bluuebunny/crossref_metadata_2025_split huggingface dataset:
A structural role for the PHP domain in E. coli DNA polymerase III
Authors: Barros Tiago , Guenther Joel , Kelch Brian , Anaya Jordan , Prabhakar Arjun , O’Donnell Mike , Kuriyan John , Lamers Meindert H 
Published: May 2013

Abstract

Background
In addition to the core catalytic machinery, bacterial replicative DNA polymerases contain a Polymerase and Histidinol Phosphatase (PHP) domain whose function is not entirely understood. The PHP domains of some bacterial replicases are active metal-dependent nucleases that may play a role in proofreading. In E. coli DNA polymerase III, however, the PHP domain has lost several metal-coordinating residues and is likely to be catalytically inactive.

Results
Genomic searches show that the loss of metal-coordinating residues in polymerase PHP domains is likely to have coevolved with the presence of a separate proofreading exonuclease that works with the polymerase. Although the E. coli Pol III PHP domain has lost metal-coordinating residues, the structure of the domain has been conserved to a remarkable degree when compared to that of metal-binding PHP domains. This is demonstrated by our ability to restore metal binding with only three point mutations, as confirmed by the metal-bound crystal structure of this mutant determined at 2.9 Å resolution. We also show that Pol III, a large multi-domain protein, unfolds cooperatively and that mutations in the degenerate metal-binding site of the PHP domain decrease the overall stability of Pol III and reduce its activity.

Conclusions
While the presence of a PHP domain in replicative bacterial polymerases is strictly conserved, its ability to coordinate metals and to perform proofreading exonuclease activity is not, suggesting additional non-enzymatic roles for the domain. Our results show that the PHP domain is a major structural element in Pol III and its integrity modulates both the stability and activity of the polymerase.
Protective effect of genistein on radiation-induced intestinal injury in tumor bearing mice
Authors: Son Tae Gen , Gong Eun Ji , Bae Min Ji , Kim Sung Dae , Heo Kyu , Moon Changjong , Yang Kwangmo , Kim Joong Sun 
Published: May 2013

AbstractBackgroundRadiation therapy is the most widely used treatment for cancer, but it causes the side effect of mucositis due to intestinal damage. We examined the protective effect of genistein in tumor-bearing mice after abdominal irradiation by evaluation of apoptosis and intestinal morphological changes.MethodsMouse colon cancer CT26 cells were subcutaneously injected at the flank of BALB/c mice to generate tumors. The tumor-bearing mice were treated with abdominal radiation at 5 and 10 Gy, and with genistein at 200 mg/kg body weight per day for 1 d before radiation. The changes in intestinal histology were evaluated 12 h and 3.5 d after irradiation. To assess the effect of the combination treatment on the cancer growth, the tumor volume was determined at sacrifice before tumor overgrowth occurred.ResultsGenistein significantly decreased the number of apoptotic nuclei compared with that in the irradiation group 12 h after 5 Gy irradiation. Evaluation of histological changes showed that genistein ameliorated intestinal morphological changes such as decreased crypt survival, villus shortening, and increased length of the basal lamina 3.5 d after 10 Gy irradiation. Moreover, the genistein-treated group exhibited more Ki-67-positive proliferating cells in the jejunum than the irradiated control group, and crypt depths were greater in the genistein-treated group than in the irradiated control group. The mean weight of the CT26 tumors was reduced in the group treated with genistein and radiation compared with the control group.ConclusionGenistein had a protective effect on intestinal damage induced by irradiation and delayed tumor growth. These results suggest that genistein is a useful candidate for preventing radiotherapy-induced intestinal damage in cancer patients.
A study of TiO2/carbon black composition as counter electrode materials for dye-sensitized solar cells
Authors: Lim Jeongmin , Ryu Sang Yeoul , Kim Jeonghun , Jun Yongseok 
Published: May 2013

Abstract
This study describes a systematic approach of TiO2/carbon black nanoparticles with respect to the loading amount in order to optimize the catalytic ability of triiodide reduction for dye-sensitized solar cells. In particular, the cell using an optimized TiO2 and carbon black electrode presents an energy conversion efficiency of 7.4% with a 5:1 ratio of a 40-nm TiO2 to carbon black. Based on the electrochemical analysis, the charge-transfer resistance of the carbon counter electrode changed based on the carbon black powder content. Electrochemical impedance spectroscopy and cyclic voltammetry study show lower resistance compared to the Pt counter electrode. The obtained nanostructures and photo electrochemical study were characterized.
Mining for hemicellulases in the fungus-growing termite Pseudacanthotermes militaris using functional metagenomics
Authors: Bastien Géraldine , Arnal Grégory , Bozonnet Sophie , Laguerre Sandrine , Ferreira Fernando , Fauré Régis , Henrissat Bernard , Lefèvre Fabrice , Robe Patrick , Bouchez Olivier , Noirot Céline , Dumon Claire , O’Donohue Michael 
Published: May 2013

Abstract

Background
The metagenomic analysis of gut microbiomes has emerged as a powerful strategy for the identification of biomass-degrading enzymes, which will be no doubt useful for the development of advanced biorefining processes. In the present study, we have performed a functional metagenomic analysis on comb and gut microbiomes associated with the fungus-growing termite, Pseudacanthotermes militaris.

Results
Using whole termite abdomens and fungal-comb material respectively, two fosmid-based metagenomic libraries were created and screened for the presence of xylan-degrading enzymes. This revealed 101 positive clones, corresponding to an extremely high global hit rate of 0.49%. Many clones displayed either β-d-xylosidase (EC 3.2.1.37) or α-l-arabinofuranosidase (EC 3.2.1.55) activity, while others displayed the ability to degrade AZCL-xylan or AZCL-β-(1,3)-β-(1,4)-glucan. Using secondary screening it was possible to pinpoint clones of interest that were used to prepare fosmid DNA. Sequencing of fosmid DNA generated 1.46 Mbp of sequence data, and bioinformatics analysis revealed 63 sequences encoding putative carbohydrate-active enzymes, with many of these forming parts of sequence clusters, probably having carbohydrate degradation and metabolic functions. Taxonomic assignment of the different sequences revealed that Firmicutes and Bacteroidetes were predominant phyla in the gut sample, while microbial diversity in the comb sample resembled that of typical soil samples. Cloning and expression in E. coli of six enzyme candidates identified in the libraries provided access to individual enzyme activities, which all proved to be coherent with the primary and secondary functional screens.

Conclusions
This study shows that the gut microbiome of P. militaris possesses the potential to degrade biomass components, such as arabinoxylans and arabinans. Moreover, the data presented suggests that prokaryotic microorganisms present in the comb could also play a part in the degradation of biomass within the termite mound, although further investigation will be needed to clarify the complex synergies that might exist between the different microbiomes that constitute the termitosphere of fungus-growing termites. This study exemplifies the power of functional metagenomics for the discovery of biomass-active enzymes and has provided a collection of potentially interesting biocatalysts for further study.
Acute 5-HT7 receptor activation increases NMDA-evoked currents and differentially alters NMDA receptor subunit phosphorylation and trafficking in hippocampal neurons
Authors: Vasefi Maryam S , Yang Kai , Li Jerry , Kruk Jeff S , Heikkila John J , Jackson Michael F , MacDonald John F , Beazely Michael A 
Published: May 2013

Abstract

Background
N-methyl-D-aspartate (NMDA) receptors are regulated by several G protein-coupled receptors (GPCRs) as well as receptor tyrosine kinases. Serotonin (5-HT) type 7 receptors are expressed throughout the brain including the thalamus and hippocampus. Long-term (2–24 h) activation of 5-HT7 receptors promotes the expression of neuroprotective growth factor receptors, including the platelet-derived growth factor (PDGF) β receptors which can protect neurons against NMDA-induced neurotoxicity.

Results
In contrast to long-term activation of 5-HT7 receptors, acute (5 min) treatment of isolated hippocampal neurons with the 5-HT7 receptor agonist 5-carboxamidotryptamine (5-CT) enhances NMDA-evoked peak currents and this increase in peak currents is blocked by the 5-HT7 receptor antagonist, SB 269970. In hippocampal slices, acute 5-HT7 receptor activation increases NR1 NMDA receptor subunit phosphorylation and differentially alters the phosphorylation state of the NR2B and NR2A subunits. NMDA receptor subunit cell surface expression is also differentially altered by 5-HT7 receptor agonists: NR2B cell surface expression is decreased whereas NR1 and NR2A surface expression are not significantly altered.

Conclusions
In contrast to the negative regulatory effects of long-term activation of 5-HT7 receptors on NMDA receptor signaling, acute activation of 5-HT7 receptors promotes NMDA receptor activity. These findings highlight the potential for temporally differential regulation of NMDA receptors by the 5-HT7 receptor.
Mediating factors of coping process in parents of children with type 1 diabetes
Authors: Oskouie Fatemeh , Mehrdad Neda , Ebrahimi Hossein 
Published: May 2013

Abstract
Background
Type 1 diabetes is a lifelong condition for children and their parents, the management for which imposes a vast responsibility. This study explores the mediating factors that affect Iranian parents’ coping processes with their children’s type 1 diabetes.

Methods
Research was conducted using the grounded theory method. Participants were selected purposefully, and we continued with theoretical sampling. Constant comparative analysis was used to analyze the data.

Results
The mediating factors of the parental coping process with their child’s diabetes consist of the child’s cooperation, crises and experiences, economic challenges, and parental participation in care.

Conclusion
Findings highlight the necessity of well-informed nurses with insightful understanding of the mediating factors in parental coping with juvenile diabetes in order to meet the particular needs of this group.
Total restrained domination in graphs of diameter 2 or 3
Authors: Tahmasbzadehbaee Zahra , Nandappa D Soner , Ahangar Hossein Abdollahzadeh , Mojdeh Doost Ali , Zhao Yancai 
Published: May 2013

Abstract
For a given connected graph G=(V,E), a set

D

tr

⊆
V
(
G
)

is a total restrained dominating set if it is a dominating set and both 〈D

t
r
〉 and 〈V(G)−D

t
r
〉 do not contain isolated vertices. The cardinality of the minimum total restrained dominating set in G is the total restrained domination number and is denoted by γ

t
r
(G). In this paper, we continue the study of total restrained domination number of graphs. We first give some results on total restrained domination number of graphs. And then, we characterize all graphs G of order n for which (1) γ

t
r
(G)=n, (2) γ(G)=1 and γ

t
r
(G)=3, and (3) γ

t
r
(G)=2. Furthermore, we give some bounds on total restrained domination number of graphs with diameter 3. Finally, we present some bounds for total restrained domination number of some planar graphs with diameter 2 and γ-set of cardinality 2.
A novel in vitro bovine cartilage punch model for assessing the regeneration of focal cartilage defects with biocompatible bacterial nanocellulose
Authors: Pretzel David , Linss Stefanie , Ahrem Hannes , Endres Michaela , Kaps Christian , Klemm Dieter , Kinne Raimund W 
Published: May 2013

Abstract
Introduction
Current therapies for articular cartilage defects fail to achieve qualitatively sufficient tissue regeneration, possibly because of a mismatch between the speed of cartilage rebuilding and the resorption of degradable implant polymers. The present study focused on the self-healing capacity of resident cartilage cells in conjunction with cell-free and biocompatible (but non-resorbable) bacterial nanocellulose (BNC). This was tested in a novel in vitro bovine cartilage punch model.

Methods
Standardized bovine cartilage discs with a central defect filled with BNC were cultured for up to eight weeks with/without stimulation with transforming growth factor-β1 (TGF-β1. Cartilage formation and integrity were analyzed by histology, immunohistochemistry and electron microscopy. Content, release and neosynthesis of the matrix molecules proteoglycan/aggrecan, collagen II and collagen I were also quantified. Finally, gene expression of these molecules was profiled in resident chondrocytes and chondrocytes migrated onto the cartilage surface or the implant material.

Results
Non-stimulated and especially TGF-β1-stimulated cartilage discs displayed a preserved structural and functional integrity of the chondrocytes and surrounding matrix, remained vital in long-term culture (eight weeks) without signs of degeneration and showed substantial synthesis of cartilage-specific molecules at the protein and mRNA level. Whereas mobilization of chondrocytes from the matrix onto the surface of cartilage and implant was pivotal for successful seeding of cell-free BNC, chondrocytes did not immigrate into the central BNC area, possibly due to the relatively small diameter of its pores (2 to 5 μm). Chondrocytes on the BNC surface showed signs of successful redifferentiation over time, including increase of aggrecan/collagen type II mRNA, decrease of collagen type I mRNA and initial deposition of proteoglycan and collagen type II in long-term high-density pellet cultures. Although TGF-β1 stimulation showed protective effects on matrix integrity, effects on other parameters were limited.

Conclusions
The present bovine cartilage punch model represents a robust, reproducible and highly suitable tool for the long-term culture of cartilage, maintaining matrix integrity and homoeostasis. As an alternative to animal studies, this model may closely reflect early stages of cartilage regeneration, allowing the evaluation of promising biomaterials with/without chondrogenic factors.
High mammographic density in women of Ashkenazi Jewish descent
Authors: Caswell Jennifer L , Kerlikowske Karla , Shepherd John A , Cummings Steven R , Hu Donglei , Huntsman Scott , Ziv Elad 
Published: May 2013

Abstract
Introduction
Percent mammographic density (PMD) adjusted for age and body mass index is one of the strongest risk factors for breast cancer and is known to be approximately 60% heritable. Here we report a finding of an association between genetic ancestry and adjusted PMD.

Methods
We selected self-identified Caucasian women in the California Pacific Medical Center Research Institute Cohort whose screening mammograms placed them in the top or bottom quintiles of age-adjusted and body mass index-adjusted PMD. Our final dataset included 474 women with the highest adjusted PMD and 469 with the lowest genotyped on the Illumina 1 M platform. Principal component analysis (PCA) and identity-by-descent analyses allowed us to infer the women's genetic ancestry and correlate it with adjusted PMD.

Results
Women of Ashkenazi Jewish ancestry, as defined by the first principal component of PCA and identity-by-descent analyses, represented approximately 15% of the sample. Ashkenazi Jewish ancestry, defined by the first principal component of PCA, was associated with higher adjusted PMD (P = 0.004). Using multivariate regression to adjust for epidemiologic factors associated with PMD, including age at parity and use of postmenopausal hormone therapy, did not attenuate the association.

Conclusions
Women of Ashkenazi Jewish ancestry, based on genetic analysis, are more likely to have high age-adjusted and body mass index-adjusted PMD. Ashkenazi Jews may have a unique set of genetic variants or environmental risk factors that increase mammographic density.
Monitoring neurodegeneration in diabetes using adult neural stem cells derived from the olfactory bulb
Authors: Hidaka Ryo , Machida Masanao , Fujimaki Shin , Terashima Kazuyuki , Asashima Makoto , Kuwabara Tomoko 
Published: May 2013

Abstract
Introduction
Neurons have the intrinsic capacity to produce insulin, similar to pancreatic cells. Adult neural stem cells (NSCs), which give rise to functional neurons, can be established and cultured not only by intracerebral collection, which requires difficult surgery, but also by collection from the olfactory bulb (OB), which is relatively easy. Adult neurogenesis in the hippocampus (HPC) is significantly decreased in diabetes patients. As a result, learning and memory functions, for which the HPC is responsible, decrease.

Methods
In the present study, we compared the effect of diabetes on neurogenesis and insulin expression in adult NSCs. Adult NSCs were derived from the HPC or OB of streptozotocin-induced diabetic rats. Comparative gene-expression analyses were carried out by using extracted tissues and established adult NSC cultures from the HPC or OB in diabetic rats.

Results
Diabetes progression influenced important genes that were required for insulin expression in both OB- and HPC-derived cells. Additionally, we found that the expression levels of several genes, such as voltage-gated sodium channels, glutamate transporters, and glutamate receptors, were significantly different in OB and HPC cells collected from diabetic rats.

Conclusions
By using identified diabetes-response genes, OB NSCs from diabetes patients can be used during diabetes progression to monitor processes that cause neurodegeneration in the central nervous system (CNS). Because hippocampal NSCs and OB NSCs exhibited similar gene-expression profiles during diabetes progression, OB NSCs, which are more easily collected and established than HPC NSCs, may potentially be used for screening of effective drugs for neurodegenerative disorders that cause malignant damage to CNS functions.
PKC-ɛ pseudosubstrate and catalytic activity are necessary for membrane delivery during IgG-mediated phagocytosis
Authors: Wood Tiffany R , Chow Rachel Y , Hanes Cheryl M , Zhang Xuexin , Kashiwagi Kaori , Shirai Yasuhito , Trebak Mohamed , Loegering Daniel J , Saito Naoaki , Lennartz Michelle R 
Published: May 2013

ABSTRACT
In RAW 264.7 cells [1], PKC-ɛ regulates FcγR-mediated phagocytosis. BMDM behave similarly; PKC-ɛ concentrates at phagosomes and internalization are reduced in PKC-ɛ−/− cells. Two questions were asked: what is the role of PKC-ɛ? and what domains are necessary for PKC-ɛ concentration? Function was studied using BMDM and frustrated phagocytosis. On IgG surfaces, PKC-ɛ−/− macrophages spread less than WT. Patch-clamping revealed that the spreading defect is a result of the failure of PKC-ɛ−/− macrophages to add membrane. The defect is specific for FcγR ligation and can be reversed by expression of full-length (but not the isolated RD) PKC-ɛ in PKC-ɛ−/− BMDM. Thus, PKC-ɛ function in phagocytosis requires translocation to phagosomes and the catalytic domain. The expression of chimeric PKC molecules in RAW cells identified the ɛPS as necessary for PKC-ɛ targeting. When placed into (nonlocalizing) PKC-δ, ɛPS was sufficient for concentration, albeit to a lesser degree than intact PKC-ɛ. In contrast, translocation of δ(ɛPSC1B) resembled that of WT PKC-ɛ. Thus, ɛPS and ɛC1B cooperate for optimal phagosome targeting. Finally, cells expressing ɛK437W were significantly less phagocytic than their PKC-ɛ-expressing counterparts, blocked at the pseudopod-extension phase. In summary, we have shown that ɛPS and ɛC1B are necessary and sufficient for targeting PKC-ɛ to phagosomes, where its catalytic activity is required for membrane delivery and pseudopod extension.
Benefits and Adverse Events in Younger Versus Older Patients Receiving Neoadjuvant Chemotherapy for Osteosarcoma: Findings From a Meta-Analysis
Authors: Collins Marnie , Wilhelm Miriam , Conyers Rachel , Herschtal Alan , Whelan Jeremy , Bielack Stefan , Kager Leo , Kühne Thomas , Sydes Matthew , Gelderblom Hans , Ferrari Stefano , Picci Piero , Smeland Sigbjørn , Eriksson Mikael , Petrilli Antonio Sérgio , Bleyer Archie , Thomas David M. 
Published: May 2013

Purpose The LIVESTRONG Young Adult Alliance has conducted a meta-analysis of individual patient data from prospective neoadjuvant chemotherapy osteosarcoma studies and registries to examine the relationships of sex, age, and toxicity on survival. Patients and Methods Suitable data sets were identified by a survey of published data reported in PubMed. The final pooled data set comprised 4,838 patients from five international cooperative groups. Results After accounting for important variables known at study entry such as tumor location and histology, females experienced higher overall survival rates than males (P = .005) and children fared better than adolescents and adults (P = .002). Multivariate landmark analysis following surgery indicated that a higher rate of chemotherapy-induced tumor necrosis was associated with longer survival (P < .001), as was female sex (P = .004) and the incidence of grade 3 or 4 mucositis (P = .03). Age group was not statistically significant in this landmark analysis (P = .12). Females reported higher rates of grade 3 or 4 thrombocytopenia relative to males (P < .001). Children reported the highest rates of grade 3 or 4 neutropenia (P < .001) and thrombocytopenia (P < .001). The achievement of good tumor necrosis was higher for females than for males (P = .002) and for children than for adults (P < .001). Conclusion These results suggest fundamental differences in the way chemotherapy is handled by females compared with males and by children compared with older populations. These differences may influence survival in a disease in which chemotherapy is critical to overall outcomes.