bluuebunny/crossref_metadata_2025_split huggingface dataset:
Differential Subcutaneous Adipose Tissue Gene Expression Patterns in a Randomized Clinical Trial of Efavirenz or Lopinavir-Ritonavir in Antiretroviral-Naive Patients
Authors: Egaña-Gorroño L. , Martínez E. , Domingo P. , Loncà M. , Escribà T. , Fontdevila J. , Vidal F. , Negredo E. , Gatell J. M. , Arnedo M. 
Published: August 2014

ABSTRACTGene expression studies of subcutaneous adipose tissue may help to better understand the mechanisms behind body fat changes in HIV-infected patients who initiate antiretroviral therapy (ART). Here, we evaluated early changes in adipose tissue gene expression and their relationship to fat changes in ART-naive HIV-infected patients randomly assigned to initiate therapy with emtricitabine/tenofovir plus efavirenz (EFV) or ritonavir-boosted lopinavir (LPV/r). Patients had abdominal subcutaneous adipose tissue biopsies at baseline and week 16 and dual-energy-X-ray absorptiometry at baseline and weeks 16 and 48. mRNA changes of 11 genes involved in adipogenesis, lipid and glucose metabolism, mitochondrial energy, and inflammation were assessed through reverse transcription-quantitative PCR (RT-qPCR). Additionally, correlations between gene expression changes and fat changes were evaluated. Fat increased preferentially in the trunk with EFV and in the limbs with LPV/r (P< 0.05). After 16 weeks of exposure to the drug regimen, transcripts ofCEBP/A,ADIPOQ,GLUT4,LPL, andCOXIVwere significantly down-regulated in the EFV arm compared to the LPV/r arm (P< 0.05). Significant correlations were observed betweenLPLexpression change and trunk fat change at week 16 in both arms and betweenCEBP/AorCOXIVchange and trunk fat change at the same time point only in the EFV arm and not in the LPV/r arm. When combined with emtricitabine/tenofovir as standard backbone therapy, EFV and LPV/r induced differential early expression of genes involved in adipogenesis and energy metabolism. Moreover, these mRNA expression changes correlated with trunk fat change in the EFV arm. (This was a substudy of a randomized clinical trial [LIPOTAR study] registered atClinicalTrials.govunder identifier NCT00759070.)
Antiviral Effects of Artesunate on JC Polyomavirus Replication in COS-7 Cells
Authors: Sharma Biswa Nath , Marschall Manfred , Rinaldo Christine Hanssen 
Published: August 2014

ABSTRACT

The human JC polyomavirus (JCPyV) causes the fatal demyelinating disease progressive multifocal leukoencephalopathy (PML). A growing number of patients with induced or acquired immunosuppression are at risk for infection, and no effective antiviral therapy is presently available. The widely used antimalarial drug artesunate has shown broad antiviral activity
in vitro
but limited clinical success. The aim of this study was to investigate the effect of artesunate on JCPyV replication
in vitro
. The permissivity for JCPyV MAD-4 was first compared in four cell lines, and the monkey kidney cell line COS-7 was selected. Artesunate caused a concentration-dependent decrease in the extracellular JCPyV DNA load 96 h postinfection, with a 50% effective concentration (EC
50
) of 2.9 μM. This effect correlated with a decreased expression of capsid protein VP1 and a reduced release of infectious viral progeny. For concentrations of <20 μM, transient reductions in cellular DNA replication and proliferation were seen, while for higher concentrations, some cytotoxicity was detected. A selective index of 16.6 was found when cytotoxicity was calculated based on cellular DNA replication in the mock-infected cells, but interestingly, cellular DNA replication in the JCPyV-infected cells was more strongly affected. In conclusion, artesunate is efficacious in inhibiting JCPyV replication at micromolar concentrations, which are achievable in plasma. The inhibition at EC
50
probably reflects an effect on cellular proteins and involves transient cytostatic effects. Our results, together with the favorable distribution of the active metabolite dihydroartemisinin to the central nervous system, suggest a potential use for artesunate in patients with PML.
Culture of the Entire Mouse To Determine whether Cultivable Borrelia burgdorferi Persists in Infected Mice Treated with a Five-Day Course of Ceftriaxone
Authors: Pavia Charles S. , Wormser Gary P. 
Published: August 2014

ABSTRACT

Although controversial, it has been suggested that antibiotic treatment of laboratory animals infected with
Borrelia burgdorferi
often leads to the persistence of residual spirochetes that are claimed to be viable but noncultivable. If viable cells of
B. burgdorferi
do persist following antibiotic therapy, one possible explanation for the lack of cultivability is that too few organisms persist in any given tissue site that might be sampled and cultured. In this study, we treated SKH (hairless) mice, with
B. burgdorferi
infection of 3 months' duration, with either ceftriaxone or saline for 5 days and then cultured a suspension extract of nearly the entire mouse using a combined
in vivo
/
in vitro
culture method. All of the saline-treated (control) mice were culture positive, compared with none of the antibiotic-treated mice. Our findings further document the effectiveness of antibiotic therapy in eradicating cultivable cells of
B. burgdorferi
, irrespective of tissue or organ site.
The Subcellular Location of Ovalbumin in Plasmodium berghei Blood Stages Influences the Magnitude of T-Cell Responses
Authors: Lin Jing-Wen , Shaw Tovah N. , Annoura Takeshi , Fougère Aurélie , Bouchier Pascale , Chevalley-Maurel Séverine , Kroeze Hans , Franke-Fayard Blandine , Janse Chris J. , Couper Kevin N. , Khan Shahid M. 
Published: August 2014

ABSTRACTModel antigens are frequently introduced into pathogens to study determinants that influence T-cell responses to infections. To address whether an antigen's subcellular location influences the nature and magnitude of antigen-specific T-cell responses, we generatedPlasmodium bergheiparasites expressing the model antigen ovalbumin (OVA) either in the parasite cytoplasm or on the parasitophorous vacuole membrane (PVM). For cytosolic expression, OVA alone or conjugated to mCherry was expressed from a strong constitutive promoter (OVAhsp70orOVA::mCherryhsp70); for PVM expression, OVA was fused to HEP17/EXP1 (OVA::Hep17hep17). Unexpectedly, OVA expression inOVAhsp70parasites was very low, but when OVA was fused to mCherry (OVA::mCherryhsp70), it was highly expressed. OVA expression inOVA::Hep17hep17parasites was strong but significantly less than that inOVA::mCherryhsp70parasites. These transgenic parasites were used to examine the effects of antigen subcellular location and expression level on the development of T-cell responses during blood-stage infections. While all OVA-expressing parasites induced activation and proliferation of OVA-specific CD8+T cells (OT-I) and CD4+T cells (OT-II), the level of activation varied:OVA::Hep17hep17parasites induced significantly stronger splenic and intracerebral OT-I and OT-II responses than those ofOVA::mCherryhsp70parasites, butOVA::mCherryhsp70parasites promoted stronger OT-I and OT-II responses than those ofOVAhsp70parasites. Despite lower OVA expression levels,OVA::Hep17hep17parasites induced stronger T-cell responses than those ofOVA::mCherryhsp70parasites. These results indicate that unconjugated cytosolic OVA is not stably expressed inPlasmodiumparasites and, importantly, that its cellular location and expression level influence both the induction and magnitude of parasite-specific T-cell responses. These parasites represent useful tools for studying the development and function of antigen-specific T-cell responses during malaria infection.
MicroRNA-155 Is Required for Clearance of Streptococcus pneumoniae from the Nasopharynx
Authors: Verschoor Chris P. , Dorrington Michael G. , Novakowski Kyle E. , Kaiser Julie , Radford Katherine , Nair Parameswaran , Anipindi Varun , Kaushic Charu , Surette Michael G. , Bowdish Dawn M. E. 
Published: August 2014

ABSTRACT

Pneumonia caused by
Streptococcus pneumoniae
is a major cause of death and an economic burden worldwide.
S. pneumoniae
is an intermittent colonizer of the human upper respiratory tract, and the ability to control asymptomatic colonization determines the likelihood of developing invasive disease. Recognition of
S. pneumoniae
by resident macrophages via Toll-like receptor 2 (TLR-2) and the macrophage receptor with collagenous structure (MARCO) and the presence of interleukin-17 (IL-17)-secreting CD4
+
T cells are required for macrophage recruitment and bacterial clearance. Despite the fact that the primary cellular effectors needed for bacterial clearance have been identified, much of the underlying regulatory mechanisms are unknown. Herein, we demonstrate that the small, noncoding RNA microRNA-155 (mir-155) is critical for the effective clearance of
S. pneumoniae
. Our studies show that mir-155-deficient mice maintain the ability to prevent acute invasive pneumococcal infection but have significantly higher bacterial burdens following colonization, independently of macrophage recognition by TLR-2, MARCO expression, or bactericidal capacity. The observed defects in bacterial clearance parallel reduced IL-17A and gamma interferon CD4
+
T-cell responses
in vivo
, lower IL-17A mRNA levels in the nasopharynx, and a reduced capacity to induce Th17 cell polarization. Given that knockout mice are also limited in the capacity to generate high-titer
S. pneumoniae
-specific antibodies, we conclude that mir-155 is a critical mediator of the cellular effectors needed to clear primary and secondary
S. pneumoniae
colonizations.
Differential Regulation of Proinflammatory Cytokine Expression by Mitogen-Activated Protein Kinases in Macrophages in Response to Intestinal Parasite Infection
Authors: Lim Mei Xing , Png Chin Wen , Tay Crispina Yan Bing , Teo Joshua Ding Wei , Jiao Huipeng , Lehming Norbert , Tan Kevin Shyong Wei , Zhang Yongliang 
Published: August 2014

ABSTRACTBlastocystisis a common enteric protistan parasite that can cause acute, as well as chronic, infection and is associated with irritable bowel syndrome (IBS). However, the pathogenic status ofBlastocystisinfection remains unclear. In this study, we found thatBlastocystisantigens induced abundant expression of proinflammatory cytokines, including interleukin 1β (IL-1β), IL-6, and tumor necrosis factor alpha (TNF-α), in mouse intestinal explants, in mouse colitis colon, and in macrophages. Further investigation utilizing RAW264.7 murine macrophages showed thatBlastocystistreatment in RAW264.7 macrophages induced the activation of ERK, JNK, and p38, the three major groups of mammalian mitogen-activated protein (MAP) kinases that play essential roles in the expression of proinflammatory cytokines. ERK inhibition in macrophages significantly suppressed both mRNA and protein expression of IL-6 and TNF-α and mRNA expression of IL-1β. On the other hand, JNK inhibition resulted in reductions in both c-Jun and ERK activation and significant suppression of all three proinflammatory cytokines at both the mRNA and protein levels. Inhibition of p38 suppressed only IL-6 protein expression with no effect on the expression of IL-1β and TNF-α. Furthermore, we found that serine proteases produced byBlastocystisplay an important role in the induction of ERK activation and proinflammatory cytokine expression by macrophages. Our study thus demonstrated for the first time thatBlastocystiscould induce the expression of various proinflammatory cytokines via the activation of MAP kinases and that infection withBlastocystismay contribute to the pathogenesis of inflammatory intestinal diseases through the activation of inflammatory pathways in host immune cells, such as macrophages.
A Synthetic Peptide Corresponding to the Extracellular Loop 2 Region of Claudin-4 Protects against Clostridium perfringens Enterotoxin
In Vitro
and
In Vivo
Authors: Shrestha Archana , Robertson Susan L. , Garcia Jorge , Beingasser Juliann , McClane Bruce A. , Uzal Francisco A. 
Published: August 2014

ABSTRACT

Clostridium perfringens
enterotoxin (CPE) action starts when the toxin binds to claudin receptors. Claudins contain two extracellular loop domains, with the second loop (ECL-2) being slightly smaller than the first. CPE has been shown to bind to ECL-2 in receptor claudins. We recently demonstrated that Caco-2 cells (a naturally CPE-sensitive enterocyte-like cell line) can be protected from CPE-induced cytotoxicity by preincubating the enterotoxin with soluble full-length recombinant claudin-4 (
r
claudin-4), which is a CPE receptor, but not with recombinant nonreceptor claudins, such as
r
claudin-1. The current study evaluated whether a synthetic peptide corresponding to the claudin-4 ECL-2 sequence can similarly inhibit CPE action
in vitro
and
in vivo
. Significant protection of Caco-2 cells was also observed using either
r
claudin-4 or the claudin-4 ECL-2 peptide in both a preincubation assay and a coincubation assay. This inhibitory effect was specific, since
r
claudin-1 and a synthetic peptide based on the claudin-1 ECL-2 offered no protection to Caco-2 cells. However, the claudin-4 ECL-2 peptide was unable to neutralize cytotoxicity if CPE had already bound to Caco-2 cells. When the study was repeated
in vivo
using a rabbit small intestinal loop assay, preincubation or coincubation of CPE with the claudin-4 ECL-2 peptide significantly and specifically inhibited the development of CPE-induced luminal fluid accumulation and histologic lesions in rabbit small intestinal loops. No similar
in vivo
protection from CPE was afforded by the claudin-1 ECL-2 peptide. These results suggest that claudin-4 ECL-2 peptides should be further investigated for their potential therapeutic application against CPE-associated disease.
Near-Real-Time Analysis of the Phenotypic Responses of Escherichia coli to 1-Butanol Exposure Using Raman Spectroscopy
Authors: Zu Theresah N. K. , Athamneh Ahmad I. M. , Wallace Robert S. , Collakova Eva , Senger Ryan S. 
Published: August 2014

ABSTRACT

Raman spectroscopy was used to study the time course of phenotypic responses of
Escherichia coli
(DH5α) to 1-butanol exposure (1.2% [vol/vol]). Raman spectroscopy is of interest for bacterial phenotyping because it can be performed (i) in near real time, (ii) with minimal sample preparation (label-free), and (iii) with minimal spectral interference from water. Traditional off-line analytical methodologies were applied to both 1-butanol-treated and control cells to draw correlations with Raman data. Here, distinct sets of Raman bands are presented that characterize phenotypic traits of
E. coli
with maximized correlation to off-line measurements. In addition, the observed time course phenotypic responses of
E. coli
to 1.2% (vol/vol) 1-butanol exposure included the following: (i) decreased saturated fatty acids levels, (ii) retention of unsaturated fatty acids and low levels of cyclopropane fatty acids, (iii) increased membrane fluidity following the initial response of increased rigidity, and (iv) no changes in total protein content or protein-derived amino acid composition. For most phenotypic traits, correlation coefficients between Raman spectroscopy and traditional off-line analytical approaches exceeded 0.75, and major trends were captured. The results suggest that near-real-time Raman spectroscopy is suitable for approximating metabolic and physiological phenotyping of bacterial cells subjected to toxic environmental conditions.
The Iho670 Fibers of Ignicoccus hospitalis Are Anchored in the Cell by a Spherical Structure Located beneath the Inner Membrane
Authors: Meyer Carolin , Heimerl Thomas , Wirth Reinhard , Klingl Andreas , Rachel Reinhard 
Published: August 2014

ABSTRACT

The Iho670 fibers of the hyperthermophilic crenarchaeon of
Ignicoccus hospitalis
were shown to contain several features that indicate them as type IV pilus-like structures. The application of different visualization methods, including electron tomography and the reconstruction of a three-dimensional model, enabled a detailed description of a hitherto undescribed anchoring structure of the cell appendages. It could be identified as a spherical structure beneath the inner membrane. Furthermore, pools of the fiber protein Iho670 could be localized in the inner as well as the outer cellular membrane of
I. hospitalis
cells and in the tubes/vesicles in the intermembrane compartment by immunological methods.
Extracellular Secretion of Noncatalytic Plant Cell Wall-Binding Proteins by the Cellulolytic Thermophile Caldicellulosiruptor bescii
Authors: Yokoyama Hiroshi , Yamashita Takahiro , Morioka Riki , Ohmori Hideyuki 
Published: August 2014

ABSTRACT

Caldicellulosiruptor bescii
efficiently degrades cellulose, xylan, and native grasses at high temperatures above 70°C under anaerobic conditions.
C. bescii
extracellularly secretes multidomain glycoside hydrolases along with proteins of unknown function. In this study, we analyzed the
C. bescii
proteins that bind to the cell walls of timothy grass by using mass spectrometry, and we identified four noncatalytic plant cell wall-binding proteins (PWBPs) with high pI values (9.2 to 9.6). A search of a conserved domain database showed that these proteins possess a common domain related to solute-binding proteins. In addition, 12 genes encoding PWBP-like proteins were detected in the
C. bescii
genomic sequence. To analyze the binding properties of PWBPs, recombinant PWBP57 and PWBP65, expressed in
Escherichia coli
, were prepared. The PWBPs displayed a wide range of binding specificities: they bound to cellulose, lichenan, xylan, arabinoxylan, glucuronoxylan, mannan, glucomannan, pectin, oligosaccharides, and the cell walls of timothy grass. The proteins showed the highest binding affinity for the plant cell wall, with association constant (

K
a

) values of 5.2 × 10
6
to 44 × 10
6
M
−1
among the insoluble polysaccharides tested, as measured using depletion binding isotherms. Affinity gel electrophoresis demonstrated that the proteins bound to the acidic polymer pectin most strongly among the soluble polysaccharides tested. Fluorescence microscopic analysis showed that the proteins bound preferentially to the cell wall in a section of grass leaf. Binding of noncatalytic PWBPs with high pI values might be necessary for efficient utilization of polysaccharides by
C. bescii
at high temperatures.
Holins in Bacteria, Eukaryotes, and Archaea: Multifunctional Xenologues with Potential Biotechnological and Biomedical Applications
Authors: Saier Milton H. , Reddy Bhaskara L. 
Published: August 2014

ABSTRACT
Holins form pores in the cytoplasmic membranes of bacteria for the primary purpose of releasing endolysins that hydrolyze the cell wall and induce cell death. Holins are encoded within bacteriophage genomes, where they promote cell lysis for virion release, and within bacterial genomes, where they serve a diversity of potential or established functions. These include (i) release of gene transfer agents, (ii) facilitation of programs of differentiation such as those that allow sporulation and spore germination, (iii) contribution to biofilm formation, (iv) promotion of responses to stress conditions, and (v) release of toxins and other proteins. There are currently 58 recognized families of holins and putative holins with members exhibiting between 1 and 4 transmembrane α-helical spanners, but many more families have yet to be discovered. Programmed cell death in animals involves holin-like proteins such as Bax and Bak that may have evolved from bacterial holins. Holin homologues have also been identified in archaea, suggesting that these proteins are ubiquitous throughout the three domains of life. Phage-mediated cell lysis of dual-membrane Gram-negative bacteria also depends on outer membrane-disrupting “spanins” that function independently of, but in conjunction with, holins and endolysins. In this minireview, we provide an overview of their modes of action and the first comprehensive summary of the many currently recognized and postulated functions and uses of these cell lysis systems. It is anticipated that future studies will result in the elucidation of many more such functions and the development of additional applications.
Intraoperative angiography does not lead to increased rates of surgical site infections
Authors: Stetler William R , Wilson Thomas J , Al-Holou Wajd N , Khan Adam , Thompson B Gregory , Pandey Aditya S 
Published: August 2014

BackgroundIntraoperative angiography (IOA) is essential in evaluating residual aneurysm following clip ligation, but it does lead to an additional procedure which increases the duration of the procedure as well as increasing room traffic. We examined whether IOA during microsurgery is a risk factor for developing cranial surgical site infection.Materials and methodsA retrospective cohort study was performed of all patients undergoing craniotomy for aneurysm treatment between 2005 and 2012 at the University of Michigan. IOA was used at the surgeons’ discretion. The primary outcome of interest was occurrence of a surgical site infection and the secondary outcome of interest was clip repositioning following IOA. Variables including IOA were tested for their independent association with the occurrence of a surgical site infection.ResultsDuring the study period 676 intracranial aneurysms were treated by craniotomy; IOA was used in 104 of these cases. There were a total of 20 surgical site infections, 2 in the IOA group (1.9%) and 18 in the non-IOA group (3.1%), indicating that IOA was not a statistically significant variable for infection (p=0.50). No additional single variable measured could be shown to have a statistically significant increase in infection, and there were no direct complications related to the use of IOA (stroke, dissection, perforation).ConclusionsIOA does not increase the risk of developing a surgical site infection. It can be conducted without exposing patients to an undue risk of infection.
A Survey of Provably Secure Searchable Encryption
Authors: Bösch Christoph , Hartel Pieter , Jonker Willem , Peter Andreas 
Published: August 2014

We survey the notion of provably secure searchable encryption (SE) by giving a complete and comprehensive overview of the two main SE techniques: searchable symmetric encryption (SSE) and public key encryption with keyword search (PEKS). Since the pioneering work of Song, Wagner, and Perrig (IEEE S&P '00), the field of provably secure SE has expanded to the point where we felt that taking stock would provide benefit to the community.The survey has been written primarily for the nonspecialist who has a basic information security background. Thus, we sacrifice full details and proofs of individual constructions in favor of an overview of the underlying key techniques. We categorize and compare the different SE schemes in terms of their security, efficiency, and functionality. For the experienced researcher, we point out connections between the many approaches to SE and identify open research problems.Two major conclusions can be drawn from our work. While the so-called IND-CKA2 security notion becomes prevalent in the literature and efficient (sublinear) SE schemes meeting this notion exist in the symmetric setting, achieving this strong form of security efficiently in the asymmetric setting remains an open problem. We observe that in multirecipient SE schemes, regardless of their efficiency drawbacks, there is a noticeable lack of query expressiveness that hinders deployment in practice.
Midpoint-Free Subsets of the Real Numbers
Authors: Eggleton Roger B. 
Published: August 2014

A set of reals S⊂R is midpoint-free if it has no subset a, b, c⊆S such that a<b<c and a+c=2b. If S⊂X⊆R and S is midpoint-free, it is a maximal midpoint-free subset of X if there is no midpoint-free set T such that S⊂T⊆X. In each of the cases X=Z+, Z, Q+,Q,R+,R, we determine two maximal midpoint-free subsets of X characterised by digit constraints on the base 3 representations of their members.