bluuebunny/crossref_metadata_2025_split huggingface dataset:
A methodology for distinguishing divergent cell fates within a common progenitor population: adenoma- and neuroendocrine-like cells are confounders of rat ileal epithelial cell (IEC-18) culture
Authors: Gordon Phillip V , Paxton Jessica B , Fox Nena S 
Published: January 2005

Abstract
Background
IEC-18 cells are a non-transformed, immortal cell line derived from juvenile rat ileal crypt cells. They may have experimental advantages over tumor-derived gastrointestinal lineages, including preservation of phenotype, normal endocrine responses and retention of differentiation potential. However, their proclivity for spontaneous differentiation / transformation may be stereotypical and could represent a more profound experimental confounder than previously realized. We hypothesized that IEC-18 cells spontaneously diverge towards a uniform mixture of epigenetic fates, with corresponding phenotypes, rather than persist as a single progenitor lineage.

Results
IEC-18 cells were cultured for 72 hours in serum free media (SFM), with and without various insulin-like growth factor agonists to differentially boost the basal rate of proliferation. A strategy was employed to identify constitutive genes as markers of divergent fates through gene array analysis by cross-referencing fold-change trends for individual genes against crypt cell abundance in each treatment. We then confirmed the cell-specific phenotype by immunolocalization of proteins corresponding to those genes. The majority of IEC-18 cells in SFM alone had a loss in expression of the adenomatous polyposis coli (APC) gene at the mRNA and protein levels, consistent with adenoma-like transformation. In addition, a small subset of cells expressed the serotonin receptor 2A gene and had neuroendocrine-like morphology.

Conclusions
IEC-18 cells commonly undergo a change in cell fate prior to reaching confluence. The most common fate switch that we were able to detect correlates with a down regulation of the APC gene and transformation into an adenoma-like phenotype.
Hinderin, a five-domains protein including coiled-coil motifs that binds to SMC3
Authors: Patel Chirag A , Ghiselli Giancarlo 
Published: January 2005

Abstract
Background
The structural maintenance of chromosome proteins SMC1 and SMC3 play an important role in the maintenance of chromosomal integrity by preventing the premature separation of the sister chromatids at the onset of anaphase. The two proteins are constitutive components of the multimeric complex cohesin and form dimers by interacting at their central globular regions.

Results
In order to identify proteins that by binding to SMC3 may interfere with the protein dimerization process, a human cDNA library was screened by the yeast two-hybrid system by using the hinge region of SMC3 as bait. This has lead to the identification of Hinderin, a novel five domains protein including two coiled-coil motifs and sharing a strikingly structural similarity to the SMC family of proteins. Hinderin is ubiquitously expressed in human tissues. Orthologue forms of the protein are present in other vertebrates but not in lower organisms. A mapping of the interaction sites revealed that the N- and C-terminal globular domains mediate the binding of Hinderin to SMC3. Hinderin/SMC3 complexes could be recovered by immunoprecipitation from cell lysates using an anti-SMC3 antibody, thus demonstrating that the two proteins interact in vivo. On the contrary, Hinderin did not interact with SMC1. In vivo the rate of SMC1/SMC3 interaction was decreased by the ectopic expression of Hinderin.

Conclusions
Hinderin is a novel binding partner of SMC3. Based on its ability to modulate SMC1/SMC3 interaction we postulate that Hinderin affects the availability of SMC3 to engage in the formation of multimeric protein complexes.
Validating viral quasispecies with digital organisms: a re-examination of the critical mutation rate
Authors: Comas Iñaki , Moya Andrés , González-Candelas Fernando 
Published: January 2005

Abstract
Background
In this report we re-examine some recent experiments with digital organisms to test some predictions of quasispecies theory. These experiments revealed that under high mutation rates populations of less fit organisms previously adapted to such high mutation rates were able to outcompete organisms with higher average fitness but adapted to low mutation rates.

Results
We have verified that these results do hold in the original conditions and, by extending the set of initial parameters, we have also detected that the critical mutation rate was independent of population size, a result that we have found to be dependent on a different, contingent factor, the initial fitness vector. Furthermore, in all but one case, the critical mutation rate is higher than the error threshold, a key parameter in quasispecies theory, which prevents its extrapolation to natural viral populations.

Conclusion
From these results we conclude that digital organisms are useful tools for investigating evolutionary patterns and processes including some predictions from the quasispecies theory.
Gene expression patterns associated with blood-feeding in the malaria mosquito Anopheles gambiae
Authors: Dana Ali N , Hong Young S , Kern Marcia K , Hillenmeyer Maureen E , Harker Brent W , Lobo Neil F , Hogan James R , Romans Patricia , Collins Frank H 
Published: January 2005

Abstract
Background
Blood feeding, or hematophagy, is a behavior exhibited by female mosquitoes required both for reproduction and for transmission of pathogens. We determined the expression patterns of 3,068 ESTs, representing ~2,000 unique gene transcripts using cDNA microarrays in adult female Anopheles gambiae at selected times during the first two days following blood ingestion, at 5 and 30 min during a 40 minute blood meal and at 0, 1, 3, 5, 12, 16, 24 and 48 hours after completion of the blood meal and compared their expression to transcript levels in mosquitoes with access only to a sugar solution.

Results
In blood-fed mosquitoes, 413 unique transcripts, approximately 25% of the total, were expressed at least two-fold above or below their levels in the sugar-fed mosquitoes, at one or more time points. These differentially expressed gene products were clustered using k-means clustering into Early Genes, Middle Genes, and Late Genes, containing 144, 130, and 139 unique transcripts, respectively. Several genes from each group were analyzed by quantitative real-time PCR in order to validate the microarray results.

Conclusion
The expression patterns and annotation of the genes in these three groups (Early, Middle, and Late genes) are discussed in the context of female mosquitoes' physiological responses to blood feeding, including blood digestion, peritrophic matrix formation, egg development, and immunity.
Expression profile of immune response genes in patients with Severe Acute Respiratory Syndrome
Authors: Reghunathan Renji , Jayapal Manikandan , Hsu Li-Yang , Chng Hiok-Hee , Tai Dessmon , Leung Bernard P , Melendez Alirio J 
Published: January 2005

Abstract
Background
Severe acute respiratory syndrome (SARS) emerged in later February 2003, as a new epidemic form of life-threatening infection caused by a novel coronavirus. However, the immune-pathogenesis of SARS is poorly understood. To understand the host response to this pathogen, we investigated the gene expression profiles of peripheral blood mononuclear cells (PBMCs) derived from SARS patients, and compared with healthy controls.

Results
The number of differentially expressed genes was found to be 186 under stringent filtering criteria of microarray data analysis. Several genes were highly up-regulated in patients with SARS, such as, the genes coding for Lactoferrin, S100A9 and Lipocalin 2. The real-time PCR method verified the results of the gene array analysis and showed that those genes that were up-regulated as determined by microarray analysis were also found to be comparatively up-regulated by real-time PCR analysis.

Conclusions
This differential gene expression profiling of PBMCs from patients with SARS strongly suggests that the response of SARS affected patients seems to be mainly an innate inflammatory response, rather than a specific immune response against a viral infection, as we observed a complete lack of cytokine genes usually triggered during a viral infection. Our study shows for the first time how the immune system responds to the SARS infection, and opens new possibilities for designing new diagnostics and treatments for this new life-threatening disease.
Factors associated with reporting multiple causes of death
Authors: Wall Melanie M , Huang Jinzhou , Oswald John , McCullen Diane 
Published: January 2005

Abstract
Background
There is analytical potential for multiple cause of death data collected from death certificates. This study examines relationships of multiple causes of death as a function of factors available on the death certificate (demographics of decedent, place of death, type of certifier, disposal method, whether an autopsy was performed, and year of death).

Methods
Data from 326,332 Minnesota death certificates from 1990–1998 are examined. Underlying and non-underlying causes of death are examined (based on record axis codes) as well as demographic and death-related covariates. Associations between covariates and prevalence of multiple causes of death and conditional probability of underlying compared to non-underlying causes of death are examined. The occurrence of ischemic heart disease or diabetes as underlying causes are specifically examined.

Results
Both the probability of multiple causes of death and the proportion of underlying cause compared to non-underlying cause of death are associated with demographic characteristics of the deceased and other non-medical conditions related to filing death certificate such as place of death.

Conclusions
Multiple cause of death data provide a potentially useful way of looking for inaccuracies in reporting of causes of death. Differences across demographics in the proportion of time a cause is selected as underlying compared to non-underlying exist and can potentially provide useful information about the overall impact of causes of death in different populations.
Enterococcal meningitis caused by Enterococcus casseliflavus. First case report
Authors: Iaria Chiara , Stassi Giovanna , Costa Gaetano Bruno , Di Leo Rita , Toscano Antonio , Cascio Antonio 
Published: January 2005

Abstract
Background
Enterococcal meningitis is an uncommon disease usually caused by Enterococcus faecalis and Enterococcus faecium and is associated with a high mortality rate. Enterococcus casseliflavus has been implicated in a wide variety of infections in humans, but never in meningitis.

Case presentation
A 77-year-old Italian female presented for evaluation of fever, stupor, diarrhea and vomiting of 3 days duration. There was no history of head injury nor of previous surgical procedures. She had been suffering from rheumatoid arthritis for 30 years, for which she was being treated with steroids and methotrexate. On admission, she was febrile, alert but not oriented to time and place. Her neck was stiff, and she had a positive Kernig's sign. The patient's cerebrospinal fluid was opalescent with a glucose concentration of 14 mg/dl, a protein level of 472 mg/dl, and a white cell count of 200/μL with 95% polymorphonuclear leukocytes and 5% lymphocytes. Gram staining of CSF revealed no organisms, culture yielded E. casseliflavus. The patient was successfully treated with meropenem and ampicillin-sulbactam.

Conclusions
E. casseliflavus can be inserted among the etiologic agents of meningitis. Awareness of infection of central nervous system with Enterococcus species that possess an intrinsic vancomycin resistance should be increased.
MDM2 negatively regulates the human telomerase RNA gene promoter
Authors: Zhao Jiangqin , Bilsland Alan , Jackson Katrina , Keith W Nicol 
Published: January 2005

Abstract
Background
We have previously demonstrated that NF-Y and Sp1 interact with the human telomerase RNA (hTR) promoter and play a central role in its regulation. We have also shown that pRB activates the hTR promoter, but the mechanism of pRb directed activation is unknown. It has recently been reported that pRB induces Sp1 activity by relieving inhibition mediated by mdm2. The aim was to investigate possible roles for mdm2 in hTR promoter regulation.

Methods
Chromatin immunoprecipitation was used to determine binding of mdm2 to the hTR promoter. Transfection and luciferase assays were used to investigate mdm2 repression of the promoter activity and interaction with known transcriptional modulators.

Results
Here we show using chromatin immunoprecipitation that mdm2 specifically binds the hTR promoter in vivo. Transient co-transfection experiments using an hTR promoter luciferase reporter construct show that hTR promoter activity is inhibited by over-expression of mdm2 in 5637 bladder carcinoma cells (p53 and pRB negative, low mdm2). Titration of mdm2 was able to antagonise activation of hTR promoter activity mediated by pRB or Sp1 over-expression, although in the presence of pRB, mdm2 could not repress promoter activity below basal levels. Using an Sp1 binding site mutation construct we showed that mdm2 repression did not absolutely require Sp1 binding sites in the hTR promoter, suggesting the possibility of pRB/Sp1 independent mechanisms of repression. Finally, we show that NF-Y mediated transactivation of the hTR promoter was also suppressed by mdm2 in a dose-dependent manner.

Conclusions
These studies suggest that mdm2 may inhibit the hTR promoter by multiple mechanisms. Mdm2 may directly repress activation by both pRB and Sp1, or activation by NF-Y. Furthermore, the ability of mdm2 to interact and interfere with components of the general transcription machinery might partly explain the general repressive effect seen here. Elucidation of new regulators affecting hTR basal promoter activity in cancer cells provides a basis for future studies aimed at improving our understanding of the differential hTR expression between normal and cancer cells.
Gene expression profiling revealed novel mechanism of action of Taxotere and Furtulon in prostate cancer cells
Authors: Li Yiwei , Hussain Maha , Sarkar Sarah H , Eliason James , Li Ran , Sarkar Fazlul H 
Published: January 2005

Abstract
Background
Both Taxotere and Capecitabine have shown anti-cancer activity against various cancers including prostate cancer. In combination, Taxotere plus Capecitabine has demonstrated higher anti-cancer activity in advanced breast cancers. However, the molecular mechanisms of action of Taxotere and Capecitabine have not been fully elucidated in prostate cancer.

Methods
The total RNA from PC3 and LNCaP prostate cells untreated and treated with 2 nM Taxotere, 110 μM Furtulon (active metabolite of Capecitabine), or 1 nM Taxotere plus 50 μM Furtulon for 6, 36, and 72 hours, was subjected to Affymetrix Human Genome U133A Array analysis. Real-time PCR and Western Blot analysis were conducted to confirm microarray data.

Results
Taxotere and Furtulon down-regulated some genes critical for cell proliferation, cell cycle progression, transcription factor, cell signaling, and oncogenesis, and up-regulated some genes related to the induction of apoptosis, cell cycle arrest, and differentiation in both cell lines. Taxotere and Furtulon also up-regulated some genes responsible for chemotherapeutic resistance, suggesting the induction of cancer cell resistance to these agents.

Conclusions
Taxotere and Furtulon caused the alternation of a large number of genes, many of which may contribute to the molecular mechanisms by which Taxotere and Furtulon inhibit the growth of prostate cancer cells. This information could be utilized for further mechanistic research and for devising optimized therapeutic strategies against prostate cancer.
Acute weight gain, gender, and therapeutic response to antipsychotics in the treatment of patients with schizophrenia
Authors: Ascher-Svanum Haya , Stensland Michael , Zhao Zhongyun , Kinon Bruce J 
Published: January 2005

Abstract
Background
Previous research indicated that women are more vulnerable than men to adverse psychological consequences of weight gain. Other research has suggested that weight gain experienced during antipsychotic therapy may also psychologically impact women more negatively. This study assessed the impact of acute treatment-emergent weight gain on clinical and functional outcomes of patients with schizophrenia by patient gender and antipsychotic treatment (olanzapine or haloperidol).

Methods
Data were drawn from the acute phase (first 6-weeks) of a double-blind randomized clinical trial of olanzapine versus haloperidol in the treatment of 1296 men and 700 women with schizophrenia-spectrum disorders. The associations between weight change and change in core schizophrenia symptoms, depressive symptoms, and functional status were examined post-hoc for men and women and for each medication group. Core schizophrenia symptoms (positive and negative) were measured with the Brief Psychiatric Rating Scale (BPRS), depressive symptoms with the BPRS Anxiety/Depression Scale and the Montgomery-Asberg Depression Rating Scale, and functional status with the mental and physical component scores on the Medical Outcome Survey-Short Form 36. Statistical analysis included methods that controlled for treatment duration.

Results
Weight gain during 6-week treatment with olanzapine and haloperidol was significantly associated with improvements in core schizophrenia symptoms, depressive symptoms, mental functioning, and physical functioning for men and women alike. The conditional probability of clinical response (20% reduction in core schizophrenia symptom), given a clinically significant weight gain (at least 7% of baseline weight), showed that about half of the patients who lost weight responded to treatment, whereas three-quarters of the patients who had a clinically significant weight gain responded to treatment. The positive associations between therapeutic response and weight gain were similar for the olanzapine and haloperidol treatment groups. Improved outcomes were, however, more pronounced for the olanzapine-treated patients, and more olanzapine-treated patients gained weight.

Conclusions
The findings of significant relationships between treatment-emergent weight gain and improvements in clinical and functional status at 6-weeks suggest that patients who have greater treatment-emergent weight gain are more likely to benefit from treatment with olanzapine or haloperidol regardless of gender.
The stability of life satisfaction in a 15-year follow-up of adult Finns healthy at baseline
Authors: Koivumaa-Honkanen Heli , Kaprio Jaakko , Honkanen Risto J , Viinamäki Heimo , Koskenvuo Markku 
Published: January 2005

Abstract
Background
While physical health has improved considerably over recent decades in Finland, the disease burden of mental health, especially that of depression, has become increasingly demanding. However, we lack long-term data on the natural course of subjective well-being in the general population. The aim of this study was to investigate the long-term course of self-reported life satisfaction.

Methods
This was a 15-year prospective cohort study on a nationwide sample of adult Finnish twins (N = 9679), aged 18–45 and healthy at baseline, who responded to postal questionnaires in 1975, 1981 and 1990 including a 4-item life satisfaction scale (happiness/easiness/interest in life and feelings of loneliness). Life satisfaction score (range: 4–20) was classified into three categories: satisfied (4–6), intermediate (7–11) and dissatisfied group (12–20). The associations between life satisfaction scores during the follow-up were studied with linear/logistic regression.

Results
Moderate stability and only a slight effect of age or birth-cohort on mean life satisfaction score (LS) were detected. In 1990, 56% of all and 31% of the dissatisfied remained in the same LS category as at baseline. Only 5.9% of the study subjects changed from being satisfied to dissatisfied or vice versa. Correlations between continuous scores (1975, 1981 and 1990) were 0.3–0.4. Baseline dissatisfaction (compared to satisfaction) predicted dissatisfaction in 1981 (OR = 10.4; 95%CI 8.3–13.1) and 1990 (5.6; 4.6–6.8). Multiple adjustments decreased the risk only slightly.

Conclusions
Life satisfaction in adult Finns was moderately stable during 15 years. Among an identifiable group (i.e. the dissatisfied) life dissatisfaction may become persistent, which places them at a greater risk of adverse health outcomes.
Effectiveness and cost-effectiveness of a multidisciplinary intervention programme to prevent new falls and functional decline among elderly persons at risk: design of a replicated randomised controlled trial [ISRCTN64716113]
Authors: Hendriks Marike RC , van Haastregt Jolanda CM , Diederiks Joseph PM , Evers Silvia MAA , Crebolder Harry FJM , van Eijk Jacques ThM 
Published: January 2005

Abstract
Background
Falls are common among community-dwelling elderly people and can have a considerable impact on quality of life and healthcare costs. People who have sustained a fall are at greater risk of falling again.
We replicated a British randomised controlled trial which demonstrated the effectiveness of a multidisciplinary intervention programme to prevent falls.
The objective is to describe the design of a replication study evaluating a multidisciplinary intervention programme on recurrent falls and functional decline among elderly persons at risk. The study consists of an effect evaluation, an economic evaluation and a process evaluation.

Methods/design
The programme is aimed at community-dwelling elderly people aged 65 years or over who have visited an accident and emergency department (A&E department) or a general practitioners' cooperative (GP cooperative) because of a fall.
The design involves a two-group randomised controlled trial. Participants are followed for twelve months after baseline. The intervention programme consists of a detailed medical and occupational therapy assessment with referral to relevant services if indicated. People in the control group receive usual care.
The main outcome measures of the effect evaluation are number of falls and daily functioning. The economic evaluation will be performed from a societal perspective. A process evaluation will be carried out to evaluate the feasibility of the intervention programme.
Concepts of patients with alopecia areata about their disease
Authors: Firooz Alireza , Firoozabadi Mehdi Rashighi , Ghazisaidi Behnaz , Dowlati Yahya 
Published: January 2005

Abstract
Background
Alopecia areata (AA) is a common and chronic skin disease with an unknown etiology. It may significantly affect the patient quality of life. This study was designed to evaluate the illness perception in patients with AA.

Methods
A questionnaire consisting of 25 questions about causes, timeline, consequences and control of disease were given to 80 patients with AA attending a skin clinic in Tehran, Iran. The impact of age, gender, duration of disease, education, extent of disease and family history of AA were also assessed.

Results
Eighty patients (38 male and 42 female) with a mean age of 27.5 years (SD = 9.3) and disease duration of 7.8 years (SD = 7.7) completed the questionnaire. 76.9% of the patients believed that the role of stress was the cause of disease. 17.1 % believed genetic background to be the main cause, this found to be more frequent in patients with positive family history of AA. More than half of patients believed that their illness had major consequences on their lives and 40% of patients believed that their illness would be likely to be permanent rather than temporary, more in patients with longer duration of disease. Only 57.5% of patients considered their treatments to be effective.

Conclusion
AA may considerably affect various aspects of patients' lives. The patient knowledge about the causes and course of this disease is limited.