bluuebunny/crossref_metadata_2025 huggingface dataset:
Petrogenesis of D'Orbigny‐like angrite meteorites and the role of spinel in the angrite source
Authors: McKibbin Seann J. , O'Neill Hugh St. C.
Published: November 2017

Angrite meteorites are samples of early planetesimal magmatic rocks, distinguished from more typical “basaltic eucrites” by compositions that are silica undersaturated, relatively oxidized, and with high CaO/Al2O3. The latter is not expected from nebular, chondritic materials that might form a primitive mantle, such as a source enriched in refractory inclusions with fixed CaO/Al2O3 (e.g., CV chondrite). Here we present results of “reversal” crystallization experiments for two possible parental angrite compositions (approximating the D'Orbigny meteorite) to investigate the role of spinel as a sink for Al2O3. This mineral has previously been produced with angritic melts during “forward” melting of CV chondrite and may be abundant in the angrite source. At oxidizing conditions, we confirm that spinel is a liquidus phase and that angritic magmas form near the olivine‐anorthite‐spinel‐liquid peritectic. A stability gap separates Al‐rich liquidus spinels and lower temperature spinels, the latter of which are similar to those in basaltic eucrites. Al‐rich spinel is likely more abundant in the angritic source than other Fe‐rich core‐forming components such as metal or sulfide, and a CV chondrite‐like composition generates most features of angrite magmas by fractionation of observed olivine and liquidus spinel. Direct CaO excess, via carbonate addition, is therefore limited. In this model, discrepancies remain for Li, Sc, Cr(‐Al), and Ba, which may record local accretion conditions or early processing. The possible role of spinel as a sink for 26Al may have strong influence on the thermal evolution of the angrite parent body.
Pneumococcal meningitis with vertebral osteomyelitis, iliopsoas abscess, and infected abdominal aortic aneurysm
Authors: Mitsutake Akihiko , Matsumoto Hideyuki , Hatano Keiko , Matsuura Sohei , Takayama Toshio , Yamamoto Kota , Hoshina Katsuyuki , Ikemura Masako , Hashida Hideji
Published: November 2017

A 69‐year‐old man with a past history of asymptomatic abdominal aortic aneurysm developed pneumococcal meningitis. Antibiotic therapy improved his meningitis. However, he also developed vertebral osteomyelitis, iliopsoas abscess, and infected abdominal aortic aneurysm. The aneurysm was sequentially dilated, suggesting the impending rupture. An emergency open aneurysm repair using a tube homograft was performed. All of the vertebral osteomyelitis, iliopsoas abscess, and infected abdominal aortic aneurysm are rare complications. In particular, if a patient with bacterial meningitis has a preexisting aortic aneurysm, infected aortic aneurysm should be noted. To prevent the rupture of the aneurysm, the emergent vascular surgery including aorto‐aortic homograft substitution should be considered.
Characterization of the enzymatic activity and physiological function of the lipid droplet‐associated triacylglycerol lipase AtOBL1
Authors: Müller Anna Ophelia , Ischebeck Till
Published: November 2017

Similar to seeds, pollen tubes contain lipid droplets that store triacylglycerol (TAG), but the fate of this TAG as well as the enzymes involved in its breakdown are unknown. Therefore, two potential TAG lipases from tobacco and Arabidopsis, NtOBL1 (Oil body lipase 1) and AtOBL1, were investigated, especially with respect to their importance for pollen tube growth.

We expressed NtOBL1 and AtOBL1 as fluorescent fusion proteins to study their localization by confocal microscopy. Furthermore, we overexpressed AtOBL1 in Nicotiana benthamiana leaves to characterize it enzymatically. The obl1 mutant was studied in respect to its pollen tube growth in vivo and its seed germination.

Both NtOBL1 and AtOBL1 localized to lipid droplets. AtOBL1 was abundant in pollen tubes and seedlings, and acted as a lipase on TAG, diacylglycerol and 1‐monoacylglycerol at a pH optimum of 5.5. The obl1 mutant was hampered in pollen tube growth, whereas seedling establishment was not affected under optimal conditions, even though AtOBL1 accounted for a major lipase activity in seeds.

TAG could be a direct precursor for the synthesis of membrane lipids in pollen tubes and proteins of the OBL family involved in the flux of acyl groups.
Risk factors for asthma occurrence in children with early‐onset atopic dermatitis: An 8‐year follow‐up study
Authors: Huang Ching‐Chun , Chiang Tung‐Liang , Chen Pau‐Chung , Lin Shio‐Jean , Wen Hui‐Ju , Guo Yue Leon
Published: November 2017

Background

Children with early‐onset atopic dermatitis (AD) are at substantial risk of developing asthma later in life, and identifying the critical window of detrimental exposure is advantageous for implementing preventive actions. The aim of this study was to evaluate the role of exposure to environmental modifiers during pregnancy and early childhood in asthma occurrence in an infantile AD cohort.

Methods

Eligible study participants were selected from the Taiwan Birth Cohort Study, which enrolled 24 200 newborns in 2005. We enrolled those cases who had been diagnosed as having AD before 3 years of age and followed them up till age 8. We excluded those ever diagnosed with asthma before AD onset. The dependent variable was defined in terms of whether the participant was diagnosed as having asthma before 8 years of age. We applied logistic regression models to evaluate the risks of exposure to different determinants in asthma occurrence.

Results

A total of 1549 children with AD had completed the 8‐year follow‐up, and 334 (21.6%) of them had asthma. The results revealed that male sex, lower birth order, maternal asthma history, maternal obesity before pregnancy, and environmental tobacco smoke exposure before 3 years of age were significant risk factors for further development of asthma. Furthermore, food allergy during early life, lower respiratory tract infection, and longer durations of symptomatic AD influenced asthma development later in life.

Conclusions

The findings confirmed the critical determinants for asthma occurrence in infantile AD, which may enable a more personalized approach to the prevention of asthma.
Vested Interests and the Diffusion of Education Reform across the States
Authors: Finger Leslie K.
Published: November 2017

How do interest groups shape the diffusion of policies they oppose across the states? This study explores this question using the case of teachers' unions and education reform policies. Using a novel dataset on charter, voucher, and performance pay policies spanning 1992–2013, I find evidence that strength of the teachers' unions decreases the likelihood of performance pay and that additional strength is less impactful with more Democratic control of the legislature. Teachers' unions are weakly related to a lack of charter laws and do not impact voucher laws. The latter two policies are more strongly associated with policymaker learning and education reform advocacy groups, respectively. These findings suggest that vested interests most strongly impact the policies that most fundamentally threaten their organizational strength and that this effect is conditioned on the party in power; increases in interest group strength are not necessary when policymakers are already sympathetic.
Tissue is the issue to confirm benign disease at pleuroscopy in lung cancer
Authors: Fielding David
Published: November 2017

See related Article
Characterizing Risk for Cumulative Risk Assessments
Authors: MacDonell Margaret M. , Hertzberg Richard C. , Rice Glenn E. , Wright J. Michael , Teuschler Linda K.
Published: November 2017

In assessing environmental health risks, the risk characterization step synthesizes information gathered in evaluating exposures to stressors together with dose–response relationships, characteristics of the exposed population, and external environmental conditions. This article summarizes key steps of a cumulative risk assessment (CRA) followed by a discussion of considerations for characterizing cumulative risks. Cumulative risk characterizations differ considerably from single chemical‐ or single source‐based risk characterization. CRAs typically focus on a specific population instead of a pollutant or pollutant source and should include an evaluation of all relevant sources contributing to the exposures in the population and other factors that influence dose–response relationships. Second, CRAs may include influential environmental and population‐specific conditions, involving multiple chemical and nonchemical stressors. Third, a CRA could examine multiple health effects, reflecting joint toxicity and the potential for toxicological interactions. Fourth, the complexities often necessitate simplifying methods, including judgment‐based and semi‐quantitative indices that collapse disparate data into numerical scores. Fifth, because of the higher dimensionality and potentially large number of interactions, information needed to quantify risk is typically incomplete, necessitating an uncertainty analysis. Three approaches that could be used for characterizing risks in a CRA are presented: the multiroute hazard index, stressor grouping by exposure and toxicity, and indices for screening multiple factors and conditions. Other key roles of the risk characterization in CRAs are also described, mainly the translational aspect of including a characterization summary for lay readers (in addition to the technical analysis), and placing the results in the context of the likely risk‐based decisions.
Information is not knowledge: Cooking and eating as skilled practice in Australian obesity education
Authors: Warin Megan
Published: November 2017

This paper examines the relationship between obesity, knowledge and education in a South Australian community setting. In public health circles and public understandings it is commonly assumed that obesity is the result of lack of knowledge about the right things to eat or how to take care of oneself. It is thought that education will fill this knowledge lacunae and most public health campaigns have education as the main platform of information dissemination to enact behavioural change. Based on long‐standing ethnographic work in a community targeted as obesogenic, I explore the limits of mainstream nutrition education, and how constructing people as having deficit knowledge has the unwarranted effect of implying ignorance. Key to the analysis is Ingold's articulation of different modalities of education, one dominant mode which inducts people into rules and regulations of already pre‐formed knowledge, and another which sees education as learning that goes on in the doing of everyday environments.
Detection of human immunodeficiency virus, hepatitis C virus, and hepatitis B virus in postmortem blood specimens using infectious disease assays licensed for cadaveric donor screening
Authors: Greenwald Melissa A. , Kerby Stephen , Francis Kori , Noller Anna C. , Gormley William T. , Biswas Robin , Forshee Richard A.
Published: November 2017

Background

Evaluation of assay performance on postmortem blood specimens (obtained after cessation of the heartbeat) presents unique scientific and regulatory challenges. In the United States, assay performance is evaluated in part by spiking postmortem specimens.

Methods

Fifty‐four specimens obtained from decedents known to be infected with human immunodeficiency virus (HIV), hepatitis C virus (HCV), or hepatitis B virus (HBV), including some coinfections, were tested for each virus using Food and Drug Administration (FDA)‐licensed donor screening tests for nucleic acid, antibody, and antigen.

Results

For each disease, >95% of subjects who were reported to have an infection at the time of death had a positive test result on at least one of the donor screening assays for that infection.

Conclusion

Licensed donor screening tests were positive on postmortem specimens obtained within 24 hours of death from individuals dying with HIV, HCV, and/or HBV, and were able to detect presence of the virus. The use of multiple tests (including antibody and direct viral detection methods) is necessary to adequately evaluate donors.
Vitamin D receptor expression in canine mammary gland and relationship with clinicopathological parameters and progesterone/oestrogen receptors
Authors: Sánchez‐Céspedes R. , Fernández‐Martínez M. D. , Raya A. , Pineda C. , López I. , Millán Y.
Published: November 2017

The vitamin D receptor (VDR) belongs to the nuclear class II receptor family. VDR is a ligand transcription factor and mediates the actions of calcitriol, the active product of vitamin D synthesis. Nowadays, it is known that the biological actions of calcitriol include the capacity to modulate cancer features, such as proliferation and differentiation, apoptosis, angiogenesis, invasion and metastasis. VDR expression has been demonstrated in human breast cancer and vitamin D has emerged as a promising targeted therapy. We analyse the VDR expression in normal and neoplastic canine mammary tissue samples and its relationship with clinicopathological parameters and progesterone/oestrogens receptors (PR/ER). Expression of VDR, Ki67 (to evaluate the proliferation index, PI), PR and ER was assessed in 50 mammary gland tissue samples from 41 female dogs by immunohistochemistry. VDR‐positive staining was found in the nuclei of both myoepithelial and luminal epithelial cell layers. VDR expression was higher in normal mammary tissue (37/37 cases, 100%) then followed by benign tumours (6/15 cases, 40%) and malignant tumours (9/34 cases, 26.5%) (P = .001). Female dogs aged ≥10 years had lower VDR expression compared with dogs younger (P = .017). Relationship between VDR and breed, number of tumours, tumour size, histologic subtype, histologic grade of malignancy, PI and PR and ER expression was not observed. Studies with more samples are necessary to further evaluate the possible role of VDR in the biological behaviour of canine mammary tumours, and to corroborate the possibility to use the dog as model for human breast cancer.
Perceptions and opinions of pet owners in theUnitedSates about surgery, pain management, and anesthesia in dogs and cats
Authors: Simon Bradley T. , Scallan Elizabeth M. , Von Pfeil Dirsko J. F. , Boruta Daniel T. , Wall Rick , Nibblett Belle M. , Odette O , Beauchamp Guy , Steagall Paulo V.
Published: November 2017

Objective

To evaluate pet owners' perceptions and understanding of surgical pain, perioperative pain management, and anesthesia.

Study Design

Prospective owner survey.

Sample Population

Eight veterinary hospitals each provided 200 surveys for distribution to pet owners.

Methods

A survey evaluated owners' perceptions and opinions related to surgical pain, perioperative pain management, anesthesia in dogs and cats, and owner demographics (sex, age, education, employment, previous surgical experience, and pet ownership) in 8 regions of the United States (Alaska, Florida, Hawaii, Massachusetts, Oregon, Ohio, Texas, Washington, DC). Effects of demographics on survey questions were analyzed by using a Cochran–Mantel–Haenszel test. Descriptive statistics and frequency distributions were calculated when applicable.

Results

948/1600 (59.25%) of distributed questionnaires were completed. Owners reported that analgesics were “always needed” more often for surgical procedures than medical conditions. Knowing what to expect during recovery (99%), being informed of procedures and risks (98%), adequate pain management (98%), and having a board‐certified anesthesiologist perform anesthesia (94%) were considered “important” or “very important” by owners. The majority of owners agreed that pain affects quality of life (81%), interactions with family and pets (73%), and that declawing is a painful procedure (59%). Older respondents (>46 years), women, owners who have had previous surgery or who have pets that have had previous surgery, and those in health care professions have a better understanding of pain but also expect effective client communication.

Conclusion

Improving our understanding of pet owners' perceptions and knowledge related to anesthesia, surgery, and pain may lead to improved client education, satisfaction, and compliance with administration of analgesics.
COMPUTATIONAL FLUID DYNAMICS STUDY OF DUSTY AIR FLOW OVER NACA 63415 AIRFOIL FOR WIND TURBINE APPLICATIONS
Authors: F. Zidane Iham , M. Saqr Khalid , Swadener Greg , Ma Xianghong , F. Shehadeh Mohamed
Published: November 2017

Gulf and South African countries have enormous potential for wind energy. However, the emergence of sand storms in this region postulates performance and reliability challenges on wind turbines. This study investigates the effects of debris flow on wind turbine blade performance. In this paper, two-dimensional incompressible Navier-Stokes equations and the transition SST turbulence model are used to analyze the aerodynamic performance of NACA 63415 airfoil under clean and sandy conditions. The numerical simulation of the airfoil under clean surface condition is performed at Reynolds number 460×103, and the numerical results have a good consistency with the experimental data. The Discrete Phase Model has been used to investigate the role sand particles play in the aerodynamic performance degradation. The pressure and lift coefficients of the airfoil have been computed under different sand particles flow rates. The performance of the airfoil under different angle of attacks has been studied. Results showed that the blade lift coefficient can deteriorate by 28% in conditions relevant to the Gulf and South African countries sand storms. As a result, the numerical simulation method has been verified to be economically available for accurate estimation of the sand particles effect on the wind turbine blades.
Numerical behavior of singular two-point boundary value problems in a comparative way
Authors: Selim Selmahan , Elver Gözde , Sari Murat
Published: November 2017

This article concentrates on discovering numerical behavior of the singular two-point boundary value problems through various numerical techniques. This is carried out in a comparative way by mainly using differential quadrature and finite element methods. Also a discussion has been done by means of advantages and disadvantages of the numerical methods of interest.To properly understand the behavior of the physical processes represented by the model equation, the calculated solutions have been discussed in detail.
Interdependent feedback regulation of breathing by the carotid bodies and the retrotrapezoid nucleus
Authors: Guyenet Patrice G. , Bayliss Douglas A. , Stornetta Ruth L. , Kanbar Roy , Shi Yingtang , Holloway Benjamin B. , Souza George M. P. R. , Basting Tyler M. , Abbott Stephen B. G. , Wenker Ian C.
Published: November 2017

The retrotrapezoid nucleus (RTN) regulates breathing in a CO2‐ and state‐dependent manner. RTN neurons are glutamatergic and innervate principally the respiratory pattern generator; they regulate multiple aspects of breathing, including active expiration, and maintain breathing automaticity during non‐REM sleep. RTN neurons encode arterial /pH via cell‐autonomous and paracrine mechanisms, and via input from other CO2‐responsive neurons. In short, RTN neurons are a pivotal structure for breathing automaticity and arterial homeostasis. The carotid bodies stimulate the respiratory pattern generator directly and indirectly by activating RTN via a neuronal projection originating within the solitary tract nucleus. The indirect pathway operates under normo‐ or hypercapnic conditions; under respiratory alkalosis (e.g. hypoxia) RTN neurons are silent and the excitatory input from the carotid bodies is suppressed. Also, silencing RTN neurons optogenetically quickly triggers a compensatory increase in carotid body activity. Thus, in conscious mammals, breathing is subject to a dual and interdependent feedback regulation by chemoreceptors. Depending on the circumstance, the activity of the carotid bodies and that of RTN vary in the same or the opposite directions, producing additive or countervailing effects on breathing. These interactions are mediated either via changes in blood gases or by brainstem neuronal connections, but their ultimate effect is invariably to minimize arterial fluctuations. We discuss the potential relevance of this dual chemoreceptor feedback to cardiorespiratory abnormalities present in diseases in which the carotid bodies are hyperactive at rest, e.g. essential hypertension, obstructive sleep apnoea and heart failure.

image
Current-induced strong diamagnetism in the Mott insulator Ca
2
RuO
4
Authors: Sow Chanchal , Yonezawa Shingo , Kitamura Sota , Oka Takashi , Kuroki Kazuhiko , Nakamura Fumihiko , Maeno Yoshiteru
Published: November 2017

Tuning diamagnetism with current

Properties of materials can be tuned by various means, such as chemical doping, magnetic field, or pressure. Sow
et al.
used electrical currents of modest density to turn the Mott insulator Ca
2
RuO
4
into a semimetal. Concurrently, its diamagnetic response—the ability to counter an externally applied magnetic field—rose to levels higher than in any other nonsuperconducting material. The use of electrical current as a powerful experimental knob may be applicable to other similar materials.

Science
, this issue p.
1084
Molecular and cellular reorganization of neural circuits in the human lineage
Authors: Sousa André M. M. , Zhu Ying , Raghanti Mary Ann , Kitchen Robert R. , Onorati Marco , Tebbenkamp Andrew T. N. , Stutz Bernardo , Meyer Kyle A. , Li Mingfeng , Kawasawa Yuka Imamura , Liu Fuchen , Perez Raquel Garcia , Mele Marta , Carvalho Tiago , Skarica Mario , Gulden Forrest O. , Pletikos Mihovil , Shibata Akemi , Stephenson Alexa R. , Edler Melissa K. , Ely John J. , Elsworth John D. , Horvath Tamas L. , Hof Patrick R. , Hyde Thomas M. , Kleinman Joel E. , Weinberger Daniel R. , Reimers Mark , Lifton Richard P. , Mane Shrikant M. , Noonan James P. , State Matthew W. , Lein Ed S. , Knowles James A. , Marques-Bonet Tomas , Sherwood Chet C. , Gerstein Mark B. , Sestan Nenad
Published: November 2017

The makings of the primate brain

Although nonhuman primate brains are similar to our own, the disparity between their and our cognitive abilities tells us that surface similarity is not the whole story. Sousa
et al.
overlaid transcriptome and histological analyses to see what makes human brains different from those of nonhuman primates. Various differentially expressed genes, such as those encoding transcription factors, could alter transcriptional programs. Others were associated with neuromodulatory systems. Furthermore, the dopaminergic interneurons found in the human neocortex were absent from the neocortex of nonhuman African apes. Such differences in neuronal transcriptional programs may underlie a variety of neurodevelopmental disorders.

Science
, this issue p.
1027
Multiplex recording of cellular events over time on CRISPR biological tape
Authors: Sheth Ravi U. , Yim Sung Sun , Wu Felix L. , Wang Harris H.
Published: November 2017

A CRISPR device to record time

The CRISPR adaptation system has been used to record the sequence and ordering of exogenous oligonucleotides that are electroporated into cell populations. Sheth
et al.
engineered a system bypassing the use of exogenous DNA to directly record temporal signals. An input biological signal is transformed into the ratio of the frequency of incorporating trigger DNA to that of incorporating reference DNA into the genomes of a bacterial population. A multiplexing strategy enables simultaneous recording of three environmental signals with high temporal resolution.

Science
, this issue p.
1457
Quantum interference beyond the fringe
Authors: Walmsley Ian
Published: November 2017

The discovery 30 years ago of the interference of pairs of photons signaled the onset of an era for quantum optics
Synthesis of ultrasmall, homogeneously alloyed, bimetallic nanoparticles on silica supports
Authors: Wong A. , Liu Q. , Griffin S. , Nicholls A. , Regalbuto J. R.
Published: November 2017

Dispersing small, bimetallic nanoparticles

For applications of nanoparticles in sensing and catalysis, smaller nanoparticles are often more effective because they expose more active surface sites. The properties of metallic nanoparticles can also be improved by creating bimetallic alloys, but typical synthetic methods yield larger nanoparticles where the metals are poorly mixed. Wong
et al.
show that well-mixed bimetallic ∼1-nm-diameter nanoparticles can be made on silica supports. To do this, they exploited strong electrostatic adsorption, in which the metal precursors are strongly adsorbed onto the surface by controlling pH relative to the surface point of zero charge. Their method was successful for a wide range of metal alloys.

Science
, this issue p.
1427
Common grounds
Where the Wild Coffee Grows
Jeff Koehler
Bloomsbury, 2017. 303 pp.
Authors: Fabiani Louise
Published: November 2017

A wide-ranging natural history illuminates the pleasures and the plight of wild coffee
Simple
In Vitro
Assay To Evaluate the Incorporation Efficiency of Ribonucleotide Analog 5′-Triphosphates into RNA by Human Mitochondrial DNA-Dependent RNA Polymerase
Authors: Lu Gaofei , Bluemling Gregory R. , Mao Shuli , Hager Michael , Gurale Bharat P. , Collop Paul , Kuiper Damien , Sana Kasinath , Painter George R. , De La Rosa Abel , Kolykhalov Alexander A.
Published: November 2017

There is a growing body of evidence suggesting that some ribonucleoside/ribonucleotide analogs may be incorporated into mitochondrial RNA by human mitochondrial DNA-dependent RNA polymerase (POLRMT) and disrupt mitochondrial RNA synthesis. An assessment of the incorporation efficiency of a ribonucleotide analog 5′-triphosphate by POLRMT may be used to evaluate the potential mitochondrial toxicity of the analog early in the development process. In this report, we provide a simple method to prepare active recombinant POLRMT. A robust
in vitro
nonradioactive primer extension assay was developed to assay the incorporation efficiency of ribonucleotide analog 5′-triphosphates. Our results show that many ribonucleotide analogs, including some antiviral compounds currently in various preclinical or clinical development stages, can be incorporated into newly synthesized RNA by POLRMT and that the incorporation of some of them can lead to chain termination. The discrimination (
D
) values of ribonucleotide analog 5′-triphosphates over those of natural ribonucleotide triphosphates (rNTPs) were measured to evaluate the incorporation efficiency of the ribonucleotide analog 5′-triphosphates by POLRMT. The discrimination values of natural rNTPs under the condition of misincorporation by POLRMT were used as a reference to evaluate the potential mitochondrial toxicity of ribonucleotide analogs. We propose the following criteria for the potential mitochondrial toxicity of ribonucleotide analogs based on
D
values: a safe compound has a
D
value of >10
5
; a potentially toxic compound has a
D
value of >10
4
but <10
5
; and a toxic compound has a
D
value of <10
4
. This report provides a simple screening method that should assist investigators in designing ribonucleoside-based drugs having lower mitochondrial toxicity.
The ABC of Biofilm Drug Tolerance: the MerR-Like Regulator BrlR Is an Activator of ABC Transport Systems, with PA1874-77 Contributing to the Tolerance of Pseudomonas aeruginosa Biofilms to Tobramycin
Authors: Poudyal Bandita , Sauer Karin
Published: November 2017

A hallmark of biofilms is their tolerance to killing by antimicrobial agents. In
Pseudomonas aeruginosa
, biofilm drug tolerance requires the c-di-GMP-responsive MerR transcriptional regulator BrlR. However, the mechanism by which BrlR mediates biofilm drug tolerance has not been elucidated. Here, we demonstrate that BrlR activates the expression of at least 7 ABC transport systems, including the PA1874-PA1875-PA1876-PA1877 (PA1874-77) operon, with chromatin immunoprecipitation and DNA binding assays confirming BrlR binding to the promoter region of PA1874-77. Insertional inactivation of the 7 ABC transport systems rendered
P. aeruginosa
PAO1 biofilms susceptible to tobramycin or norfloxacin. Susceptibility was linked to drug accumulation, with BrlR contributing to norfloxacin accumulation in a manner dependent on multidrug efflux pumps and the PA1874-77 ABC transport system. Inactivation of the respective ABC transport system, furthermore, eliminated the recalcitrance of biofilms to killing by tobramycin but not norfloxacin, indicating that drug accumulation is not linked to biofilm drug tolerance. Our findings indicate for the first time that BrlR, a MerR-type transcriptional activator, activates genes encoding several ABC transport systems, in addition to multiple multidrug efflux pump genes. Moreover, our data confirm a BrlR target contributing to drug tolerance, likely countering the prevailing dogma that biofilm tolerance arises from a multiplicity of factors.
Integrated Resistance Analysis of CERTAIN-1 and CERTAIN-2 Studies in Hepatitis C Virus-Infected Patients Receiving Glecaprevir and Pibrentasvir in Japan
Authors: Krishnan Preethi , Schnell Gretja , Tripathi Rakesh , Beyer Jill , Reisch Thomas , Dekhtyar Tatyana , Irvin Michelle , Xie Wangang , Fu Bo , Burroughs Margaret , Redman Rebecca , Kumada Hiromitsu , Chayama Kazuaki , Collins Christine , Pilot-Matias Tami
Published: November 2017

Glecaprevir and pibrentasvir are hepatitis C virus (HCV) pangenotypic inhibitors targeting NS3/4A protease and NS5A, respectively. This once-daily, fixed-dose combination regimen demonstrated high sustained virologic response 12 weeks postdosing (SVR
12
) rates in CERTAIN-1 and CERTAIN-2 studies in Japanese HCV-infected patients, with a low virologic failure rate (1.2%). There were no virologic failures among direct-acting antiviral (DAA)-treatment-naive genotype 1a (GT1a) (
n
= 4)-, GT1b (
n
= 128)-, and GT2 (
n
= 97)-infected noncirrhotic patients treated for 8 weeks or among GT1b (
n
= 38)- or GT2 (
n
= 20)-infected patients with compensated cirrhosis treated for 12 weeks. Two of 33 DAA-experienced and 2 of 12 GT3-infected patients treated for 12 weeks experienced virologic failure. Pooled resistance analysis, grouped by HCV subtype, treatment duration, prior treatment experience, and cirrhosis status, was conducted. Among DAA-naive GT1b-infected patients, the baseline prevalence of NS3-D168E was 1.2%, that of NS5A-L31M was 3.6%, and that of NS5A-Y93H was 17.6%. Baseline polymorphisms in NS3 or NS5A were less prevalent in GT2, with the exception of the common L/M31 polymorphism in NS5A. Among DAA-experienced GT1b-infected patients (30/32 daclatasvir plus asunaprevir-experienced patients), the baseline prevalence of NS3-D168E/T/V was 48.4%, that of NS5A-L31F/I/M/V was 81.3%, that of the NS5A P32deletion was 6.3%, and that of NS5A-Y93H was 59.4%. Common baseline polymorphisms in NS3 and/or NS5A had no impact on treatment outcomes in GT1- and GT2-infected patients; the impact on GT3-infected patients could not be assessed due to the enrollment of patients infected with diverse subtypes and the limited number of patients. The glecaprevir-pibrentasvir combination regimen allows a simplified treatment option without the need for HCV subtyping or baseline resistance testing for DAA-naive GT1- or GT2-infected patients. (The CERTAIN-1 and CERTAIN-2 studies have been registered at ClinicalTrials.gov under identifiers NCT02707952 and NCT02723084, respectively.)
Production of 1-Dodecanol, 1-Tetradecanol, and 1,12-Dodecanediol through Whole-Cell Biotransformation in Escherichia coli
Authors: Hsieh Shan-Chi , Wang Jung-Hao , Lai Yu-Chen , Su Ching-Yeuh , Lee Kung-Ta
Published: November 2017

Medium- and long-chain 1-alkanol and α,ω-alkanediols are used in personal care products, in industrial lubricants, and as precursors for polymers synthesized for medical applications. The industrial production of α,ω-alkanediols by alkane hydroxylation primarily occurs at high temperature and pressure using heavy metal catalysts. However, bioproduction has recently emerged as a more economical and environmentally friendly alternative. Among alkane monooxygenases, CYP153A from
Marinobacter aquaeolei
VT8 (CYP153A

M.aq

; the strain is also known as
Marinobacter hydrocarbonoclasticus
VT8) possesses low overoxidation activity and high regioselectivity and thus has great potential for use in terminal hydroxylation. However, the application of CYP153A

M.aq

is limited because it is encoded by a dysfunctional operon. In this study, we demonstrated that the operon regulator AlkR

M.aq

is functional, can be induced by alkanes of various lengths, and does not suffer from product inhibition. Additionally, we identified a transposon insertion in the CYP153A

M.aq

operon. When the transposon was removed, the expression of the operon genes could be induced by alkanes, and the alkanes could then be oxyfunctionalized by the resulting proteins. To increase the accessibility of medium- and long-chain alkanes, we coexpressed a tunable alkane facilitator (AlkL) from
Pseudomonas putida
GPo1. Using a recombinant
Escherichia coli
strain, we produced 1.5 g/liter 1-dodecanol in 20 h and 2 g/liter 1-tetradecanol in 50 h by adding dodecane and tetradecane, respectively. Furthermore, in 68 h, we generated 3.76 g/liter of 1,12-dodecanediol by adding a dodecane–1-dodecanol substrate mixture. This study reports a very efficient method of producing C
12
/C
14
alkanols and C
12
1,12-alkanediol by whole-cell biotransformation.

IMPORTANCE
To produce terminally hydroxylated medium- to long-chain alkane compounds by whole-cell biotransformation, substrate permeability, enzymatic activity, and the control of overoxidability should be considered. Due to difficulties in production, small amounts of 1-dodecanol, 1-tetradecanol, and 1,12-dodecanediol are typically produced. In this study, we identified an alkane-inducible monooxygenase operon that can efficiently catalyze the conversion of alkane to 1-alkanol with no detection of the overoxidation product. By coexpressing an alkane membrane facilitator, high levels of 1-dodecanol, 1-tetradecanol, and 1,12-dodecanediol could be generated. This study is significant for the bioproduction of medium- and long-chain 1-alkanol and α,ω-alkanediols.
Quality of Irrigation Water Affects Soil Functionality and Bacterial Community Stability in Response to Heat Disturbance
Authors: Frenk Sammy , Hadar Yitzhak , Minz Dror
Published: November 2017

Anthropogenic activities alter the structure and function of a bacterial community. Furthermore, bacterial communities structured by the conditions the anthropogenic activities present may consequently reduce their stability in response to an unpredicted acute disturbance. The present mesocosm-scale study exposed soil bacterial communities to different irrigation water types, including freshwater, fertilized freshwater, treated wastewater, and artificial wastewater, and evaluated their response to a disturbance caused by heat. These effectors may be considered deterministic and stochastic forces common in agricultural operations of arid and semiarid regions. Bacterial communities under conditions of high mineral and organic carbon availability (artificial wastewater) differed from the native bacterial community and showed a proteobacterial dominance. These bacterial communities had a lower resistance to the heat treatment disturbance than soils under conditions of low resource availability (high-quality treated wastewater or freshwater). The latter soil bacterial communities showed a higher abundance of operational taxonomic units (OTUs) classified asBacilli. These results were elucidated by soil under conditions of high resource availability, which lost higher degrees of functional potential and had a greater bacterial community composition change. However, the functional resilience, after the disturbance ended, was higher under a condition of high resource availability despite the bacterial community composition shift and the decrease in species richness. The functional resilience was directly connected to the high growth rates of certainBacteroidetesand proteobacterial groups. A high stability was found in samples that supported the coexistence of both resistant OTUs and fast-growing OTUs.

IMPORTANCEThis report presents the results of a study employing a hypothesis-based experimental approach to reveal the forces involved in determining the stability of a soil bacterial community to disturbance. The resultant postdisturbance bacterial community composition dynamics and functionality were analyzed. The paper demonstrates the relatedness of community structure and stability under cultivation conditions prevalent in an arid area under irrigation with water of different qualities. The use of common agricultural practices to demonstrate these features has not been described before. The combination of a fundamental theoretical issue in ecology with common and concerning disturbances caused by agricultural practice makes this study unique. Furthermore, the results of the present study have applicable importance regarding soil conservation, as it enables a better characterization and monitoring of stressed soil bacterial communities and possible intervention to reduce the stress. It will also be of valued interest in coming years, as fresh water scarcity and the use of alternative water sources are expected to rise globally.
Formation and Characterization of Early Bacterial Biofilms on Different Wood Typologies Applied in Dairy Production
Authors: Cruciata Margherita , Gaglio Raimondo , Scatassa Maria Luisa , Sala Giovanna , Cardamone Cinzia , Palmeri Marisa , Moschetti Giancarlo , La Mantia Tommaso , Settanni Luca
Published: November 2017

The main hypothesis of this work was that Sicilian forestry resources are suitable for the production of equipment to be used in cheese making and indigenous milk lactic acid bacteria (LAB) are able to develop stable biofilms providing starter and nonstarter cultures necessary for curd fermentation and cheese ripening, respectively. Hence, the present work was carried out with deproteinized whey to evaluate LAB biofilm formation on different woods derived from tree species grown in Sicily. Microbiological and scanning electron microscopy analyses showed minimal differences in microbial levels and compositions for the neoformed biofilms. The specific investigation of
Salmonella
spp.,
Listeria monocytogenes
,
Escherichia coli
, coagulase-positive staphylococci (CPS), and sulfite-reducing anaerobes did not generate any colony for all vats before and after bacterial adhesion. LAB populations dominated all vat surfaces. The highest levels (7.63 log CFU/cm
2
) were registered for thermophilic cocci. Different colonies were characterized physiologically, biochemically, and genetically (at strain and species levels). Six species within the genera
Enterococcus
,
Lactobacillus
,
Lactococcus
, and
Streptococcus
were identified. The species most frequently present were
Lactobacillus fermentum
and
Lactococcus lactis
. LAB found on the surfaces of the wooden vats in this study showed interesting characteristics important for dairy manufacture. To thoroughly investigate the safety of the wooden vat, a test of artificial contamination on new Calabrian chestnut (control wood) vats was carried out. The results showed that LAB represent efficient barriers to the adhesion of the main dairy pathogens, probably due to their acidity and bacteriocin generation.

IMPORTANCE
This study highlights the importance of using wooden vats for traditional cheese production and provides evidence for the valorization of the Sicilian forest wood resources via the production of dairy equipment.
Meningococcal Antigen Typing System (MATS)-Based Neisseria meningitidis Serogroup B Coverage Prediction for the MenB-4C Vaccine in the United States
Authors: Rajam Gowrisankar , Stella Maria , Kim Ellie , Paulos Simon , Boccadifuoco Giuseppe , Serino Laura , Carlone George , Medini Duccio
Published: November 2017

The meningococcal antigen typing system (MATS) is an enzyme-linked immunosorbent assay (ELISA)-based system that assesses the levels of expression and immune reactivity of the three recombinant MenB-4C antigens and, in conjunction with PorA variable 2 (VR2) sequencing, provides an estimate of the susceptibility of NmB isolates to killing by MenB-4C-induced antibodies. MATS assays or similar antigen phenotype analyses assume importance under conditions in which analyses of vaccine coverage predictions are not feasible with existing strategies, including large efficacy trials or functional antibody screening of an exhaustive strain panel. MATS screening of a panel of NmB U.S. isolates (n= 442) predicts high MenB-4C vaccine coverage in the United States.
The effect of nut consumption on markers of inflammation and endothelial function: a systematic review and meta-analysis of randomised controlled trials
Authors: Neale Elizabeth P , Tapsell Linda C , Guan Vivienne , Batterham Marijka J
Published: November 2017

Objectives

To examine the effect of nut consumption on inflammatory biomarkers and endothelial function.

Design

A systematic review and meta-analysis.

Data sources

MEDLINE, PubMed, Cumulative Index to Nursing and Allied Health Literature and Cochrane Central Register of Controlled Trials (all years to 13 January 2017).

Eligibility criteria

Randomised controlled trials (with a duration of 3 weeks or more) or prospective cohort designs conducted in adults; studies assessing the effect of consumption of tree nuts or peanuts on C-reactive protein (CRP), adiponectin, tumour necrosis factor alpha, interleukin-6, intercellular adhesion molecule 1, vascular cell adhesion protein 1 and flow-mediated dilation (FMD).

Data extraction and analysis

Relevant data were extracted for summary tables and analyses by two independent researchers. Random effects meta-analyses were conducted to explore weighted mean differences (WMD) in change or final mean values for each outcome.

Results

A total of 32 studies (all randomised controlled trials) were included in the review. The effect of nut consumption on FMD was explored in nine strata from eight studies (involving 652 participants), with consumption of nuts resulting in significant improvements in FMD (WMD: 0.79%(95% CI 0.35 to 1.23)). Nut consumption resulted in small, non-significant differences in CRP (WMD: −0.01 mg/L (95% CI −0.06 to 0.03)) (26 strata from 25 studies), although sensitivity analyses suggest results for CRP may have been influenced by two individual studies. Small, non-significant differences were also found for other biomarkers of inflammation.

Conclusions

This systematic review and meta-analysis of the effects of nut consumption on inflammation and endothelial function found evidence for favourable effects on FMD, a measure of endothelial function. Non-significant changes in other biomarkers indicate a lack of consistent evidence for effects of nut consumption on inflammation. The findings of this analysis suggest a need for more research in this area, with a particular focus on randomised controlled trials.

PROSPERO registration number

CRD42016045424.
Cerebrospinal fluid biomarkers for the diagnosis and prognosis of Parkinson’s disease: protocol for a systematic review and individual participant data meta-analysis
Authors: Eusebi Paolo , Hansson Oskar , Paciotti Silvia , Orso Massimiliano , Chiasserini Davide , Calabresi Paolo , Blennow Kaj , Parnetti Lucilla
Published: November 2017

Introduction

Idiopathic Parkinson’s disease (PD) is a progressive neurodegenerative disorder related to α-synuclein misfolding and aggregation. For this reason, it belongs to the family of ‘synucleinopathies’, which also includes some other neurological diseases. Although imaging and ancillary investigations may be helpful in the diagnostic workup, the diagnosis of PD mostly relies on the clinician’s expertise. Furthermore, there is a need today for markers that can track the disease progression in PD that might improve the evaluation of novel disease-modifying therapies. The cerebrospinal fluid (CSF) has been widely investigated with the purpose of finding useful diagnostic and prognostic biomarkers for PD.

Methods and analysis

This systematic review protocol has been developed according to the Preferred Reporting Items for Systematic reviews and Meta-Analyses Protocol 2015 statement and was registered on the PROSPERO international prospective register of systematic reviews. An international collaboration will be established. We will search the Cochrane Library, Web of Science, Medline and Embase from inception, using appropriate search strategies. Individual participant data from all included studies will be merged into a single database. We will include any study assessing the diagnostic and prognostic role of CSF biomarkers in PD. To evaluate the risk of bias and applicability of primary diagnostic accuracy studies, we will use Quality Assessment of Diagnostic Accuracy Studies-2 and Quality in Prognostic Studies. We will use standard meta-analytic procedures. We will first explore the utility of each CSF biomarker in turn. For each biomarker, we will assess its diagnostic and prognostic utility by means of receiver operating characteristic analysis and regression models. We will then move towards a multivariate approach considering different panels of biomarkers.

Ethics and dissemination

Our study will not include confidential data, and no intervention will be involved, so ethical approval is not required. The results of the study will be reported in international peer-reviewed journals.
Core outcome research measures in anal cancer (CORMAC): protocol for systematic review, qualitative interviews and Delphi survey to develop a core outcome set in anal cancer
Authors: Fish Rebecca , Sanders Caroline , Williamson Paula R , Renehan Andrew G
Published: November 2017

Introduction

The incidence of anal squamous cell carcinoma (ASCC) has increased threefold in the last 30 years. Initial treatment is chemoradiotherapy, associated with short-term and long-term side effects. Future therapy innovations aim to reduce morbidity in treatment of early tumours while maintaining treatment efficacy, and to escalate treatment intensity in locally advanced tumours with acceptable quality of life (QoL). However, all phase III randomised controlled trials to-date have utilised different primary outcomes, which hinders evidence synthesis and presents challenges to the selection of optimal outcomes in future trials. No trial comprehensively assessed long-term side effects and QoL, suggesting outcomes reflecting issues important to patients are under-represented. This project aims to determine the priority outcomes for all stakeholders and reach agreement on a standardised core set of outcomes to be measured and reported on in all future ASCC trials.

Methods and analysis

A systematic review will identify all outcomes reported in trials and observational studies of chemoradiotherapy as primary treatment for ASCC. Outcomes of importance to patients will be identified through patient interviews. The long list of outcomes generated from the systematic review and interviews will be used to create a two-round Delphi process, including key stakeholders (patients and healthcare professionals). The results of the Delphi will be discussed at a face-to-face consensus meeting. Discussion will focus on outcomes that did not achieve consensus through the Delphi process and conclude with anonymous voting to ratify the final core outcome set (COS).

Ethics and dissemination

The final COS will feed directly into the PersonaLising Anal cancer radioTherapy dOse (PLATO) national anal cancer trials and the Association of coloproctologists of Great Britain and Ireland (ACPGBI) supported national anal cancer database. Utilisation of the COS will increase the relevance of research output to all stakeholders and increase the capacity for data synthesis between trials. This study has ethical approval and is registered with the Core Outcome Measures in Effectiveness Trials (COMET) initiative.

Trial registration number

PROSPERO registration ID:CRD42016036540