bluuebunny/crossref_metadata_2025_split huggingface dataset:
Sustained signaling through the B-cell receptor induces Mcl-1 and promotes survival of chronic lymphocytic leukemia B cells
Authors: Petlickovski Aleksandar , Laurenti Luca , Li Xiaoping , Marietti Sara , Chiusolo Patrizia , Sica Simona , Leone Giuseppe , Efremov Dimitar G. 
Published: February 2005

AbstractThe clinical course of chronic lymphocytic leukemia (CLL) differs significantly between patients with mutated (M-CLL) and unmutated (U-CLL) immunoglobulin (Ig) variable heavy-chain (VH) genes, implying a role for B-cell receptor (BCR) signaling in the pathogenesis of this disease. We have now investigated activation of downstream BCR signaling pathways in U-CLL and M-CLL B cells using soluble anti-IgM (sol-IgM) and immobilized anti-IgM (imm-IgM) antibodies as models for antigenic stimulation. Ligation of the BCR with sol-IgM induced incomplete responses in both CLL subsets, resembling the pattern described for tolerant B cells. This response was characterized by transient phosphorylation of extracellular signal-related kinase (ERK) and Akt (protein kinase B [PKB]), lack of activation of c-JUN NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK), and variable activation of phospholipase Cγ2 (PLCγ2) and nuclear factor-κB (NF-κB). Stimulation with imm-IgM elicited a more complete BCR signal and significantly prolonged phosphorylation of ERK and Akt, indicating persistent or repetitive BCR signaling. Moreover, this type of stimulation increased the levels of the antiapoptotic protein myeloid cell leukemia-1 (Mcl-1) and protected from chemotherapy-induced apoptosis, whereas induction of apoptosis and down-regulation of Mcl-1 was observed following stimulation with sol-IgM. These data demonstrate that only sustained BCR signaling can promote survival of CLL B cells and indicate that the main difference between CLL with mutated and unmutated VH genes may reside in the availability of such stimulation. (Blood. 2005;105:4820-4827)
A subset of natural killer cells achieves self-tolerance without expressing inhibitory receptors specific for self-MHC molecules
Authors: Fernandez Nadine C. , Treiner Emmanuel , Vance Russell E. , Jamieson Amanda M. , Lemieux Suzanne , Raulet David H. 
Published: February 2005

AbstractIt is widely believed that self-tolerance of natural killer (NK) cells occurs because each NK cell expresses at least one inhibitory receptor specific for a host major histocompatibility complex (MHC) class I molecule. Here we report that some NK cells lack all known self-MHC–specific inhibitory receptors, yet are nevertheless self-tolerant. These NK cells exhibit a normal cell surface phenotype and some functional activity. However, they respond poorly to class I–deficient normal cells, tumor cells, or cross-linking of stimulatory receptors, suggesting that self-tolerance is established by dampening stimulatory signaling. Thus, self-tolerance of NK cells in normal animals can occur independently of MHC-mediated inhibition, and hyporesponsiveness plays a role in self-tolerance of NK cells, as also proposed for B and T cells.
The homeobox gene HEX regulates proliferation and differentiation of hemangioblasts and endothelial cells during ES cell differentiation
Authors: Kubo Atsushi , Chen Vincent , Kennedy Marion , Zahradka Elizabeth , Daley George Q. , Keller Gordon 
Published: February 2005

AbstractIn this report we have investigated the role of the homeobox gene Hex in the development and differentiation of the blast colony-forming cell (BL-CFC), a progenitor with hemangioblast characteristics generated in embryonic stem (ES) cell-derived embryoid bodies (EBs). Molecular analysis showed that Hex is expressed in mesoderm, in populations that contain BL-CFCs, and in blast cell colonies, the progeny of the BL-CFCs. Hex-/- EBs displayed a defect in macrophage development but generated higher numbers of BL-CFCs than did wild-type EBs. In addition to differences in these progenitor populations, we also found that endothelial cells from the Hex-/- EBs showed enhanced proliferative potential compared with those from wild-type EBs. Forced expression of Hex at the onset of ES cell differentiation resulted in reduced EB cellularity, fetal liver kinase-1 (Flk-1) expression, and BL-CFC development. Taken together, these findings demonstrate that Hex functions at multiple stages of development within the differentiating EBs and uncover a novel role for this transcription factor as a negative regulator of the hemangioblast and the endothelial lineage. (Blood. 2005;105: 4590-4597)
HIV-1 incorporates ABO histo-blood group antigens that sensitize virions to complement-mediated inactivation
Authors: Neil Stuart J. D. , McKnight Áine , Gustafsson Kenth , Weiss Robin A. 
Published: February 2005

AbstractABO histo-blood group antigens have been postulated to modify pathogen spread through the action of natural antibodies and complement. The antigens are generated by a polymorphic glycosyl-transferase encoded by 2 dominant active and a recessive inactive allele. In this study we investigated whether ABO sugars are incorporated into the envelope of HIV-1 virions. HIV vectors derived from cells expressing ABO antigens displayed sensitivity to fresh human serum analogous to ABO incompatibility, and ABO histo-blood group sugars were detected on the viral envelope protein, glycoprotein 120 (gp120). Moreover, lymphocyte-derived virus also displayed serum sensitivity, reflecting the ABO phenotype of the host when cultured in autologous serum due to adsorption of antigens to cell surfaces. Serum sensitivity required both active complement and specific anti-ABO antibodies. Thus, incorporation of ABO antigens by HIV-1 may affect transmission of virus between individuals of discordant blood groups by interaction with host natural antibody and complement. (Blood. 2005;105:4693-4699)
CXCR3/CXCL10 interactions in the development of hypersensitivity pneumonitis
Authors: Agostini Carlo , Calabrese Fiorella , Poletti Venerino , Marcer Guido , Facco Monica , Miorin Marta , Cabrelle Anna , Baesso Ilenia , Zambello Renato , Trentin Livio , Semenzato Gianpietro 
Published: February 2005

Abstract
Background
Hypersensitivity pneumonitis (HP) is an interstitial lung disease caused by repeated inhalations of finely dispersed organic particles or low molecular weight chemicals. The disease is characterized by an alveolitis sustained by CD8(+) cytotoxic T lymphocytes, granuloma formation, and, whenever antigenic exposition continues, fibrosis. Although it is known that T-cell migration into the lungs is crucial in HP reaction, mechanisms implicated in this process remain undefined.

Methods
Using flow cytometry, immunohistochemistry, confocal microscopy analysis and chemotaxis assays we evaluated whether CXCL10 and its receptor CXCR3 regulate the trafficking of CD8(+) T cells in HP lung.

Results
Our data demonstrated that lymphocytes infiltrating lung biopsies are CD8 T cells which strongly stain for CXCR3. However, T cells accumulating in the BAL of HP were CXCR3(+)/IFNγ(+) Tc1 cells exhibiting a strong in vitro migratory capability in response to CXCL10. Alveolar macrophages expressed and secreted, in response to IFN-γ, definite levels of CXCL10 capable of inducing chemotaxis of the CXCR3(+) T-cell line. Interestingly, striking levels of CXCR3 ligands could be demonstrated in the fluid component of the BAL in individuals with HP.

Conclusion
These data indicate that IFN-γ mediates the recruitment of lymphocytes into the lung via production of the chemokine CXCL10, resulting in Tc1-cell alveolitis and granuloma formation.
Two-part permutation tests for DNA methylation and microarray data
Authors: Neuhäuser Markus , Boes Tanja , Jöckel Karl-Heinz 
Published: February 2005

Abstract
Background
One important application of microarray experiments is to identify differentially expressed genes. Often, small and negative expression levels were clipped-off to be equal to an arbitrarily chosen cutoff value before a statistical test is carried out. Then, there are two types of data: truncated values and original observations. The truncated values are not just another point on the continuum of possible values and, therefore, it is appropriate to combine two statistical tests in a two-part model rather than using standard statistical methods. A similar situation occurs when DNA methylation data are investigated. In that case, there are null values (undetectable methylation) and observed positive values. For these data, we propose a two-part permutation test.

Results
The proposed permutation test leads to smaller p-values in comparison to the original two-part test. We found this for both DNA methylation data and microarray data. With a simulation study we confirmed this result and could show that the two-part permutation test is, on average, more powerful. The new test also reduces, without any loss of power, to a standard test when there are no null or truncated values.

Conclusion
The two-part permutation test can be used in routine analyses since it reduces to a standard test when there are positive values only. Further advantages of the new test are that it opens the possibility to use other test statistics to construct the two-part test and that it avoids the use of any asymptotic distribution. The latter advantage is particularly important for the analysis of microarrays since sample sizes are usually small.
GANN: Genetic algorithm neural networks for the detection of conserved combinations of features in DNA
Authors: Beiko Robert G , Charlebois Robert L 
Published: February 2005

Abstract
Background
The multitude of motif detection algorithms developed to date have largely focused on the detection of patterns in primary sequence. Since sequence-dependent DNA structure and flexibility may also play a role in protein-DNA interactions, the simultaneous exploration of sequence- and structure-based hypotheses about the composition of binding sites and the ordering of features in a regulatory region should be considered as well. The consideration of structural features requires the development of new detection tools that can deal with data types other than primary sequence.

Results
GANN (available at http://bioinformatics.org.au/gann) is a machine learning tool for the detection of conserved features in DNA. The software suite contains programs to extract different regions of genomic DNA from flat files and convert these sequences to indices that reflect sequence and structural composition or the presence of specific protein binding sites. The machine learning component allows the classification of different types of sequences based on subsamples of these indices, and can identify the best combinations of indices and machine learning architecture for sequence discrimination. Another key feature of GANN is the replicated splitting of data into training and test sets, and the implementation of negative controls. In validation experiments, GANN successfully merged important sequence and structural features to yield good predictive models for synthetic and real regulatory regions.

Conclusion
GANN is a flexible tool that can search through large sets of sequence and structural feature combinations to identify those that best characterize a set of sequences.
Possible role of eclosion rhythm in mediating the effects of light-dark environments on pre-adult development in Drosophila melanogaster
Authors: Paranjpe Dhanashree A , Anitha D , Chandrashekaran MK , Joshi Amitabh , Sharma Vijay Kumar 
Published: February 2005

Abstract
Background
In insects, circadian clocks have been implicated in affecting life history traits such as pre-adult development time and adult lifespan. Studies on the period (per) mutants of Drosophila melanogaster, and laboratory-selected lines of Bactrocera cucurbitae suggested a close link between circadian clocks and development time. There is a possibility of clock genes having pleiotropic effects on clock period and pre-adult development time. In order to avoid such pleiotropic effects we have used wild type flies of same genotype under environments of different periodicities, which phenotypically either speeded up or slowed down the eclosion clock of D. melanogaster.

Results
We assayed pre-adult development time and pre-adult survivorship of four laboratory populations of D. melanogaster, under five different light regimes, continuous light (LL), continuous darkness (DD), and light-dark (LD) cycles of 10:10 h (T20), 12:12 h (T24), and 14:14 h (T28). Although the development time was significantly different in most light regimes, except for females under T24 &T28, pre-adult survivorship remained largely unaffected. The development time was shortest under LL, followed by T20, DD, T24 and T28 regimes, in that order. Interestingly the development time showed a positive correlation with the period of eclosion rhythm, i.e., faster oscillations were associated with faster development, and slower oscillations with slower development.

Conclusion
Based on these results we conclude that periodicity of imposed LD cycles, and/or of eclosion rhythm plays a key role in regulating the duration of pre-adult development in D. melanogaster in a manner that does not involve direct pleiotropic effects of clock genes on both clock period and development time.
Consequences of the historical demography on the global population structure of two highly migratory cosmopolitan marine fishes: the yellowfin tuna (Thunnus albacares) and the skipjack tuna (Katsuwonus pelamis)
Authors: Ely Bert , Viñas Jordi , Alvarado Bremer Jaime R , Black Donna , Lucas Luciano , Covello Kelly , Labrie Alexis V , Thelen Eric 
Published: February 2005

Abstract
Background
Yellowfin and skipjack tuna are globally distributed in the world's tropical and sub-tropical oceans. Since little, if any, migration of these fishes occurs between the Atlantic and Indo-Pacific Oceans, one might expect to see genetic differences between sub-populations in these ocean basins. However, yellowfin and skipjack tuna have extremely large population sizes. Thus, the rate of genetic drift should be slower than that observed for other tunas.

Results
Low levels of genetic differentiation were observed between Atlantic and Pacific samples of yellowfin tuna. In contrast, no genetic differentiation was observed between Atlantic and Pacific samples of skipjack tuna.

Conclusion
Much lower levels of genetic differentiation were found among sub-populations of yellowfin tuna compared to those observed for other large tunas, probably due to the large population size of yellowfin tuna. Since skipjack tuna appear to have even larger population sizes, it is not surprising that no genetic differentiation was detected between Atlantic and Pacific samples of these fish.
parkinmutation dosage and the phenomenon of anticipation: a molecular genetic study of familial parkinsonism
Authors: Poorkaj Parvoneh , Moses Lina , Montimurro Jennifer S , Nutt John G , Schellenberg Gerard D , Payami Haydeh 
Published: February 2005

Abstract
Background
parkin mutations are a common cause of parkinsonism. Possessing two parkin mutations leads to early-onset parkinsonism, while having one mutation may predispose to late-onset disease. This dosage pattern suggests that some parkin families should exhibit intergenerational variation in age at onset resembling anticipation. A subset of familial PD exhibits anticipation, the cause of which is unknown. The aim of this study was to determine if anticipation was due to parkin mutation dosage.

Methods
We studied 19 kindreds that had early-onset parkinsonism in the offspring generation, late-onset parkinsonism in the parent generation, and ≥ 20 years of anticipation. We also studied 28 early-onset parkinsonism cases without anticipation. Patients were diagnosed by neurologists at a movement disorder clinic. parkin analysis included sequencing and dosage analysis of all 12 exons.

Results
Only one of 19 cases had compound parkin mutations, but contrary to our postulate, the affected relative with late-onset parkinsonism did not have a parkin mutation. In effect, none of the anticipation cases could be attributed to parkin. In contrast, 21% of early-onset parkinsonism patients without anticipation had parkin mutations.

Conclusion
Anticipation is not linked to parkin, and may signify a distinct disease entity.
Recombinant Tula hantavirus shows reduced fitness but is able to survive in the presence of a parental virus: analysis of consecutive passages in a cell culture
Authors: Plyusnina Angelina , Plyusnin Alexander 
Published: February 2005

Abstract
Tula hantavirus carrying recombinant S RNA segment (recTULV) grew in a cell culture to the same titers as the original cell adapted variant but presented no real match to the parental virus. Our data showed that the lower competitiveness of recTULV could not be increased by pre-passaging in the cell culture. Nevertheless, the recombinant virus was able to survive in the presence of the parental virus during five consecutive passages. The observed survival time seems to be sufficient for transmission of newly formed recombinant hantaviruses in nature.
Herpesvirus saimiri-transformed CD8+ T cells as a tool to study Chediak-Higashi syndrome cytolytic lymphocytes
Authors: Martín-Fernández José M , Cabanillas Juan A , Rivero-Carmena Miguel , Lacasa Esther , Pardo Julián , Anel Alberto , Ramírez-Duque Pedro R , Merino Fernando , Rodríguez-Gallego Carlos , Regueiro José R 
Published: February 2005

AbstractCytolytic CD8+ T lymphocytes are the main cell type involved in the fatal lymphoproliferative-accelerated phase of the Chediak-Higashi syndrome (CHS). To generate a cellular tool to study the defects of this T cell subset in vitro, we have used Herpesvirus saimiri, a lymphotropic virus that transforms human T lymphocytes into extended growth and in addition, endows them with natural killer (NK) features. Transformed CHS CD8+ T cells were generated and characterized in comparison with healthy controls. The results showed that transformed CHS T cells maintained the defects described in primary CHS lymphocytes, such as giant secretory lysosomes and impaired NK and T cell receptor/CD3-induced, perforin-mediated cytolytic activity [which, however, could be restored after extended culture in the presence of interleukin-2 (IL-2)]. Upon activation with phorbol ester plus calcium ionophore or upon extended culture with IL-2, transformed CHS T cells showed normal, perforin-independent plasma membrane CD178/CD95L/FasL-mediated cytolytic activity but negligible secretion of microvesicle-bound CD95L. Transformed (and primary) CHS T cells were otherwise normal for cytolysis-independent activation functions, such as proliferation, surface expression of several activation markers including major histocompatibility complex class II, and cytokine or surface activation-marker induction. Therefore, the CHS protein [CHS1/LYST (for lysosomal traffic regulator)] can be dispensable for certain NK and T cell cytolytic activities of activated CHS CD8+ T lymphocytes, but it seems to be required for microvesicle secretion of CD95L. We conclude that transformed CHS T cells may be useful as a tool to study in vitro the relative role of CHS1/LYST in NK and T lymphocyte cytolysis and antigen presentation.
Inflammation-mediated dysfunction and apoptosis in pancreatic islet transplantation: implications for intrahepatic grafts
Authors: Barshes Neal R , Wyllie Samuel , Goss John A 
Published: February 2005

AbstractRecent advances in clinical protocols have improved the outcomes of pancreatic islet transplantation (PIT), yet PIT recipients typically require pancreatic islet grafts derived from multiple donors to achieve insulin independence. This along with experimental models of syngeneic PIT, showing that up to 60% of pancreatic islet tissue undergoes apoptosis within the first several days post-transplantation, strongly suggest the involvement of nonalloantigen-specific, inflammatory events in partial destruction of the graft following PIT. Interleukin-1β appears to be among the most important inflammatory mediators, causing pancreatic islet dysfunction and apoptosis through the up-regulation of inducible nitric oxide (NO) synthase and cyclooxygenase-2. Kupffer cells secrete many molecules, including cytokines, NO, and free radicals, which are known to be directly toxic to the pancreatic islets, and depletion or inhibition of Kupffer cells improves outcomes following experimental PIT. Imediately after transplantation, the pancreatic islets are perfused only by portal vein blood until the process of angiogenesis restores arterial blood flow some 7–10 days later. This delayed vascularization may have implications for the expression of leukocyte adhesion molecules, the effects of free radicals, and the role of ischemia-reperfusion injury. Finally, in the immediate post-transplant period, hepatocytes may contribute to pancreatic islet injury through the production of NO. This paper reviews literature regarding the inflammatory events that follow PIT as well as the pathogenesis of diabetes and the pathophysiology of hepatic ischemia-reperfusion and their relation to the survival and function of intrahepatic pancreatic islet grafts.
Renal medullary hypoxia during experimental cardiopulmonary bypass: a pilot study
Authors: Stafford-Smith Mark , Grocott Hilary P. 
Published: February 2005

Objectives: To determine the effect of cardiopulmonary bypass (CPB) on renal medullary oxygenation. Design: Observational. Setting: Laboratory. Participants: Pigs ( n=3). Interventions: Following induction of general anesthesia, a Paratrend™ blood gas probe was placed directly into the left renal medulla. Two animals were subjected to 90 min of CPB, while a third served as a non-CPB control. A probe was also placed in the left renal pelvis of one (CPB) animal to allow direct urine PO2measurements. Measurements and main results: Medullary hypoxia (PO2B < 65 mmHg) was evident prior to CPB. With the onset of CPB, medullary PO2 further declined to nearly unmeasurable levels; PCO2 and pH were unchanged. Brief circulatory arrest during CPB in one animal resulted in rapid additional PCO2 rise and pH decline that corrected with reperfusion. Following the cessation of CPB, medullary PO2 gradually increased, but remained lower than pre-CPB levels. No changes in medullary PO2 were observed in the sham animal. Renal pelvis urine PO2, but not pH or PCO2, appeared to correlate with medullary values at all times. Conclusions: Our findings indicate that renal medullary hypoxia is extreme during CPB and may persist following CPB. These data suggest a basis for the vulnerability of the kidney to injury during cardiac surgery. Renal pelvis urine PO2 appears to correlate closely with medullary PO2 and may be a useful tool for studying medullary oxygenation during CPB in humans.