bluuebunny/crossref_metadata_2025_split huggingface dataset:
Resistance of mature T cells to oncogene transformation
Authors: Newrzela Sebastian , Cornils Kerstin , Li Zhixiong , Baum Christopher , Brugman Martijn H. , Hartmann Marianne , Meyer Johann , Hartmann Sylvia , Hansmann Martin-Leo , Fehse Boris , von Laer Dorothee 
Published: June 2008

AbstractLeukemia caused by retroviral insertional mutagenesis after stem cell gene transfer has been reported in several experimental animals and in patients treated for X-linked severe combined immunodeficiency. Here, we analyzed whether gene transfer into mature T cells bears the same genotoxic risk. To address this issue in an experimental “worst case scenario,” we transduced mature T cells and hematopoietic progenitor cells from C57BL/6 (Ly5.1) donor mice with high copy numbers of gamma retroviral vectors encoding the potent T-cell oncogenes LMO2, TCL1, or ΔTrkA, a constitutively active mutant of TrkA. After transplantation into RAG-1–deficient recipients (Ly5.2), animals that received stem cell transplants developed T-cell lymphoma/leukemia for all investigated oncogenes with a characteristic phenotype and after characteristic latency periods. Ligation-mediated polymerase chain reaction analysis revealed monoclonality or oligoclonality of the malignancies. In striking contrast, none of the mice that received T-cell transplants transduced with the same vectors developed leukemia/lymphoma despite persistence of gene-modified cells. Thus, our data provide direct evidence that mature T cells are less prone to transformation than hematopoietic progenitor cells.
The influence of N-acetyl-L-cysteine on oxidative stress and nitric oxide synthesis in stimulated macrophages treated with a mustard gas analogue
Authors: Paromov Victor , Qui Min , Yang Hongsong , Smith Milton , Stone William L 
Published: June 2008

AbstractBackgroundSulphur mustard gas, 2, 2'-dichlorodiethyl sulphide (HD), is a chemical warfare agent. Both mustard gas and its monofunctional analogue, 2-chloroethyl ethyl sulphide (CEES), are alkylating agents that react with and diminish cellular thiols and are highly toxic. Previously, we reported that lipopolysaccharide (LPS) significantly enhances the cytotoxicity of CEES in murine RAW 264.7 macrophages and that CEES transiently inhibits nitric oxide (NO) production via suppression of inducible NO synthase (iNOS) protein expression. NO generation is an important factor in wound healing. In this paper, we explored the hypotheses that LPS increases CEES toxicity by increasing oxidative stress and that treatment with N-acetyl-L-cysteine (NAC) would block LPS induced oxidative stress and protect against loss of NO production. NAC stimulates glutathione (GSH) synthesis and also acts directly as a free radical scavenger. The potential therapeutic use of the antibiotic, polymyxin B, was also evaluated since it binds to LPS and could thereby block the enhancement of CEES toxicity by LPS and also inhibit the secondary infections characteristic of HD/CEES wounds.ResultsWe found that 10 mM NAC, when administered simultaneously or prior to treatment with 500 μM CEES, increased the viability of LPS stimulated macrophages. Surprisingly, NAC failed to protect LPS stimulated macrophages from CEES induced loss of NO production. Macrophages treated with both LPS and CEES show increased oxidative stress parameters (cellular thiol depletion and increased protein carbonyl levels). NAC effectively protected RAW 264.7 cells simultaneously treated with CEES and LPS from GSH loss and oxidative stress. Polymyxin B was found to partially block nitric oxide production and diminish CEES toxicity in LPS-treated macrophages.ConclusionThe present study shows that oxidative stress is an important mechanism contributing to CEES toxicity in LPS stimulated macrophages and supports the notion that antioxidants could play a therapeutic role in preventing mustard gas toxicity. Although NAC reduced oxidative stress in LPS stimulated macrophages treated with CEES, it did not reverse CEES-induced loss of NO production. NAC and polymyxin B were found to help prevent CEES toxicity in LPS-treated macrophages.
Coupling amplified DNA from flow-sorted chromosomes to high-density SNP mapping in barley
Authors: Šimková Hana , Svensson Jan T , Condamine Pascal , Hřibová Eva , Suchánková Pavla , Bhat Prasanna R , Bartoš Jan , Šafář Jan , Close Timothy J , Doležel Jaroslav 
Published: June 2008

Abstract

Background
Flow cytometry facilitates sorting of single chromosomes and chromosome arms which can be used for targeted genome analysis. However, the recovery of microgram amounts of DNA needed for some assays requires sorting of millions of chromosomes which is laborious and time consuming. Yet, many genomic applications such as development of genetic maps or physical mapping do not require large DNA fragments. In such cases time-consuming de novo sorting can be minimized by utilizing whole-genome amplification.

Results
Here we report a protocol optimized in barley including amplification of DNA from only ten thousand chromosomes, which can be isolated in less than one hour. Flow-sorted chromosomes were treated with proteinase K and amplified using Phi29 multiple displacement amplification (MDA). Overnight amplification in a 20-microlitre reaction produced 3.7 – 5.7 micrograms DNA with a majority of products between 5 and 30 kb. To determine the purity of sorted fractions and potential amplification bias we used quantitative PCR for specific genes on each chromosome. To extend the analysis to a whole genome level we performed an oligonucleotide pool assay (OPA) for interrogation of 1524 loci, of which 1153 loci had known genetic map positions. Analysis of unamplified genomic DNA of barley cv. Akcent using this OPA resulted in 1426 markers with present calls. Comparison with three replicates of amplified genomic DNA revealed >99% concordance. DNA samples from amplified chromosome 1H and a fraction containing chromosomes 2H – 7H were examined. In addition to loci with known map positions, 349 loci with unknown map positions were included. Based on this analysis 40 new loci were mapped to 1H.

Conclusion
The results indicate a significant potential of using this approach for physical mapping. Moreover, the study showed that multiple displacement amplification of flow-sorted chromosomes is highly efficient and representative which considerably expands the potential of chromosome flow sorting in plant genomics.
Roles of ArabidopsisWRKY3 and WRKY4 Transcription Factors in Plant Responses to Pathogens
Authors: Lai Zhibing , Vinod KM , Zheng Zuyu , Fan Baofang , Chen Zhixiang 
Published: June 2008

Abstract

Background
Plant WRKY DNA-binding transcription factors are involved in plant responses to biotic and abiotic responses. It has been previously shown that Arabidopsis WRKY3 and WRKY4, which encode two structurally similar WRKY transcription factors, are induced by pathogen infection and salicylic acid (SA). However, the role of the two WRKY transcription factors in plant disease resistance has not been directly analyzed.

Results
Both WRKY3 and WRKY4 are nuclear-localized and specifically recognize the TTGACC W-box sequences in vitro. Expression of WRKY3 and WRKY4 was induced rapidly by stress conditions generated by liquid infiltration or spraying. Stress-induced expression of WRKY4 was further elevated by pathogen infection and SA treatment. To determine directly their role in plant disease resistance, we have isolated T-DNA insertion mutants and generated transgenic overexpression lines for WRKY3 and WRKY4. Both the loss-of-function mutants and transgenic overexpression lines were examined for responses to the biotrophic bacterial pathogen Pseudomonas syringae and the necrotrophic fungal pathogen Botrytis cinerea. The wrky3 and wrky4 single and double mutants exhibited more severe disease symptoms and support higher fungal growth than wild-type plants after Botrytis infection. Although disruption of WRKY3 and WRKY4 did not have a major effect on plant response to P. syringae, overexpression of WRKY4 greatly enhanced plant susceptibility to the bacterial pathogen and suppressed pathogen-induced PR1 gene expression.

Conclusion
The nuclear localization and sequence-specific DNA-binding activity support that WRKY3 and WRKY4 function as transcription factors. Functional analysis based on T-DNA insertion mutants and transgenic overexpression lines indicates that WRKY3 and WRKY4 have a positive role in plant resistance to necrotrophic pathogens and WRKY4 has a negative effect on plant resistance to biotrophic pathogens.
Modified cell cycle status in a mouse model of altered neuronal vulnerability (slow Wallerian degeneration; Wld

s
)
Authors: Wishart Thomas M , Pemberton Helen N , James Sally R , McCabe Chris J , Gillingwater Thomas H 
Published: June 2008

Abstract
Background
Altered neuronal vulnerability underlies many diseases of the human nervous system, resulting in degeneration and loss of neurons. The neuroprotective slow Wallerian degeneration (Wld
s
) mutation delays degeneration in axonal and synaptic compartments of neurons following a wide range of traumatic and disease-inducing stimuli, providing a powerful experimental tool with which to investigate modulation of neuronal vulnerability. Although the mechanisms through which Wld
s
confers neuroprotection remain unclear, a diverse range of downstream modifications, incorporating several genes/pathways, have been implicated. These include the following: elevated nicotinamide adenine dinucleotide (NAD) levels associated with nicotinamide mononucleotide adenylyltransferase 1 (Nmnat1; a part of the chimeric Wld
s
gene); altered mRNA expression levels of genes such as pituitary tumor transforming gene 1 (Pttg1); changes in the location/activity of the ubiquitin-proteasome machinery via binding to valosin-containing protein (VCP/p97); and modified synaptic expression of proteins such as ubiquitin-activating enzyme E1 (Ube1).

Results
Wld
s
expression in mouse cerebellum and HEK293 cells induced robust increases in a broad spectrum of cell cycle-related genes. Both NAD-dependent and Pttg1-dependent pathways were responsible for mediating different subsets of these alterations, also incorporating changes in VCP/p97 localization and Ube1 expression. Cell proliferation rates were not modified by Wld
s
, suggesting that later mitotic phases of the cell cycle remained unaltered. We also demonstrate that Wld
s
concurrently altered endogenous cell stress pathways.

Conclusion
We report a novel cellular phenotype in cells with altered neuronal vulnerability. We show that previous reports of diverse changes occurring downstream from Wld
s
expression converge upon modifications in cell cycle status. These data suggest a strong correlation between modified cell cycle pathways and altered vulnerability of axonal and synaptic compartments in postmitotic, terminally differentiated neurons.
Estimating mean sojourn time and screening sensitivity using questionnaire data on time since previous screening
Authors: Weedon-Fekjær Harald , Lindqvist Bo H , Vatten Lars J , Aalen Odd O , Tretli Steinar 
Published: June 2008

Objectives Mean sojourn time (MST) and screening test sensitivity (STS), is usually estimated by Markov models using incidence data from the first screening round and the interval between screening examinations. However, several screening programmes do not have full registration of cancers submerging after screening, and increased use of opportunistic screening over time can raise questions regarding the quality of interval cancer registration. Methods/settings Based on the earlier used Markov model, formulas for expected number of cases given time since former screening activity was developed. Using questionnaire data for 336,533 women in the Norwegian Breast Cancer Screening Programme (NBCSP), mean square regression estimates of MST and STS were calculated. Results In contrast to the previously used method, the new approach gave satisfactory model fit. MST was estimated to 5.6 years for women aged 50–59 years, and 6.9 years for women aged 60–69 years, and STS was estimated to 55% and 60%, respectively. Attempts to add separate parameters for breast cancer incidence without screening, or previous STS, resulted in wide confidence intervals if estimated separately, and non-identifiably if combined. Conclusion Previously published results of long MST and low screen test sensitivity were confirmed with the new approach. Questionnaire data on time since previous screening can be used to estimate MST and STS, but the approach is sensitive to relaxing the assumptions regarding the expected breast cancer incidence without screening and constant STS over time.
The false-positive and false-negative predictive value of HIV antibody test in the Chinese population
Authors: Liu Pei , Shi Zhixu , Wang Cannan , Yang Haitao , Li Lei , Dai Yudong , Liu Yuanbao , Sun Jinfang , Pu Yuepu 
Published: June 2008

Objectives To analyse the relationship between the false-positive/false-negative predictive value (FPPV/FNPV) of the HIV-antibody (HIV-Ab) test and prevalence in different Chinese population groups. Methods HIV prevalence among different population groups was obtained by a screening survey of blood donors and the national HIV/AIDS surveillance programme in China. Given the sensitivity and specificity of a test kit and the prevalence of HIV infection, the estimated values of FPPV/FNPV were calculated using Bayes' formula. The actual value of FPPV of blood donors was obtained by screening 1,195,286 blood donors. Results This study indicates that the FPPV of HIV-Ab enzyme-linked immunosorbent assay (ELISA) assays varies widely in different Chinese populations: about 99.5% in the blood donor population, but only 3.2% in the injecting-drug users in high-risk areas. In 1,195,286 sera specimens from the blood donors, 2439 specimens were HIV-Ab positive by third ELISA, and 11 HIV cases were confirmed by Western blot. The HIV prevalence of the blood donor population in this survey was 0.0009% (11/1,195,286), but the HIV-Ab positive rate of third ELISA is 0.2% (2439/1,195,286) and 222 times higher than the prevalence. Conclusions Evaluation of HIV prevalence through the HIV-Ab positive rate by third ELISA will significantly overestimate the true prevalence in a low-prevalence population. Individual HIV-infection status should be taken into consideration when analysing the results of HIV-Ab tests in a population with low infection.
The Ability of Heart Failure Specialists to Accurately Predict NT-proBNP Levels Based on Clinical Assessment and a Previous NT-proBNP Measurement
Authors: Sedlak Tara L , Chandavimol Mann , Calleja Anna , Clark Catherine , Edmonds Margaret , Pu Aihua , Humphries Karin H , Ignaszewski Andrew 
Published: June 2008

Background:The value of routine aminoterminal pro type B natriuretic peptide (NT-proBNP) measurements in outpatient clinics remains unknown.Objectives:We sought to determine the accuracy with which heart failure (HF) specialists can predict NT-proBNP levels in HF outpatients based on clinical assessment.Methods:We prospectively studied 160 consecutive HF patients followed in an outpatient multidisciplinary HF clinic. During a regular office visit, HF specialists were asked to estimate a patient’s current NT-proBNP level based upon their clinical assessment and all available information from their chart, including a previous NT-proBNP level (if available). NT-proBNP estimations were grouped into prognostic categories (<125, 125-1000, 1000-4998, or ≥4999 pg/mL) and comparisons made between actual and estimate values.Results:Overall, HF specialists estimated 67.5% of NT-proBNP levels correctly. After adjusting for clinical characteristics, knowledge of a prior NT-proBNP measurement was the only significant predictor of estimation accuracy (p=0.01). Compared to patients with a prior NT-proBNP level <125 pg/mL, physicians were 95% less likely to get a correct estimation in patients with the highest prior NT-proBNP level (≥4999 pg/mL).Conclusion:HF specialists are reasonably accurate at estimating current NT-proBNP levels based upon clinical assessment and a previous NT-proBNP level, if those levels were < 4999 pg/mL. Likely, initial but not routine NT-proBNP measurements are useful in outpatient HF clinics.
What Balances the Decrease in Net Upward Thermal Radiation at the Surface in Climate Change Experiments?
Authors: Storch Jin-Song von , Botzet Michael , Ehlert Iris 
Published: June 2008

The direct response of surface fluxes to an increase in green house gas concentration is a decrease in net upward long-wave radiation (NLW). This paper examines the responses of the other three surface fluxes, i.e. the latent heat flux (HL), the sensible heat flux (HS) and the net short wave radiation (NSW), using a set of IPCC AR4 climate experiments performed with the coupled ECHAM5/MPI-OM AO-GCM. In particular, the questions of whether and how these fluxes compensate the warming effect due to a decrease in upward NLW are studied.
Consistent with the earlier studies, the decrease in upward NLW is strongly compensated by an increase in upward HL. By using the IPCC scenarios and a coupled AO-GCM, two new aspects of this compensation are identified. First, the degree of compensation decreases with the rate of increase in GHG concentration. Secondly, the compensation does not work over the North Atlantic, where the decrease in upward NLW develops parallel to a reduction in upward HL. This leads to large increases in the net downward heat flux over the North Atlantic and a reduction of the MOC. The responses in HS and NSW can further strengthen or suppress the warming effect of NLW, depending on geographical regions considered. There is a general tendency that HS changes in the same direction as NLW over sea, but in the opposite direction over land. For NSW, the response strengthens the NLW changes over land and suppresses the NLW changes over sea.
Associations of Renal Vascular Resistance With Albuminuria and Other Macroangiopathy in Type 2 Diabetic Patients
Authors: Hamano Kumiko , Nitta Ai , Ohtake Takayasu , Kobayashi Shuzo 
Published: June 2008

OBJECTIVE—Albuminuria can be caused by endothelial dysfunction as a result of ischemic nephropathy rather than classic diabetic nephropathy. We studied whether renal vascular resistance (resistive index [RI]) of the main renal arteries could be associated with albuminuria and further assessed the relationship between RI and aorta stiffness measured by brachial-ankle pulse-wave velocity (baPWV).
RESEARCH DESIGN AND METHODS—We consecutively studied 150 patients with type 2 diabetes and the absence of clinically overt renal artery stenosis. Renal function expressed as the estimated glomerular filtration rate (eGFR) was calculated using the modified formula of modification of diet in renal disease (MDRD). The RI [(peak systolic velocity –end-diastolic velocity)/peak systolic velocity] was measured with duplex Doppler ultrasonography.
RESULTS—When the presence of albuminuria (uAlb) was defined as urinary albumin-to-creatinine ratio (μg/mg · creatinine) &gt;30, mean RI [(left RI + right RI)/2] was significantly higher in uAlb, compared with that in patients without uAlb. RI had significant associations with age (r = 0.398, P &lt; 0.0001), diastolic blood pressure (r = −0.398, P &lt; 0.0001), eGFR (r = −0.373, P &lt; 0.0001), and baPWV (r = 0.223, P &lt; 0.05), respectively. Multivariate logistic regression analysis showed that increased RI when defined as RI &gt;0.72 (median) was significantly associated with age (P &lt; 0.01, 95%CI 1.02–1.19), diastolic blood pressure (P &lt; 0.01, 0.86–0.97), and uAlb (P &lt; 0.01, 1.53–15.46), respectively. Moreover, RI was an independent risk factor for uAlb after adjustment of both diastolic blood pressure and eGFR.
CONCLUSIONS—Renal vascular resistance was associated with albuminuria and aorta stiffness. Increased RI may imply the presence of any type of underlying renal damage, including ischemic nephropathy.
Diagnostic and mutational spectrum of progressive osseous heteroplasia (POH) and other forms of GNAS‐based heterotopic ossification
Authors: Adegbite N.S. , Xu M. , Kaplan F.S. , Shore E.M. , Pignolo R.J. 
Published: June 2008

AbstractProgressive osseous heteroplasia (POH) is a rare, disabling disease of heterotopic ossification (HO) that progresses from skin and subcutaneous tissues into deep skeletal muscle. POH occurs in the absence of multiple developmental features of Albright hereditary osteodystrophy (AHO) or hormone resistance, clinical manifestations that are also associated with GNAS inactivation. However, occasional patients with AHO and pseudohypoparathyroidism 1a/c (PHP1a/c; AHO features plus hormone resistance) have also been described who have progressive HO. This study was undertaken to define the diagnostic and mutational spectrum of POH and progressive disorders of HO, and to distinguish them from related disorders in which HO remains confined to the skin and subcutaneous tissues. We reviewed the charts of 111 individuals who had cutaneous and subcutaneous ossification. All patients were assessed for eight characteristics: age of onset of HO, presence and location of HO, depth of HO, type of HO, progression of HO, features of AHO, PTH resistance, and GNAS mutation analysis. We found, based on clinical criteria, that POH and progressive HO syndromes are at the severe end of a phenotypic spectrum of GNAS‐inactivating conditions associated with extra‐skeletal ossification. While most individuals with superficial or progressive ossification had mutations in GNAS, there were no specific genotype‐phenotype correlations that distinguished the more progressive forms of HO (e.g., POH) from the non‐progressive forms (osteoma cutis, AHO, and PHP1a/c). © 2008 Wiley‐Liss, Inc.
Autosomal recessive acro‐fronto‐facio‐nasal dysostosis associated with genitourinary anomalies: A third case report
Authors: Chaabouni Myriam , Maazoul Faouzi , Hamida Amira Ben , Berhouma Moncef , Marrakchi Zahra , Chaabouni Habiba 
Published: June 2008

AbstractWe report on a 22‐day‐old Tunisian boy born to consanguineous (first‐cousin) parents (F = 1/16). The patient presents wide forehead with frontal encephalocele, wide anterior fontanel, marked hypertelorism, coloboma of the upper lids, proptosis, congenital glaucoma, broad nose, syndactyly between fingers 3 and 4, hypoplastic 3rd, 4th and 5th toes with nail dysplasia, hypospadias with cleft glans, bifid scrotum. Brain MRI showed right frontal encephalocele with anomalies of the cortical gyration without any corpus callosum abnormality. Normal chromosomes and parents' consanguinity are suggestive of autosomal recessive inheritance. Facial midline anomalies associated with limb and genitourinary anomalies is very uncommon. We present the third case reported in the literature. © 2008 Wiley‐Liss, Inc.