bluuebunny/crossref_metadata_2025 huggingface dataset:
Pooling mRNA in microarray experiments and its effect on power
Authors: Zhang Wuyan , Carriquiry Alicia , Nettleton Dan , Dekkers Jack C.M.
Published: March 2007

Motivation: Microarrays can simultaneously measure the expression levels of many genes and are widely applied to study complex biological problems at the genetic level. To contain costs, instead of obtaining a microarray on each individual, mRNA from several subjects can be first pooled and then measured with a single array. mRNA pooling is also necessary when there is not enough mRNA from each subject. Several studies have investigated the impact of pooling mRNA on inferences about gene expression, but have typically modeled the process of pooling as if it occurred in some transformed scale. This assumption is unrealistic.

Results: We propose modeling the gene expression levels in a pool as a weighted average of mRNA expression of all individuals in the pool on the original measurement scale, where the weights correspond to individual sample contributions to the pool. Based on these improved statistical models, we develop the appropriate F statistics to test for differentially expressed genes. We present formulae to calculate the power of various statistical tests under different strategies for pooling mRNA and compare resulting power estimates to those that would be obtained by following the approach proposed by Kendziorski et al. (2003). We find that the Kendziorski estimate tends to exceed true power and that the estimate we propose, while somewhat conservative, is less biased. We argue that it is possible to design a study that includes mRNA pooling at a significantly reduced cost but with little loss of information.

Contact:  alicia@iastate.edu
The statistical energy analysis of coupled sets of oscillators
Authors: Mace B.R , Ji L
Published: March 2007

The paper concerns the statistical energy analysis (SEA) of two conservatively coupled oscillators, sets of oscillators and continuous subsystems under broadband excitation. The oscillator properties are assumed to be random and ensemble averages found. Account is taken of the correlation between the coupling parameters and the oscillator energies. For coupled sets of oscillators or continuous subsystems, it is assumed that the coupling power between a pair of oscillators is proportional to the difference of either their actual energies or their ‘blocked’ energies, and expressions for the ensemble averages and coupling loss factors (CLFs) are found. Various observations are made, some of which differ from those that are commonly assumed within SEA. The coupling power and CLF are governed by two parameters: the ‘strength of connection’ and the ‘strength of coupling’. The CLF is proportional to damping at low damping and independent of damping in the high damping, weak coupling limit. Equipartition of energy does not occur as damping tends to zero, except for the case of two oscillators that have identical natural frequencies. While attention is focused on spring-coupled oscillators, similar results hold for more general forms of conservative coupling. The examples of two spring-coupled rods and two spring-coupled plates are considered. Conventional SEA and the coupled oscillator results are in good agreement for weak coupling but diverge for strong coupling. For strong coupling and weak connection, the coupled oscillator results agree well with an exact wave analysis and Monte Carlo simulations.
Prey synchronize their vigilant behaviour with other group members
Authors: Pays Olivier , Renaud Pierre-Cyril , Loisel Patrice , Petit Maud , Gerard Jean-François , Jarman Peter J
Published: March 2007

It is generally assumed that an individual of a prey species can benefit from an increase in the number of its group's members by reducing its own investment in vigilance. But what behaviour should group members adopt in relation to both the risk of being preyed upon and the individual investment in vigilance? Most models assume that individuals scan independently of one another. It is generally argued that it is more profitable for each group member owing to the cost that coordination of individual scans in non-overlapping bouts of vigilance would require. We studied the relationships between both individual and collective vigilance and group size in Defassa waterbuck,
Kobus ellipsiprymnus defassa
, in a population living under a predation risk. Our results confirmed that the proportion of time an individual spent in vigilance decreased with group size. However, the time during which at least one individual in the group scanned the environment (collective vigilance) increased. Analyses showed that individuals neither coordinated their scanning in an asynchronous way nor scanned independently of one another. On the contrary, scanning and non-scanning bouts were synchronized between group members, producing waves of collective vigilance. We claim that these waves are triggered by allelomimetic effects i.e. they are a phenomenon produced by an individual copying its neighbour's behaviour.
A potential resolution to the lek paradox through indirect genetic effects
Authors: Miller Christine W , Moore Allen J
Published: March 2007

Females often prefer males with elaborate traits, even when they receive no direct benefits from their choice. In such situations, mate discrimination presumably has genetic advantages; selective females will produce offspring of higher genetic quality. Over time, persistent female preferences for elaborate secondary-sexual traits in males should erode genetic variance in these traits, eventually eliminating any benefit to the preferences. Yet, strong female preferences persist in many taxa. This puzzle is called the lek paradox and raises two primary questions: do females obtain genetic benefits for offspring by selecting males with elaborate secondary-sexual characteristics and, if so, how is the genetic variation in these male traits maintained? We suggest that indirect genetic effects may help to resolve the lek paradox. Maternal phenotypes, such as habitat selection behaviours and offspring provisioning, often influence the condition and the expression of secondary-sexual traits in sons. These maternal influences are commonly genetic based (i.e. they are indirect genetic effects). Females choosing mates with elaborate traits may receive ‘good genes’ for daughters in the form of effective maternal characteristics. Recognizing the significance of indirect genetic effects may be important to our understanding of the process and consequences of sexual selection.
Spreading free-riding snow sports represent a novel serious threat for wildlife
Authors: Arlettaz Raphaël , Patthey Patrick , Baltic Marjana , Leu Thomas , Schaub Michael , Palme Rupert , Jenni-Eiermann Susanne
Published: March 2007

Stress generated by humans on wildlife by continuous development of outdoor recreational activities is of increasing concern for biodiversity conservation. Human disturbance often adds to other negative impact factors affecting the dynamics of vulnerable populations. It is not known to which extent the rapidly spreading free-riding snow sports actually elicit detrimental stress (allostatic overload) upon wildlife, nor what the potential associated fitness and survival costs are. Using a non-invasive technique, we evaluated the physiological stress response induced by free-riding snow sports on a declining bird species of Alpine ecosystems. The results of a field experiment in which radiomonitored black grouse (
Tetrao tetrix
) were actively flushed from their snow burrows once a day during four consecutive days showed an increase in the concentration of faecal stress hormone (corticosterone) metabolites after disturbance. A large-scale comparative analysis across the southwestern Swiss Alps indicated that birds had higher levels of these metabolites in human-disturbed versus undisturbed habitats. Disturbance by snow sport free-riders appears to elevate stress, which potentially represents a new serious threat for wildlife. The fitness and survival costs of allostatic adjustments have yet to be estimated.
Anaphase Onset Before Complete DNA Replication with Intact Checkpoint Responses
Authors: Torres-Rosell Jordi , De Piccoli Giacomo , Cordon-Preciado Violeta , Farmer Sarah , Jarmuz Adam , Machin Felix , Pasero Philippe , Lisby Michael , Haber James E. , Aragón Luis
Published: March 2007

Cellular checkpoints prevent mitosis in the presence of stalled replication forks. Whether checkpoints also ensure the completion of DNA replication before mitosis is unknown. Here, we show that in yeast
smc5-smc6
mutants, which are related to cohesin and condensin, replication is delayed, most significantly at natural replication-impeding loci like the ribosomal DNA gene cluster. In the absence of Smc5-Smc6, chromosome nondisjunction occurs as a consequence of mitotic entry with unfinished replication despite intact checkpoint responses. Eliminating processes that obstruct replication fork progression restores the temporal uncoupling between replication and segregation in
smc5-smc6
mutants. We propose that the completion of replication is not under the surveillance of known checkpoints.
Dynamics of Replication-Independent Histone Turnover in Budding Yeast
Authors: Dion Michael F. , Kaplan Tommy , Kim Minkyu , Buratowski Stephen , Friedman Nir , Rando Oliver J.
Published: March 2007

Chromatin plays roles in processes governed by different time scales. To assay the dynamic behavior of chromatin in living cells, we used genomic tiling arrays to measure histone H3 turnover in G1-arrested
Saccharomyces cerevisiae
at single-nucleosome resolution over 4% of the genome, and at lower (∼265 base pair) resolution over the entire genome. We find that nucleosomes at promoters are replaced more rapidly than at coding regions and that replacement rates over coding regions correlate with polymerase density. In addition, rapid histone turnover is found at known chromatin boundary elements. These results suggest that rapid histone turnover serves to functionally separate chromatin domains and prevent spread of histone states.
Multifunctional Encoded Particles for High-Throughput Biomolecule Analysis
Authors: Pregibon Daniel C. , Toner Mehmet , Doyle Patrick S.
Published: March 2007

High-throughput screening for genetic analysis, combinatorial chemistry, and clinical diagnostics benefits from multiplexing, which allows for the simultaneous assay of several analytes but necessitates an encoding scheme for molecular identification. Current approaches for multiplexed analysis involve complicated or expensive processes for encoding, functionalizing, or decoding active substrates (particles or surfaces) and often yield a very limited number of analyte-specific codes. We present a method based on continuous-flow lithography that combines particle synthesis and encoding and probe incorporation into a single process to generate multifunctional particles bearing over a million unique codes. By using such particles, we demonstrate a multiplexed, single-fluorescence detection of DNA oligomers with encoded particle libraries that can be scanned rapidly in a flow-through microfluidic channel. Furthermore, we demonstrate with high specificity the same multiplexed detection using individual multiprobe particles.
Structural Insight into the Transglycosylation Step of Bacterial Cell-Wall Biosynthesis
Authors: Lovering Andrew L. , de Castro Liza H. , Lim Daniel , Strynadka Natalie C. J.
Published: March 2007

Peptidoglycan glycosyltransferases (GTs) catalyze the polymerization step of cell-wall biosynthesis, are membrane-bound, and are highly conserved across all bacteria. Long considered the “holy grail” of antibiotic research, they represent an essential and easily accessible drug target for antibiotic-resistant bacteria, including methicillin-resistant
Staphylococcus aureus
. We have determined the 2.8 angstrom structure of a bifunctional cell-wall cross-linking enzyme, including its transpeptidase and GT domains, both unliganded and complexed with the substrate analog moenomycin. The peptidoglycan GTs adopt a fold distinct from those of other GT classes. The structures give insight into critical features of the catalytic mechanism and key interactions required for enzyme inhibition.
Humoral Immune Response after Primary Rubella Virus Infection and after Vaccination
Authors: Vauloup-Fellous C. , Grangeot-Keros L.
Published: March 2007

We measured rubella virus immunoglobulin G (IgG) and IgM levels, as well as IgG avidity indexes, in serum samples taken before or after 6 months either after infection or after vaccination. The results obtained indicate that humoral immune responses are different after primary infection and after vaccination. This may have important consequences on the serological diagnosis of rubella virus infection.
Histoplasmosis-Associated Cross-Reactivity in the BioRad Platelia
Aspergillus
Enzyme Immunoassay
Authors: Wheat L. Joseph , Hackett Emily , Durkin Michelle , Connolly Patricia , Petraitiene Ruta , Walsh Thomas J. , Knox Kenneth , Hage Chadi
Published: March 2007

We observed false-positive results in the Platelia
Aspergillus
enzyme-linked immunoassay (EIA) for specimens from patients with histoplasmosis and mice with experimental infection. Platelia
Aspergillus
EIA-positive specimens were negative in the second-generation
Histoplasma
antigen EIA. Care must be taken to exclude histoplasmosis for patients with positive Platelia
Aspergillus
EIA results.
Use of Serum or Buffer-Changed EDTA-Plasma in a Rapid, Inexpensive, and Easy-To-Perform Hemolytic Complement Assay for Differential Diagnosis of Systemic Lupus Erythematosus and Monitoring of Patients with the Disease
Authors: Ekdahl Kristina N. , Norberg Dan , Bengtsson Anders A. , Sturfelt Gunnar , Nilsson Ulf R. , Nilsson Bo
Published: March 2007

We previously described a simplified quantitative hemolytic assay for classical pathway (CP) hemolytic function in serum that has been shown to correlate with the 50% hemolytic complement (CH50) assay. In the present study, we used this assay to compare CP functions; plasma levels of C3, C4, and C3dg; and ratios of C3dg to C3 in healthy individuals and patients with systemic lupus erythematosus (SLE) or rheumatoid arthritis (RA) with different degrees of complement activation. A significant depression in CP function and levels of C4 and C3 and increased C3dg levels and C3dg/C3 ratios were observed in the SLE patients. In patients with RA, CP function was normal, whereas C3, C4, and C3dg levels and the C3dg/C3 ratio were elevated. The SLE results are compatible with systemic complement consumption, whereas the RA data suggest an acute-phase reaction with a normal C3 catabolic rate. To facilitate the handling of patient samples, we also developed a method to restore the hemolytic function of EDTA-plasma by transferring it to Veronal-buffered saline containing the thrombin inhibitor lepirudin. This process inhibits coagulation and enables complement activation, allowing a longer time lag between sample harvesting and testing. These results, combined with previous correlation studies, suggest that the CP hemolytic assay can effectively replace the CH50assay for routine SLE differential diagnosis and monitoring of disease activity.
Genotypes and Related Factors Reflecting Macrolide Resistance in Pneumococcal Pneumonia Infections in Japan
Authors: Isozumi Rie , Ito Yutaka , Ishida Tadashi , Osawa Makoto , Hirai Toyohiro , Ito Isao , Maniwa Ko , Hayashi Michio , Kagioka Hitoshi , Hirabayashi Masataka , Onari Koichi , Tomioka Hiromi , Tomii Keisuke , Gohma Iwao , Imai Seiichiro , Takakura Shunji , Iinuma Yoshitsugu , Ichiyama Satoshi , Mishima Michiaki
Published: March 2007

Although macrolide-resistant
Streptococcus pneumoniae
strains possessing either the
ermB
or
mefA
gene are very common in Japan, clinical and microbial factors in community-acquired pneumonia (CAP) caused by different macrolide resistance genotypes have not been evaluated. A multicenter study of CAP caused by
S. pneumoniae
was performed in Japan from 2003 to 2005. A total of 156 isolates were tested for susceptibility to antibiotics correlated with
ermB
and
mefA
genotyping. Independent relationships between tested variables and possession of either the
ermB
or the
mefA
gene were identified. Of 156 isolates, 127 (81.4%) were resistant to erythromycin, with the following distribution of resistance genotypes:
ermB
alone (50.0%),
mefA
alone (23.7%), and both
ermB
and
mefA
(7.1%). All isolates were susceptible to telithromycin. By multivariate analysis, oxygen saturation of <90% on admission increased the risk for
ermB
-positive pneumococcal pneumonia (odds ratio [OR] = 11.1; 95% confidence interval [CI] = 1.30 to 95.0;
P
= 0.03), but there were no associations with
mefA
or with
ermB mefA
positivity. Penicillin nonsusceptibility was associated with
mefA
-positive and with
ermB
- and
mefA
-positive isolates (OR = 14.2; 95% CI = 4.27 to 46.9;
P
< 0.0001 and
P
< 0.0001, respectively) but not with
ermB
-positive isolates. The overall patient mortality was 5.1%. Mortality, the duration of hospitalization, and the resolution of several clinical markers were not associated with the different erythromycin resistance genotypes. In Japan,
S. pneumoniae
with erythromycin resistance or possession of
ermB
,
mefA
, or both genes was highly prevalent in patients with CAP. The risk factors for
ermB
-positive,
mefA
-positive, and double
ermB
-
mefA
-positive pneumococcal pneumonia were different, but the clinical outcomes did not differ.
Clostridium glycolicum
Bacteremia in a Bone Marrow Transplant Patient
Authors: Elsayed Sameer , Zhang Kunyan
Published: March 2007

We describe a case of
Clostridium glycolicum
bacteremia and septic shock in an adult woman with a recent bone marrow transplant for relapsed Hodgkin's disease. The bacterium was identified by 16S rRNA gene sequencing. This is the first published report of the recovery of this organism from human clinical material.
Human Cytomegalovirus Downregulates Expression of Receptors for Platelet-Derived Growth Factor by Smooth Muscle Cells
Authors: Gredmark Sara , Strååt Klas , Homman-Loudiyi Mohammed , Kannisto Katja , Söderberg-Nauclér Cecilia
Published: March 2007

Infection by human cytomegalovirus (HCMV) is associated with the development of vascular diseases and may cause severe brain damage in infected fetuses. Platelet-derived growth factor receptors alpha and beta (PDGFR-α and -β) control important cellular processes associated with atherosclerosis and fetal development. In the present investigation, our goal was to determine whether infection by HCMV can influence the expression of PDGFR-α and -β in human smooth muscle cells (SMCs). In connection with HCMV infection in vitro the levels of PDGFR-α and -β at the cell surface and in the total cellular protein of SMCs were reduced in parallel with decreases in the levels of the corresponding mRNAs. These effects were dependent on immediate-early (IE) or early (E) HCMV gene products, since inhibition of late genes did not prevent HCMV from affecting the expression of PDGFR-α and -β. The downregulation of PDGFR caused by HCMV was dose dependent. Furthermore, confocal microscopy revealed that the localization of PDGFR-β was altered in HCMV-infected cells, in which this protein colocalized with proteins associated with endosomes (Rab4 and -5) and lysosomes (Lamp1 and -2), indicating entrance into pathways for protein degradation. Altogether these observations indicate that an IE and/or E HCMV protein(s) downregulates the expression of PDGFR-α and -β in SMCs. This phenomenon may disrupt cellular processes of importance in connection with cellular differentiation, migration, and/or proliferation. These observations may explain why congenital infection with HCMV can cause fetal brain damage.
Antiviral Effects of Antisense Morpholino Oligomers in Murine Coronavirus Infection Models
Authors: Burrer Renaud , Neuman Benjamin W. , Ting Joey P. C. , Stein David A. , Moulton Hong M. , Iversen Patrick L. , Kuhn Peter , Buchmeier Michael J.
Published: March 2007

The recent emergence of novel pathogenic human and animal coronaviruses has highlighted the need for antiviral therapies that are effective against a spectrum of these viruses. We have used several strains of murine hepatitis virus (MHV) in cell culture and in vivo in mouse models to investigate the antiviral characteristics of peptide-conjugated antisense phosphorodiamidate morpholino oligomers (P-PMOs). Ten P-PMOs directed against various target sites in the viral genome were tested in cell culture, and one of these (5TERM), which was complementary to the 5′ terminus of the genomic RNA, was effective against six strains of MHV. Further studies were carried out with various arginine-rich peptides conjugated to the 5TERM PMO sequence in order to evaluate efficacy and toxicity and thereby select candidates for in vivo testing. In uninfected mice, prolonged P-PMO treatment did not result in weight loss or detectable histopathologic changes. 5TERM P-PMO treatment reduced viral titers in target organs and protected mice against virus-induced tissue damage. Prophylactic 5TERM P-PMO treatment decreased the amount of weight loss associated with infection under most experimental conditions. Treatment also prolonged survival in two lethal challenge models. In some cases of high-dose viral inoculation followed by delayed treatment, 5TERM P-PMO treatment was not protective and increased morbidity in the treated group, suggesting that P-PMO may cause toxic effects in diseased mice that were not apparent in the uninfected animals. However, the strong antiviral effect observed suggests that with further development, P-PMO may provide an effective therapeutic approach against a broad range of coronavirus infections.
Artificial MicroRNA-Mediated Virus Resistance in Plants
Authors: Qu Jing , Ye Jian , Fang Rongxiang
Published: March 2007

RNA silencing in plants is a natural defense system against foreign genetic elements including viruses. This natural antiviral mechanism has been adopted to develop virus-resistant plants through expression of virus-derived double-stranded RNAs or hairpin RNAs, which in turn are processed into small interfering RNAs (siRNAs) by the host's RNA silencing machinery. While these virus-specific siRNAs were shown to be a hallmark of the acquired virus resistance, the functionality of another set of the RNA silencing-related small RNAs, microRNAs (miRNAs), in engineering plant virus resistance has not been extensively explored. Here we show that expression of an artificial miRNA, targeting sequences encoding the silencing suppressor 2b of
Cucumber mosaic virus
(CMV), can efficiently inhibit 2b gene expression and protein suppressor function in transient expression assays and confer on transgenic tobacco plants effective resistance to CMV infection. Moreover, the resistance level conferred by the transgenic miRNA is well correlated to the miRNA expression level. Comparison of the anti-CMV effect of the artificial miRNA to that of a short hairpin RNA-derived small RNA targeting the same site revealed that the miRNA approach is superior to the approach using short hairpin RNA both in transient assays and in transgenic plants. Together, our data demonstrate that expression of virus-specific artificial miRNAs is an effective and predictable new approach to engineering resistance to CMV and, possibly, to other plant viruses as well.
Preferential Selection of Human T-Cell Leukemia Virus Type 1 Provirus Lacking the 5′ Long Terminal Repeat during Oncogenesis
Authors: Miyazaki Maki , Yasunaga Jun-Ichirou , Taniguchi Yuko , Tamiya Sadahiro , Nakahata Tatsutoshi , Matsuoka Masao
Published: March 2007

In adult T-cell leukemia (ATL) cells, a defective human T-cell leukemia virus type 1 (HTLV-1) provirus lacking the 5′ long terminal repeat (LTR), designated type 2 defective provirus, is frequently observed. To investigate the mechanism underlying the generation of the defective provirus, we sequenced HTLV-1 provirus integration sites from cases of ATL. In HTLV-1 proviruses retaining both LTRs, 6-bp repeat sequences were adjacent to the 5′ and 3′ LTRs. In 8 of 12 cases with type 2 defective provirus, 6-bp repeats were identified at both ends. In five of these cases, a short repeat was bound to CA dinucleotides of thepolandenvgenes at the 5′ end, suggesting that these type 2 defective proviruses were formed before integration. In four cases lacking the 6-bp repeat, short (6- to 26-bp) deletions in the host genome were identified, indicating that these defective proviruses were generated after integration. Quantification indicated frequencies of type 2 defective provirus of less than 3.9% for two carriers, which are much lower than those seen for ATL cases (27.8%). In type 2 defective proviruses, the second exons of thetax,rex, andp30genes were frequently deleted, leaving Tax unable to activate NF-κB and CREB pathways. TheHTLV-1 bZIP factorgene, located on the minus strand, is expressed in ATL cells with this defective provirus, and its coding sequences are intact, suggesting its significance in oncogenesis.
Fitness Declines in
Tobacco Etch Virus
upon Serial Bottleneck Transfers
Authors: de la Iglesia Francisca , Elena Santiago F.
Published: March 2007

It has been well established that populations of RNA viruses transmitted throughout serial bottlenecks suffer from significant fitness declines as a consequence of the accumulation of deleterious mutations by the onset of Muller's ratchet. Bottlenecks are unavoidably linked to different steps of the infectious cycle of most plant RNA viruses, such as vector-mediated transmissions and systemic colonization of new leaves. Here we report evidence for fitness declines by the accumulation of deleterious mutations in the potyvirus
Tobacco etch virus
(TEV). TEV was inoculated into the nonsystemic host
Chenopodium quinoa
, and local lesions were isolated and used to initiate 20 independent mutation accumulation lineages. Weekly, a random lesion from each lineage was isolated and used to inoculate the next set of plants. At each transfer, the Malthusian growth rate was estimated. After 11 consecutive transfers, all lineages suffered significant fitness losses, and one even became extinct. The average rate of fitness decline was 5% per day. The average pattern of fitness decline was consistent with antagonistic epistasis between deleterious mutations, as postulated for antiredundant genomes. Temporal fitness fluctuations were not explained by random noise but reflected more complex underlying processes related to emergence and self-organization phenomena.
Multifunctional Human Immunodeficiency Virus (HIV) Gag-Specific CD8+T-Cell Responses in Rectal Mucosa and Peripheral Blood Mononuclear Cells during Chronic HIV Type 1 Infection
Authors: Critchfield J. William , Lemongello Donna , Walker Digna H. , Garcia Juan C. , Asmuth David M. , Pollard Richard B. , Shacklett Barbara L.
Published: March 2007

The intestinal tract is a lymphocyte-rich site that undergoes severe depletion of memory CD4+T cells within days of simian immunodeficiency virus or human immunodeficiency virus type 1 (HIV-1) infection. An ensuing influx of virus-specific CD8+T cells, which persist throughout the chronic phase of infection, has also been documented in the gastrointestinal tract. However, little is known of the functionality of these effector cells or their relationship to the disease course. In this study, we measured CD8+T-cell responses to HIV-1 peptides in paired rectal and blood samples from chronically infected patients. In both blood and rectum, there was an immunodominant CD8+T-cell response to HIV Gag compared to Pol and Env (P< 0.01). In contrast, cytomegalovirus pp65 peptides elicited gamma interferon (IFN-γ) secretion strongly in peripheral blood mononuclear cells (PBMC) but weakly in rectal CD8+T cells (P= 0.015). Upon stimulation with HIV peptides, CD8+T cells from both sites were capable of mounting complex responses including degranulation (CD107 expression) and IFN-γ and tumor necrosis factor alpha (TNF-α) production. In rectal tissue, CD107 release was frequently coupled with production of IFN-γ or TNF-α. In patients not on antiretroviral therapy, the magnitude of Gag-specific responses, as a percentage of CD8+T cells, was greater in the rectal mucosa than in PBMC (P= 0.054); however, the breakdown of responding cells into specific functional categories was similar in both sites. These findings demonstrate that rectal CD8+T cells are capable of robust and varied HIV-1-specific responses and therefore likely play an active role in eliminating infected cells during chronic infection.
Increased prevalence of gastrointestinal symptoms in patients with allergic disease
Authors: Powell Nick , Huntley Benedict , Beech Thomas , Knight William , Knight Hannah , Corrigan Christopher J
Published: March 2007

Background

Children with allergic diseases such as asthma and atopic dermatitis experience increased gastrointestinal symptoms. Further, physiological and histological abnormalities of the gastrointestinal tract in patients with allergic diseases have been reported. It is not certain whether adult patients experience increased gastrointestinal symptoms.

Methods

A retrospective, case–control study of 7235 adult (⩾20 years old) primary care patients was conducted. A general practitioner diagnosis of irritable bowel syndrome was used to serve as a marker of lower gastrointestinal symptoms. The prevalence of lower gastrointestinal symptoms was calculated in patients with asthma or allergic rhinitis and compared with that in patients with other chronic diseases (insulin-dependent diabetes mellitus, osteoarthritis and rheumatoid arthritis) and with the remaining population.

Results

Gastrointestinal symptoms were significantly more common in patients with asthma (9.9%) as compared with patients with chronic diseases (4.9%; odds ratio (OR) 2.13, 95% confidence interval (CI) 1.39 to 2.56; p<0.002) or the remaining non-asthmatic population (5.5%; OR 1.89, 95% CI 1.39 to 2.56; p<0.001). Gastrointestinal symptoms were also significantly more common in patients with allergic rhinitis (7.9%) as compared with patients with chronic diseases (4.9%; OR 1.66, 95% CI 1.02 to 2.7; p<0.05) and the remaining population (5.5%; OR 1.47, 95% CI 1.04 to 2.1; p<0.02). This phenomenon was independent of age, sex and inhaled asthma therapy in the case of patients with asthma.

Conclusions

Our findings support the hypothesis that lower gastrointestinal symptoms are more common in patients with allergic diseases such as asthma and allergic rhinitis.
Patent foramen ovale and atrial septal aneurysm in cryptogenic stroke
Authors: Ghosh Sujoy , Ghosh Arjun Kumar , Ghosh Sandip Kumar
Published: March 2007

Up to 40% of acute ischaemic strokes in young adults are cryptogenic in nature, that is, no cause is determined. In more than half of these patients, patent foramen ovale (PFO) is seen along with an increased incidence of atrial septal aneurysm. The commonest method of investigation is echocardiography (preferably transoesophageal echocardiography). On the basis of available evidence, low risk patients are treated with antiplatelet agents and high risk patients with warfarin. There are inconclusive data on the efficacy of PFO closure to prevent stroke recurrence. However, if there is recurrent stroke or intolerance to medical therapy, percutaneous closure is carried out.
Simvastatin-induced bilateral leg compartment syndrome and myonecrosis associated with hypothyroidism
Authors: Ramdass Michael J , Singh Gurpreet , Andrews Brian
Published: March 2007

A 54-year-old hypothyroid male taking thyroxine and simvastatin presented with bilateral leg compartment syndrome and myonecrosis. Urgent fasciotomies were performed and the patient made an uneventful recovery with the withdrawal of simvastatin. It is likely that this complication will be seen more often with the increased worldwide use of this drug and its approval for all arteriopathic patients.
Developing your teaching style: increasing effectiveness in healthcare teaching
Authors: Mohanna Kay , Chambers Ruth , Wall David
Published: March 2007

This paper reports the first stage in the development of a tool, the Six Staffordshire Teaching Styles Questionnaire, designed to raise awareness in teachers about their teaching style. Effective teachers are adaptable and flexible in providing variety in their teaching activities, aiming to match their manipulation of the teaching and learning environment to the needs of the learner, but teachers should also know what type of activities they are most effective at delivering. Just as mismatched learning styles can cause dysfunctional learning situations, one of the causes of stress in teachers can be an incongruency between the type of activities they believe are effective, or feel they are good at carrying out, and external expectations of “good teaching”.
Liquefaction potential of silts from CPTu
Authors: Shuttle Dawn A , Cunning John
Published: March 2007

Silt tailings (slimes) are difficult materials to test in that, like sands, it is extremely difficult to obtain undisturbed samples and subsequently re-establish them in a triaxial cell for element testing in a laboratory in anything approaching their in situ condition. Evaluation of silt tailing behaviour has to depend on in situ tests, and the piezocone (CPTu) in particular. However, CPTs in silt generate substantial excess pore pressure and there is no established methodology to evaluate the measured responses in terms of soil properties, as drained sand-based CPT interpretation is inapplicable. A case history of particularly loose silt tailings is reported in which the National Center for Earthquake Engineering Research (NCEER) liquefaction assessment method would lead to uncertainty in the liquefaction potential. However, the extremely high CPTu excess pore pressure ratio, Bq, and low dimensionless CPT resistance, Qp, at this site indicates liquefaction is likely occurring during pushing of the CPT. Detailed finite element simulations of the CPT using a critical state model provided an effective stress framework to evaluate the in situ state parameter of the silt from the measured CPT data. This framework shows that the group of dimensionless CPT variables Q(1 – Bq) + 1 is fundamental for the evaluation of undrained response during CPT sounding. And, despite the high silt content, the interpretation indicates that the tailings are indeed liquefiable.Key words: liquefaction, CPT, silt, finite element, critical state.
Measurement of unsaturated soil – geomembrane interface shear-strength parameters
Authors: Sharma J S , Fleming I R , Jogi M B
Published: March 2007

Laboratory tests of soil–geomembrane interface shear strength are typically carried out with no provision for the measurement of pore pressures at the soil–geomembrane interface. This paper describes a series of soil–geomembrane interface shear tests carried out with continuous measurement of suction close to the interface during the shearing process. The tests were conducted using a modified direct shear box with a miniature pore-pressure transducer installed adjacent to the surface of the geomembrane. Results of the interface shear tests conducted using this method show that it is quite effective in evaluating shear behaviour at the interface between a geomembrane and an unsaturated soil at low matric suction values. The results suggest that soil suction contributes to shearing resistance at low normal stress values. At higher normal stress values, the interface shear behaviour appears to be governed only by the magnitude of total normal stress.Key words: geomembrane, interface shear strength, suction, direct shear test, pore-pressure transducer.
USING (4+1) SPLIT AND ENERGY CONDITIONS TO STUDY THE INDUCED MATTER IN 5D RICCI-FLAT COSMOLOGY
Authors: PING YONGLI , LIU HONGYA , XU LIXIN
Published: March 2007

We use (4+1) split to derive the 4D induced energy density ρ and pressure p of the 5D Ricci-flat cosmological solutions which are characterized by having a bounce instead of a bang. The solutions contain two arbitrary functions of time t and, therefore, are mathematically rich in giving various cosmological models. By using four known energy conditions (null, weak, strong, and dominant) to pick out and study physically meaningful solutions, we find that the 4D part of the 5D solutions asymptotically approaches to the standard 4D FRW models and the expansion of the universe is decelerating for normal induced matter for which all the four energy conditions are satisfied. We also find that quintessence might be normal or abnormal, depending on the parameter w of the equation of state. If -1 ≤ w < -1/3, the expansion of the universe is accelerating and the quintessence is abnormal because the strong energy condition is violated while other three are satisfied. For phantom, all the four energy conditions are violated. Before the bounce, all the four energy conditions are violated, implying that the cosmic matter before the bounce could be explained as a phantom that has a large negative pressure and makes the universe bouncing. In the early times after the bounce, the dominant energy condition is violated, while the other three are satisfied, and so the cosmic matter could be explained as a super-luminal acoustic matter.
MODELS OF DIFFUSION OF GALACTIC COSMIC RAYS FROM SUPERBUBBLES
Authors: ZANINETTI LORENZO
Published: March 2007

Superbubbles are shells in the interstellar medium produced by the simultaneous explosions of many supernova remnants. The solutions of the mathematical diffusion and of the Fourier expansion in 1D, 2D and 3D were deduced in order to describe the diffusion of nucleons from such structures. The mean number of visits in the the case of the Levy flights in 1D was computed with a Monte Carlo simulation. The diffusion of cosmic rays has its physical explanation in the relativistic Larmor gyro-radius which is energy dependent. The mathematical solution of the diffusion equation in 1D with variable diffusion coefficient was computed. Variable diffusion coefficient means magnetic field variable with the altitude from the Galactic plane. The analytical solutions allow us to calibrate the code that describes the Monte Carlo diffusion. The maximum energy that can be extracted from the superbubbles is deduced. The concentration of cosmic rays is a function of the distance from the nearest superbubble and the selected energy. The interaction of the cosmic rays on the target material allows us to trace the theoretical map of the diffuse Galactic continuum gamma-rays. The streaming of the cosmic rays from the Gould Belts that contains the sun at its internal was described by a Monte Carlo simulation. Ten new formulas are derived.
Upregulation of γ-glutamate-cysteine ligase as part of the long-term adaptation process to iron accumulation in neuronal SH-SY5Y cells
Authors: Aguirre Pabla , Valdés Pamela , Aracena-Parks Paula , Tapia Victoria , Núñez Marco T.
Published: March 2007

Reactive iron is an important prooxidant factor, whereas GSH is a crucial component of a long-term adaptive system that allows cells to function during extended periods of high oxidative stress. In this work, the adaptive response of the GSH system to prolonged iron loads was characterized in human dopaminergic SH-SY5Y neuroblastoma cells. After the initial death of a substantial portion of the cell population, the surviving cells increased their GSH content by up to fivefold. This increase was traced to increased expression of the catalytic and modulatory subunits of γ-glutamate-cysteine ligase. Under conditions of high iron load, cells maintained a low GSSG content through two mechanisms: 1) GSSG reductase-mediated recycling of GSSG to GSH and 2) multidrug resistant protein 1-mediated extrusion of GSSG. Increased GSH synthesis and low GSSG levels contributed to recover the cell reduction potential from −290 mV at the time of cell death to about −320 mV. These results highlight the fundamental role of GSH homeostasis in the antioxidant response to cellular iron accumulation and provide novel insights into the adaptive mechanisms of neurons subjected to increased iron loads, such as those observed in Parkinson's disease.
Microvascular and capillary perfusion following glycocalyx degradation
Authors: Cabrales Pedro , Vázquez Beatriz Y. Salazar , Tsai Amy G. , Intaglietta Marcos
Published: March 2007

Systemic parameters and microvascular and capillary hemodynamics were studied in the hamster window chamber model before and after hyaluronan degradation by intravenous injection of Streptomyces hyaluronidase (100 units, 40–50 U/ml plasma). Glycocalyx permeation was estimated using fluorescent markers of different molecular size (40, 70, and 2,000 kDa), and electrical charge. Systemic parameters (blood pressure, heart rate, blood gases) and microhemodynamics (vascular tone, velocity, and blood flow) remained statistically unchanged after injection of hyaluronidase, compared with inactivated hyaluronidase. Conversely, capillary hemodynamics were drastically affected. Functional capillary density, the capillaries perfused with red blood cells (RBCs), decreased by 35%, capillary Hct of the remaining functional capillaries increased from 16 to 27%, and penetration of 70-kDa fluorescent marker increased. Furthermore, plasma-only perfused capillaries statistically increased 30 min after hyaluronidase. The decrease in functional capillary density accounted for an increased RBC flux in the remainder of the capillaries, since the same number of RBCs had to traverse a reduced number of capillaries. Flux balances showed a reduction from baseline of 11% for the RBC flux and 20% for the plasma flux after treatment. These discrepancies are within the margin of error of the techniques used and could be explained by accounting for RBC over-velocity compared with plasma. These findings suggest that the decrease in the glycocalyx leads to capillary perfusion impairments.
A Novel Effect of Cochlear Efferents: In Vivo Response Enhancement Does Not Require α9 Cholinergic Receptors
Authors: Maison Stéphane F. , Vetter Douglas E. , Liberman M. Charles
Published: March 2007

Outer hair cells in the mammalian cochlea receive a cholinergic efferent innervation that constitutes the effector arm of a sound-evoked negative feedback loop. The well-studied suppressive effects of acetylcholine (ACh) release from efferent terminals are mediated by α9/α10 ACh receptors and are potently blocked by strychnine. Here, we report a novel, efferent-mediated enhancement of cochlear sound-evoked neural responses and otoacoustic emissions in mice. In controls, a slow enhancement of response amplitude to supranormal levels appears after recovery from the classic suppressive effects seen during a 70-s epoch of efferent shocks. The magnitude of post-shock enhancement can be as great as 10 dB and tends to be greater for high-frequency acoustic stimuli. Systemic strychnine at 10 mg/kg eliminates efferent-induced suppression, revealing a purely enhancing effect of efferent shocks, which peaks within 5 s after efferent-stimulation onset, maintains a constant level through the stimulation epoch, and slowly decays back to baseline with a time constant of ∼100 s. In mice with targeted deletion of the α9 ACh receptor subunit, efferent-evoked effects resemble those in wild types with strychnine blockade, further showing that this novel efferent effect is fundamentally different from all cholinergic effects previously reported.
Visual Adaptation: Physiology, Mechanisms, and Functional Benefits
Authors: Kohn Adam
Published: March 2007

Recent sensory experience affects both perception and the response properties of visual neurons. Here I review a rapid form of experience-dependent plasticity that follows adaptation, the presentation of a particular stimulus or ensemble of stimuli for periods ranging from tens of milliseconds to minutes. Adaptation has a rich history in psychophysics, where it is often used as a tool for dissecting the perceptual mechanisms of vision. Although we know comparatively little about the neurophysiological effects of adaptation, work in the last decade has revealed a rich repertoire of effects. This review focuses on this recent physiological work, the cellular and biophysical mechanisms that may underlie the observed effects, and the functional benefit that they may afford. I conclude with a brief discussion of some important open questions in the field.
Riluzole-Induced Oscillations in Spinal Networks
Authors: Yvon Cédric , Czarnecki Antonny , Streit Jürg
Published: March 2007

We previously showed in dissociated cultures of fetal rat spinal cord that disinhibition-induced bursting is based on intrinsic spiking, network recruitment, and a network refractory period after the bursts. A persistent sodium current ( INaP) underlies intrinsic spiking, which, by recurrent excitation, generates the bursting activity. Although full blockade of INaPwith riluzole disrupts such bursting, the present study shows that partial blockade of INaPwith low doses of riluzole maintains bursting activity with unchanged burst rate and burst duration. More important, low doses of riluzole turned bursts composed of persistent activity into bursts composed of oscillatory activity at around 5 Hz. In a search for the mechanisms underlying the generation of such intraburst oscillations, we found that activity-dependent synaptic depression was not changed with low doses of riluzole. On the other hand, low doses of riluzole strongly increased spike-frequency adaptation and led to early depolarization block when bursts were simulated by injecting long current pulses into single neurons in the absence of fast synaptic transmission. Phenytoin is another INaPblocker. When applied in doses that reduced intrinsic activity by 80–90%, as did low doses of riluzole, it had no effect either on spike-frequency adaptation or on depolarization block. Nor did phenytoin induce intraburst oscillations after disinhibition. A theoretical model incorporating a depolarization block mechanism could reproduce the generation of intraburst oscillations at the network level. From these findings we conclude that riluzole-induced intraburst oscillations are a network-driven phenomenon whose major accommodation mechanism is depolarization block arising from strong sodium channel inactivation.
Thermal Bending of the Rotor Due to Rotor‐to‐Stator Rub
Authors: Goldman Paul , Muszynska Agnes , Bently Donald E.
Published: March 2007

The rotor thermal bending due to the rotor‐to‐stator rubbing can lead to one of three types of observed rotor lateral motion: (1) spiral with increasing amplitude, (2) oscillating between rub]no‐rub conditions, and (3) asymptotical approach to the rotor limit cycle. Based on the machinery observations, it is assumed in the analytical part of the paper that the speed scale of transient thermal effects is considerably lower than that of rotor vibrations, and that the thermal effect reflects only on the rotor steady‐state vibrational response. This response would change due to thermally induced bow of the rotor, which can be considered to slowly vary in timefor the purpose of rotor vibration calculations. Thus uncoupled from the thermal problem, the rotor vibration is analyzed. The major consideration is given to the rotor which experiences intermittent contact with the stator, due to predetermined thermal bow, unbalance force, and radial constant load force. In the case of inelastic impact, it causes an on/off, step‐change in the stiffness of the system. Using a specially developed variable transformation for the system with discontinuities, and averaging technique the resonance regimes of motion are obtained. These regimes are used to calculate the heat generated during contact stage, as a function of thermal bow modal parameters, which is used as a boundary condition for the rotor heat transfer problem. The latter is treated as quasi‐static, which reduces the problem to an ordinary differential equation for the thermal bow vector. It is investigated from the stability standpoint.