bluuebunny/crossref_metadata_2025_split huggingface dataset:
Inhibition of Expression of the Chromatin Remodeling Gene, SNF2L, Selectively Leads to DNA Damage, Growth Inhibition, and Cancer Cell Death
Authors: Ye Yin , Xiao Yi , Wang Wenting , Wang Qien , Yearsley Kurtis , Wani Altaf A. , Yan Qintao , Gao Jian-Xin , Shetuni Brandon S. , Barsky Sanford H. 
Published: December 2009

Abstract
SNF2L, a chromatin remodeling gene expressed in diverse tissues, cancers, and derived cell lines, contributes to the chromatin remodeling complex that facilitates transcription. Because of this wide expression, it has not been exploited as a cancer therapeutic target. However, based on our present studies, we find that cancer cells, although expressing SNF2L at similar levels as their normal counterparts, are sensitive to its knockdown. This is not observed when its imitation SWI ortholog, SNF2H, is inhibited. SNF2L siRNA inhibition using two different siRNAs separately reduced SNF2L transcript levels and protein in both normal and cancer lines, but only the cancer lines showed significant growth inhibition, DNA damage, a DNA damage response, and phosphorylation of checkpoint proteins and marked apoptosis. DNA damage and the damage response preceded apoptosis rather than being consequences of it. The damage response consisted of increased phosphorylation of multiple substrates including ATR, BRCA1, CHK1, CHK2, and H2AX. Both the total and phosphorylated levels of p53 increased. The downstream targets of p53, p21, GADD45A, and 14-3-3σ, were also upregulated. The alterations in checkpoint proteins included increased phosphorylated cdc2 but not Rb, which resulted in a modest G2-M arrest. Although apoptosis may be mediated by Apaf-1/caspase 9, other caspases could be involved. Other members of the chromatin remodeling or SWI/SNF gene families exhibited overall reduced levels of expression in the cancer lines compared with the normal lines. This raised the hypothesis that cancers are sensitive to SNF2L knockdown because, unlike their normal counterparts, they lack sufficient compensation from other family members. (Mol Cancer Res 2009;7(12):1984–99)
Gallic Acid Suppresses Lipopolysaccharide-Induced Nuclear Factor-κB Signaling by Preventing RelA Acetylation in A549 Lung Cancer Cells
Authors: Choi Kyung-Chul , Lee Yoo-Hyun , Jung Myung Gu , Kwon Seung Hyun , Kim Mi-Jeong , Jun Woo Jin , Lee Jeongmin , Lee Jae Myun , Yoon Ho-Geun 
Published: December 2009

Abstract
Although multiple studies have revealed that gallic acid plays an important role in the inhibition of malignant transformation, cancer development, and inflammation, the molecular mechanism of gallic acid in inflammatory diseases is still unclear. In this study, we identified gallic acid from Rosa rugosa as a histone acetyltransferase (HAT) inhibitor with global specificity for the majority of HAT enzymes, but with no activity toward epigenetic enzymes including sirtuin (silent mating type information regulation 2 homologue) 1 (S. cerevisiae), histone deacetylase, and histone methyltransferase. Enzyme kinetic studies indicated that gallic acid uncompetitively inhibits p300/CBP-dependent HAT activities. We found that gallic acid inhibits p300-induced p65 acetylation, both in vitro and in vivo, increases the level of cytosolic IκBα, prevents lipopolysaccharide (LPS)-induced p65 translocation to the nucleus, and suppresses LPS-induced nuclear factor-κB activation in A549 lung cancer cells. We have also shown that gallic acid treatment inhibits the acetylation of p65 and the LPS-induced serum levels of interleukin-6 in vivo. Importantly, gallic acid generally inhibited inflammatory responses caused by other stimuli, including LPS, IFN-γ, and interleukin-1β, and further downregulated the expression of nuclear factor-κB–regulated antiapoptotic genes. These results show the crucial role of acetylation in the development of inflammatory diseases. (Mol Cancer Res 2009;7(12):2011–21)
A Novel Inhibitor of DNA Polymerase β Enhances the Ability of Temozolomide to Impair the Growth of Colon Cancer Cells
Authors: Jaiswal Aruna S. , Banerjee Sanjeev , Panda Harekrushna , Bulkin Charles D. , Izumi Tadahide , Sarkar Fazlul H. , Ostrov David A. , Narayan Satya 
Published: December 2009

Abstract
The recent emerging concept to sensitize cancer cells to DNA-alkylating drugs is by inhibiting various proteins in the base excision repair (BER) pathway. In the present study, we used structure-based molecular docking of DNA polymerase β (Pol-β) and identified a potent small molecular weight inhibitor, NSC-666715. We determined the specificity of this small molecular weight inhibitor for Pol-β by using in vitro activities of APE1, Fen1, DNA ligase I, and Pol-β–directed single-nucleotide and long-patch BER. The binding specificity of NSC-666715 with Pol-β was also determined by using fluorescence anisotropy. The effect of NSC-666715 on the cytotoxicity of the DNA-alkylating drug temozolomide (TMZ) to colon cancer cells was determined by in vitro clonogenic and in vivo xenograft assays. The reduction in tumor growth was higher in the combination treatment relative to untreated or monotherapy treatment. NSC-666715 showed a high specificity for blocking Pol-β activity. It blocked Pol-β–directed single-nucleotide and long-patch BER without affecting the activity of APE1, Fen1, and DNA ligase I. Fluorescence anisotropy data suggested that NSC-666715 directly and specifically interacts with Pol-β and interferes with binding to damaged DNA. NSC-666715 drastically induces the sensitivity of TMZ to colon cancer cells both in in vitro and in vivo assays. The results further suggest that the disruption of BER by NSC-666715 negates its contribution to drug resistance and bypasses other resistance factors, such as mismatch repair defects. Our findings provide the “proof-of-concept” for the development of highly specific and thus safer structure-based inhibitors for the prevention of tumor progression and/or treatment of colorectal cancer. (Mol Cancer Res 2009;7(12):1973–83)
Power and Social Work in the United Kingdom
Authors: Gilbert Tony , Powell Jason L. 
Published: December 2009

• Summary: This article explores relations of power in social work using insights drawn from the critical ‘toolkit’ emanating from work of French philosopher, Michel Foucault. The article discusses the relationship between Foucault’s conceptual tools of ‘knowledge and power’, the emergence of ‘the modern subject’ and the concept of ‘governmentality’. Despite ongoing pressures, professional expertise persists as a core element of neo-liberal government in the management of the population. We use a Foucauldian perspective to explore two issues central to contemporary practice: surveillance and discretion that epitomise dualism of power relations. On the one hand, surveillance brings with it a potentially problematic process especially in context of top down managerial power; yet, on the other hand, discretion is much more focused on what Foucault (1977) calls ‘the microphysics of power’ with opportunities for ‘resistance’ from the bottom up. • Findings: Professional expertise creates a paradox where surveillance and discretion operate within similar social space as the expression of power relations that encompass the matrix of users, carers and social workers. On one hand, surveillance restricts practice however; on the other, complexity opens the space for resistance and new formulations of power relations. • Applications : Exposing social work activity to a critical stance enables the exploration of relations of power identifying how commitments such as empowerment and anti-oppressive practice become detached from their original radical and humanitarian moorings to feature now as components of oppressive discourses they might once have challenged.
Socialization Factors Conducive to Social Work Students’ Gain in Competence
Authors: Cheung Chau-Kiu , Tang Kwong-Leung 
Published: December 2009

• Summary: Socialization experiences related to background and secondary education are likely to affect academic achievement in university education, according to extant theory and research. How these experiences affect Hong Kong social work students’ grade-point-average (GPA) and self-assessed gain in competence in social work is the focus of examination in the present study. It is argued that among the experiences, that of volunteering during secondary school is likely to benefit the student, because of value congruence between volunteering and social work education. • Findings: This effect bears out in a survey of social work undergraduates in Hong Kong. Another important finding is the absence of privilege accruing from the socioeconomic status of students’ parents. In contrast, some indicators of the status negatively affected the students’ grade-point-averages. • Applications : These findings favor the use of the applicant’s volunteering experience as an admission criterion for the social work education program in university.
Children Exposed to Domestic Violence
Authors: Øverlien Carolina 
Published: December 2009

• Summary: This article examines and discusses the research field of children exposed to domestic violence, a field which has greatly expanded during the last 10 years. The author presents an overview of this research, discusses its implications, and describes future challenges and contemporary knowledge gaps. • Findings: The author argues that the field is dominated by studies that a) are quantitative, b) use the mothers as the informant and c) are represented by traditional psychology and social medicine, rather than social work. These studies have found substantial support for the negative emotional and behavioral consequences that children exposed to domestic violence suffer. However, many questions and problems remain unanswered. These questions include both the research field itself and the need for new approaches such as qualitative research including the voice of the child, longitudinal studies, and questions regarding methodology and research ethics. • Applications : The author argues that there is a need for more qualitative research in general and social work research in particular. The implications for social work practice and policy are discussed.
Fluorinated per-acetylated GalNAc metabolically alters glycan structures on leukocyte PSGL-1 and reduces cell binding to selectins
Authors: Marathe Dhananjay D. , Buffone Alexander , Chandrasekaran E. V. , Xue Jun , Locke Robert D. , Nasirikenari Mehrab , Lau Joseph T. Y. , Matta Khushi L. , Neelamegham Sriram 
Published: December 2009

AbstractNovel strategies to control the binding of adhesion molecules belonging to the selectin family are required for the treatment of inflammatory diseases. We tested the possibility that synthetic monosaccharide analogs can compete with naturally occurring sugars to alter the O-glycan content on human leukocyte cell surface selectin-ligand, P-selectin glycoprotein ligand-1 (PSGL-1). Resulting reduction in the sialyl Lewis-X–bearing epitopes on this ligand may reduce cell adhesion. Consistent with this hypothesis, 50μM per-acetylated 4F-GalNAc added to the growth media of promyelocytic HL-60 cells reduced the expression of the cutaneous lymphocyte associated-antigen (HECA-452 epitope) by 82% within 2 cell doubling cycles. Cell binding to all 3 selectins (L-, E-, and P-selectin) was reduced in vitro. 4F-GalNAc was metabolically incorporated into PSGL-1, and this was accompanied by an approximately 20% reduction in PSGL-1 glycan content. A 70% to 85% reduction in HECA-452 binding epitope and N-acetyl lactosamine content in PSGL-1 was also noted on 4F-GalNAc addition. Intravenous 4F-GalNAc infusion reduced leukocyte migration to the peritoneum in a murine model of thioglycolate-induced peritonitis. Thus, the compound has pharmacologic activity. Overall, the data suggest that 4F-GalNAc may be applied as a metabolic inhibitor to reduce O-linked glycosylation, sialyl Lewis-X formation, and leukocyte adhesion via the selectins.
Single-cell analysis of the common lymphoid progenitor compartment reveals functional and molecular heterogeneity
Authors: Mansson Robert , Zandi Sasan , Welinder Eva , Tsapogas Panagiotis , Sakaguchi Nobuo , Bryder David , Sigvardsson Mikael 
Published: December 2009

AbstractTo investigate molecular events involved in the regulation of lymphoid lineage commitment, we crossed λ5 reporter transgenic mice to Rag1-GFP knockin mice. This allowed us to subfractionate common lymphoid progenitors and pre-pro-B (fraction A) cells into λ5−Rag1low, λ5−Rag1high, and λ5+Rag1high cells. Clonal in vitro differentiation analysis demonstrated that Rag1low cells gave rise to B/T and NK cells. Rag1high cells displayed reduced NK-cell potential with preserved capacity to generate B- and T-lineage cells, whereas the λ5+ cells were B-lineage restricted. Ebf1 and Pax5 expression was largely confined to the Rag1high populations. These cells also expressed a higher level of the surface protein LY6D, providing an additional tool for the analysis of early lymphoid development. These data suggest that the classic common lymphoid progenitor compartment composes a mixture of cells with relatively restricted lineage potentials, thus opening new possibilities to investigate early hematopoiesis.
RNRdb, a curated database of the universal enzyme family ribonucleotide reductase, reveals a high level of misannotation in sequences deposited to Genbank
Authors: Lundin Daniel , Torrents Eduard , Poole Anthony M , Sjöberg Britt-Marie 
Published: December 2009

Abstract

Background
Ribonucleotide reductases (RNRs) catalyse the only known de novo pathway for deoxyribonucleotide synthesis, and are therefore essential to DNA-based life. While ribonucleotide reduction has a single evolutionary origin, significant differences between RNRs nevertheless exist, notably in cofactor requirements, subunit composition and allosteric regulation. These differences result in distinct operational constraints (anaerobicity, iron/oxygen dependence and cobalamin dependence), and form the basis for the classification of RNRs into three classes.

Description
In RNRdb (Ribonucleotide Reductase database), we have collated and curated all known RNR protein sequences with the aim of providing a resource for exploration of RNR diversity and distribution. By comparing expert manual annotations with annotations stored in Genbank, we find that significant inaccuracies exist in larger databases. To our surprise, only 23% of protein sequences included in RNRdb are correctly annotated across the key attributes of class, role and function, with 17% being incorrectly annotated across all three categories. This illustrates the utility of specialist databases for applications where a high degree of annotation accuracy may be important. The database houses information on annotation, distribution and diversity of RNRs, and links to solved RNR structures, and can be searched through a BLAST interface. RNRdb is accessible through a public web interface at http://rnrdb.molbio.su.se.

Conclusion
RNRdb is a specialist database that provides a reliable annotation and classification resource for RNR proteins, as well as a tool to explore distribution patterns of RNR classes. The recent expansion in available genome sequence data have provided us with a picture of RNR distribution that is more complex than believed only a few years ago; our database indicates that RNRs of all three classes are found across all three cellular domains. Moreover, we find a number of organisms that encode all three classes.
Divergent effects of norepinephrine, dopamine and substance P on the activation, differentiation and effector functions of human cytotoxic T lymphocytes
Authors: Strell Carina , Sievers Anne , Bastian Philipp , Lang Kerstin , Niggemann Bernd , Zänker Kurt S , Entschladen Frank 
Published: December 2009

AbstractBackgroundNeurotransmitters are important regulators of the immune system, with very distinct and varying effects on different leukocyte subsets. So far little is known about the impact of signals mediated by neurotransmitters on the function of CD8+T lymphocytes. Therefore, we investigated the influence of norepinephrine, dopamine and substance P on the key tasks of CD8+T lymphocytes: activation, migration, extravasation and cytotoxicity.ResultsThe activation of naïve CD8+T lymphocytes by CD3/CD28 cross-linking was inhibited by norepinephrine and dopamine, which was caused by a downregulation of interleukin (IL)-2 expressionviaErk1/2 and NF-κB inhibition. Furthermore, all of the investigated neurotransmitters increased the spontaneous migratory activity of naïve CD8+T lymphocytes with dopamine being the strongest inducer. In contrast, activated CD8+T lymphocytes showed a reduced migratory activity in the presence of norepinephrine and substance P. With regard to extravasation we found norepinephrine to induce adhesion of activated CD8+T cells: norepinephrine increased the interleukin-8 release from endothelium, which in turn had effect on the activated CXCR1+CD8+T cells. At last, release of cytotoxic granules from activated cells in response to CD3 cross-linking was not influenced by any of the investigated neurotransmitters, as we have analyzed by measuring the β-hexosamidase release.ConclusionNeurotransmitters are specific modulators of CD8+T lymphocytes not by inducing any new functions, but by fine-tuning their key tasks. The effect can be either stimulatory or suppressive depending on the activation status of the cells.
Ascorbate metabolism and the developmental demand for tartaric and oxalic acids in ripening grape berries
Authors: Melino Vanessa J , Soole Kathleen L , Ford Christopher M 
Published: December 2009

AbstractBackgroundFresh fruits are well accepted as a good source of the dietary antioxidant ascorbic acid (Asc, Vitamin C). However, fruits such as grapes do not accumulate exceptionally high quantities of Asc. Grapes, unlike most other cultivated fruits do however use Asc as a precursor for the synthesis of both oxalic (OA) and tartaric acids (TA). TA is a commercially important product in the wine industry and due to its acidifying effect on crushed juice it can influence the organoleptic properties of the wine. Despite the interest in Asc accumulation in fruits, little is known about the mechanisms whereby Asc concentration is regulated. The purpose of this study was to gain insights into Asc metabolism in wine grapes (Vitis viniferac.v. Shiraz.) and thus ascertain whether the developmental demand for TA and OA synthesis influences Asc accumulation in the berry.ResultsWe provide evidence for developmentally differentiated up-regulation of Asc biosynthetic pathways and subsequent fluctuations in Asc, TA and OA accumulation. Rapid accumulation of Asc and a low Asc to dehydroascorbate (DHA) ratio in young berries was co-ordinated with up-regulation of three of the primary Asc biosynthetic (Smirnoff-Wheeler) pathway genes. Immature berries synthesised Ascin-situfrom the primary pathway precursorsD-mannose andL-galactose. Immature berries also accumulated TA in early berry development in co-ordination with up-regulation of a TA biosynthetic gene. In contrast, ripe berries have up-regulated expression of the alternative Asc biosynthetic pathway geneD-galacturonic acid reductase with only residual expression of Smirnoff-Wheeler Asc biosynthetic pathway genes and of the TA biosynthetic gene. The ripening phase was further associated with up-regulation of Asc recycling genes, a secondary phase of increased accumulation of Asc and an increase in the Asc to DHA ratio.ConclusionWe demonstrate strong developmental regulation of Asc biosynthetic, recycling and catabolic genes in grape berries. Integration of the transcript, radiotracer and metabolite data demonstrates that Asc and TA metabolism are developmentally regulated in grapevines; resulting in low accumulated levels of the biosynthetic intermediate Asc, and high accumulated levels of the metabolic end-product TA.
Evaluation of early coronary graft patency after coronary artery bypass graft surgery using multislice computed tomography angiography
Authors: Bassri Hosseinali , Salari Farzad , Noohi Fereidoun , Motevali Marzieh , Abdi Seifollah , Givtaj Nader , Raissi Kamal , Haghjoo Majid 
Published: December 2009

Abstract

Background
Coronary artery bypass graft (CABG) surgery is the standard of care in the treatment of advanced coronary artery disease, and its long-term results are affected by the failure of bypass grafts. The aim of the present study was to evaluate the early patency rate in coronary bypass grafts.

Methods
A total of 107 consecutive patients who underwent CABG were included in this study. Early graft patency was evaluated via computed tomography (CT) angiography in the first week after surgery.

Results
There were a total of 366 grafts, comprised of 250 venous grafts and 116 arterial grafts. Multi-slice CT detected acute graft occlusions in 32 (8.7%) of all the grafts, including 26 (10%) of the 250 venous grafts and 6 (5%) of the 116 arterial grafts. The patency rates obtained were 97.3% for the left internal mammary (IMA) grafts, 50% for the radial artery grafts, and 50% for the right IMA grafts. Additionally, 107 (96.4%) grafts to the left anterior descending artery (LAD) were classified as patent, whereas 1 (30%) of the 3 grafts in the left circumflex (LCX) region and 1 (50%) of the 2 grafts in the right coronary artery (RCA) territory were found to be occluded. In the venous category, 8 (13.7%) of the 58 grafts to LAD were found to be occluded. In the LCX region, 9 (8.5%) of the 106 grafts were classified as occluded, while the remaining 97 (91.5%) grafts were patent. The venous grafts to RCA were occluded in 9 (10.4%) of the 86 grafts. Amongst the multiple preoperative, intraoperative, and postoperative factors, pump time was significantly longer in the patients with occluded grafts than in those with patent grafts (P = 0.04).

Conclusion
The IMA grafts had the highest early patency rate amongst the coronary bypass grafts. However, the other arterial grafts were associated with a high rate of acute occlusions.
DYRK1A genetic variants are not linked to Alzheimer's disease in a Spanish case-control cohort
Authors: Vázquez-Higuera José Luis , Sánchez-Juan Pascual , Rodríguez-Rodríguez Eloy , Mateo Ignacio , Pozueta Ana , Frank Ana , Sastre Isabel , Valdivieso Fernando , Berciano José , Bullido María J , Combarros Onofre 
Published: December 2009

Abstract

Background
As dual-specificity tyrosine phosphorylation-regulated kinase 1A (DYRK1A) has been implicated in the abnormal hyperphosphorylation of tau in Alzheimer's disease (AD) brain, and the development of neurofibrillary tangles, we examined the contribution of this gene to the susceptibility for AD.

Methods
We examined genetic variations of DYRK1A by genotyping haplotype tagging SNPs (htSNPs) (rs11701483, rs2835740, rs1137600, rs2835761, rs2835762, rs2154545 and rs8132976) in a group of 634 Spanish AD cases and 733 controls.

Results
There were no differences in the genotypic, allelic or haplotypic distributions between cases and controls in the overall analysis or after stratification by APOE ε4 allele.

Conclusion
Our negative findings in the Spanish population argue against the hypothesis that DYRK1A genetic variations are causally related to AD risk. Still, additional studies using different sets of patients and control subjects deserve further attention, since supporting evidence for association between DYRK1A gene and AD risk in the Japanese population exists.