bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effects of systemic pretreatment with CpG oligodeoxynucleotides on skin wound healing in mice
Authors: Hergert Bettina , Grambow Eberhard , Butschkau Antje , Vollmar Brigitte 
Published: August 2013

AbstractUnmethylated CpG oligodeoxynucleotides (ODN) bind to the Toll‐like receptor 9, thus stimulating the immune system. To study the effects of systemic pretreatment with CpG ODN on dermal regeneration, C57BL6/J Tyr mice were treated with CpG or control ODN 6 days prior to implantation of a dorsal skinfold chamber and skin wounding. Wound epithelialization was analyzed by planimetric microscopy. On day 18, wound tissues were taken for (immuno)histochemical staining. CpG ODN increased epithelialization compared with control ODN treatment. Histological analysis revealed reduced capillary density, reduced wound cellularity, and reduced numbers of infiltrating leukocytes, as well as reduced F4/80‐positive macrophages, but increased numbers of RELM‐α‐positive M2 macrophages after CpG ODN treatment, reflecting a better quality of wound healing on day 18 compared with control ODN treatment. Reverse transcription‐polymerase chain reaction analysis of Toll‐like receptor 9 showed the receptor expression on both fibroblasts and keratinocytes. Fibroblasts showed an increase of migration upon increasing dosages of CpG and not control ODN, reaching ∼50% of the response of basic fibroblast growth factor‐exposed cells. Keratinocytes dose‐dependently responded to both CpG and control ODN up to values found in keratinocyte growth factor‐exposed cells. In summary, CpG ODN support late tissue‐remodeling processes that contribute to resolution of inflammation and solid wounds during skin regeneration.
High bacterial load in negative pressure wound therapy (NPWT) foams used in the treatment of chronic wounds
Authors: Yusuf Erlangga , Jordan Xavier , Clauss Martin , Borens Olivier , Mäder Mark , Trampuz Andrej 
Published: August 2013

AbstractNo earlier study has investigated the microbiology of negative pressure wound therapy (NPWT) foam using a standardized manner. The purpose of this study is to investigate the bacterial load and microbiological dynamics in NPWT foam removed from chronic wounds (>3 months). To determine the bacterial load, a standardized size of the removed NPWT foam was sonicated. The resulting sonication fluid was cultured, and the colony‐forming units (CFU) of each species were enumerated. Sixty‐eight foams from 17 patients (mean age 63 years, 71% males) were investigated. In 65 (97%) foams, ≥ 1 and in 37 (54%) ≥2 bacterial types were found. The bacterial load remained high during NPWT treatment, ranging from 104 to 106 CFU/ml. In three patients (27%), additional type of bacteria was found in subsequent foam cultures. The mean bacterial count ± standard deviation was higher in polyvinyl alcohol foam (6.1 ± 0.5 CFU/ml) than in polyurethane (5.5 ± 0.8 CFU/ml) (p = 0.02). The mean of log of sum of CFU/ml in foam from 125 mmHg (5.5 ± 0.8) was lower than in foam from 100 mmHg pressure (5.9 ± 0.5) (p = 0.01). Concluding, bacterial load remains high in NPWT foam, and routine changing does not reduce the load.
Sequence-Controlled Polymers
Authors: Lutz Jean-François , Ouchi Makoto , Liu David R. , Sawamoto Mitsuo 
Published: August 2013

Background
During the last few decades, progress has been made in manipulating the architecture of synthetic polymer materials. However, the primary structure—that is, the sequential arrangement of monomer units in a polymer chain—is generally poorly controlled in synthetic macromolecules. Common synthetic polymers are usually homopolymers, made of the same monomer unit, or copolymers with simple chain microstructures, such as random or block copolymers. These polymers are used in many areas but do not have the structural and functional complexity of sequence-defined biopolymers, such as nucleic acids or proteins. Indeed, monomer sequence regulation plays a key role in biology and is a prerequisite for crucial features of life, such as heredity, self-replication, complex self-assembly, and molecular recognition. In this context, developing synthetic polymers containing controlled monomer sequences is an important area for research.

Advances
Various synthetic methods for controlling monomer sequences in polymers have been identified, and two major trends in the field of sequence-controlled polymers have emerged. Some approaches use biological concepts that have been optimized by nature for sequence regulation. For instance, DNA templates, enzymes, or even living organisms can be used to prepare sequence-defined polymers. These natural mechanisms can be adapted to tolerate nonnatural monomers. The other trend is the preparation of sequence-controlled polymers by synthetic chemistry. In the most popular approach, monomer units are attached one by one to a support, which is an efficient method but demanding in practice. Recently, some strategies have been proposed for controlling sequences in chain-growth and step-growth polymerizations. These mechanisms usually allow fast and large-scale synthesis of polymers. Specific kinetics and particular catalytic or template conditions allow sequence regulation in these processes.

Outlook
The possibility of controlling monomer sequences in synthetic macromolecules has many scientific and technological implications. Information can be controlled at the molecular level in synthetic polymer chains. This opens up interesting perspectives for the field of data storage. In addition, having power over monomer sequences could mean structural control of the resulting polymer, as it strongly influences macromolecular folding and self-assembly. For instance, functional synthetic assemblies that mimic the properties of globular proteins, such as enzymes and transporters, can be foreseen. Moreover, monomer sequence control influences some macroscopic properties. For example, bulk properties such as conductivity, rigidity, elasticity, or biodegradability can be finely tuned in sequence-controlled polymers. The behavior of polymers in solution, particularly in water, is also strongly dependent on monomer sequences. Thus, sequence regulation may enable a more effective control of structure-property relations in tomorrow’s polymer materials.
Expansion of Serotype Coverage in the Universal Pediatric Vaccination Calendar: Short-Term Effects on Age- and Serotype-Dependent Incidence of Invasive Pneumococcal Clinical Presentations in Madrid, Spain
Authors: Picazo Juan , Ruiz-Contreras Jesus , Casado-Flores Juan , Negreira Sagrario , García-de-Miguel Maria-Jesus , Hernández-Sampelayo Teresa , Otheo Enrique , Méndez Cristina 
Published: August 2013

ABSTRACTIn Madrid, Spain, the 13-valent pneumococcal conjugate vaccine (PCV13) replaced PCV7 in the pediatric universal vaccination calendar in June 2010. A prospective clinical surveillance that included all children hospitalized with culture- and/or PCR-confirmed invasive pneumococcal disease (IPD) was performed in all Madrid hospitals. The incidence rates (IRs) (defined as the number of cases/100,000 inhabitants aged <15 years) in the PCV7 (May 2007 to April 2010) versus PCV13 (May 2011 to April 2012) periods were compared. There were 499 cases in the PCV7 period and 79 cases in the PCV13 period. Globally, the IR significantly decreased from 17.09 (PCV7 period) to 7.70 (PCV13 period), with significant decreases (PCV7 versus PCV13 periods) in all age groups for bacteremic pneumonia (5.51 versus 1.56), parapneumonic pneumococcal empyema (PPE) (5.72 versus 3.12), and meningitis (2.16 versus 0.97). In the PCV13 period, significant reductions (the IR in the PCV7 period versus the IR in the PCV13 period) were found in IPDs caused by PCV13 serotypes (13.49 versus 4.38), and specifically by serotypes 1 (globally [4.79 versus 2.53], for bacteremic pneumonia [2.23 versus 0.97], and for PPE [2.26 versus 1.17]), serotype 5 (globally [1.88 versus 0.00], for bacteremic pneumonia [0.89 versus 0.00], and for PPE [0.55 versus 0.00]), and serotype 19A (globally [3.77 versus 0.49], for bacteremic pneumonia [0.72 versus 0.00], for PPE [0.89 versus 0.00], and for meningitis [0.62 versus 0.00]). IPDs caused by non-PCV13 serotypes did not increase (IR, 3.60 in the PCV7 period versus 3.31 in the PCV13 period), regardless of age or presentation. No IPDs caused by the PCV13 serotypes were found in children who received 3 doses of PCV13. The number of hospitalization days and sanitary costs were significantly lower in the PCV13 period. The switch from PCV7 to PCV13 in the universal pediatric vaccination calendar provided sanitary and economical benefits without a replacement by non-PCV13 serotypes.
Lipids Derived from Virulent Francisella tularensis Broadly Inhibit Pulmonary Inflammation via Toll-Like Receptor 2 and Peroxisome Proliferator-Activated Receptor α
Authors: Crane Deborah D. , Ireland Robin , Alinger Joshua B. , Small Pamela , Bosio Catharine M. 
Published: August 2013

ABSTRACTFrancisella tularensisis a Gram-negative facultative intracellular pathogen that causes an acute lethal respiratory disease in humans. The heightened virulence of the pathogen is linked to its unique ability to inhibit Toll-like receptor (TLR)-mediated inflammatory responses. The bacterial component and mechanism of this inhibition are unknown. Here we show that lipids isolated from virulent but not attenuated strains ofF. tularensisare not detected by host cells, inhibit production of proinflammatory cytokines by primary macrophages in response to known TLR ligands, and suppress neutrophil recruitmentin vivo. We further show that lipid-mediated inhibition of inflammation is dependent on TLR2, MyD88, and the nuclear hormone and fatty acid receptor peroxisome proliferator-activated receptor α (PPARα). Pathogen lipid-mediated interference with inflammatory responses through the engagement of TLR2 and PPARα represents a novel manipulation of host signaling pathways consistent with the ability of highly virulentF. tularensisto efficiently evade host immune responses.
A Case of Mild Pulmonary Disease Due to Mycobacterium shimoidei with a Favorable Outcome
Authors: Galizzi Nadia , Tortoli Enrico , Gori Andrea , Morini Fulvia , Lapadula Giuseppe 
Published: August 2013

ABSTRACT

We describe a case of mild
Mycobacterium shimoidei
disease with a favorable course after treatment. Characteristics of nine
M. shimoidei
isolates in Italy between 1989 and 2009 were also reviewed. The
M. shimoidei
genome was highly conserved. Based on antimicrobial susceptibility, the combination of ethambutol, clarithromycin, and rifabutin appears to be a reasonable treatment.
Comparison of Perirectal versus Rectal Swabs for Detection of Asymptomatic Carriers of Toxigenic Clostridium difficile
Authors: Rogers David S. , Kundrapu Sirisha , Sunkesula Venkata C. K. , Donskey Curtis J. 
Published: August 2013

ABSTRACT

For long-term care and spinal cord injury patients, the sensitivity, specificity, and positive and negative predictive values of perirectal versus rectal cultures for detection of asymptomatic carriers of
Clostridium difficile
were 95%, 100%, 100%, and 97%, respectively. Perirectal cultures provide an accurate method to detect asymptomatic carriers of
C. difficile
.
Multiple Broad-Spectrum Beta-Lactamase Targets for Comprehensive Surveillance
Authors: Mangold Kathy A. , Voss Barbara L. , Singh Kamaljit , Thomson Richard B. , Schora Donna M. , Peterson Lance R. , Kaul Karen L. 
Published: August 2013

ABSTRACT

Real-time PCR testing for
bla
KPC
,
bla
NDM
,
bla
VIM
,
bla
IMP
, and
bla
CTX-M
was performed on rectal swabs obtained from residents of two long-term acute-care facilities. While
bla
KPC
was detected in 69/102 swabs (67.6%), testing for four other targets increased the positivity rate for a broad-spectrum β-lactamase to 73.5% (McNemar's
P
= 0.03).
Antimicrobial Stewardship Programs
Authors: Leuthner Kimberly D. , Doern Gary V. 
Published: August 2013

ABSTRACT
The development of antimicrobial agents represents one of the most significant achievements in medicine during the past century. However, the emergence of antimicrobial resistance combined with the downturn in the development of new antimicrobial agents in the pharmaceutical industry poses unanticipated challenges in the effective management of infection. The issue of how we can most effectively utilize these invaluable resources, antimicrobials, in the face of infections that are ever more difficult to treat arises. This issue serves as the fundamental basis for the concept of antimicrobial stewardship, the topic of this minireview.
The PA and HA Gene-Mediated High Viral Load and Intense Innate Immune Response in the Brain Contribute to the High Pathogenicity of H5N1 Avian Influenza Virus in Mallard Ducks
Authors: Hu Jiao , Hu Zenglei , Mo Yiqun , Wu Qiwen , Cui Zhu , Duan Zhiqiang , Huang Junqing , Chen Hongzhi , Chen Yuxin , Gu Min , Wang Xiaoquan , Hu Shunlin , Liu Huimou , Liu Wenbo , Liu Xiaowen , Liu Xiufan 
Published: August 2013

ABSTRACT
Most highly pathogenic avian influenza A viruses cause only mild clinical signs in ducks, serving as an important natural reservoir of influenza A viruses. However, we isolated two H5N1 viruses that are genetically similar but differ greatly in virulence in ducks. A/Chicken/Jiangsu/k0402/2010 (CK10) is highly pathogenic, whereas A/Goose/Jiangsu/k0403/2010 (GS10) is low pathogenic. To determine the genetic basis for the high virulence of CK10 in ducks, we generated a series of single-gene reassortants between CK10 and GS10 and tested their virulence in ducks. Expression of the CK10 PA or hemagglutinin (HA) gene in the GS10 context resulted in increased virulence and virus replication. Conversely, inclusion of the GS10 PA or HA gene in the CK10 background attenuated the virulence and virus replication. Moreover, the PA gene had a greater contribution. We further determined that residues 101G and 237E in the PA gene contribute to the high virulence of CK10. Mutations at these two positions produced changes in virulence, virus replication, and polymerase activity of CK10 or GS10. Position 237 plays a greater role in determining these phenotypes. Moreover, the K237E mutation in the GS10 PA gene increased PA nuclear accumulation. Mutant GS10 viruses carrying the CK10 HA gene or the PA101G or PA237E mutation induced an enhanced innate immune response. A sustained innate response was detected in the brain rather than in the lung and spleen. Our results suggest that the PA and HA gene-mediated high virus replication and the intense innate immune response in the brain contribute to the high virulence of H5N1 virus in ducks.
Emergence of a C-Terminal Seven-Amino-Acid Elongation of NS1 in Around 1950 Conferred a Minor Growth Advantage to Former Seasonal Influenza A Viruses
Authors: Lohrmann Florens , Dijkman Ronald , Stertz Silke , Thiel Volker , Haller Otto , Staeheli Peter , Kochs Georg 
Published: August 2013

ABSTRACT
Influenza A viruses circulating in humans from ∼1950 to ∼1987 featured a nonstructural (NS1) protein with a C-terminal extension of seven amino acids. The biological significance of this NS1 elongation remained elusive. We observed that replication kinetics of the wild-type virus A/Hong Kong/01/68 (H3N2) and a mutant encoding a truncated NS1 were indistinguishable in most experimental systems. However, wild-type virus outcompeted the mutant during mixed infections, suggesting that the NS1 extension conferred minor growth advantages.
The Genome-Packaging Signal of the Influenza A Virus Genome Comprises a Genome Incorporation Signal and a Genome-Bundling Signal
Authors: Goto Hideo , Muramoto Yukiko , Noda Takeshi , Kawaoka Yoshihiro 
Published: August 2013

ABSTRACT
The influenza A virus genome comprises eight single-stranded negative-sense RNA segments (vRNAs). All eight vRNAs are selectively packaged into each progeny virion via so-called segment-specific genome-packaging signal sequences that are located in the noncoding and terminal coding regions of both the 3′ and the 5′ ends of the vRNAs. However, it remains unclear how these signals ensure that eight different vRNAs are packaged. Here, by using a reverse genetics system, we demonstrated that, in the absence of the other seven vRNAs, a recombinant NP vRNA bearing only a reporter gene flanked by the noncoding NP regions was incorporated into virus-like particles (VLPs) as efficiently as a recombinant NP vRNA bearing the reporter gene flanked by the complete NP packaging signals (i.e., the noncoding sequences and the terminal coding regions). Viruses that comprised a recombinant NP vRNA whose packaging signal was disrupted, and the remaining seven authentic vRNAs, did not undergo multiple cycles of replication; however, a recombinant NP vRNA with only the noncoding regions was readily incorporated into VLPs, suggesting that the packaging signal as currently defined is not necessarily essential for the packaging of the vRNA in which it resides; rather, it is required for the packaging of the full set of vRNAs. We propose that the 3′ and 5′ noncoding regions of each vRNA bear a virion incorporation signal for that vRNA and that the terminal coding regions serve as a bundling signal that ensures the incorporation of the complete set of eight vRNAs into the virion.
Dual Myxovirus Screen Identifies a Small-Molecule Agonist of the Host Antiviral Response
Authors: Yan Dan , Krumm Stefanie A. , Sun Aiming , Steinhauer David A. , Luo Ming , Moore Martin L. , Plemper Richard K. 
Published: August 2013

ABSTRACT

As we are confronted with an increasing number of emerging and reemerging viral pathogens, the identification of novel pathogen-specific and broad-spectrum antivirals has become a major developmental objective. Targeting of host factors required for virus replication presents a tangible approach toward obtaining novel hits with a broadened indication range. However, the identification of developable host-directed antiviral candidates remains challenging. We describe a novel screening protocol that interrogates the myxovirus host-pathogen interactome for broad-spectrum drug candidates and simultaneously probes for conventional, pathogen-directed hits. With resource efficiency and pan-myxovirus activity as the central developmental parameters, we explored coscreening against two distinct, independently traceable myxoviruses in a single-well setting. Having identified a pair of unrelated pathogenic myxoviruses (influenza A virus and measles virus) with comparable replication kinetics, we observed unimpaired coreplication of both viruses, generated suitable firefly and
Renilla
luciferase reporter constructs, respectively, and validated the protocol for up to a 384-well plate format. Combined with an independent counterscreen using a recombinant respiratory syncytial virus luciferase reporter, implementation of the protocol identified candidates with a broadened antimyxovirus profile, in addition to pathogen-specific hits. Mechanistic characterization revealed a newly discovered broad-spectrum lead that does not block viral entry but stimulates effector pathways of the innate cellular antiviral response. In summary, we provide proof of concept for the efficient discovery of broad-spectrum myxovirus inhibitors in parallel to para- and orthomyxovirus-specific hit candidates in a single screening campaign. The newly identified compound provides a basis for the development of a novel broad-spectrum small-molecule antiviral class.
Sustained Protein Kinase D Activation Mediates Respiratory Syncytial Virus-Induced Airway Barrier Disruption
Authors: Rezaee Fariba , DeSando Samantha A. , Ivanov Andrei I. , Chapman Timothy J. , Knowlden Sara A. , Beck Lisa A. , Georas Steve N. 
Published: August 2013

ABSTRACT
Understanding the regulation of airway epithelial barrier function is a new frontier in asthma and respiratory viral infections. Despite recent progress, little is known about how respiratory syncytial virus (RSV) acts at mucosal sites, and very little is known about its ability to influence airway epithelial barrier function. Here, we studied the effect of RSV infection on the airway epithelial barrier using model epithelia. 16HBE14o- bronchial epithelial cells were grown on Transwell inserts and infected with RSV strain A2. We analyzed (i) epithelial apical junction complex (AJC) function, measuring transepithelial electrical resistance (TEER) and permeability to fluorescein isothiocyanate (FITC)-conjugated dextran, and (ii) AJC structure using immunofluorescent staining. Cells were pretreated or not with protein kinase D (PKD) inhibitors. UV-irradiated RSV served as a negative control. RSV infection led to a significant reduction in TEER and increase in permeability. Additionally it caused disruption of the AJC and remodeling of the apical actin cytoskeleton. Pretreatment with two structurally unrelated PKD inhibitors markedly attenuated RSV-induced effects. RSV induced phosphorylation of the actin binding protein cortactin in a PKD-dependent manner. UV-inactivated RSV had no effect on AJC function or structure. Our results suggest that RSV-induced airway epithelial barrier disruption involves PKD-dependent actin cytoskeletal remodeling, possibly dependent on cortactin activation. Defining the mechanisms by which RSV disrupts epithelial structure and function should enhance our understanding of the association between respiratory viral infections, airway inflammation, and allergen sensitization. Impaired barrier function may open a potential new therapeutic target for RSV-mediated lung diseases.
Lack of B Cell Dysfunction Is Associated with Functional, gp120-Dominant Antibody Responses in Breast Milk of Simian Immunodeficiency Virus-Infected African Green Monkeys
Authors: Amos Joshua D. , Wilks Andrew B. , Fouda Genevieve G. , Smith Shannon D. , Colvin Lisa , Mahlokozera Tatenda , Ho Carrie , Beck Krista , Overman R. Glenn , DeMarco C. Todd , Hodge Terry L. , LaBranche Celia C. , Montefiori David C. , Denny Thomas N. , Liao Hua-Xin , Tomaras Georgia D. , Moody M. Anthony , Permar Sallie R. 
Published: August 2013

ABSTRACT
The design of an effective vaccine to reduce the incidence of mother-to-child transmission (MTCT) of human immunodeficiency virus (HIV) via breastfeeding will require identification of protective immune responses that block postnatal virus acquisition. Natural hosts of simian immunodeficiency virus (SIV) sustain nonpathogenic infection and rarely transmit the virus to their infants despite high milk virus RNA loads. This is in contrast to HIV-infected women and SIV-infected rhesus macaques (RhMs), nonnatural hosts which exhibit higher rates of postnatal virus transmission. In this study, we compared the systemic and mucosal B cell responses of lactating, SIV-infected African green monkeys (AGMs), a natural host species, to that of SIV-infected RhMs and HIV-infected women. AGMs did not demonstrate hypergammaglobulinemia or accumulate circulating memory B cells during chronic SIV infection. Moreover, the milk of SIV-infected AGMs contained higher proportions of naive B cells than RhMs. Interestingly, AGMs exhibited robust milk and plasma Env binding antibody responses that were one to two logs higher than those in RhMs and humans and demonstrated autologous neutralizing responses in milk at 1 year postinfection. Furthermore, the plasma and milk Env gp120-binding antibody responses were equivalent to or predominant over Env gp140-binding antibody responses in AGMs, in contrast to that in RhMs and humans. The strong gp120-specific, functional antibody responses in the milk of SIV-infected AGMs may contribute to the rarity of postnatal transmission observed in natural SIV hosts.