bluuebunny/crossref_metadata_2025_split huggingface dataset:
The radioresistance kinase TLK1B protects the cells by promoting repair of double strand breaks
Authors: Sunavala-Dossabhoy Gulshan , Balakrishnan Sri Kripa , Sen Siddhartha , Nuthalapaty Sam , De Benedetti Arrigo 
Published: September 2005

Abstract

Background
The mammalian protein kinase TLK1 is a homologue of Tousled, a gene involved in flower development in Arabidopsis thaliana. The function of TLK1 is not well known, although knockout of the gene in Drosophila or expression of a dominant negative mutant in mouse cells causes loss of nuclear divisions and missegregation of chromosomes probably, due to alterations in chromatin remodeling capacity. Overexpression of TLK1B, a spliced variant of the TLK1 mRNA, in a model mouse cell line increases it's resistance to ionizing radiation (IR) or the radiomimetic drug doxorubicin, also likely due to changes in chromatin remodeling. TLK1B is translationally regulated by the availability of the translation factor eIF4E, and its synthesis is activated by IR. The reason for this mechanism of regulation is likely to provide a rapid means of promoting repair of DSBs. TLK1B specifically phosphorylates histone H3 and Asf1, likely resulting in changes in chromatin structure, particularly at double strand breaks (DSB) sites.

Results
In this work, we provide several lines of evidence that TLK1B protects the cells from IR by facilitating the repair of DSBs. First, the pattern of phosphorylation and dephosphorylation of H2AX and H3 indicated that cells overexpressing TLK1B return to pre-IR steady state much more rapidly than controls. Second, the repair of episomes damaged with DSBs was much more rapid in cells overexpressing TLK1B. This was also true for repair of genomic damage. Lastly, we demonstrate with an in vitro repair system that the addition of recombinant TLK1B promotes repair of a linearized plasmid incubated with nuclear extract. In addition, TLK1B in this in vitro system promotes the assembly of chromatin as shown by the formation of more highly supercoiled topomers of the plasmid.

Conclusion
In this work, we provide evidence that TLK1B promotes the repair of DSBs, likely as a consequence of a change in chromatin remodeling capacity that must precede the assembly of repair complexes at the sites of damage.
Ethanol induces cell-cycle activity and reduces stem cell diversity to alter both regenerative capacity and differentiation potential of cerebral cortical neuroepithelial precursors
Authors: Santillano Daniel R , Kumar Leena S , Prock Terasa L , Camarillo Cynthia , Tingling Joseph D , Miranda Rajesh C 
Published: September 2005

AbstractBackgroundThe fetal cortical neuroepithelium is a mosaic of distinct progenitor populations that elaborate diverse cellular fates. Ethanol induces apoptosis and interferes with the survival of differentiating neurons. However, we know little about ethanol's effects on neuronal progenitors. We therefore exposed neurosphere cultures from fetal rat cerebral cortex, to varying ethanol concentrations, to examine the impact of ethanol on stem cell fate.ResultsEthanol promoted cell cycle progression, increased neurosphere number and increased diversity in neurosphere size, without inducing apoptosis. Unlike controls, dissociated cortical progenitors exposed to ethanol exhibited morphological evidence for asymmetric cell division, and cells derived from ethanol pre-treated neurospheres exhibited decreased proliferation capacity. Ethanol significantly reduced the numbers of cells expressing the stem cell markers CD117, CD133, Sca-1 and ABCG2, without decreasing nestin expression. Furthermore, ethanol-induced neurosphere proliferation was not accompanied by a commensurate increase in telomerase activity. Finally, cells derived from ethanol-pretreated neurospheres exhibited decreased differentiation in response to retinoic acid.ConclusionThe reduction in stem cell number along with a transient ethanol-driven increase in cell proliferation, suggests that ethanol promotes stem to blast cell maturation, ultimately depleting the reserve proliferation capacity of neuroepithelial cells. However, the lack of a concomitant change in telomerase activity suggests that neuroepithelial maturation is accompanied by an increased potential for genomic instability. Finally, the cellular phenotype that emerges from ethanol pre-treated, stem cell depleted neurospheres is refractory to additional differentiation stimuli, suggesting that ethanol exposure ablates or delays subsequent neuronal differentiation.
Different patterns of HIV-1 DNA after therapy discontinuation
Authors: Re Maria Carla , Vitone Francesca , Sighinolfi Laura , Schiavone Pasqua , Ghinelli Florio , Gibellini Davide 
Published: September 2005

Abstract

Background
By persisting in infected cells for a long period of time, proviral HIV-1 DNA can represent an alternative viral marker to RNA viral load during the follow-up of HIV-1 infected individuals. In the present study sequential blood samples of 10 patients under antiretroviral treatment from 1997 with two NRTIs, who refused to continue any antiviral regimen, were analyzed for 16 – 24 weeks to study the possible relationship between DNA and RNA viral load.

Methods
The amount of proviral DNA was quantified by SYBR green real-time PCR in peripheral blood mononuclear cells from a selected group of ten patients with different levels of plasmatic viremia (RNA viral load).

Results
Variable levels of proviral DNA were found without any significant correlation between proviral load and plasma HIV-1 RNA levels. Results obtained showed an increase or a rebound in viral DNA in most patients, suggesting that the absence of therapy reflects an increase and/or a persistence of cells containing viral DNA.

Conclusion
Even though plasma HIV RNA levels remain the basic parameter to monitor the intensity of viral replication, the results obtained seem to indicate that DNA levels could represent an adjunct prognostic marker in monitoring HIV-1 infected subjects.
Translation elongation factor eEF1A2 is a potential oncoprotein that is overexpressed in two-thirds of breast tumours
Authors: Tomlinson Victoria AL , Newbery Helen J , Wray Naomi R , Jackson Juliette , Larionov Alexey , Miller William R , Dixon J Michael , Abbott Catherine M 
Published: September 2005

Abstract

Background
The tissue-specific translation elongation factor eEF1A2 was recently shown to be a potential oncogene that is overexpressed in ovarian cancer. Although there is no direct evidence for an involvement of eEF1A2 in breast cancer, the genomic region to which EEF1A2 maps, 20q13, is frequently amplified in breast tumours. We therefore sought to establish whether eEF1A2 expression might be upregulated in breast cancer.

Methods
eEF1A2 is highly similar (98%) to the near-ubiquitously expressed eEF1A1 (formerly known as EF1-α) making analysis with commercial antibodies difficult. We have developed specific anti-eEF1A2 antibodies and used them in immunohistochemical analyses of tumour samples. We report the novel finding that although eEF1A2 is barely detectable in normal breast it is moderately to strongly expressed in two-thirds of breast tumours. This overexpression is strongly associated with estrogen receptor positivity.

Conclusion
eEF1A2 should be considered as a putative oncogene in breast cancer that may be a useful diagnostic marker and therapeutic target for a high proportion of breast tumours. The oncogenicity of eEF1A2 may be related to its role in protein synthesis or to its potential non-canonical functions in cytoskeletal remodelling or apoptosis.
Relationship between visual field loss and contrast threshold elevation in glaucoma
Authors: Tochel CM , Morton JS , Jay JL , Morrison JD 
Published: September 2005

Abstract

Background
There is a considerable body of literature which indicates that contrast thresholds for the detection of sinusoidal grating patterns are abnormally high in glaucoma, though just how these elevations are related to the location of visual field loss remains unknown. Our aim, therefore, has been to determine the relationship between contrast threshold elevation and visual field loss in corresponding regions of the peripheral visual field in glaucoma patients.

Methods
Contrast thresholds were measured in arcuate regions of the superior, inferior, nasal and temporal visual field in response to laser interference fringes presented in the Maxwellian view. The display consisted of vertical green stationary laser interference fringes of spatial frequency 1.0 c deg-1 which appeared in a rotatable viewing area in the form of a truncated quadrant extending from 10 to 20° from fixation which was marked with a central fixation light. Results were obtained from 36 normal control subjects in order to provide a normal reference for 21 glaucoma patients and 5 OHT (ocular hypertensive) patients for whom full clinical data, including Friedmann visual fields, had been obtained.

Results
Abnormally high contrast thresholds were identified in 20 out of 21 glaucoma patients and in 2 out of 5 OHT patients when compared with the 95% upper prediction limit for normal values from one eye of the 36 normal age-matched control subjects. Additionally, inter-ocular differences in contrast threshold were also abnormally high in 18 out of 20 glaucoma patients who had vision in both eyes compared with the 95% upper prediction limit. Correspondence between abnormally high contrast thresholds and visual field loss in the truncated quadrants was significant in 5 patients, borderline in 4 patients and absent in 9 patients.

Conclusion
While the glaucoma patients tested in our study invariably had abnormally high contrast thresholds in one or more of the truncated quadrants in at least one eye, reasonable correspondence with the location of the visual field loss only occurred in half the patients studied. Hence, while contrast threshold elevations are indicative of glaucomatous damage to vision, they are providing a different assessment of visual function from conventional visual field tests.
Validation of self reported diagnosis of hypertension in a cohort of university graduates in Spain
Authors: Alonso Alvaro , Beunza Juan José , Delgado-Rodríguez Miguel , Martínez-González Miguel Angel 
Published: September 2005

Abstract

Background
The search for risk factors of hypertension requires the study of large populations. Sometimes, the only feasible way of studying these populations is to rely on self-reported data of the outcome. The objective of this study was to evaluate validity of self-reported diagnosis of hypertension in a cohort of university graduates in Spain.

Methods
The Seguimiento Universidad de Navarra (SUN) Study is a cohort of more than 15,000 university graduates in Spain. We selected a random sample of 79 cohort participants who reported a diagnosis of hypertension and 48 participants who did not report such diagnosis (76% participation proportion). Then, we compared information on the self-reported diagnosis of hypertension and hypertension status as assessed through two personal blood pressure measurements and an interview. Additionally, we compared self-reported and measured blood pressure levels with intraclass correlation coefficients and the survival-agreement plot.

Results
From those 79 reporting a diagnosis of hypertension, 65 (82.3%, 95% CI 72.8–92.8) were confirmed through conventional measurement of blood pressure and the interview. From those 48 that did not report a diagnosis of hypertension, 41 (85.4%, 95% CI 72.4–89.1) were confirmed as non hypertensives. Results were similar among men and women, but were worse for overweight and obese individuals, and for those with a family history of hypertension. The agreement between self-reported and measured blood pressure levels (as a continuous variable), as estimated by the intraclass correlation coefficient, was 0.35 for both systolic and diastolic blood pressure.

Conclusion
Self-reported hypertension among highly educated participants in a cohort study is a relatively valid tool to assess the hypertensive status of participants. However, the investigators should be cautious when using self-reported blood pressure values.
Temporal response of the tiger salamander (Ambystoma tigrinum) to 3,000 years of climatic variation
Authors: Bruzgul Judsen E , Long Webb , Hadly Elizabeth A 
Published: September 2005

Abstract

Background
Amphibians are sensitive indicators of environmental conditions and show measurable responses, such as changes in phenology, abundance and range limits to local changes in precipitation and temperature regimes. Amphibians offer unique opportunities to study the important ecological and evolutionary implications of responses in life history characteristics to climatic change. We analyzed a late-Holocene fossil record of the Tiger Salamander (Ambystoma tigrinum) for evidence of population-level changes in body size and paedomorphosis to climatic change over the last 3000 years.

Results
We found a significant difference in body size index between paedomorphic and metamorphic individuals during the time interval dominated by the Medieval Warm Period. There is a consistent ratio of paedomorphic to metamorphic specimens through the entire 3000 years, demonstrating that not all life history characteristics of the population were significantly altered by changes in climate on this timescale.

Conclusion
The fossil record of Ambystoma tigrinum we used spans an ecologically relevant timescale appropriate for understanding population and community response to projected climatic change. The population-level responses we documented are concordant with expectations based on modern environmental studies, and yield insight into population-level patterns across hundreds of generations, especially the independence of different life history characteristics. These conclusions lead us to offer general predictions about the future response of this species based on likely scenarios of climatic warming in the Rocky Mountain region.
Selection of indicators for tonsillectomy in adults with recurrent tonsillitis
Authors: Kasenõmm Priit , Piirsoo Andres , Kull Mart , Kull Mart , Mikelsaar Marika 
Published: September 2005

AbstractBackgroundWe aimed to find some new indicators for tonsillectomy (TE) in adults with recurrent tonsillitis (RT) by exploring whether the frequency of tonsillitis episodes and the length of morbidity period are associated with the macroscopic signs of sclerotic process in tonsils and microbiological data assessed by culture, molecular (PCR) and transmission electron microscopy (EM) methods.MethodsThe study involved 62 RT patients admitted for TE (age range 15–35, median 22 years) and 54 healthy volunteers (age range 18–24, median 20 years). The index of tonsillitis (IT) was calculated by multiplying the number of tonsillitis episodes per year by the morbidity period in years. On oropharyngeal examination the presence or absence of three sclerotic signs was evaluated: tonsillar sclerosis, obstruction of tonsillar crypts and scar tissue on the tonsils. The occurrence ofStreptococcus pyogeneswas assessed by culture and PCR methods in 24 tonsillar core specimens. The samples for EM investigation of crypt epithelium were taken from 10 removed tonsils.ResultsThe IT values were in positive correlation with the number of sclerotic signs on oropharyngeal examination (r = 0.325, P = 0.010). Based on the IT values and the presence or absence of tonsillar sclerosis and obstruction of tonsillar crypts the receiver-operating curve (ROC) was constructed. It revealed that an IT score of 36 is an optimal cut-off value for prediction of sclerotic type tonsils.S. pyogeneswas never found by culture, but its presence by PCR in nearly one third (29%) of diseased tonsillar tissue specimens was tightly associated with longer morbidity. EM revealed coccoid forms of intracellular bacteria in the crypt epithelium, which was accompanied with the damage of tight junctions between epithelial cells.ConclusionThe index of tonsillitis ≥36, being a combination between the frequency of tonsillitis and the length of morbidity period, predicts the sclerotic process in recurrently inflamed tonsils. Therefore, the high IT values could serve as an indicator for TE in adults. The correlation between the longer morbidity period and the presence ofS. pyogenesby PCR suggests that persistent infection may have a role in maintenance of recurrent inflammation in tonsils.
Arterial oxygen saturation in healthy newborns delivered at term in Cerro de Pasco (4340 m) and Lima (150 m)
Authors: Gonzales Gustavo F , Salirrosas Amelia 
Published: September 2005

Abstract

Background
High altitude is associated with both low pulse oxygen saturation at birth and more pre-term deliveries. The present study was performed to determine pulse oxygen saturation in newborns at term in Cerro de Pasco (4340 m) and Lima (150 m) to test the hypothesis that low pulse oxygen saturation at birth at high altitudes was not observed at term deliveries.

Methods
The present study was designed to determine pulse oxygen saturation values through 1 minute to 24 hours and values of Apgar score at 1 and 5 minutes in newborns delivered at term in Cerro de Pasco (4340 m) and Lima (150 m). Pulse oxygen saturation was recorded in 39 newborns from Cerro de Pasco (4340 m) and 131 from Lima (150 m) at 1, 2, 3, 4, 5, 10, 15, 30 minutes and 1, 2, 8 and 24 hours after delivery. Apgar score was assessed at 1 and 5 minutes after birth. Neurological score was assessed at 24 h of birth by Dubowitz exam.

Results
Pulse oxygen saturation increased significantly from 1 to 15 min after birth at sea level and from 1 to 30 minutes at Cerro de Pasco. Thereafter, it increased slightly such that at 30 min at sea level and at 60 minutes in Cerro de Pasco it reached a plateau up to 24 hours after birth. At all times, pulse oxygen saturation was significantly higher at sea level than at high altitude (P < 0.01). At 1 minute of life, pulse oxygen saturation was 15% lower at high altitude than at sea level. Apgar score at 1 minute was significantly lower at high altitude (P < 0.05). Neurological score at 24 hours was also lower at high altitude than at sea level. Head circumference, and Apgar score at 5 minutes were similar at sea level and at high altitude (P:NS). Incidence of low birth-weight (<2500 g) at high altitude (5.4%) was similar to that observed at sea level (2.29%) (P:NS). Incidences of low pulse oxygen saturation (<30%), low Apgar score at first minute (<7) and low neurological score at 24 h (<19) were significantly higher at high altitude than at sea level (P < 0.0001; P < 0.0001; and P < 0.001, respectively).

Conclusion
From these analyses may be concluded that pulse oxygen saturation at 4340 m was significantly low despite the fact that births occurred at term. Apgar scores at first minute and neurological scores were also lower at high altitudes.
Activation of microglial NADPH oxidase is synergistic with glial iNOS expression in inducing neuronal death: a dual-key mechanism of inflammatory neurodegeneration
Authors: Mander Palwinder , Brown Guy C 
Published: September 2005

AbstractBackgroundInflammation-activated glia are seen in many CNS pathologies and may kill neurons through the release of cytotoxic mediators, such as nitric oxide from inducible NO synthase (iNOS), and possibly superoxide from NADPH oxidase (NOX). We set out to determine the relative role of these species in inducing neuronal death, and to test the dual-key hypothesis that the production of both species simultaneously is required for significant neuronal death.MethodsPrimary co-cultures of cerebellar granule neurons and glia from rats were used to investigate the effect of NO (from iNOS, following lipopolysaccharide (LPS) and/or cytokine addition) or superoxide/hydrogen peroxide (from NOX, following phorbol 12-myristate 13-acetate (PMA), ATP analogue (BzATP), interleukin-1β (IL-1β) or arachidonic acid (AA) addition) on neuronal survival.ResultsInduction of glial iNOS caused little neuronal death. Similarly, activation of NOX alone resulted in little or no neuronal death. However, if NOX was activated (by PMA or BzATP) in the presence of iNOS (induced by LPS and interferon-γ) then substantial delayed neuronal death occurred over 48 hours, which was prevented by inhibitors of iNOS (1400W), NOX (apocynin) or a peroxynitrite decomposer (FeTPPS). Neurons and glia were also found to stain positive for nitrotyrosine (a putative marker of peroxynitrite) only when both iNOS and NOX were simultaneously active. If NOX was activated by weak stimulators (IL-1β, AA or the fibrillogenic prion peptide PrP106-126) in the presence of iNOS, it caused microglial proliferation and delayed neurodegeneration over 6 days, which was prevented by iNOS or NOX inhibitors, a peroxynitrite decomposer or a NMDA-receptor antagonist (MK-801).ConclusionThese results suggest a dual-key mechanism, whereby glial iNOS or microglial NOX activation alone is relatively benign, but if activated simultaneously are synergistic in killing neurons, through generating peroxynitrite. This mechanism may mediate inflammatory neurodegeneration in response to cytokines, bacteria, ATP, arachidonate and pathological prions, in which case neurons may be protected by iNOS or NOX inhibitors, or scavengers of NO, superoxide or peroxynitrite.
Assessment of HIV-1 entry inhibitors by MLV/HIV-1 pseudotyped vectors
Authors: Siegert Sandra , Thaler Sonja , Wagner Ralf , Schnierle Barbara S 
Published: September 2005

Abstract

Background
Murine leukemia virus (MLV) vector particles can be pseudotyped with a truncated variant of the human immunodeficiency virus type 1 (HIV-1) envelope protein (Env) and selectively target gene transfer to human cells expressing both CD4 and an appropriate co-receptor. Vector transduction mimics the HIV-1 entry process and is therefore a safe tool to study HIV-1 entry.

Results
Using FLY cells, which express the MLV gag and pol genes, we generated stable producer cell lines that express the HIV-1 envelope gene and a retroviral vector genome encoding the green fluorescent protein (GFP). The BH10 or 89.6 P HIV-1 Env was expressed from a bicistronic vector which allowed the rapid selection of stable cell lines. A codon-usage-optimized synthetic env gene permitted high, Rev-independent Env expression. Vectors generated by these producer cells displayed different sensitivity to entry inhibitors.

Conclusion
These data illustrate that MLV/HIV-1 vectors are a valuable screening system for entry inhibitors or neutralizing antisera generated by vaccines.