bluuebunny/crossref_metadata_2025_split huggingface dataset:
Methane-Fueled Syntrophy through Extracellular Electron Transfer: Uncovering the Genomic Traits Conserved within Diverse Bacterial Partners of Anaerobic Methanotrophic Archaea
Authors: Skennerton Connor T. , Chourey Karuna , Iyer Ramsunder , Hettich Robert L. , Tyson Gene W. , Orphan Victoria J. 
Published: August 2017

ABSTRACT

The anaerobic oxidation of methane by anaerobic methanotrophic (ANME) archaea in syntrophic partnership with deltaproteobacterial sulfate-reducing bacteria (SRB) is the primary mechanism for methane removal in ocean sediments. The mechanism of their syntrophy has been the subject of much research as traditional intermediate compounds, such as hydrogen and formate, failed to decouple the partners. Recent findings have indicated the potential for extracellular electron transfer from ANME archaea to SRB, though it is unclear how extracellular electrons are integrated into the metabolism of the SRB partner. We used metagenomics to reconstruct eight genomes from the globally distributed SEEP-SRB1 clade of ANME partner bacteria to determine what genomic features are required for syntrophy. The SEEP-SRB1 genomes contain large multiheme cytochromes that were not found in previously described free-living SRB and also lack periplasmic hydrogenases that may prevent an independent lifestyle without an extracellular source of electrons from ANME archaea. Metaproteomics revealed the expression of these cytochromes at
in situ
methane seep sediments from three sites along the Pacific coast of the United States. Phylogenetic analysis showed that these cytochromes appear to have been horizontally transferred from metal-respiring members of the
Deltaproteobacteria
such as
Geobacter
and may allow these syntrophic SRB to accept extracellular electrons in place of other chemical/organic electron donors.

IMPORTANCE
Some archaea, known as anaerobic methanotrophs, are capable of converting methane into carbon dioxide when they are growing syntopically with sulfate-reducing bacteria. This partnership is the primary mechanism for methane removal in ocean sediments; however, there is still much to learn about how this syntrophy works. Previous studies have failed to identify the metabolic intermediate, such as hydrogen or formate, that is passed between partners. However, recent analysis of methanotrophic archaea has suggested that the syntrophy is formed through direct electron transfer. In this research, we analyzed the genomes of multiple partner bacteria and showed that they also contain the genes necessary to perform extracellular electron transfer, which are absent in related bacteria that do not form syntrophic partnerships with anaerobic methanotrophs. This genomic evidence shows a possible mechanism for direct electron transfer from methanotrophic archaea into the metabolism of the partner bacteria.
Key Role of the Scavenger Receptor MARCO in Mediating Adenovirus Infection and Subsequent Innate Responses of Macrophages
Authors: Maler Mareike D. , Nielsen Peter J. , Stichling Nicole , Cohen Idan , Ruzsics Zsolt , Wood Connor , Engelhard Peggy , Suomalainen Maarit , Gyory Ildiko , Huber Michael , Müller-Quernheim Joachim , Schamel Wolfgang W. A. , Gordon Siamon , Jakob Thilo , Martin Stefan F. , Jahnen-Dechent Willi , Greber Urs F. , Freudenberg Marina A. , Fejer György 
Published: August 2017

ABSTRACTThe scavenger receptor MARCO is expressed in several subsets of naive tissue-resident macrophages and has been shown to participate in the recognition of various bacterial pathogens. However, the role of MARCO in antiviral defense is largely unexplored. Here, we investigated whether MARCO might be involved in the innate sensing of infection with adenovirus and recombinant adenoviral vectors by macrophages, which elicit vigorous immune responsesin vivo. Using cells derived from mice, we show that adenovirus infection is significantly more efficient in MARCO-positive alveolar macrophages (AMs) and in AM-like primary macrophage lines (Max Planck Institute cells) than in MARCO-negative bone marrow-derived macrophages. Using antibodies blocking ligand binding to MARCO, as well as gene-deficient and MARCO-transfected cells, we show that MARCO mediates the rapid adenovirus transduction of macrophages. By enhancing adenovirus infection, MARCO contributes to efficient innate virus recognition through the cytoplasmic DNA sensor cGAS. This leads to strong proinflammatory responses, including the production of interleukin-6 (IL-6), alpha/beta interferon, and mature IL-1α. These findings contribute to the understanding of viral pathogenesis in macrophages and may open new possibilities for the development of tools to influence the outcome of infection with adenovirus or adenovirus vectors.IMPORTANCEMacrophages play crucial roles in inflammation and defense against infection. Several macrophage subtypes have been identified with differing abilities to respond to infection with both natural adenoviruses and recombinant adenoviral vectors. Adenoviruses are important respiratory pathogens that elicit vigorous innate responsesin vitroandin vivo. The cell surface receptors mediating macrophage type-specific adenovirus sensing are largely unknown. The scavenger receptor MARCO is expressed on some subsets of naive tissue-resident macrophages, including lung alveolar macrophages. Its role in antiviral macrophage responses is largely unexplored. Here, we studied whether the differential expression of MARCO might contribute to the various susceptibilities of macrophage subtypes to adenovirus. We demonstrate that MARCO significantly enhances adenovirus infection and innate responses in macrophages. These results help to understand adenoviral pathogenesis and may open new possibilities to influence the outcome of infection with adenoviruses or adenovirus vectors.
Genomic Dissection of an Icelandic Epidemic of Respiratory Disease in Horses and Associated Zoonotic Cases
Authors: Björnsdóttir Sigríður , Harris Simon R. , Svansson Vilhjálmur , Gunnarsson Eggert , Sigurðardóttir Ólöf G. , Gammeljord Kristina , Steward Karen F. , Newton J. Richard , Robinson Carl , Charbonneau Amelia R. L. , Parkhill Julian , Holden Matthew T. G. , Waller Andrew S. 
Published: August 2017

ABSTRACT

Iceland is free of the major infectious diseases of horses. However, in 2010 an epidemic of respiratory disease of unknown cause spread through the country’s native horse population of 77,000. Microbiological investigations ruled out known viral agents but identified the opportunistic pathogen
Streptococcus equi
subsp.
zooepidemicus
(
S. zooepidemicus
) in diseased animals. We sequenced the genomes of 257 isolates of
S. zooepidemicus
to differentiate epidemic from endemic strains. We found that although multiple endemic clones of
S. zooepidemicus
were present, one particular clone, sequence type 209 (ST209), was likely to have been responsible for the epidemic. Concurrent with the epidemic, ST209 was also recovered from a human case of septicemia, highlighting the pathogenic potential of this strain. Epidemiological investigation revealed that the incursion of this strain into one training yard during February 2010 provided a nidus for the infection of multiple horses that then transmitted the strain to farms throughout Iceland. This study represents the first time that whole-genome sequencing has been used to investigate an epidemic on a national scale to identify the likely causative agent and the link to an associated zoonotic infection. Our data highlight the importance of national biosecurity to protect vulnerable populations of animals and also demonstrate the potential impact of
S. zooepidemicus
transmission to other animals, including humans.

IMPORTANCE
An epidemic of respiratory disease affected almost the entire native Icelandic horse population of 77,000 animals in 2010, resulting in a self-imposed ban on the export of horses and significant economic costs to associated industries. Although the speed of transmission suggested that a viral pathogen was responsible, only the presence of the opportunistic pathogen
Streptococcus zooepidemicus
was consistent with the observed clinical signs. We applied genomic sequencing to differentiate epidemic from endemic strains and to shed light on the rapid transmission of the epidemic strain throughout Iceland. We further highlight the ability of epidemic and endemic strains of
S. zooepidemicus
to infect other animals, including humans. This study represents the first time that whole-genome sequencing has been used to elucidate an outbreak on a national scale and identify the likely causative agent.
Signal Peptide Hydrophobicity Modulates Interaction with the Twin-Arginine Translocase
Authors: Huang Qi , Palmer Tracy 
Published: August 2017

ABSTRACT

The general secretory pathway (Sec) and twin-arginine translocase (Tat) operate in parallel to export proteins across the cytoplasmic membrane of prokaryotes and the thylakoid membrane of plant chloroplasts. Substrates are targeted to their respective machineries by N-terminal signal peptides that share a tripartite organization; however, Tat signal peptides harbor a conserved and almost invariant arginine pair that is critical for efficient targeting to the Tat machinery. Tat signal peptides interact with a membrane-bound receptor complex comprised of TatB and TatC components, with TatC containing the twin-arginine recognition site. Here, we isolated suppressors in the signal peptide of the Tat substrate, SufI, that restored Tat transport in the presence of inactivating substitutions in the TatC twin-arginine binding site. These suppressors increased signal peptide hydrophobicity, and copurification experiments indicated that they restored binding to the variant TatBC complex. The hydrophobic suppressors could also act in
cis
to suppress substitutions at the signal peptide twin-arginine motif that normally prevent targeting to the Tat pathway. Highly hydrophobic variants of the SufI signal peptide containing four leucine substitutions retained the ability to interact with the Tat system. The hydrophobic signal peptides of two Sec substrates, DsbA and OmpA, containing twin lysine residues, were shown to mediate export by the Tat pathway and to copurify with TatBC. These findings indicate that there is unprecedented overlap between Sec and Tat signal peptides and that neither the signal peptide twin-arginine motif nor the TatC twin-arginine recognition site is an essential mechanistic feature for operation of the Tat pathway.

IMPORTANCE
Protein export is an essential process in all prokaryotes. The Sec and Tat export pathways operate in parallel, with the Sec machinery transporting unstructured precursors and the Tat pathway transporting folded proteins. Proteins are targeted to the Tat pathway by N-terminal signal peptides that contain an almost invariant twin-arginine motif. Here, we make the surprising discovery that the twin arginines are not essential for recognition of substrates by the Tat machinery and that this requirement can be bypassed by increasing the signal peptide hydrophobicity. We further show that signal peptides of bona fide Sec substrates can also mediate transport by the Tat pathway. Our findings suggest that key features of the Tat targeting mechanism have evolved to prevent mistargeting of substrates to the Sec pathway rather than being a critical requirement for function of the Tat pathway.
Role of Fatty Acid Kinase in Cellular Lipid Homeostasis and SaeRS-Dependent Virulence Factor Expression in
Staphylococcus aureus
Authors: Ericson Megan E. , Subramanian Chitra , Frank Matthew W. , Rock Charles O. 
Published: August 2017

ABSTRACT

The SaeRS two-component system is a master activator of virulence factor transcription in
Staphylococcus aureus
, but the cellular factors that control its activity are unknown. Fatty acid (FA) kinase is a two-component enzyme system required for extracellular FA uptake and SaeRS activity. Here, we demonstrate the existence of an intracellular nonesterified FA pool in
S. aureus
that is elevated in strains lacking FA kinase activity. SaeRS-mediated transcription is restored in FA kinase-negative strains when the intracellular FA pool is reduced either by growth with FA-depleted bovine serum albumin to extract the FA into the medium or by the heterologous expression of
Neisseria gonorrhoeae
acyl-acyl carrier protein synthetase to activate FA for phospholipid synthesis. These data show that FAs act as negative regulators of SaeRS signaling, and FA kinase activates SaeRS-dependent virulence factor production by lowering inhibitory FA levels. Thus, FA kinase plays a role in cellular lipid homeostasis by activating FA for incorporation into phospholipid, and it indirectly regulates SaeRS signaling by maintaining a low intracellular FA pool.

IMPORTANCE
The SaeRS two-component system is a master transcriptional activator of virulence factor production in response to the host environment in
S. aureus
, and strains lacking FA kinase have severely attenuated SaeRS-dependent virulence factor transcription. FA kinase is required for the activation of exogenous FAs, and it plays a role in cellular lipid homeostasis by recycling cellular FAs into the phospholipid biosynthetic pathway. Activation of the sensor kinase, SaeS, is mediated by its membrane anchor domain, and the FAs which accumulate in FA kinase knockout strains are potent inhibitors of SaeS-dependent signaling. This work identifies FAs as physiological effectors for the SaeRS system and reveals a connection between cellular lipid homeostasis and the regulation of virulence factor transcription. FA kinase is widely distributed in Gram-positive bacteria, suggesting similar roles for FA kinase in these organisms.
Percutaneous valve in valve in the tricuspid position in a patient with Tetralogy of Fallot
Authors: Challa Abhinay , Markham Ryan , Walters Darren 
Published: August 2017

Here, we describe a case of a successful percutaneous insertion of a transcatheter 29 mm Edwards Sapien XT valve into a tricuspid valve in a patient with repaired tetralogy of fallot.Similar procedures have been performed with the Edwards Sapien valve and Melody valves; however, this is the first case described in the literature of an Edwards Sapien valve used in a patient with Tetralogy of Fallot.With procedural safety being demonstrated, this case illustrates an important alternative treatment option for patients with congenital heart disease. Although long-term data is required to compare its efficacy with surgically replaced valves, percutaneous procedures can serve as a delay to surgical valve replacement which over a patients’ lifetime with congenital heart disease, can minimise the amount of invasive surgeries and potential complications.
Comparing optical coherence tomography findings in different aetiologies of infectious necrotising retinitis
Authors: Invernizzi Alessandro , Agarwal Aniruddha Kishandutt , Ravera Vittoria , Mapelli Chiara , Riva Agostino , Staurenghi Giovanni , McCluskey Peter J , Viola Francesco 
Published: August 2017

AimsTo compare optical coherence tomography (OCT) features of active necrotising infectious retinitis (NIR) due to toxoplasmosis or herpesviruses and to determine distinctive OCT signs for these two causes of infectious retinitis.MethodsOCT scans from eyes with active NIR due to varicella zoster virus (VZV), herpes simplex virus (HSV), cytomegalovirus (CMV), and toxoplasmosis (TOXO) were reviewed. All images were evaluated for the presence of previously described OCT findings in TOXO-NIR and compared with the viral group. New OCT findings were recorded and compared. Retinal and choroidal thickness were measured at the site of NIR and compared.Results10 eyes diagnosed with TOXO-NIR and 13 eyes affected by viral-NIR (9 CMV and 4 VZV) were analysed. All eyes showed full thickness hyper-reflectivity, disruption of the retina and a variable degree of vitritis. Among previously described OCT signs, hyper-reflective oval deposits and hypo-reflectivity of the choroid had a higher prevalence in TOXO (p=0.018 and p<0.0001, respectively). Among the new signs, hyper-reflective round deposits along the posterior hyaloid, retrohyaloid hyper-reflective spots and a disruption of the choroidal architecture were more frequent in TOXO eyes (all p<0.01). Intra-retinal oedema and hyper-reflective vertical strips within the outer nuclear layer were suggestive of a viral aetiology (p=0.045). Retinal thickness at the site of NIR did not differ between the two groups. Choroidal thickness was significantly higher in TOXO eyes (p=0.01).ConclusionsThe diagnosis of NIR is largely based on clinical and laboratory findings. OCT changes may be useful in differentiating different causes of NIR.
Changes in multiple cytokine concentrations in the aqueous humour of neovascular age-related macular degeneration after 2 months of ranibizumab therapy
Authors: Sakamoto Shinichi , Takahashi Hidenori , Tan Xue , Inoue Yuji , Nomura Yoko , Arai Yusuke , Fujino Yujiro , Kawashima Hidetoshi , Yanagi Yasuo 
Published: August 2017

PurposeTo determine changes in multiple cytokine concentrations in the anterior chamber during the induction phase of ranibizumab treatment in patients with neovascular age-related macular degeneration (AMD).MethodsThis prospective study included 48 treatment-naïve neovascular AMD eyes of 48 patients who received three consecutive monthly injections of ranibizumab at the Japan Community Health Care Organization Tokyo Shinjuku Medical Center between November 2010 and August 2012. We collected ~0.2 mL aqueous humour before the first and third (2 months later) injections. Controls were 80 eyes with cataracts without retinal disease. The cytokines C-X-C motif chemokine ligand 1 (CXCL1), interferon-γ-induced protein 10 (IP-10), C-X-C motif chemokine ligand 12 (CXCL12), C-X-C motif chemokine ligand 13 (CXCL13), monocyte chemoattractant protein 1 (MCP-1), CCL11, C-C motif chemokine ligand 11 (CCL11), interleukin-6 (IL-6), interleukin-10 (IL-10) and matrix metalloproteinase 9 (MMP-9) were analysed using multiplex cytokine assays.ResultsMean ages of the patients with AMD and controls were 73 and 75 years, respectively, and 31 (65%) and 37 (46%) subjects were men, respectively. Polypoidal choroidal vasculopathy was found in 27 eyes (56%). Mean concentrations of cytokines in aqueous humour in patients with neovascular AMD before the first and third ranibizumab injections were as follows (in pg/mL): CXCL1, 8.4 and 3.3; IP-10, 110 and 55; CXCL12, 480 and 240; CXCL13, 9.2 and 2.6; MCP-1, 620 and 220; CCL11, 7.1 and 2.8; IL-6, 5.9 and 1.6; IL-10, 0.15 and 0.015 (all p<0.0001), and MMP-9, 0.92 and 1.5 (p=0.0216), respectively. Concentrations of all cytokines decreased significantly after two consecutive ranibizumab injections, except for MMP-9, which increased significantly.ConclusionsAfter two monthly consecutive antivascular endothelial growth factor injections, inflammatory cytokine levels in the aqueous humour of the eyes with AMD were strongly suppressed, while MMP-9 levels increased.
The association between ocular surface measurements with visual field reliability indices and gaze tracking results in preperimetric glaucoma
Authors: Arai Takahiro , Murata Hiroshi , Matsuura Masato , Usui Tomohiko , Asaoka Ryo 
Published: August 2017

Background/aimsTo investigate the relationship between gaze tracking (GT) results and ocular surface condition in glaucoma.MethodThe Humphrey 24–2 visual field (VF) was measured in 34 eyes of 30 patients with open-angle glaucoma without VF damage. Tear break-up time, Schirmer’s test, tear meniscus volume (TMV) and presence of superficial punctate keratopathy (SPK) were also measured in order to describe the condition of the ocular surface. Various GT parameters were calculated: the average frequency of eye movements per stimulus between 1° and 2° (move1-2), the average frequency of eye movements per stimulus between 3° and 5° (move3-5), the average frequency of eye movements per stimulus more than 6° (move≥6), the average tracking failure frequency per stimulus (TFF) and the average blinking frequency. The relationship between GT parameters, reliability indices and ocular surface measurements was investigated using linear mixed modelling.ResultsSPK was positively associated with high rates of move3-5 (coefficient=0.12 for SPK+, p=0.003) and move≥6 (coefficient=0.052 for SPK+, p=0.023). High TMV was significantly related to TFF (coefficient=0.37, p=0.023). Fixation losses, false-positives and false-negatives were not significantly associated with any GT parameters or ocular surface measurements.ConclusionSPK is associated with increased frequency of eye movements (move3-5 and move≥6). In addition, large TMV is associated with increased rate of TFF. Careful attention should be paid when interpreting GT parameters in patients with SPK or a large TMV.
Reliability of Cyclotorsion measurements using Scanning Laser Ophthalmoscopy imaging in healthy subjects: the CySLO study
Authors: Lengwiler Fabian , Rappoport Daniel , Jaggi Gregor P , Landau Klara , Traber Ghislaine L 
Published: August 2017

Background/aimsTo evaluate inter-rater and intra-rater reliability of objective cyclotorsion measurements obtained in healthy subjects using the Heidelberg Spectralis spectral domain—optical coherence tomography (SD-OCT) device.MethodsIn this prospective methodological study, 32 healthy subjects (14 men, 18 women; aged 21–64 years) were enrolled, 31 right eyes were examined and their foveo-papillary angles (FPAs) were measured. The retinal nerve fibre layer (RNFL) programme by Heidelberg Spectralis (Heidelberg Engineering, Heidelberg, Germany) was used to measure cyclotorsion based on the in-built algorithm for the measurement of the FPA on the scanning laser ophthalmoscopy (SLO) image. Repeated scans of the fixating and non-fixating right eye without and with eye tracker each were obtained by three different examiners.ResultsThe mean FPA measured overall by all three examiners was 6.6°±2.8°. The inter-rater reliability of the measured FPAs using the linear mixed effects model is estimated as rhointer=0.8803. The intra-rater reliability is estimated as rhointra=0.9589.ConclusionsRepeatability of objective cyclotorsion measurements within and between observers using the Heidelberg Spectralis OCT is very high. SD-OCT/SLO imaging is a reliable imaging technique to measure and study cyclotorsion.Clinical trial numberNCT02631369, Results.