bluuebunny/crossref_metadata_2025 huggingface dataset:
Postprandial intestinal and whole body nitrogen kinetics and distribution in piglets fed a single meal
Authors: Bos Cécile , Stoll Barbara , Fouillet Hélène , Gaudichon Claire , Guan Xinfu , Grusak Michael A. , Reeds Peter J. , Burrin Douglas G. , Tomé Daniel
Published: October 2004

Our aim was to characterize the postprandial total and dietary N fluxes in the portal drained viscera (PDV) and whole body after administration of a single meal in young pigs. Seven 4-wk-old piglets, implanted with a portal flow probe and portal, arterial and venous catheters, received a primed constant [18O]urea intravenous infusion and were studied for 8 h after a bolus mixed meal ingestion (46 mmol N/kg body wt) intrinsically labeled with15N to trace dietary N fluxes. The real cecal digestibility of the formula was 94.3% (SD 1.8). PDV output of dietary N was found principally in the pool of circulating protein (51% of the measured dietary N PDV output), in the free α-amino N pool (44%), and to a lesser extent in ammonia (5%). Dietary N release in α-amino N and ammonia mainly occurred during the first 3 h. Total and exogenous postprandial urea productions were 5.8 and 2.0 mmol N/kg body wt, respectively. At the end of the postprandial period, losses of dietary N amounted to 10.3% of the dose: 5.7% through ileal losses and 4.6% by deamination and transfer to urea. Net postprandial retention of dietary N was 90.4% (SD 1.3), of which 20% was found in splanchnic zone (small intestine 10%, liver 5%, and plasma protein 3%) and 42% in peripheral zone (muscle 31%, skin 6%). In conclusion, our results show a high efficiency of dietary N utilization for muscular uptake and anabolic utilization. However, the results obtained point out the necessity to further explore the form of dietary N released into the portal blood.
Human soleus and vastus lateralis muscle protein metabolism with an amino acid infusion
Authors: Carroll Chad C. , Fluckey James D. , Williams Rick H. , Sullivan Dennis H. , Trappe Todd A.
Published: October 2004

The calf muscles, compared with the thigh, are less responsive to resistance exercise in ambulatory and bed-rested individuals, apparently due to muscle-specific differences in protein metabolism. We chose to evaluate the efficacy of using amino acids to elevate protein synthesis in the soleus, because amino acids have been shown to have a potent anabolic effect in the vastus lateralis. Mixed muscle protein synthesis in the soleus and vastus lateralis was measured before and after infusion of mixed amino acids in 10 individuals (28 ± 1 yr). Phosphorylation of ribosomal protein p70 S6 kinase (p70S6K; Thr389) and eukaryotic initiation factor 4E-binding protein-1 (4E-BP1; Thr37/46) was also evaluated at rest and after 3 h of amino acid infusion. Basal protein synthesis was similar ( P = 0.126), and amino acids stimulated protein synthesis to a similar extent ( P = 0.004) in the vastus lateralis (0.043 ± 0.011%/h) and soleus (0.032 ± 0.017%/h). Phosphorylation of p70S6K( P = 0.443) and 4E-BP1 ( P = 0.192) was not increased in either muscle; however, the soleus contained more total ( P = 0.002) and phosphorylated ( P = 0.013) 4E-BP1 than the vastus lateralis. These data support the need for further study of amino acid supplementation as a means to compensate for the reduced effectiveness of calf resistance exercise in ambulatory individuals and those exposed to extended periods of unloading. The greater 4E-BP1 in the soleus suggests that there is a muscle-specific distribution of general translational initiation machinery in human skeletal muscle.
HMG-CoA reductase inhibition reverses LCAT and LDL receptor deficiencies and improves HDL in rats with chronic renal failure
Authors: Liang K. , Kim C. H. , Vaziri N. D.
Published: October 2004

Dyslipidemia is a prominent feature of chronic renal failure (CRF) and a major risk factor for atherosclerosis and the progression of renal disease. CRF-induced dyslipidemia is marked by hypertriglyceridemia and a shift in plasma cholesterol from HDL to the ApoB-containing lipoproteins. Several studies have demonstrated a favorable response to administration of 3-hydroxy-3-methylglutaryl (HMG)-CoA reductase inhibitors (statins) in CRF. This study was intended to explore the effect of statin therapy on key enzymes and receptors involved in cholesterol metabolism. Accordingly, CRF ( nephrectomized) and sham-operated rats were randomized to untreated and statin-treated (rosuvastatin 20 mg·kg−1·day−1) groups and observed for 6 wk. The untreated CRF rats exhibited increased total cholesterol-to-HDL cholesterol ratio, diminished plasma lecithin:cholesterol acyltransferase (LCAT) and the hepatic LDL receptor, elevated hepatic acyl-CoA:cholesterol acyltransferase (ACAT), and no change in hepatic HMG-CoA reductase, cholesterol 7α-hydroxylase, or HDL receptor (SRB-1). Statin administration lowered HMG-CoA reductase activity, normalized plasma LCAT, total cholesterol-to-HDL cholesterol ratio, and hepatic LDL receptor but did not significantly change either plasma total cholesterol, hepatic cholesterol 7α-hydroxylase, total ACAT activity, or SRB-1 in the CRF animals. Statin administration to the normal control rats led to significant increases in plasma LCAT and hepatic LDL receptor, significant reductions of total cholesterol-to-HDL cholesterol ratio, hepatic HMG-CoA reductase activity, and cholesterol 7α-hydroxylase abundance with virtually no change in plasma cholesterol concentration. Thus administration of rosuvastatin reversed LCAT and LDL receptor deficiencies and promoted a shift in plasma cholesterol from ApoB-containing lipoproteins to HDL in CRF rats.
Bureaucratic Rationality and Nodal Agency in a Developmental State
Authors: Tsui-Auch Lai Si
Published: October 2004

Theorists in the sociology of development have extensively discussed the capacity of a developmental state to intervene in the industrialization process of a nation. Evans argued that state capacity could be enhanced through the securing of internal cohesiveness, for which the establishment of an effective, rule-following bureaucracy was the key. Chibber amended Evans’s view by arguing that bureaucratic rationality would lead to state cohesiveness only in the presence of disciplinary coordination by a ‘nodal agency’ which was endowed with power over other state agencies that might compete for scarce resources for national development. Based on a study of the state-led biotech development in Singapore, the author of this article makes two further amendments. First, a nodal agency, as shown by the Economic Development Board of Singapore, can maximize the coordination of industrial and technology policy by maintaining an interlocking directorship with other state agencies and externalizing its culture rather than exercising coercion over other state agencies. Second, bureaucratic rationality in the presence of a powerful nodal agency can be a double-edged sword that enables and inhibits technological development.
Contentious Public Religion: Two Conceptions of Islam in Revolutionary Iran
Authors: Ghamari-Tabrizi Behrooz
Published: October 2004

Theorists of secularization considered modernity an irreversible process of differentiation between mutually exclusive spheres of private vs public life. In contrast, proponents of a new paradigm argue that differentiation has strengthened religion in modern society through the establishment of religious market economies. Contrary to both views, the resurgence of religious movements in the last 20 years, particularly Islamist movements, has introduced a new form of contentious public religion that calls into question the interconnectedness of modernity with the privatization of religion. This article shows how the reintroduction of religion in the public sphere contributed to a new understanding of Islam and its relation to contemporary social life. Two distinct articulations of Islam before and after the Iranian revolution of 1979 are examined, those of Ali Shari`ati and Abdolkarim Soroush. Whereas Shari`ati transformed Islam into an ideology of social change, in his ideology critique, Soroush reinstated the enigmatic core of Islam through a hermeneutic distinction between religion and the knowledge of it. The article argues that what religion is, a theological question, is intimately linked to the sociological question what religion does.
Personal relations and moral residue
Authors: Stump Eleonore
Published: October 2004

To what extent can one be saddled with responsibility or guilt as a result of actions committed not by oneself but by others with whom one has a familial or national connection or some other communal association? The issue of communal guilt has been extensively discussed, and there has been no shortage of writers willing to apply the notion of communal responsibility and guilt to Germany after the Holocaust. But the whole notion of communal guilt is deeply puzzling. How can evil actions cast a shadow over the future in this way to generate obligations or guilt on the part of those who did not in any way participate in those actions? In this article, I will focus on a question that is a smaller-scale analogue of the question of communal guilt, one which raises similar perplexities but in a more tractable way. I will concentrate on the restoration of relations with perpetrators of great evil in cases in which their whole-hearted repentance is not in doubt. Most of us feel a strong antipathy to the restoration of relations with such a perpetrator. What explains and supports that emotive reaction is the subject of this article, and its conclusions are suggestive of promising approaches to the question of communal guilt.
Testing the limits of trauma: the long-term psychological effects of the Holocaust on individuals and collectives
Authors: Kansteiner Wulf
Published: October 2004

In light of the great interest in interdisciplinary trauma research, this article explores the philosophical-literary concept of cultural trauma from the perspective of psychiatric and psychoanalytical studies of the long-term consequences of the Holocaust. The extensive literature on the psychological after-effects of the Final Solution offers an exceptional opportunity to study the aftermath of extreme violence from different subject positions, including the perspectives of survivors, perpetrators, bystanders, and their descendants. Moving from the epicenter of the historical event of the Holocaust to its psychological periphery, the survey reveals how much the concept of trauma has changed in the course of five decades as a result of political and cultural developments. But the review of the literature also demonstrates that none of the existing concepts of Holocaust trauma is well suited to explain the effects of Holocaust representations on individuals or collectives who encounter the Final Solution only as a media event for educational or entertainment purposes.
Hearts of darkness: ‘perpetrator history’ and why there is no why
Authors: Roth Paul A.
Published: October 2004

Three theories contend as explanations of perpetrator behavior in the Holocaust as well as other cases of genocide: structural, intentional, and situational. Structural explanations emphasize the sense in which no single individual or choice accounts for the course of events. In opposition, intentional/cutltural accounts insist upon the genocides as intended outcomes, for how can one explain situations in which people ‘step up’ and repeatedly kill defenseless others in large numbers over sustained periods of time as anything other than a choice? Situational explanations offer a type of behavioral account; this is how people act in certain environments. Critical to the situational account as I discuss it is the ‘Asch paradigm’, i.e. experimentally attested conditions for eliciting conformityof behavior regardlesss of available evidence of prior beliefs. In what follows, I defend what I term above a version of situational explanations of perpetrator behavior. Moreover, I maintain that the factors that explain provide an understanding as well. While not committed to the complete irrelevance or exclusion of cultural or structural factors, nonetheless situational analyses can account both for what happened and why. A cardinal virtue of this version of situational explanations consists in showing how shallow the problem of understanding turns out to be for such cases.
Multibody Dynamics and Nonlinear Control of Flexible Space Structures
Authors: Suleman A.
Published: October 2004

A multibody dynamics formulation for studying the response of large space structures with interconnected flexible bodies is presented. The use of system modes to model the structural flexibility results in a compact form of the nonlinear equations of motion. Next, the nonlinear control based feedback linearization technique is applied to effectively control the attitude motion of a flexible space platform. Using the original nonlinear dynamics of the multibody system, the controller determines the effort to effectively linearize the system and introduces a linear compensator to achieve the desired output in the presence of structural flexibility of the spacecraft.
Guidance matters: a pupil perspective on guidance within a Scottish Council
Authors: Boyd Brian , Lawson John
Published: October 2004

In early 2003, a Council commissioned a research project involving four secondary schools to get a pupil perspective of the Guidance system. The context for the project was the implementation of the McCrone agreement and, in particular, discussions about the future role of Guidance in secondary and primary, schools. The evidence from the project was to inform the discussions going on within the Council. The timescale for the completion of the research was tight: the project was to be undertaken and the report produced within three months. As has been demonstrated by previous studies, young people have insights to offer on the way schools organize educational experiences for them. For the most part, their views of Guidance are positive. However, they have clear suggestions to make about what is worth keeping and what needs to change.
The influence of service-learning on intercultural sensitivity
Authors: Westrick Jan
Published: October 2004

This quantitative study examines the influence of service-learning on levels of intercultural sensitivity of international school students in Hong Kong using the Intercultural Development Inventory (IDI). IDI scores are found to correlate with a variety of demographic variables and variables related to four models of service programs. One service-learning model evidences statistically significant posttest gains in the Encapsulated Marginality stage.
Relative antithrombotic effect of soluble GPVI dimer compared with anti-GPVI antibodies in mice
Authors: Grüner Sabine , Prostredna Miroslava , Koch Martina , Miura Yoshiki , Schulte Valerie , Jung Stephanie M. , Moroi Masaaki , Nieswandt Bernhard
Published: October 2004

Glycoprotein VI (GPVI) is an essential platelet collagen receptor; therefore, the inhibition of GPVI-collagen interactions may be an attractive antithrombotic strategy. We have previously shown that targeting of GPVI with antibodies leads to the depletion of the receptor and to long-term antithrombotic protection in mice. An alternative agent to interfere with GPVI-collagen interactions might be soluble GPVI acting as a competitive inhibitor, thereby averting undesired effects on platelets. To test this, we expressed soluble dimeric human GPVI, comprising the extracellular domain of the receptor fused to the human immunoglobulin Fc domain (GPVI-Fc), and compared its antithrombotic potential with that of anti-GPVI antibodies in mice. In contrast to a recent report, we found by intravital fluorescence microscopy and ultrasonic flow measurements that GPVI-Fc had no effect on platelet adhesion and thrombus formation at the injured arterial wall, whereas anti-GPVI antibodies profoundly inhibited these processes. Similar results were obtained with a fusion protein comprising the extracellular domain of mouse GPVI and human IgG-Fc. This indicates that direct targeting of GPVI provides significantly stronger protection against arterial thrombosis than soluble GPVI dimer.
PSK and Trx80 inhibit B-cell growth in EBV-infected cord blood mononuclear cells through T cells activated by the monocyte products IL-15 and IL-12
Authors: Liu Anquan , Arbiser Jack L. , Holmgren Arne , Klein George , Klein Eva
Published: October 2004

Epstein-Barr virus (EBV)–specific immunologic memory is not transferred from mother to child. In vitro infection of cord blood cells can therefore readily lead to the outgrowth of transformed B lymphocytes. We found that the immunomodulator polysaccharide K (PSK) or the mitogenic cytokine truncated thioredoxin (Trx80) inhibited the EBV-induced B-cell proliferation. Using signaling lymphocytic activation molecule (SLAM)–associated protein (SAP) induction as a sign for T- and natural killer (NK) cell activation, we could follow it without any need for cell separation because neither macrophages nor B lymphocytes express SAP. The results suggest the following scenario: EBV infected and activated B lymphocytes. Upon interacting with these cells, T cells became posed for responding to cytokines produced by monocytes. Both PSK and Trx80, which is a secreted C-terminally truncated thioredoxin, activated the monocytes, which then produced cytokines in the presence of the primed T cells. PSK induced interleukin-15 (IL-15), while Trx80 induced IL-12 production. Both cytokines activated the T cells for function. Phosphatidylinositol 3–(PI 3)–kinase and reactive oxygen species (ROSs) were involved in the PSK-induced activation of monocytes. Restimulation of the cultures with EBV-transformed B cells generated specific cytotoxic activity.
Long-term pharmacologically regulated expression of erythropoietin in primates following AAV-mediated gene transfer
Authors: Rivera Victor M. , Gao Guang-ping , Grant Rebecca L. , Schnell Michael A. , Zoltick Philip W. , Rozamus Leonard W. , Clackson Tim , Wilson James M.
Published: October 2004

Gene therapy is a potential route for the delivery of secreted therapeutic proteins, but pharmacologic control of expression will generally be required for optimal safety and efficacy. Previous attempts to achieve regulated expression in largeanimal models have been thwarted by transient expression or immune responses to regulatory proteins. We evaluated the ability of the dimerizer-regulated gene expression system to achieve controlled, long-term production of erythropoietin (Epo) following intramuscular administration of adeno-associated virus (AAV) vectors to 16 primates. All animals showed dose-responsive and completely reversible elevation of Epo and hematocrit in response to the dimerizer rapamycin, or analogs with reduced immunosuppressive activity, administered intravenously or orally. Animals that received optimized dual vectors showed persistent regulated expression for the duration of the study, with no apparent immune response to Epo or the regulatory proteins. Similar results were obtained with single vectors incorporating both the Epo and regulatory genes, including those packaged into serotype 1 AAV vectors to allow use of lower viral doses. For the longest-studied animal, regulated expression has persisted for more than 6 years and 26 induction cycles. These data indicate that one-time or infrequent gene transfer followed by dimerizer regulation is a promising approach for delivery of therapeutic proteins.
IgG antibodies that recognize epitope Gly40-Arg43 in domain I of β2–glycoprotein I cause LAC, and their presence correlates strongly with thrombosis
Authors: de Laat Bas , Derksen Ronald H. W. M. , Urbanus Rolf T. , de Groot Philip G.
Published: October 2004

Anti–β2–glycoprotein I antibodies are known to have a heterogeneous reactivity against β2–glycoprotein I. We performed this study to characterize the epitope on β2–glycoprotein I to which pathologic anti–β2–glycoprotein I antibodies are directed. Plasma samples from 198 patients with various systemic autoimmune diseases were tested for the presence of lupus anticoagulant and anti–β2–glycoprotein I immunoglobulin G (IgG) antibodies. The reactivity of the anti–β2–glycoprotein I–positive samples was further tested by coating recombinant full-length β2–glycoprotein I and 8 deletion mutants of β2–glycoprotein I onto hydrophilic and hydrophobic enzyme-linked immunosorbent assay (ELISA) plates. Full-length β2–glycoprotein I with point mutations in domain I at positions 8, 40, and 43 were used in inhibition experiments. Fifty-two patients with anti–β2–glycoprotein I IgG antibodies could be divided into 2 patterns. Type A antibodies only recognize domain I when coated onto hydrophobic plates; they do not recognize domain I coated onto hydrophilic plates. Type B antibodies have heterogeneous reactivity for all domains. Type A antibodies recognize the epitope around amino acids Gly40-Arg43 and cause lupus anticoagulant activity. In contrast to type B antibodies, those of type A strongly correlated with thrombosis. In conclusion, antibodies directed at domain I (epitope comprising Gly40 and Arg43) have lupus anticoagulant activity and strongly associate with thrombosis.
Inhibitory effects of proanthocyanidins from Ribes nigrum leaves on carrageenin acute inflammatory reactions induced in rats
Authors: Garbacki Nancy , Tits Monique , Angenot Luc , Damas Jacques
Published: October 2004

Background

The anti-inflammatory effects of proanthocyanidins (PACs), isolated from blackcurrant (Ribes nigrum L.) leaves, were analysed using carrageenin-induced paw oedema and carrageenin-induced pleurisy in rats.

Results

Pretreatment of the animals with PACs (10, 30, 60 and 100 mg/kg, i.p.) reduced paw oedema induced by carrageenin in a dose and time-dependent manner. PACs also inhibited dose-dependently carrageenin-induced pleurisy in rats. They reduced (A) lung injury, (B) pleural exudate formation, (C) polymorphonuclear cell infiltration, (D) pleural exudate levels of TNF-α, IL-1β and CINC-1 but did not affect IL-6 and IL-10 levels. They reduced (E) pleural exudate levels of nitrite/nitrate (NOx). In indomethacin treated rats, the volume of pleural exudate was low, its content in leukocytes and its contents in TNF-α, IL-1β, IL-6 and IL-10 but not in NOx were reduced. These data suggest that the anti-inflammatory properties of PACs are achieved through a different pattern from those of indomethacin.

Conclusion

These results suggest that the main mechanism of the anti-inflammatory effect of PACs mainly lies in an interference with the migration of the leukocytes. Moreover, PACs inhibited in vivo nitric oxide release.
The use of warfarin in veterans with atrial fibrillation
Authors: Bravata Dawn M , Rosenbeck Karen , Kancir Sue , Brass Lawrence M
Published: October 2004

Background

Warfarin therapy is effective for the prevention of stroke in patients with atrial fibrillation. However, warfarin therapy is underutilized even among ideal anticoagulation candidates. The purpose of this study was to examine the use of warfarin in both inpatients and outpatients with atrial fibrillation within a Veterans Affairs (VA) hospital system.

Methods

This retrospective medical record review included outpatients and inpatients with atrial fibrillation. The outpatient cohort included all patients seen in the outpatient clinics of the VA Connecticut Healthcare System during June 2000 with a diagnosis of atrial fibrillation. The inpatient cohort included all patients discharged from the VA Connecticut Healthcare System West Haven Medical Center with a diagnosis of atrial fibrillation during October 1999 – March 2000. The outcome measure was the rate of warfarin prescription in patients with atrial fibrillation.

Results

A total of 538 outpatients had a diagnosis of atrial fibrillation and 73 of these had a documented contraindication to anticoagulation. Among the 465 eligible outpatients, 455 (98%) were prescribed warfarin. For the inpatients, a total of 212 individual patients were discharged with a diagnosis of atrial fibrillation and 97 were not eligible for warfarin therapy. Among the 115 eligible inpatients, 106 (92%) were discharged on warfarin.

Conclusions

Ideal anticoagulation candidates with atrial fibrillation are being prescribed warfarin at very high rates within one VA system, in both the inpatient and outpatient settings; we found warfarin use within our VA was much higher than that observed for Medicare beneficiaries in our state.
Mental health first aid training of the public in a rural area: a cluster randomized trial [ISRCTN53887541]
Authors: Jorm Anthony F , Kitchener Betty A , O'Kearney Richard , Dear Keith BG
Published: October 2004

Background

A Mental Health First Aid course has been developed which trains members of the public in how to give initial help in mental health crisis situations and to support people developing mental health problems. This course has previously been evaluated in a randomized controlled trial in a workplace setting and found to produce a number of positive effects. However, this was an efficacy trial under relatively ideal conditions. Here we report the results of an effectiveness trial in which the course is given under more typical conditions.

Methods

The course was taught to members of the public in a large rural area in Australia by staff of an area health service. The 16 Local Government Areas that made up the area were grouped into pairs matched for size, geography and socio-economic level. One of each Local Government Area pair was randomised to receive immediate training while one served as a wait-list control. There were 753 participants in the trial: 416 in the 8 trained areas and 337 in the 8 control areas. Outcomes measured before the course started and 4 months after it ended were knowledge of mental disorders, confidence in providing help, actual help provided, and social distance towards people with mental disorders. The data were analysed taking account of the clustered design and using an intention-to-treat approach.

Results

Training was found to produce significantly greater recognition of the disorders, increased agreement with health professionals about which interventions are likely to be helpful, decreased social distance, increased confidence in providing help to others, and an increase in help actually provided. There was no change in the number of people with mental health problems that trainees had contact with nor in the percentage advising someone to seek professional help.

Conclusions

Mental Health First Aid training produces positive changes in knowledge, attitudes and behaviour when the course is given to members of the public by instructors from the local health service.
Trends in suicide in Scotland 1981 – 1999: age, method and geography
Authors: Stark Cameron , Hopkins Paddy , Gibbs Diane , Rapson Tracey , Belbin Alan , Hay Alistair
Published: October 2004

Background

Male suicide rates continued to increase in Scotland when rates in England and Wales declined. Female rates decreased, but at a slower rate than in England and Wales. Previous work has suggested higher than average rates in some rural areas of Scotland. This paper describes trends in suicide and undetermined death in Scotland by age, gender, geographical area and method for 1981 – 1999.

Methods

Deaths from suicide and undetermined cause in Scotland from 1981 – 1999 were identified using the records of the General Registrar Office. The deaths of people not resident in Scotland were excluded from the analysis. Death rates were calculated by area of residence, age group, gender, and method. Standardised Mortality Ratios (SMRs) and 95% confidence intervals were calculated for rates by geographical area.

Results

Male rates of death by suicide and undetermined death increased by 35% between 1981 – 1985 and 1996 – 1999. The largest increases were in the youngest age groups. All age female rates decreased by 7% in the same period, although there were increases in younger female age groups.

The commonest methods of suicide in men were hanging, self-poisoning and car exhaust fumes. Hanging in males increased by 96.8% from 45 per million to 89 per million, compared to a 30.7% increase for self-poisoning deaths. In females, the commonest method of suicide was self-poisoning. Female hanging death rates increased in the time period.

Male SMRs for 1981 – 1999 were significantly elevated in Western Isles (SMR 138, 95% CI 112 – 171), Highland (135, CI 125 – 147), and Greater Glasgow (120, CI 115 – 125). The female SMR was significantly high only in Greater Glasgow (120, CI 112 – 128).

Conclusion

All age suicide rates increased in men and decreased in women in Scotland in 1981 – 1999. Previous findings of higher than expected male rates in some rural areas were supported. Rates were also high in Greater Glasgow, one of the most deprived areas of Scotland. There were changes in the methods used, with an increase in hanging deaths in men, and a smaller increase in hanging in women. Altered choice of method may have contributed to the increased male deaths.
Detecting imbalanced expression of SNP alleles by minisequencing on microarrays
Authors: Liljedahl Ulrika , Fredriksson Mona , Dahlgren Andreas , Syvänen Ann-Christine
Published: October 2004

Background

Each of the human genes or transcriptional units is likely to contain single nucleotide polymorphisms that may give rise to sequence variation between individuals and tissues on the level of RNA. Based on recent studies, differential expression of the two alleles of heterozygous coding single nucleotide polymorphisms (SNPs) may be frequent for human genes. Methods with high accuracy to be used in a high throughput setting are needed for systematic surveys of expressed sequence variation. In this study we evaluated two formats of multiplexed, microarray based minisequencing for quantitative detection of imbalanced expression of SNP alleles. We used a panel of ten SNPs located in five genes known to be expressed in two endothelial cell lines as our model system.

Results

The accuracy and sensitivity of quantitative detection of allelic imbalance was assessed for each SNP by constructing regression lines using a dilution series of mixed samples from individuals of different genotype. Accurate quantification of SNP alleles by both assay formats was evidenced for by R2 values > 0.95 for the majority of the regression lines. According to a two sample t-test, we were able to distinguish 1–9% of a minority SNP allele from a homozygous genotype, with larger variation between SNPs than between assay formats. Six of the SNPs, heterozygous in either of the two cell lines, were genotyped in RNA extracted from the endothelial cells. The coefficient of variation between the fluorescent signals from five parallel reactions was similar for cDNA and genomic DNA. The fluorescence signal intensity ratios measured in the cDNA samples were compared to those in genomic DNA to determine the relative expression levels of the two alleles of each SNP. Four of the six SNPs tested displayed a higher than 1.4-fold difference in allelic ratios between cDNA and genomic DNA. The results were verified by allele-specific oligonucleotide hybridisation and minisequencing in a microtiter plate format.

Conclusions

We conclude that microarray based minisequencing is an accurate and accessible tool for multiplexed screening for imbalanced allelic expression in multiple samples and tissues in parallel.
Enhanced cell-permeant Cre protein for site-specific recombination in cultured cells
Authors: Lin Qing , Jo Daewoong , Gebre-Amlak Kassatihun D , Ruley H Earl
Published: October 2004

Background

Cell-permeant Cre DNA site-specific recombinases provide an easily controlled means to regulate gene structure and function in living cells. Since recombination provides a stable and unambiguous record of protein uptake, the enzyme may also be used for quantitative studies of cis- and trans-acting factors that influence the delivery of proteins into cells.

Results

In the present study, 11 recombinant fusion proteins were analyzed to characterize sequences and conditions that affect protein uptake and/or activity and to develop more active cell-permeant enzymes. We report that the native enzyme has a low, but intrinsic ability to enter cells. The most active Cre proteins tested contained either an N-terminal 6xHis tag and a nuclear localization sequence from SV40 large T antigen (HNC) or the HIV Tat transduction sequence and a C-terminal 6xHis tag (TCH6). The NLS and 6xHis elements separately enhanced the delivery of the HNC protein into cells; moreover, transduction sequences from fibroblast growth factor 4, HIV Tat or consisting of the (KFF)3K sequence were not required for efficient protein transduction and adversely affected enzyme solubility. Transduction of the HNC protein required 10 to 15 min for half-maximum uptake, was greatly decreased at 4°C and was inhibited by serum. Efficient recombination was observed in all cell types tested (a T-cell line, NIH3T3, Cos7, murine ES cells, and primary splenocytes), and did not require localization of the enzyme to the nucleus.

Conclusions

The effects of different sequences on the delivery and/or activity of Cre in cultured cells could not be predicted in advance. Consequently, the process of developing more active cell-permeant recombinases was largely empirical. The HNC protein, with an excellent combination of activity, solubility and yield, will enhance the use of cell-permeant Cre proteins to regulate gene structure and function in living cells.
Decrease of resistance to air flow with nasal strips as measured with the airflow perturbation device
Authors: Wong Lily S , Johnson Arthur T
Published: October 2004

Background

Nasal strips are used by athletes, people who snore, and asthmatics to ease the burden of breathing. Although there are some published studies that demonstrate higher flow with nasal strips, none had directly measured the effect of the strips on nasal resistance using the airflow perturbation device (APD). The APD is an inexpensive instrument that can measure respiratory resistance based on changes in mouth pressure and rate of airflow.

Method

This study tested forty-seven volunteers (14 men and 33 women), ranging in age from 17 to 51. Each volunteer was instructed to breathe normally into the APD using an oronasal mask with and without nasal strips. The APD measured respiratory resistance during inhalation, exhalation, and an average of the two.

Results

Results of a paired mean t-test comparing nasal strip against no nasal strip were statistically significant at the p = 0.05 level. The Breathe Right™ nasal dilator strips lowered nasal resistance by an average of 0.5 cm H20/Lps from an average nasal resistance of 5.5 cm H20/Lps.

Conclusions

Nasal strips reduce nasal resistance when measured with the APD. The effect is equal during exhalation and during inhalation.
Methylation of histones in myeloid leukemias as a potential marker of granulocyte abnormalities
Authors: Lukášová Emilie , Kořistek Zdeněk , Falk Martin , Kozubek Stanislav , Grigoryev Sergei , Kozubek Michal , Ondřej Vladan , Kroupová Iva
Published: October 2004

We show that common heterochromatin antigenic protein markers [HP1α, -β, -γ and mono-, di-, and trimethylated histone H3 lysine 9 (H3K9)], although present in human blood progenitor CD34+ cells, differentiated lymphocytes, and monocytes, are absent in neutrophil granulocytes and to large extent, in eosinophils. Monomethylated and in particular, dimethylated H3K9 are present to variable degrees in the granulocytes of chronic myeloid leukemia (CML) patients, without being accompanied by HP1 proteins. In patients with an acute phase of CML and in acute myeloid leukemia patients, strong methylation of H3K9 and all isoforms of HP1 are detected. In chronic forms of CML, no strong correlations among the level of histone methylation, disease progression, and modality of treatment were observed. Histone methylation was found even in “cured” patients without Philadelphia chromosome (Ph) resulting from +(9;22)(q34;q11) BCR/ABL translocation, suggesting an incomplete process of developmentally regulated chromatin remodeling in the granulocytes of these patients. Similarly, reprogramming of leukemia HL-60 cells to terminal differentiation by retinoic acid does not eliminate H3K9 methylation and the presence of HP1 isoforms from differentiated granulocytes. Thus, our study shows for the first time that histone H3 methylation may be changed dramatically during normal cell differentiation. The residual histone H3 methylation in myeloid leukemia cells suggests an incomplete chromatin condensation that may be linked to the leukemia cell proliferation and may be important for the prognosis of disease treatment and relapse.
2004 Teaching Award Winners
Authors: Hammer Elizabeth Yost
Published: October 2004

The Society for the Teaching of Psychology (Division Two) celebrated the 25th year of its annual Teaching Awards Program at the July convention of the American Psychological Association in Honolulu, Hawaii. The 2004 winners received a plaque and a check for $750. Recognition for outstanding teaching was given in each of the following categories: (a) Robert S. Daniel Award (4-year college or university professor), (b) 2-year College Award, (c) Moffett Memorial Award (high school teacher), and (d) McKeachie Early Career Award (graduate student).
Where History, Philosophy, and Psychology Meet: An Interview with Wayne Viney
Authors: Rutherford Alexandra
Published: October 2004

Wayne Viney is Professor of Psychology and University Distinguished Teaching Scholar at Colorado State University where he teaches graduate and undergraduate courses in the history of psychology. He is also inaugurating a new course, The Development of Scientific Thought, for the College of Natural Sciences at Colorado State. Earlier in his career, he served as Head of the Department of Psychology, Associate Dean of the College of Natural Sciences, and Director of the University Core Curriculum in the Biological Sciences. Viney was elected President of Division 26 (History of Psychology) and of the Rocky Mountain Psychological Association. He has been the recipient of 15 teaching awards at Colorado State University. In 1998, he served as a G. Stanley Hall lecturer for the American Psychological Association. He is coauthor with D. Brett King of A History of Psychology: Ideas and Context. He is also coauthor with Michael and Marilyn Wertheimer of a major bibliography entitled History of Psychology: A Guide to Information Sources. The focus of Viney's historical research has been the psychology and philosophy of William James as well as the life and work of the American humanitarian reformer, Dorothea Lynde Dix.

Alexandra Rutherford is Assistant Professor of Psychology at York University in Toronto, Ontario, Canada, where she is a faculty member in the History and Theory of Psychology Graduate Program. She teaches undergraduate and graduate courses in the history of psychology and undergraduate courses in abnormal psychology and personality psychology. She supervises both undergraduate and graduate students in historical and theoretical research projects and serves as the assistant editor of the Journal of the History of the Behavioral Sciences. She also edits the Heritage Column for The Feminist Psychologist, the newsletter of the Society for the Psychology of Women (Division 35 of the American Psychological Association). She has developed a Heritage Web site for Division 35 that is devoted to documenting the role of women in the history of psychology and promoting feminist approaches to writing, teaching, and understanding psychology's history ( www.psych.yorku.ca/femhop/ ). Her primary research areas are the history of B. F. Skinner's system in science and culture and the history of women and feminism in psychology. In 2001 she received the Division 26 (History of Psychology) Early Career Award for scholarship in the history of psychology. She is also a clinical psychologist in private practice.
Annotated Bibliography on the Teaching of Psychology: 2003
Authors: Johnson David E. , Kirkbride Abby L. , Schroder Simone I.
Published: October 2004

This bibliography is a continuation ofthose previously published in Teaching of Psychology (e.g., Berry & Daniel, 1984; Fulkerson & Wise, 1987; Johnson & Schroder, 1997; Wise & Fulkerson, 1996). We maintained similar search methods and criteria for inclusion that were used in previous bibliographies. We also continued the cumulative numbering of the items.

To help the reader locate relevant articles, we arranged items into a small number of subject categories. Generally, if fewer than three items fell into a specific subject category, they were relegated to a category labeled miscellaneous.
Evaluation of a Brief Homework Assignment Designed to Reduce Citation Problems
Authors: Schuetze Pamela
Published: October 2004

I evaluated a brief homework assignment designed to reduce citation problems in research-based term papers. Students in 2 developmental psychology classes received a brief presentation and handout defining plagiarism with tips on how to cite sources to avoid plagiarizing. In addition, students in 1 class completed 2 brief homework assignments in which they had to identify information in 1 page of text that required a citation. Results found that students who completed the homework assignments had fewer problems with citations, believed that they had a better understanding of situations that comprised plagiarism, and had more confidence in their ability to avoid plagiarism.
Using CHAINS, a QuickBASIC 4.5 Program, to Teach Single-Subject Experimentation with Humans
Authors: Dermer Marshall Lev
Published: October 2004

Students enrolled in a single-subject design course studied the repeated acquisition of response sequences by using CHAINS, a QuickBASIC 4.5 program, which runs in DOS or Windows. For about 2 months, students examined the learning of such sequences as a function of various treatments. Each week students graphed their data, discussed their research, modified their experiments, and then wrote American Psychological Association-style manuscripts. Students positively evaluated CHAINS and the instructional process. Suggestions for future instruction include distributing students' manuscripts the following semester so new students can replicate earlier work and using the alternating treatments design, which quickly permits comparing treatments.
Novel and Efficient Lewis Acids as Catalysts for Single-step Synthesis of Pyrano- and Furoquinolines
Authors: Das Biswanath , Reddy M Ravinder , Reddy V Saidi , Ramu R
Published: October 2004

Some Lewis acids such as ZrCl4, SnCl4, TiCl4, and PtCl4 have been found to be novel and highly efficient catalysts for one-pot coupling of the three components, anilines, aldehydes, and 3,4-dihydro-2H-pyran or 2,3-dihydrofuran to produce the corresponding pyrano- or furoqinolines in high yields and high diastereoselectivity.
Genetic influences on ovulation of primary oocytes in LT/Sv strain mice
Authors: Everett Clare A , Auchincloss Catherine A , Kaufman Matthew H , Abbott Catherine M , West John D
Published: October 2004

A high proportion of LT/Sv strain oocytes arrest in meiotic metaphase I (MI) and are ovulated as diploid primary oocytes rather than haploid secondary oocytes. (Mus musculus castaneus× LT/SvKau)F1 × LT/SvKau backcross females were analysed for the proportion of oocytes that arrested in MI and typed by PCR for a panel of microsatellite DNA sequences (simple sequence repeat polymorphisms) that differed between strain LT/SvKau andM. m. castaneus. This provided a whole genome scan of 86 genetic markers distributed over all 19 autosomes and the X chromosome, and revealed genetic linkage of the MI arrest phenotype to markers on chromosomes 1 and 9. Identification of these two chromosomal regions should facilitate the identification of genes involved in mammalian oocyte maturation and the control of meiosis.
A close correlation in the expression patterns of Af-6 and Usp9x in Sertoli and granulosa cells of mouse testis and ovary
Authors: Sato Takeshi , Kanai Yoshiakira , Noma Takashi , Kanai-Azuma Masami , Taya Shinichiro , Matsui Toshiyasu , Ishii Maki , Kawakami Hayato , Kurohmaru Masamichi , Kaibuchi Kozo , Wood Stephen A , Hayashi Yoshihiro
Published: October 2004

Usp9x, an X-linked deubiquitylating enzyme, is stage dependently expressed in the supporting cells (i.e. Sertoli cells and granulosa cells) and germ cells during mouse gametogenesis. Af-6, a cell junction protein, has been identified as a substrate of Usp9x, suggesting a possible association between Usp9x and Af-6 in spermatogenesis and oogenesis. In this study, we examined the expression pattern of Af-6 and Usp9x and their intracellular localization in testes and ovaries of mice treated with or without pregnant mare serum gonadotropin (PMSG), an FSH-like hormone. In both testes and ovaries, Af-6 expression was predominantly observed in supporting cells, as well as in steroidogenic cells, but not in any germ cells. In Sertoli cells, Af-6 was continuously expressed throughout postnatal and adult stages, where both Af-6 and Usp9x were enriched at the sites of Sertoli–Sertoli and Sertoli–spermatid junctions especially at stages XI–VI. In the granulosa cells, Af-6, as well as Usp9x, was highly expressed in primordial and primary follicles, but its expression rapidly decreased after the late-secondary follicle stage. Interestingly, in PMSG-treated mice, the expression levels of Af-6 and Usp9x were synchronously enhanced, slightly in Sertoli cells and strongly in granulosa cells of the late-secondary and Graafian follicles. Such closely correlated expression patterns between Af-6 and Usp9x clearly suggest that Af-6 may be deubiquitylated by Usp9x in both Sertoli and granulosa cells. It further suggests that the post-translational regulation of Af-6 by Usp9x may be one potential pathway to control the cell adhesion dynamics in mammalian gametogenesis.
Molecular cloning of porcine growth differentiation factor 9 (GDF-9) cDNA and its role in early folliculogenesis: direct ovarian injection of GDF-9 gene fragments promotes early folliculogenesis
Authors: Shimizu Takashi , Miyahayashi Yasunori , Yokoo Masaki , Hoshino Yumi , Sasada Hiroshi , Sato Eimei
Published: October 2004

Growth differentiation factor-9 (GDF-9) is a growth factor secreted by oocytes in growing ovarian follicles. To investigate the ovarian function of GDF-9 in pigs, we first cloned porcine GDF-9 complementary DNA (cDNA), and then injected its gene fragments into the ovary in gilts. Porcine GDF-9 has open reading frame (ORF) homologies of 81.4%, 84.6%, 84.2%, 72.7% and 72.6% with its human, bovine, ovine, rat and mouse counterparts respectively. Regarding the deduced amino-acid sequence of the mature protein, the corresponding homologies reach 92.1%, 97.8%, 97.0%, 89.6% and 88.1% respectively. To investigate the role of GDF-9 in early folliculogenesis, the ovaries of 2-month-old prepubertal gilts were injected with GDF-9 gene fragments. The injection of porcine GDF-9 gene fragments resulted in an increase in the number of primary, secondary and tertiary follicles, concomitant with a decrease in the number of primordial follicles. These results indicated that exogenous GDF-9 can promote early folliculogenesis in the porcine ovary, and that a technique for direct ovarian injection of GFD-9 gene fragments may contribute to a novel therapy for prevention and treatment of infertility associated with ovarian dysfunction.