bluuebunny/crossref_metadata_2025 huggingface dataset:
Genomic diversity of a nectar yeast clusters into metabolically, but not geographically, distinct lineages
Authors: Dhami Manpreet K. , Hartwig Thomas , Letten Andrew D. , Banf Michael , Fukami Tadashi
Published: February 2018

Both dispersal limitation and environmental sorting can affect genetic variation in populations, but their contribution remains unclear, particularly in microbes. We sought to determine the contribution of geographic distance (as a proxy for dispersal limitation) and phenotypic traits (as a proxy for environmental sorting), including morphology, metabolic ability and interspecific competitiveness, to the genotypic diversity in a nectar yeast species, Metschnikowia reukaufii. To measure genotypic diversity, we sequenced the genomes of 102 strains of M. reukaufii isolated from the floral nectar of hummingbird‐pollinated shrub, Mimulus aurantiacus, along a 200‐km coastline in California. Intraspecific genetic variation showed no detectable relationship with geographic distance, but could be grouped into three distinct lineages that correlated with metabolic ability and interspecific competitiveness. Despite ample evidence for strong competitive interactions within and among nectar yeasts, a full spectrum of the genotypic and phenotypic diversity observed across the 200‐km coastline was represented even at a scale as small as 200 m. Further, more competitive strains were not necessarily more abundant. These results suggest that dispersal limitation and environmental sorting might not fully explain intraspecific diversity in this microbe and highlight the need to also consider other ecological factors such as trade‐offs, source‐sink dynamics and niche modification.
ClpC and MecA, components of a proteolytic machine, prevent Spo0A‐P‐dependent transcription without degradation
Authors: Tanner Andrew W. , Carabetta Valerie J. , Dubnau David
Published: February 2018

In Bacillus subtilis, a proteolytic machine composed of MecA, ClpC and ClpP degrades the transcription factor ComK, controlling its accumulation during growth. MecA also inhibits sporulation and biofilm formation by down‐regulating spoIIG and sinI, genes that are dependent for their transcription on the phosphorylated protein Spo0A‐P. Additionally, MecA has been shown to interact in vitro with Spo0A. Although the inhibitory effect on transcription requires MecA's binding partner ClpC, inhibition is not accompanied by the degradation of Spo0A, pointing to a previously unsuspected regulatory mechanism involving these proteins. Here, we further investigate the MecA and ClpC effects on Spo0A‐P‐dependent transcription. We show that MecA inhibits the transcription of several Spo0A‐P activated genes, but fails to de‐repress several Spo0A‐P repressed promoters. This demonstrates that MecA and ClpC do not act by preventing the binding of Spo0A‐P to its target promoters. Consistent with this, MecA by itself has no effect in vitro on the transcription from PspoIIG while the addition of both MecA and ClpC has a strong inhibitory effect. A complex of MecA and ClpC likely binds to Spo0A‐P on its target promoters, preventing the activation of transcription. Thus, components of a degradative machine have been harnessed to directly repress transcription.
‘Forgotten Europeans’: transnational minority activism in the age of European integration
Authors: Smith David J. , Germane Marina , Housden Martyn
Published: February 2018

This article examines transnational activism by coalitions of national minorities in Europe from the early 20th century to the present, setting this within the broader ‘security versus democracy dilemma’ that continues to surround international discussions on minority rights. Specifically, we analyse two organisations – the European Nationalities Congress (1925–1938) and the Federal Union of European Nationalities (1949–) – which, while linked, have never been subject to a detailed comparison based on primary sources. In so far as comparisons do exist, they present these bodies in highly negative terms, as mere fronts for inherently particularistic nationalisms that threaten political stability, state integrity and peace. Our more in‐depth analysis provides a fresh and more nuanced perspective: it shows that, in both cases, concepts of European integration and ‘unity in diversity’ have provided the motivating goals and frameworks for transnational movements advocating common rights for all minorities and seeking positive interaction with the interstate world.
Eudicots from severely phosphorus‐impoverished environments preferentially allocate phosphorus to their mesophyll
Authors: Guilherme Pereira Caio , Clode Peta L. , Oliveira Rafael S. , Lambers Hans
Published: February 2018

Plants allocate nutrients to specific leaf cell types, with commelinoid monocots preferentially allocating phosphorus (P) to the mesophyll and calcium (Ca) to the epidermis, whereas the opposite is thought to occur in eudicots. However, Proteaceae from severely P‐impoverished habitats present the same P‐allocation pattern as monocots. This raises the question of whether preferential P allocation to mesophyll cells is a phylogenetically conserved trait, exclusive to commelinoid monocots and a few Proteaceae, or a trait that has evolved multiple times to allow plants to cope with very low soil P availability.

We analysed the P‐allocation patterns of 16 species from 10 genera, eight families and six orders within three major clades of eudicots across different P‐impoverished environments in Australia and Brazil, using elemental X‐ray mapping to quantitatively determine leaf cell‐specific nutrient concentrations.

Many of the analysed species showed P‐allocation patterns that differed substantially from that expected for eudicots. Instead, P‐allocation patterns were strongly associated with the P availability in the natural habitat of the species, suggesting a convergent evolution of P‐allocation patterns at the cellular level, with P limitation as selective pressure and without a consistent P‐allocation pattern within eudicots.

Here, we show that most eudicots from severely P‐impoverished environments preferentially allocated P to their mesophyll. We surmise that this preferential P allocation to photosynthetically active cells might contribute to the very high photosynthetic P‐use efficiency of species adapted to P‐impoverished habitats.
Wittgenstein's Legacy: The Principles of the Private Language Arguments
Authors: Hacker Peter
Published: February 2018

The article extracts the most general principles established by Wittgenstein's private language arguments in Investigations §§243‐316 and investigates their general application both in philosophy and in the sciences of the mind.
Thyroid carcinoma producing β‐human chorionic gonadotropin shows different clinical behavior
Authors: Gu Haiyan , Sui Shaofeng , Cui Xiujie , Han Bo , Zhang Chunyan , Qi Mei , Li Congcong , Liu Zhiyan
Published: February 2018

Columnar cell variant of papillary thyroid carcinoma (CCV‐PTC) is an unusual neoplasm, the clinical behavior of which mainly depends on the encapsulation or infiltration. Patients with extensive extrathyroidal extension usually have an aggressive biological behavior. This study confirmed that beta‐human chorionic gonadotropin (β‐hCG) secreting invasive CCV‐PTC has good prognosis comparing with a cohort of follicular cell differentiated thyroid carcinoma. On the contrary, positive immunoreaction with β‐hCG was proved in three anaplastic thyroid carcinoma patients showing aggressive clinical courses. The clinicopathologic characteristics of CCV‐PTC and the paraneoplastic syndromes in follicular cell differentiated thyroid carcinoma were further summarized using literature review.
Inoculum potential of Sclerotinia sclerotiorum sclerotia depends on isolate and host plant
Authors: Taylor A. , Coventry E. , Handy C. , West J. S. , Young C. S. , Clarkson J. P.
Published: February 2018

The soilborne fungus Sclerotinia sclerotiorum infects many important crop plants. Central to the success of this pathogen is the production of sclerotia, which enables survival in soil and constitutes the primary inoculum. This study aimed to determine how crop plant type and S. sclerotiorum isolate impact sclerotial production and germination and hence inoculum potential. Three S. sclerotiorum isolates (L6, L17, L44) were used to inoculate plants of bean, carrot, lettuce, oilseed rape (OSR) and potato, and the number and weight of sclerotia per plant quantified. Carpogenic germination of sclerotia collected from different hosts was also assessed for L6. Production of sclerotia was dependent on both crop plant type and S. sclerotiorum isolate, with OSR and lettuce supporting the greatest number (42–122) and weight (1.6–3.0 g) of sclerotia per plant. The largest sclerotia were produced on OSR (33–66 mg). The three S. sclerotiorum isolates exhibited a consistent pattern of sclerotial production irrespective of crop type; L6 produced large numbers of small sclerotia while L44 produced smaller numbers of large sclerotia, with L17 intermediate between the two. Germination rate and percentage was greatest for larger sclerotia (4.0–6.7 mm) and also varied between host plants. Combining sclerotial production data and typical field crop densities suggested that infected carrot and OSR could produce the greatest number (3944 m−2) and weight (73 g m−2) of S. sclerotiorum sclerotia, respectively, suggesting these crops potentially contribute a greater increase in inoculum. This information, once further validated in field trials, could be used to inform future crop rotation decisions.
Lack of mitochondrial thioredoxin o1 is compensated by antioxidant components under salinity in Arabidopsis thaliana plants
Authors: Calderón Aingeru , Sánchez‐Guerrero Antonio , Ortiz‐Espín Ana , Martínez‐Alcalá Isabel , Camejo Daymi , Jiménez Ana , Sevilla Francisca
Published: February 2018

In a changing environment, plants are able to acclimate to new conditions by regulating their metabolism through the antioxidant and redox systems involved in the stress response. Here, we studied a mitochondrial thioredoxin in wild‐type (WT) Arabidopis thaliana and two Attrxo1 mutant lines grown in the absence or presence of 100 mM NaCl. Compared to WT plants, no evident phenotype was observed in the mutant plants under control condition, although they had higher number of stomata, loss of water, nitric oxide and carbonyl protein contents as well as higher activity of superoxide dismutase (SOD) and catalase enzymes than WT plants. Under salinity, the mutants presented lower water loss and higher stomatal closure, H2O2 and lipid peroxidation levels accompanied by higher enzymatic activity of catalase and the different SOD isoenzymes compared to WT plants. These inductions may collaborate in the maintenance of plant integrity and growth observed under saline conditions, possibly as a way to compensate the lack of TRXo1. We discuss the potential of TRXo1 to influence the development of the whole plant under saline conditions, which have great value for the agronomy of plants growing under unfavorable environment.
Species transfer via topsoil translocation: lessons from two large Mediterranean restoration projects
Authors: Buisson Elise , Jaunatre Renaud , Römermann Christine , Bulot Adeline , Dutoit Thierry
Published: February 2018

Restoration success of species‐rich grasslands is often limited by low seed dispersal. To reintroduce target species of local provenances, bulk topsoil transfer is performed by excavating soil and vegetation from donor sites and spreading these on receptor sites. Our first objective was to determine the most advantageous season for transferring topsoil in Mediterranean grasslands. The second objective was to assess which treatment—combination of season (spring or autumn) and transfer ratio (1:1 or 1:3)—performed best in restoring a Mediterranean grassland through bulk topsoil transfer after two large restoration projects. Just‐in‐time soil transfer (i.e. with no stockpiling) was implemented: (1) on a former 3 ha orchard where topsoil was spread after removing trees and leveling soil; and (2) after a 5 ha oil pipeline leak where polluted soil was removed prior to treatment (soil horizons were reconstituted). A seed bank study showed that the summer seed bank contained higher seed densities, species richness, and similarity to the reference site than the spring seed bank. Spring transfers gave better results than autumn transfers in terms of species richness and composition similarity with the reference site, while transfer ratios gave similar results. Long‐term success was not driven by season or transfer ratio but by the underlying seed bank at receptor sites: the former orchard's weed‐containing seed bank hampered topsoil transfer success. This study also suggests that restoration success cannot be deduced from seed bank studies alone, as species establishment is highly dependent on differences in growing conditions (including competition at receptor sites).
Statistical Inference and Applications of Mixture of Varying Coefficient Models
Authors: Huang Mian , Yao Weixin , Wang Shaoli , Chen Yixin
Published: February 2018

In this paper, we consider a new mixture of varying coefficient models, in which each mixture component follows a varying coefficient model and the mixing proportions and dispersion parameters are also allowed to be unknown smooth functions. We systematically study the identifiability, estimation and inference for the new mixture model. The proposed new mixture model is rather general, encompassing many mixture models as its special cases such as mixtures of linear regression models, mixtures of generalized linear models, mixtures of partially linear models and mixtures of generalized additive models, some of which are new mixture models by themselves and have not been investigated before. The new mixture of varying coefficient model is shown to be identifiable under mild conditions. We develop a local likelihood procedure and a modified expectation–maximization algorithm for the estimation of the unknown non‐parametric functions. Asymptotic normality is established for the proposed estimator. A generalized likelihood ratio test is further developed for testing whether some of the unknown functions are constants. We derive the asymptotic distribution of the proposed generalized likelihood ratio test statistics and prove that the Wilks phenomenon holds. The proposed methodology is illustrated by Monte Carlo simulations and an analysis of a CO2‐GDP data set.
A Class of Semiparametric Transformation Models for Doubly Censored Failure Time Data
Authors: Li Shuwei , Hu Tao , Wang Peijie , Sun Jianguo
Published: February 2018

Doubly censored failure time data occur in many areas including demographical studies, epidemiology studies, medical studies and tumorigenicity experiments, and correspondingly some inference procedures have been developed in the literature (Biometrika, 91, 2004, 277; Comput. Statist. Data Anal., 57, 2013, 41; J. Comput. Graph. Statist., 13, 2004, 123). In this paper, we discuss regression analysis of such data under a class of flexible semiparametric transformation models, which includes some commonly used models for doubly censored data as special cases. For inference, the non‐parametric maximum likelihood estimation will be developed and in particular, we will present a novel expectation–maximization algorithm with the use of subject‐specific independent Poisson variables. In addition, the asymptotic properties of the proposed estimators are established and an extensive simulation study suggests that the proposed methodology works well for practical situations. The method is applied to an AIDS study.
Tacrolimus concentration to dose ratio in solid organ transplant patients treated with fecal microbiota transplantation for recurrent Clostridium difficile infection
Authors: Woodworth Michael H. , Kraft Colleen S. , Meredith Erika J. , Mehta Aneesh K. , Wang Tiffany , Mamo Yafet T. , Dhere Tanvi , Sitchenko Kaitlin L. , Patzer Rachel E. , Friedman‐Moraco Rachel J.
Published: February 2018

Fecal microbiota transplantation (FMT) is increasingly being performed for Clostridium difficile infection in solid organ transplant (SOT) patients; however, little is known about the potential pharmacokinetic or pharmacomicrobial effects this may have on tacrolimus levels. We reviewed the medical records of 10 SOT patients from September 2012‐December 2016 who were taking tacrolimus at time of FMT for recurrent C. difficile infection. We compared the differences in tacrolimus concentration/dose ratio (C/D ratio) 3 months prior to FMT vs 3 months after FMT. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/kg/d) was −17.65 (95% CI −1.25 to 0.58) (ng/mL)/(mg/kg/d), P‐value .43 by Wilcoxon signed‐rank test. The mean of the differences in C/D ratio calculated as (ng/mL)/(mg/d) was −0.33 (95% CI −1.25 to 0.58) (ng/mL)/(mg/d), P‐value .28 by Wilcoxon signed‐rank test. Of these patients, 2/10 underwent allograft biopsy for allograft dysfunction in the year after FMT, with no evidence of allograft rejection on pathology. These preliminary data suggest that FMT may not predictably alter tacrolimus levels and support its safety for SOT patients however further study in randomized trials is needed.
Development of a clinical prediction rule for tuberculous meningitis in adults in Lima, Peru
Authors: Solari Lely , Soto Alonso , Van der Stuyft Patrick
Published: February 2018

Objectives

Diagnosis of tuberculous meningitis (TM) is a challenge in countries with a high burden of the disease and constrained resources and clinical prediction rules (CPRs) could be of assistance. We aimed at developing a CPR for diagnosis of TM in a Latin American setting with high tuberculosis incidence and a concentrated HIV epidemic.

Methods

We enrolled adult patients with clinical suspicion of TM attending two hospitals in Lima, Peru. We obtained information on potential anamnestic, clinical and laboratory predictive findings that are easy to collect and promptly available. We independently diagnosed TM according to a composite reference standard that included a series of microbiological tests. We performed bivariate analysis and constructed a logistic regression model to select the predictive findings associated with TM. With the selected predictors included in the model, we developed a score‐based CPR. We assessed its internal validity and diagnostic performance.

Results

Of 155 analysed patients, 59 (38%) had TM. The CPR we derived includes three predictors: cough for 14 days or more, 10–500 cells in CSF and adenosine deaminase ≥ 6 U/l in CSF. It classifies patients into high‐, moderate‐ or low‐score groups and has an overall area under the ROC curve of 0.87. 59% of patients were assigned to either the high‐ or the low‐score group, permitting prompt decision‐making. In patients in the high‐score group, it attains a positive likelihood ratio for TM of 10.6 and in patients with low scores, a negative likelihood ratio of 0.10. Bootstrap analysis indicated high internal validity.

Conclusion

This CPR could support decision‐making in patients with clinical suspicion of TM. External validation and further assessment of its clinical impact are necessary before application in other settings.
CRISPR/Cas9‐mediated mutagenesis of lncRNA1459 alters tomato fruit ripening
Authors: Li Ran , Fu Daqi , Zhu Benzhong , Luo Yunbo , Zhu Hongliang
Published: February 2018

With the development of high‐throughput sequencing, many long non‐coding RNAs (lncRNAs) have been found to play important roles in diverse biological processes. However, the biological functions of most plant lncRNAs are still unknown. We have previously discovered a tomato ripening‐related lncRNA, lncRNA1459. Here, we cloned the full‐length lncRNA1459, giving two transcript isoforms. In addition, lncRNA1459 exhibited a specific location in the nucleus. Furthermore, in order to fully identify the function of lncRNA1459 in tomato ripening, loss‐of‐function mutants of lncRNA1459 were developed using clustered regularly interspaced short palindromic repeats (CRISPR)/‐associated protein 9 (Cas9)‐induced genome editing technology. Compared with wild‐type fruits, the tomato ripening process was significantly repressed in lncRNA1459 mutants. Ethylene production and lycopene accumulation were largely repressed in lncRNA1459 mutants. Additionally, genes related to ethylene and carotenoid biosynthesis were distinctly downregulated in lncRNA1459 mutants compared with wild‐type fruits. Moreover, expression of numerous ripening‐related genes was changed significantly when lncRNA1459 was knocked out. Expression of potential tomato ripening‐related lncRNAs was also specifically changed after knocking out lncRNA1459. Taken together, these results provide insight into the role of lncRNA1459 in tomato fruit ripening.
Characterization of source plasma from self‐identified vaccinated or convalescent donors during the 2009 H1N1 pandemic
Authors: Khalenkov Alexey , He Yong , Reed Jennifer L. , Kreil Thomas R. , McVey John , Norton Malgorzata , Scott John , Scott Dorothy E.
Published: February 2018

BACKGROUND

Influenza immune globulin, manufactured from plasma of convalescent or vaccinated donors has been proposed as a potential therapy for severe influenza. In 2009, a program was initiated to collect plasma from donors who self‐identified as having had H1N1 influenza or having received the H1N1 pandemic vaccine. The goal of this study was to determine the efficiency of donor screening by self‐identification without antibody testing, and to evaluate demographic predictors of high‐titer donations.

STUDY DESIGN AND METHODS

Plasma samples from self‐identified or control donors were randomly selected to evaluate hemagglutination inhibition (HAI) antibody responses. HAI titers were correlated with donor age, gender, location, and influenza exposure history.

RESULTS

Both self‐identified vaccinated and convalescent donor groups had higher geometric mean titers (GMTs) against A/California/07/2009 (H1N1) virus compared to the control donors (39.9, 24, and 8.5, respectively). The proportion of samples with titers ≥64 in vaccinated, convalescent, and control donors were 54%, 37%, and 10%, respectively. Donations with titers ≤16 were predominant in control donors (80%) and substantial in convalescent (47%) and vaccinated (40%) donors. Titers did not correlate with donor age, gender, or geographical location. GMTs for vaccinated donors were significantly higher than for convalescent donors and in both groups significantly higher than in the control.

CONCLUSION

Targeted collection of plasma containing high levels of anti‐influenza antibodies from self‐identified donors was effective, but could be further improved by reducing the number of low‐titer donations. More selective donor screening and/or testing for influenza antibodies could increase the potency of an influenza antibody‐rich immune globulin (FLUIGIV).
Comparison of detergent‐based decellularization protocols for the removal of antigenic cellular components in porcine aortic valve
Authors: Liu Xiaohong , Li Ning , Gong Dejun , Xia Cuiping , Xu Zhiyun
Published: February 2018

Background

Various detergent‐based protocols are used to remove cells and cellular debris in porcine aortic valve (PAV). However, the removal of antigenic cellular components has not been thoroughly elucidated to date. In this study, we used 4 detergent‐based protocols to decellularize PAVs and aimed to evaluate their effects on removing antigenic cellular components.

Methods

Porcine aortic valves were decellularized using sodium dodecyl sulfate (SDS), SDS in combination with sodium deoxycholate (SDS/SD), Triton X‐100, and Triton X‐100 in combination with SD (Triton X‐100/SD), respectively. Untreated PAVs were used as controls. Immunohistochemical and SDS‐polyacrylamide gel electrophoresis (SDS‐PAGE) analyses were performed to determine the removal of antigenic protein components. Histological, biochemical, and biomechanical analyses were performed to determine the preservation and mechanical properties of the extracellular matrix. PAV tissues were implanted subcutaneously in Sprague Dawley rats to evaluate the host immune response. Implanted PAVs were taken out at the indicated time points for histological and immunohistochemical examinations.

Results

All 4 protocols effectively removed the membrane antigenic proteins major histocompatibility complex I molecule and galactose‐α‐1,3 galactose. The SDS/SD protocol was the most effective method to remove the cytoplasmic cytoskeletal proteins, vimentin and α‐SMA, and SDS alone partly removed vimentin protein. The SDS/SD protocol was the most effective method to remove nuclear DNA with residual DNA below 50 ng/mg, followed by the SDS protocol with residual DNA of 74.9 ng/mg. The SDS protocol was the most effective method to remove proteins ranged from 10 to 55 kDa, followed by the SDS/SD protocol. SDS and SDS/SD PAV implants attracted fewer neutrophils in vivo on postoperative day 3. The infiltration of macrophages and T lymphocytes was significantly lower in SDS and SDS/SD implants on days 14 and day 28. All of the decellularized protocols that were examined greatly reduced the contents of collagen, elastin, and glycosaminoglycan compared to controls. Biomechanical analysis revealed significant differences in ultimate tensile strength and Young's modulus between control PAVs and decellularized PAVs generated using SDS, SDS/SD, Triton X‐100, or Triton X‐100/SD.

Conclusions

These results indicated that SDS‐based protocols more effectively removed antigenic cellular components compared to Triton X‐100‐based protocols. These results are clinically significant because complete removal of antigenic determinants is critical to decrease adverse immune‐mediated and inflammatory responses to a PAV when used in xenogeneic application.
Atmospheric plasma-enhanced spatial-ALD of InZnO for high mobility thin film transistors
Authors: Illiberi Andrea , Katsouras Ilias , Gazibegovic Sasa , Cobb Brian , Nekovic Elida , van Boekel Willem , Frijters Corne , Maas Joris , Roozeboom Fred , Creyghton Yves , Poodt Paul , Gelinck Gerwin
Published: February 2018

In this manuscript, the authors investigate the growth of indium zinc oxide, indium zinc oxide (InZnO, IZO) as a channel material for thin-film transistors. IZO is grown at atmospheric pressure and a high deposition rate using spatial atomic layer deposition (S-ALD). By varying the ratio of diethylzinc and trimethylindium vapor, the In/(In + Zn) ratio of the film can be accurately tuned in the entire range from zinc oxide to indium oxide. Thin film transistors with an In to Zn ratio of 2:1 show high field-effect mobility—exceeding 30 cm2/V s—and excellent stability. The authors demonstrate large scale integration in the form of 19-stage ring oscillators operating at 110 kHz. These electrical characteristics, in combination with the intrinsic advantages of atomic layer deposition, demonstrate the great potential of S-ALD for future display production.
Characterization of a polymer, open-cell rigid foam that simulates the ultrasonic properties of cancellous bone
Authors: Hoffmeister Brent K. , Huber Matthew T. , Viano Ann M. , Huang Jinsong
Published: February 2018

Materials that simulate the ultrasonic properties of tissues are used widely for clinical and research purposes. However, relatively few materials are known to simulate the ultrasonic properties of cancellous bone. The goal of the present study was to investigate the suitability of using a polymer, open-cell rigid foam (OCRF) produced by Sawbones®. Measurements were performed on OCRF specimens with four different densities. Ultrasonic speed of sound and normalized broadband ultrasonic attenuation were measured with a 0.5 MHz transducer. Three backscatter parameters were measured with a 5 MHz transducer: apparent integrated backscatter, frequency slope of apparent backscatter, and normalized mean of the backscatter difference. X-ray micro-computed tomography was used to measure the microstructural characteristics of the OCRF specimens. The trabecular thickness and relative bone volume of the OCRF specimens were similar to those of human cancellous bone, but the trabecular separation was greater. In most cases, the ultrasonic properties of the OCRF specimens were similar to values reported in the literature for cancellous bone, including dependence on density. In addition, the OCRF specimens exhibited an ultrasonic anisotropy similar to that reported for cancellous bone.
Temporal weights in the perception of sound intensity: Effects of sound duration and number of temporal segments
Authors: Oberfeld Daniel , Hots Jan , Verhey Jesko L.
Published: February 2018

Loudness is a fundamental aspect of auditory perception that is closely related to the physical level of the sound. However, it has been demonstrated that, in contrast to a sound level meter, human listeners do not weight all temporal segments of a sound equally. Instead, the beginning of a sound is more important for loudness estimation than later temporal portions. The present study investigates the mechanism underlying this primacy effect by varying the number of equal-duration temporal segments (5 and 20) and the total duration of the sound (1.0 to 10.0 s) in a factorial design. Pronounced primacy effects were observed for all 20-segment sounds. The temporal weights for the five-segment sounds are similar to those for the 20-segment sounds when the weights of the segments covering the same temporal range as a segment of the five-segment sounds are averaged. The primacy effect can be described by an exponential decay function with a time constant of about 200 ms. Thus, the temporal weight assigned to a specific temporal portion of a sound is determined by the time delay between sound onset and segment onset rather than by the number of segments or the total duration of the sound.
Acoustic pulse propagation in forests
Authors: Muhlestein Michael B. , Ostashev Vladimir E. , Wilson D. Keith , Albert Donald G.
Published: February 2018

The propagation of acoustic pulses through a forest is considered. Multiple-scattering effects are accounted for by using the energy-based radiative transfer theory under a modified Born approximation, resulting in an expression for the diffuse intensity as a function of time and dominant frequency. While this expression is a complicated set of three integrals, certain practical approximations enable analytic evaluation of one, two, or even all three integrals. Any remaining integrals may be numerically calculated. The simple case of an impulse in an infinite homogeneous forest of diffuse scatterers is first considered, and then the effects of successively including non-diffuse scatterers, ground reflections in a forest of finite height, and finally a realistic forest model are analyzed with an emphasis on long-time decay and reverberation times. These theoretical findings are then compared with experimental results.
GRL-079, a Novel HIV-1 Protease Inhibitor, Is Extremely Potent against Multidrug-Resistant HIV-1 Variants and Has a High Genetic Barrier against the Emergence of Resistant Variants
Authors: Delino Nicole S. , Aoki Manabu , Hayashi Hironori , Hattori Shin-ichiro , Chang Simon B. , Takamatsu Yuki , Martyr Cuthbert D. , Das Debananda , Ghosh Arun K. , Mitsuya Hiroaki
Published: February 2018

We identified four novel nonpeptidic human immunodeficiency virus type 1 (HIV-1) protease inhibitors (PIs), GRL-078, -079, -077, and -058, containing an alkylamine at the C-5 position of P2 tetrahydropyrano-tetrahydrofuran (Tp-THF) and a P2′ cyclopropyl (Cp) (or isopropyl)-aminobenzothiazole (Abt) moiety. Their 50% effective concentrations (EC
50
s) were 2.5 to 30 nM against wild-type HIV-1
NL4-3
, 0.3 to 6.7 nM against HIV-2
EHO
, and 0.9 to 90 nM against laboratory-selected PI-resistant HIV-1 and clinical HIV-1 variants resistant to multiple FDA-approved PIs (HIV
MDR
). GRL-078, -079, -077, and -058 also effectively blocked the replication of HIV-1 variants highly resistant to darunavir (DRV) (HIV
DRV
r
p51
), with EC
50
s of 38, 62, 61, and 90 nM, respectively, while four FDA-approved PIs examined (amprenavir, atazanavir, lopinavir [LPV], and DRV) had virtually no activity (EC
50
s of >1,000 nM) against HIV
DRV
r
p51
. Structurally, GRL-078, -079, and -058 form strong hydrogen bond interactions between Tp-THF modified at C-5 and Asp29/Asp30/Gly48 of wild-type protease, while the P2′ Cp-Abt group forms strong hydrogen bonds with Asp30′. The Tp-THF and Cp-Abt moieties also have good nonpolar interactions with protease residues located in the flap region. For selection with LPV and DRV by use of a mixture of 11 HIV
MDR
strains (HIV
11MIX
), HIV
11MIX
became highly resistant to LPV and DRV over 13 to 32 and 32 to 41 weeks, respectively. However, for selection with GRL-079 and GRL-058, HIV
11MIX
failed to replicate at >0.08 μM and >0.2 μM, respectively. Thermal stability results supported the highly favorable anti-HIV-1 potency of GRL-079 as well as other PIs. The present data strongly suggest that the P2 Tp-THF group modified at C-5 and the P2′ Abt group contribute to the potent anti-HIV-1 profiles of the four PIs against HIV-1
NL4-3
and a wide spectrum of HIV
MDR
strains.
Molecular and Functional Study of a Branching Sucrase-Like Glucansucrase Reveals an Evolutionary Intermediate between Two Subfamilies of the GH70 Enzymes
Authors: Yan Minghui , Wang Bing-hua , Xu Xiaofen , Chang Peng , Hang Feng , Wu Zhengjun , You Chunping , Liu Zhenmin
Published: February 2018

Glucansucrases (GSs) in glycoside hydrolase family 70 (GH70) catalyze the synthesis of α-glucans from sucrose, a reaction that is widely seen in lactic acid bacteria (LAB). These enzymes have been implicated in many aspects of microbial life. Products of GSs have great commercial value as food supplements and medical materials; therefore, these enzymes have attracted much attention from both science and industry. Certain issues concerning the origin and evolution of GSs are still to be addressed, although an increasing number of GH70 enzymes have been characterized. This study describes a GS enzyme with the appearance of a branching sucrase (BrS). Structural analysis indicated that this GS enzyme produced a type of glucan composed of an α-(1→6) glucosidic backbone and α-(1→4) branches, as well as a considerable amount of α-(1→3) branches, distinguishing it from the GSs identified so far. Moreover, sequence-based analysis of the catalytic core of this enzyme suggested that it might be an evolutionary intermediate between the BrS and GS subgroups. These results provide an evolutionary link between these subgroups of GH70 enzymes and shed new light on the origination of GSs.

IMPORTANCE
GH70 GSs catalyze the synthesis of α-glucans from sucrose, a reaction that is widely seen in LAB. Products of these enzymes have great commercial value as food supplements and medical materials. Moreover, these enzymes have attracted much attention from scientists because they have potential in tailored synthesis of α-glucans with desired structures and properties. Although more and more GSs have been characterized, the origin and evolution of these enzymes have not been well addressed. This study describes a GS with the appearance of a BrS (i.e., high levels of similarity to BrSs in sequence analysis). Further analysis indicated that this enzyme synthesized a type of insoluble glucan composed of an α-(1→6) glucosidic backbone and many α-(1→4)- and α-(1→3)-linked branches, the linkage composition of which has rarely been reported in the literature. This BrS-like GS enzyme might be an evolutionary intermediate between BrS and GS enzymes.
A mos oncogene-containing retrovirus, myeloproliferative sarcoma virus, transforms rat thyroid epithelial cells and irreversibly blocks their differentiation pattern
Authors: Fusco A , Portella G , Di Fiore P P , Berlingieri M T , Di Lauro R , Schneider A B , Vecchio G
Published: February 2018

Differentiated, cloned rat thyroid epithelial cells (424 cells) were infected with a wild-type and a temperature-sensitive strain of the myeloproliferative variant of the Moloney murine sarcoma virus. The thyroid cells were productively infected and transformed by both virus strains and displayed some of the typical properties of malignant cells, such as morphological changes, growth in soft agar, and in vivo tumorigenicity. The acquisition of the transformed phenotype by the virus-infected cells was accompanied by a loss of the typical differentiated features of the thyroid epithelium, such as thyroglobulin (TG) secretion, iodide uptake, and dependence for growth on six factors including thyrotropin, the physiological thyroid stimulator. TG mRNA could not be demonstrated in cells transformed by both viral strains, suggesting a block at the level of the TG gene transcription. While the transformed state of the cell clones infected with the temperature-sensitive strain could be reverted by shifting the cultures to the temperature nonpermissive for transformation (39 degrees C), no reversion of the differentiated functions took place after such a shift, showing that the v-mos oncogene irreversibly shuts off the differentiation of thyroid epithelial cells in vitro. These results demonstrate, for the first time, an oncogenic potential of the v-mos oncogene family towards differentiated epithelial cells in vitro.
Antimicrobial activity of a novel bioengineered honey against non-typeableHaemophilus influenzaebiofilms: an in vitro study
Authors: Newby Rachel S , Dryden Matthew , Allan Raymond N , Salib Rami J
Published: February 2018

The opportunistic pathogen non-typeableHaemophilus influenzae(NTHi) plays an important role in many chronic respiratory diseases including otitis media, chronic rhinosinusitis, cystic fibrosis and chronic obstructive pulmonary disease. Biofilm formation has been implicated in NTHi colonisation, persistence of infection and recalcitrance towards antimicrobials. There is therefore a pressing need for the development of novel treatment strategies that are effective against NTHi biofilm-associated diseases. SurgihoneyRO is a honey-based product that has been bioengineered to enable the slow release of H2O2, a reactive oxygen species to whichH. influenzaeis susceptible. Treatment of established NTHi biofilms with SurgihoneyRO significantly reduced biofilm viability through enhanced H2O2production and was shown to be more effective than the conventional antibiotic co-amoxiclav.
No inferiority of Tonbridge thrombectomy device for acute thrombus retrial compared with Solitaire device: an experimental evaluation with a canine distal external carotid-maxillary artery occlusion model
Authors: Zhou Geng , Li Ming-Hua , Lu Hai-Tao , Deng Jiang-Shan , Zhao Yu-Wu , Wang Yi Xiang J , Zhu Yue-Qi
Published: February 2018

Introduction

Mechanical thrombectomy (MT) has been widely accepted as a safe and effective treatment for acute ischemic stroke (AIS). Development of stent retriever devices has been intensively developed over the past two decades. In this study, we compared the effectiveness and safety of a new thrombectomy device with Solitaire FR for the treatment of AIS models.

Methods

Mechanical performance of stent retrievers was tested in vitro. Thrombin-induced thrombus was pre-injected into the right distal external carotid-maxillary artery in 18 dogs to create an acute thrombus occlusion model, and these animals were divided into a Tonbridge group (n=9, with Tonbridge stent Tonbridge Medical Technology) and a Solitaire group as control (n=9, with Solitaire stent, ev3 Neurovascular). Final flow restoration, side branches, recanalization time, distal vessel embolism, and device-related complications were recorded and compared. A post-procedure angiogram was obtained at 30 and 90 days after thrombectomy. Device manipulation-related damage to the arterial walls was evaluated histologically.

Results

In vitro test showed that the maximum friction within the microcatheter was 0.763 for the Tonbridge device and 0.784 n for the Solitaire (P>0.05). Slight increase in radial force was noticed for the Tonbridge (0.035 N/mm vs 0.031 N/mm of Solitaire, P>0.05). Eighteen and 16 retriever attempts were done in the Tonbridge (mean 2.0 attempts) and the Solitaire (mean 1.8 attempts) groups (P=0.74). The Tonbridge device led to good flow restoration in all nine (100%) models compared with eight (88.9%) in the Solitaire group (P=0.30). Side branches' influence (P=0.39), distal thromboembolism (P=0.60), and device-related complications (P=1.00) found no difference between the two groups. The rates of disruption of the internal elastic lamina (IEL) were 8.3% (2/24) and 4.2% (1/24) of the specimens, respectively (P=0.683). TICI 2b/3 flow of the right CCA were similar between the two groups at 1 (6/6 vs 6/6) and 3 months (6/6 vs 6/6) follow-up (P>0.05).

Conclusion

Our preliminary study indicated this new device was technically feasible and effective to be used in thrombectomy for the treatment of acute thrombus occlusion in canine models.
Lung clearance index to monitor treatment response in pulmonary exacerbations in preschool children with cystic fibrosis
Authors: Rayment Jonathan H , Stanojevic Sanja , Davis Stephanie D , Retsch-Bogart George , Ratjen Felix
Published: February 2018

Background

Antibiotic treatment for pulmonary symptoms in preschool children with cystic fibrosis (CF) varies among clinicians. The lung clearance index (LCI) is sensitive to early CF lung disease, but its utility to monitor pulmonary exacerbations in young children has not been assessed.

Objective

We aim to (1) understand how LCI changes during lower respiratory tract symptoms relative to a recent clinically stable measurement, (2) determine whether LCI can identify antibiotic treatment response and (3) compare LCI changes to changes in spirometric indices.

Methods

LCI and spirometry were measured at quarterly clinic visits over a 12-month period in preschool children with CF. Symptomatic visits were identified and classified as treated or untreated. Treatment response was estimated using propensity score matching methods.

Results

104 symptomatic visits were identified in 78 participants. LCI increased from baseline in both treated (mean relative change +23.8% (95% CI 16.2 to 31.4)) and untreated symptomatic visits (mean relative change +11.2% (95% CI 2.4 to 19.9)). A significant antibiotic treatment effect was observed when LCI was used as the outcome measure (average treatment effect −15.5% (95% CI −25.4 to −5.6)) but not for z-score FEV1.

Conclusion

LCI significantly deteriorated with pulmonary symptoms relative to baseline and improved with antibiotic treatment. These data suggest that LCI may have a role in the routine clinical care of preschool children with CF.
Role of NADPH oxidase-2 and oxidative stress in children exposed to passive smoking
Authors: Loffredo Lorenzo , Zicari Anna Maria , Occasi Francesca , Perri Ludovica , Carnevale Roberto , Angelico Francesco , Del Ben Maria , Martino Francesco , Nocella Cristina , De Castro Giovanna , Cammisotto Vittoria , Battaglia Simona , Duse Marzia , Violi Francesco
Published: February 2018

This study explored oxidative stress, nicotinamide adenine dinucleotide phosphate oxidase-2 (Nox2) activity and endothelial function in children exposed or not to passive smoking. Compared with controls (n=57), Nox2 activity and isoprostanes were higher in children exposed to passive smoking (n=57); conversely, nitric oxide (NO) bioavailability and flow-mediated dilation were lower in children exposed to passive smoking. A bivariate analysis showed that Nox2 activity correlated with flow-mediated dilation, NO bioavailability and isoprostanes. A multivariate analysis showed that Nox2 activity was significantly associated with serum isoprostanes and cotinine levels; flow-mediated dilation was associated with isoprostanes and carotid intima-media thickness.

In children exposed to passive smoking, Nox2-derived oxidative stress is upregulated and inversely associated with impaired artery dilation.
Gordon Hugh Kerr Lawson
Authors: Smith Geoffrey , Brown Duncan , Rowland Alan
Published: February 2018

A brilliant research academic who identified a new genus of bacteria, Lawsonia intracellularis. He was also a man of integrity and kindness, always willing to don his white coat to help any technician or student.
Parental overweight is associated with less encouragement of child dietary balance and variety and involvement in meal planning and preparation
Authors: Krystia Owen , Darlington Gerarda , Haines Jess , Ma David W.L. , Buchholz Andrea C.
Published: February 2018

Little is known about how the body composition of parents of preschool-aged children is associated with their food parenting practices. In this study, we examined associations between parental body composition and food parenting practices in a sample of Canadian families with preschool-aged children. We conducted a cross-sectional analysis of 68 parents and 52 preschool-aged children. Measures included height, weight, waist circumference (WC), and percentage of fat mass (%FM) measured by BOD POD™. Parents completed an adapted version of the Comprehensive Feeding Practices Questionnaire. To account for correlated observations within families, we used generalized estimating equations with linear regression modelling to examine associations between parent body composition and food parenting practices, with child body mass index (BMI) z-score, child sex, parental sex, and family household income entered as covariates in all models. Parent BMI, WC, and %FM were each significantly and inversely associated with the encouragement of a balanced diet ([Formula: see text] = −0.021, p = 0.006; [Formula: see text] = −0.007, p = 0.038; [Formula: see text] = −0.010, p = 0.034, respectively) and child involvement in meal planning and preparation ([Formula: see text] = −0.082, p = 0.002; [Formula: see text] = −0.025, p = 0.032; [Formula: see text] = −0.038, p = 0.049, respectively). We provide preliminary evidence that overweight/obesity may be associated with select food parenting practices in Canadian families with preschool-age children. Parental body composition may be an important consideration in intervention strategies that target food parenting practices.
In silico genome-wide identification and characterization of the glutathione S-transferase gene family in Vigna radiata
Authors: Vaish Swati , Awasthi Praveen , Tiwari Siddharth , Tiwari Shailesh Kumar , Gupta Divya , Basantani Mahesh Kumar
Published: February 2018

Plant glutathione S-transferases (GSTs) are integral to normal plant metabolism and biotic and abiotic stress tolerance. The GST gene family has been characterized in diverse plant species using molecular biology and bioinformatics approaches. In the current study, in silico analysis identified 44 GSTs in Vigna radiata. Of the total 44 GSTs identified, chromosomal locations of 31 GSTs were confirmed. The pI value of GST proteins ranged from 5.10 to 9.40. The predicted molecular weights ranged from 13.12 to 50 kDa. Subcellular localization analysis revealed that all GSTs were predominantly localized in the cytoplasm. The active site amino acids were confirmed to be serine in tau, phi, theta, zeta, and TCHQD; cysteine in lambda, DHAR, and omega; and tyrosine in EF1G. The gene architecture conformed to the two-exon/one-intron and three-exon/two-intron organization in the case of tau and phi classes, respectively. MEME analysis identified 10 significantly conserved motifs with the width of 8–50 amino acids. The motifs identified were either specific to a specific GST class or were shared by multiple GST classes. The results of the current study will be of potential importance in the characterization of the GST gene family in V. radiata, an economically important leguminous crop.