bluuebunny/crossref_metadata_2025 huggingface dataset:
Greater endurance capacity and improved dyspnoea with acute oxygen supplementation in idiopathic pulmonary fibrosis patients without resting hypoxaemia
Authors: Dowman Leona M. , McDonald Christine F. , Bozinovski Steven , Vlahos Ross , Gillies Rebecca , Pouniotis Dodie , Hill Catherine J. , Goh Nicole S.L. , Holland Anne E
Published: February 2017

ABSTRACT

Background and objective

Supplemental oxygen is commonly prescribed in patients with idiopathic pulmonary fibrosis (IPF), although its benefits have not been proven. The aims of this study were to investigate the effect of oxygen on oxidative stress, cytokine production, skeletal muscle metabolism and physiological response to exercise in IPF.

Methods

Eleven participants with IPF received either oxygen, at an FiO2
of 0.50, or compressed air for 1 h at rest and during a cycle endurance test at 85% of peak work rate. Blood samples collected at rest and during exercise were analysed for markers of oxidative stress, skeletal muscle metabolism and cytokines. The protocol was repeated a week later with the alternate intervention.

Results

Compared with air, oxygen did not adversely affect biomarker concentrations at rest and significantly improved endurance time (mean difference = 99 ± 81s, P = 0.002), dyspnoea (−1 ± 1 U, P = 0.02), systolic blood pressure (BP; −11 ± 11 mm Hg, P = 0.006), nadir oxyhaemoglobin saturation (SpO2
; 8 ± 6%, P = 0.001), SpO2
at 2‐min (7 ± 6%, P = 0.003) and 5‐min isotimes (5 ± 3, P < 0.001) and peak exercise xanthine concentrations (−42 ± 73 µmol/L, P = 0.03). Air significantly increased IL‐10 (5 ± 5 pg/mL, P = 0.04) at 2‐min isotime. Thiobarbituric acid‐reactive substances (TBARs), IL‐6, TNF‐α, creatine kinase, lactate, heart rate and fatigue did not differ between the two interventions at any time point.

Conclusion

In patients with IPF, breathing oxygen at FiO2 of 0.50 at rest seems safe. During exercise, oxygen improves exercise tolerance, alleviates exercise‐induced hypoxaemia and reduces dyspnoea. A potential relationship between oxygen administration and improved skeletal muscle metabolism should be explored in future studies.
A 7‐year follow‐up study of obstructive sleep apnoea in healthy elderly: The PROOF cohort study
Authors: Sforza Emilia , Hupin David , Pichot Vincent , Barthélémy Jean Claude , Roche Frédéric
Published: February 2017

ABSTRACT

Background and objective

Clinical and epidemiological cohort studies have shown that obstructive sleep apnoea (OSA) is a common but largely undiagnosed disorder in senior subjects, where progressive deterioration of the pathology would be expected as a consequence of the ageing processes. Our study examines the longitudinal progression of OSA over a 7‐year period in a community‐based sample of healthy subjects.

Methods

The sample consisted of 284 volunteers, aged >65 years (52% women, 48% men) accepting clinical and instrumental follow‐up at 7 years. OSA was defined as an apnoea–hypopnoea index (AHI) of ≥15.

Results

Between evaluations in the total sample, AHI slightly decreased from 17.8 ± 14 to 16.7 ± 11 with a decrease affecting more the hypopnoea index (P < 0.001) and associated with significant changes (P < 0.001) in all indices of hypoxaemia. While in the non‐OSA group there was a slight but significant increase of AHI, a significant AHI decrease was noted in mild‐moderate patients (P < 0.01) and a significant rise of nocturnal hypoxaemia in severe OSA patients (P < 0.001). The AHI decrease was not associated with clinical, weight, metabolic and blood pressure changes between the two evaluations; the baseline AHI value being the only factor correlated to the degree of AHI decline.

Conclusions

In elderlies, the severity and prevalence of OSA decrease progressively with ageing without effect of factors commonly influencing OSA severity. This trend may support the hypothesis that in healthy elderly, OSA is a phenomenon related to ageing.
Mobilization in the European Public Sphere: The Struggle Over Genetically Modified Organisms
Authors: Tosun Jale , Schaub Simon
Published: February 2017

The objective of this study is to investigate the extent to which supporters and opponents at the European Union (EU) level strive to mobilize the public with regard the issue of genetically modified organisms (GMOs). To this end, it addresses two research questions: First, to which concepts do GMO opponents and supporters refer when seeking to mobilize the public? Second, do GMO opponents and supporters differ in the coherence of the concepts they use to attain public mobilization? The empirical findings show that the pro‐GMO coalition is composed of biotechnology companies as well as representatives of Argentina, Canada, the United Kingdom, the United States, and the World Trade Organization. The anti‐GMO coalition consists of environmental nongovernmental organizations and representatives from most of the EU member states. Altogether, the anti‐GMO coalition has been more coherent in the concepts they invoke in the last few years.
Climate Adaptation in Canada: Governing a Complex Policy Regime
Authors: Henstra Daniel
Published: February 2017

Climate adaptation is a complex policy area, in which knowledge, authority, and resources are fragmented among numerous public agencies, multiple levels of government, and a wide range of nongovernmental actors. Mobilizing and coordinating disparate public and private efforts is a key challenge in this policy domain, and this has focused research attention on the governance of adaptation, including the dynamics of interaction among interests and the institutions that facilitate collective action. This paper contributes to the study of adaptation governance by adopting the policy regimes perspective, an analytical framework designed to make sense of the loose governing arrangements surrounding complex, fragmented problems. The perspective's constructs are applied to a longitudinal case study of adaptation governance in Canada, which identifies, analyzes, and evaluates the policy ideas, institutions, and interests that comprise Canada's adaptation policy regime.
Cultural Schemas of Religion, Science, and Law in Talk About Social Controversies
Authors: Edgell Penny , Hull Kathleen E.
Published: February 2017

We analyze cultural schemas of religion, science, and law reflected in the way ordinary citizens discuss contemporary social controversies and assess whether these schemas accord with a modernization narrative or whether people's experiences with each of these institutional arenas lead them to adopt realistic or critical schemas not predicted by modernization accounts. Focus group participants in three metropolitan areas were asked to talk about one of three vignettes on faith‐based prison ministries, parents’ refusal of medical treatment for a child on religious grounds, or preimplantation genetic diagnosis of human embryos. We find that people's everyday experiences, grounded in specific institutional contexts, produce perceptions of the domains of religion, science, and law that are not fully captured by the modernization account. Further, our findings illustrate that schemas of law, science, and religion are varied and evoked by social context and the specific issues under consideration. Schemas that do not fit the modernization framework provide a way for people to address concerns about power and effectively level the playing field between more and less rationalized social domains. Future research on a broader range of issues is needed to develop a theory of when different schemas of law, science, and religion are activated.
Using Changes in U.S. Immigration Laws to Estimate the Effect of Deportations on Crime in Latin America and the Caribbean
Authors: Blake Garfield O.
Published: February 2017

Objectives

The objective of this article is to obtain estimates of the effect of criminal deportees from the United States on home country crime that are not affected by the presence of simultaneity. Simultaneity between criminal deportation from the United States and crime rates in Latin America and the Caribbean (LAC) makes it difficult to isolate the causal effect of changes in the number of criminal deportees from the United States on crime in LAC.

Method

To break that simultaneity, this article uses the timing of changes to U.S. immigration laws as an instrument for changes in the number of criminal deportees.

Result

Increases in criminal deportations are shown to be disproportionately concentrated in years when there are changes to U.S. immigration laws. The resulting elasticity is two times greater than the OLS estimate. One of every 14 prisoners deported as a result of changes in U.S. immigration legislation is associated with one homicide per year in the receiving country.

Conclusion

The process of accomplishing deportation can be greatly improved if the United States provides the receiving countries with more information on deportees, including more detailed criminal records and increased assistance with the resettlement and reintegration process, especially if they are not allowed to be incarcerated upon returning home.
The Structural and Cultural Role to the Family House Hold of Self-employment Woman in Malang Regency, Indonesia
Authors: Wisadirana Darsono
Published: February 2017

Family is also the first pillar to meet the social, economic, psychological and culture aspect to the individual. In prostitution aspect, someone who decides to be self-employment woman can be known from the socialization style in the family. Because of that, it is important to know about family role and function in solving prostitution problem. Therefore, the problem is how the structural and cultural role is occupied by each family member in the daily life of house hold.This research aims to analyze the process of someone to be self-employment woman from the aspect of instilling the moral and norm by each family member, analyze the social relation in the family, one of whose member is a self-employment woman, and analyze the function which is acted by each member to the self-employment woman. This research used Functional Imperatives Talcott Parson theory to analyze the structural and cultural role of self-employment woman’s family. The methodology used in this case was qualitative research design.The result of the research shows the economic factor. Besides the factor of young marriage culture which causes the divorce. After divorce, the women start to work as self-employment woman. Lacking of the education awareness can be one of the causes in increasing the number of self-employment woman.Lacking of communication among the family can cause the parents are not able to keep the children from social deviation. Social deviation which has been occupied for long time can be human habit and common activity in society.
Breaking Open the Closed Nature of Japanese Forestry
Authors: Mizuno Katsushi , Igusa Go , Takeda Eiji , Doi Takumu , Omata Jun
Published: February 2017

We have applied the system-wide approach, a theory developed by the economist H. Theil, to input-output analysis to demonstrate the closed nature of forestry in Japan. We have also advocated the necessity of opening up the forestry industry in order to optimize production (minimize costs). Specifically, with the methodology employed here, we calculated input coefficients for Japanese forestry using input-output tables. We compared actual input coefficients with the input coefficients calculated to achieve optimal production. The results revealed that intermediate product transactions among forestry industry members were about 12% above the amount required for forestry to achieve optimal production, while intermediate product transactions with other industries were about 11% too low. This means that forest-related commissioned projects are carried out primarily by forestry players, so work is not being allocated to other industries. The results lead us to the conclusion that forestry in Japan is closed and that commissioned projects should be allocated to other sectors. We show compelling examples from prior research on opening up forestry to the construction industry and nonprofit organizations. Opening forestry projects to other sectors will improve forestry technologies in those sectors and lead to technological innovation in Japanese forestry.
Rapid frequency‐dependent changes in free mitochondrial calcium concentration in rat cardiac myocytes
Authors: Wüst Rob C. I. , Helmes Michiel , Martin Jody L. , van der Wardt Thomas J. T. , Musters René J. P. , van der Velden Jolanda , Stienen Ger J. M.
Published: February 2017

Key points

Calcium ions regulate mitochondrial ATP production and contractile activity and thus play a pivotal role in matching energy supply and demand in cardiac muscle.

The magnitude and kinetics of the changes in free mitochondrial calcium concentration in cardiac myocytes are largely unknown.

Rapid stimulation frequency‐dependent increases but relatively slow decreases in free mitochondrial calcium concentration were observed in rat cardiac myocytes. This asymmetry caused a rise in the mitochondrial calcium concentration with stimulation frequency.

These results provide insight into the mechanisms of mitochondrial calcium uptake and release that are important in healthy and diseased myocardium.

Calcium ions regulate mitochondrial ATP production and contractile activity and thus play a pivotal role in matching energy supply and demand in cardiac muscle. Little is known about the magnitude and kinetics of the changes in free mitochondrial calcium concentration in cardiomyocytes. Using adenoviral infection, a ratiometric mitochondrially targeted Förster resonance energy transfer (FRET)‐based calcium indicator (4mtD3cpv, MitoCam) was expressed in cultured adult rat cardiomyocytes and the free mitochondrial calcium concentration ([Ca2+]m) was measured at different stimulation frequencies (0.1–4 Hz) and external calcium concentrations (1.8–3.6 mm) at 37°C. Cytosolic calcium concentrations were assessed under the same experimental conditions in separate experiments using Fura‐4AM. The increases in [Ca2+]m during electrical stimulation at 0.1 Hz were rapid (rise time = 49 ± 2 ms), while the decreases in [Ca2+]m occurred more slowly (decay half time = 1.17 ± 0.07 s). Model calculations confirmed that this asymmetry caused the rise in [Ca2+]m during diastole observed at elevated stimulation frequencies. Inhibition of the mitochondrial sodium–calcium exchanger (mNCE) resulted in a rise in [Ca2+]m at baseline and, paradoxically, in an acceleration of Ca2+ release. In conclusion: rapid increases in [Ca2+]m allow for fast adjustment of mitochondrial ATP production to increases in myocardial demand on a beat‐to‐beat basis and mitochondrial calcium release depends on mNCE activity and mitochondrial calcium buffering.
Effect of scan speed on moisture barrier properties of aluminum oxide using spatial atomic layer deposition
Authors: Shin Seokyoon , Choi Hagyoung , Ham Giyul , Park Joohyun , Lee Juhyun , Choi Hyeongsu , Lee Seungjin , Kim Hyunjung , Jeon Hyeongtag
Published: February 2017

Atomic layer deposition (ALD) has been shown to produce high-quality thin films with superior moisture barrier performance on polymer substrates. However, the conventional time-sequenced mode is incompatible with industrial needs due to its low deposition rate. One solution to overcome this throughput issue is to use spatial ALD. Recently, various approaches have been reported. The authors also developed a fast spatial ALD system using an industrial 2G (370 × 470 mm2) glass substrate. Using this system, the authors investigated the effect of a scan speed on the moisture barrier properties of aluminum oxide (Al2O3) thin films. While the scan speeds were varied over a wide range of 100–800 mm/s, the water vapor transmission rate increased only slightly, from 1.4 × 10−3 to 3.0 × 10−3 g/m2/day. At a scan speed of 800 mm/s, the deposition rate was 70 Å/min, which was about seven times higher than that of conventional ALD. Moreover, the physical and chemical properties of the thin films slightly worsened with the increase in the scan speed. Based on the above results, Al2O3 thin films prepared using the newly developed high-throughput and scalable spatial ALD system are a promising candidate for thin film encapsulation of large-scale flexible electronic applications.
Enhanced photocathode performance through optimization of film thickness and substrate
Authors: Alexander Anna , Moody Nathan A. , Bandaru Prabhakar R.
Published: February 2017

It is shown that the efficiency of photoelectron emission may be enhanced, several-fold, through optimization of photocathode film thickness and appropriate substrate configuration. Such an enhancement is based on a careful consideration of wave interference effects in the film and the consequent modulation of the absorption profiles and electron emission probabilities. The inadequacy of the well-known Lambert-Beer law for modeling photon absorption in thin films is also discussed.
The influence of temporally varying noise from seismic air guns on the detection of underwater sounds by seals
Authors: Sills Jillian M. , Southall Brandon L. , Reichmuth Colleen
Published: February 2017

Standard audiometric data are often applied to predict how noise influences hearing. With regard to auditory masking, critical ratios—obtained using tonal signals and flat-spectrum maskers—can be combined with noise spectral density levels derived from 1/3-octave band levels to predict signal amplitudes required for detection. However, the efficacy of this conventional model of masking may vary based on features of the signal and noise in question. The ability of resource managers to quantify masking from intermittent seismic noise is relevant due to widespread geophysical exploration. To address this, spotted and ringed seals with previously measured critical ratios were trained to detect low-frequency tonal signals within seismic pulses recorded 1 and 30 km from an operational air gun array. The conventional model of masking accurately predicted the extent of masking only in certain cases. When noise amplitude varied significantly in time, the results suggested that detection was driven by higher signal-to-noise ratios within time windows shorter than the full signal duration. This study evaluates when it is appropriate to use average noise levels and critical ratios to predict auditory masking experienced by marine mammals, and suggests how masking models can be improved by incorporating time-based analyses of signals and noise.
A divergent population of autoantigen-responsive CD4+T cells in infants prior to β cell autoimmunity
Authors: Heninger Anne-Kristin , Eugster Anne , Kuehn Denise , Buettner Florian , Kuhn Matthias , Lindner Annett , Dietz Sevina , Jergens Sibille , Wilhelm Carmen , Beyerlein Andreas , Ziegler Anette-G. , Bonifacio Ezio
Published: February 2017

A divergent autoantigen-responsive CD4+T cell population is present in infancy, before autoimmunity in type 1 diabetes.
Beware! Are bacteria raising your oxidative stress?
Authors: Kashyap Purna
Published: February 2017

Peptostreptococcus anaerobius
, enriched in patients with colon cancer, induces cellular proliferation and dysplasia by toll-like receptor (TLR) 2– and TLR4-dependent increase in oxidative stress and cholesterol biosynthesis.
Addicted to love?
Authors: Stanley Sarah A.
Published: February 2017

Reproductive hormones alter activity in neural circuits linking reward and social interactions.
Porous polymeric platform repairs primates after spinal cord injury
Authors: Ulery Bret D.
Published: February 2017

Amine-containing polymers immobilized on mesh and placed at trauma sites scavenge biomolecules that initiate a damaging immune response.
Analysis of Serial Isolates of
mcr-1
-Positive Escherichia coli Reveals a Highly Active IS
Apl1
Transposon
Authors: Snesrud Erik , Ong Ana C. , Corey Brendan , Kwak Yoon I. , Clifford Robert , Gleeson Todd , Wood Shannon , Whitman Timothy J. , Lesho Emil P. , Hinkle Mary , McGann Patrick
Published: February 2017

The emergence of a transferable colistin resistance gene (
mcr-1
) is of global concern. The insertion sequence IS
Apl1
is a key component in the mobilization of this gene, but its role remains poorly understood. Six
Escherichia coli
isolates were cultured from the same patient over the course of 1 month in Germany and the United States after a brief hospitalization in Bahrain for an unconnected illness. Four carried
mcr-1
as determined by real-time PCR, but two were negative. Two additional
mcr-1
-negative
E. coli
isolates were collected during follow-up surveillance 9 months later. All isolates were analyzed by whole-genome sequencing (WGS). WGS revealed that the six initial isolates were composed of two distinct strains: an initial ST-617
E. coli
strain harboring
mcr-1
and a second, unrelated,
mcr-1
-negative ST-32
E. coli
strain that emerged 2 weeks after hospitalization. Follow-up swabs taken 9 months later were negative for the ST-617 strain, but the
mcr-1
-negative ST-32 strain was still present.
mcr-1
was associated with a single copy of IS
Apl1
, located on a 64.5-kb IncI2 plasmid that shared >95% homology with other
mcr-1
IncI2 plasmids. IS
Apl1
copy numbers ranged from 2 for the first isolate to 6 for the final isolate, but IS
Apl1
movement was independent of
mcr-1
. Some movement was accompanied by gene disruption, including the loss of genes encoding proteins involved in stress responses, arginine catabolism, and
l
-arabinose utilization. These data represent the first comprehensive analysis of IS
Apl1
movement in serial clinical isolates and reveal that, under certain conditions, IS
Apl1
is a highly active IS element whose movement may be detrimental to the host cell.
Novel Bacterial Topoisomerase Inhibitors with Potent Broad-Spectrum Activity against Drug-Resistant Bacteria
Authors: Charrier Cédric , Salisbury Anne-Marie , Savage Victoria J. , Duffy Thomas , Moyo Emmanuel , Chaffer-Malam Nathan , Ooi Nicola , Newman Rebecca , Cheung Jonathan , Metzger Richard , McGarry David , Pichowicz Mark , Sigerson Ralph , Cooper Ian R. , Nelson Gary , Butler Hayley S. , Craighead Mark , Ratcliffe Andrew J. , Best Stuart A. , Stokes Neil R.
Published: February 2017

The novel bacterial topoisomerase inhibitor class is an investigational type of antibacterial inhibitor of DNA gyrase and topoisomerase IV that does not have cross-resistance with the quinolones. Here, we report the evaluation of the
in vitro
properties of a new series of this type of small molecule. Exemplar compounds selectively and potently inhibited the catalytic activities of
Escherichia coli
DNA gyrase and topoisomerase IV but did not block the DNA breakage-reunion step. Compounds showed broad-spectrum inhibitory activity against a wide range of Gram-positive and Gram-negative pathogens, including biodefence microorganisms and
Mycobacterium tuberculosis
. No cross-resistance with fluoroquinolone-resistant
Staphylococcus aureus
and
E. coli
isolates was observed. Measured MIC
90
values were 4 and 8 μg/ml against a panel of contemporary multidrug-resistant isolates of
Acinetobacter baumannii
and
E. coli
, respectively. In addition, representative compounds exhibited greater antibacterial potency than the quinolones against obligate anaerobic species. Spontaneous mutation rates were low, with frequencies of resistance typically <10
−8
against
E. coli
and
A. baumannii
at concentrations equivalent to 4-fold the MIC. Compound-resistant
E. coli
mutants that were isolated following serial passage were characterized by whole-genome sequencing and carried a single Arg38Leu amino acid substitution in the GyrA subunit of DNA gyrase. Preliminary
in vitro
safety data indicate that the series shows a promising therapeutic index and potential for low human ether-a-go-go-related gene (hERG) inhibition (50% inhibitory concentration [IC
50
], >100 μM). In summary, the compounds' distinct mechanism of action relative to the fluoroquinolones, whole-cell potency, low potential for resistance development, and favorable
in vitro
safety profile warrant their continued investigation as potential broad-spectrum antibacterial agents.
Evaluation of
para
-Aminosalicylic Acid as a Substrate of Multiple Solute Carrier Uptake Transporters and Possible Drug Interactions with Nonsteroidal Anti-inflammatory Drugs
In Vitro
Authors: Parvez M. Masud , Shin Ho Jung , Jung Jin Ah , Shin Jae-Gook
Published: February 2017

para
-Aminosalicylic acid (PAS) is a second-line antituberculosis drug that has been used to treat multidrug-resistant and extensively drug-resistant tuberculosis for more than 60 years. Renal secretion and glomerular filtration are the major pathways for the elimination of PAS. We comprehensively studied PAS transport by using cell lines that overexpressed various transporters and found that PAS acts as a novel substrate of an organic anionic polypeptide (OATP1B1), organic cationic transporters (OCT1 and OCT2), and organic anion transporters (OAT1 and OAT3) but is not a substrate of any ATP-binding cassette (ABC) transporters. Net PAS uptake was measured, and the transport affinities (

K
m

values) for OATP1B1, OCT1, OCT2, OAT1, and OAT3 were found to be 50.0, 20.3, 28.7, 78.1, and 100.1 μM, respectively. The net uptake rates suggested that renal OAT1 and OAT3 play relatively major roles in PAS elimination. The representative inhibitors rifampin for OATP1B1, probenecid for OAT1 and OAT3, and verapamil for OCT1 and OCT2 greatly inhibited PAS uptake, suggesting that PAS is dependent on multiple transporters for uptake. We also evaluated nonsteroidal anti-inflammatory drugs (NSAIDs), proton pump inhibitors (PPIs), and metformin for the inhibition of PAS uptake via these transporters. Half-maximal (50%) inhibitory concentrations (IC
50
s) were kinetically determined and used to predict the drug-drug interactions (DDIs) affecting these transporters' activity toward PAS. We found that rifampin, probenecid, ibuprofen, naproxen, cimetidine, and quinidine each exhibited a significant potential for
in vivo
DDIs with PAS. In this study, PAS was found to be a novel substrate of several transporters, and drugs that inhibit these transporters can reduce PAS elimination.
The Emerging Pathogen Candida auris: Growth Phenotype, Virulence Factors, Activity of Antifungals, and Effect of SCY-078, a Novel Glucan Synthesis Inhibitor, on Growth Morphology and Biofilm Formation
Authors: Larkin Emily , Hager Christopher , Chandra Jyotsna , Mukherjee Pranab K. , Retuerto Mauricio , Salem Iman , Long Lisa , Isham Nancy , Kovanda Laura , Borroto-Esoda Katyna , Wring Steve , Angulo David , Ghannoum Mahmoud
Published: February 2017

Candida
auris
, a new multidrug-resistant
Candida
spp. which is associated with invasive infection and high rates of mortality, has recently emerged. Here, we determined the virulence factors (germination, adherence, biofilm formation, phospholipase and proteinase production) of 16
C. auris
isolates and their susceptibilities to 11 drugs belonging to different antifungal classes, including a novel orally bioavailable 1,3-β-
d
-glucan synthesis inhibitor (SCY-078). We also examined the effect of SCY-078 on the growth, ultrastructure, and biofilm-forming abilities of
C. auris
. Our data showed that while the tested strains did not germinate, they did produce phospholipase and proteinase in a strain-dependent manner and had a significantly reduced ability to adhere and form biofilms compared to that of
Candida albicans
(
P
= 0.01).
C. auris
isolates demonstrated reduced susceptibility to fluconazole and amphotericin B, while, in general, they were susceptible to the remaining drugs tested. SCY-078 had an MIC
90
of 1 mg/liter against
C. auris
and caused complete inhibition of the growth of
C. auris
and
C. albicans
. Scanning electron microscopy analysis showed that SCY-078 interrupted
C. auris
cell division, with the organism forming abnormal fused fungal cells. Additionally, SCY-078 possessed potent antibiofilm activity, wherein treated biofilms demonstrated significantly reduced metabolic activity and a significantly reduced thickness compared to the untreated control (
P
< 0.05 for both comparisons). Our study shows that
C. auris
expresses several virulence determinants (albeit to a lesser extent than
C. albicans
) and is resistant to fluconazole and amphotericin B. SCY-078, the new orally bioavailable antifungal, had potent antifungal/antibiofilm activity against
C. auris
, indicating that further evaluation of this antifungal is warranted.
Streptococcus mitis and S. oralis Lack a Requirement for CdsA, the Enzyme Required for Synthesis of Major Membrane Phospholipids in Bacteria
Authors: Adams Hannah M. , Joyce Luke R. , Guan Ziqiang , Akins Ronda L. , Palmer Kelli L.
Published: February 2017

Synthesis and integrity of the cytoplasmic membrane are fundamental to cellular life. Experimental evolution studies have hinted at unique physiology in the Gram-positive bacteria
Streptococcus mitis
and
S. oralis
. These organisms commonly cause bacteremia and infectious endocarditis (IE) but are rarely investigated in mechanistic studies of physiology and evolution. Unlike in other Gram-positive pathogens, high-level (MIC ≥ 256 μg/ml) daptomycin resistance rapidly emerges in
S. mitis
and
S. oralis
after a single drug exposure. In this study, we found that inactivating mutations in
cdsA
are associated with high-level daptomycin resistance in
S. mitis
and
S. oralis
IE isolates. This is surprising given that
cdsA
is an essential gene for life in commonly studied model organisms. CdsA is the enzyme responsible for the synthesis of CDP-diacylglycerol, a key intermediate for the biosynthesis of all major phospholipids in prokaryotes and most anionic phospholipids in eukaryotes. Lipidomic analysis by liquid chromatography-mass spectrometry (LC-MS) showed that daptomycin-resistant strains have an accumulation of phosphatidic acid and completely lack phosphatidylglycerol and cardiolipin, two major anionic phospholipids in wild-type strains, confirming the loss of function of CdsA in the daptomycin-resistant strains. To our knowledge, these daptomycin-resistant streptococci represent the first model organisms whose viability is CdsA independent. The distinct membrane compositions resulting from the inactivation of
cdsA
not only provide novel insights into the mechanisms of daptomycin resistance but also offer unique opportunities to study the physiological functions of major anionic phospholipids in bacteria.
Immunoactive Clostridial Membrane Vesicle Production Is Regulated by a Sporulation Factor
Authors: Obana Nozomu , Nakao Ryoma , Nagayama Kyoko , Nakamura Kouji , Senpuku Hidenobu , Nomura Nobuhiko
Published: February 2017

Recently, many Gram-positive bacteria as well as Gram-negative bacteria have been reported to produce membrane vesicles (MVs), but little is known regarding the regulators involved in MV formation. We found that a Gram-positive anaerobic pathogen,
Clostridium perfringens
, produces MVs predominantly containing membrane proteins and cell wall components. These MVs stimulated proinflammatory cytokine production in mouse macrophage-like cells. We suggested that MVs induced interleukin-6 production through the Toll-like receptor 2 (TLR2) signaling pathway. Thus, the MV could have a role in the bacterium-host interaction and bacterial infection pathogenesis. Moreover, we found that the sporulation master regulator gene
spo0A
was required for vesiculogenesis. A conserved, phosphorylated aspartate residue of Spo0A was indispensable for MV production, suggesting that the phosphorylation of Spo0A triggers MV production. Multiple orphan sensor kinases necessary for sporulation were also required to maximize MV production. These findings imply that
C. perfringens
actively produces immunoactive MVs in response to the environment changing, as recognized by membrane-spanning sensor kinases and by modulating the phosphorylation level of Spo0A.
Raising the Alarmone: Within-Host Evolution of Antibiotic-Tolerant
Enterococcus faecium
Authors: Van Tyne Daria , Gilmore Michael S.
Published: February 2017

Enterococci are ancient commensal bacteria that recently emerged as leading causes of antibiotic-resistant, hospital-acquired infection. Vancomycin-resistant enterococci (VRE) epitomize why drug-resistant enterococcal infections are a problem: VRE readily colonize the antibiotic-perturbed gastrointestinal (GI) tract where they amplify to large numbers, and from there, they infect other body sites, including the bloodstream, urinary tract, and surgical wounds. VRE are resistant to many antimicrobials and host defenses, which facilitates establishment at the site of infection and confounds therapeutic clearance. Having evolved to colonize the GI tract, VRE are comparatively ill adapted to the human bloodstream. A recent study by Honsa and colleagues (E. S. Honsa et al., mBio 8:e02124-16, 2017,
https://doi.org/10.1128/mBio.02124-16
) found that a strain of vancomycin-resistant
Enterococcus faecium
evolved antibiotic tolerance within the bloodstream of an immunocompromised host by activating the stringent response through mutation of
relA
. Precisely how VRE colonize and infect and the selective pressures that led to the outgrowth of
relA
mutants are the subjects of ongoing research.
Mycobacterium tuberculosis
Proteasome Accessory Factor A (PafA) Can Transfer Prokaryotic Ubiquitin-Like Protein (Pup) between Substrates
Authors: Zhang Susan , Burns-Huang Kristin E. , Janssen Guido V. , Li Huilin , Ovaa Huib , Hedstrom Lizbeth , Darwin K. Heran
Published: February 2017

The protein degradation machinery of
Mycobacterium tuberculosis
includes a proteasome and a ubiquitin-like protein (Pup). Proteasome accessory factor A (PafA) attaches Pup to proteins to target them for degradation by the proteasome. Free Pup is unstable and never observed in extracts of
M. tuberculosis
, an observation that led us to hypothesize that PafA may need alternative sources of Pup. Here, we show that PafA can move Pup from one proteasome substrate, inositol 1-phosphate synthetase (Ino1), to two different proteins, malonyl coenzyme A (CoA)-acyl carrier protein transacylase (FabD) and lonely guy (Log). This apparent “transpupylation” reaction required a previously unrecognized depupylase activity in PafA, and, surprisingly, this depupylase activity was much more efficient than the activity of the dedicated depupylase Dop (deamidase of Pup). Thus, PafA can potentially use both newly synthesized Pup and recycled Pup to doom proteins for degradation.

IMPORTANCE
Unlike eukaryotes, which contain hundreds of ubiquitin ligases, Pup-containing bacteria appear to have a single ligase to pupylate dozens if not hundreds of different proteins. The observation that PafA can depupylate and transpupylate
in vitro
offers new insight into how protein stability is regulated in proteasome-bearing bacteria. Importantly, PafA and the dedicated depupylase Dop are each required for the full virulence of
Mycobacterium tuberculosis
. Thus, inhibition of both enzymes may be extremely attractive for the development of therapeutics against tuberculosis.
Fallacy of the Unique Genome: Sequence Diversity within Single
Helicobacter pylori
Strains
Authors: Draper Jenny L. , Hansen Lori M. , Bernick David L. , Abedrabbo Samar , Underwood Jason G. , Kong Nguyet , Huang Bihua C. , Weis Allison M. , Weimer Bart C. , van Vliet Arnoud H. M. , Pourmand Nader , Solnick Jay V. , Karplus Kevin , Ottemann Karen M.
Published: February 2017

Many bacterial genomes are highly variable but nonetheless are typically published as a single assembled genome. Experiments tracking bacterial genome evolution have not looked at the variation present at a given point in time. Here, we analyzed the mouse-passaged
Helicobacter pylori
strain SS1 and its parent PMSS1 to assess intra- and intergenomic variability. Using high sequence coverage depth and experimental validation, we detected extensive genome plasticity within these
H. pylori
isolates, including movement of the transposable element IS
607
, large and small inversions, multiple single nucleotide polymorphisms, and variation in
cagA
copy number. The
cagA
gene was found as 1 to 4 tandem copies located off the
cag
island in both SS1 and PMSS1; this copy number variation correlated with protein expression. To gain insight into the changes that occurred during mouse adaptation, we also compared SS1 and PMSS1 and observed 46 differences that were distinct from the within-genome variation. The most substantial was an insertion in
cagY
, which encodes a protein required for a type IV secretion system function. We detected modifications in genes coding for two proteins known to affect mouse colonization, the HpaA neuraminyllactose-binding protein and the FutB α-1,3 lipopolysaccharide (LPS) fucosyltransferase, as well as genes predicted to modulate diverse properties. In sum, our work suggests that data from consensus genome assemblies from single colonies may be misleading by failing to represent the variability present. Furthermore, we show that high-depth genomic sequencing data of a population can be analyzed to gain insight into the normal variation within bacterial strains.

IMPORTANCE
Although it is well known that many bacterial genomes are highly variable, it is nonetheless traditional to refer to, analyze, and publish “the genome” of a bacterial strain. Variability is usually reduced (“only sequence from a single colony”), ignored (“just publish the consensus”), or placed in the “too-hard” basket (“analysis of raw read data is more robust”). Now that whole-genome sequences are regularly used to assess virulence and track outbreaks, a better understanding of the baseline genomic variation present within single strains is needed. Here, we describe the variability seen in typical working stocks and colonies of pathogen
Helicobacter pylori
model strains SS1 and PMSS1 as revealed by use of high-coverage mate pair next-generation sequencing (NGS) and confirmed by traditional laboratory techniques. This work demonstrates that reliance on a consensus assembly as “the genome” of a bacterial strain may be misleading.
Two faces of gamma–delta mycosis fungoides: before and after renal transplantation
Authors: Prillinger Knut Erich , Trautinger Franz , Kitzwögerer Melitta , Eder Johanna
Published: February 2017

We describe a patient with a 30-year history of mycosis fungoides (MF) and renal transplantation performed 3 years before he presented with an ulcerated tumour in the lumbosacral area. Biopsy revealed a lymphatic infiltrate of medium-sized, pleomorphic T cells expressing the gamma–delta T-cell receptor. Radiological staging and bone marrow biopsy revealed no extracutaneous involvement. Despite reduction in systemic immunosuppressants, total skin electron beam radiotherapy and systemic chemotherapy, the disease followed a highly aggressive course and the patient died 31 years after initial diagnosis of MF. Pre-existing MF is not listed as a contraindication for solid organ transplantation. With an ever-increasing number of organ recipients, the number of MF patients undergoing solid organ transplantation will be likely to increase. Systematic collection and analysis of such cases is thus warranted to lead to a better understanding to what kind MF gets influenced by solid organ transplantation and ongoing immunosuppression.
Eighty-three per cent of elite athletes return to preinjury sport after anterior cruciate ligament reconstruction: a systematic review with meta-analysis of return to sport rates, graft rupture rates and performance outcomes
Authors: Lai Courtney C H , Ardern Clare L , Feller Julian A , Webster Kate E
Published: February 2017

Objectives

The primary objective was to calculate the rate of return to sport (RTS) following anterior cruciate ligament (ACL) reconstruction in elite athletes. Secondary objectives were to estimate the time taken to RTS, calculate rates of ACL graft rupture, evaluate postsurgical athletic performance and identify determinants of RTS.

Design

Pooled RTS and graft rupture rates were calculated using random effects proportion meta-analysis. Time to RTS, performance data and determinants of RTS were synthesised descriptively.

Data sources

MEDLINE, EMBASE, AMED, CINAHL, AMI, PEDro, SPORTDiscus and The Cochrane Library were searched from inception to 19 January 2016. Hand searching of 10 sports medicine journals and reference checking were also performed.

Eligibility criteria for selecting studies

Studies were included if they reported the ratio of elite athletes who returned to their preinjury level of sport following ACL reconstruction. Twenty-four studies were included.

Results

The pooled RTS rate was 83% (95% CI 77% to 88%). The mean time to RTS ranged from 6 to 13 months. The pooled graft rupture rate was 5.2% (95% CI 2.8% to 8.3%). Six out of nine studies that included a noninjured control group found no significant deterioration in athletic performance following ACL reconstruction. Indicators of greater athletic skill or value to the team were associated with RTS.

Summary and conclusions

Eighty-three per cent of elite athletes returned to sport following ACL reconstruction, while 5.2% sustained a graft rupture. Most athletes who returned to sport performed comparably with matched, uninjured controls. This information may assist in guiding expectations of athletes and clinicians following ACL reconstruction.
Dietary inflammatory index and odds of colorectal cancer in a case-control study from Jordan
Authors: Shivappa Nitin , Hébert James R. , Steck Susan E. , Hofseth Lorne J. , Shehadah Ihab , Bani-Hani Kamal E. , Al-Jaberi Tareq , Al-Nusairr Majed , Heath Dennis , Tayyem Reema
Published: February 2017

Dietary components that promote inflammation of the colon have been suggested to be risk factors in the development of colorectal cancer (CRC). The possible link between inflammatory potential of diet and CRC has been investigated in several developed or Western countries. Despite the fact that dietary choices in the Middle East differ markedly from those in the West, results have not been reported from any study conducted in a Middle-Eastern population. We examined the association between dietary inflammatory index (DII) scores and CRC in a case-control study conducted in Jordan. This study included 153 histopathologically confirmed CRC cases and 202 disease-free control subjects’ frequency matched on age, sex, and occupation. Data were collected between January 2010 and December 2012, using interviewer-administered questionnaires. DII scores were computed from dietary data reported using a food frequency questionnaire. Logistic regression models were used to estimate odds ratios (ORs) and 95% confidence intervals (CIs) adjusted for age, sex, education, physical activity, body mass index, smoking, and family history of CRC. Subjects with higher DII scores were at increased odds of CRC, with the DII being used both as a continuous variable (ORcontinuous = 1.45, 95% CI: 1.13–1.85; 1-unit increase corresponding to ≈20% of its range in the current study) and as a categorical variable (ORtertile 3 vs tertile 1 = 2.13, 95%CI: 1.23–3.72). Our results, based on a Jordanian population, add to the growing literature indicating that a pro-inflammatory diet is associated with increased odds of CRC.
Peak punch-through capacity of spudcan in sand with interbedded clay: numerical and analytical modelling
Authors: Ullah Shah Neyamat , Hu Yuxia
Published: February 2017

The presence of a thin soft clay layer inside a bed of sand may significantly reduce the bearing capacity of the sand layer, imposing a risk of punch-through failure. In this paper, finite element (FE) simulations are reported using a hardening soil (HS) model for sand. The FE model has been verified against centrifuge tests involving loose and dense sand layers overlying clay soil. The effects of sand stiffness, foundation roughness, sand friction angle, undrained clay strength, clay strength nonhomogeneity, and sand and clay layer geometries on the foundation peak capacities have been studied. Punch-through failure is initiated with an inclined sand plug being sheared and pushed into the underlying soft clay. During punch-through, the clay layer fails due to significant radial squeezing. Existing analytical models do not capture the combined failure mechanism of sand shearing and clay radial squeezing. A new analytical model is developed to estimate the peak punch-through capacity of a spudcan in sand with an interbedded clay layer, showing improved performance over the current industry guidelines.
Otolith shape differences between ecotypes of Icelandic cod (Gadus morhua) with known migratory behaviour inferred from data storage tags
Authors: Bardarson Hlynur , McAdam Bruce. J. , Thorsteinsson Vilhjalmur , Hjorleifsson Einar , Marteinsdottir Gudrun
Published: February 2017

Otolith shape can be used to identify ecotypes of the Icelandic cod (Gadus morhua) stock. The use of data storage tags has increased our knowledge of the stock structure of Icelandic cod. The profiles of tagged cod reveal different migratory strategies. This has led to the definition of two ecotypes within the cod stock. Frontal ecotypes reside in deep waters during feeding season and express a highly variable temperature profile associated with thermal fronts, while coastal ecotypes stay in shallow waters all year round. In this study, the data storage tag profiles were analysed with cluster analysis, which revealed the existence of an intermediate behaviour that expresses a variable depth profile and feeding migration that is both shorter in time and not as deep. The main objective was to develop a morphological key based on otoliths to distinguish the ecotypes. The shape of the otoliths was extracted with shape measurements and fast Fourier transforms. A discriminant function analysis indicated a difference in morphology between the ecotypes, resulting in successful classification.
Modulation of electromagnetic local density of states by coupling of surface phonon-polariton
Authors: Li Yao , Zhang Chao-Jie , Wang Tong-Biao , Liu Jiang-Tao , Yu Tian-Bao , Liao Qing-Hua , Liu Nian-Hua
Published: February 2017

We studied the electromagnetic local density of state (EM-LDOS) near the surface of a one-dimensional multilayer structure (1DMS) alternately stacked by SiC and Si. EM-LDOS of a semi-infinite bulk appears two intrinsic peaks due to the resonance of surface phonon-polariton (SPhP) in SiC. In contrast with that of SiC bulk, SPhP can exist at the interface of SiC and Si for the 1DMS. The SPhPs from different interfaces can couple together, which can lead to a significant modulation of EM-LDOS. When the component widths of 1DMS are large, the spectrum of EM-LDOS exhibits oscillation behavior in the frequency regime larger than the resonance frequency of SPhP. While the component widths are small, due to the strong coupling of SPhPs, another peak appears in the EM-LDOS spectrum besides the two intrinsic ones. And the position of the new peak move toward high frequency when the width ratio of SiC and Si increases. The influences of distance from the surfaces and period of 1DMS on EM-LDOS have also been studied in detail. The results are helpful in studying the near-field radiative heat transfer and spontaneous emission.
Finite element investigation into the thermal conductivity of carbon nanotube/aluminum nanocomposites
Authors: Rouhi S. , Ansari R. , Ahmadi M.
Published: February 2017

This paper aims to study the thermal conductivity coefficient of aluminum matrices reinforced by single-walled carbon nanotubes. To obtain the thermal conductivity coefficient of the nanocomposites, a small temperature difference is applied on two opposite edges of a representative volume element. The nanotubes are distributed in Al matrix by using three different patterns, including random pattern, regular pattern with nanotube direction along the temperature difference and regular pattern with nanotube direction perpendicular to the temperature change. It is shown that the best enhancement in the thermal conductivity of aluminum matrix occurs by the regular distribution of the nanotubes along the temperature change. Also, increasing the volume fraction of nanotubes in aluminum matrix leads to increasing the thermal conductivity coefficient of the nanocomposite.