bluuebunny/crossref_metadata_2025_split huggingface dataset:
A suboptimal 5' splice site downstream of HIV-1 splice site A1 is required for unspliced viral mRNA accumulation and efficient virus replication
Authors: Madsen Joshua M , Stoltzfus C Martin 
Published: February 2006

Abstract

Background
Inefficient alternative splicing of the human immunodeficiency virus type 1(HIV-1) primary RNA transcript results in greater than half of all viral mRNA remaining unspliced. Regulation of HIV-1 alternative splicing occurs through the presence of suboptimal viral 5' and 3' splice sites (5' and 3'ss), which are positively regulated by exonic splicing enhancers (ESE) and negatively regulated by exonic splicing silencers (ESS) and intronic splicing silencers (ISS). We previously showed that splicing at HIV-1 3'ss A2 is repressed by ESSV and enhanced by the downstream 5'ss D3 signal. Disruption of ESSV results in increased vpr mRNA accumulation and exon 3 inclusion, decreased accumulation of unspliced viral mRNA, and decreased virus production.

Results
Here we show that optimization of the 5'ss D2 signal results in increased splicing at the upstream 3'ss A1, increased inclusion of exon 2 into viral mRNA, decreased accumulation of unspliced viral mRNA, and decreased virus production. Virus production from the 5'ss D2 and ESSV mutants was rescued by transient expression of HIV-1 Gag and Pol. We further show that the increased inclusion of either exon 2 or 3 does not significantly affect the stability of viral mRNA but does result in an increase and decrease, respectively, in HIV-1 mRNA levels. The changes in viral mRNA levels directly correlate with changes in tat mRNA levels observed upon increased inclusion of exon 2 or 3.

Conclusion
These results demonstrate that splicing at HIV-1 3'ss A1 is regulated by the strength of the downstream 5'ss signal and that suboptimal splicing at 3'ss A1 is necessary for virus replication. Furthermore, the replication defective phenotype resulting from increased splicing at 3'ss A1 is similar to the phenotype observed upon increased splicing at 3'ss A2. Further examination of the role of 5'ss D2 and D3 in the alternative splicing of 3'ss A1 and A2, respectively, is necessary to delineate a role for non-coding exon inclusion in HIV-1 replication.
Causal analysis of case-control data
Authors: Newman Stephen C 
Published: February 2006

AbstractIn a series of papers, Robins and colleagues describe inverse probability of treatment weighted (IPTW) estimation in marginal structural models (MSMs), a method of causal analysis of longitudinal data based on counterfactual principles. This family of statistical techniques is similar in concept to weighting of survey data, except that the weights are estimated using study data rather than defined so as to reflect sampling design and post-stratification to an external population. Several decades ago Miettinen described an elementary method of causal analysis of case-control data based on indirect standardization. In this paper we extend the Miettinen approach using ideas closely related to IPTW estimation in MSMs. The technique is illustrated using data from a case-control study of oral contraceptives and myocardial infarction.
Y chromosome microdeletions in infertile men with idiopathic oligo- or azoospermia
Authors: Hellani Ali , Al-Hassan Saad , Iqbal Muhammed A , Coskun Serdar 
Published: February 2006

AbstractAbout 30–40% of male infertility is due to unknown reasons. Genetic contributions to the disruption of spermatogenesis are suggested and amongst the genetic factors studied, Y chromosome microdeletions represent the most common one. Screening for microdeletions in AZFa, b and c region of Y chromosome showed a big variation among different studies. The purpose of this study was to investigate the prevalence of such deletions in Saudi men. A total of 257 patients with idiopathic oligo- or azoospermia were screened for Y chromosome microdeletions by 19 markers in AZF region. Ten (3.9%) patients had chromosomal rearrangements, six of them showed sex chromosome abnormalities and four patients had apparently balanced autosomal rearrengements. Eight of the remaining 247 patients (3.2%) with a normal karyotype and no known causes of impaired spermatogenesis had Y chromosome microdeletions. Among these, six patients had deletions in AZFc region, one case had a deletion in AZFb and another had both AZFa and AZFc deletions.In conclusion, our study shows that Y chromosome microdeletions are low in our population. We also report for the first time a case with unique point deletions of AZFa and AZFc regions. The lower frequency of deletions in our study suggest that other genetic, epigenetic, nutritional and local factors may be responsible for idiopathic oligo- or azoospermia in the Saudi population.
Epstein-barr virus induced cellular changes in nasal mucosa
Authors: Gelardi Matteo , Tomaiuolo Marilena , Cassano Michele , Besozzi Gaspare , Fiorella Maria Luisa , Calvario Agata , Castellano Maria Antonia , Cassano Pasquale 
Published: February 2006

Abstract
A 21-year-old man presented with nasal obstruction of the right nasal fossa of 1 year duration. Nasal endoscopy revealed in the right inferior turbinate head a rounded neoplasm about 1 cm in diameter.
Cytologic study of a nasal scraping specimen disclosed numerous clusters containing columnar cells with cytomegaly, prominent multinucleation, markedly sparse shortened cilia; the cytoplasm contained an acidophil area and a small round area that stained poorly; cells with a large intracytoplasmic vacuole that was acidophil and PAS+. Serology tests using the nested polymer chain reaction (PCR) technique on serum, nasal and pharyngeal smears revealed an Epstein-Barr virus (EBV) infection that was confirmed at electron microscopy. The clinical and cytological features resolved 19 months after the initial evaluation.

Conclusion

The authors advise carrying out clinical (endoscopy, serology, etc.) evaluation of all endonasal neoplasms and to routinely perform cytological study on nasal scraping specimens. When samples test positive for EBV, nasal and nasopharyngeal endoscopy should be performed regularly to detect possible evidence for nasopharyngeal carcinoma (NPC).
Intrathecal Long-Term Gene Expression by Self-Complementary Adeno-Associated Virus type 1 Suitable for Chronic Pain Studies in Rats
Authors: Storek Benjamin , Harder Nina M , Banck Michaela S , Wang Cheng , McCarty Douglas M , Janssen William GM , Morrison John H , Walsh Christopher E , Beutler Andreas S 
Published: February 2006

Background Intrathecal (IT) gene transfer is an attractive approach for targeting spinal mechanisms of nociception but the duration of gene expression achieved by reported methods is short (up to two weeks) impairing their utility in the chronic pain setting. The overall goal of this study was to develop IT gene transfer yielding true long-term transgene expression defined as ≥ 3 mo following a single vector administration. We defined “IT” administration as atraumatic injection into the lumbar cerebrospinal fluid (CSF) modeling a lumbar puncture. Our studies focused on recombinant adeno-associated virus (rAAV), one of the most promising vector types for clinical use. Results Conventional single stranded rAAV2 vectors performed poorly after IT delivery in rats. Pseudotyping of rAAV with capsids of serotypes 1, 3, and 5 was tested alone or in combination with a modification of the inverted terminal repeat. The former alters vector tropism and the latter allows packaging of self-complementary rAAV (sc-rAAV) vectors. Combining both types of modification led to the identification of sc-rAAV2/l as a vector that performed superiorly in the IT space. IT delivery of 3 × 10e9 sc-rAAV2/l particles per animal led to stable expression of enhanced green fluorescent protein (EGFP) for ≥ 3 mo detectable by Western blotting, quantitative PCR, and in a blinded study by confocal microscopy. Expression was strongest in the cauda equina and the lower sections of the spinal cord and only minimal in the forebrain. Microscopic examination of the SC fixed in situ with intact nerve roots and meninges revealed strong EGFP fluorescence in the nerve roots. Conclusion sc-rAAVl mediates stable IT transgene expression for ≥ 3 mo. Our findings support the underlying hypothesis that IT target cells for gene transfer lack the machinery for efficient conversion of the single-stranded rAAV genome into double-stranded DNA and favor uptake of serotype 1 vectors over 2. Experiments presented here will provide a rational basis for utilizing IT rAAV gene transfer in basic and translational studies on chronic pain.
Color naming deficits and attention-deficit/hyperactivity disorder: A retinal dopaminergic hypothesis
Authors: Tannock Rosemary , Banaschewski Tobias , Gold David 
Published: February 2006

Abstract

Background
Individuals with Attention-Deficit/Hyperactive Disorder (ADHD) have unexplained difficulties on tasks requiring speeded processing of colored stimuli. Color vision mechanisms, particularly short-wavelength (blue-yellow) pathways, are highly sensitive to various diseases, toxins and drugs that alter dopaminergic neurotransmission. Thus, slow color processing might reflect subtle impairments in the perceptual encoding stage of stimulus color, which arise from hypodopaminergic functioning.

Presentation of hypotheses
1) Color perception of blue-yellow (but not red-green) stimuli is impaired in ADHD as a result of deficient retinal dopamine; 2) Impairments in the blue-yellow color mechanism in ADHD contribute to poor performance on speeded color naming tasks that include a substantial proportion of blue-yellow stimuli; and 3) Methylphenidate increases central dopamine and is also believed to increase retinal dopamine, thereby normalizing blue-yellow color perception, which in turn improves performance on the speeded color naming tasks.

Testing the hypothesis
Requires three approaches, including:1) direct assessment of color perception in individuals with ADHD to determine whether blue-yellow color perception is selectively impaired; 2) determination of relationship between performance on neuropsychological tasks requiring speeded color processing and color perception; and 3) randomized, controlled pharmacological intervention with stimulant medication to examine the effects of enhancing central dopamine on color perception and task performance

Implications of hypothesis
If substantiated, the findings of color perception problems would necessitate a re-consideration of current neuropsychological models of attention-deficit/hyperactivity disorder, guide psycho-education, academic instruction, and require consideration of stimulus color in many of the widely used neuropsychological tests.
Mutational hotspots in the TP53gene and, possibly, other tumor suppressors evolve by positive selection
Authors: Glazko Galina V , Babenko Vladimir N , Koonin Eugene V , Rogozin Igor B 
Published: February 2006

Abstract

Background
The mutation spectra of the TP53 gene and other tumor suppressors contain multiple hotspots, i.e., sites of non-random, frequent mutation in tumors and/or the germline. The origin of the hotspots remains unclear, the general view being that they represent highly mutable nucleotide contexts which likely reflect effects of different endogenous and exogenous factors shaping the mutation process in specific tissues. The origin of hotspots is of major importance because it has been suggested that mutable contexts could be used to infer mechanisms of mutagenesis contributing to tumorigenesis.

Results
Here we apply three independent tests, accounting for non-uniform base compositions in synonymous and non-synonymous sites, to test whether the hotspots emerge via selection or due to mutational bias. All three tests consistently indicate that the hotspots in the TP53 gene evolve, primarily, via positive selection. The results were robust to the elimination of the highly mutable CpG dinucleotides. By contrast, only one, the least conservative test reveals the signature of positive selection in BRCA1, BRCA2, and p16. Elucidation of the origin of the hotspots in these genes requires more data on somatic mutations in tumors.

Conclusion
The results of this analysis seem to indicate that positive selection for gain-of-function in tumor suppressor genes is an important aspect of tumorigenesis, blurring the distinction between tumor suppressors and oncogenes.

Reviewers
This article was reviewed by Sandor Pongor, Christopher Lee and Mikhail Blagosklonny.
Occupational medicine and toxicology
Authors: Groneberg David A , Fischer Axel 
Published: February 2006

Abstract
This editorial is to announce the Journal of Occupational Medicine and Toxicology, a new Open Access, peer-reviewed, online journal published by BioMed Central. Occupational medicine and toxicology belong to the most wide ranging disciplines of all medical specialties. The field is devoted to the diagnosis, prevention, management and scientific analysis of diseases from the fields of occupational and environmental medicine and toxicology. It also covers the promotion of occupational and environmental health. The complexity of modern industrial processes has dramatically changed over the past years and today's areas include effects of atmospheric pollution, carcinogenesis, biological monitoring, ergonomics, epidemiology, product safety and health promotion. We hope that the launch of the Journal of Occupational Medicine and Toxicology will aid in the advance of these important areas of research bringing together multi-disciplinary research findings.
Chronic cough due to occupational factors
Authors: Groneberg David A , Nowak Dennis , Wussow Anke , Fischer Axel 
Published: February 2006

AbstractWithin the large variety of subtypes of chronic cough, either defined by their clinical or pathogenetic causes, occupational chronic cough may be regarded as one of the most preventable forms of the disease. Next to obstructive airway diseases such as asthma or chronic obstructive pulmonary disease, which are sometimes concomitant with chronic cough, this chronic airway disease gains importance in the field of occupational medicine since classic fiber-related occupational airway diseases will decrease in the future.Apart from acute accidents and incidental exposures which may lead to an acute form of cough, there are numerous sources for the development of chronic cough within the workplace. Over the last years, a large number of studies has focused on occupational causes of respiratory diseases and it has emerged that chronic cough is one of the most prevalent work-related airway diseases. Best-known examples of occupations related to the development of cough are coal miners, hard-rock miners, tunnel workers, or concrete manufacturing workers.As chronic cough is often based on a variety of non-occupational factors such as tobacco smoke, a distinct separation into either occupational or personally -evoked can be difficult. However, revealing the occupational contribution to chronic cough and to the symptom cough in general, which is the commonest cause for the consultation of a physician, can significantly lead to a reduction of the socioeconomic burden of the disease.
The description of cough sounds by healthcare professionals
Authors: Smith Jaclyn A , Ashurst H Louise , Jack Sandy , Woodcock Ashley A , Earis John E 
Published: February 2006

AbstractBackgroundLittle is known of the language healthcare professionals use to describe cough sounds. We aimed to examine how they describe cough sounds and to assess whether these descriptions suggested they appreciate the basic sound qualities (as assessed by acoustic analysis) and the underlying diagnosis of the patient coughing.Methods53 health professionals from two large respiratory tertiary referral centres were recruited; 22 doctors and 31 staff from professions allied to medicine. Participants listened to 9 sequences of spontaneous cough sounds from common respiratory diseases. For each cough they selected patient gender, the most appropriate descriptors and a diagnosis. Cluster analysis was performed to assess which cough sounds attracted similar descriptions.ResultsGender was correctly identified in 93% of cases. The presence or absence of mucus was correct in 76.1% and wheeze in 39.3% of cases. However, identifying clinical diagnosis from cough was poor at 34.0%. Cluster analysis showed coughs with the same acoustics properties rather than the same diagnoses attracted the same descriptions.ConclusionThese results suggest that healthcare professionals can recognise some of the qualities of cough sounds but are poor at making diagnoses from them. It remains to be seen whether in the future cough sound acoustics will provide useful clinical information and whether their study will lead to the development of useful new outcome measures in cough monitoring.
Diversity and utilization of antimalarial ethnophytotherapeutic remedies among the Kikuyus (Central Kenya)
Authors: Njoroge Grace N , Bussmann Rainer W 
Published: February 2006

Abstract
Plants in Kenya are becoming increasingly important as sources of traditional medicines. The World Health Organization (WHO) has estimated that malaria kills about 2.7 million people every year, 90% of who are from Africa. Malaria continues to be a national concern in Kenya as it plays a major role in the high mortality rates being experienced currently. The use and miss-use of chloroquine to prevent and treat falciparium malaria has led to widespread appearance of chloroquine resistant parasites in Kenya and other tropical countries. These factors and the rising costs of non-chloroquine drugs have made the local people to turn to traditional remedies for management of this menace.
This paper examines the current utilization of traditional plant medicines in managing malaria menace in Central Kenya. The results show both indigenous and introduced species are in use indicating traditional medicinal practices in this region are dynamic. In total 58 species in 54 genera and 33 families were identified. The family Rubiaceae was found to have the highest number of reported species. Use of the various taxa is compared between five districts within Central Province of Kenya. The commonest species in this pharmacopoeia are: Caesalpinia volkensii Harms, Strychnos henningsii Gilg, Ajuga remota Benth., Warbugia ugandensis Sprague and Olea europaea L. The first three species are used in all the five districts while the others are restricted in some of the districts. In 74% of the anti-malarial plant species reported in this study, the remedies are obtained in destructive manner and may need conservation measures to ensure sustainable utilization. The results of this study become a basis for selecting plants for further pharmacological and phytochemical studies in developing new and locally relevant anti-malarial agents.
Prevalence of virulence factors in Staphylococcus intermediusisolates from dogs and pigeons
Authors: Futagawa-Saito Keiko , Ba-Thein William , Sakurai Naomi , Fukuyasu Tsuguaki 
Published: February 2006

Abstract

Background

Staphylococcus intermedius has been isolated from healthy dogs and pigeons as well as diseased dogs. Similar to Staphylococcus aureus, S. intermedius is known to carry many virulence factors but most of these factors remain to be studied. In this study, we examined 106 S. intermedius isolates (44 dog isolates and 62 pigeon isolates) for their hemolytic activity, biofilm formation, protease activity, and clumping factor and protein A production.

Results
Forty-three dog isolates (97.7%) and all pigeon isolates were hemolytic on sheep RBCs with a mean hemolytic titer of 336.7 and 47.32, respectively, whereas 43 dog isolates (97.7%) and 11 pigeon isolates (17.7%) exhibited a significant difference in their hemolytic activity on rabbit RBCs with a mean hemolytic titer of 11.04 and 3.76, respectively (p < 0.0005). The mean biofilm formation activity for dog isolates was 0.49, which was significantly higher than that (0.33) for pigeon isolates (p < 0.0005). Twenty-four dog isolates (54.5%) and 11 pigeon isolates (17.7%) were protease positive. Twenty-four dog isolates (54.5%) were clumping factor- and protein A- positive.

Conclusion

S. intermedius strains carrying the virulence factors examined in this study were more prevalent in dogs than pigeons.
Comparing attitudes about legal sanctions and teratogenic effects for cocaine, alcohol, tobacco and caffeine: A randomized, independent samples design
Authors: Ginsburg Harvey J , Raffeld Paul , Alanis Kelly L , Boyce Angela S 
Published: February 2006

Abstract

Background
Establishing more sensible measures to treat cocaine-addicted mothers and their children is essential for improving U.S. drug policy. Favorable post-natal environments have moderated potential deleterious prenatal effects. However, since cocaine is an illicit substance having long been demonized, we hypothesized that attitudes toward prenatal cocaine exposure would be more negative than for licit substances, alcohol, nicotine and caffeine. Further, media portrayals about long-term outcomes were hypothesized to influence viewers' attitudes, measured immediately post-viewing. Reducing popular crack baby stigmas could influence future policy decisions by legislators.
In Study 1, 336 participants were randomly assigned to 1 of 4 conditions describing hypothetical legal sanction scenarios for pregnant women using cocaine, alcohol, nicotine or caffeine. Participants rated legal sanctions against pregnant women who used one of these substances and risk potential for developing children.
In Study 2, 139 participants were randomly assigned to positive, neutral and negative media conditions. Immediately post-viewing, participants rated prenatal cocaine-exposed or non-exposed teens for their academic performance and risk for problems at age18.

Results
Participants in Study 1 imposed significantly greater legal sanctions for cocaine, perceiving prenatal cocaine exposure as more harmful than alcohol, nicotine or caffeine. A one-way ANOVA for independent samples showed significant differences, beyond .0001. Post-hoc Sheffe test illustrated that cocaine was rated differently from other substances.
In Study 2, a one-way ANOVA for independent samples was performed on difference scores for the positive, neutral or negative media conditions about prenatal cocaine exposure. Participants in the neutral and negative media conditions estimated significantly lower grade point averages and more problems for the teen with prenatal cocaine exposure than for the non-exposed teen beyond .0001 alpha level. The positive media program closed estimated grade point average differences and risks of later problems to a non-statistically significant margin, p >.05.

Conclusion
Ratings for prenatal cocaine were more negative than comparable ratings for alcohol, nicotine or caffeine exposure. Stereotypes can be reduced, showing viewers that positive postnatal environments ameliorate potential teratogenic effects of cocaine. Reducing negative stereotypes for crack babies may be a requisite for substantive changes in current policy.