bluuebunny/crossref_metadata_2025_split huggingface dataset:
Globin-like proteins in Caenorhabditis elegans: in vivo localization, ligand binding and structural properties
Authors: Geuens Eva , Hoogewijs David , Nardini Marco , Vinck Evi , Pesce Alessandra , Kiger Laurent , Fago Angela , Tilleman Lesley , De Henau Sasha , Marden Michael C , Weber Roy E , Van Doorslaer Sabine , Vanfleteren Jacques , Moens Luc , Bolognesi Martino , Dewilde Sylvia 
Published: April 2010

Abstract

Background
The genome of the nematode Caenorhabditis elegans contains more than 30 putative globin genes that all are transcribed. Although their translated amino acid sequences fit the globin fold, a variety of amino-acid substitutions and extensions generate a wide structural diversity among the putative globins. No information is available on the physicochemical properties and the in vivo expression.

Results
We expressed the globins in a bacterial system, characterized the purified proteins by optical and resonance Raman spectroscopy, measured the kinetics and equilibria of O2 binding and determined the crystal structure of GLB-1* (CysGH2 → Ser mutant). Furthermore, we studied the expression patterns of glb-1 (ZK637.13) and glb-26 (T22C1.2) in the worms using green fluorescent protein technology and measured alterations of their transcript abundances under hypoxic conditions.GLB-1* displays the classical three-over-three α-helical sandwich of vertebrate globins, assembled in a homodimer associated through facing E- and F-helices. Within the heme pocket the dioxygen molecule is stabilized by a hydrogen bonded network including TyrB10 and GlnE7.GLB-1 exhibits high ligand affinity, which is, however, lower than in other globins with the same distal TyrB10-GlnE7 amino-acid pair. In the absence of external ligands, the heme ferrous iron of GLB-26 is strongly hexacoordinated with HisE7, which could explain its extremely low affinity for CO. This globin oxidizes instantly to the ferric form in the presence of oxygen and is therefore incapable of reversible oxygen binding.

Conclusion
The presented data indicate that GLB-1 and GLB-26 belong to two functionally-different globin classes.
Predicting protein-protein interactions in unbalanced data using the primary structure of proteins
Authors: Yu Chi-Yuan , Chou Lih-Ching , Chang Darby Tien-Hao 
Published: April 2010

AbstractBackgroundElucidating protein-protein interactions (PPIs) is essential to constructing protein interaction networks and facilitating our understanding of the general principles of biological systems. Previous studies have revealed that interacting protein pairs can be predicted by their primary structure. Most of these approaches have achieved satisfactory performance on datasets comprising equal number of interacting and non-interacting protein pairs. However, this ratio is highly unbalanced in nature, and these techniques have not been comprehensively evaluated with respect to the effect of the large number of non-interacting pairs in realistic datasets. Moreover, since highly unbalanced distributions usually lead to large datasets, more efficient predictors are desired when handling such challenging tasks.ResultsThis study presents a method for PPI prediction based only on sequence information, which contributes in three aspects. First, we propose a probability-based mechanism for transforming protein sequences into feature vectors. Second, the proposed predictor is designed with an efficient classification algorithm, where the efficiency is essential for handling highly unbalanced datasets. Third, the proposed PPI predictor is assessed with several unbalanced datasets with different positive-to-negative ratios (from 1:1 to 1:15). This analysis provides solid evidence that the degree of dataset imbalance is important to PPI predictors.ConclusionsDealing with data imbalance is a key issue in PPI prediction since there are far fewer interacting protein pairs than non-interacting ones. This article provides a comprehensive study on this issue and develops a practical tool that achieves both good prediction performance and efficiency using only protein sequence information.
Italian hospitals on the web: a cross-sectional analysis of official websites
Authors: Maifredi Giovanni , Orizio Grazia , Bressanelli Maura , Domenighini Serena , Gasparotti Cinzia , Perini Eleonora , Caimi Luigi , Schulz Peter J , Gelatti Umberto 
Published: April 2010

Abstract

Background
Although the use of the Internet for health purposes has increased steadily in the last decade, only a few studies have explored the information provided by the websites of health institutions and no studies on the on-line activities of Italian hospitals have been performed to date. The aim of this study was to explore the characteristics of the contents and the user-orientation of Italian hospital websites.

Methods
The cross-sectional analysis considered all the Italian hospitals with a working website between December 2008 and February 2009. The websites were coded using an ad hoc Codebook, comprising eighty-nine items divided into five sections: technical characteristics, hospital information and facilities, medical services, interactive on-line services and external activities. We calculated a website evaluation score, on the basis of the items satisfied, to compare private (PrHs) and public hospitals, the latter divided into ones with their own website (PubHs-1) and ones with a section on the website of their Local Health Authority (PubHs-2). Lastly, a descriptive analysis of each item was carried out.

Results
Out of the 1265 hospitals in Italy, we found that 419 of the 652 public hospitals (64.3%) and 344 of the 613 PrHs (56.1%) had a working website (p = 0.01). The mean website evaluation score was 41.9 for PubHs-1, 21.2 for PubHs-2 and 30.8 for PrHs (p < 0.001).
Only 5 hospitals out of 763 (< 1%) provided specific clinical performance indicators, such as the nosocomial infection rate or the surgical mortality rates. Regarding interactive on-line services, although nearly 80% of both public and private hospitals enabled users to communicate on-line, less than 18% allowed the reservation of medical services, and only 8 websites (1%) provided a health-care forum.

Conclusions
A high percentage of hospitals did not provide an official website and the majority of the websites found had several limitations. Very few hospitals provided information to increase the credibility of the hospital and user confidence in the institution. This study suggests that Italian hospital websites are more a source of information on admissions and services than a means of communication between user and hospital.
Partnership disengagement from primary community care networks (PCCNs): A qualitative study for a national demonstration project
Authors: Liau Chia-Yi , Lin Cheng-Chieh , Lin Yung-Kai , Lin Blossom Yen-Ju 
Published: April 2010

Abstract

Background
The Primary Community Care Network (PCCN) Demonstration Project, launched by the Bureau of National Health Insurance (BNHI) in 2003, is still in progress. Partnership structures in PCCNs represent both contractual clinic-to-clinic and clinic-to-hospital member relationships of organizational aspects. The partnership structures are the formal relationships between individuals and the total network. Their organizational design aims to ensure effective communication, coordination, and integration across the total network. Previous studies have focused largely on how contractual integration among the partnerships works and on its effects. Few studies, however, have tried to understand partnership disengagement in PCCNs. This study explores why some partnerships in PCCNs disengage.

Methods
This study used a qualitative methodology with semi-structured questions for in-depth interviews. The semi-structured questions were pre-designed to explore the factors driving partnership disengagement. Thirty-seven clinic members who had withdrawn from their PCCNs were identified from the 2003-2005 Taiwan Primary Community Care Network Lists.

Results
Organization/participant factors (extra working time spend and facility competency), network factors (partner collaboration), and community factors (health policy design incompatibility, patient-physician relationship, and effectiveness) are reasons for clinic physicians to withdraw or change their partnerships within the PCCNs.

Conclusions
To strengthen partnership relationships, several suggestions are made, including to establish clinic and hospital member relationships, and to reduce administrative work. In addition, both educating the public about the concept of family doctors and ensuring well-organized national health policies could help health care providers improve the integration processes.
PCBP-1 regulates alternative splicing of the CD44 gene and inhibits invasion in human hepatoma cell line HepG2 cells
Authors: Zhang Tong , Huang Xian-Hong , Dong Lan , Hu Deqing , Ge Changhui , Zhan Yi-Qun , Xu Wang-Xiang , Yu Miao , Li Wei , Wang Xiaohui , Tang Liujun , Li Chang-Yan , Yang Xiao-Ming 
Published: April 2010

Abstract

Background
PCBP1 (or alpha CP1 or hnRNP E1), a member of the PCBP family, is widely expressed in many human tissues and involved in regulation of transcription, transportation process, and function of RNA molecules. However, the role of PCBP1 in CD44 variants splicing still remains elusive.

Results
We found that enforced PCBP1 expression inhibited CD44 variants expression including v3, v5, v6, v8, and v10 in HepG2 cells, and knockdown of endogenous PCBP1 induced these variants splicing. Invasion assay suggested that PCBP1 played a negative role in tumor invasion and re-expression of v6 partly reversed the inhibition effect by PCBP1. A correlation of PCBP1 down-regulation and v6 up-regulation was detected in primary HCC tissues.

Conclusions
We first characterized PCBP1 as a negative regulator of CD44 variants splicing in HepG2 cells, and loss of PCBP1 in human hepatic tumor contributes to the formation of a metastatic phenotype.
Recombinant phospholipase A1 (Ves v 1) from yellow jacket venom for improved diagnosis of hymenoptera venom hypersensitivity
Authors: Seismann Henning , Blank Simon , Cifuentes Liliana , Braren Ingke , Bredehorst Reinhard , Grunwald Thomas , Ollert Markus , Spillner Edzard 
Published: April 2010

Abstract

Background
Hymenoptera venoms are known to cause life-threatening IgE-mediated anaphylactic reactions in allergic individuals. Proper diagnosis of hymenoptera venom allergy using venom extracts is severely affected by molecular cross-reactivities. Although non-glycosylated marker allergens would facilitate the identification of the culprit venom, the major allergen phospholipase A1 (Ves v 1) from yellow jacket venom (YJV) remained unavailable so far.

Methods
Expression of Ves v 1 as wild type and enzymatically inactivated mutant and Ves v 5 in insect cells yielded soluble proteins that were purified via affinity chromatography. Functionality of the recombinant allergens was assessed by enzymatic and biophysical analyses as well as basophil activation tests. Diagnostic relevance was addressed by ELISA-based analyses of sera of YJV-sensitized patients.

Results
Both major allergens Ves v 1 and Ves v 5 could be produced in insect cells in secreted soluble form. The recombinant proteins exhibited their particular biochemical and functional characteristics and were capable for activation of human basophils. Assessment of IgE reactivity of sera of YJV-sensitized and double-sensitized patients emphasised the relevance of Ves v 1 in hymenoptera venom allergy. In contrast to the use of singular molecules the combined use of both molecules enabled a reliable assignment of sensitisation to YJV for more than 90% of double-sensitised patients.

Conclusions
The recombinant availability of Ves v 1 from yellow jacket venom will contribute to a more detailed understanding of the molecular and allergological mechanisms of insect venoms and may provide a valuable tool for diagnostic and therapeutic approaches in hymenoptera venom allergy.
A novel serum-free medium for the expansion of human mesenchymal stem cells
Authors: Chase Lucas G , Lakshmipathy Uma , Solchaga Luis A , Rao Mahendra S , Vemuri Mohan C 
Published: April 2010

Abstract
Introduction
Human multipotent mesenchymal stem cell (MSC) therapies are being tested clinically for a variety of disorders, including Crohn's disease, multiple sclerosis, graft-versus-host disease, type 1 diabetes, bone fractures, and cartilage defects. However, despite the remarkable clinical advancements in this field, most applications still use traditional culture media containing fetal bovine serum. The ill-defined and highly variable nature of traditional culture media remains a challenge, hampering both the basic and clinical human MSC research fields. To date, no reliable serum-free medium for human MSCs has been available.

Methods
In this study, we developed and tested a serum-free growth medium on human bone marrow-derived MSCs through the investigation of multiple parameters including primary cell isolation, multipassage expansion, mesoderm differentiation, cellular phenotype, and gene-expression analysis.

Results
Similar to that achieved with traditional culture medium, human MSCs expanded in serum-free medium supplemented with recombinant human platelet-derived growth factor-BB (PDGF-BB), basic fibroblast growth factor (bFGF), and transforming growth factor (TGF)-β1 showed extensive propagation with retained phenotypic, differentiation, and colony-forming unit potential. To monitor global gene expression, the transcriptomes of bone marrow-derived MSCs expanded under serum-free and serum-containing conditions were compared, revealing similar expression profiles. In addition, the described serum-free culture medium supported the isolation of human MSCs from primary human marrow aspirate with continual propagation.

Conclusions
Although the described serum-free MSC culture medium is not free of xenogeneic components, this medium provides a substitute for serum-containing medium for research applications, setting the stage for future clinical applications.
Adipose tissue macrophages: their role in adipose tissue remodeling
Authors: Suganami Takayoshi , Ogawa Yoshihiro 
Published: April 2010

Abstract
This review summarizes the role of macrophages in adipose tissue remodeling, particularly focusing on the paracrine loop between adipocytes and macrophages.
The adipose tissue secretes a large number of bioactive substances, adipocytokines, which may be involved in a variety of physiologic and pathologic processes. Unbalanced production of pro- and anti-inflammatory adipocytokines seen in visceral fat obesity contributes critically to the development of the metabolic syndrome. Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation, suggesting that inflammation may be a potential mechanism, whereby obesity leads to insulin resistance. Indeed, obese adipose tissue is characterized by adipocyte hypertrophy, followed by increased angiogenesis, immune cell infiltration, extracellular matrix overproduction, and thus, increased production of proinflammatory adipocytokines during the progression of chronic inflammation. The dynamic change found in the adipose tissue can be referred to as “adipose tissue remodeling,” in which stromal cells change dramatically in number and cell type during the course of obesity. Among stromal cells, infiltration of macrophages in the adipose tissue precedes the development of insulin resistance in animal models, suggesting that they are crucial for obesity-related adipose tissue inflammation. We have demonstrated that a paracrine loop involving saturated fatty acids and TNF-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for TLR4 complex, thereby activating macrophages. Understanding the molecular mechanism underlying adipose tissue remodeling may lead to the identification of novel, therapeutic strategies to prevent or treat obesity-induced adipose tissue inflammation.
Release of IL-12 by dendritic cells activated by TLR ligation is dependent on MyD88 signaling, whereas TRIF signaling is indispensable for TLR synergy
Authors: Krummen Mathias , Balkow Sandra , Shen Limei , Heinz Stefanie , Loquai Carmen , Probst Hans-Christian , Grabbe Stephan 
Published: April 2010

Abstract
Synergistic activation of dendritic cells by combinations of TLR ligands requires both MyD88- and TRIF-dependent signaling.
Recently, it has been shown that certain combinations of TLR ligands act in synergy to induce the release of IL-12 by DCs. In this study, we sought to define the critical parameters underlying TLR synergy. Our data show that TLR ligands act synergistically if MyD88- and TRIF-dependent ligands are combined. TLR4 uses both of these adaptor molecules, thus activation via TLR4 proved to be a synergistic event on its own. TLR synergy did not affect all aspects of DC activation but enhanced primarily the release of certain cytokines, particularly IL-12, whereas the expression of costimulatory molecules remained unchanged. Consequently, synergistic activation of DC did not affect their ability to induce T cell proliferation but resulted in TH1-biased responses in vitro and in vivo. Furthermore, we examined the impact of TLR ligand combinations on primary DC in vitro but observed only modest effects with a combination of CpG + Poly (I:C). However, noticeable synergy in terms of IL-12 production by DCs was detectable in vivo after systemic administration of CpG + Poly (I:C). Finally, we show that synergy is partially dependent on IFNAR signaling but does not require the release of IFNs to the enviroment, suggesting an autocrine action of type I IFNs.
Differential polarization of alveolar macrophages and bone marrow-derived monocytes following chemically and pathogen-induced chronic lung inflammation
Authors: Redente Elizabeth F , Higgins David M , Dwyer-Nield Lori D , Orme Ian M , Gonzalez-Juarrero Mercedes , Malkinson Alvin M 
Published: April 2010

Abstract
Alveolar macrophages undergo similar polarization to chemically and pathogen-induced chronic lung inflammation, but the phenotype of bone marrow-derived monocytes varies between inflammations.
Alveolar macrophages and BDMCs undergo sequential biochemical changes during the chronic inflammatory response to chemically induced lung carcinogenesis in mice. Herein, we examine two chronic lung inflammation models—repeated exposure to BHT and infection with Mycobacterium tuberculosis—to establish whether similar macrophage phenotype changes occur in non-neoplastic pulmonary disease. Exposure to BHT or M. tuberculosis results in pulmonary inflammation characterized by an influx of macrophages, followed by systemic effects on the BM and other organs. In both models, pulmonary IFN-γ and IL-4 production coincided with altered polarization of alveolar macrophages. Soon after BHT administration or M. tuberculosis infection, IFN-γ content in BALF increased, and BAL macrophages became classically (M1) polarized, as characterized by increased expression of iNOS. As inflammation progressed in both models, the amount of BALF IFN-γ content and BAL macrophage iNOS expression decreased, and BALF IL-4 content and macrophage arginase I expression rose, indicating alternative/M2 polarization. Macrophages present in M. tuberculosis-induced granulomas remained M1-polarized, implying that these two pulmonary macrophage populations, alveolar and granuloma-associated, are exposed to different activating cytokines. BDMCs from BHT-treated mice displayed polarization profiles similar to alveolar macrophages, but BDMCs in M. tuberculosis-infected mice did not become polarized. Thus, only alveolar macrophages in these two models of chronic lung disease exhibit a similar progression of polarization changes; polarization of BDMCs was specific to BHT-induced pulmonary inflammation, and polarization of granuloma macrophages was specific to the M. tuberculosis infection.
Dual targeting of CCR2 and CCR5: therapeutic potential for immunologic and cardiovascular diseases
Authors: Zhao Qihong 
Published: April 2010

Abstract
This review presents evidence that dual targeting of CCR2 and CCR5 has greater therapeutic potential than targeting either receptor alone.
A cardinal feature of inflammation is the tissue recruitment of leukocytes, a process that is mediated predominantly by chemokines via their receptors on migrating cells. CCR2 and CCR5, two CC chemokine receptors, are important players in the trafficking of monocytes/macrophages and in the functions of other cell types relevant to disease pathogenesis. This review provides a brief overview of the biological actions of CCR2 and CCR5 and a comprehensive summary of published data that demonstrate the involvement of both receptors in the pathogenesis of immunologic diseases (RA, CD, and transplant rejection) and cardiovascular diseases (atherosclerosis and AIH). In light of the potential for functional redundancy of chemokine receptors in mediating leukocyte trafficking and the consequent concern over insufficient efficacy offered by pharmacologically inhibiting one receptor, this review presents evidence supporting dual targeting of CCR2 and CCR5 as a more efficacious strategy than targeting either receptor alone. It also examines potential safety issues associated with such dual targeting.
Distinct roles of complement receptor 3, Dectin-1, and sialic acids in murine macrophage interaction with Histoplasma yeast
Authors: Lin Jr-Shiuan , Huang Juin-Hua , Hung Li-Yin , Wu Sheng-Yang , Wu-Hsieh Betty A 
Published: April 2010

Abstract
CR3 on primary macrophage participates in phagocytosis of Histoplasma yeast and collaborates with dectin-1 in macrophage cytokine response to the fungus.
The yeast cells of dimorphic fungal pathogen Histoplasma reside primarily within the macrophages of an infected host; the interaction between the yeast and macrophage has a profound impact on host defense against the fungus. We used blocking antibodies and saccharides to identify the receptors that participate in the phagocytosis of and the cytokine response to Histoplasma. The phagocytosis and cytokine response results show that sialic acids on the macrophages were involved in the interaction between macrophages and Histoplasma. CR3, although not the only receptor involved, was responsible for phagocytosis and cytokine response. It is unclear which receptors other than CR3 are responsible for phagocytosis, but we did rule out the participation of TLR2, TLR4, MR, DC-SIGN/SIGNR1, FcγR, VLA-5, and Dectin-1. Even though Dectin-1 did not participate in phagocytosis, it collaborated with CR3 in the cytokine response to Histoplasma, suggesting that in the presence of phagocytic receptors, Histoplasma triggers cytokine signals through Dectin-1. Moreover, macrophage phagocytosis of and cytokine response to Histoplasma are Syk kinase-dependent. Our study delineated the distinct roles of CR3, Dectin-1, and sialic acids in the interaction with Histoplasma and suggested that multiple receptor use might be important to host defense against Histoplasma.