bluuebunny/crossref_metadata_2025_split huggingface dataset:
Cyclic di-AMP Released from Staphylococcus aureus Biofilm Induces a Macrophage Type I Interferon Response
Authors: Gries Casey M. , Bruger Eric L. , Moormeier Derek E. , Scherr Tyler D. , Waters Christopher M. , Kielian Tammy 
Published: October 2016

ABSTRACT

Staphylococcus aureus
is a leading cause of community- and nosocomial-acquired infections, with a propensity for biofilm formation.
S. aureus
biofilms actively skew the host immune response toward an anti-inflammatory state; however, the biofilm effector molecules and the mechanism(s) of action responsible for this phenomenon remain to be fully defined. The essential bacterial second messenger cyclic diadenylate monophosphate (c-di-AMP) is an emerging pathogen-associated molecular pattern during intracellular bacterial infections, as c-di-AMP secretion into the infected host cytosol induces a robust type I interferon (IFN) response. Type I IFNs have the potential to exacerbate infectious outcomes by promoting anti-inflammatory effects; however, the type I IFN response to
S. aureus
biofilms is unknown. Additionally, while several intracellular proteins function as c-di-AMP receptors in
S. aureus
, it has yet to be determined if any extracellular role for c-di-AMP exists and its release during biofilm formation has not yet been demonstrated. This study examined the possibility that c-di-AMP released during
S. aureus
biofilm growth polarizes macrophages toward an anti-inflammatory phenotype via type I interferon signaling. DacA, the enzyme responsible for c-di-AMP synthesis in
S. aureus
, was highly expressed during biofilm growth, and 30 to 50% of total c-di-AMP produced from
S. aureus
biofilm was released extracellularly due to autolytic activity.
S. aureus
biofilm c-di-AMP release induced macrophage type I IFN expression via a STING-dependent pathway and promoted
S. aureus
intracellular survival in macrophages. These findings identify c-di-AMP as another mechanism for how
S. aureus
biofilms promote macrophage anti-inflammatory activity, which likely contributes to biofilm persistence.
Interleukin-17A (IL-17A) and IL-17F Are Critical for Antimicrobial Peptide Production and Clearance of Staphylococcus aureus Nasal Colonization
Authors: Archer Nathan K. , Adappa Nithin D. , Palmer James N. , Cohen Noam A. , Harro Jan M. , Lee Steven K. , Miller Lloyd S. , Shirtliff Mark E. 
Published: October 2016

ABSTRACT

Approximately 20% of the population is persistently colonized by
Staphylococcus aureus
in the nares. Th17-like immune responses mediated by the interleukin-17 (IL-17) family of cytokines and neutrophils are becoming recognized as relevant host defense mechanisms for resolution of
S. aureus
mucocutaneous infections. Since antimicrobial peptides are regulated by the IL-17 cytokines, we sought to determine the role of IL-17 cytokines in production of antimicrobial peptides in a murine model of
S. aureus
nasal carriage. We discovered that nasal tissue supernatants have antistaphylococcal activity, and mice deficient in both IL-17A and IL-17F lost the ability to clear
S. aureus
nasal colonization. IL-17A was found to be sufficient for nasal mBD-3 production
ex vivo
and was required for CRAMP, mBD-3, and mBD-14 expression in response to
S. aureus
colonization
in vivo
. These data were confirmed in a clinical study of nasal secretions in which elevated levels of the human forms of these antimicrobial peptides were found in nasal secretions from healthy human subjects when they were colonized with
S. aureus
but not in secretions from noncolonized subjects. Together, these data provide evidence for the importance of IL-17A regulation of antimicrobial peptides and IL-17F in the clearance of
S. aureus
nasal carriage.
Enoyl-Acyl Carrier Protein Reductase I (FabI) Is Essential for the Intracellular Growth of Listeria monocytogenes
Authors: Yao Jiangwei , Ericson Megan E. , Frank Matthew W. , Rock Charles O. 
Published: October 2016

ABSTRACT

Enoyl-acyl carrier protein reductase catalyzes the last step in each elongation cycle of type II bacterial fatty acid synthesis and is a key regulatory protein in bacterial fatty acid synthesis. Genes of the facultative intracellular pathogen
Listeria monocytogenes
encode two functional enoyl-acyl carrier protein isoforms based on their ability to complement the temperature-sensitive growth phenotype of
Escherichia coli
strain JP1111 [
fabI
(Ts)]. The FabI isoform was inactivated by the FabI selective inhibitor AFN-1252, but the FabK isoform was not affected by the drug, as expected. Inhibition of FabI by AFN-1252 decreased endogenous fatty acid synthesis by 80% and lowered the growth rate of
L. monocytogenes
in laboratory medium. Robust exogenous fatty acid incorporation was not detected in
L. monocytogenes
unless the pathway was partially inactivated by AFN-1252 treatment. However, supplementation with exogenous fatty acids did not restore normal growth in the presence of AFN-1252. FabI inactivation prevented the intracellular growth of
L. monocytogenes
, showing that neither FabK nor the incorporation of host cellular fatty acids was sufficient to support the intracellular growth of
L. monocytogenes
. Our results show that FabI is the primary enoyl-acyl carrier protein reductase of type II bacterial fatty acid synthesis and is essential for the intracellular growth of
L. monocytogenes
.
Dynamic Interactions of a Conserved Enterotoxigenic Escherichia coli Adhesin with Intestinal Mucins Govern Epithelium Engagement and Toxin Delivery
Authors: Kumar Pardeep , Kuhlmann F. Matthew , Bhullar Kirandeep , Yang Hyungjun , Vallance Bruce A. , Xia Lijun , Luo Qingwei , Fleckenstein James M. 
Published: October 2016

ABSTRACT

At present, there is no vaccine for enterotoxigenic
Escherichia coli
(ETEC), an important cause of diarrheal illness. Nevertheless, recent microbial pathogenesis studies have identified a number of molecules produced by ETEC that contribute to its virulence and are novel antigenic targets to complement canonical vaccine approaches. EtpA is a secreted two-partner adhesin that is conserved within the ETEC pathovar. EtpA interacts with the tips of ETEC flagella to promote bacterial adhesion, toxin delivery, and intestinal colonization by forming molecular bridges between the bacteria and the epithelial surface. However, the nature of EtpA interactions with the intestinal epithelium remains poorly defined. Here, we demonstrate that EtpA interacts with glycans presented by transmembrane and secreted intestinal mucins at epithelial surfaces to facilitate pathogen-host interactions that culminate in toxin delivery. Moreover, we found that a major effector molecule of ETEC, the heat-labile enterotoxin (LT), may enhance these interactions by stimulating the production of the gel-forming mucin MUC2. Our studies suggest, however, that EtpA participates in complex and dynamic interactions between ETEC and the gastrointestinal mucosae in which host glycoproteins promote bacterial attachment while simultaneously limiting the epithelial engagement required for effective toxin delivery. Collectively, these data provide additional insight into the intricate nature of ETEC interactions with the intestinal epithelium that have potential implications for rational approaches to vaccine design.
The Type III Secretion System Effector SeoC of Salmonella enterica subsp. salamae and S. enterica subsp. arizonae ADP-Ribosylates Src and Inhibits Opsonophagocytosis
Authors: Pollard Dominic J. , Young Joanna C. , Covarelli Valentina , Herrera-León Silvia , Connor Thomas R. , Fookes Maria , Walker Danielle , Echeita Aurora , Thomson Nicholas R. , Berger Cedric N. , Frankel Gad 
Published: October 2016

ABSTRACT

Salmonella
species utilize type III secretion systems (T3SSs) to translocate effectors into the cytosol of mammalian host cells, subverting cell signaling and facilitating the onset of gastroenteritis. In this study, we compared a draft genome assembly of
Salmonella enterica
subsp.
salamae
strain 3588/07 against the genomes of
S. enterica
subsp.
enterica
serovar Typhimurium strain LT2 and
Salmonella bongori
strain 12419.
S. enterica
subsp.
salamae
encodes the
Salmonella
pathogenicity island 1 (SPI-1), SPI-2, and the locus of enterocyte effacement (LEE) T3SSs. Though several key
S
. Typhimurium effector genes are missing (e.g.,
avrA
,
sopB
, and
sseL
),
S. enterica
subsp.
salamae
invades HeLa cells and contains homologues of
S. bongori sboK
and
sboC
, which we named
seoC
. SboC and SeoC are homologues of EspJ from enteropathogenic and enterohemorrhagic
Escherichia coli
(EPEC and EHEC, respectively), which inhibit Src kinase-dependent phagocytosis by ADP-ribosylation. By screening 73 clinical and environmental
Salmonella
isolates, we identified EspJ homologues in
S. bongori
,
S. enterica
subsp.
salamae
, and
Salmonella enterica
subsp.
arizonae
. The β-lactamase TEM-1 reporter system showed that SeoC is translocated by the SPI-1 T3SS. All the
Salmonella
SeoC/SboC homologues ADP-ribosylate Src E310
in vitro
. Ectopic expression of SeoC/SboC inhibited phagocytosis of IgG-opsonized beads into Cos-7 cells stably expressing green fluorescent protein (GFP)-FcγRIIa. Concurrently,
S. enterica
subsp.
salamae
infection of J774.A1 macrophages inhibited phagocytosis of beads, in a
seoC
-dependent manner. These results show that
S. bongori
,
S. enterica
subsp.
salamae
, and
S. enterica
subsp.
arizonae
share features of the infection strategy of extracellular pathogens EPEC and EHEC and shed light on the complexities of the T3SS effector repertoires of
Enterobacteriaceae
.
Protein Malnutrition Impairs Intestinal Epithelial Cell Turnover, a Potential Mechanism of Increased Cryptosporidiosis in a Murine Model
Authors: Liu J. , Bolick D. T. , Kolling G. L. , Fu Z. , Guerrant R. L. 
Published: October 2016

ABSTRACT

Malnutrition and cryptosporidiosis form a vicious cycle and lead to acute and long-term growth impairment in children from developing countries. Insights into mechanisms underlying the vicious cycle will help to design rational therapies to mitigate this infection. We tested the effect of short-term protein malnutrition on
Cryptosporidium parvum
infection in a murine model by examining stool shedding, tissue burden, and histologic change and explored the mechanism underlying the interaction between malnutrition and cryptosporidiosis through immunostaining and immunoblotting. Protein malnutrition increased stool shedding and the number of intestine-associated
C. parvum
organisms, accompanied by significant suppression of
C. parvum
-induced caspase 3 activity and expression of PCNA and Ki67, but activation of the Akt survival pathway in intestinal epithelial cells. We find that even very brief periods of protein malnutrition may enhance (or intensify) cryptosporidiosis by suppressing
C. parvum
-induced cell turnover and caspase-dependent apoptosis of intestinal epithelial cells. This implicates a potential strategy to attenuate
C. parvum
's effects by modulating apoptosis and promoting regeneration in the intestinal epithelium.
Antibodies Targeting Hsa and PadA Prevent Platelet Aggregation and Protect Rats against Experimental Endocarditis Induced by Streptococcus gordonii
Authors: Mancini Stefano , Menzi Carmen , Oechslin Frank , Moreillon Philippe , Entenza José Manuel 
Published: October 2016

ABSTRACT

Streptococcus gordonii
and related species of oral viridans group streptococci (VGS) are common etiological agents of infective endocarditis (IE). We explored vaccination as a strategy to prevent VGS-IE, using a novel antigen-presenting system based on non-genetically modified
Lactococcus lactis
displaying vaccinogens on its surface. Hsa and PadA are surface-located
S. gordonii
proteins implicated in platelet adhesion and aggregation, which are key steps in the pathogenesis of IE. This function makes them ideal targets for vaccination against VGS-IE. In the present study, we report the use of nonliving
L. lactis
displaying at its surface the N-terminal region of Hsa or PadA by means of the cell wall binding domain of
Lactobacillus casei
A2 phage lysine LysA2 (Hsa-LysA2 and PadA-LysA2, respectively) and investigation of their ability to elicit antibodies in rats and to protect them from
S. gordonii
experimental IE. Immunized and control animals with catheter-induced sterile aortic valve vegetations were inoculated with 10
6
CFU of
S. gordonii
. The presence of IE was evaluated 24 h later. Immunization of rats with
L. lactis
Hsa-LysA2,
L. lactis
PadA-LysA2, or both protected 6/11 (55%), 6/11 (55%), and 11/12 (91%) animals, respectively, from
S. gordonii
IE (
P
< 0.05 versus controls). Protection correlated with the induction of high levels of functional antibodies against both Hsa and PadA that delayed or totally inhibited platelet aggregation by
S. gordonii
. These results support the value of
L. lactis
as a system for antigen delivery and of Hsa and PadA as promising candidates for a vaccine against VGS-IE.
Human Papillomavirus
Authors: Burd Eileen M. , Dean Christina L. 
Published: October 2016

ABSTRACT
Individuals with inherited immunodeficiencies, autoimmune disorders, organ or bone marrow transplantation, or infection with human immunodeficiency virus (HIV) are at increased risk of infection with both low-risk and high-risk human papillomavirus (HPV) types. Chronic immunosuppression provides an environment for persistent HPV infection which carries a higher risk of malignant transformation. Screening guidelines have been developed or advocated for processes that have detectable premalignant lesions, such as anal cancer or cervical cancer. For other anatomic locations, such as cutaneous, penile, and oropharyngeal, a biopsy of suspicious lesions is necessary for diagnosis. HPV cannot be cultured from clinical specimens in the laboratory, and diagnosis relies on cytologic, histologic, or molecular methods.
Chronic Hepatitis B, C, and D
Authors: Cobb Bryan R. , Valsamakis Alexandra 
Published: October 2016

ABSTRACTChronic hepatitis B, C, and D virus infections contribute significantly to the morbidity and mortality of immunocompromised individuals. To contextualize discussion of these infections in immunocompromised patients, this paper provides an overview of aspects of infection in normal hosts. It then describes differences in disease, diagnostic testing, and therapeutic management observed in immunocompromised patients.
Importance of Soil Amendments: Survival of Bacterial Pathogens in Manure and Compost Used as Organic Fertilizers
Authors: Sharma Manan , Reynnells Russell 
Published: October 2016

ABSTRACT

Biological soil amendments (BSAs) such as manure and compost are frequently used as organic fertilizers to improve the physical and chemical properties of soils. However, BSAs have been known to be a reservoir for enteric bacterial pathogens such as enterohemorrhagic
Escherichia coli
(EHEC),
Salmonella
spp., and
Listeria
spp. There are numerous mechanisms by which manure may transfer pathogens to growing fruits and vegetables, and several outbreaks of infections have been linked to manure-related contamination of leafy greens. In the United States several commodity-specific guidelines and current and proposed federal rules exist to provide guidance on the application of BSAs as fertilizers to soils, some of which require an interval between the application of manure to soils and the harvest of fruits and vegetables. This review examines the survival, persistence, and regrowth/resuscitation of bacterial pathogens in manure, biosolids, and composts. Moisture, along with climate and the physicochemical properties of soil, manure, or compost, plays a significant role in the ability of pathogens to persist and resuscitate in amended soils. Adaptation of enteric bacterial pathogens to the nonhost environment of soils may also extend their persistence in manure- or compost-amended soils. The presence of antibiotic-resistance genes in soils may also be increased by manure application. Overall, BSAs applied as fertilizers to soils can support the survival and regrowth of pathogens. BSAs should be handled and applied in a manner that reduces the prevalence of pathogens in soils and the likelihood of transfer of food-borne pathogens to fruits and vegetables. This review will focus on two BSAs—raw manure and composted manure (and other feedstocks)—and predominantly on the survival of enteric bacterial pathogens in BSAs as applied to soils as organic fertilizers.
Influence of sintering temperature on structure, microstructure and piezoelectric properties of doped BZT–BCT ceramics
Authors: Dang Anh Tuan , Vo Thanh Tung , Truong Van Chuong , Le Van Hong 
Published: October 2016

This work reports the influence of sintering temperature on structure, microstructure and piezoelectric properties of 0.48 Ba(Zr[Formula: see text]Ti[Formula: see text])O3–0.52 (Ba[Formula: see text]Ca[Formula: see text])TiO3(BZT–BCT) doped with ZnO nanoparticle ceramics manufactured by a conventional solid state reaction method. By increasing sintering temperature, the piezoelectric behaviors were improved and rose up to the best parameters at a sintering temperature of 1450[Formula: see text]C ([Formula: see text] pC/N and [Formula: see text]). The corresponding properties of undoped BZT–BCT ceramics were investigated as a comparison. The received results show that the sintering behavior and piezo-parameters of doped BZT–BCT samples are better than the undoped BZT–BCT samples at each sintering temperature.
Connecting (T)issues: How Research in Fascia Biology Can Impact Integrative Oncology
Authors: Langevin Helene M. , Keely Patricia , Mao Jun , Hodge Lisa M. , Schleip Robert , Deng Gary , Hinz Boris , Swartz Melody A. , de Valois Beverley A. , Zick Suzanna , Findley Thomas 
Published: October 2016

Abstract
Complementary and integrative treatments, such as massage, acupuncture, and yoga, are used by increasing numbers of cancer patients to manage symptoms and improve their quality of life. In addition, such treatments may have other important and currently overlooked benefits by reducing tissue stiffness and improving mobility. Recent advances in cancer biology are underscoring the importance of connective tissue in the local tumor environment. Inflammation and fibrosis are well-recognized contributors to cancer, and connective tissue stiffness is emerging as a driving factor in tumor growth. Physical-based therapies have been shown to reduce connective tissue inflammation and fibrosis and thus may have direct beneficial effects on cancer spreading and metastasis. Meanwhile, there is currently little knowledge on potential risks of applying mechanical forces in the vicinity of tumors. Thus, both basic and clinical research are needed to understand the full impact of integrative oncology on cancer biology as well as whole person health. Cancer Res; 76(21); 6159–62. ©2016 AACR.
Alternative Polyadenylation in Triple-Negative Breast Tumors Allows NRAS and c-JUN to Bypass PUMILIO Posttranscriptional Regulation
Authors: Miles Wayne O. , Lembo Antonio , Volorio Angela , Brachtel Elena , Tian Bin , Sgroi Dennis , Provero Paolo , Dyson Nicholas 
Published: October 2016

Abstract
Alternative polyadenylation (APA) is a process that changes the posttranscriptional regulation and translation potential of mRNAs via addition or deletion of 3′ untranslated region (3′ UTR) sequences. To identify posttranscriptional-regulatory events affected by APA in breast tumors, tumor datasets were analyzed for recurrent APA events. Motif mapping of the changed 3′ UTR regions found that APA-mediated removal of Pumilio regulatory elements (PRE) was unusually common. Breast tumor subtype–specific APA profiling identified triple-negative breast tumors as having the highest levels of APA. To determine the frequency of these events, an independent cohort of triple-negative breast tumors and normal breast tissue was analyzed for APA. APA-mediated shortening of NRAS and c-JUN was seen frequently, and this correlated with changes in the expression of downstream targets. mRNA stability and luciferase assays demonstrated APA-dependent alterations in RNA and protein levels of affected candidate genes. Examination of clinical parameters of these tumors found those with APA of NRAS and c-JUN to be smaller and less proliferative, but more invasive than non-APA tumors. RT-PCR profiling identified elevated levels of polyadenylation factor CSTF3 in tumors with APA. Overexpression of CSTF3 was common in triple-negative breast cancer cell lines, and elevated CSTF3 levels were sufficient to induce APA of NRAS and c-JUN. Our results support the hypothesis that PRE-containing mRNAs are disproportionately affected by APA, primarily due to high sequence similarity in the motifs utilized by polyadenylation machinery and the PUM complex. Cancer Res; 76(24); 7231–41. ©2016 AACR.
Signal-Oriented Pathway Analyses Reveal a Signaling Complex as a Synthetic Lethal Target for p53 Mutations
Authors: Lu Songjian , Cai Chunhui , Yan Gonghong , Zhou Zhuan , Wan Yong , Chen Vicky , Chen Lujia , Cooper Gregory F. , Obeid Lina M. , Hannun Yusuf A. , Lee Adrian V. , Lu Xinghua 
Published: October 2016

Abstract
Defining processes that are synthetic lethal with p53 mutations in cancer cells may reveal possible therapeutic strategies. In this study, we report the development of a signal-oriented computational framework for cancer pathway discovery in this context. We applied our bipartite graph–based functional module discovery algorithm to identify transcriptomic modules abnormally expressed in multiple tumors, such that the genes in a module were likely regulated by a common, perturbed signal. For each transcriptomic module, we applied our weighted k-path merge algorithm to search for a set of somatic genome alterations (SGA) that likely perturbed the signal, that is, the candidate members of the pathway that regulate the transcriptomic module. Computational evaluations indicated that our methods-identified pathways were perturbed by SGA. In particular, our analyses revealed that SGA affecting TP53, PTK2, YWHAZ, and MED1 perturbed a set of signals that promote cell proliferation, anchor-free colony formation, and epithelial–mesenchymal transition (EMT). These proteins formed a signaling complex that mediates these oncogenic processes in a coordinated fashion. Disruption of this signaling complex by knocking down PTK2, YWHAZ, or MED1 attenuated and reversed oncogenic phenotypes caused by mutant p53 in a synthetic lethal manner. This signal-oriented framework for searching pathways and therapeutic targets is applicable to all cancer types, thus potentially impacting precision medicine in cancer. Cancer Res; 76(23); 6785–94. ©2016 AACR.
Evaluation of Power Quality Issues in grid Connected PV Systems
Authors: Varshney Gunjan , Chauhan D S , Dave M P 
Published: October 2016

<p>This paper deals with the evaluation of power quality issues in grid connected PV systems. This paper also presents complete simulation, modeling and control of three phase grid connected solar PV module with Maximum Power Point Tracking. Perturb and Observe (P&amp;O) method has been used for Maximum Power Point Tracking. In the proposed model DC bus voltage control , harmonic mitigation and power factor control are discussed as power quality issues. The simulation results are shown in the graphical waveforms and simulation is performed in MATLAB using SIMULINK environment and PSB toolboxes. <strong> </strong></p>