bluuebunny/crossref_metadata_2025_split huggingface dataset:
An Integrated Proteomics/Transcriptomics Approach Points to Oxygen as the Main Electron Sink for Methanol Metabolism in Methylotenera mobilis
Authors: Beck David A. C. , Hendrickson Erik L. , Vorobev Alexey , Wang Tiansong , Lim Sujung , Kalyuzhnaya Marina G. , Lidstrom Mary E. , Hackett Murray , Chistoserdova Ludmila 
Published: July 2011

ABSTRACT

Methylotenera
species, unlike their close relatives in the genera
Methylophilus
,
Methylobacillus
, and
Methylovorus
, neither exhibit the activity of methanol dehydrogenase nor possess
mxaFI
genes encoding this enzyme, yet they are able to grow on methanol. In this work, we integrated a genome-wide proteomics approach, shotgun proteomics, and a genome-wide transcriptomics approach, shotgun transcriptome sequencing (RNA-seq), of
Methylotenera mobilis
JLW8 to identify genes and enzymes potentially involved in methanol oxidation, with special attention to alternative nitrogen sources, to address the question of whether nitrate could play a role as an electron acceptor in place of oxygen. Both proteomics and transcriptomics identified a limited number of genes and enzymes specifically responding to methanol. This set includes genes involved in oxidative stress response systems, a number of oxidoreductases, including XoxF-type alcohol dehydrogenases, a type II secretion system, and proteins without a predicted function. Nitrate stimulated expression of some genes in assimilatory nitrate reduction and denitrification pathways, while ammonium downregulated some of the nitrogen metabolism genes. However, none of these genes appeared to respond to methanol, which suggests that oxygen may be the main electron sink during growth on methanol. This study identifies initial targets for future focused physiological studies, including mutant analysis, which will provide further details into this novel process.
Human NK Cells Are Alerted to Induction of p53 in Cancer Cells by Upregulation of the NKG2D Ligands ULBP1 and ULBP2
Authors: Textor Sonja , Fiegler Nathalie , Arnold Annette , Porgador Angel , Hofmann Thomas G. , Cerwenka Adelheid 
Published: July 2011

Abstract
Natural killer (NK) cells are immune cells sensing and eliminating foreign, stressed, transformed, and senescent cells through specialized surface receptors, such as NKG2D, that interacts with several virus- or stress-inducible ligands, including ULBP1 and -2, which are expressed on target cell surfaces. For example, induction of DNA damage or cellular senescence pathways in tumor cells led to upregulation of NKG2D ligands that activate NK cells. Although, both pathways activate p53, the relationship of p53 activation to upregulation of NKG2D ligands has not been addressed. In this study, we report that induction of wild-type p53, but not mutant p53, strongly upregulated mRNA and cell surface expression of ULBP1 and -2, whereas expression of other NK cell ligands was not affected. We defined intronic p53-responsive elements in these two novel p53 target genes. Coculture of wild-type p53-induced human tumor cells with primary human NK cells enhanced NKG2D-dependent degranulation and IFN-γ production by NK cells. Accordingly, treatment of certain wild-type p53-expressing tumor cell lines with the p53-reactivating small molecular compound RITA resulted in upregulation of ULBP2 mRNA and cell surface protein expression. Taken together, our findings define the involvement of p53 in the regulation of specific NKG2D ligands that enhance NK cell–mediated target recognition. One implication of our work is that activating p53 after adoptive transfer of NK cells might constitute an effective combinatorial strategy of NK cell–based immunochemotherapy in cancers in which wild-type p53 function is preserved. Cancer Res; 71(18); 5998–6009. ©2011 AACR.
Incidence of a first thromboembolic event in asymptomatic carriers of high-risk antiphospholipid antibody profile: a multicenter prospective study
Authors: Pengo Vittorio , Ruffatti Amelia , Legnani Cristina , Testa Sophie , Fierro Tiziana , Marongiu Francesco , De Micheli Valeria , Gresele Paolo , Tonello Marta , Ghirarduzzi Angelo , Bison Elisa , Denas Gentian , Banzato Alessandra , Padayattil Jose Seena , Iliceto Sabino 
Published: July 2011

Abstract
Persistent antiphospholipid (aPL) antibodies are occasionally found in subjects without prior history of thromboembolic events (TEs), raising the dilemma of whether to initiate or not a primary thromboprophylaxis. A first TE is considered rare in aPL carriers, but previous studies did not consider the aPL profile nor was the test positivity confirmed in a reference laboratory. In this study, 104 subjects with high-risk aPL profile (positive lupus anticoagulant, anticardiolipin, and anti-β2–glycoprotein I antibodies, triple positivity) confirmed in a reference laboratory, were followed up for a mean of 4.5 years. There were 25 first TEs (5.3% per year): the cumulative incidence after 10 years was 37.1% (95% confidence interval [CI], 19.9%-54.3%). On multivariate analysis, male sex (hazard ratio = 4.4; 95% CI, 1.5-13.1, P = .007) and risk factors for venous thromboembolism (hazard ratio = 3.3; 95% CI, 1.3-8.5, P = .01) were independent predictors for TEs. Aspirin did not significantly affect the incidence of TE. In conclusion, the occurrence of a first TE in carriers of high-risk aPL profile is considerable; it is more frequent among male subjects and in the presence of additional risk factors for venous TE. These data can help in the decision to initiate primary thromboprophylaxis in these subjects.
Differential MHC class I expression in distinct leukocyte subsets
Authors: Greene Justin M , Wiseman Roger W , Lank Simon M , Bimber Benjamin N , Karl Julie A , Burwitz Benjamin J , Lhost Jennifer J , Hawkins Oriana E , Kunstman Kevin J , Broman Karl W , Wolinsky Steven M , Hildebrand William H , O'Connor David H 
Published: July 2011

Abstract

Background
MHC class I proteins are partly responsible for shaping the magnitude and focus of the adaptive cellular immune response. In humans, conventional wisdom suggests that the HLA-A, -B, and -C alleles are equally expressed on the majority of cell types. While we currently have a thorough understanding of how total MHC class I expression varies in different tissues, it has been difficult to examine expression of single MHC class I alleles due to the homogeneity of MHC class I sequences. It is unclear how cDNA species are expressed in distinct cell subsets in humans and particularly in macaques which transcribe upwards of 20 distinct MHC class I alleles at variable levels.

Results
We examined MHC gene expression in human and macaque leukocyte subsets. In humans, while we detected overall differences in locus transcription, we found that transcription of MHC class I genes was consistent across the leukocyte subsets we studied with only small differences detected. In contrast, transcription of certain MHC cDNA species in macaques varied dramatically by up to 45% between different subsets. Although the Mafa-B*134:02 RNA is virtually undetectable in CD4+ T cells, it represents over 45% of class I transcripts in CD14+ monocytes. We observed parallel MHC transcription differences in rhesus macaques. Finally, we analyzed expression of select MHC proteins at the cell surface using fluorescent peptides. This technique confirmed results from the transcriptional analysis and demonstrated that other MHC proteins, known to restrict SIV-specific responses, are also differentially expressed among distinct leukocyte subsets.

Conclusions
We assessed MHC class I transcription and expression in human and macaque leukocyte subsets. Until now, it has been difficult to examine MHC class I allele expression due to the similarity of MHC class I sequences. Using two novel techniques we showed that expression varies among distinct leukocyte subsets of macaques but does not vary dramatically in the human cell subsets we examined. These findings suggest pathogen tropism may have a profound impact on the shape and focus of the MHC class I restricted CD8+ T cell response in macaques.
Dynamic Portfolio Optimization with Transaction Costs: Heuristics and Dual Bounds
Authors: Brown David B. , Smith James E. 
Published: July 2011

We consider the problem of dynamic portfolio optimization in a discrete-time, finite-horizon setting. Our general model considers risk aversion, portfolio constraints (e.g., no short positions), return predictability, and transaction costs. This problem is naturally formulated as a stochastic dynamic program. Unfortunately, with nonzero transaction costs, the dimension of the state space is at least as large as the number of assets, and the problem is very difficult to solve with more than one or two assets. In this paper, we consider several easy-to-compute heuristic trading strategies that are based on optimizing simpler models. We complement these heuristics with upper bounds on the performance with an optimal trading strategy. These bounds are based on the dual approach developed in Brown et al. (Brown, D. B., J. E. Smith, P. Sun. 2009. Information relaxations and duality in stochastic dynamic programs. Oper. Res. 58(4) 785–801). In this context, these bounds are given by considering an investor who has access to perfect information about future returns but is penalized for using this advance information. These heuristic strategies and bounds can be evaluated using Monte Carlo simulation. We evaluate these heuristics and bounds in numerical experiments with a risk-free asset and 3 or 10 risky assets. In many cases, the performance of the heuristic strategy is very close to the upper bound, indicating that the heuristic strategies are very nearly optimal. This paper was accepted by Dimitris Bertsimas, optimization.
CGS 21680, an Agonist of the Adenosine (A2A) Receptor, Reduces Progression of Murine Type II Collagen-induced Arthritis
Authors: MAZZON EMANUELA , ESPOSITO EMANUELA , IMPELLIZZERI DANIELA , DI PAOLA ROSANNA , MELANI ALESSIA , BRAMANTI PLACIDO , PEDATA FELICITA , CUZZOCREA SALVATORE 
Published: July 2011

Objective.The aim of our study was to investigate the effect of an adenosine A2A receptor agonist, 2-[p-(2-carboxyethyl)phenylethylamino]-50 ethylcarboxamidoadenosine (CGS 21680), on modulation of the inflammatory response in mice subjected to collagen-induced arthritis (CIA).Methods.CIA was induced by intradermal injection of 100 μl of emulsion containing 100 μg of bovine type II collagen (CII) and complete Freund’s adjuvant (CFA) at the base of the tail. On Day 21, a second injection of CII in CFA was administered. Immunized mice developed erosive hind paw arthritis. Macroscopic clinical evidence of CIA first appeared as periarticular erythema and edema in the hind paws. The incidence of CIA was 100% by Day 27 in the CII challenged mice and the severity of CIA progressed over a 35-day period, with radiographic evaluation revealing focal resorption of bone. The histopathology of CIA included erosion of cartilage at the joint margins.Results.Treatment of mice with CGS 21680 starting at the onset of arthritis (Day 25) ameliorated the clinical signs at Days 26–35 and improved histological status in the joint and paw. The degree of oxidative and nitrosative damage was significantly reduced in CGS 21680-treated mice as indicated by elevated levels of malondialdehyde, formation of nitrotyrosine, and activation of poly(ADP-ribose) polymerase. Plasma levels of proinflammatory cytokines such as tumor necrosis factor, interleukin 1ß (IL-1ß) and IL-6 were also reduced by CGS 21680. Treatment with CGS 21680 also decreased the expression of inducible nitric oxide synthase and cyclooxygenase-2.Conclusion.We demonstrate that CGS 21680 exerts an antiinflammatory effect during chronic inflammation and ameliorates the tissue damage associated with CIA.
25-Hydroxyvitamin D Levels and Vitamin D Deficiency in Children with Rheumatologic Disorders and Controls
Authors: PELAJO CHRISTINA F. , LOPEZ-BENITEZ JORGE M. , MILLER LAURIE C. 
Published: July 2011

Objective.To evaluate the prevalence of vitamin D deficiency, as well as factors associated with serum 25-hydroxyvitamin D [25(OH)D] levels, in children attending a pediatric rheumatology clinic, and to determine whether there was a difference in serum 25(OH)D levels and in vitamin D deficiency between children with autoimmune disorders and nonautoimmune conditions.Methods.Cross-sectional analysis of serum 25(OH)D levels of patients between the ages of 2 and 19 years, seen between November 2008 and October 2009.Results.A total of 254 patients were studied (169 autoimmune disorders, 85 nonautoimmune conditions). The mean age of study patients was 12.3 years; 67% were female and 80% were white. In the autoimmune disorders group, 23% had vitamin D deficiency [serum 25(OH)D < 20 ng/ml], and in the nonautoimmune conditions group 14% were vitamin D deficient. The average level of serum 25(OH)D was 28.6 (± 11) ng/ml (range 2 to 59). Age, ethnicity, body mass index, use of supplements, and season were significantly associated with serum levels of 25(OH)D (all p ≤ 0.02). The OR of patients with autoimmune disorders being vitamin D deficient was 2.3, in relation to patients with nonautoimmune conditions (p = 0.04).Conclusion.Twenty percent of patients attending a pediatric rheumatology clinic were vitamin D deficient. Patients with autoimmune disorders were more likely to be vitamin D deficient than patients with nonautoimmune conditions. Screening of serum 25(OH)D levels should be performed for patients with autoimmune disorders.
Canadian Recommendations for Clinical Trials of Pharmacologic Interventions in Rheumatoid Arthritis: Inclusion Criteria and Study Design: Table 1.
Authors: KARSH JACOB , KEYSTONE EDWARD C. , HARAOUI BOULOS , THORNE J. CARTER , POPE JANET E. , BYKERK VIVIAN P. , MAKSYMOWYCH WALTER P. , ZUMMER MICHEL , BENSEN WILLIAM G. , KRAISHI MAJED M. 
Published: July 2011

Objective.Current clinical trial designs for pharmacologic interventions in rheumatoid arthritis (RA) do not reflect the innovations in RA diagnosis, treatment, and care in countries where new drugs are most often used. The objective of this project was to recommend revised entry criteria and other study design features for RA clinical trials.Methods.Recommendations were developed using a modified nominal group consensus method. Canadian Rheumatology Research Consortium (CRRC) members were polled to rank the greatest challenges to clinical trial recruitment in their practices. Initial recommendations were developed by an expert panel of rheumatology trialists and other experts. A scoping study methodology was then used to examine the evidence available to support or refute each initial recommendation. The potential influence of CRRC recommendations on primary outcomes in future trials was examined. Recommendations were finalized using a consensus process.Results.Recommendations for clinical trial inclusion criteria addressed measures of disease activity [Disease Activity Score 28 using erythrocyte sedimentation rate (DAS28-ESR) > 3.2 PLUS ≥ 3 tender joints using 28-joint count (TJC28) PLUS ≥ 3 swollen joint (SJC28) OR C-reactive protein (CRP) or ESR > upper limit of normal PLUS ≥ 3 TJC28 PLUS ≥ 3 SJC28], functional classification, disease classification and duration, and concomitant RA treatments. Additional recommendations regarding study design addressed rescue strategies and longterm extension.Conclusion.There is an urgent need to modify clinical trial inclusion criteria and other study design features to better reflect the current characteristics of people living with RA in the countries where the new drugs will be used.
Role of IL-17 and Th17 Cells in Herpes Simplex Virus-Induced Corneal Immunopathology
Authors: Suryawanshi Amol , Veiga-Parga Tamara , Rajasagi Naveen K. , Reddy Pradeep Babu Jagdeesh , Sehrawat Sharvan , Sharma Shalini , Rouse Barry T. 
Published: July 2011

Abstract
HSV-1 infection of the cornea leads to a blinding immunoinflammatory lesion of the eye termed stromal keratitis (SK). Recently, IL-17–producing CD4+ T cells (Th17 cells) were shown to play a prominent role in many autoimmune conditions, but the role of IL-17 and/or of Th17 cells in virus immunopathology is unclear. In this study, we show that, after HSV infection of the cornea, IL-17 is upregulated in a biphasic manner with an initial peak production around day 2 postinfection and a second wave starting from day 7 postinfection with a steady increase until day 21 postinfection, a time point when clinical lesions are fully evident. Further studies demonstrated that innate cells, particularly γδ T cells, were major producers of IL-17 early after HSV infection. However, during the clinical phase of SK, the predominant source of IL-17 was Th17 cells that infiltrated the cornea only after the entry of Th1 cells. By ex vivo stimulation, the half fraction of IFN-γ–producing CD4+ T cells (Th1 cells) were HSV specific, whereas very few Th17 cells responded to HSV stimulation. The delayed influx of Th17 cells in the cornea was attributed to the local chemokine and cytokine milieu. Finally, HSV infection of IL-17R knockout mice as well as IL-17 neutralization in wild-type mice showed diminished SK severity. In conclusion, our results show that IL-17 and Th17 cells contribute to the pathogenesis of SK, the most common cause of infectious blindness in the Western world.
Role of Zooplankton Diversity in Vibrio cholerae Population Dynamics and in the Incidence of Cholera in the Bangladesh Sundarbans
Authors: de Magny Guillaume Constantin , Mozumder Pronob K. , Grim Christopher J. , Hasan Nur A. , Naser M. Niamul , Alam Munirul , Sack R. Bradley , Huq Anwar , Colwell Rita R. 
Published: July 2011

ABSTRACT

Vibrio cholerae
, a bacterium autochthonous to the aquatic environment, is the causative agent of cholera, a severe watery, life-threatening diarrheal disease occurring predominantly in developing countries.
V. cholerae
, including both serogroups O1 and O139, is found in association with crustacean zooplankton, mainly copepods, and notably in ponds, rivers, and estuarine systems globally. The incidence of cholera and occurrence of pathogenic
V. cholerae
strains with zooplankton were studied in two areas of Bangladesh: Bakerganj and Mathbaria. Chitinous zooplankton communities of several bodies of water were analyzed in order to understand the interaction of the zooplankton population composition with the population dynamics of pathogenic
V. cholerae
and incidence of cholera. Two dominant zooplankton groups were found to be consistently associated with detection of
V. cholerae
and/or occurrence of cholera cases, namely, rotifers and cladocerans, in addition to copepods. Local differences indicate there are subtle ecological factors that can influence interactions between
V. cholerae
, its plankton hosts, and the incidence of cholera.
Ligands of Thermophilic ABC Transporters Encoded in a Newly Sequenced Genomic Region of Thermotoga maritima MSB8 Screened by Differential Scanning Fluorimetry
Authors: Boucher Nathalie , Noll Kenneth M. 
Published: July 2011

ABSTRACT

The chromosome of
Thermotoga maritima
strain MSB8 was found to have an 8,870-bp region that is not present in its published sequence. The isolate that was sequenced by The Institute for Genomic Research (TIGR) in 1999 is apparently a laboratory variant of the isolate deposited at the Deutsche Sammlung von Mikroorganismen und Zellkulturen (DSM 3109) in 1986. This newly sequenced region from the DSMZ culture was located between TM1848 (
cbp
, cellobiose phosphorylase) and TM1847 (the 3′ end of a truncated ROK regulator). The new region contained seven genes: a beta glucosidase gene (
bglA
), three trehalose ABC transporter genes (
treEFG
), three xylose ABC transporter genes (
xylE2F2K2
), and the 5′ end of a gene encoding the ROK regulator TM1847. We present a new differential scanning fluorimetry method using a low pH that was necessary to screen potential ligands of these exceptionally thermostable periplasmic substrate-binding proteins. This method showed that trehalose, sucrose, and glucose stabilized TreE, and their binding was confirmed by measuring changes in intrinsic fluorescence upon ligand binding. Binding constants of 0.024 μM, 0.300 μM, and 56.78 μM at 60°C, respectively, were measured. XylE2 ligands were similarly determined and xylose, glucose, and fucose bound with

K
d

(dissociation constant) values of 0.042 μM, 0.059 μM, and 1.436 μM, respectively. Since there is no discernible phenotypic difference between the TIGR isolate and the DSMZ isolate despite the variance in their genomes, we propose that they be called genomovars:
T. maritima
MSB8 genomovar TIGR and
T. maritima
MSB8 genomovar DSM 3109, respectively.
Reinventing Heterochromatin in Budding Yeasts: Sir2 and the Origin Recognition Complex Take Center Stage
Authors: Hickman Meleah A. , Froyd Cara A. , Rusche Laura N. 
Published: July 2011

ABSTRACT

The transcriptional silencing of the cryptic mating-type loci in
Saccharomyces cerevisiae
is one of the best-studied models of repressive heterochromatin. However, this type of heterochromatin, which is mediated by the Sir proteins, has a distinct molecular composition compared to the more ubiquitous type of heterochromatin found in
Schizosaccharomyces pombe
, other fungi, animals, and plants and characterized by the presence of HP1 (heterochromatin protein 1). This review discusses how the loss of important heterochromatin proteins, including HP1, in the budding yeast lineage presented an evolutionary opportunity for the development and diversification of alternative varieties of heterochromatin, in which the conserved deacetylase Sir2 and the replication protein Orc1 play key roles. In addition, we highlight how this diversification has been facilitated by gene duplications and has contributed to adaptations in lifestyle.
Antibiotic Production by Myxobacteria Plays a Role in Predation
Authors: Xiao Yao , Wei Xueming , Ebright Richard , Wall Daniel 
Published: July 2011

ABSTRACT

Myxobacteria are predatory and are prolific producers of secondary metabolites. Here, we tested a hypothesized role that secondary metabolite antibiotics function as weapons in predation. To test this, a
Myxococcus xanthus
Δta1
mutant, blocked in antibiotic TA (myxovirescin) production, was constructed. This TA
−
mutant was defective in producing a zone of inhibition (ZOI) against
Escherichia coli
. This shows that TA is the major
M. xanthus
-diffusible antibacterial agent against
E. coli
. Correspondingly, the TA
−
mutant was defective in
E. coli
killing. Separately, an engineered
E. coli
strain resistant to TA was shown to be resistant toward predation. Exogenous addition of spectinomycin, a bacteriostatic antibiotic, rescued the predation defect of the TA
−
mutant. In contrast, against
Micrococcus luteus
the TA
−
mutant exhibited no defect in ZOI or killing. Thus, TA plays a selective role on prey species. To extend these studies to other myxobacteria, the role of antibiotic corallopyronin production in predation was tested and also found to be required for
Corallococcus coralloides
killing on
E. coli
. Next, a role of TA production in myxobacterial fitness was assessed by measuring swarm expansion. Here, the TA
−
mutant had a specific swarm rate reduction on prey lawns, and thus reduced fitness, compared to an isogenic TA
+
strain. Based on these observations, we conclude that myxobacterial antibiotic production can function as a predatory weapon. To our knowledge, this is the first report to directly show a link between secondary metabolite production and predation.