to help them understand ambiguous questions; and they may find it easier to recall instances of events related to the survey presentation. In a study that framed the survey in two different ways––one sponsored by a feminist organisation fighting against sexual harassment and the other sponsored by a neutral research institute––we found significant differences in the ways people understood and answered questions about sexual harassment. We show that all of the three mechanisms we distinguish might have affected the results. Copyright © 2007 John Wiley & Sons, Ltd.
Applying a timeline as a recall aid in a telephone survey: a record check study
Authors: van der Vaart Wander , Glasner Tina
Published: February 2007

This study examines the effects of a timeline tool that was employed as a visual recall aid for respondents in a standardised telephone survey. The timeline was tested in a split‐ballot field experiment on the purchase behaviour of clients of opticians, the recall period being approximately 7 years. Optician database information was used as gold standard for recall accuracy. Respondents' retrospective reports about purchases of pairs of glasses were compared to the records regarding the price and the date of the most recent purchase and the number of purchases. In most cases, the timeline enhanced recall accuracy. Furthermore, it appeared to be especially helpful when the respondent's recall task was relatively difficult. The advantages and limitations of employing the timeline are discussed in relationship to the supposed underlying cognitive mechanisms. Copyright © 2007 John Wiley & Sons, Ltd.
Stainable iron in aspirated and needle‐biopsy specimens of marrow: A source of error
Authors: Fong T. P. , Okafor L. A. , Thomas W. , Westerman M. P.
Published: February 2007

Marrow iron was assessed in needle biopsy sections and in simultaneously obtained aspirated smears and aspirated clot sections from 251 patients. Significantly different amounts of stainable iron were observed in needle biopsy sections and aspirated smears in 15% of the specimens. The usual difference consisted of significantly less stainable iron in needle biopsy sections as compared to the aspirated smears (13%). Of clinical importance was the finding of absent stainable iron in 8% of the needle biopsy sections, in contrast to the definite deposits observed in the corresponding aspirated smear. Of similar interest was the observation that 6% of the needle biospy sections had significantly less stainable iron than corresponding hemosiderotic smears. The amounts of stainable iron in needle biopsy sections were similar to the amounts observed in the corresponding aspirated clot sections. Evaluation of marrow iron using needle biopsy sections as well as aspirated clot sections differs from results observed in aspirated smears and could be a source of significant error in the assessment of iron stores.
Partial trisomy of the long arm of chromosome 1 in myelofibrosis and polycythemia vera
Authors: Hsu Lillian Y. F. , Pinchiaroli Dona , Gilbert Harriet S. , Wittman Ruth , Hirschhorn Kurt
Published: February 2007

We have identified partial trisomy 1q in 2 patients with different hematologic disorders. The first patient was a 55‐year‐old female with myelosclerosis and myeloid metaplasia diagnosed at age 38 years presenting with anemia, fatigue, bruising, fever, and splenomegaly. At age 56, she had 50–95% myeloblast cells and 95–100 nucleated RBC precursors per 100 WBC. Chromosome analysis of unstimulated leukocytes with Q, G, and C banding showed 46,XX,‐6,+t(1;6) (q25;p22) in all metaphase cells. In vitro incorporation of Fe55 was demonstrated in 90% of metaphases by autoradiography. The second patient, a 49‐year‐old male, was diagnosed as having polycythemia vera at age 30 during a regular checkup. He since developed hepatosplenomegaly. Chromosome analysis from a direct bone marrow preparation at age 44 and 45 showed grossly normal karyotypes. At age 49, his marrow by Q and G banding showed almost 100% of cells with 46,XY,–13,+t(1;13) (q12;p12). Eleven cases of trisomy of 1q have been reported in various hematologic disorders. It is apparent that partial trisomy 1q represents another nonrandom chromosomal abnormality, in addition to the most common nonrandom chromosomal aberrations, such as the Philadelphia chromosome, trisomy 8, trisomy 9, and monosomy 7 in hematologic disorders.
Hemoglobin A1C separation by isoelectric focusing
Authors: Beccaria Luciano , Chiumello Giuseppe , Gianazza Elisabetta , Luppis Benedetta , Righetti Pier Giorgio
Published: February 2007

A modified type of isoelectric focusing has been applied successfully to the separation of hemoglobin A1C (HbA1C) from HbA in normal and diabetic cell lysates. It consists of transforming a linear pH gradient into a nonlinear one, by the addition of an amphoteric substance (“separator” or “pH gradient modifier”) with an isoelectric point (pI) close to the pI's of the two hemoglobins. Among the “modifiers” tested, histidine, proline, threonine, β‐alanine, 6‐amino caproic acid, and 5‐amino valeric acid are not useful in the hemoglobin pI range (pH 6.9–7.0). The dipeptide histidyl‐glycine (pI = 6.8; pI −pK1 = 1) is very efficient in flattening the pH gradient, in the hemoglobin region, even when added in low concentrations (10–100 mM), thus affording full resolution of the two hemoglobin species.
Post‐transfusion alloimmunization in patients with sickle cell disease
Authors: Orlina Armando R. , Unger Phyllis J. , Koshy Mabel
Published: February 2007

The transfusion histories over a 33‐month period of 50 patients with sickle cell disease were reviewed to determine the frequency of alloimmunization to red cell antigens following transfusion in these patients. There were 30 females and 20 males, aged 19‐49 years. Eighteen (36%) were immunized of which thirteen were females. Five of the patients have formed only one antibody so far, while the other 13 have formed two or more. Thirty‐six antibodies were identified: 16 against various Rh antigens, 12 anti‐Lewis, 5 anti‐Kell and one each of anti‐Jka, ‐Fya and ‐M. The immunized patients received, on the average, more transfusions although there was a considerable degree of overlap between the immunized and nonimmunized groups. An approach to the hemotherapy of patients with sickle cell disease (SCD) is discussed.
Effect of chloramphenicol on colony formation from erythrocytic precursors
Authors: Hara Hiroshi , Kohsaki Masatoshi , Noguchi Kohji , Nagai Kyoyasu
Published: February 2007

In the present experiments, we compare the behavior of erythropoietic precursors and granulocytic precurosors exposed to chloramphenicol. Subcutaneous injection of 20 mg of chloramphenicol sodium succinate on five successive days induced a reduction in the number of erythrocytic colony‐forming units (CFU‐E) and erythropoietic burst‐forming units (BFU‐E) in murine marrow and spleen, while no change in number of granulocytic precursors (CFU‐C) in murine hemopoietic organs was observed.

In vitro studies demonstrated concentration‐dependent inhibition of chloramphenicol or chloramphenicol sodium succinate in the colony formation of all these precursors from murine and human bone marrow. However, erythropoietic burst formation of murine and human BFU‐E was completely suppressed by the addition of chloramphenicol or chloramphenicol sodium succinate to the culture medium at therapeutic concentrations (20‐40 μ/ml).

From the present results, it can be concluded that the reduced number of BFU‐E in mice after injection of chloramphenicol sodium succinate resulted from the selective toxicity of chloramphenicol to BFU‐E at therapeutic con centrations.
Sickle cell anemia and trait in Southern India: Further studies
Authors: Brittenham G. , Lozoff B. , Harris J. W. , Mayson S. M. , Miller A. , Huisman T. H. J.
Published: February 2007

Population surveys and family studies among 568 members of nine ethnic groups in southern India identified 15 homozygotes for sickle hemoglobin (Hb S) who had mild clinical and hematological manifestations with high levels of fetal hemoglobin (mean = 20%, range 8–36%) in a heterogeneous red cell distribution. In one family, the heterozygous mother had a hemoglobin pattern consistent with a form of the heterocellular hereditary persistence of fetal hemoglobin. Sickle cell trait was found in 153 (27%) of those studied. Chromatographic quantitation of the hemoglobin fractions in these heterozygotes showed a trimodal distribution of the proportion of Hb S explicable by a genetic model postulating the presence of genotypes with two (−α/−α), three (−α/αα) and four (αα/αα) active α‐globin genes. Globin synthesis studies in four heterozygotes believed to have two active α‐globin genes demonstrated an α/non‐α total activity ratio (0.57) consistent with this model.
Acquired hemoglobin H disease in idiopathic myelofibrosis
Authors: Veer Ashabala , Kosciolek Barbara A. , Bauman Arthur W. , Rowley Peter T.
Published: February 2007

A 68‐year‐old white male, diagnosed 1 year previously as having myelofibrosis, developed hemolysis, red cell inclusions, and 37% Hb H. The alpha/beta globin synthetic ratio for circulating reticulocytes, determined by 3H‐leucine incorporation and globin chain separation by carboxymethylcellulose chromatography in urea, was 0.049. When total RNA was purified from peripheral blood cells and translated in a wheat germ cell‐free translation system, the alpha/beta ratio of the translation products was 0.26, indicting mRNA as a major cause of the globin synthetic imbalance. This study demonstrates that myelofibrosis is one setting in which acquired Hb H disease occurs; that the synthetic imbalance may be extreme; and that it can be associated with an imbalance in the activities of specific globin mRNAs.
The decline in energetic metabolism with aging of the erythrocyte and its relationship to cell death
Authors: Seaman Carol , Wyss Sonja , Piomelli Sergio
Published: February 2007

Human erythrocytes were separated by buoyant density ultracentrifugation into fractions of progressively increasing mean cell age to measure the changes in glycolytic activity that occur during their 120‐day life‐span. The maximal activities of all glycolytic enzymes were shown to decline exponentially with cell age. Only three glycolytic enzymes exhibited a marked rate of decline with a t1/2 shorter than the cell life‐span: hexokinase, aldolase, and pyruvate kinase.

Glucose utilization, when measured in steady‐state conditions (1 mM inorganic phosphate), showed a fourfold decrease through the erythrocyte life‐span; lactate production also declined, but at a slower rate. When incubating conditions were altered by the introduction of a metabolic stimulus (either high phosphate for glycolysis, or methylene blue for the pentose pathway) the youngest cell fractions responded with decidedly increased rates of glucose consumption and lactate production. However, this ability gradually declined with cell aging, and ultimately, the oldest cells had metabolic rates as low as if there were no stimulus present. The oldest erythrocytes appear to have lost the flexibility needed to respond to metabolic stress and are more vulnerable to events in the circulation that may require the ability to increase the basal rate. This defect is probably responsible for the disappearance of aged erythrocytes from the circulation.
Increased bone marrow delta‐aminolevulinic acid synthetase activity in the acute reversible sideroblastic anemia of alcoholics
Authors: Fraser M. B. , Schacter B. A.
Published: February 2007

In an effort to clarify the biochemical pathogenesis of the acute reversible siderblastic anemia of alcoholics, bone marrow delta‐aminolevulinic acid (ALA) synthetase activity was measured in anemic alcoholic patients with and without pathological ring sideroblasts in their marrows and compared with the activity of this enzyme in normal subjects and in patients with idiopathic sideroblastic anemia. Mean ALA‐synthetase activity measured (following addition of exogenous pyridoxal phosphate in three patients with the ring sideroblast morphologic abnormality) was 502 ± 147 (SE) pmoles ALA per 106 erythroblasts per 30 minutes, as compared with 201 ± 69 in the seven alcoholic patients without pathologic sideroblastic marrow abnormalities, 169 ± 32 in the six normal subjects, and 52 ± 4 pmoles ALA per 106 erythroblasts per 30 minutes in two patients with idiopathic sideroblastic anemia. Comparison of enzyme activity in the presence and absence of pyridoxal phosphate revealed that addition of this enzyme cofactor accentuated ALA‐synthetase activity by an average of only 24% in the alcoholic sideroblastic group, as compared with 42% accentuation in the normal group and 8% accentuation in the idiopathic sideroblastic group. These results suggest that abnormalities in pyridoxal phosphate metabolism in alcoholics may not be of importance in the inhibition of heme biosynthesis at the level of ALA synthetase but, rather, that an enzymatic or metabolic block should be sought at a more distal site in the heme biosynthetic pathway.