bluuebunny/crossref_metadata_2025 huggingface dataset:
Mutations in the major gas vesicle protein GvpA and impacts on gas vesicle formation in Haloferax volcanii
Authors: Knitsch Regine , Schneefeld Marie , Weitzel Kerstin , Pfeifer Felicitas
Published: September 2017

Gas vesicles are proteinaceous, gas‐filled nanostructures produced by some bacteria and archaea. The hydrophobic major structural protein GvpA forms the ribbed gas vesicle wall. An in‐silico 3D‐model of GvpA of the predicted coil‐α1‐β1‐β2‐α2‐coil structure is available and implies that the two β‐chains constitute the hydrophobic interior surface of the gas vesicle wall. To test the importance of individual amino acids in GvpA we performed 85 single substitutions and analyzed these variants in Haloferax volcanii ΔA + Amut transformants for their ability to form gas vesicles (Vac+ phenotype). In most cases, an alanine substitution of a non‐polar residue did not abolish gas vesicle formation, but the replacement of single non‐polar by charged residues in β1 or β2 resulted in Vac– transformants. A replacement of residues near the β‐turn altered the spindle‐shape to a cylindrical morphology of the gas vesicles. Vac– transformants were also obtained with alanine substitutions of charged residues of helix α1 suggesting that these amino acids form salt‐bridges with another GvpA monomer. In helix α2, only the alanine substitution of His53 or Tyr54, led to Vac– transformants, whereas most other substitutions had no effect. We discuss our results in respect to the GvpA structure and data available from solid‐state NMR.
Impact of renal replacement therapy on survival in patients with KDIGO stage 3 acute kidney injury: A propensity score matched analysis
Authors: Shum Hoi‐Ping , Chan King‐Chung , Tam Catherine W‐Y , Yan Wing‐Wa , Chan Tak‐Mao
Published: September 2017

Aim

To investigate the impact of renal replacement therapy (RRT) on 90‐day mortality in critically ill patients suffering from KDIGO stage 3 acute kidney injury (AKI) with or without life‐threatening complications using propensity score matching analysis.

Methods

We conducted a retrospective analysis of critically ill adult patients with KDIGO Stage 3 AKI with or without RRT during ICU stay between 1/1/2011‐31/12/2013. Cox regression analysis and propensity score matching methods were used to determine predictors for 90‐day mortality.

Results

Among 661 patients, 50.5% received RRT. The unadjusted 90‐day mortality rate was 42.5% and 54.1% in patients who had or had not received RRT, respectively. After adjustment with propensity score based on the probability of receiving RRT, the cox regression analysis showed that RRT was associated with a lower 90‐day mortality (p<0.001). Among 322 propensity‐matched pairs, RRT was associated with lower ICU (23.6% vs. 39.8%, p=0.002), hospital (33.5% vs. 55.9%, p<0.001) and 90‐day mortality (34.2% vs. 58.4%, p<0.001), and a higher 90‐day renal recovery rate (57.8% vs. 45.3% full recovery, p=0.026) compared with no RRT. When an alternate propensity model was used, the benefits associated with RRT were very similar, except 90‐day renal recovery became insignificant.

Conclusion

Our observational study found that in critically ill patients with KDIGO Stage 3 AKI, RRT may be associated with lower 90‐day mortality. The benefit of RRT on renal recovery was less prominent. Medical futility and practice variations may complicate study interpretation. To avoid these limitations, large‐scale multicenter, non‐observational study is recommended.
Chamaesium jiulongense sp. nov. (Apiaceae) from Sichuan, China
Authors: Guo Xian-Lin , Xie Chuan , Bai Juan , He Xing-Jin
Published: September 2017

Chamaesium jiulongense X. L. Guo & X. J. He, a new species of Apiaceae from Mt Haite in Jiulong County, Sichuan Province, China, is described. The new species differs from other Chamaesium species by its ultimate segments of the leaves which are 1–3‐lobed, rarely entire, with a narrow, minutely incised, pale brown margin, as well as by the presence of leaf‐like bracts, bracteoles longer than flowers, pubescent styles and oblong fruit with obsolete calyx. Morphological and micromorphological characters of the new species are provided and illustrated.
What Drives Fraud in a Credence Goods Market? – Evidence from a Field Study
Authors: Rasch Alexander , Waibel Christian
Published: September 2017

This paper investigates the impact of competition on an expert firm's incentive to defraud its customers in a credence goods market. Controlling for the competence of car repair shops, their financial situation, and reputational concerns, we use and complement the data set from a nationwide field study conducted by the German Automobile Association that regularly checks the reliability of garages in Germany. We find that more intense competition lowers a firm's incentive to defraud its customers.
Treatment with Naloxegol Versus Placebo: Pain Assessment in Patients with Noncancer Pain and Opioid‐Induced Constipation
Authors: Webster Lynn , Diva Ulysses , Tummala Raj , Sostek Mark
Published: September 2017

Objective

To summarize results from pain and opioid use assessments with naloxegol in adults with opioid‐induced constipation (OIC) and chronic noncancer pain.

Methods

Two phase 3 randomized, double‐blind, 12‐week studies evaluated the efficacy and safety of oral naloxegol (12.5 or 25 mg daily) in adults (18 to < 85 years) with confirmed OIC and chronic noncancer pain: KODIAC‐04 (NCT01309841) and KODIAC‐05 (NCT01323790). Pain level was assessed daily (11‐point numeric rating scale [NRS]; 0 = no pain, 10 = worst imaginable pain). Changes from baseline in mean weekly pain scores and opioid dose (weeks 1 through 12) were analyzed using mixed‐model repeated measures.

Results

At baseline, mean daily NRS average pain scores ranged from 4.5 to 4.8 for all groups in KODIAC‐04 (N = 652) and were 4.6 for each group in KODIAC‐05 (N = 700). Respective mean ± SD changes from baseline average pain for placebo, naloxegol 12.5 mg, and naloxegol 25 mg were −0.2 ± 1.07, −0.3 ± 1.05 (P = 0.773 vs. placebo), and 0.2 ± 0.95 (P = 0.837 vs. placebo; KODIAC‐04) and −0.1 ± 0.94, −0.1 ± 0.87 (P = 0.744), and 0.0 ± 1.18 (P = 0.572; KODIAC‐05). At baseline, mean daily opioid doses ranged from 135.6 to 143.2 morphine equivalent units (MEUs)/day in KODIAC‐04, and from 119.9 to 151.7 MEUs/day in KODIAC‐05. Respective mean ± SD changes from baseline dose were −1.8 ± 30.19, −2.3 ± 20.52 (P = 0.724 vs. placebo), and 0.4 ± 13.01 (P = 0.188 vs. placebo; KODIAC‐04) and −0.3 ± 17.14, −1.3 ± 17.11 (P = 0.669 vs. placebo), and 0.1 ± 8.54 (P = 0.863 vs. placebo; KODIAC‐05). Changes in maintenance opioid dose were few; reasons for such changes were similar across treatment groups.

Conclusion

Centrally mediated opioid analgesia was maintained during treatment with naloxegol in patients with noncancer pain and OIC.
Reconsidering what enclosure and exclosure mean in restoration ecology
Authors: Yirdaw Eshetu , Monge Adrian
Published: September 2017

There is ambiguity in the use of the terms “enclosure” and “exclosure” in describing the passive method used for the restoration of degraded ecosystems. We argue that in the context of ecological restoration, the term enclosure is generally more appropriate to use than exclosure. Unlike exclosure, the term enclosure focuses on the degraded area to be restored, does not exclude selective permeability of external factors, and potentially accommodates local people's livelihood needs. However, the term exclosure is appropriate to use in the case of experimental exclosures or management of restoration sites which explicitly exclude specific disturbance factors.
Role of microtopography in the expression of soil propagule banks on reclamation sites
Authors: Melnik Katharine , Landhäusser Simon M. , Devito Kevin
Published: September 2017

The legacy propagule banks of salvaged topsoils are excellent sources of plant propagules for reclamation of mine sites; however, earlier studies show that less than 50% of the species found in original propagule banks actually establish. We hypothesize that the expression of this legacy propagule bank is limited by a lack of diversity of microsites and appropriate growing conditions. In an operational‐scale field experiment we manipulated topographical characteristics and substrate materials and explored early vegetation establishment on an east‐ and south‐facing slope. Three different site treatments with different microtopographic characteristics: (1) leveled surface, (2) parallel ridges, and (3) large loose piles were created using salvaged upland and lowland forest floor soil materials. Placing materials in loose hills and providing heterogeneity in substrates more than doubled plant abundance, species richness, and increased the proportion of species that require higher soil moisture. Lower micro‐elevations and northern microaspects of the microtopographic treatments had up to three times higher soil water content and double the species richness. However, the overall slope aspect had a modulating effect on microtopographic positions. The greatest treatment effect of micro‐elevation and microaspect on species richness and plant abundance occurred on the east‐facing slope, while the greatest effect of treatment on the proportion of species requiring higher soil moisture conditions was observed on the south‐facing slope. Variability in microtopography and substrate can create favorable growing conditions at an operational scale and help express a wider range of species from the legacy propagule bank.
Regulation, Minimum Wage and Informality: Introduction to Symposium
Authors: Basu Kaushik , Dercon Stefan , Kanbur Ravi , Svejnar Jan
Published: September 2017

Are markets in developing and transition economies over‐regulated or under‐regulated? This is a perennial question in the development discourse, but one for which answers appear to come more from preset ideology than from context‐specific analysis and evidence. These issues become even more pressing when the debate turns to the links between regulation, deregulation and inequality. The recent experience of rising inequality in many countries has also brought to the fore predictable policy positions. A key aspect of labor regulation in developing countries, and one becoming more prominent in the era of rising inequality, is the minimum wage. The range of issues around regulation, minimum wage and informality was addressed by papers presented to a conference held in New Delhi on December 17–18, 2014. The conference was co‐sponsored by the World Bank, UK Department for International Development, Cornell University and Columbia University. The organizers of the conference were Kaushik Basu, Stefan Dercon, Ravi Kanbur and Jan Svejnar. A selection of papers from the conference which passed the usual review procedures of the Review of Development Economics, and a further selection of papers from those submitted to the journal, form this symposium.
Time‐Varying Dynamics of the Norwegian Economy
Authors: Farooq Akram Q. , Mumtaz Haroon
Published: September 2017

We use time‐varying parameter vector autoregressive models to investigate possible changes in the time‐series properties of key Norwegian macroeconomic variables since the 1980s. Notably, we find that inflation persistence falls during the inflation targeting period, while the volatility of inflation and nominal exchange rates increases. The observed time‐variation in the correlations between the interest rates and the macro variables largely reflects the prevailing monetary policy regimes. An increase in the correlations between oil prices and other macro variables over time is also documented. Using a counterfactual analysis, we discuss the observed time‐varying dynamics of the Norwegian economy in the light of monetary policy and oil price shocks.
More Black than Blue? Comparing the Racial Attitudes of Police to Citizens
Authors: LeCount Ryan Jerome
Published: September 2017

How are the racial attitudes of police officers distinct from those of the public? How might the officer's own race shape those attitudes? Recent high‐profile cases of contested uses of lethal force by white police officers against citizens of color have reanimated a long‐established debate about the way(s) that race shapes police contact. While research has documented substantial racial disparities across a variety of criminal justice outcomes, little is known about how law enforcement officers might differ from citizens in the way that they think about citizens of color. Existing studies of such attitudes are often limited by the idiosyncrasies of small and unrepresentative samples. The present study overcomes these limitations by employing the first nationally representative survey comparing citizens and police a range of racial attitudes. Findings suggest that white police are, indeed, more racially resentful, more likely to see blacks as violent, and more likely to minimize anti‐black discrimination than are white nonpolice. Black police officers, however, are not significantly more racially conservative than black citizens on any of the measures examined, lending modest evidence to the “selection effect” theory of Police Personality.
“I Don't Want to Be With Those Guys!”: Speaking Up Against Bias and Injustice
Authors: Cerulo Karen A.
Published: September 2017

Demonstrations, rallies, changes to the law, increased prosecutions—all of these things are vital to making sure that all lives—black, brown, or white; female or male; Christian, Jewish, or Muslim; gay or straight—are equally valued by the public and in the execution of the law. But just as important is the stand that ordinary people take in everyday situations… the raising of voice as situations arise in the forums of our lives. Giving voice is the driving force of this essay and the logic behind this special issue of Sociological Forum: Whose Lives Matter?: Violence, Social Control, and the Racial Divide.
Transmission loss characteristics of an annular cavity with arbitrary port locations using Green's function method
Authors: Keskar Harshad , Venkatesham B.
Published: September 2017

The prediction of transmission loss characteristics of a short chamber requires the study of both longitudinal as well as transverse modes. This prompts the development of a three-dimensional (3D) transfer matrix, which can address the wave propagation in all three directions. Accordingly, an analytical methodology for transmission loss characteristics of an annular cavity using Green's function method is presented in this paper. The 3D wave equation is used to derive the mode shape functions for the cavity. The average pressure on the inlet and outlet ports is predicted using the Green's function derived from the mode shapes. Three different port location configurations of the annular cavity are considered for establishing the analytical methodology, viz., face-inlet-face-outlet (FIFO), side-inlet-side-outlet (SISO), and face-inlet-side-outlet (FISO). Numerical model results are used to corroborate the analytical results. The effects of geometrical parameters on the transmission loss are studied.
Regulation of autophagy, NF-κB signaling, and cell viability by miR-124 in
KRAS
mutant mesenchymal-like NSCLC cells
Authors: Mehta Anita K. , Hua Kevin , Whipple William , Nguyen Minh-Thuy , Liu Ching-Ti , Haybaeck Johannes , Weidhaas Joanne , Settleman Jeff , Singh Anurag
Published: September 2017

The loss of microRNA miR-124 enables prosurvival autophagy signaling and metastatic features in
KRAS
mutant mesenchymal lung cancer cells.
Chemotherapy, pain, and gut microbiota
Authors: Ferrarelli Leslie K.
Published: September 2017

Chemotherapy triggers gut microbiota to stimulate pain-associated peripheral inflammation.
Mycobacterium tuberculosis Subculture Results in Loss of Potentially Clinically Relevant Heteroresistance
Authors: Metcalfe John Z. , Streicher Elizabeth , Theron Grant , Colman Rebecca E. , Penaloza Renee , Allender Christopher , Lemmer Darrin , Warren Robin M. , Engelthaler David M.
Published: September 2017

Multidrug-resistant tuberculosis (TB) presents a major public health dilemma. Heteroresistance, the coexistence of drug-resistant and drug-susceptible strains or of multiple drug-resistant strains with discrete haplotypes, may affect accurate diagnosis and the institution of effective treatment. Subculture, or passage of cells onto fresh growth medium, is utilized to preserve
Mycobacterium tuberculosis
cell lines and is universally employed in TB diagnostics. The impact of such passages, typically performed in the absence of drug, on drug-resistant subpopulations is hypothesized to vary according to the competitive costs of genotypic resistance-associated variants. We applied ultradeep next-generation sequencing to 61 phenotypically rifampin-monoresistant (
n
= 17) and preextensively (
n
= 41) and extensively (
n
= 3) drug-resistant isolates with presumptive heteroresistance at two time points in serial subculture. We found significant dynamic loss of minor-variant resistant subpopulations across all analyzed resistance-determining regions, including eight isolates (13%) whose antibiogram data would have transitioned from resistant to susceptible for at least one drug through subculture. Surprisingly, some resistance-associated variants appeared to be selected for in subculture.
Protocol for Identifying Natural Agents That Selectively Affect Adhesion, Thickness, Architecture, Cellular Phenotypes, Extracellular Matrix, and Human White Blood Cell Impenetrability of Candida albicans Biofilms
Authors: Park Yang-Nim , Srikantha Thyagarajan , Daniels Karla J. , Jacob Melissa R. , Agarwal Ameeta K. , Li Xing-Cong , Soll David R.
Published: September 2017

In the screening of natural plant extracts for antifungal activity, assessment of their effects on the growth of cells in suspension or in the wells of microtiter plates is expedient. However, microorganisms, including
Candida albicans
, grow in nature as biofilms, which are organized cellular communities with a complex architecture capable of conditioning their microenvironment, communicating, and excluding low- and high-molecular-weight molecules and white blood cells. Here, a confocal laser scanning microscopy (CLSM) protocol for testing the effects of large numbers of agents on biofilm development is described. The protocol assessed nine parameters from a single z-stack series of CLSM scans for each individual biofilm analyzed. The parameters included adhesion, thickness, formation of a basal yeast cell polylayer, hypha formation, the vertical orientation of hyphae, the hyphal bend point, pseudohypha formation, calcofluor white staining of the extracellular matrix (ECM), and human white blood cell impenetrability. The protocol was applied first to five plant extracts and derivative compounds and then to a collection of 88 previously untested plant extracts. They were found to cause a variety of phenotypic profiles, as was the case for 64 of the 88 extracts (73%). Half of the 46 extracts that did not affect biofilm thickness affected other biofilm parameters. Correlations between specific effects were revealed. The protocol will be useful not only in the screening of chemical libraries but also in the analysis of compounds with known effects and mutations.
Modulation of Staphylococcus aureus Response to Antimicrobials by the Candida albicans Quorum Sensing Molecule Farnesol
Authors: Kong Eric F. , Tsui Christina , Kucharíková Sona , Van Dijck Patrick , Jabra-Rizk Mary Ann
Published: September 2017

In microbial biofilms, microorganisms utilize secreted signaling chemical molecules to coordinate their collective behavior. Farnesol is a quorum sensing molecule secreted by the fungal species
Candida albicans
and shown to play a central physiological role during fungal biofilm growth. Our pervious
in vitro
and
in vivo
studies characterized an intricate interaction between
C. albicans
and the bacterial pathogen
Staphylococcus aureus
, as these species coexist in biofilm. In this study, we aimed to investigate the impact of farnesol on
S. aureus
survival, biofilm formation, and response to antimicrobials. The results demonstrated that in the presence of exogenously supplemented farnesol or farnesol secreted by
C. albicans
in biofilm,
S. aureus
exhibited significantly enhanced tolerance to antimicrobials. By using gene expression studies,
S. aureus
mutant strains, and chemical inhibitors, the mechanism for the enhanced tolerance was attributed to upregulation of drug efflux pumps. Importantly, we showed that sequential exposure of
S. aureus
to farnesol generated a phenotype of high resistance to antimicrobials. Based on the presence of intracellular reactive oxygen species upon farnesol exposure, we hypothesize that antimicrobial tolerance in
S. aureus
may be mediated by farnesol-induced oxidative stress triggering the upregulation of efflux pumps, as part of a general stress response system. Hence, in mixed biofilms,
C. albicans
may influence the pathogenicity of
S. aureus
through acquisition of a drug-tolerant phenotype, with important therapeutic implications. Understanding interspecies signaling in polymicrobial biofilms and the specific drug resistance responses to secreted molecules may lead to the identification of novel targets for drug development.
Role of Activins in Hepcidin Regulation during Malaria
Authors: Spottiswoode Natasha , Armitage Andrew E. , Williams Andrew R. , Fyfe Alex J. , Biswas Sumi , Hodgson Susanne H. , Llewellyn David , Choudhary Prateek , Draper Simon J. , Duffy Patrick E. , Drakesmith Hal
Published: September 2017

Epidemiological observations have linked increased host iron with malaria susceptibility, and perturbed iron handling has been hypothesized to contribute to the potentially life-threatening anemia that may accompany blood-stage malaria infection. To improve our understanding of these relationships, we examined the pathways involved in regulation of the master controller of iron metabolism, the hormone hepcidin, in malaria infection. We show that hepcidin upregulation in
Plasmodium berghei
murine malaria infection was accompanied by changes in expression of bone morphogenetic protein (BMP)/sons of mothers against decapentaplegic (SMAD) pathway target genes, a key pathway involved in hepcidin regulation. We therefore investigated known agonists of the BMP/SMAD pathway and found that
Bmp
gene expression was not increased in infection. In contrast, activin B, which can signal through the BMP/SMAD pathway and has been associated with increased hepcidin during inflammation, was upregulated in the livers of
Plasmodium berghei
-infected mice; hepatic activin B was also upregulated at peak parasitemia during infection with
Plasmodium chabaudi
. Concentrations of the closely related protein activin A increased in parallel with hepcidin in serum from malaria-naive volunteers infected in controlled human malaria infection (CHMI) clinical trials. However, antibody-mediated neutralization of activin activity during murine malaria infection did not affect hepcidin expression, suggesting that these proteins do not stimulate hepcidin upregulation directly. In conclusion, we present evidence that the BMP/SMAD signaling pathway is perturbed in malaria infection but that activins, although raised in malaria infection, may not have a critical role in hepcidin upregulation in this setting.
Hyperbiofilm Formation by Bordetella pertussis Strains Correlates with Enhanced Virulence Traits
Authors: Cattelan Natalia , Jennings-Gee Jamie , Dubey Purnima , Yantorno Osvaldo M. , Deora Rajendar
Published: September 2017

Pertussis, or whooping cough, caused by the obligate human pathogen
Bordetella pertussis
is undergoing a worldwide resurgence. The majority of studies of this pathogen are conducted with laboratory-adapted strains which may not be representative of the species as a whole. Biofilm formation by
B. pertussis
plays an important role in pathogenesis. We conducted a side-by-side comparison of the biofilm-forming abilities of the prototype laboratory strains and the currently circulating isolates from two countries with different vaccination programs. Compared to the reference strain, all strains examined herein formed biofilms at high levels. Biofilm structural analyses revealed country-specific differences, with strains from the United States forming more structured biofilms. Bacterial hyperaggregation and reciprocal expression of biofilm-promoting and -inhibitory factors were observed in clinical isolates. An association of increased biofilm formation with augmented epithelial cell adhesion and higher levels of bacterial colonization in the mouse nose and trachea was detected. To our knowledge, this work links for the first time increased biofilm formation in bacteria with a colonization advantage in an animal model. We propose that the enhanced biofilm-forming capacity of currently circulating strains contributes to their persistence, transmission, and continued circulation.
Enterococcus faecalis Promotes Innate Immune Suppression and Polymicrobial Catheter-Associated Urinary Tract Infection
Authors: Tien Brenda Yin Qi , Goh Hwee Mian Sharon , Chong Kelvin Kian Long , Bhaduri-Tagore Soumili , Holec Sarah , Dress Regine , Ginhoux Florent , Ingersoll Molly A. , Williams Rohan B. H. , Kline Kimberly A.
Published: September 2017

Enterococcus faecalis, a member of the human gastrointestinal microbiota, is an opportunistic pathogen associated with hospital-acquired wound, bloodstream, and urinary tract infections.E. faecaliscan subvert or evade immune-mediated clearance, although the mechanisms are poorly understood. In this study, we examinedE. faecalis-mediated subversion of macrophage activation. We observed thatE. faecalisactively prevents NF-κB signaling in mouse RAW264.7 macrophages in the presence of Toll-like receptor agonists and during polymicrobial infection withEscherichia coli.E. faecalisandE. colicoinfection in a mouse model of catheter-associated urinary tract infection (CAUTI) resulted in a suppressed macrophage transcriptional response in the bladder compared to that withE. coliinfection alone. Finally, we demonstrated that coinoculation ofE. faecaliswith a commensal strain ofE. coliinto catheterized bladders significantly augmentedE. coliCAUTI. Taken together, these results support the hypothesis thatE. faecalissuppression of NF-κB-driven responses in macrophages promotes polymicrobial CAUTI pathogenesis, especially during coinfection with less virulent or commensalE. colistrains.
Stenotrophomonas maltophilia Serine Protease StmPr1 Induces Matrilysis, Anoikis, and Protease-Activated Receptor 2 Activation in Human Lung Epithelial Cells
Authors: DuMont Ashley L. , Cianciotto Nicholas P.
Published: September 2017

Stenotrophomonas maltophilia
is an emerging, opportunistic nosocomial pathogen that can cause severe disease in immunocompromised individuals. We recently identified the StmPr1 and StmPr2 serine proteases to be the substrates of the Xps type II secretion system in
S. maltophilia
strain K279a. Here, we report that a third serine protease, StmPr3, is also secreted in an Xps-dependent manner. By constructing a panel of protease mutants in strain K279a, we were able to determine that StmPr3 contributes to the previously described Xps-mediated rounding and detachment of cells of the A549 human lung epithelial cell line as well as the Xps-mediated degradation of fibronectin, fibrinogen, and the cytokine interleukin-8 (IL-8). We also determined that StmPr1, StmPr2, and StmPr3 account for all Xps-mediated effects toward A549 cells and that StmPr1 contributes the most to Xps-mediated activities. Thus, we purified StmPr1 from the
S. maltophilia
strain K279a culture supernatant and evaluated the protease's activity toward A549 cells. Our analyses revealed that purified StmPr1 behaves more similarly to subtilisin than to trypsin. We also determined that purified StmPr1 likely induces cell rounding and detachment of A549 cells by targeting cell integrin-extracellular matrix connections (matrilysis) as well as adherence and tight junction proteins for degradation. In this study, we also identified anoikis as the mechanism by which StmPr1 induces the death of A549 cells and found that StmPr1 induces A549 IL-8 secretion via activation of protease-activated receptor 2. Altogether, these results suggest that the degradative and cytotoxic activities exhibited by StmPr1 may contribute to
S. maltophilia
pathogenesis in the lung by inducing tissue damage and inflammation.
Phenol-Soluble Modulin Peptides Contribute to Influenza A Virus-Associated Staphylococcus aureus Pneumonia
Authors: Bloes Dominik Alexander , Haasbach Emanuel , Hartmayer Carmen , Hertlein Tobias , Klingel Karin , Kretschmer Dorothee , Planz Oliver , Peschel Andreas
Published: September 2017

Influenza A virus (IAV) infection is often followed by secondary bacterial lung infection, which is a major reason for severe, often fatal pneumonia. Community-associated methicillin-resistantStaphylococcus aureus(CA-MRSA) strains such as USA300 cause particularly severe and difficult-to-treat cases of IAV-associated pneumonia. CA-MRSA strains are known to produce extraordinarily large amounts of phenol-soluble modulin (PSM) peptides, which are important cytotoxins and proinflammatory molecules that contribute to several types ofS. aureusinfection. However, their potential role in pneumonia has remained elusive. We determined the impact of PSMs on human lung epithelial cells and found that PSMs are cytotoxic and induce the secretion of the proinflammatory cytokine interleukin-8 (IL-8) in these cells. Both effects were boosted by previous infection with the 2009 swine flu pandemic IAV H1N1 strain, suggesting that PSMs may contribute to lung inflammation and damage in IAV-associatedS. aureuspneumonia. Notably, the PSM-producing USA300 strain caused a higher mortality rate than did an isogenic PSM-deficient mutant in a mouse IAV-S. aureuspneumonia coinfection model, indicating that PSMs are major virulence factors in IAV-associatedS. aureuspneumonia and may represent important targets for future anti-infective therapies.
Clustered Regularly Interspaced Short Palindromic Repeat (CRISPR) RNAs in the Porphyromonas gingivalis CRISPR-Cas I-C System
Authors: Burmistrz Michal , Rodriguez Martinez Jose Ignacio , Krochmal Daniel , Staniec Dominika , Pyrc Krzysztof
Published: September 2017

The CRISPR-Cas (clustered regularly interspaced short palindromic repeat–CRISPR-associated protein) system is unique to prokaryotes and provides the majority of bacteria and archaea with immunity against nucleic acids of foreign origin. CRISPR RNAs (crRNAs) are the key element of this system, since they are responsible for its selectivity and effectiveness. Typical crRNAs consist of a spacer sequence flanked with 5′ and 3′ handles originating from repeat sequences that are important for recognition of these small RNAs by the Cas machinery. In this investigation, we studied the type I-C CRISPR-Cas system in
Porphyromonas gingivalis
, a human pathogen associated with periodontitis, rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. We demonstrated the importance of the 5′ handle for crRNA recognition by the effector complex and consequently activity, as well as secondary trimming of the 3′ handle, which was not affected by modifications of the repeat sequence.

IMPORTANCE
Porphyromonas gingivalis
, a clinically relevant Gram-negative, anaerobic bacterium, is one of the major etiologic agents of periodontitis and has been linked with the development of other clinical conditions, including rheumatoid arthritis, cardiovascular disease, and aspiration pneumonia. The presented results on the biogenesis and functions of crRNAs expand our understanding of CRISPR-Cas cellular defenses in
P. gingivalis
and of horizontal gene transfer in bacteria.
Concussion knowledge and experience among Welsh amateur rugby union coaches and referees
Authors: Griffin Steffan Arthur , Ranson Craig , Moore Isabel , Mathema Prabhat
Published: September 2017

Background

Rugby union is a collision sport where participants are at high risk of sustaining a concussion. In settings where there is little qualified medical supervision, certain stakeholders (eg, coaches and officials) should possess sufficient knowledge in regard to the recognition and management of concussion.

Aim

The aim of this study was to assess the knowledge and experience of various aspects of concussion among coaches and referees involved in Welsh amateur rugby union.

Methods

A questionnaire was distributed to 1843 coaches and 420 referees.

Results

A total of 333 coaches and 283 referees completed the questionnaire (18% and 68% response rates, respectively). Participants exhibited greater knowledge of concussion symptom recognition relative to knowledge of both the consequences of concussion and associated return-to-play protocols, both of which could be considered poor. There were no differences in knowledge levels between coaches and referees or between participants with or without a history of concussion. Two-thirds of participants incorrectly believed that headgear could prevent concussion, and nearly 30% of coaches reported having witnessed other coaches allowing a potentially concussed player to continue playing.

Conclusions

Identification of several misconceptions indicates that concussion management within Welsh amateur rugby union needs to be improved, warranting a multi-faceted educational intervention.
Molecular profile of nasopharyngeal carcinoma: analysing tumour suppressor gene promoter hypermethylation by multiplex ligation-dependent probe amplification
Authors: Ooft Marc L , van Ipenburg Jolique , van Loo Rob , de Jong Rick , Moelans Cathy , Braunius Weibel , de Bree Remco , van Diest Paul , Koljenović Senada , Baatenburg de Jong Rob , Hardillo Jose , Willems Stefan M
Published: September 2017

Aims

To assess differences in methylation profiles, and thus pathogenesis, between Epstein-Barr virus (EBV)-positive and negative nasopharyngeal carcinomas (NPCs). Also, promoter hypermethylation is a common phenomenon in early carcinogenesis to inactivate tumour suppressor genes. Since epigenetic changes are reversible, the therapeutic application of methylation inhibitors could provide treatment options.

Methods

We evaluated promoter hypermethylation profiles of 22 common tumour suppressor genes in 108 NPCs using methylation-specific multiplex ligation-dependent probe amplification. Correlation between methylation, clinicopathological features (including EBV) and survival was examined. Cluster analysis was also performed.

Results

Hypermethylation of RASSF1A and ESR1 was significantly more frequent in EBV-positive NPC, while hypermethylation of DAPK1 was more frequent in EBV-negative NPC. In logistic regression, age, with EBV-positive NPC occurring at earlier age, and RASSF1, with RASSF1 hypermethylation being more frequent in EBV-positive NPC, remained significant. In EBV-positive NPC, hypermethylation of RASSF1A predicted worse overall survival (OS) (HR 3.058,95% CI 1.027 to 9.107). In EBV-negative NPC, hypermethylated adenomatous polyposis coli (APC) was a predictor of poor disease-free survival (DFS) (HR 6.868, 95% CI 2.142 to 22.022).

Conclusion

There are important epigenetic differences between EBV-negative and EBV-positive NPCs, with EBV-negative NPC having a more similar hypermethylation profile to other head and neck squamous cell carcinomas than EBV-positive NPC. Hypermethylation of RASSF1A might contribute to worse OS in EBV-positive NPC, and may be an important event in the pathogenesis of EBV-infected NPC. Hypermethylation of APC might contribute to worse DFS in EBV-negative NPC.
A review of 10 years of scapula injuries sustained by UK military personnel on operations
Authors: Roberts Darren C , Power D M , Stapley S A
Published: September 2017

Background

Scapula fractures are relatively uncommon injuries, mostly occurring due to the effects of high-energy trauma. Rates of scapula fractures are unknown in the military setting. The aim of this study is to analyse the incidence, aetiology, associated injuries, treatment and complications of these fractures occurring in deployed military personnel.

Methods

All UK military personnel returning with upper limb injuries from Afghanistan and Iraq were retrospectively reviewed using the Royal Centre for Defence Medicine database and case notes (2004–2014).

Results

Forty-four scapula fractures out of 572 upper limb fractures (7.7%) were sustained over 10 years. Blast and gunshot wounds (GSW) were leading causative factors in 85%. Over half were open fractures (54%), with open blast fractures often having significant bone and soft tissue loss requiring extensive reconstruction. Multiple injuries were noted including lung, head, vascular and nerve injuries. Injury Severity Scores (ISS) were significantly higher than the average upper limb injury without a scapula fracture (p<0.0001). Brachial plexus injuries occurred in 17%. While military personnel with GSW have a favourable chance of nerve recovery, 75% of brachial plexus injuries that are associated with blast have poorer outcomes. Fixation occurred with either glenoid fractures or floating shoulders (10%); these were as a result of high velocity GSW or mounted blast ejections. There were no cases of deep soft tissue infection or osteomyelitis and all scapula fractures united.

Conclusion

Scapula fractures have a 20 times higher incidence in military personnel compared with the civilian population, occurring predominantly as a result of blast and GSW, and a higher than average ISS. These fractures are often associated with multiple injuries, including brachial plexus injuries, where those sustained from blast have less favourable outcome. High rates of union following fixation and low rates of infection are expected despite significant contamination and soft tissue loss.
Understanding the primary care paradigm: an experiential learning focus of the early veterinary graduate
Authors: Dixon William H R , Kinnison Tierney , May Stephen A
Published: September 2017

At a time where high levels of stress are reported in the veterinary profession, this study explores the challenges that veterinary graduates encounter when they enter general (first opinion) practice. Participants had written reflective accounts of their ‘Most Puzzling Cases’ for the postgraduate Professional Key Skills module of the Certificate in Advanced Veterinary Practice, offered by the Royal Veterinary College. Reasons that a case was puzzling, or became challenging, were thematically analysed. Fifteen summaries were analysed. Three core themes were identified: ‘clinical reasoning’, centred on the limitations of pattern recognition and the methods used to overcome this; the ‘veterinary healthcare system’, focusing on the need for continuity of care, time pressure and support in the transition to practice; and the ‘owner’, looking at the broader clinical skills needed to succeed in general practice. Clinical reasoning was raised as an issue; discussion of when pattern recognition is not appropriate and what to do in these cases was common. A lack of experience in general practice case types, and how to best operate in the resource‐constrained environment in which they present, is the likely cause of this, suggesting that a greater focus on the primary care paradigm is needed within veterinary education.
Field study on the safety and efficacy of intradermal versus intramuscular vaccination against Mycoplasma hyopneumoniae
Authors: Beffort Lisa , Weiß Christine , Fiebig Kerstin , Jolie Rika , Ritzmann Mathias , Eddicks Matthias
Published: September 2017

The present study compares the safety and efficacy of a needle‐free, intradermal Mycoplasma hyopneumoniae vaccine to an intramuscular one. 420 piglets (21+3 days of age) were randomly assigned to two vaccination groups (intradermal vaccination V1 (n=138), intramuscular vaccination V2 (n=144)) and one unvaccinated control group (CG, n=138). As safety parameters clinical observations, local injection site reactions (ISR) and rectal temperatures were assessed. Average daily weight gain (ADWG) and pneumonic lung lesions (LL) were measured as efficacy parameters. ISRs were minor in V1. After both vaccinations, no adverse impact on appetite was observed and mean rectal temperatures remained within physiological range. ADWG during the fattening period was significantly higher in vaccinated groups (V1: 913.4 g, V2: 924.5 g) compared with CG (875.6 g). No differences in ADWG were observed between V1 and V2. Vaccinated pigs had a significantly reduced mean extent of LL compared with CG. V1 was superior in reducing the extent and prevalence of LL compared with V2. These results reveal that a needle‐free intradermal vaccination is safe and efficacious in reducing both the prevalence and extent of lung lesions, as well as in improving performance parameters, in a farrow‐to‐finish farm with a late onset of M hyopneumoniae infection.
Transcerebral net exchange of vasoactive peptides and catecholamines during lipopolysaccharide-induced systemic inflammation in healthy humans
Authors: Berg Ronan M.G. , Taudorf Sarah , Bailey Damian M. , Dahl Rasmus H. , Lundby Carsten , Møller Kirsten
Published: September 2017

The systemic inflammatory response triggered by lipopolysaccharide (LPS) is associated with cerebral vasoconstriction, but the underlying mechanisms are unknown. We therefore examined whether a 4-hour intravenous LPS infusion (0.3 ng·kg−1) induces any changes in the transcerebral net exchange of the vasoactive peptides endothelin-1 (ET-1) and calcitonin-gene related peptide (CGRP) and catecholamines in human volunteers. Cerebral blood flow was measured by the Kety–Schmidt technique, and paired arterial-to-jugular venous blood samples were obtained for estimating the transcerebral exchange of ET-1, CGRP, and catecholamines by the Fick principle in 12 volunteers before and after LPS infusion. The cerebrovascular release of ET-1 was enhanced, whereas the transcerebral net exchange of CGRP and catecholamines was unaffected. Our findings thus point towards locally produced ET-1 within the cerebrovasculature as a contributor to cerebral vasoconstriction after LPS infusion.
Lutein Induces Autophagy via Beclin-1 Upregulation in IEC-6 Rat Intestinal Epithelial Cells
Authors: Chang Chi-Jen , Lin Ji-Fan , Hsiao Chien-Yu , Chang Hsun-Hao , Li Hsin-Ju , Chang Hsun-Hsien , Lee Gon-Ann , Hung Chi-Feng
Published: September 2017

Lutein is a carotenoid with anti-oxidant properties. Autophagy, an evolutionarily conserved catabolic cellular pathway for coping with stress conditions, is responsive to reactive oxygen species (ROS) and degrades damaged organelles. We previously demonstrated that lutein can induce anti-oxidant enzymes to relieve methotrexate-induced ROS stress. We therefore hypothesized that lutein, which activates ROS-scavenging enzymes, can also induce autophagy for cell survival. In this study, we demonstrated that lutein treatment attenuated the reduction in cell viability caused by H2O2. Lutein dose-dependently induced the processing of microtubule-associated protein light chain 3 (LC3)-II, an autophagy marker protein, and accumulation of LC3-positive puncta in rat intestinal IEC-6 cells. Furthermore, (a) direct observation of autophagosome formation through transmission electron microscopy, (b) upregulation of autophagy-related genes including ATG4A, ATG5, ATG7, ATG12, and beclin-1 (BENC1), and (c) increased BECN1/Bcl-2 ratio confirmed the induction of autophagy by lutein. The results revealed that bafilomycin-A1-induced inhibition of autophagy reduced cell viability and increased apoptosis in lutein-treated cells, indicating a protective role of lutein-induced autophagy. Lutein treatment also activated adenosine monophosphate–activated protein kinase (AMPK), c-Jun N-terminal kinase (JNK), and p-38, but had no effects on the induction of extracellular signal-related kinase or inhibition of mTOR; however, the inhibition of activated AMPK, JNK, or p-38 did not attenuate lutein-induced autophagy. Finally, increased BECN1 expression levels were detected in lutein-treated cells, and BECN1 knockdown abolished autophagy induction. These results suggest that lutein-induced autophagy was mediated by the upregulation of BECN1 in IEC-6 cells. We are the first to demonstrate that lutein induces autophagy. Elevated autophagy in lutein-treated IEC-6 cells may have a protective role against various stresses, and this warrants further investigation.
Cocommutative elements form a maximal commutative subalgebra in quantum matrices
Authors: Mészáros Szabolcs
Published: September 2017

In this paper, we prove that the subalgebras of cocommutative elements in the quantized coordinate rings of [Formula: see text], [Formula: see text] and [Formula: see text] are the centralizers of the trace [Formula: see text] in each algebra, for [Formula: see text] being not a root of unity. In particular, it is not only a commutative subalgebra as it was known before, but it is a maximal one.
Identification of potential inhibitors of PARP-1, a regulator of caspase-independent cell death pathway, fromWithania somniferaphytochemicals for combating neurotoxicity: A structure-basedin-silicostudy
Authors: Mukherjee Sumedha , Kumar Gaurav , Patnaik Ranjana
Published: September 2017

Poly (ADP-ribose) polymerase-1 (PARP-1) reverses DNA damage by repairing DNA nicks and breaks in the normal cellular environment. However, during abnormal conditions like stroke and other neurological disorders, overactivation of PARP-1 leads to neuronal cell death via a caspase-independent programmed cell death pathway. Strategies involving inhibition or knockout of PARP-1 have proved beneficial in combating neuro-cytotoxicity. In this study, we performed in-silico analysis of 27 phytochemicals of Withania somnifera (Ashwagandha), to investigate their inhibition efficiency against PARP-1. Out of 27 phytochemicals, we report 12 phytochemicals binding to the catalytic domain of PARP-1 with an affinity higher than FR257517, PJ34 and Talazoparib (highly potent inhibitors of the enzyme). Among these 12 compounds, five phytochemicals namely Stigmasterol, Withacnistin, Withaferin A, Withanolide G and Withanolide B show an exceptionally high binding affinity for the catalytic domain of PARP-1 and bind to the enzyme with similar hydrogen bond formation and hydrophobic interaction pattern as their inhibitors. All of these phytochemicals are BBB permeable so that they can be further developed into potential future neuro-therapeutic drugs against neurodegenerative disorders involving neuronal cell death.
Boundary Element Crystal Plasticity Method
Authors: Benedetti Ivano , Gulizzi Vincenzo , Mallardo Vincenzo
Published: September 2017

A three-dimensional (3D) boundary element method for small strains crystal plasticity is described. The method, developed for polycrystalline aggregates, makes use of a set of boundary integral equations for modeling the individual grains, which are represented as anisotropic elasto-plastic domains. Crystal plasticity is modeled using an initial strains boundary integral approach. The integration of strongly singular volume integrals in the anisotropic elasto-plastic grain-boundary equations are discussed. Voronoi-tessellation micro-morphologies are discretized using nonstructured boundary and volume meshes. A grain-boundary incremental/iterative algorithm, with rate-dependent flow and hardening rules, is developed and discussed. The method has been assessed through several numerical simulations, which confirm robustness and accuracy.
On a conjecture of George Beck
Authors: Chern Shane
Published: September 2017

In this paper, we prove a conjecture proposed by George Beck, which involves gap-free partitions and partitions with distinct parts.
Families of even non-congruent numbers with prime factors in each odd congruence class modulo eight
Authors: Reinholz Lindsey , Spearman Blair K. , Yang Qiduan
Published: September 2017

New families of even non-congruent numbers with arbitrarily many distinct prime factors are presented. Methods for generating even non-congruent numbers from existing non-congruent numbers are also given. These results yield new even non-congruent numbers whose factorizations contain primes in all four odd congruence classes modulo eight.