bluuebunny/crossref_metadata_2025_split huggingface dataset:
Toll-like receptor 9 signaling by CpG-B oligodeoxynucleotides induces an apoptotic pathway in human chronic lymphocytic leukemia B cells
Authors: Liang Xueqing , Moseman E. Ashley , Farrar Michael A. , Bachanova Veronika , Weisdorf Daniel J. , Blazar Bruce R. , Chen Wei 
Published: March 2010

AbstractChronic lymphocytic leukemia (CLL) is the most prevalent human leukemia and is characterized by the progressive accumulation of long-lived malignant B cells. Here we show that human B-CLL cells selectively express high levels of Toll-like receptor 9 (TLR9) mRNA and proteins. Treating B-CLL cells with TLR9 agonists, type B CpG oligodeoxynucleotides (CpG-B ODNs), induces significant morphologic and phenotypic activation, altered cytokine production, reversal of signal transducer, and activator of transcription 1 (STAT1) phosphorylation state, followed by profound apoptosis of B-CLL cells that is CpG-B ODN treatment time- and dose-dependent. TLR9-CpG ODN ligation-induced apoptosis of B-CLL cells is confirmed by viable cell counts, annexin V/propidium iodide and tetramethyl-rhodamine ethylester staining, Western blots of the activation, and cleaved caspases and poly (ADP-ribose) polymerase. Triggering TLR9 by CpG-B ODN leads to nuclear factor-κB-dependent production of autocrine interleukin-10, which activates JAK/STAT pathway-dependent tyrosine phosphorylation of STAT1 proteins and thereby provokes an apoptosis pathway in B-CLL cells. Treating B-CLL cells in vitro or in vivo with CpG-B ODN reduces the number of leukemia cells that engraft in NOD-scid mice. These findings provide new understanding of CpG ODN-mediated antitumor effects and support for the development of TLR9-targeted therapy for human CLL.
Down-regulation of GATA1 uncouples STAT5-induced erythroid differentiation from stem/progenitor cell proliferation
Authors: Wierenga Albertus T. J. , Vellenga Edo , Schuringa Jan Jacob 
Published: March 2010

AbstractPreviously, we have shown that overexpression of an activated mutant of signal transducer and activator of transcription-5 (STAT5) induces erythropoiesis, impaired myelopoiesis, and an increase in long-term proliferation of human hematopoietic stem/progenitor cells. Because GATA1 is a key transcription factor involved in erythropoiesis, the involvement of GATA1 in STAT5-induced phenotypes was studied by shRNA-mediated knockdown of GATA1. CD34+ cord blood cells were double transduced with a conditionally active STAT5 mutant and a lentiviral vector expressing a short hairpin against GATA1. Erythropoiesis was completely abolished in the absence of GATA1, indicating that STAT5-induced erythropoiesis is GATA1-dependent. Furthermore, the impaired myelopoiesis in STAT5-transduced cells was restored by GATA1 knockdown. Interestingly, early cobblestone formation was only modestly affected, and long-term growth of STAT5-positive cells was increased in the absence of GATA1, whereby high progenitor numbers were maintained. Thus, GATA1 down-regulation allowed the dissection of STAT5-induced differentiation phenotypes from the effects on long-term expansion of stem/progenitor cells. Gene expression profiling allowed the identification of GATA1-dependent and GATA1-independent STAT5 target genes, and these studies revealed that several proliferation-related genes were up-regulated by STAT5 independent of GATA1, whereas several erythroid differentiation-related genes were found to be GATA1 as well as STAT5 dependent.
Genome-wide copy number analysis of Hodgkin Reed-Sternberg cells identifies recurrent imbalances with correlations to treatment outcome
Authors: Steidl Christian , Telenius Adele , Shah Sohrab P. , Farinha Pedro , Barclay Lorena , Boyle Merrill , Connors Joseph M. , Horsman Douglas E. , Gascoyne Randy D. 
Published: March 2010

AbstractIn classical Hodgkin lymphoma (cHL) the mechanisms underlying primary refractory disease and relapse remain unknown. To gain further insight into cHL pathogenesis and genomic changes linked to treatment response, we studied 53 cHL patients by array comparative genomic hybridization, including 23 patients whose primary treatment failed, using DNA from microdissected HRS cells. Copy number alterations found in more than 20% of cases included gains of 2p, 9p, 16p, 17q, 19q, 20q, and losses of 6q, 11q, and 13q. We identified at high resolution recurrent changes defining minimally gained and lost regions harboring genes involved in nuclear factor κB signaling, such as REL, IKBKB, CD40, and MAP3K14. Gains of chromosome 16p11.2-13.3 were significantly more frequent in pretreatment and relapse biopsies of unresponsive patients and were associated with shortened disease-specific survival (P = .028). In the therapy-resistant HL cell line KMH2, we found genomic gains and overexpression of the multidrug resistance gene ABCC1 mapping to cytoband 16p13.11. We show that doxorubicin exposure to KMH2 induces ABCC1 expression and that siRNA silencing of ABCC1 sensitizes KMH2 cells to doxorubicin toxicity in vitro, suggesting that overexpression of ABCC1 contributes to the drug resistance phenotype found in KMH2.
CD16− natural killer cells: enrichment in mucosal and secondary lymphoid tissues and altered function during chronic SIV infection
Authors: Reeves R. Keith , Gillis Jacqueline , Wong Fay E. , Yu Yi , Connole Michelle , Johnson R. Paul 
Published: March 2010

AbstractNatural killer (NK) cells contribute to control of HIV/SIV infection. We defined macaque NK-cell subsets based on expression of CD56 and CD16 and found their distribution to be highly disparate. CD16+ NK cells predominated in peripheral blood, whereas most mucosal NK cells were CD56+, and lymph nodes contained both CD56+ and CD16−CD56− (double-negative [DN]) subsets. Functional profiles were also distinct among subsets—CD16+ NK cells expressed high levels of cytolytic molecules, and CD56+ NK cells were predominantly cytokine-secreting cells, whereas DN NK possessed both functions. In macaques chronically infected with SIV, circulating CD16+ and DN NK cells were expanded in number and, although markers of cytoxicity increased, cytokine secretion decreased. Notably, CD56+ NK cells in SIV-infected animals up-regulated perforin, granzyme B, and CD107a. In contrast, the lymph node–homing molecules CD62 ligand (CD62L) and C-C chemokine receptor type 7 (CCR7), which are expressed primarily on CD56+ and DN NK cells, were significantly down-regulated on NK cells from infected animals. These data demonstrate that SIV infection drives a shift in NK-cell function characterized by decreased cytokine production, expanded cytotoxicity, and trafficking away from secondary lymphoid organs, suggesting that the NK-cell repertoire is not only heterogeneous but also plastic.
Genomic analysis of expressed sequence tags in American black bear Ursus americanus
Authors: Zhao Sen , Shao Chunxuan , Goropashnaya Anna V , Stewart Nathan C , Xu Yichi , Tøien Øivind , Barnes Brian M , Fedorov Vadim B , Yan Jun 
Published: March 2010

Abstract

Background
Species of the bear family (Ursidae) are important organisms for research in molecular evolution, comparative physiology and conservation biology, but relatively little genetic sequence information is available for this group. Here we report the development and analyses of the first large scale Expressed Sequence Tag (EST) resource for the American black bear (Ursus americanus).

Results
Comprehensive analyses of molecular functions, alternative splicing, and tissue-specific expression of 38,757 black bear EST sequences were conducted using the dog genome as a reference. We identified 18 genes, involved in functions such as lipid catabolism, cell cycle, and vesicle-mediated transport, that are showing rapid evolution in the bear lineage Three genes, Phospholamban (PLN), cysteine glycine-rich protein 3 (CSRP3) and Troponin I type 3 (TNNI3), are related to heart contraction, and defects in these genes in humans lead to heart disease. Two genes, biphenyl hydrolase-like (BPHL) and CSRP3, contain positively selected sites in bear. Global analysis of evolution rates of hibernation-related genes in bear showed that they are largely conserved and slowly evolving genes, rather than novel and fast-evolving genes.

Conclusion
We provide a genomic resource for an important mammalian organism and our study sheds new light on the possible functions and evolution of bear genes.
Detection of novel 3' untranslated region extensions with 3' expression microarrays
Authors: Thorrez Lieven , Tranchevent Leon-Charles , Chang Hui Ju , Moreau Yves , Schuit Frans 
Published: March 2010

Abstract

Background
The 3' untranslated regions (UTRs) of transcripts are not well characterized for many genes and often extend beyond the annotated regions. Since Affymetrix 3' expression arrays were designed based on expressed sequence tags, many probesets map to intergenic regions downstream of genes. We used expression information from these probesets to predict transcript extension beyond currently known boundaries.

Results
Based on our dataset encompassing expression in 22 different murine tissues, we identified 845 genes with predicted 3'UTR extensions. These extensions have a similar conservation as known 3'UTRs, which is distinctly higher than intergenic regions. We verified 8 of the predictions by PCR and found all of the predicted regions to be expressed. The method can be extended to other 3' expression microarray platforms as we demonstrate with human data. Additional confirming evidence was obtained from public paired end read data.

Conclusions
We show that many genes have 3'UTR regions extending beyond currently known gene regions and provide a method to identify such regions based on microarray expression data. Since 3' UTR contain microRNA binding sites and other stability determining regions, identification of the full length 3' UTR is important to elucidate posttranscriptional regulation.
The ancient mammalian KRAB zinc finger gene cluster on human chromosome 8q24.3 illustrates principles of C2H2 zinc finger evolution associated with unique expression profiles in human tissues
Authors: Lorenz Peter , Dietmann Sabine , Wilhelm Thomas , Koczan Dirk , Autran Sandra , Gad Sophie , Wen Gaiping , Ding Guohui , Li Yixue , Rousseau-Merck Marie-Françoise , Thiesen Hans-Juergen 
Published: March 2010

Abstract

Background
Expansion of multi-C2H2 domain zinc finger (ZNF) genes, including the Krüppel-associated box (KRAB) subfamily, paralleled the evolution of tetrapodes, particularly in mammalian lineages. Advances in their cataloging and characterization suggest that the functions of the KRAB-ZNF gene family contributed to mammalian speciation.

Results
Here, we characterized the human 8q24.3 ZNF cluster on the genomic, the phylogenetic, the structural and the transcriptome level. Six (ZNF7, ZNF34, ZNF250, ZNF251, ZNF252, ZNF517) of the seven locus members contain exons encoding KRAB domains, one (ZNF16) does not. They form a paralog group in which the encoded KRAB and ZNF protein domains generally share more similarities with each other than with other members of the human ZNF superfamily. The closest relatives with respect to their DNA-binding domain were ZNF7 and ZNF251. The analysis of orthologs in therian mammalian species revealed strong conservation and purifying selection of the KRAB-A and zinc finger domains. These findings underscore structural/functional constraints during evolution. Gene losses in the murine lineage (ZNF16, ZNF34, ZNF252, ZNF517) and potential protein truncations in primates (ZNF252) illustrate ongoing speciation processes. Tissue expression profiling by quantitative real-time PCR showed similar but distinct patterns for all tested ZNF genes with the most prominent expression in fetal brain. Based on accompanying expression signatures in twenty-six other human tissues ZNF34 and ZNF250 revealed the closest expression profiles. Together, the 8q24.3 ZNF genes can be assigned to a cerebellum, a testis or a prostate/thyroid subgroup. These results are consistent with potential functions of the ZNF genes in morphogenesis and differentiation. Promoter regions of the seven 8q24.3 ZNF genes display common characteristics like missing TATA-box, CpG island-association and transcription factor binding site (TFBS) modules. Common TFBS modules partly explain the observed expression pattern similarities.

Conclusions
The ZNF genes at human 8q24.3 form a relatively old mammalian paralog group conserved in eutherian mammals for at least 130 million years. The members persisted after initial duplications by undergoing subfunctionalizations in their expression patterns and target site recognition. KRAB-ZNF mediated repression of transcription might have shaped organogenesis in mammalian ontogeny.
Neural computation of visual imaging based on Kronecker product in the primary visual cortex
Authors: Songnian Zhao , Qi Zou , Zhen Jin , Guozheng Yao , Li Yao 
Published: March 2010

Abstract

Background
What kind of neural computation is actually performed by the primary visual cortex and how is this represented mathematically at the system level? It is an important problem in the visual information processing, but has not been well answered. In this paper, according to our understanding of retinal organization and parallel multi-channel topographical mapping between retina and primary visual cortex V1, we divide an image into orthogonal and orderly array of image primitives (or patches), in which each patch will evoke activities of simple cells in V1. From viewpoint of information processing, this activated process, essentially, involves optimal detection and optimal matching of receptive fields of simple cells with features contained in image patches. For the reconstruction of the visual image in the visual cortex V1 based on the principle of minimum mean squares error, it is natural to use the inner product expression in neural computation, which then is transformed into matrix form.

Results
The inner product is carried out by using Kronecker product between patches and function architecture (or functional column) in localized and oriented neural computing. Compared with Fourier Transform, the mathematical description of Kronecker product is simple and intuitive, so is the algorithm more suitable for neural computation of visual cortex V1. Results of computer simulation based on two-dimensional Gabor pyramid wavelets show that the theoretical analysis and the proposed model are reasonable.

Conclusions
Our results are:
1. The neural computation of the retinal image in cortex V1 can be expressed to Kronecker product operation and its matrix form, this algorithm is implemented by the inner operation between retinal image primitives and primary visual cortex's column. It has simple, efficient and robust features, which is, therefore, such a neural algorithm, which can be completed by biological vision.
2. It is more suitable that the function of cortical column in cortex V1 is considered as the basic unit of visual image processing (such unit can implement basic multiplication of visual primitives, such as contour, line, and edge), rather than a set of tiled array filter. Fourier Transformation is replaced with Kronecker product, which greatly reduces the computational complexity. The neurobiological basis of this idea is that a visual image can be represented as a linear combination of orderly orthogonal primitive image containing some local feature. In the visual pathway, the image patches are topographically mapped onto cortex V1 through parallel multi-channels and then are processed independently by functional columns. Clearly, the above new perspective has some reference significance to exploring the neural mechanisms on the human visual information processing.
Differential responses of the mosquito Aedes albopictus from the Indian Ocean region to two chikungunya isolates
Authors: Martin Estelle , Moutailler Sara , Madec Yoann , Failloux Anna-Bella 
Published: March 2010

Abstract

Background

Aedes aegypti and Aedes albopictus are both vectors of chikungunya virus (CHIKV). The two Aedes species co-exist in the Indian Ocean region and were involved in the 2005-2006 CHIKV outbreaks. In the Reunion Island, a single mutation in the viral envelope has been selected that leads to high levels of replication in Ae. albopictus, and a short extrinsic incubation period as the virus could be found in saliva as early as two days after infection. An important question is whether this variant is associated with adverse effects impacting some mosquito life-history traits such as survival and reproduction.

Results
We performed experimental infections using three mosquito strains of Ae. aegypti Mayotte and Ae. albopictus (Mayotte and Reunion), and two CHIKV strains (E1-226A and E1-226V). Ae. aegypti Mayotte were similarly susceptible to both viral strains, whereas Ae. albopictus Mayotte and Ae. albopictus Reunion were more susceptible to CHIKV E1-226V than to E1-226A. In terms of life-history traits measured by examining mosquito survival and reproduction, we found that: (1) differences were observed between responses of mosquito species to the two viruses, (2) CHIKV infection only affected significantly some life-history traits of Ae. albopictus Reunion and not of the other two mosquito strains, and (3) CHIKV reduced the lifespan of Ae. albopictus Reunion and shortened the time before egg laying.

Conclusion
We demonstrated that CHIKV only reduces the survival of Ae. albopictus from the Reunion Island. By laying eggs just before death, reproduction of Ae. albopictus from the Reunion Island is not reduced since other parameters characterizing oviposition and hatching were not affected.
Visual acuity in larval zebrafish: behavior and histology
Authors: Haug Marion F , Biehlmaier Oliver , Mueller Kaspar P , Neuhauss Stephan CF 
Published: March 2010

Abstract

Background
Visual acuity, the ability of the visual system to distinguish two separate objects at a given angular distance, is influenced by the optical and neuronal properties of the visual system. Although many factors may contribute, the ultimate limit is photoreceptor spacing. In general, at least one unstimulated photoreceptor flanked by two stimulated ones is needed to perceive two objects as separate. This critical interval is also referred to as the Nyquist frequency and is according to the Shannon sampling theorem the highest spatial frequency where a pattern can be faithfully transmitted. We measured visual acuity in a behavioral experiment and compared the data to the physical limit given by photoreceptor spacing in zebrafish larvae.

Results
We determined visual acuity by using the optokinetic response (OKR), reflexive eye movements in response to whole field movements of the visual scene. By altering the spatial frequency we determined the visual acuity at approximately 0.16 cycles/degree (cpd) (minimum separable angle = 3.1°). On histological sections we measured the retinal magnification factor and the distance between double cones, that are thought to mediate motion perception. These measurements set the physical limit at 0.24 cpd (2.1°).

Conclusion
The maximal spatial information as limited by photoreceptor spacing can not be fully utilized in a motion dependent visual behavior, arguing that the larval zebrafish visual system has not matured enough to optimally translate visual information into behavior. Nevertheless behavioral acuity is remarkable close to its maximal value, given the immature state of young zebrafish larvae.
Are Nepali students at risk of HIV? A cross‐sectional study of condom use at first sexual intercourse among college students in Kathmandu
Authors: Adhikari Ramesh 
Published: March 2010

BackgroundCondoms offer the best protection against unintended pregnancies and sexually transmitted infections. Little research has been conducted to determine the prevalence and investigate the influencing factors of condom use at first sexual intercourse among college students.MethodsA self‐administered questionnaire was completed by 1137 college students (573 male and 564 female) in the Kathmandu Valley. Analyses were confined to 428 students who reported that they have ever had sexual intercourse. The association between condom use at first sexual intercourse and the explanatory variables was assessed in bivariate analysis using Chi‐square tests. The associations were further explored using multivariate logistic analysis in order to identify the significant predictors after controlling for other variables.ResultsAmong the sexually active students, less than half (48%) had used condoms during first sexual intercourse. The results from the logistic regression analysis revealed that age, caste and/or ethnicity, age at first sexual intercourse, types of first sex partner, alcohol consumption and mass media exposure are significant predictors for condom use at first sexual intercourse among the college students. Students in the older age groups who had first sex were about four times (16 to 19 years old) (OR = 3.5) more likely and nine times (20 or older) (OR = 8.9) more likely than the students who had sex before 16 years of age to use condoms at first sexual intercourse.Moreover, those students who had first sex with commercial sex worker were five times (OR = 4.9) more likely than those who had first sex with their spouse to use condoms at first sex. Furthermore, students who had higher exposure to both print and electronic media were about twice (OR = 1.75) as likely as those who had lower media exposure to use condoms. On the other hand, students who frequently consumed alcohol were 54% (OR = 0.46) less likely to use condoms at first sexual intercourse than those who never or rarely consumed alcohol.ConclusionsThe rate of condom use at first sexual intercourse is low among the students. It indicates students are exposed to health hazards through their sexual behaviour. If low use of condom at first sex continues, vulnerable sexual networks will grow among them that allow quicker spreading of sexually transmitted diseases and HIV. Findings from this study point to areas that policy and programmes can address to provide youth with access to the kinds of information and services they need to achieve healthy sexual and reproductive lives.
In vivo mechanical response of human Achilles tendon to a single bout of hopping exercise
Authors: Peltonen Jussi , Cronin Neil J. , Avela Janne , Finni Taija 
Published: March 2010

SUMMARY
Stiffness of the human Achilles tendon (AT) was determined in vivo before and after a single bout of hopping exercise. It was hypothesized, based on published data using in vitro specimens, that a reduction in AT stiffness may occur after just 1000 loading cycles at physiological stress levels. Ten healthy subjects performed two-legged hopping exercise consisting of 1150–2600 high impacts. Tendon stiffness was determined in several isometric ramp contractions [20%, 40%, 60%, 80% and 100% maximum voluntary contraction (MVC)] during which tendon elongation was measured using ultrasonography and two cameras. Tendon force was calculated by dividing measured ankle torque by magnetic resonance imaging-derived AT lever arm length. Tendon stiffness remained unchanged, being 430±200 N mm−1 before and 390±190 N mm−1 after the exercise [not significant (n.s.)]. Despite the lack of changes in stiffness, maximum tendon force during MVC was reduced from 3.5±0.6 kN to 2.8±0.7 kN (P&lt;0.01). As the proposed decline in stiffness was not observed, it is concluded that mechanical fatigue did not take place in the AT of healthy individuals after a single bout of high-impact exercise performed until exhaustion.