bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Specialized Peptidoglycan Synthase Promotes
Salmonella
Cell Division inside Host Cells
Authors: Castanheira Sónia , Cestero Juan J. , Rico-Pérez Gadea , García Pablo , Cava Felipe , Ayala Juan A. , Pucciarelli M. Graciela , García-del Portillo Francisco 
Published: January 2018

ABSTRACT

Bacterial cell division has been studied extensively under laboratory conditions. Despite being a key event in the bacterial cell cycle, cell division has not been explored
in vivo
in bacterial pathogens interacting with their hosts. We discovered in
Salmonella enterica
serovar Typhimurium a gene absent in nonpathogenic bacteria and encoding a peptidoglycan synthase with 63% identity to penicillin-binding protein 3 (PBP3). PBP3 is an essential cell division-specific peptidoglycan synthase that builds the septum required to separate daughter cells. Since
S
. Typhimurium carries genes that encode a PBP3 paralog—which we named PBP3
SAL
—and PBP3, we hypothesized that there are different cell division events in host and nonhost environments. To test this, we generated
S
. Typhimurium isogenic mutants lacking PBP3
SAL
or the hitherto considered essential PBP3. While PBP3 alone promotes cell division under all conditions tested, the mutant producing only PBP3
SAL
proliferates under acidic conditions (pH ≤ 5.8) but does not divide at neutral pH. PBP3
SAL
production is tightly regulated with increased levels as bacteria grow in media acidified up to pH 4.0 and in intracellular bacteria infecting eukaryotic cells. PBP3
SAL
activity is also strictly dependent on acidic pH, as shown by beta-lactam antibiotic binding assays. Live-cell imaging microscopy revealed that PBP3
SAL
alone is sufficient for
S
. Typhimurium to divide within phagosomes of the eukaryotic cell. Additionally, we detected much larger amounts of PBP3
SAL
than those of PBP3
in vivo
in bacteria colonizing mouse target organs. Therefore, PBP3
SAL
evolved in
S
. Typhimurium as a specialized peptidoglycan synthase promoting cell division in the acidic intraphagosomal environment.

IMPORTANCE
During bacterial cell division, daughter cells separate by a transversal structure known as the division septum. The septum is a continuum of the cell wall and therefore is composed of membrane(s) and a peptidoglycan layer. To date, actively growing bacteria were reported to have only a “cell division-specific” peptidoglycan synthase required for the last steps of septum formation and consequently, essential for bacterial life. Here, we discovered that
Salmonella enterica
has two peptidoglycan synthases capable of synthesizing the division septum. One of these enzymes, PBP3
SAL
, is present only in bacterial pathogens and evolved in
Salmonella
to function exclusively in acidic environments. PBP3
SAL
is used preferentially by
Salmonella
to promote cell division
in vivo
in mouse target organs and inside acidified phagosomes. Our data challenge the concept of only one essential cell division-specific peptidoglycan synthase and demonstrate that pathogens can divide in defined host locations using alternative mechanisms.
Homoacetogenesis in Deep-Sea
Chloroflexi
, as Inferred by Single-Cell Genomics, Provides a Link to Reductive Dehalogenation in Terrestrial
Dehalococcoidetes
Authors: Sewell Holly L. , Kaster Anne-Kristin , Spormann Alfred M. 
Published: January 2018

ABSTRACT

The deep marine subsurface is one of the largest unexplored biospheres on Earth and is widely inhabited by members of the phylum
Chloroflexi
. In this report, we investigated genomes of single cells obtained from deep-sea sediments of the Peruvian Margin, which are enriched in such
Chloroflexi
. 16S rRNA gene sequence analysis placed two of these single-cell-derived genomes (DscP3 and Dsc4) in a clade of subphylum I
Chloroflexi
which were previously recovered from deep-sea sediment in the Okinawa Trough and a third (DscP2-2) as a member of the previously reported DscP2 population from Peruvian Margin site 1230. The presence of genes encoding enzymes of a complete Wood-Ljungdahl pathway, glycolysis/gluconeogenesis, a
Rhodobacter
nitrogen fixation (Rnf) complex, glyosyltransferases, and formate dehydrogenases in the single-cell genomes of DscP3 and Dsc4 and the presence of an NADH-dependent reduced ferredoxin:NADP oxidoreductase (Nfn) and Rnf in the genome of DscP2-2 imply a homoacetogenic lifestyle of these abundant marine
Chloroflexi
. We also report here the first complete pathway for anaerobic benzoate oxidation to acetyl coenzyme A (CoA) in the phylum
Chloroflexi
(DscP3 and Dsc4), including a class I benzoyl-CoA reductase. Of remarkable evolutionary significance, we discovered a gene encoding a formate dehydrogenase (FdnI) with reciprocal closest identity to the formate dehydrogenase-like protein (complex iron-sulfur molybdoenzyme [CISM], DET0187) of terrestrial
Dehalococcoides/Dehalogenimonas
spp. This formate dehydrogenase-like protein has been shown to lack formate dehydrogenase activity in
Dehalococcoides/Dehalogenimonas
spp. and is instead hypothesized to couple HupL hydrogenase to a reductive dehalogenase in the catabolic reductive dehalogenation pathway. This finding of a close functional homologue provides an important missing link for understanding the origin and the metabolic core of terrestrial
Dehalococcoides/Dehalogenimonas
spp. and of reductive dehalogenation, as well as the biology of abundant deep-sea
Chloroflexi
.

IMPORTANCE
The deep marine subsurface is one of the largest unexplored biospheres on Earth and is widely inhabited by members of the phylum
Chloroflexi
. In this report, we investigated genomes of single cells obtained from deep-sea sediments and provide evidence for a homacetogenic lifestyle of these abundant marine
Chloroflexi
. Moreover, genome signature and key metabolic genes indicate an evolutionary relationship between these deep-sea sediment microbes and terrestrial, reductively dehalogenating
Dehalococcoides
.
Corneal endothelial alterations in alcohol dependence syndrome
Authors: Sati Alok , Moulick Parthasarathi , Shankar Sandeep , Chatterjee Kaushik , Dwivedi Arun Kumar , Vazirani Jayesh 
Published: January 2018

Background/aimsTo evaluate the corneal endothelial changes in patients with alcohol dependence syndrome (ADS).MethodsA total of 322 corneas of 322 subjects were studied, and two groups were formed. The first, the ADS group, included 161 corneas of 161 patients and the second, the age-matched control group, was composed of 161 corneas of 161 healthy subjects. Both the groups were examined by specular microscope and the endothelial parameters were compared. The endothelial parameters were also compared before and after the abstinence of alcohol in the former group. The ADS group was further analysed to assess the influence of life time alcohol consumption, years/pattern of drinking, levels of Liver enzymes, levels of mean corpuscular volume, screening questionnaires and stages of fatty liver on corneal endothelium.ResultsOn comparing the two groups using Mann-Whitney U test, a significant difference was found in central corneal thickness (CCT) and endothelial cell density (CD) between the ADS (CCT: 529±29 µm, CD: 2571±236 cells/mm2) and control groups (CCT: 510±32 µm, CD: 2752±291 cells/mm2) (P<0.001 (CCT); P<0.001 (CD)). Using Wilcoxon sign-rank test, a significant difference was found in CCT (P<0.001) and CD (P<0.001) with abstinence of alcohol. Kruskal-Wallis test was used to compare the endothelial parameters in four stages of fatty liver and found a significant difference in terms of CCT (P<0.001) and CD (P<0.001).ConclusionsCorneal endothelial alteration is present in patients with ADS, more marked in patients with an increase in stage of fatty liver.
Beyond prognostication: ambulance personnel’s lived experiences of cardiac arrest decision-making
Authors: Anderson Natalie Elizabeth , Gott Merryn , Slark Julia 
Published: January 2018

IntroductionThe purpose of this study was to explore ambulance personnel’s decisions to commence, continue, withhold or terminate resuscitation efforts for patients with out-of-hospital cardiac arrest.MethodSemistructured interviews with a purposive sample of 16 demographically diverse ambulance personnel, currently employed in a variety of emergency ambulance response roles, around New Zealand.ResultsParticipants sought and integrated numerous factors, beyond established prognostic indicators, when making resuscitation decisions. Factors appeared to be integrated in four distinct phases, described under four main identified themes: prearrival impressions, immediate on-scene impressions, piecing together the big picture and transition to termination of resuscitation. Commencing or continuing resuscitation was sometimes a default action, particularly where ambulance personnel felt the context was uncertain, unfamiliar or overwhelming. Managing the impact of termination of resuscitation and resulting scene of a death required significant confidence, psychosocial skills and experience.ConclusionThis unique, exploratory study provides new insights into ambulance personnel’s experiences of prehospital resuscitation decision-making. Prognostication in out-of-hospital cardiac arrest is known to be challenging, but results from this study suggest that confidence in a poor prognosis for the cardiac arrested patient is only part of the resuscitation decision-making picture. Results suggest ambulance personnel may benefit from greater educational preparation and mentoring in managing the scene of a death to avoid inappropriate or prolonged resuscitation efforts.
Possible relationship between antiphospholipid antibodies and embolic events in infective endocarditis
Authors: Selton-Suty Christine , Maigrat Charles-Henry , Devignes Jean , Goehringer François , Erpelding Marie-Line , Alla François , Thivilier Carine , Huttin Olivier , Venner Clément , Juilliere Yves , Doco-Lecompte Thanh , Lecompte Thomas 
Published: January 2018

ObjectiveAntiphospholipid (aPL) antibodies may activate platelets and contribute to vegetation growth and embolisation in infective endocarditis (IE). We aimed to determine the value of aPL as predictors of embolic events (EE) in IE.MethodsWe studied 186 patients with definite IE (Duke-Li criteria, all types of IE) from the Nanc-IE prospective registry (2007–2012) who all had a frozen blood sample and at least one imaging procedure to detect asymptomatic or confirm symptomatic EE. Anticardiolipin (aCL) and anti-β2-glycoprotein I (β2GPI) antibodies (IgG and IgM) were assessed after the end of patients’ inclusion. The relationship between antibodies and the detection of EE after IE diagnosis were studied with Kaplan-Meier and Cox multivariate analyses.ResultsAt least one EE was detected in 118 (63%) patients (52 cerebral, 95 other locations) after IE diagnosis in 80 (time interval between IE and EE diagnosis: 5.9±11.3 days). At least one aPL antibody was found in 31 patients (17%).Detection of EE over time after IE diagnosis was more frequent among patients with anti-β2GPI IgM (log-rank P=0.0036) and that of cerebral embolisms, among patients with aCL IgM and anti-β2GPI IgM (log-rank P=0.002 and P<0.0001, respectively).Factors predictive of EE were anti-β2GPI IgM (HR=3.45 (1.47–8.08), P=0.0045), creatinine (2.74 (1.55–4.84), P=0.0005) and vegetation size (2.41 (1.41–4.12), P=0.0014). Those of cerebral embolism were aCL IgM (2.84 (1.22–6.62), P=0.016) and anti-β2GPI IgM (4.77 (1.79–12.74), P=0.0018).ConclusionThe presence of aCL and anti-β2GPI IgM was associated with EE, particularly cerebral ones, and could contribute to assess the embolic risk of IE.
Trends in cardiovascular risk factor and disease prevalence in patients undergoing non-cardiac surgery
Authors: Smilowitz Nathaniel R , Gupta Navdeep , Guo Yu , Beckman Joshua A , Bangalore Sripal , Berger Jeffrey S 
Published: January 2018

ObjectivesCardiovascular risk factors are prevalent in the population undergoing non-cardiac surgery. Changes in perioperative cardiovascular risk factor profiles over time are unknown. The objective of this study was to evaluate national trends in cardiovascular risk factors and atherosclerotic cardiovascular disease (ASCVD) among patients undergoing non-cardiac surgery.MethodsAdults aged ≥45 years old who underwent non-cardiac surgery were identified using the US National Inpatient Sample from 2004 to 2013. The prevalence of traditional cardiovascular risk factors (hypertension, dyslipidaemia, diabetes mellitus, obesity and chronic kidney disease) and ASCVD (coronary artery disease, peripheral artery disease and prior stroke] were evaluated over time.ResultsA total of 10 581 621 hospitalisations for major non-cardiac surgery were identified. Between 2008 and 2013, ≥2 cardiovascular risk factors and ASCVD were present in 44.5% and 24.3% of cases, respectively. Over time, the prevalence of multiple (≥2) cardiovascular risk factors increased from 40.5% in 2008–2009 to 48.2% in 2012–2013, P<0.001. The proportion of patients with coronary artery disease (17.2% in 2004–2005 vs 18.2% in 2012–2013, P<0.001), peripheral artery disease (6.3% in 2004–2005 vs 7.4% in 2012–2013, P<0.001) and prior stroke (3.5% in 2008–2009 vs 4.7% 2012–2013, P<0.001) also increased over time. The proportion of patients with a modified Revised Cardiac Risk Index score ≥3 increased from 6.6% in 2008–2009 to 7.7% in 2012–2013 (P<0.001).ConclusionsAmong patients undergoing major non-cardiac surgery, the burden of cardiovascular risk factors and the prevalence of ASCVD increased over time. Adverse trends in risk profiles require continued attention to improve perioperative cardiovascular outcomes.
Allergy teaching is suboptimal and heterogeneous in the undergraduate medical curriculum in the UK
Authors: Reid Emily Frances , Krishna Mamidipudi Thirumala , Bethune Claire 
Published: January 2018

AimTo record the level of allergy teaching occurring in UK medical schools. The UK has experienced an ‘allergy epidemic’ during the last 3–4 decades. Previous government reviews have emphasised the importance of allergy education and training, treating common allergies in primary care with referral pathways to a specialist and the creation of regional networks. It is acknowledged that the delivery of allergy teaching in UK medical schools is variable, despite the well-recognised need.MethodsAll consultant members of the British Society for Allergy and Clinical Immunology involved in teaching medical students were invited to partake in qualitative research, employing an online questionnaire for data collection. Participants were asked to comment on the format of the allergy teaching delivered, the student participation and the clinical opportunities provided. Students were recruited to complete a similar survey as supporting evidence.Results44 responses were collected, representing 64.7% of medical schools in the UK. Clinical allergy placements were compulsory in 31.8% of medical schools that responded. In 36.4%, it was reported that less than 10% of students had an opportunity to take an independent history from a patient with allergic disease, or practise using an epinephrine autoinjector. 90.9% responded that an allergy rotation was not offered to final year students.ConclusionsAllergy undergraduate teaching is suboptimal and heterogeneous in UK medical schools and there is a real need for standardisation as a means to enhance quality of care.
Clinical outcomes and costs of cardiac revascularisation in England and New York state
Authors: Leyva Francisco , Qiu Tian , Evison Felicity , Christoforou Christopher , McNulty David , Ludman Peter , Ray Daniel 
Published: January 2018

ObjectivesHealthcare expenditure per-capita in the USA is higher than in England. We hypothesised that clinical outcomes after cardiac revascularisation are better in the USA. We compared costs and outcomes of patients undergoing coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) in England and New York State (NYS).MethodsCosts and total mortality were assessed using the Hospital Episode Statistics for England and the Statewide Planning and Research Cooperative System for NYS. Outcomes after a first CABG or PCI were assessed in patients undergoing a first CABG (n=142 969) or PCI (n=431 416).ResultsAfter CABG, crude total mortality in England was 0.72% lower at 30 days and 3.68% lower at 1 year (both P<0.001). After PCI, crude total mortality was 0.35% lower at 30 days and 3.55% lower at 1 year (both P<0.001). No differences emerged in total mortality at 30 days after either CABG (England: HR 1.02,95% CI 0.94 to 1.10) or PCI (HR 1.04, 95% CI 0.99 to 1.09) after covariate adjustment. At 1 year, adjusted total mortality was lower in England after both CABG (HR 0.74, 95% CI 0.71 to 0.78) and PCI (HR 0.66, 95% CI 0.65 to 0.68). After adjustment for cost-to-charge ratios and purchasing power parities, costs in NYS amounted to uplifts of 3.8-fold for CABG and 3.6-fold for PCI.ConclusionsTotal mortality after CABG and PCI was similar at 30 days and lower in England at 1 year. Costs were approximately fourfold higher in NYS.
Simplicial Palatini action
Authors: Khatsymovsky V. M. 
Published: January 2018

We consider the piecewise flat spacetime and a simplicial analog of the Palatini form of the general relativity (GR) action where the discrete Christoffel symbols are given on the tetrahedra as variables that are independent of the metric. Excluding these variables with the help of the equations of motion gives exactly the Regge action. This paper continues our previous work. Now, we include the parity violation term and the analog of the Barbero–Immirzi parameter introduced in the orthogonal connection form of GR. We consider the path integral and the functional integration over the connection. The result of the latter (for certain limiting cases of some parameters) is compared with the earlier found result of the functional integration over the connection for the analogous orthogonal connection representation of Regge action. These results, mainly as some measures on the lengths/areas, are discussed for the possibility of the diagram technique where the perturbative diagrams for the Regge action calculated using the measure obtained are finite. This finiteness is due to these measures providing elementary lengths being mostly bounded and separated from zero, just as the finiteness of a theory on a lattice with an analogous probability distribution of spacings.
Particle physics today, tomorrow and beyond
Authors: Ellis John 
Published: January 2018

The most important discovery in particle physics in recent years was that of the Higgs boson, and much effort is continuing to measure its properties, which agree obstinately with the Standard Model, so far. However, there are many reasons to expect physics beyond the Standard Model, motivated by the stability of the electroweak vacuum, the existence of dark matter and the origin of the visible matter in the Universe, neutrino physics, the hierarchy of mass scales in physics, cosmological inflation and the need for a quantum theory for gravity. Most of these issues are being addressed by the experiments during Run 2 of the LHC, and supersymmetry could help resolve many of them. In addition to the prospects for the LHC, I also review briefly those for direct searches for dark matter and possible future colliders.
Evaluating the susceptibility to anthropogenic sinkholes in Apulian calcarenites, southern Italy
Authors: Fiore A. , Fazio N. L. , Lollino P. , Luisi M. , Miccoli M. N. , Pagliarulo R. , Perrotti M. , Pisano L. , Spalluto L. , Vennari C. , Vessia G. , Parise M. 
Published: January 2018

Abstract
Sinkholes are the main hazard related to underground voids of both natural and anthropogenic origin. Instabilities developing underground may propagate upwards in a dramatic manner and reach the surface in the form of a sinkhole. The Apulia region in southern Italy is an interesting case study due to the outcropping of soluble rocks throughout the region. These rocks are affected by karst processes and have a high number of anthropogenic cavities. The latter were excavated by humans at different times for a variety of purposes. The worrying recent increase in the number of sinkhole events registered in Apulia led us to collect information on natural and anthropogenic sinkholes in Apulia. We focused on anthropogenic cavities, mostly excavated in Plio-Pleistocene calcarenites, and characterized the rock masses before using two- and three-dimensional parametric numerical analyses to model the instability processes, with the aim of exploring the failure mechanisms that lead to the occurrence of sinkholes. The parametric studies allowed us to carry out a preliminary evaluation of the stability conditions through simple charts designed for use in the field.
Lower Cretaceous reservoir development in the North Sea Central Graben, and potential analogue settings in the Southern Permian Basin and South Viking Graben
Authors: Zwaan Frank 
Published: January 2018

Abstract
Much of the future hydrocarbon exploration potential in the North Sea lies in locating stratigraphic traps and discrete reservoir intervals. This study assesses the potential for Lower Cretaceous reservoirs, with particular focus on the Norwegian Central Graben and methods to identify future prospects over a wider area. Seismic interpretation and well data reveal the structure and sedimentology of the study area. Although the region was isolated from a large hinterland in the Early Cretaceous, potential local sediment sources, sediment transport routes and areas with possible reservoir development are identified. The greater Mandal High area, where Lower Cretaceous shoreface deposits and submarine fan systems are postulated, is suggested for primary focus. Similar deposits may have developed around the other exposed highs in the region, although several were drowned towards the end of the Early Cretaceous. Detailed seismic and stratigraphic analysis will be necessary to identify individual reservoir units. Since comparable settings may have occurred in the adjacent South Viking Graben and Southern Permian Basin regions during the Early Cretaceous, further reservoir assessment is recommended for the North Sea in general.
Cyclic-GMP–Elevating Agents Suppress Polyposis in ApcMin Mice by Targeting the Preneoplastic Epithelium
Authors: Sharman Sarah K. , Islam Bianca N. , Hou Yali , Singh Nagendra , Berger Franklin G. , Sridhar Subbaramiah , Yoo Wonsuk , Browning Darren D. 
Published: January 2018

Abstract
The cGMP signaling axis has been implicated in the suppression of intestinal cancers, but the inhibitory mechanism and the extent to which this pathway can be targeted remains poorly understood. This study has tested the effect of cGMP-elevating agents on tumorigenesis in the ApcMin/+ mouse model of intestinal cancer. Treatment of ApcMin/+ mice with the receptor guanylyl-cyclase C (GCC) agonist linaclotide, or the phosphodiesterase-5 (PDE5) inhibitor sildenafil, significantly reduced the number of polyps per mouse (67% and 50%, respectively). Neither of the drugs affected mean polyp size, or the rates of apoptosis and proliferation. This was possibly due to increased PDE10 expression, as endogenous GCC ligands were not deficient in established polyps. These results indicated that the ability of these drugs to reduce polyp multiplicity was primarily due to an effect on nonneoplastic tissues. In support of this idea, ApcMin/+ mice exhibited reduced levels of endogenous GCC agonists in the nonneoplastic intestinal mucosa compared with wild-type animals, and this was associated with crypt hyperplasia and a loss of goblet cells. Administration of either sildenafil or linaclotide suppressed proliferation, and increased both goblet cell numbers and luminal apoptosis in the intestinal mucosa. Taken together, the results demonstrate that targeting cGMP with either PDE5 inhibitors or GCC agonists alters epithelial homeostasis in a manner that reduces neoplasia, and suggests that this could be a viable chemoprevention strategy for patients at high risk of developing colorectal cancer. Cancer Prev Res; 11(2); 81–92. ©2018 AACR.