bluuebunny/crossref_metadata_2025_split huggingface dataset:
Wild and domestic bird faeces likely source of psittacosis transmission—A case–control study in Sweden, 2014–2016
Authors: Chereau Fanny , Rehn Moa , Pini Alessandro , Kühlmann‐Berenzon Sharon , Ydring Elsie , Ringberg Håkan , Runehagen Arne , Ockborn Gunilla , Dotevall Leif , Wallensten Anders 
Published: July 2018

AbstractPsittacosis is a zoonotic disease transmitted by birds. In Sweden, where psittacosis is notifiable, an average of eight cases per year were reported between 2002 and 2012. In 2013, an unusual increase in cases in southern Sweden was associated with exposure to wild birds. To further explore specific risk factors connected to wild birds and identify other risk factors for sporadic psittacosis, we conducted a case–control study including all domestically acquired psittacosis cases reported between December 2014 and April 2016 in Sweden. Cases were age‐, sex‐ and geo‐matched to controls randomly selected from a population register. Cases and controls completed a questionnaire investigating detailed exposures to wild and domestic birds. We compared cases to controls, calculating adjusted matched odds ratios (amOR) using conditional logistic regression. Thirty‐one cases were notified: all cases lived in southern Sweden and 26 were ill during winter season. Two risk factors were independently associated with psittacosis infection: cleaning a wild bird feeder (amOR = 18.95; 95% CI: 2.11–170.03) and owning domestic birds (amOR = 5.55, 95% CI: 1.16–26.61). Our results suggest that exposure to bird faeces, for example when cleaning a wild bird feeder, was the main route of transmission. Following this study, the Public Health Agency of Sweden published recommendations on good practices when cleaning surfaces contaminated with bird faeces and recommended use of bird feeders with a design limiting faeces accumulation.
RIG-I Detects Kaposi’s Sarcoma-Associated Herpesvirus Transcripts in a RNA Polymerase III-Independent Manner
Authors: Zhang Yugen , Dittmer Dirk P. , Mieczkowski Piotr A. , Host Kurtis M. , Fusco William G. , Duncan Joseph A. , Damania Blossom 
Published: July 2018

ABSTRACT

Retinoic acid-inducible gene I (RIG-I) is a cytosolic pathogen recognition receptor that initiates the innate immune response against many RNA viruses. We previously showed that RIG-I restricts Kaposi's sarcoma-associated herpesvirus (KSHV) reactivation (J. A. West et al., J Virol 88:5778–5787, 2014,
https://doi.org/10.1128/JVI.03226-13
). In this study, we report that KSHV stimulates the RIG-I signaling pathway in a RNA polymerase (Pol) III-independent manner and subsequently induces type I interferon (IFN) responses. Knockdown or inhibition of RNA Pol III had no effect on beta interferon (IFN-β) induction by KSHV. By using high-throughput sequencing of RNA isolated by cross-linking immunoprecipitation (HITS-CLIP) approach, we identified multiple KSHV regions that give rise to RNA fragments binding to RIG-I, such as ORF8
10420-10496
, Repeat region (LIR1)
119059-119204
, and ORF25
43561-43650
. The sequence dissimilarity between these fragments suggests that RIG-I detects a particular structure rather than a specific sequence motif. Synthesized ORF8
10420-10496
RNA stimulated RIG-I-dependent but RNA Pol III-independent IFN-β signaling. In summary, several KSHV RNAs are sensed by RIG-I in a RNA Pol III-independent manner.

IMPORTANCE
Kaposi’s sarcoma-associated herpesvirus (KSHV) is the causative agent of Kaposi’s sarcoma, primary effusion lymphoma, and multicentric Castleman’s disease. Innate immune responses against viral infections, especially the induction of type I interferon, are critical for limiting the replication of viruses. Retinoic acid-inducible gene I (RIG-I), a cytosolic RNA helicase sensor, plays a significant role in the induction of type I interferon responses following viral infection. Here, we identified multiple RNA regions in KSHV as potential virus ligands that bind to RIG-I and stimulate RIG-I-dependent but RNA Pol III-independent IFN-β signaling. Our results expand the role of RIG-I by providing an example of a DNA virus activating a canonical RNA-sensing pathway.
Type 2 NADH Dehydrogenase Is the Only Point of Entry for Electrons into the Streptococcus agalactiae Respiratory Chain and Is a Potential Drug Target
Authors: Lencina Andrea M. , Franza Thierry , Sullivan Matthew J. , Ulett Glen C. , Ipe Deepak S. , Gaudu Philippe , Gennis Robert B. , Schurig-Briccio Lici A. 
Published: July 2018

ABSTRACT

The opportunistic pathogen
Streptococcus agalactiae
is the major cause of meningitis and sepsis in a newborn’s first week, as well as a considerable cause of pneumonia, urinary tract infections, and sepsis in immunocompromised adults. This pathogen respires aerobically if heme and quinone are available in the environment, and a functional respiratory chain is required for full virulence. Remarkably, it is shown here that the entire respiratory chain of
S. agalactiae
consists of only two enzymes, a type 2 NADH dehydrogenase (NDH-2) and a cytochrome
bd
oxygen reductase. There are no respiratory dehydrogenases other than NDH-2 to feed electrons into the respiratory chain, and there is only one respiratory oxygen reductase to reduce oxygen to water. Although
S. agalactiae
grows well in
vitro
by fermentative metabolism, it is shown here that the absence of NDH-2 results in attenuated virulence, as observed by reduced colonization in heart and kidney in a mouse model of systemic infection. The lack of NDH-2 in mammalian mitochondria and its important role for virulence suggest this enzyme may be a potential drug target. For this reason, in this study,
S. agalactiae
NDH-2 was purified and biochemically characterized, and the isolated enzyme was used to screen for inhibitors from libraries of FDA-approved drugs. Zafirlukast was identified to successfully inhibit both NDH-2 activity and aerobic respiration in intact cells. This compound may be useful as a laboratory tool to inhibit respiration in
S. agalactiae
and, since it has few side effects, it might be considered a lead compound for therapeutics development.

IMPORTANCE
S. agalactiae
is part of the human intestinal microbiota and is present in the vagina of ~30% of healthy women. Although a commensal, it is also the leading cause of septicemia and meningitis in neonates and immunocompromised adults. This organism can aerobically respire, but only using external sources of heme and quinone, required to have a functional electron transport chain. Although bacteria usually have a branched respiratory chain with multiple dehydrogenases and terminal oxygen reductases, here we establish that
S. agalactiae
utilizes only one type 2 NADH dehydrogenase (NDH-2) and one cytochrome
bd
oxygen reductase to perform respiration. NADH-dependent respiration plays a critical role in the pathogen in maintaining NADH/NAD
+
redox balance in the cell, optimizing ATP production, and tolerating oxygen. In summary, we demonstrate the essential role of NDH-2 in respiration and its contribution to
S. agalactiae
virulence and propose it as a potential drug target.
The Escherichia coli Type III Secretion System 2 Has a Global Effect on Cell Surface
Authors: Shulman Alexander , Yair Yael , Biran Dvora , Sura Thomas , Otto Andreas , Gophna Uri , Becher Dörte , Hecker Michael , Ron Eliora Z. 
Published: July 2018

ABSTRACT

Many strains of
Escherichia coli
carry a 29,250-bp ETT2 pathogenicity island (PAI), which includes genes predicted to encode type III secretion system (T3SS) components. Because it is similar to the
Salmonella
pathogenicity island 1 (SPI-1) system, encoding a T3SS in
Salmonella enterica
, it was assumed that ETT2 also encodes a secretion system injecting effectors into host cells. This assumption was checked in
E. coli
serotype O2—associated with urinary tract infections and septicemia—which has an intact ETT2 gene cluster, in contrast to most strains in which this cluster carries deletions and mutations. A proteomic search did not reveal any putative secreted effector. Instead, the majority of the secreted proteins were identified as flagellar proteins. A deletion of the ETT2 gene cluster significantly reduced the secretion of flagellar proteins, resulting in reduced motility. There was also a significant reduction in the transcriptional level of flagellar genes, indicating that ETT2 affects the synthesis, rather than secretion, of flagellar proteins. The ETT2 deletion also resulted in additional major changes in secretion of fimbrial proteins and cell surface proteins, resulting in relative resistance to detergents and hydrophobic antibiotics (novobiocin), secretion of large amounts of outer membrane vesicles (OMVs), and altered multicellular behavior. Most important, the ETT2 deletion mutants were sensitive to serum. These major changes indicate that the ETT2 gene cluster has a global effect on cell surface and physiology, which is especially important for pathogenicity, as it contributes to the ability of the bacteria to survive serum and cause sepsis.

IMPORTANCE
Drug-resistant extraintestinal pathogenic
E. coli
(ExPEC) strains are major pathogens, especially in hospital- and community-acquired infections. They are the major cause of urinary tract infections and are often involved in septicemia with high mortality. ExPEC strains are characterized by broad-spectrum antibiotic resistance, and development of a vaccine is not trivial because the ExPEC strains include a large number of serotypes. It is therefore important to understand the virulence factors that are involved in pathogenicity of ExPEC and identify new targets for development of antibacterial drugs or vaccines. Such a target could be ETT2, a unique type III secretion system present (complete or in parts) in many ExPEC strains. Here, we show that this system has a major effect on the bacterial surface—it affects sensitivity to drugs, motility, and secretion of extracellular proteins and outer membrane vesicles. Most importantly, this system is important for serum resistance, a prerequisite for septicemia.
HtrA of Borrelia burgdorferi Leads to Decreased Swarm Motility and Decreased Production of Pyruvate
Authors: Coleman James L. , Toledo Alvaro , Benach Jorge L. 
Published: July 2018

ABSTRACT

Borrelia burgdorferi
HtrA (HtrABb) is a serine protease that targets damaged or improperly folded proteins. In our previous studies, HtrABb specifically degraded basic membrane protein BmpD, chemotaxis phosphatase CheX, and outer membrane protein P66. In addition, HtrABb degrades virulence factor BB0323 and components of the extracellular matrix fibronectin and aggrecan. A proteomics-based analysis (two-dimensional difference gel electrophoresis [2-D DIGE], liquid chromatography-mass spectrometry [LC-MS]) of an HtrABb-overexpressing strain of
B. burgdorferi
(A3HtrAOE) revealed that protein levels of P66 were reduced in comparison to wild-type
B. burgdorferi
, confirming its status as an HtrABb substrate. Hbb, a P66-DNA-binding transcription factor, was specifically degraded by HtrABb, providing supportive evidence for a role for both in the regulation of P66. A3HtrAOE exhibited reduced motility in swarm assays, a possible link between overabundance of HtrABb and its enzymatic specificity for P66. However, the ΔP66 strain did not have reduced motility in the swarm assays, negating a role for this protein. The proteomics analyses also identified three enzymes of the glycolytic pathway, glyceraldehyde-3-phosphate dehydrogenase (GAPDH), glycerol-3-phosphate dehydrogenase (GPDH), and glycerol kinase (GK), and one enzyme involved in carbohydrate metabolism, diphosphate-fructose-6-phosphate 1-phosphotransferase, which were reduced in A3HtrAOE. Consistent with its reduced protein levels of these glycolytic enzymes, A3HtrAOE was also deficient in production of pyruvate. We propose a model for a role for HtrABb in contributing to a decrease in metabolic activity of
B. burgdorferi
.

IMPORTANCE
Being a vector-borne bacterium,
B. burgdorferi
must remodel its protein content as it transfers from tick to mammal. Proteolysis is a mechanism whereby remodeling can be accomplished. HtrABb degrades a number of proteins whose disappearance may help in preparing this organism for a stage of low metabolic activity.
Energy Conservation via Hydrogen Cycling in the Methanogenic Archaeon Methanosarcina barkeri
Authors: Kulkarni Gargi , Mand Thomas D. , Metcalf William W. 
Published: July 2018

ABSTRACT

Energy conservation via hydrogen cycling, which generates proton motive force by intracellular H
2
production coupled to extracellular consumption, has been controversial since it was first proposed in 1981. It was hypothesized that the methanogenic archaeon
Methanosarcina barkeri
is capable of energy conservation via H
2
cycling, based on genetic data that suggest that H
2
is a preferred, but nonessential, intermediate in the electron transport chain of this organism. Here, we characterize a series of hydrogenase mutants to provide direct evidence of H
2
cycling.
M. barkeri
produces H
2
during growth on methanol, a phenotype that is lost upon mutation of the cytoplasmic hydrogenase encoded by
frhADGB
, although low levels of H
2
, attributable to the Ech hydrogenase, accumulate during stationary phase. In contrast, mutations that conditionally inactivate the extracellular Vht hydrogenase are lethal when expression of the
vhtGACD
operon is repressed. Under these conditions, H
2
accumulates, with concomitant cessation of methane production and subsequent cell lysis, suggesting that the inability to recapture extracellular H
2
is responsible for the lethal phenotype. Consistent with this interpretation, double mutants that lack both Vht and Frh are viable. Thus, when intracellular hydrogen production is abrogated, loss of extracellular H
2
consumption is no longer lethal. The common occurrence of both intracellular and extracellular hydrogenases in anaerobic microorganisms suggests that this unusual mechanism of energy conservation may be widespread in nature.

IMPORTANCE
ATP is required by all living organisms to facilitate essential endergonic reactions required for growth and maintenance. Although synthesis of ATP by substrate-level phosphorylation is widespread and significant, most ATP is made via the enzyme ATP synthase, which is energized by transmembrane chemiosmotic gradients. Therefore, establishing this gradient across the membrane is of central importance to sustaining life. Experimental validation of H
2
cycling adds to a short list of mechanisms for generating a transmembrane electrochemical gradient that is likely to be widespread, especially among anaerobic microorganisms.
The Plasmodesmal Localization Signal of TMV MP Is Recognized by Plant Synaptotagmin SYTA
Authors: Yuan Cheng , Lazarowitz Sondra G. , Citovsky Vitaly 
Published: July 2018

ABSTRACT

Plant viruses cross the barrier of the plant cell wall by moving through intercellular channels, termed plasmodesmata, to invade their hosts. They accomplish this by encoding movement proteins (MPs), which act to alter plasmodesmal gating. How MPs target to plasmodesmata is not well understood. Our recent characterization of the first plasmodesmal localization signal (PLS) identified in a viral MP, namely, the MP encoded by the
Tobamovirus Tobacco mosaic virus
(TMV), now provides the opportunity to identify host proteins that recognize this PLS and may be important for its plasmodesmal targeting. One such candidate protein is
Arabidopsis
synaptotagmin A (SYTA), which is required to form endoplasmic reticulum (ER)-plasma membrane contact sites and regulates the MP-mediated trafficking of begomoviruses, tobamoviruses, and potyviruses. In particular, SYTA interacts with, and regulates the cell-to-cell transport of, both TMV MP and the MP encoded by the
Tobamovirus Turnip vein clearing virus
(TVCV). Using
in planta
bimolecular fluorescence complementation (BiFC) and yeast two-hybrid assays, we show here that the TMV PLS interacted with SYTA. This PLS sequence was both necessary and sufficient for interaction with SYTA, and the plasmodesmal targeting activity of the TMV PLS was substantially reduced in an
Arabidopsis syta
knockdown line. Our findings show that SYTA is one host factor that can recognize the TMV PLS and suggest that this interaction may stabilize the association of TMV MP with plasmodesmata.

IMPORTANCE
Plant viruses use their movement proteins (MPs) to move through host intercellular connections, plasmodesmata. Perhaps one of the most intriguing, yet least studied, aspects of this transport is the MP signal sequences and their host recognition factors. Recently, we have described the plasmodesmal localization signal (PLS) of the
Tobacco mosaic virus
(TMV) MP. Here, we identified the
Arabidopsis
synaptotagmin A (SYTA) as a host factor that recognizes TMV MP PLS and promotes its association with the plasmodesmal membrane. The significance of these findings is two-fold: (i) we identified the TMV MP association with the cell membrane at plasmodesmata as an important PLS-dependent step in plasmodesmal targeting, and (ii) we identified the plant SYTA protein that specifically recognizes PLS as a host factor involved in this step.
Compared performance of Spot and SW800 photoscreeners on Chinese children
Authors: Qian Xuehan , Li Ying , Ding Gang , Li Jing , Lv Hongyu , Hua Ning , Wei Nan , He Li , Wei Lirong , Li Xue , Wang Jiaxing 
Published: July 2018

PurposeTo evaluate the effectiveness of Spot photoscreener and SW800 vision screener in detecting amblyopia risk factors in Chinese children between 4 and 6 years of age.MethodsOne hundred and thirteen children (226 eyes) underwent complete ophthalmologic examination, cycloplegic retinoscopy refraction, prism cover tests and photoscreen using both Spot (v2.1.4) and SW800 (v1.0.1.0) photoscreeners. The agreement of results obtained from photoscreener and retinoscopy was evaluated by paired t-test as well as Pearson correlation test. The sensitivity and specificity of detecting amblyopia risk factors were calculated based on the American Association of Pediatric Ophthalmology and Strabismus 2013 guidelines. The overall effectiveness of detecting amblyopia risk factors by using either photoscreener was analysed by receiver operating characteristic (ROC) curves.ResultsA strong linear agreement was observed between Spot and retinoscopy (p<0.01) in aspects of spherical equivalent (SE, Pearson’s r=0.95), dioptre sphere (DS, r=0.97), dioptre cylinder (DC, r=0.84) and horizontal deviation (Hdev, r=0.91), with overall −0.17 D myopic shift of SE. Significant correlation was also shown between SW800 and retinoscopy (p<0.01) in aspects of SE (r=0.90), DS (r=0.93), DC (r=0.82) and Hdev (r=0.80), with overall −0.12 D myopic shift of SE. The overall sensitivity and specificity in detecting amblyopia risk factors were 94.0% and 80.0% for Spot and 88.8% and 81.1% for SW800.ConclusionThe measurements of Spot and SW800 photoscreener showed a strong agreement with cycloplegic retinoscopy refraction and prism cover tests. The performance of both screeners in detecting individual amblyopia risk factors is satisfactory. ROC analysis indicates that the Spot and SW800 performed very similarly in detecting amblyopia risk factors.
Increased risk of hospital-acquired foot ulcers in people with diabetes: large prospective study and implications for practice
Authors: Wensley Frances , Kerry Christopher , Rayman Gerry 
Published: July 2018

AimsDiabetes increases the risk of costly and potentially preventable hospital-acquired pressure ulceration. Given that peripheral arterial disease and neuropathy, important risk factors for foot ulceration, are more common in people with diabetes, their risk of hospital-acquired foot ulceration (HAFU) in particular may be even greater. This study aims to determine this risk.MethodsUsing data collected over 2 years from all admissions to the Ipswich Hospital NHS Trust, we conducted a prospective multilevel regression analysis of the risk of HAFU in 5043 admissions of people with diabetes versus 23 599 without diabetes. Patients over 50 years who developed HAFU at least 48 hours after admission were included in analyses. Progressive adjustment for important risk factors and subgroup analyses were conducted to compare patients with and without diabetes.ResultsThere were significant differences between patients with and without diabetes among a range of covariates including sex, Comorbidity Score, and length of stay (p value <0.001). After progressive adjustment for age, sex, and other risk factors, there persisted a significant increase risk of HAFU in people with diabetes (OR 2.24; 95% CI 1.80 to 2.69). There were no substantial differences between clinically relevant subgroups.ConclusionsThese analyses demonstrate at least a twofold increase in the risk of HAFU in patients with diabetes and suggest further work should focus on specific processes to detect those inpatients with diabetes at increased risk, in whom preventative measures may reduce the prevalence of this costly complication.
Aging-related increase in store-operated Ca2+ influx in human ventricular fibroblasts
Authors: Mohis Momin , Edwards Stacie , Ryan Sean , Rizvi Farhan , Tajik A. Jamil , Jahangir Arshad , Ross Gracious R. 
Published: July 2018

Senescence-related fibrosis contributes to cardiac dysfunction. Profibrotic processes are Ca2+ dependent. The effect of aging on the Ca2+ mobilization processes of human ventricular fibroblasts (hVFs) is unclear. Therefore, we tested whether aging altered intracellular Ca2+ release and store-operated Ca2+ entry (SOCE). Disease-free hVFs from 2- to 63-yr-old trauma victims were assessed for cytosolic Ca2+ dynamics with fluo 3/confocal imaging. Angiotensin II or thapsigargin was used to release endoplasmic reticulum Ca2+ in Ca2+-free solution; CaCl2 (2 mM) was then added to assess SOCE, which was normalized to ionomycin-induced maximal Ca2+. The angiotensin II experiments were repeated after phosphoenolpyruvate pretreatment to determine the role of energy status. The expression of genes encoding SOCE-related ion channel subunits was assessed by quantitative PCR, and protein expression was assessed by immunoblot analysis. Age groups of <50 and ≥50 yr were compared using unpaired t-test or regression analysis. Ca2+ release by angiotensin II or thapsigargin was not different between the groups, but SOCE was significantly elevated in the ≥50-yr group. Regression analysis showed an age-dependent phosphoenolpyruvate-sensitive increase in SOCE of hVFs. Aging did not alter the mRNA expression of SOCE-related genes. The profibrotic phenotype of hVFs was evident by sprouty1 downregulation with age. Thus, an age-associated increase in angiotensin II- and thapsigargin-induced SOCE occurs in hVFs, independent of receptor mechanisms or alterations of mRNA expression level of SOCE-related ion channel subunits but related to the cellular bioenergetics status. Elucidation of mechanisms underlying enhanced hVF SOCE with aging may refine SOCE targets to limit aging-related progression of Ca2+-dependent cardiac fibrosis. NEW & NOTEWORTHY Human ventricular fibroblasts exhibit an age-related increase in store-operated Ca2+ influx induced by angiotensin II, an endogenous vasoactive hormone, or thapsigargin, an inhibitor of endoplasmic reticulum Ca2+-ATPase, independent of receptor mechanisms or genes encoding store-operated Ca2+ entry-related ion channel subunits. Selective inhibition of this augmented store-operated Ca2+ entry could therapeutically limit aging-related cardiac fibrosis.