bluuebunny/crossref_metadata_2025_split huggingface dataset:
The glutathione transferase of Nicotiana benthamiana NbGSTU4 plays a role in regulating the early replication of Bamboo mosaic virus
Authors: Chen I‐Hsuan , Chiu Meng‐Hsuen , Cheng Shun‐Fang , Hsu Yau‐Heiu , Tsai Ching‐Hsiu 
Published: May 2013

Summary

Bamboo mosaic virus (BaMV) is a single‐stranded positive‐sense RNA virus. One of the plant glutathione S‐transferase (GST) genes, NbGSTU4, responds as an upregulated gene in Nicotiana benthamiana post BaMV infection.

In order to identify the role of NbGSTU4 in BaMV infection, the expression of NbGSTU4 was knocked down using a virus‐induced gene silencing technique or was transiently expressed in N. benthamiana in BaMV inoculation.

The results show a significant decrease in BaMV RNA accumulation when the expression level of NbGSTU4 is reduced; whereas the viral RNA accumulation increases when NbGSTU4 is transiently expressed. Furthermore, this study identified that the involvement of NbGSTU4 in viral RNA accumulation occurs by its participation in the viral early replication step. The findings show that the NbGSTU4 protein expressed from Escherichia coli can interact with the 3′ untranslated region (UTR) of the BaMV RNA in vitro in the presence of glutathione (GSH). The addition of GSH in the in vitro replication assay shows an enhancement of minus‐strand but not plus‐strand RNA synthesis.

The results suggest that the plant GST protein plays a role in binding viral RNA and delivering GSH to the replication complex to create a reduced condition for BaMV minus‐strand RNA synthesis.
An annales school-based serious game creation framework for taiwanese indigenous cultural heritage
Authors: Huang Chih-Hong , Huang Yi-Ting 
Published: May 2013

This study utilizes the characteristics of the Annales School, including their emphasis on total history and space and time integration, their focus on the economic world, and their use of structural analysis to develop a creation framework for a serious video game related to the cultural and life history of Taiwan's indigenous people. Game development comprised the tiers of data, logic, and presentation. During the data tier, we used taxonomy to extract the cultural components of Taiwan's Atayal tribe. During the logic tier, we employed an analysis of cultural characteristics and comparisons of historical education goals to confirm the game's framework and storytelling engine, selecting a construction management simulation game genre to present tribal life and economic operations. Finally, in the presentation tier, we converted cultural components into elements in the game's user interface.
The game evaluation results showed that “Papakwaqa” (our serious game) had positive benefits for enhancing schoolchildren's learning motivation and performance regarding indigenous life and history. Our research verified that integrating the cross-disciplinary methods of anthropologists, history teachers, tribal elders, and game designers to establish instructional goals and design foci for game development and to create a cultural heritage serious game-creation framework warrants further study and effort.
ATR-Dependent Phosphorylation of FANCM at Serine 1045 Is Essential for FANCM Functions
Authors: Singh Thiyam Ramsing , Ali Abdullah Mahmood , Paramasivam Manikandan , Pradhan Arun , Wahengbam Kebola , Seidman Michael M. , Meetei Amom Ruhikanta 
Published: May 2013

Abstract
Fanconi anemia (FA) is a genome instability syndrome that has been associated with both cancer predisposition and bone marrow failure. FA proteins are involved in cellular response to replication stress in which they coordinate DNA repair with DNA replication and cell-cycle progression. One regulator of the replication stress response is the ATP-dependent DNA translocase FANCM, which we have shown to be hyperphosphorylated in response to various genotoxic agents. However, the significance of this phosphorylation remained unclear. Here, we show that genotoxic stress–induced FANCM phosphorylation is ATR-dependent and that this modification is highly significant for the cellular response to replication stress. We identified serine (S1045) residue of FANCM that is phosphorylated in response to genotoxic stress and this effect is ATR-dependent. We show that S1045 is required for FANCM functions including its role in FA pathway integrity, recruiting FANCM to the site of interstrand cross links, preventing the cells from entering mitosis prematurely, and efficient activation of the CHK1 and G2–M checkpoints. Overall, our data suggest that an ATR-FANCM feedback loop is present in the FA and replication stress response pathways and that it is required for both efficient ATR/CHK1 checkpoint activation and FANCM function. Cancer Res; 73(14); 4300–10. ©2013 AACR.
Microtubule-Associated Histone Deacetylase 6 Supports the Calcium Store Sensor STIM1 in Mediating Malignant Cell Behaviors
Authors: Chen Ying-Ting , Chen Yih-Fung , Chiu Wen-Tai , Liu Kuan-Yu , Liu Yu-Lin , Chang Jang-Yang , Chang Hsien-Chang , Shen Meng-Ru 
Published: May 2013

Abstract
Stromal-interaction molecule 1 (STIM1) is an endoplasmic reticulum Ca2+ storage sensor that promotes cell growth, migration, and angiogenesis in breast and cervical cancers. Here, we report that the microtubule-associated histone deacetylase 6 (HDAC6) differentially regulates activation of STIM1-mediated store-operated Ca2+ entry (SOCE) between cervical cancer cells and normal cervical epithelial cells. Confocal microscopy of living cells indicated that microtubule integrity was necessary for STIM1 trafficking to the plasma membrane and interaction with Orai1, an essential pore subunit of SOCE. Cancer cells overexpressed both STIM1 and Orai1 compared with normal cervical epithelial cells. HDAC6 upregulation in cancer cells was accompanied by hypoacetylated α-tubulin. Tubastatin-A, a specific HDAC6 inhibitor, inhibited STIM1 translocation to plasma membrane and blocked SOCE activation in cancer cells but not normal epithelial cells. Genetic or pharmacologic inhibition of HDAC6 blocked STIM1 membrane trafficking and downstream Ca2+ influx, as evidenced by total internal reflection fluorescent images and intracellular Ca2+ determination. In contrast, HDAC6 inhibition did not affect interactions between STIM1 and the microtubule plus end-binding protein EB1. Analysis of surgical specimens confirmed that most cervical cancer tissues overexpressed STIM1 and Orai1, accompanied by hypoacetylated α-tubulin. Together, our results identify HDAC6 as a candidate target to disrupt STIM1-mediated SOCE as a general strategy to block malignant cell behavior. Cancer Res; 73(14); 4500–9. ©2013 AACR.
Lactate Dehydrogenase B: A Metabolic Marker of Response to Neoadjuvant Chemotherapy in Breast Cancer
Authors: Dennison Jennifer B. , Molina Jennifer R. , Mitra Shreya , González-Angulo Ana M. , Balko Justin M. , Kuba María G. , Sanders Melinda E. , Pinto Joseph A. , Gómez Henry L. , Arteaga Carlos L. , Brown Robert E. , Mills Gordon B. 
Published: May 2013

Abstract
Purpose: Although breast cancers are known to be molecularly heterogeneous, their metabolic phenotype is less well-understood and may predict response to chemotherapy. This study aimed to evaluate metabolic genes as individual predictive biomarkers in breast cancer.
Experimental Design: mRNA microarray data from breast cancer cell lines were used to identify bimodal genes—those with highest potential for robust high/low classification in clinical assays. Metabolic function was evaluated in vitro for the highest scoring metabolic gene, lactate dehydrogenase B (LDHB). Its expression was associated with neoadjuvant chemotherapy response and relapse within clinical and PAM50-derived subtypes.
Results: LDHB was highly expressed in cell lines with glycolytic, basal-like phenotypes. Stable knockdown of LDHB in cell lines reduced glycolytic dependence, linking LDHB expression directly to metabolic function. Using patient datasets, LDHB was highly expressed in basal-like cancers and could predict basal-like subtype within clinical groups [OR = 21 for hormone receptor (HR)-positive/HER2-negative; OR = 10 for triple-negative]. Furthermore, high LDHB predicted pathologic complete response (pCR) to neoadjuvant chemotherapy for both HR-positive/HER2-negative (OR = 4.1, P &lt; 0.001) and triple-negative (OR = 3.0, P = 0.003) cancers. For triple-negative tumors without pCR, high LDHB posttreatment also identified proliferative tumors with increased risk of recurrence (HR = 2.2, P = 0.006).
Conclusions: Expression of LDHB predicted response to neoadjuvant chemotherapy within clinical subtypes independently of standard prognostic markers and PAM50 subtyping. These observations support prospective clinical evaluation of LDHB as a predictive marker of response for patients with breast cancer receiving neoadjuvant chemotherapy. Clin Cancer Res; 19(13); 3703–13. ©2013 AACR.
NF-κB2/p52 Induces Resistance to Enzalutamide in Prostate Cancer: Role of Androgen Receptor and Its Variants
Authors: Nadiminty Nagalakshmi , Tummala Ramakumar , Liu Chengfei , Yang Joy , Lou Wei , Evans Christopher P. , Gao Allen C. 
Published: May 2013

Abstract
Resistance of prostate cancer cells to the next-generation antiandrogen enzalutamide may be mediated by a multitude of survival signaling pathways. In this study, we tested whether increased expression of NF-κB2/p52 induces prostate cancer cell resistance to enzalutamide and whether this response is mediated by aberrant androgen receptor (AR) activation and AR splice variant production. LNCaP cells stably expressing NF-κB2/p52 exhibited higher survival rates than controls when treated with enzalutamide. C4-2B and CWR22Rv1 cells chronically treated with enzalutamide were found to express higher levels of NF-κB2/p52. Downregulation of NF-κB2/p52 in CWR22Rv1 cells chronically treated with enzalutamide rendered them more sensitive to cell growth inhibition by enzalutamide. Analysis of the expression levels of AR splice variants by quantitative reverse transcription PCR and Western blotting revealed that LNCaP cells expressing p52 exhibit higher expression of AR splice variants. Downregulation of expression of NF-κB2/p52 in VCaP and CWR22Rv1 cells by short hairpin RNA abolished expression of splice variants. Downregulation of expression of either full-length AR or the splice variant AR-V7 led to an increase in sensitivity of prostate cancer cells to enzalutamide. These results collectively demonstrate that resistance to enzalutamide may be mediated by NF-κB2/p52 via activation of AR and its splice variants. Mol Cancer Ther; 12(8); 1629–37. ©2013 AACR.
Effect of nitrogen supply form on the invasion of rice roots by the root-knot nematode, Meloidogyne graminicola
Authors: Patil Jagadeesh , Miller Anthony J. , Gaur Hari S. 
Published: May 2013

Rice is capable of taking up both nitrate (NO3−) and ammonical (NH4+) forms of nitrogen (N). It is largely grown under flooded cultivation when NH4+ is the main form of available soil N. The root knot nematode, Meloidogyne graminicola, can cause serious damage to rice crops and disturb N uptake and translocation. We have investigated if the N supply form can influence the susceptibility of rice to this important pest. Roots supplied with a 100-fold lower supply of calcium nitrate (0.1 mM Ca(NO3)2) showed a higher level of nematode infection as measured by the gall index. Plants supplied with 2.85 mM of Ca(NO3)2 were more infected compared with the same dose of ammonium nitrate (NH4NO3) or ammonium chloride (NH4Cl). 15NO3− influx studies showed significantly smaller uptake of nitrate in nematode-infected roots when compared with non-infected control plants. The electrophysiological studies showed that resting cell membrane potentials of nematode-infected plants were significantly smaller (less negative) than those of non-infected control rice. Furthermore, when the cellular responses to NO3− were compared, these also showed significantly smaller nitrate transport activity in nematode-infected roots (4.7 ± 1.2 mV) when compared with non-infected control plants (11.9 ± 3.4 mV). Taken together, the 15NO3− influx and electrophysiological measurements clearly showed that the root NO3− transport activity was severely decreased in nematode-infected roots. The results also show that regulation of NO3− concentration at critical periods of nematode infection of rice root can provide a non-nematicidal method of nematode management.
Biology, growth parameters and enzymatic activity of Pochonia chlamydosporia isolated from potato cyst and root-knot nematodes
Authors: Vieira dos Santos M. Clara , Esteves Ivânia , Kerry Brian , Abrantes Isabel 
Published: May 2013

Pochonia chlamydosporia, a widespread fungal parasite of potato cyst nematodes (PCN), Globodera spp., and root-knot nematodes (RKN), Meloidogyne spp., has been studied as a biological control agent. Three Portuguese isolates (Pc1, Pc2, Pc3) obtained from PCN eggs and two non-native isolates (Vc10, Pc280) were characterised using ERIC-PCR and screened by in vitro assays for their ability to produce chlamydospores, parasitise eggs of Globodera rostochiensis and Meloidogyne chitwoodi and colonise the rhizosphere of barley. The effects of temperature on growth, sporulation, parasitism and enzymatic activity were also evaluated. Isolates Pc1 and Pc3, despite their different geographical origins, had identical molecular profiles. Pc2 produced the higher numbers of chlamydospores in solid medium (1.15 × 107 chlamydospores g−1), whereas Pc3 produced the least (3 × 105 chlamydospores g−1). These isolates extensively colonised the rhizosphere of barley (>90% root fragments) and the proportion of parasitised eggs, detected on agar plates, was low (<60% for RKN and <55% for PCN), Pc1 being the best parasite against both nematode species. The influence of temperature was similar for all isolates: no growth was observed at 10, 33 and 35°C. Spores/hyphal fragments remained viable for nearly 1 month at 10 and 33°C and isolates resumed growth after incubation at 25°C, although chlamydospores and conidia production, viability and nematode egg parasitism were affected. Exposure to 35°C was lethal for isolates Pc1, Pc2 and Pc280. When grown in liquid media all isolates produced esterases, but protease activity was only observed in Pc2 and Vc10. The highest enzymatic activity was detected in isolate Pc2 in low nutrient media. Enzymatic activity decreased in the presence of nematode eggs for both Pc2 and Vc10. Molecular, biochemical and biological analyses, including biotic and abiotic factors, are important in the screening of potential biological control agents, particularly in the case of P. chlamydosporia, due to the high variability among isolates.
A study on drug–drug interactions through prescription analysis in a South Indian teaching hospital
Authors: Kulkarni Vijay , Bora Swathi Swaroopa , Sirisha Sapineni , Saji Mohammed , Sundaran Siraj 
Published: May 2013

Objective: The objective of this study was to assess the drug–drug interactions (DDIs) through prescription analysis among the inpatients of a South Indian teaching hospital. Methods: The study was a prospective observational prescription analysis conducted for a period of 6 months, from October 2010 to March 2011. The prescriptions having two or more drugs and where a DDI was suspected were selected by the physician in charge of the ward. The drugs in the prescription were then entered into the drug interaction checker software. The DDIs were classified based on the mechanism of interactions, severity of interactions, relation to the number of drugs prescribed, and disease conditions were also determined. Results: A total of 204 prescriptions were analyzed, of which 186 prescriptions had 856 DDIs. Most of the DDIs were pharmacokinetic drug interactions (42%) followed by unknown mechanisms (34%) and pharmacodynamic mechanisms (24%). The study findings showed that the prescriptions for cardiovascular with respiratory disease conditions had the greatest number of drug interactions on average. A severity assessment showed that majority of the DDIs were moderate (70%) followed by minor (28%). The study results showed that as the number of drugs increases in a prescription, the number of DDIs also increases. The interventions determined showed that dosage adjustment (12%) was to be followed in most of the DDIs. Conclusion: This study assists in understanding the factors associated with DDIs that can help in safe and effective use of drugs in the future.
Global methylation analysis identifies prognostically important epigenetically inactivated tumor suppressor genes in multiple myeloma
Authors: Kaiser Martin F. , Johnson David C. , Wu Ping , Walker Brian A. , Brioli Annamaria , Mirabella Fabio , Wardell Christopher P. , Melchor Lorenzo , Davies Faith E. , Morgan Gareth J. 
Published: May 2013

Key Points
Epigenetic inactivation of tumor suppressor genes is associated with an unfavorable prognosis in multiple myeloma. Drug response and microenvironment interaction pathways are affected by epigenetic inactivation, linking tumor biology to prognosis.
Late-in-life surgery associated with Creutzfeldt-Jakob disease: a methodological outline for evidence-based guidance
Authors: Cruz Mabel , Mahillo-Fernandez Ignacio , Rábano Alberto , Siden Åke , Calero Miguel , Laursen Henning , Mølbak Kåre , Almazán Javier , de Pedro-Cuesta Jesus 
Published: May 2013

Abstract
Background
There is increasing epidemiological evidence of etiological links between general surgery and sporadic Creutzfeldt-Jakob disease (sCJD) with long incubation periods. The purpose of this study was to identify specific surgical procedures potentially associated with sCJD to be targeted for preventive presurgical-intervention guidance.

Results
We propose a three-step clinical guidance outline where surgical procedures associated with sCJD clinical onset – potentially more contaminant - are taken into account. Data on hospital discharges and surgical procedures were obtained from Danish and Swedish national in-patient hospital registries for 167 sCJD cases, onset 1987–2003, and for 835 matched and 2,224 unmatched population controls. Surgery was allocated to different life-time periods as previously reported, and frequencies were compared using logistic regression analysis. In the year preceding clinical onset, persons with sCJD underwent a statistically significant higher number of minor surgical interventions (OR (95% CI): 17.50 (3.64-84.24)), transluminal endoscopies (OR: 2.73 (1.01–7.37)) and gastrointestinal operations (OR: 3.51 (1.21–10.19)) compared to matched controls. Surgical discharges clustered towards clinical onset. These differences increased during the clinical period, with statistically significant higher frequencies for both endoscopies and minor surgery (OR: 13.91 (5.87-32.95), and for main surgical procedures (OR: 2.10 (1.00-4.39)), particularly gastrointestinal surgery (OR: 6.00 (1.83-19.66)), and surgery contacting skeletal muscle. Comparisons with unmatched controls yielded similar results for neurosurgery in the clinical period (OR: 19.40 (2.22-168.34)).

Conclusions
These results suggest that some types of surgical procedures are associated with sCJD, after clinical onset or particularly just before onset. Selective planning of such surgery to minimize instrument/device contamination or quarantining might be feasible. Conditional to progress in sCJD etiological research, results are relevant for guidance development.
Severe Hyperaldosteronism in Neonatal Task3 Potassium Channel Knockout Mice Is Associated With Activation of the Intraadrenal Renin-Angiotensin System
Authors: Bandulik Sascha , Tauber Philipp , Penton David , Schweda Frank , Tegtmeier Ines , Sterner Christina , Lalli Enzo , Lesage Florian , Hartmann Michaela , Barhanin Jacques , Warth Richard 
Published: May 2013

Abstract
Task3 K+ channels are highly expressed in the adrenal cortex and contribute to the angiotensin II and K+ sensitivity of aldosterone-producing glomerulosa cells. Adult Task3−/− mice display a partially autonomous aldosterone secretion, subclinical hyperaldosteronism, and salt-sensitive hypertension. Here, we investigated the age dependence of the adrenal phenotype of Task3−/− mice. Compared with adults, newborn Task3−/− mice displayed a severe adrenal phenotype with strongly increased plasma levels of aldosterone, corticosterone, and progesterone. This adrenocortical dysfunction was accompanied by a modified gene expression profile. The most strongly up-regulated gene was the protease renin. Real-time PCR corroborated the strong increase in adrenal renin expression, and immunofluorescence revealed renin-expressing cells in the zona fasciculata. Together with additional factors, activation of the local adrenal renin system is probably causative for the severely disturbed steroid hormone secretion of neonatal Task3−/− mice. The changes in gene expression patterns of neonatal Task3−/− mice could also be relevant for other forms of hyperaldosteronism.
Novel Methods for the Guidance and Monitoring of Single Cells and Simple Networks in Culture
Authors: Dow J. A. T. , Clark P. , Connolly P. , Curtis A. S. G. , Wilkinson C. D. W. 
Published: May 2013

ABSTRACT
The effects of the topography, adhesiveness and chemistry of surfaces in modulating the behaviour of cells in vivo and in vitro have been extensively researched. However, few natural systems are simple enough to allow straightforward conclusions to be drawn, as many different cues are likely to be present at one time. Microelectronic fabrication, normally employed in making integrated circuits, can produce substrates patterned on scales highly relevant to studies of cell behaviour.
In this paper, we describe progress in fabricating simple artificial substrata both at the micrometre and sub-micrometre scales. The former can be considered as models for contact guidance along other cells or axonal processes: the latter, models for guidance along aligned collagen matrices. We have systematically studied the reactions of different cell types to simple cues (steps and grooves). Additionally, it may be possible to produce fine-resolution patterns with differential adhesiveness, or with other cell-specific surface-chemical properties, such as the differential deposition of proteins, e.g. cell adhesion molecules. We also describe early results in using topographic and other cues to guide cells onto patterned metal electrodes, forming simple electrically active networks of controlled design, from which long-term recordings can conveniently be made.
The bending of sliding microtubules imaged by confocal light microscopy and negative stain electron microscopy
Authors: Amos L. A. , Amos W. B. 
Published: May 2013

ABSTRACT
Individual microtubules can be visualised by confocal microscopy in reflection mode; when associated with a glass surface, they show up as black lines against the bright reflection from the surface. The high contrast imaging allows details of the behaviour of sliding microtubules to be studied easily.
Taxol-stabilised microtubules sliding over kinesin- coated surfaces are normally straight, but can bend into tight loops if the leading end sticks to the surface. Some remain curved after release and move in circles. In such cases, the microtubule lattice must have become stably deformed. Electron microscopy of microtubules fixed during sliding shows no gross rearrangement of the subunit lattice and indicates that microtubule bending is mainly achieved by increased twisting of the longitudinal protofilaments around the microtubule.