bluuebunny/crossref_metadata_2025_split huggingface dataset:
Enhanced killing of human B-cell lymphoma targets by combined use of cytokine-induced killer cell (CIK) cultures and anti-CD20 antibodies
Authors: Pievani Alice , Belussi Camilla , Klein Christian , Rambaldi Alessandro , Golay Josée , Introna Martino 
Published: November 2010

AbstractWe have investigated combining adoptive immunotherapy with cytokine-induced killer (CIK) cells and anti-CD20 monoclonal antibodies (mAb) GA101 or rituximab to optimize B-cell non-Hodgkin lymphoma (B-NHL) therapy. CIK cultures alone demonstrated significant cytotoxic activity against B-NHL cell lines or freshly isolated samples in either an autologous or allogeneic combination. This natural cytotoxicity (NC) was mainly due to the predominating CD3+CD56+ CIK population (40%–75%) present in the cultures. The addition of anti-CD20 mAb GA101 or rituximab further increased cytotoxicity by 35% and 15%, respectively. This enhancement was mainly due to antibody-dependent cytotoxicity (ADCC) mediated by the 1%–10% NK cells contaminating CIK cultures. The addition of human serum (HS) inhibited NK-cell activation induced by rituximab, but not activation induced by GA101.Overall lysis in presence of serum, even of a resistant B-NHL cell line, was significantly increased by 100 μg/mL of rituximab, but even more so by GA101, with respect to CIK cultures alone. This was due to the combined action of complement-mediated cytotoxicity (CDC), ADCC, and CIK-mediated NC. These data suggest that rituximab, and even more so GA101, could be used in vivo to enhance CIK therapeutic activity in B-NHL.
FNAIT: the fetus pleads guilty!
Authors: Kaplan Cécile 
Published: November 2010

Abstract
Fetal/neonatal alloimmune thrombocytopenia (FNAIT) resulting from fetal platelet destruction by maternal alloantibodies is the most common cause of severe fetal thrombocytopenia and of neonatal thrombocytopenia in maternity wards.1 The pathophysiology is largely unknown. The fetus has long been considered as an “innocent bystander.”
Gremlin: vexing VEGF receptor agonist
Authors: Claesson-Welsh Lena 
Published: November 2010

Abstract
Gremlins are mischievous creatures in English folklore, believed to be the cause of otherwise unexplainable breakdowns (the word gremlins is derived from the Old English “gremian” or “gremman,” “to vex”). Gremlin (or Gremlin-1) is also the designation of a secreted protein that is known to regulate bone formation during development. In this issue of Blood, Mitola et al report the novel role of Gremlin as a VEGFR2 agonist1 and the function of the Gremlin protein seems vexing indeed.
BMP-2: a culprit for anemia in myeloma
Authors: Ludwig Heinz 
Published: November 2010

Abstract
Maes and colleagues1 have found increased BMP-2 in the blood of multiple myeloma patients as an important stimulator of hepcidin in addition to other well-known mediators of hepcidin induction. These findings were obtained by transfection of human liver HuH7 cells with reporter constructs for the hepcidin promoter carrying either mutations in BMP-response elements or in STAT3-binding sites.
Bioactive conformational generation of small molecules: A comparative analysis between force-field and multiple empirical criteria based methods
Authors: Bai Fang , Liu Xiaofeng , Li Jiabo , Zhang Haoyun , Jiang Hualiang , Wang Xicheng , Li Honglin 
Published: November 2010

Abstract

Background
Conformational sampling for small molecules plays an essential role in drug discovery research pipeline. Based on multi-objective evolution algorithm (MOEA), we have developed a conformational generation method called Cyndi in the previous study. In this work, in addition to Tripos force field in the previous version, Cyndi was updated by incorporation of MMFF94 force field to assess the conformational energy more rationally. With two force fields against a larger dataset of 742 bioactive conformations of small ligands extracted from PDB, a comparative analysis was performed between pure force field based method (FFBM) and multiple empirical criteria based method (MECBM) hybrided with different force fields.

Results
Our analysis reveals that incorporating multiple empirical rules can significantly improve the accuracy of conformational generation. MECBM, which takes both empirical and force field criteria as the objective functions, can reproduce about 54% (within 1Å RMSD) of the bioactive conformations in the 742-molecule testset, much higher than that of pure force field method (FFBM, about 37%). On the other hand, MECBM achieved a more complete and efficient sampling of the conformational space because the average size of unique conformations ensemble per molecule is about 6 times larger than that of FFBM, while the time scale for conformational generation is nearly the same as FFBM. Furthermore, as a complementary comparison study between the methods with and without empirical biases, we also tested the performance of the three conformational generation methods in MacroModel in combination with different force fields. Compared with the methods in MacroModel, MECBM is more competitive in retrieving the bioactive conformations in light of accuracy but has much lower computational cost.

Conclusions
By incorporating different energy terms with several empirical criteria, the MECBM method can produce more reasonable conformational ensemble with high accuracy but approximately the same computational cost in comparison with FFBM method. Our analysis also reveals that the performance of conformational generation is irrelevant to the types of force field adopted in characterization of conformational accessibility. Moreover, post energy minimization is not necessary and may even undermine the diversity of conformational ensemble. All the results guide us to explore more empirical criteria like geometric restraints during the conformational process, which may improve the performance of conformational generation in combination with energetic accessibility, regardless of force field types adopted.
An Sp185/333 gene cluster from the purple sea urchin and putative microsatellite-mediated gene diversification
Authors: Miller Chase A , Buckley Katherine M , Easley Rebecca L , Smith L Courtney 
Published: November 2010

AbstractBackgroundThe immune system of the purple sea urchin,Strongylocentrotus purpuratus, is complex and sophisticated. An important component of sea urchin immunity is theSp185/333gene family, which is significantly upregulated in immunologically challenged animals. TheSp185/333genes are less than 2 kb with two exons and are members of a large diverse family composed of greater than 40 genes. TheS. purpuratusgenome assembly, however, contains only sixSp185/333genes. This underrepresentation could be due to the difficulties that large gene families present in shotgun assembly, where multiple similar genes can be collapsed into a single consensus gene.ResultsTo understand the genomic organization of theSp185/333gene family, a BAC insert containingSp185/333genes was assembled, with careful attention to avoiding artifacts resulting from collapse or artificial duplication/expansion of very similar genes. Twelve candidate BAC assemblies were generated with varying parameters and the optimal assembly was identified by PCR, restriction digests, and subclone sequencing. The validated assembly contained sixSp185/333genes that were clustered in a 34 kb region at one end of the BAC with five of the six genes tightly clustered within 20 kb. TheSp185/333genes in this cluster were no more similar to each other than to previously sequencedSp185/333genes isolated from three different animals. This was unexpected given their proximity and putative effects of gene homogenization in closely linked, similar genes. All six genes displayed significant similarity including both 5' and 3' flanking regions, which were bounded by microsatellites. Three of theSp185/333genes and their flanking regions were tandemly duplicated such that each repeated segment consisted of a gene plus 0.7 kb 5' and 2.4 kb 3' of the gene (4.5 kb total). Both edges of the segmental duplications were bounded by different microsatellites.ConclusionsThe high sequence similarity of theSp185/333genes and flanking regions, suggests that the microsatellites may promote genomic instability and are involved with gene duplication and/or gene conversion and the extraordinary sequence diversity of this family.
A comparative genome-wide study of ncRNAs in trypanosomatids
Authors: Doniger Tirza , Katz Rodolfo , Wachtel Chaim , Michaeli Shulamit , Unger Ron 
Published: November 2010

Abstract

Background
Recent studies have provided extensive evidence for multitudes of non-coding RNA (ncRNA) transcripts in a wide range of eukaryotic genomes. ncRNAs are emerging as key players in multiple layers of cellular regulation. With the availability of many whole genome sequences, comparative analysis has become a powerful tool to identify ncRNA molecules. In this study, we performed a systematic genome-wide in silico screen to search for novel small ncRNAs in the genome of Trypanosoma brucei using techniques of comparative genomics.

Results
In this study, we identified by comparative genomics, and validated by experimental analysis several novel ncRNAs that are conserved across multiple trypanosomatid genomes. When tested on known ncRNAs, our procedure was capable of finding almost half of the known repertoire through homology over six genomes, and about two-thirds of the known sequences were found in at least four genomes. After filtering, 72 conserved unannotated sequences in at least four genomes were found, 29 of which, ranging in size from 30 to 392 nts, were conserved in all six genomes. Fifty of the 72 candidates in the final set were chosen for experimental validation. Eighteen of the 50 (36%) were shown to be expressed, and for 11 of them a distinct expression product was detected, suggesting that they are short ncRNAs. Using functional experimental assays, five of the candidates were shown to be novel H/ACA and C/D snoRNAs; these included three sequences that appear as singletons in the genome, unlike previously identified snoRNA molecules that are found in clusters. The other candidates appear to be novel ncRNA molecules, and their function is, as yet, unknown.

Conclusions
Using comparative genomic techniques, we predicted 72 sequences as ncRNA candidates in T. brucei. The expression of 50 candidates was tested in laboratory experiments. This resulted in the discovery of 11 novel short ncRNAs in procyclic stage T. brucei, which have homologues in the other trypansomatids. A few of these molecules are snoRNAs, but most of them are novel ncRNA molecules. Based on this study, our analysis suggests that the total number of ncRNAs in trypanosomatids is in the range of several hundred.
Phenotype, functions and fate of adoptively transferred tumor draining lymphocytes activated ex vivo in mice with an aggressive weakly immunogenic mammary carcinoma
Authors: Miller Catriona HT , Graham Laura , Bear Harry D 
Published: November 2010

AbstractBackgroundRegression of established tumors can be induced by adoptive immunotherapy with tumor draining lymph node lymphocytes activated with bryostatin and ionomycin. We hypothesized that tumor regression is mediated by a subset of the transferred T lymphocytes, which selectively infiltrate the tumor draining lymph nodes and proliferatein vivo.ResultsAdoptive transfer of B/I activated tumor draining lymphocytes induces regression of advanced 4T1 tumors, and depletion of CD8, but not CD4 T cells, abrogated tumor regression in mice. The predominant mediators of tumor regression are CD8+ and derived from CD62L-T cells. Transferred lymphocytes reached their peak concentration (10.5%) in the spleen 3 days after adoptive transfer and then rapidly declined. Adoptively transferred cells preferentially migrated to and/or proliferated in the tumor draining lymph nodes, peaking at day 5 (10.3%) and remained up to day 28. CFSE-stained cells were seen in tumors, also peaking at day 5 (2.1%). Bryostatin and ionomycin-activated cells proliferated vigorouslyin vivo, with 10 generations evident in the tumor draining lymph nodes on day 3. CFSE-stained cells found in the tumor draining lymph nodes on day 3 were 30% CD8+, 72% CD4+, 95% CD44+, and 39% CD69+. Pre-treatment of recipient mice with cyclophosphamide dramatically increased the number of interferon-gamma producing cells.ConclusionsAdoptively transferred CD8+ CD62LlowT cells are the principal mediators of tumor regression, and host T cells are not required. These cells infiltrate 4T1 tumors, track preferentially to tumor draining lymph nodes, have an activated phenotype, and proliferatein vivo. Cyclophosphamide pre-treatment augments the anti-tumor effect by increasing the proliferation of interferon-gamma producing cells in the adoptive host.
High level transgenic expression of soybean (Glycine max) GmERF and Gmubi gene promoters isolated by a novel promoter analysis pipeline
Authors: Hernandez-Garcia Carlos M , Bouchard Robert A , Rushton Paul J , Jones Michelle L , Chen Xianfeng , Timko Michael P , Finer John J 
Published: November 2010

Abstract

Background
Although numerous factors can influence gene expression, promoters are perhaps the most important component of the regulatory control process. Promoter regions are often defined as a region upstream of the transcriptional start. They contain regulatory elements that interact with regulatory proteins to modulate gene expression. Most genes possess their own unique promoter and large numbers of promoters are therefore available for study. Unfortunately, relatively few promoters have been isolated and characterized; particularly from soybean (Glycine max).

Results
In this research, a bioinformatics approach was first performed to identify members of the Gmubi (
G.

m

ax
ubiquitin) and the GmERF (
G

.

m

ax
Ethylene Response Factor) gene families of soybean. Ten Gmubi and ten GmERF promoters from selected genes were cloned upstream of the gfp gene and successfully characterized using rapid validation tools developed for both transient and stable expression. Quantification of promoter strength using transient expression in lima bean (Phaseolus lunatus) cotyledonary tissue and stable expression in soybean hairy roots showed that the intensity of gfp gene expression was mostly conserved across the two expression systems. Seven of the ten Gmubi promoters yielded from 2- to 7-fold higher expression than a standard CaMV35S promoter while four of the ten GmERF promoters showed from 1.5- to 2.2-times higher GFP levels compared to the CaMV35S promoter. Quantification of GFP expression in stably-transformed hairy roots of soybean was variable among roots derived from different transformation events but consistent among secondary roots, derived from the same primary transformation events. Molecular analysis of hairy root events revealed a direct relationship between copy number and expression intensity; higher copy number events displayed higher GFP expression.

Conclusion
In this study, we present expression intensity data on 20 novel soybean promoters from two different gene families, ubiquitin and ERF. We also demonstrate the utility of lima bean cotyledons and soybean hairy roots for rapid promoter analyses and provide novel insights towards the utilization of these expression systems. The soybean promoters characterized here will be useful for production of transgenic soybean plants for both basic research and commercial plant improvement.
Statistics teaching in medical school: Opinions of practising doctors
Authors: Miles Susan , Price Gill M , Swift Louise , Shepstone Lee , Leinster Sam J 
Published: November 2010

Abstract

Background
The General Medical Council expects UK medical graduates to gain some statistical knowledge during their undergraduate education; but provides no specific guidance as to amount, content or teaching method. Published work on statistics teaching for medical undergraduates has been dominated by medical statisticians, with little input from the doctors who will actually be using this knowledge and these skills after graduation. Furthermore, doctor's statistical training needs may have changed due to advances in information technology and the increasing importance of evidence-based medicine. Thus there exists a need to investigate the views of practising medical doctors as to the statistical training required for undergraduate medical students, based on their own use of these skills in daily practice.

Methods
A questionnaire was designed to investigate doctors' views about undergraduate training in statistics and the need for these skills in daily practice, with a view to informing future teaching. The questionnaire was emailed to all clinicians with a link to the University of East Anglia Medical School. Open ended questions were included to elicit doctors' opinions about both their own undergraduate training in statistics and recommendations for the training of current medical students. Content analysis was performed by two of the authors to systematically categorise and describe all the responses provided by participants.

Results
130 doctors responded, including both hospital consultants and general practitioners. The findings indicated that most had not recognised the value of their undergraduate teaching in statistics and probability at the time, but had subsequently found the skills relevant to their career. Suggestions for improving undergraduate teaching in these areas included referring to actual research and ensuring relevance to, and integration with, clinical practice.

Conclusions
Grounding the teaching of statistics in the context of real research studies and including examples of typical clinical work may better prepare medical students for their subsequent career.
HIV-1 subtype C envelope characteristics associated with divergent rates of chronic disease progression
Authors: Archary Derseree , Gordon Michelle L , Green Taryn N , Coovadia Hoosen M , Goulder Philip JR , Ndung'u Thumbi 
Published: November 2010

Abstract

Background
HIV-1 envelope diversity remains a significant challenge for the development of an efficacious vaccine. The evolutionary forces that shape the diversity of envelope are incompletely understood. HIV-1 subtype C envelope in particular shows significant differences and unique characteristics compared to its subtype B counterpart. Here we applied the single genome sequencing strategy of plasma derived virus from a cohort of therapy naïve chronically infected individuals in order to study diversity, divergence patterns and envelope characteristics across the entire HIV-1 subtype C gp160 in 4 slow progressors and 4 progressors over an average of 19.5 months.

Results
Sequence analysis indicated that intra-patient nucleotide diversity within the entire envelope was higher in slow progressors, but did not reach statistical significance (p = 0.07). However, intra-patient nucleotide diversity was significantly higher in slow progressors compared to progressors in the C2 (p = 0.0006), V3 (p = 0.01) and C3 (p = 0.005) regions. Increased amino acid length and fewer potential N-linked glycosylation sites (PNGs) were observed in the V1-V4 in slow progressors compared to progressors (p = 0.009 and p = 0.02 respectively). Similarly, gp41 in the progressors was significantly longer and had fewer PNGs compared to slow progressors (p = 0.02 and p = 0.02 respectively). Positive selection hotspots mapped mainly to V1, C3, V4, C4 and gp41 in slow progressors, whereas hotspots mapped mainly to gp41 in progressors. Signature consensus sequence differences between the groups occurred mainly in gp41.

Conclusions
These data suggest that separate regions of envelope are under differential selective forces, and that envelope evolution differs based on disease course. Differences between slow progressors and progressors may reflect differences in immunological pressure and immune evasion mechanisms. These data also indicate that the pattern of envelope evolution is an important correlate of disease progression in chronic HIV-1 subtype C infection.
Role of aspartyl-(asparaginyl)-β-hydroxylase mediated notch signaling in cerebellar development and function
Authors: Silbermann Elizabeth , Moskal Peter , Bowling Nathaniel , Tong Ming , de la Monte Suzanne M 
Published: November 2010

AbstractBackgroundAspartyl-(Asparaginyl)-β-Hydroxylase (AAH) is a hydroxylating enzyme that promotes cell motility by enhancing Notch-Jagged-HES-1 signaling. Ethanol impaired cerebellar neuron migration during development is associated with reduced expression of AAH.MethodsTo further characterize the role of AAH in relation to cerebellar development, structure, and function, we utilized an in vivo model of early postnatal (P2) intracerebro-ventricular gene delivery to silence AAH with small interfering RNA (siAAH), or over-express it with recombinant plasmid DNA (pAAH). On P20, we assessed cerebellar motor function by rotarod testing. Cerebella harvested on P21 were used to measure AAH, genes/proteins that mediate AAH's downstream signaling, i.e. Notch-1, Jagged-1, and HES-1, and immunoreactivity corresponding to neuronal and glial elements.ResultsThe findings demonstrated that: 1) siAAH transfection impaired motor performance and blunted cerebellar foliation, and decreased expression of neuronal and glial specific genes; 2) pAAH transfection enhanced motor performance and increased expression of neuronal and glial cytoskeletal proteins; and 3) alterations in AAH expression produced similar shifts in Notch-1, Jagged-1, and HES-1 protein or gene expression.ConclusionsThe results support our hypothesis that AAH is an important mediator of cerebellar development and function, and link AAH expression to Notch signaling pathways in the developing brain.
Man-animal relationships in Central Nepal
Authors: Lohani Usha 
Published: November 2010

Abstract
Background
Nepal is small in size but rich in bio-cultural diversity. The rugged terrain of the country is home to a number of unique assemblages of fauna, some of which are endemic. Not only faunal resources the country also harbors some very ancient populations whose interrelationship with these diverse faunal resources is very intimate and thus demands scientific study. Animals play important role in both material and spiritual spheres of their life. There are more than hundred groups of such populations in the country and the group Tamang is one of these. The present paper studies Tamang-animal relationships in central Nepal.
There is a growing trend of scientific ethnozoological studies all across the globe, but this field is yet in its infancy in Nepal. The country is losing important fauna as well as ancient human cultures at the advent of development processes. As a result, ethnozoological knowledge is also teetering on the brink of extinction.

Methods
Ethnozoological data were collected by applying different participatory approaches techniques such as semi-structured interviews, participatory rural appraisal, key informant interviews and focus group discussions.
Quantitative data were obtained by employing a household level questionnaire survey. Data were collected from the period of September 2004 to August 2005.
Most of the animals were identified up to the species level with the help of standard taxonomic keys.

Results
The Tamang community treasures knowledge on various uses of 41 genera belonging to 28 families. Out of total number of animals, 14.6% belong to the Invertebrate group and the rest to the Vertebrate group. Of the total uses 58% fall in the food and medicinal use category, 16% in the magico-religious use category, 18% in the category of omen indication, and 2% each in the categories such as weather forecasting, trophy, ethnomusical and taboos.

Conclusions
The Tamang maintain strong ties with animals both at a material as well as spiritual level. While some animals are the sources of important traditional medicines, others are omen indicators and weather forecasters. High priority should be given in conservation of those animals which are of high consensus value to the community.