bluuebunny/crossref_metadata_2025 huggingface dataset:
Exopolysaccharides promote Myxococcus xanthus social motility by inhibiting cellular reversals
Authors: Zhou Tianyi , Nan Beiyan
Published: November 2016

The biofilm‐forming bacterium Myxococcus xanthus moves on surfaces as structured swarms utilizing type IV pili‐dependent social (S) motility. In contrast to isolated cells that reverse their moving direction frequently, individual cells within swarms rarely reverse. The regulatory mechanisms that inhibit cellular reversal and promote the formation of swarms are not well understood. Here we show that exopolysaccharides (EPS), the major extracellular components of M. xanthus swarms, inhibit cellular reversal in a concentration‐dependent manner. Thus, individual wild‐type cells reverse less frequently in swarms due to high local EPS concentrations. In contrast, cells defective in EPS production hyper‐reverse their moving direction and show severe defects in S‐motility. Surprisingly, S‐motility and wild‐type reversal frequency are restored in double mutants that are defective in both EPS production and the Frz chemosensory system, indicating that EPS regulates cellular reversal in parallel to the Frz pathway. Here we clarify that besides functioning as the structural scaffold in biofilms, EPS is a self‐produced signal that coordinates the group motion of the social bacterium M. xanthus.
Antimicrobial resistance surveillance in the genomic age
Authors: McArthur Andrew G. , Tsang Kara K.
Published: November 2016

The loss of effective antimicrobials is reducing our ability to protect the global population from infectious disease. However, the field of antibiotic drug discovery and the public health monitoring of antimicrobial resistance (AMR) is beginning to exploit the power of genome and metagenome sequencing. The creation of novel AMR bioinformatics tools and databases and their continued development will advance our understanding of the molecular mechanisms and threat severity of antibiotic resistance, while simultaneously improving our ability to accurately predict and screen for antibiotic resistance genes within environmental, agricultural, and clinical settings. To do so, efforts must be focused toward exploiting the advancements of genome sequencing and information technology. Currently, AMR bioinformatics software and databases reflect different scopes and functions, each with its own strengths and weaknesses. A review of the available tools reveals common approaches and reference data but also reveals gaps in our curated data, models, algorithms, and data‐sharing tools that must be addressed to conquer the limitations and areas of unmet need within the AMR research field before DNA sequencing can be fully exploited for AMR surveillance and improved clinical outcomes.
The effects of menstrual phase on orthodontic pain following initial archwire engagement
Authors: Long H , Gao M , Zhu Y , Liu H , Zhou Y , Liao L , Lai W
Published: November 2016

Objectives

To explore the effects of menstrual cycle on orthodontic pain following initial archwire engagement.

Methods

Female participants with regular menstrual cycles were recruited and assigned into follicular group or luteal group. Demographical and baseline variables were collected: age, education, menstrual duration, anxiety, oral health impact profile‐14 (OHIP‐14), and index of complexity outcome and need (ICON). Following initial archwire engagement, orthodontic pain was determined through visual analogue scale (VAS) on 1st day, 2nd day, and 3rd day. Demographical and baseline variables were compared between the two groups. Two‐way repeated‐measures anova was used to examine the effects of menstrual phase, time, and their interactions on orthodontic pain. Multivariate linear regression was employed to examine the independent effect of each variable on orthodontic pain.

Results

Finally, 37 and 39 were assigned to the follicular and luteal groups, respectively, with balanced demographical and baseline data. Orthodontic pain was significantly affected by menstrual phase and time (both P < 0.001), but there was no interaction (P > 0.05). Moreover, orthodontic pain was independently predicted by menstrual phase, OHIP, education level, and anxiety (all P < 0.05).

Conclusion

We suggest that practitioners arrange female patients to receive initial archwire engagement during their follicular phases to relieve orthodontic pain.
Animal movement in the absence of predation: environmental drivers of movement strategies in a partial migration system
Authors: Bastille‐Rousseau Guillaume , Gibbs James P. , Yackulic Charles B. , Frair Jacqueline L. , Cabrera Fredy , Rousseau Louis‐Philippe , Wikelski Martin , Kümmeth Franz , Blake Stephen
Published: November 2016

Animal movement strategies including migration, dispersal, nomadism, and residency are shaped by broad‐scale spatial‐temporal structuring of the environment, including factors such as the degrees of spatial variation, seasonality and inter‐annual predictability. Animal movement strategies, in turn, interact with the characteristics of individuals and the local distribution of resources to determine local patterns of resource selection with complex and poorly understood implications for animal fitness. Here we present a multi‐scale investigation of animal movement strategies and resource selection. We consider the degree to which spatial variation, seasonality, and inter‐annual predictability in resources drive migration patterns among different taxa and how movement strategies in turn shape local resource selection patterns. We focus on adult Galapagos giant tortoises Chelonoidis spp. as a model system since they display many movement strategies and evolved in the absence of predators of adults. Specifically, our analysis is based on 63 individuals among four taxa tracked on three islands over six years and almost 106 tortoise re‐locations. Tortoises displayed a continuum of movement strategies from migration to sedentarism that were linked to the spatio‐temporal scale and predictability of resource distributions. Movement strategies shaped patterns of resource selection. Specifically, migratory individuals displayed stronger selection toward areas where resources were more predictable among years than did non‐migratory individuals, which indicates a selective advantage for migrants in seasonally structured, more predictable environments. Our analytical framework combines large‐scale predictions for movement strategies, based on environmental structuring, with finer‐scale analysis of space‐use. Integrating different organizational levels of analysis provides a deeper understanding of the eco‐evolutionary dynamics at play in the emergence and maintenance of migration and the critical role of resource predictability. Our results highlight that assessing the potential benefits of differential behavioral responses first requires an understanding of the interactions among movement strategies, resource selection and individual characteristics.
High myopes have lower normalised corneal tangent moduli (less ‘stiff’ corneas) than low myopes
Authors: Hon Ying , Chen Guo‐Zhen , Lu Shu‐Hao , Lam David C. C. , Lam Andrew K. C.
Published: November 2016

Purpose

To compare corneal tangent moduli between low and high myopes.

Methods

Corneal hysteresis (CH) and corneal resistance factor (CRF) of 32 low and 32 high myopes were obtained using an Ocular Response Analyzer, followed by a corneal indentation device that measured corneal stiffness. Corneal topography, pachymetry, Goldmann applanation tonometry intraocular pressure (GAT‐IOP), and corneal compensated intraocular pressure (IOPcc) were also obtained. Corneal tangent modulus was calculated on the basis of corneal stiffness, central corneal thickness and corneal radius. Comparisons between groups and associations between corneal biomechanical and ocular parameters were performed.

Results

Corneal tangent moduli were positively correlated with GAT‐IOP (R2 = 0.078, p = 0.025), and IOPcc (R2 = 0.12, p = 0.006). Despite similarity in corneal thickness and radius, high myopes exhibited a significantly higher IOPcc (16.4 ± 2.51 mmHg) than low myopes (13.1 ± 1.96 mmHg; t(62) = −5.57, p < 0.0001). Both groups had similar corneal stiffness (0.063 ± 0.0085 and 0.063 ± 0.0079 N mm−1 for low and high myopes, respectively) and CRF (9.6 ± 1.58 and 9.5 ± 1.90 mmHg for low and high myopes, respectively). Moreover, high myopes exhibited a significantly lower CH (9.5 ± 1.51 mmHg) than low myopes (10.6 ± 1.38 mmHg; t(62) = 2.92, p = 0.005). After normalising corneal tangent moduli to the mean intraocular pressure in normal eyes (15.5 mmHg) using IOPcc, high myopes showed a significantly lower corneal tangent moduli (0.47 ± 0.087 MPa) than low myopes (0.57 ± 0.099 MPa; t(62) = 4.17, p < 0.0001).

Conclusions

High myopes had lower normalised corneal tangent moduli than low myopes, which indicated that their corneas were less stiff. This is the first in vivo study comparing elastic moduli of the cornea in different refractive groups. Further studies are warranted to understand whether a less stiff cornea is a cause for or an outcome from myopia development.
Investigation and genetic mapping of a Glomerella leaf spot resistance locus in apple
Authors: Liu Yuanxia , Lan Jinhao , Wang Caihong , Li Baohua , Zhu Jun , Liu Chunxiao , Dai Hongyi
Published: November 2016

Apple Glomerella leaf spot (GLS) is a severe fungal disease that damages apple leaves during the summer in China. Breeding new apple varieties that are resistant to the disease is considered the best way of controlling GLS. Fine mapping and tightly linked marker are critically essential for the preselection of resistant seedlings. In this study, a population of 207 F1 individuals derived from a cross between ‘Golden Delicious’ and ‘Fuji’ was used to construct a fine simple sequence repeat (SSR)‐based genetic linkage map. The position of Rgls, a locus responsible for resistance to GLS, was identified on apple linkage group (LG) 15 using SSR markers CH05g05 and CH01d08, which was adapted from a published set of 300 SSR markers that were developed using the bulked segregant analysis (BSA) method. These two SSR markers flanked the gene, and its recombination rate was 8.7% and 23.2%, respectively. A total of 276 newly developed SSR markers around the target region and designed from the genome apple assembly contig of LG15 were screened. Only nine of these were determined to be linked to the Rgls locus. Thus, a total of 11 SSR markers were in linkage with Rgls, and mapped at distances ranging from 0.5 to 33.8 cM. The closest marker to the Rgls locus was S0405127, which showed a genetic distance of approximately 0.5 cM. The first mapping of the gene Rgls was constructed, and the locations of the 11 effective primers in the ‘Golden Delicious’ apple genome sequence were anchored. This result facilitates better understanding of the molecular mechanisms underlying the trait of resistance to GLS and could be used in improving the breeding efficiency of GLS‐resistant apple varieties.
Does improvement of cognitive functioning by cognitive remediation therapy effect work outcomes in severe mental illness? A secondary analysis of a randomized controlled trial
Authors: Ikebuchi Emi , Sato Sayaka , Yamaguchi Sosei , Shimodaira Michiyo , Taneda Ayano , Hatsuse Norifumi , Watanabe Yukako , Sakata Masuhiro , Satake Naoko , Nishio Masaaki , Ito Jun‐ichiro
Published: November 2016

Aim

The aim of this study was to clarify whether improvement of cognitive functioning by cognitive remediation therapy can improve work outcome in schizophrenia and other severe mental illnesses when combined with supported employment.

Methods

The subjects of this study were persons with severe mental illness diagnosed with schizophrenia, major depression, or bipolar disorder (ICD‐10) and cognitive dysfunction who participated in both cognitive remediation using the Thinking Skills for Work program and a supported employment program in a multisite, randomized controlled study. Logistic and multiple linear regression analyses were performed to clarify the influence of cognitive functioning on vocational outcomes, adjusting for demographic and clinical variables.

Results

Improvement of cognitive functioning with cognitive remediation significantly contributed to the total days employed and total earnings of competitive employment in supported employment service during the study period. Any baseline demographic and clinical variables did not significantly contribute to the work‐related outcomes.

Conclusion

A cognitive remediation program transferring learning skills into the real world is useful to increase the quality of working life in supported employment services for persons with severe mental illness and cognitive dysfunction who want to work competitively.
Infantile Hemangioma with Minimal or Arrested Growth: Further Observations on Clinical and Histopathologic Findings of this Unique but Underrecognized Entity
Authors: Ma Ellen Hui , Robertson Susan J. , Chow Chung W. , Bekhor Philip S.
Published: November 2016

Background

Infantile hemangioma (IH) with minimal or arrested growth (IH‐MAG) is becoming increasingly recognized in the literature. It is important to be aware of their existence, because the correct diagnosis is essential for prognostication and treatment and, in the case of facial segmental lesions, the direction of further investigations if PHACE (posterior fossa abnormalities and other structural brain abnormalities; hemangioma(s) of the cervical facial region; arterial cerebrovascular anomalies; cardiac defects, aortic coarctation, and other aortic abnormalities; eye anomalies) syndrome or Sturge–Weber syndrome is suspected. Although the clinical and histologic characteristics of IH‐MAG resemble capillary malformations, positive GLUT‐1 status is a delineating feature.

Methods

We reviewed nine cases of infants who presented after 2000 with birthmarks showing unique clinical features suggestive of a special variant of IHs. All patients had serial photographs taken demonstrating resolution of the birthmark over time. Five of these cases had skin biopsy performed, all of which confirmed GLUT‐1 positivity.

Results

This photographic series of IH‐MAG demonstrates their unique clinical, histologic, and immunochemistry features. They were nearly fully formed at birth, and their common clinical features included telangiectasia, venules, and matte erythema with light and dark areas. Spontaneous resolution over time without cosmetic disfigurement was the observed natural history in the majority of cases.

Conclusion

IH‐MAG is a unique clinical subset of hemangioma for which close observation is the preferred treatment. When in doubt, a biopsy for histology and GLUT‐1 status may be needed to confirm the diagnosis before embarking on unnecessary laser treatment or medical interventions.
Lifestyle and bowel movements in school children: Results from the Toyama Birth Cohort Study
Authors: Yamada Masaaki , Sekine Michikazu , Tatsuse Takashi
Published: November 2016

Background

Constipation is a prevalent health disorder. There have been few epidemiological surveys on constipation in Japanese children. The aim of this study was to evaluate the prevalence of non‐daily bowel movements (BM) and irregular BM among children and to identify modifiable lifestyle factors relevant to bowel habits.

Methods

Subjects were from the Toyama Birth Cohort Study in Japan. A total of 7762 children aged 9–10 years were investigated via questionnaire in 1999. We evaluated bowel habit and the relationship between lifestyle and BM. Non‐daily BM and totally irregular BM were defined as dependent variables in the present study.

Results

Non‐daily BM were reported by 21.8% of boys and by 31.6% of girls, while 10.6% of boys and 18.3% of girls had totally irregular BM. Non‐daily BM were significantly associated with skipping breakfast (OR, 1.23), slow eating (OR, 1.13), physical inactivity (OR, 1.50) and late wake up (OR, 1.29). Totally irregular BM were significantly correlated with skipping breakfast (OR, 1.30), slow eating (OR, 1.41), physical inactivity (OR, 1.27), long TV viewing (OR, 1.52), late bedtime (OR, 1.43), and short sleep duration (OR, 1.33). More girls had non‐daily and totally irregular BM than boys, and these sex differences were not reduced after adjusting for lifestyle variables.

Conclusions

Non‐daily and totally irregular BM are common in children, and there are many relevant lifestyle factors. Establishing regular lifestyle habits may lessen constipation.
From Equality‐Based Respect to Environmental Activism: Antecedents and Consequences of Global Identity
Authors: Renger Daniela , Reese Gerhard
Published: November 2016

Global identity reflects social identification with the world and the largest, most inclusive human ingroup and is generally associated with behavior that serves the world and all humans, such as transnational cooperation or proenvironmental engagement. While the outcomes of being globally identified are well‐established, the antecedents of global identity are only partially explored. Drawing from research suggesting that respect fosters identification in small groups, we argue that the general experience of being respected as an equal by others increases global identification. In an online study with 469 Germans (students and nonstudents), we tested the relation between equality‐based respect and global identification in a structural equation model, with proenvironmental intentions and donation behavior as outcome variables. As expected, equality‐based respect, but not other forms of social recognition (need‐based care and achievement‐based social esteem), predicted global identity while higher global identity, in turn, predicted proenvironmental activism. These effects were substantial beyond known predictors of proenvironmental behavior and thus suggest that equality‐based respect represents an important facet of responses to global challenges.
Consequences of an Extended Recruitment on Participation in the Follow‐Up of a Child Study: Results from the German IDEFICS Cohort
Authors: Langeheine Malte , Pohlabeln Hermann , Ahrens Wolfgang , Rach Stefan ,   the IDEFICS consortium
Published: November 2016

Background

Declining response proportions in population‐based studies are often countered by extended recruitment efforts at baseline that may, however, result in higher attrition in a subsequent follow‐up. This study analysed the effect of extended recruitment efforts on attrition at the first follow‐up of a child cohort.

Methods

We used paradata (i.e. information about the process of data collection) from the German IDEFICS cohort investigating dietary‐ and life style‐induced health effects on children to quantify recruitment effort and classify respondents as completing the recruitment early vs. late for baseline and follow‐up separately. Multilevel logistic regression models were used to investigate the association between recruitment effort and attrition at follow‐up (loss to follow‐up) adjusted for sociodemographic and health related variables.

Results

Individuals who were late respondents at baseline and early respondents at the follow‐up had a higher chance of attrition (odds ratio 1.65, 95% confidence interval (CI) 1.19, 2.28) as compared to other groups. An investigation of reasons for non‐participation revealed that members of this group were more likely to be not reachable by phone.

Conclusions

An extended recruitment effort at baseline of a child cohort study is not per se associated with a higher chance of attrition at follow‐up. Much care should be taken to collect valid telephone numbers.
When Governance Networks Become the Agenda
Authors: Gerrits Lasse , Verweij Stefan
Published: November 2016

Related Content: Balfour and Newbold (PAR January/February 2017)

Related Content: Roberts (PAR January/February 2017)

Related Content: Eckerd (PAR January/February 2017)

Related Content: Vidal‐Aparicio (PAR January/February 2017)

Related Content: Robbins (PAR January/February 2017)
Separating Risk from Heterogeneity in Education: A Semiparametric Approach
Authors: Mazza Jacopo , van Ophem Hans
Published: November 2016

Returns to education are variable both within and between educational group. If uncertain pay-offs are a concern to individuals when selecting an education, wage variance is relevant. The variation is a combination of unobserved heterogeneity and pure uncertainty or risk. The first element is known to the individual, but unknown to the researcher; the second is unknown to both. As a result, the variance of wages observed in the data will overestimate the real magnitude of educational uncertainty and the effect that risk has on educational decisions. We apply a semiparametric estimation technique to tackle the selectivity issues. This method does not rely on distributional assumptions of the errors in the schooling choice and wage equations. Our results suggest that risk is decreasing in schooling. Private information accounts for a share varying between 0% and 13% of total wage variance observed depending on the educational level. Finally, we conclude that the estimation results are very sensitive to the functional relation that is imposed on the error structure.
Impact of Model Choice on LR Assessment in Case of Rare Haplotype Match (Frequentist Approach)
Authors: Cereda Giulia
Published: November 2016

The likelihood ratio (LR) measures the relative weight of forensic data regarding two hypotheses. Several levels of uncertainty arise if frequentist methods are chosen for its assessment: the assumed population model only approximates the true one, and its parameters are estimated through a limited database. Moreover, it may be wise to discard part of data, especially that only indirectly related to the hypotheses. Different reductions define different LRs. Therefore, it is more sensible to talk about ‘a’ LR instead of ‘the’ LR, and the error involved in the estimation should be quantified. Two frequentist methods are proposed in the light of these points for the ‘rare type match problem’, that is, when a match between the perpetrator's and the suspect's DNA profile, never observed before in the database of reference, is to be evaluated.
An adaptive dual clustering algorithm based on hierarchical structure: A case study of settlement zoning
Authors: Liu Yaolin , Wang Xiaomi , Liu Dianfeng , Liu Leilei
Published: November 2016

Traditional dual clustering algorithms cannot adaptively perform clustering well without sufficient prior knowledge of the dataset. This article aims at accommodating both spatial and non‐spatial attributes in detecting clusters without the need to set parameters by default or prior knowledge. A novel adaptive dual clustering algorithm (ADC+) is proposed to obtain satisfactory clustering results considering the spatial proximity and attribute similarity with the presence of noise and barriers. In this algorithm, Delaunay triangulation is utilized to adaptively obtain spatial proximity and spatial homogenous patterns based on particle swarm optimization (PSO). Then, a hierarchical clustering method is employed to obtain clusters with similar attributes. The hierarchical clustering method adopts a discriminating coefficient to adaptively control the depth of the hierarchical architecture. The clustering results are further refined using an optimization approach. The advantages and practicability of the ADC+ algorithm are illustrated by experiments on both simulated datasets and real‐world applications. It is found that the proposed ADC+ algorithm can adaptively and accurately detect clusters with arbitrary shapes, similar attributes and densities under the consideration of barriers.
Idiopathic myelofibrosis accompanied by peritoneal extramedullary hematopoiesis presenting as refractory ascites in a dog
Authors: Rautenbach Yolandi , Goddard Amelia , Clift Sarah J.
Published: November 2016

A 2.5‐year‐old spayed female American Pit Bull Terrier dog presented with a primary complaint of chronic refractory ascites. The dog's CBC displayed a moderate to severe macrocytic, hypochromic, nonregenerative anemia, and a moderate leukopenia as result of a moderate neutropenia and monocytopenia. Microscopic examination of the blood smear showed marked anisocytosis, mild polychromasia, mild acanthocytosis and ovalocytosis, moderate schistocytosis and poikilocytosis, and 4 metarubricytes/100 WBC. Abdominal ultrasonography revealed a homogenous, mild to moderately hyperechoic appearing liver as well as marked amounts of speckled anechoic to slightly hypoechoic peritoneal fluid. Cytology of the ascitic fluid demonstrated a sterile transudate, with evidence of a chronic inflammatory reaction as well as erythroid and myeloid precursor cells, and a few megakaryocytes with occasional micromegakaryocytes. Histologic sections of bone marrow, spleen, and liver were examined, using routine H&E stains, as well as a variety of immunohistochemistry and other special stains. Histopathology of the bone marrow and spleen revealed varying degrees of fibrosis, erythroid, and myeloid hyperplasia, as well as multiple small hyperplastic clusters of megakaryocytes. The megakaryocytes displayed many features of atypia such as increased cytoplasmic basophilia and occasional abnormal chromatin clumping with mitoses. Histopathologic examination of the liver disclosed evidence of mild extramedullary hematopoiesis. This case represents the first report of canine idiopathic myelofibrosis associated with peritoneal extramedullary hematopoiesis, resulting in refractory ascites. Although idiopathic myelofibrosis is a relatively rare condition in dogs, this case demonstrates that ascites caused by peritoneal implants of hematopoietic tissue may be the initial manifestation of myelofibrosis.
Methods and Processes of Developing the Strengthening the Reporting of Observational Studies in Epidemiology – Veterinary (STROBE‐Vet) Statement
Authors: Sargeant J. M. , O'Connor A. M. , Dohoo I. R. , Erb H. N. , Cevallos M. , Egger M. , Ersbøll A. K. , Martin S. W. , Nielsen L. R. , Pearl D. L. , Pfeiffer D. U. , Sanchez J. , Torrence M. E. , Vigre H. , Waldner C. , Ward M. P.
Published: November 2016

The reporting of observational studies in veterinary research presents many challenges that often are not adequately addressed in published reporting guidelines. A consensus meeting of experts was organized to develop an extension of the STROBE statement to address observational studies in veterinary medicine with respect to animal health, animal production, animal welfare and food safety outcomes. The consensus meeting was held 11–13 May 2014 in Mississauga, Ontario, Canada. Seventeen experts from North America, Europe and Australia attended the meeting. The experts were epidemiologists and biostatisticians, many of whom hold or have held editorial positions with relevant journals. Prior to the meeting, 19 experts completed a survey about whether they felt any of the 22 items of the STROBE statement should be modified and whether items should be added to address unique issues related to observational studies in animal species with health, production, welfare or food safety outcomes. At the meeting, the participants were provided with the survey responses and relevant literature concerning the reporting of veterinary observational studies. During the meeting, each STROBE item was discussed to determine whether or not re‐wording was recommended, and whether additions were warranted. Anonymous voting was used to determine whether there was consensus for each item change or addition. The consensus was that six items needed no modifications or additions. Modifications or additions were made to the STROBE items numbered as follows: 1 (title and abstract), 3 (objectives), 5 (setting), 6 (participants), 7 (variables), 8 (data sources/measurement), 9 (bias), 10 (study size), 12 (statistical methods), 13 (participants), 14 (descriptive data), 15 (outcome data), 16 (main results), 17 (other analyses), 19 (limitations) and 22 (funding). Published literature was not always available to support modification to, or inclusion of, an item. The methods and processes used in the development of this statement were similar to those used for other extensions of the STROBE statement. The use of this extension to the STROBE statement should improve the reporting of observational studies in veterinary research related to animal health, production, welfare or food safety outcomes by recognizing the unique features of observational studies involving food‐producing and companion animals, products of animal origin, aquaculture and wildlife.
Using line acceleration to measure false killer whale (Pseudorca crassidens) click and whistle source levels during pelagic longline depredation
Authors: Thode Aaron , Wild Lauren , Straley Janice , Barnes Dustin , Bayless Ali , O'Connell Victoria , Oleson Erin , Sarkar Jit , Falvey Dan , Behnken Linda , Martin Sean
Published: November 2016

False killer whales (Pseudorca crassidens) depredate pelagic longlines in offshore Hawaiian waters. On January 28, 2015 a depredation event was recorded 14 m from an integrated GoPro camera, hydrophone, and accelerometer, revealing that false killer whales depredate bait and generate clicks and whistles under good visibility conditions. The act of plucking bait off a hook generated a distinctive 15 Hz line vibration. Two similar line vibrations detected at earlier times permitted the animal's range and thus signal source levels to be estimated over a 25-min window. Peak power spectral density source levels for whistles (4–8 kHz) were estimated to be between 115 and 130 dB re 1 μPa2/Hz @ 1 m. Echolocation click source levels over 17–32 kHz bandwidth reached 205 dB re 1 μPa @ 1 m pk-pk, or 190 dB re 1 μPa @ 1 m (root-mean-square). Predicted detection ranges of the most intense whistles are 10 to 25 km at respective sea states of 4 and 1, with click detection ranges being 5 times smaller than whistles. These detection range analyses provide insight into how passive acoustic monitoring might be used to both quantify and avoid depredation encounters.
Sound production on a “coaxial saxophone”
Authors: Doc J.-B. , Vergez C. , Guillemain P. , Kergomard J.
Published: November 2016

Sound production on a “coaxial saxophone” is investigated experimentally. The coaxial saxophone is a variant of the cylindrical saxophone made up of two tubes mounted in parallel, which can be seen as a low-frequency analogy of a truncated conical resonator with a mouthpiece. Initially developed for the purposes of theoretical analysis, an experimental verification of the analogy between conical and cylindrical saxophones has never been reported. The present paper explains why the volume of the cylindrical saxophone mouthpiece limits the achievement of a good playability. To limit the mouthpiece volume, a coaxial alignment of pipes is proposed and a prototype of coaxial saxophone is built. An impedance model of coaxial resonator is proposed and validated by comparison with experimental data. Sound production is also studied through experiments with a blowing machine. The playability of the prototype is then assessed and proven for several values of the blowing pressure, of the embouchure parameter, and of the instrument's geometrical parameters.
Paralympic Legacy: Exploring the Impact of the Games on the Perceptions of Young People With Disabilities
Authors: Coates Janine , Vickerman Philip B.
Published: November 2016

The London 2012 Olympic and Paralympic Games aimed to deliver a legacy to citizens of the United Kingdom, which included inspiring a generation of young people to participate in sport. This study aimed to understand the legacy of the Paralympic Games for children with disabilities. Eight adolescents (11–16 yr) with physical disabilities were interviewed about their perceptions of the Paralympic Games. Thematic analysis found 3 key themes that further our understanding of the Paralympic legacy. These were Paralympians as role models, changing perceptions of disability, and the motivating nature of the Paralympics. Findings demonstrate that the Games were inspirational for children with disabilities, improving their self-perceptions. This is discussed in relation to previous literature, and core recommendations are made.
Power and Speed Differences Between Brazilian Paralympic Sprinters With Visual Impairment and Their Guides
Authors: Pereira Lucas , Winckler Ciro , Abad Cesar C. Cal , Kobal Ronaldo , Kitamura Katia , Veríssimo Amaury , Nakamura Fabio Y. , Loturco Irineu
Published: November 2016

This study compared the physical performance of Paralympic sprinters with visual impairments (PSVI) and their guides in jump and sprint tests. Ten PSVI and guides executed squat jumps (SJ), countermovement jumps (CMJ), horizontal quintuple right/left-leg jumps (QR/QL), decuple jumps (DEC), and 50-m-sprint tests. The guides were superior to the PSVI in SJ (35.9 ± 6.3 vs 45.6 ± 3.2 cm), CMJ (38.5 ± 6.2 vs 46.7 ± 4.0 cm), QR (9.2 ± 1.9 vs 12.7 ± 1.0 m), QL (9.4 ± 1.9 vs 13.1 ± 0.8 m), DEC (21.0 ± 3.3 vs. 27.2 ± 1.7 m), and 50-m sprints (8.4 ± 0.4 vs 7.6 ± 0.5 m/s). The average differences between the PSVI and guides in the sprint tests was 10%, range 1–24%. Therefore, substantial differences in sprinting speed (in favor of the guides) between the peers were observed. Coaches should develop strategies to train the guides to improve their muscle-power performance.
Physical Activity Patterns in Youth With Intellectual Disabilities
Authors: Downs Samantha J. , Fairclough Stuart J. , Knowles Zoe R. , Boddy Lynne M.
Published: November 2016

The aim of this study was to assess the physical activity (PA) patterns of youth with intellectual disabilities (ID). PA was monitored for 7 days in 70 participants, 5–15 years old, using accelerometers. There were 32 participants included in the final analysis. Habitual PA and the number of continuous bouts accrued for a range of bout lengths (5–600 s) for light (LPA), moderate (MPA), and vigorous (VPA) PA were calculated. Multivariate analysis of covariance was used to assess differences in the number of continuous bouts by sex, age, and ID group and between week and weekend days. Participants exhibited short sporadic bursts of activity. The number of continuous bouts decreased as the intensity and duration increased. Few differences in PA patterns were reported by sex, ID group, and age group and between week and weekend days, possibly due to the generally low PA levels in this population.
Selective control of up-regulated and down-regulated genes by temporal patterns and doses of insulin
Authors: Sano Takanori , Kawata Kentaro , Ohno Satoshi , Yugi Katsuyuki , Kakuda Hiroaki , Kubota Hiroyuki , Uda Shinsuke , Fujii Masashi , Kunida Katsuyuki , Hoshino Daisuke , Hatano Atsushi , Ito Yuki , Sato Miharu , Suzuki Yutaka , Kuroda Shinya
Published: November 2016

Transcriptomic analysis and mathematical modeling reveal selective gene regulation by insulin.
A computationally identified compound antagonizes excess FGF-23 signaling in renal tubules and a mouse model of hypophosphatemia
Authors: Xiao Zhousheng , Riccardi Demian , Velazquez Hector A. , Chin Ai L. , Yates Charles R. , Carrick Jesse D. , Smith Jeremy C. , Baudry Jerome , Quarles L. Darryl
Published: November 2016

A ligand-targeted compound may alleviate hypophosphatemia-associated metabolic deficiencies in patients with excess production of FGF-23.
A noncanonical role for Janus kinase 1 in lymphoma
Authors: Mushegian Alexandra A.
Published: November 2016

JAK1-dependent chromatin phosphorylation promotes the survival of aggressive lymphoma cells.
TRAF6 targets p53
Authors: Gough Nancy R.
Published: November 2016

TRAF6-mediated ubiquitylation of p53 regulates both mitochondrial apoptosis and cell cycle arrest.
Fludioxonil Induces Drk1, a Fungal Group III Hybrid Histidine Kinase, To Dephosphorylate Its Downstream Target, Ypd1
Authors: Lawry Stephanie M. , Tebbets Brad , Kean Iain , Stewart Douglas , Hetelle Joel , Klein Bruce S.
Published: November 2016

Novel antifungal drugs and targets are urgently needed. Group III hybrid histidine kinases (HHKs) represent an appealing new therapeutic drug target because they are widely expressed in fungi but absent from humans. We investigated the mode of action of the widely utilized, effective fungicide fludioxonil. The drug acts in an HHK-dependent manner by constitutive activation of the HOG (
h
igh-
o
smolarity
g
lycerol) pathway, but its mechanism of action is poorly understood. Here, we report a new mode of drug action that entails conversion of the HHK from a kinase into a phosphatase. We expressed Drk1 (
d
imorphism-
r
egulating
k
inase), which is an intracellular group III HHK from the fungal pathogen
Blastomyces dermatitidis
, in
Saccharomyces cerevisiae
. Drk1 engendered drug sensitivity in
B. dermatitidis
and conferred sensitivity upon
S. cerevisiae
. In response to fludioxonil, Drk1 behaved as a phosphatase rather than as a kinase, leading to dephosphorylation of its downstream target, Ypd1, constitutive activation of the HOG pathway, and yeast cell death. Aspartic acid residue 1140 in the Drk1 receiver domain was required for
in vivo
phosphatase activity on Ypd1, and Hog1 was required for drug effect, indicating fidelity in HHK-dependent drug action. In
in vitro
assays with purified protein, intact Drk1 demonstrated intrinsic kinase activity, and the Drk1 receiver domain exhibited intrinsic phosphatase activity. However, fludioxonil failed to induce intact Drk1 to dephosphorylate Ypd1. We conclude that fludioxonil treatment
in vivo
likely acts on an upstream target that triggers HHK to become a phosphatase, which dephosphorylates its downstream target, Ypd1.
In Vitro
Exposure to Increasing Micafungin Concentrations Easily Promotes Echinocandin Resistance in Candida glabrata Isolates
Authors: Bordallo-Cardona María Ángeles , Escribano Pilar , de la Pedrosa Elia Gómez G. , Marcos-Zambrano Laura Judith , Cantón Rafael , Bouza Emilio , Guinea Jesús
Published: November 2016

We assessed the
in vitro
susceptibility of five echinocandin-susceptible
Candida glabrata
isolates after exposure to micafungin. The direct exposure to plates at different micafungin concentrations resulted in the inhibition of growth at 0.062 μg/ml. The progressive exposure was performed on plates using 0.031 μg/ml of micafungin and sequential propagation on plates containing the next 2-fold concentration; the MICs of micafungin and anidulafungin increased sequentially, and all the isolates became echinocandin resistant, showing
fks2
mutations.
In Vitro
Activity of Ceftazidime-Avibactam against Isolates in a Phase 3 Open-Label Clinical Trial for Complicated Intra-Abdominal and Urinary Tract Infections Caused by Ceftazidime-Nonsusceptible Gram-Negative Pathogens
Authors: Stone Gregory G. , Bradford Patricia A. , Newell Paul , Wardman Angela
Published: November 2016

The
in vitro
activity of ceftazidime-avibactam was evaluated against 341 Gram-negative isolates from 333 patients in a randomized, phase 3 clinical trial of patients with complicated urinary tract or intra-abdominal infections caused by ceftazidime-nonsusceptible pathogens (NCT01644643). Ceftazidime-avibactam MIC
90
values against
Enterobacteriaceae
and
Pseudomonas aeruginosa
(including several class B or D enzyme producers that avibactam does not inhibit) were 1 and 64 μg/ml, respectively. Overall, the ceftazidime-avibactam activity against ceftazidime-nonsusceptible isolates was comparable to the activity of ceftazidime-avibactam previously reported against ceftazidime-susceptible isolates. (This study has been registered at ClinicalTrials.gov under identifier NCT01644643.)
Novel Effects of Lapatinib Revealed in the African Trypanosome by Using Hypothesis-Generating Proteomics and Chemical Biology Strategies
Authors: Guyett Paul J. , Behera Ranjan , Ogata Yuko , Pollastri Michael , Mensa-Wilmot Kojo
Published: November 2016

Human African trypanosomiasis is a neglected tropical disease caused by the protozoan parasite
Trypanosoma brucei
. Lapatinib, a human epidermal growth factor receptor (EGFR) inhibitor, can cure 25% of trypanosome-infected mice, although the parasite lacks EGFR-like tyrosine kinases. Four trypanosome protein kinases associate with lapatinib, suggesting that the drug may be a multitargeted inhibitor of phosphoprotein signaling in the bloodstream trypanosome. Phosphoprotein signaling pathways in
T. brucei
have diverged significantly from those in humans. As a first step in the evaluation of the polypharmacology of lapatinib in
T. brucei
, we performed a proteome-wide phosphopeptide analysis before and after drug addition to cells. Lapatinib caused dephosphorylation of Ser/Thr sites on proteins predicted to be involved in scaffolding, gene expression, and intracellular vesicle trafficking. To explore the perturbation of phosphotyrosine (pTyr)-dependent signaling by lapatinib, proteins in lapatinib-susceptible pTyr complexes were identified by affinity chromatography; they included BILBO-1, MORN, and paraflagellar rod (PFR) proteins PFR1 and PFR2. These data led us to hypothesize that lapatinib disrupts PFR functions and/or endocytosis in the trypanosome. In direct chemical biology tests of these speculations, lapatinib-treated trypanosomes (i) lost segments of the PFR inside the flagellum, (ii) were inhibited in the endocytosis of transferrin, and (iii) changed morphology from long and slender to rounded. Thus, our hypothesis-generating phosphoproteomics strategy predicted novel physiological pathways perturbed by lapatinib, which were verified experimentally. General implications of this workflow for identifying signaling pathways perturbed by drug hits discovered in phenotypic screens are discussed.
Polymyxin B in Combination with Rifampin and Meropenem against Polymyxin B-Resistant KPC-Producing Klebsiella pneumoniae
Authors: Diep John K. , Jacobs David M. , Sharma Rajnikant , Covelli Jenna , Bowers Dana R. , Russo Thomas A. , Rao Gauri G.
Published: November 2016

Safe and effective therapies are urgently needed to treat polymyxin-resistant KPC-producing
Klebsiella pneumoniae
infections and suppress the emergence of resistance. We investigated the pharmacodynamics of polymyxin B, rifampin, and meropenem alone and as polymyxin B-based double and triple combinations against KPC-producing
K. pneumoniae
isolates. The rates and extents of killing with polymyxin B (1 to 128 mg/liter), rifampin (2 to 16 mg/liter), and meropenem (10 to 120 mg/liter) were evaluated against polymyxin B-susceptible (PB
s
) and polymyxin B-resistant (PB
r
) clinical isolates using 48-h static time-kill studies. Additionally, humanized triple-drug regimens of polymyxin B (concentration at steady state [
C
ss
] values of 0.5, 1, and 2 mg/liter), 600 mg rifampin every 12 or 8 h, and 1 or 2 g meropenem every 8 h dosed as an extended 3-h infusion were simulated over 48 h by using a one-compartment
in vitro
dynamic infection model. Serial bacterial counts were performed to quantify the pharmacodynamic effect. Population analysis profiles (PAPs) were used to assess the emergence of polymyxin B resistance. Monotherapy was ineffective against both isolates. Polymyxin B with rifampin demonstrated early bactericidal activity against the PB
s
isolate, followed by regrowth by 48 h. Bactericidal activity was sustained at all polymyxin B concentrations of ≥2 mg/liter in combination with meropenem. No two-drug combinations were effective against the PB
r
isolate, but all simulated triple-drug regimens showed early bactericidal activity against both strains by 8 h that was sustained over 48 h. PAPs did not reveal the emergence of resistant subpopulations. The triple-drug combination of polymyxin B, rifampin, and meropenem may be a viable consideration for the treatment of PB
r
KPC-producing
K. pneumoniae
infections. Further investigation is warranted to optimize triple-combination therapy.
Missense Mutations in the Unfoldase ClpC1 of the Caseinolytic Protease Complex Are Associated with Pyrazinamide Resistance in Mycobacterium tuberculosis
Authors: Yee Michelle , Gopal Pooja , Dick Thomas
Published: November 2016

Previously, we showed that mutations in
Mycobacterium tuberculosis
panD
, involved in coenzyme A biosynthesis, cause resistance against pyrazinoic acid, the bioactive component of the prodrug pyrazinamide. To identify additional resistance mechanisms, we isolated mutants resistant against pyrazinoic acid and subjected
panD
wild-type strains to whole-genome sequencing. Eight of the nine resistant strains harbored missense mutations in the unfoldase ClpC1 associated with the caseinolytic protease complex.
The Type III Effector NleD from Enteropathogenic Escherichia coli Differentiates between Host Substrates p38 and JNK
Authors: Creuzburg Kristina , Giogha Cristina , Wong Fok Lung Tania , Scott Nichollas E. , Mühlen Sabrina , Hartland Elizabeth L. , Pearson Jaclyn S.
Published: November 2016

Enteropathogenic
Escherichia coli
(EPEC) is a gastrointestinal pathogen that utilizes a type III secretion system (T3SS) to inject an array of virulence effector proteins into host enterocytes to subvert numerous cellular processes for successful colonization and dissemination. The T3SS effector NleD is a 26-kDa zinc metalloprotease that is translocated into host enterocytes, where it directly cleaves and inactivates the mitogen-activated protein kinase signaling proteins JNK and p38. Here a library of 91 random transposon-based, in-frame, linker insertion mutants of NleD were tested for their ability to cleave JNK and p38 during transient transfection of cultured epithelial cells. Immunoblot analysis of p38 and JNK cleavage showed that 7 mutant derivatives of NleD no longer cleaved p38 but maintained the ability to cleave JNK. Site-directed mutation of specific regions surrounding the insertion sites within NleD revealed that a single amino acid, R203, was essential for cleavage of p38 but not JNK in a direct
in vitro
cleavage assay, in transiently transfected cells, or in EPEC-infected cells. Mass spectrometry analysis narrowed the cleavage region to within residues 187 and 213 of p38. Mutation of residue R203 within NleD to a glutamate residue abolished the cleavage of p38 and impaired the ability of NleD to inhibit AP-1-dependent gene transcription of a luciferase reporter. Furthermore, the R203 mutation abrogated the ability of NleD to dampen interleukin-6 production in EPEC-infected cells. Overall, this work provides greater insight into substrate recognition and specificity by the type III effector NleD.
Flagellin-Mediated Protection against Intestinal Yersinia pseudotuberculosis Infection Does Not Require Interleukin-22
Authors: Porte Rémi , Van Maele Laurye , Muñoz-Wolf Natalia , Foligné Benoit , Dumoutier Laure , Tabareau Julien , Cayet Delphine , Gosset Pierre , Jonckheere Nicolas , Van Seuningen Isabelle , Chabalgoity José A. , Simonet Michel , Lamkanfi Mohamed , Renauld Jean-Christophe , Sirard Jean-Claude , Carnoy Christophe
Published: November 2016

Signaling through Toll-like receptors (TLRs), the main receptors in innate immunity, is essential for the defense of mucosal surfaces. It was previously shown that systemic TLR5 stimulation by bacterial flagellin induces an immediate, transient interleukin-22 (IL-22)-dependent antimicrobial response to bacterial or viral infections of the mucosa. This process was dependent on the activation of type 3 innate lymphoid cells (ILCs). The objective of the present study was to analyze the effects of flagellin treatment in a murine model of oral infection with
Yersinia pseudotuberculosis
(an invasive, Gram-negative, enteropathogenic bacterium that targets the small intestine). We found that systemic administration of flagellin significantly increased the survival rate after intestinal infection (but not systemic infection) by
Y. pseudotuberculosis
. This protection was associated with a low bacterial count in the gut and the spleen. In contrast, no protection was afforded by administration of the TLR4 agonist lipopolysaccharide, suggesting the presence of a flagellin-specific effect. Lastly, we found that TLR5- and MyD88-mediated signaling was required for the protective effects of flagellin, whereas neither lymphoid cells nor IL-22 was involved.