bluuebunny/crossref_metadata_2025 huggingface dataset:
Theoretical analysis of Hall factor and hole mobility in p-type 4H-SiC considering anisotropic valence band structure
Authors: Tanaka H. , Asada S. , Kimoto T. , Suda J.
Published: June 2018

The temperature dependencies of hole density and hole mobility of p-type 4H-SiC obtained by Hall effect measurement were theoretically analyzed taking account of its anisotropic valence band structure. The experimental Hall factor, which was derived from the ratio of theoretical hole density to experimental Hall hole density, was reproduced by theoretical Hall factor computed using the valence band structure and relaxation times of scattering mechanisms. The product of the theoretical Hall factor and drift mobility computed by the same transport model agreed well with the experimental Hall mobility. Based on analyses of the results, it was revealed that the temperature dependence of Hall factor can be explained by considering the anisotropic valence band structure along with consideration of anisotropic relaxation times. The contribution of each scattering mechanism was also discussed, and empirical formulas for Hall and drift mobilities are presented.
Study on wave absorption properties of carbonyl iron and SiO2 coated carbonyl iron particles
Authors: Yan Honghao , Song Xinhua , Wang Yang
Published: June 2018

Because of the excellent properties, carbonyl iron powder particles and their surface modified products are often used as radar absorbers. The electromagnetic wave attenuation mechanism of the carbonyl iron powders and SiO2 coated carbonyl iron particles were analyzed on the basis of the studies of scholars from all over the world and compared with the solutions calculated by the COMSOL software. The results obtained through the analytical solution and COMSOL simulated calculation values tend to be consistent; the ratio of the complex magnetic permittivity to the complex permittivity of the nano-SiO2 coated carbonyl iron powder particles tend to be 1, and the impedance matching performance of nano-SiO2 coated carbonyl iron powder particles is improved. Compared with the carbonyl iron particles, SiO2 coated carbonyl iron particles have lower electromagnetic wave absorptivity.
Proposed mechanism describes the transition to turbulent flow in shocked heavy gases
Authors: DeJarnette Drew
Published: June 2018

Transient finite volume simulations reveal a possible new mechanism to describe heavy gases exposed to primary and secondary shocks that mix and transition to 3-D turbulent flows.
Genetic dissection of neuropeptide cell biology at high and low activity in a defined sensory neuron
Authors: Laurent Patrick , Ch’ng QueeLim , Jospin Maëlle , Chen Changchun , Lorenzo Ramiro , de Bono Mario
Published: June 2018

Significance

Neuropeptides are ubiquitous modulators of behavior and physiology. They are packaged in specialized secretory organelles called dense core vesicles (DCVs) that are released upon neural stimulation. Whereas local recycling of synaptic vesicles has been investigated intensively, there are few studies on recycling of DCV proteins. We set up a paradigm to study DCVs in a neuron whose activity we can control. We validate our model by confirming many previous observations on DCV cell biology. We identify a set of genes involved in recycling of DCV proteins. We also find evidence that different mechanisms of DCV priming and exocytosis may operate at high and low neural activity.
The Camino de Santiago de Compostela: the most important historic pilgrimage way in Europe.
Authors: Lois-González R. C. , Santos X. M. , Romero P. T. Z.
Published: June 2018

This chapter examines the growth and development of the Camino de Santiago de Compostela and the challenges that presently face what is probably the most famous pilgrimage trail in the Western world. It is shown that the Camino de Santiago is much more than a tourism product. It has a political-ideological aspect which is essential to understand in order to have a complete vision of the Santiago phenomenon. It is also shown, from the tourism perspective, that the Camino de Santiago is a success. This is measured by the growing number of pilgrims who travel the different Caminos each year, but also by the internationalization of the demand, the incorporation of the tourism industry and, ultimately, the complexity that it has acquired over time.
CLIP and cohibin separate rDNA from nucleolar proteins destined for degradation by nucleophagy
Authors: Mostofa Md. Golam , Rahman Muhammad Arifur , Koike Naoki , Yeasmin Akter MST , Islam Nafisa , Waliullah Talukdar Muhammad , Hosoyamada Shun , Shimobayashi Mitsugu , Kobayashi Takehiko , Hall Michael N. , Ushimaru Takashi
Published: June 2018

Nutrient starvation or inactivation of target of rapamycin complex 1 (TORC1) in budding yeast induces nucleophagy, a selective autophagy process that preferentially degrades nucleolar components. DNA, including ribosomal DNA (rDNA), is not degraded by nucleophagy, even though rDNA is embedded in the nucleolus. Here, we show that TORC1 inactivation promotes relocalization of nucleolar proteins and rDNA to different sites. Nucleolar proteins move to sites proximal to the nuclear–vacuolar junction (NVJ), where micronucleophagy (or piecemeal microautophagy of the nucleus) occurs, whereas rDNA dissociates from nucleolar proteins and moves to sites distal to NVJs. CLIP and cohibin, which tether rDNA to the inner nuclear membrane, were required for repositioning of nucleolar proteins and rDNA, as well as effective nucleophagic degradation of the nucleolar proteins. Furthermore, micronucleophagy itself was necessary for the repositioning of rDNA and nucleolar proteins. However, rDNA escaped from nucleophagic degradation in CLIP- or cohibin-deficient cells. This study reveals that rDNA–nucleolar protein separation is important for the nucleophagic degradation of nucleolar proteins.
Étale fundamental groups of affinoid 𝑝-adic curves
Authors: Saïdi Mohamed
Published: June 2018

We prove that the geometric étale fundamental group of a (geometrically connected) rigid smooth

p
p

-adic affinoid curve is a semi-direct factor of a certain profinite free group. We prove that the maximal pro-

p
p

(resp. maximal prime-to-

p
p

) quotient of this geometric étale fundamental group is pro-

p
p

free of infinite rank (resp. (pro-)prime-to-

p
p

free of finite computable rank).
MrBait: universal identification and design of targeted-enrichment capture probes
Authors: Chafin Tyler K , Douglas Marlis R , Douglas Michael E
Published: June 2018

Motivation

It is a non-trivial task to identify and design capture probes (‘baits’) for the diverse array of targeted-enrichment methods now available (e.g. ultra-conserved elements, anchored hybrid enrichment, RAD-capture). This often involves parsing large genomic alignments, followed by multiple steps of curating candidate genomic regions to optimize targeted information content (e.g. genetic variation) and to minimize potential probe dimerization and non-target enrichment.

Results

In this context, we developed MrBait, a user-friendly, generalized software pipeline for identification, design and optimization of targeted-enrichment probes across a range of target-capture paradigms. MrBait is an open-source codebase that leverages native parallelization capabilities in Python and mitigates memory usage via a relational-database back-end. Numerous filtering methods allow comprehensive optimization of designed probes, including built-in functionality that employs BLAST, similarity-based clustering and a graph-based algorithm that ‘rescues’ failed probes.

Availability and implementation

Complete code for MrBait is available on GitHub (https://github.com/tkchafin/mrbait), and is also available with all dependencies via one-line installation using the conda package manager. Online documentation describing installation and runtime instructions can be found at: https://mrbait.readthedocs.io.

Supplementary information

Supplementary data are available at Bioinformatics online.
Non-parametric recurrent events analysis with BART and an application to the hospital admissions of patients with diabetes
Authors: Sparapani Rodney A , Rein Lisa E , Tarima Sergey S , Jackson Tourette A , Meurer John R
Published: June 2018

Much of survival analysis is concerned with absorbing events, i.e., subjects can only experience a single event such as mortality. This article is focused on non-absorbing or recurrent events, i.e., subjects are capable of experiencing multiple events. Recurrent events have been studied by many; however, most rely on the restrictive assumptions of linearity and proportionality. We propose a new method for analyzing recurrent events with Bayesian Additive Regression Trees (BART) avoiding such restrictive assumptions. We explore this new method via a motivating example of hospital admissions for diabetes patients and simulated data sets.
The Stolypin reform and agricultural productivity in late imperial Russia
Authors: Castañeda Dower Paul , Markevich Andrei
Published: June 2018

We study the effect of changes in land tenure, launched by the 1906 Stolypin reform, on agricultural productivity in Imperial Russia. The reform allowed peasants to obtain individual land titles and consolidate separated land strips into a single privatized allotment. We present evidence that land consolidations enabled peasants to make independent production decisions from the village commune and take advantage of readily accessible technological advancements. In contrast, land titles decreased land productivity in the short-run, but the overall effect of the reform on land productivity was still positive.
Daily Control Beliefs and Cognition: The Mediating Role of Physical Activity
Authors: Robinson Stephanie A , Lachman Margie E
Published: June 2018

Objectives

Recent work suggests that physical activity may underlie the positive relationship between control beliefs and cognition. Despite the well-known cognitive benefits, most adults do not engage in enough physical activity, perhaps due to low perceived control. The current study aimed to expand upon past work by investigating these constructs over the short-term by studying the intraindividual variability in daily control beliefs, physical activity, and cognition. We examined whether these constructs were related on a day-to-day basis and if daily physical activity mediated the relationship between control beliefs and cognition.

Method

Over 7 consecutive days, 145 participants (M = 50.54 years) completed daily diaries to measure domain-specific control beliefs, wore an ActiGraph to capture objective physical activity, and were administered 2 tasks each day via phone to measure cognition.

Results

Using multilevel structural equation modeling, our results indicated that on days with higher control beliefs cognition was also higher and this relationship was mediated by one’s level of physical activity.

Discussion

These findings demonstrate the role of physical activity in linking control beliefs and cognition on a daily level using a within-person approach to investigate the dynamic processes in beliefs and cognition.
The Impact of Intraoperative Electrocorticography on Seizure Outcome After Resection of Pediatric Brain Tumors: A Cohort Study
Authors: Robertson Faith C , Ullrich Nicole J , Manley Peter E , Al-Sayegh Hasan , Ma Clement , Goumnerova Liliana C
Published: June 2018

BACKGROUND

Intraoperative electrocorticography (ECoG) has been utilized in patients with tumor-associated seizures; however, its effectiveness for seizure control remains controversial.

OBJECTIVE

To evaluate clinical outcomes in pediatric patients undergoing lesionectomy with or without ECoG.

METHODS

Patients undergoing brain tumor resection at Boston Children's Hospital were examined retrospectively (2005-2014). Inclusion criteria involved diagnosis of a supratentorial tumor, ≥2 unequivocal seizures, and ≥6 mo follow-up. Patients with isolated cortical dysplasia or posterior fossa tumors were excluded. Logistic regression models evaluated predictors of ECoG use, and the impact of ECoG, gross total resection, and focal cortical dysplasia with tumors on seizure freedom by Engel Class and anti-epileptic drug use (AED).

RESULTS

A total of 119 pediatric patients were included (n = 69 males, 58%; median age, 11.3 yr). Forty-one patients (34.5%) had ECoG-guided surgery. Preoperative seizure duration and number and duration of AED use were significant predictors for undergoing ECoG. There were no differences in seizure freedom (Engel Class I) or improved Engel Score (Class I-II vs III-IV) in patients who did or did not have ECoG at 30 d, 6 mo, and 1, 2, or 5 yr. Patients undergoing ECoG required a greater number of AEDs at 6 mo (P = .01), although this difference disappeared at subsequent time intervals. Gross total resection predicted seizure freedom at 30 d and 6 mo postsurgery (P = .045).

CONCLUSION

This retrospective study, one of the largest evaluating the use of ECoG during tumor resection, suggests that ECoG does not provide improved seizure freedom compared to lesionectomy alone for children.
Evidence-Based Treatment for the Eating Disorders
Authors: Hay Phillipa J. , Claudino Angélica de M.
Published: June 2018

This chapter comprises a focused review of the best available evidence for psychological and pharmacological treatments of choice for anorexia nervosa (AN), bulimia nervosa (BN), binge eating disorder (BED), and other specified and unspecified feeding and eating disorders (OSFED and UFED), discusses the role of primary care and online therapies, and presents treatment algorithms. In AN, although there is consensus on the need for specialist care that includes nutritional rehabilitation in addition to psychological therapy, no single approach has yet been found to offer a distinct advantage. In contrast, manualized cognitive behavior therapy (CBT) for BN has attained “first-line” treatment status with a stronger evidence base than other psychotherapies. Similarly, CBT has a good evidence base in treatment of BED and for BN, and BED has been successfully adapted into less intensive and non-specialist forms. Behavioral and pharmacological weight loss management in treatment of co-morbid obesity/overweight and BED may be helpful in the short term, but long-term maintenance of effects is unclear. Primary care practitioners are in a key role, both with regard to providing care and with coordination and initiation of specialist care. There is an emerging evidence base for online therapies in BN and BED where access to care is delayed or problematic.
Combining Pharmacotherapy and Psychological Treatments for OCD
Authors: Tolin David F. , Worden Blaise L.
Published: June 2018

This chapter reviews the outcome literature on the efficacy of combined pharmacotherapy and cognitive-behavioral therapy (CBT) for obsessive compulsive disorder (OCD). By far, most research on combinations of CBT and pharmacotherapy for OCD has examined antidepressant medications, particularly those in the serotonin reuptake inhibitor (SRI) class. Quantitative review of randomized studies in which treatments were combined simultaneously indicated that combined therapy shows a small but significant advantage over exposure and response prevention (ERP) monotherapy, and a moderate advantage over pharmacologic (antidepressant) monotherapy. Studies of sequential treatment combination, in which CBT was added after a trial of antidepressant medication, suggest a significant incremental benefit of CBT, including for patients who show minimal response to antidepressant medication alone. The chapter concludes by discussing new pharmacologic possibilities for combined therapy, such as the use of D-cycloserine (DCS).
Broadcasting versus Narrowcasting
Authors: Metzger Miriam J.
Published: June 2018

This chapter explores the question of the continuing relevance of “mass media” due to recent technological changes in the media landscape. The chapter traces the history of media content production, distribution, and consumption from broadcasting to narrowcasting, and considers recent trends toward “hyperpersonalization” afforded by digital networked media. The chapter examines what these changes mean for politics and for political communication theory, and concludes by posing some questions about the future of mass media that serve as a call for research into the changing nature, circumstances, and effects of mass communication in the contemporary media environment.
Authenticity in Early Childhood Assessment
Authors: Macy Marisa , Bagnato Steven J.
Published: June 2018

Conventional tests and testing practices are at odds with professional “best practice” standards in early childhood intervention. Moreover, conventional tests have been neither developed for nor field-validated on young children with disabilities for early intervention purposes. Dramatic changes are emerging in the assessment of young children, particularly those with developmental delays/disabilities. Interdisciplinary professionals must know and adhere to the professional practice standards for assessment in early childhood intervention. The National Association for the Education of Young Children (NAEYC) and the Division for Early Childhood (DEC) standards promote authentic assessment as the evidence-based alternative for young children to prevent the misrepresentation of young children with disabilities—the mismeasure of young children (Bagnato, Neisworth & Pretti-Frontczak, 2010).
Intersectionalities
Authors: Carter Bruce
Published: June 2018

The purpose of this chapter is to broadly explore several intersections of the social world and music education as investigated through qualitative methodologies. Specifically, this chapter will examine topics of LGBT2Q studies, gender studies, and feminist studies within music education research. The summary includes a call for more sociological research utilizing multidimensional approaches to studying marginalized communities.
Potential risk factors related to pig body weight variability from birth to slaughter in commercial conditions
Authors: López-Vergé Sergi , Gasa Josep , Farré Mercè , Coma Jaume , Bonet Jordi , Solà-Oriol David
Published: June 2018

The aim of this observational study is to identify risk factors associated with body weight (BW) variability in three data sets (DS) in commercial conditions. A total of 1,009 (DS1), 460 (DS2), and 1304 (DS3) male and female crossbreed pigs (Pietrain × [Landrace × Large White]), respectively, were included in each trial. Pigs were periodically weighed until slaughter. Then, variables such as length of gestation, length of lactation, parity, litter size, sex, birth BW, and ADG were considered. Pigs remaining on the farm after two loads to the slaughterhouse were defined as last group of animals sent to slaughterhouse (LGS). Descriptive statistics of variability were calculated, and a risk analysis approach was used to look for the factors related to LGS. A multiple logistic regression was performed to identify all variables that were significant (P < 0.05). The risk ratio (RR), odds ratio (OR), and population attributable risk (PAR) were calculated for all of the significant variables after transforming all of them into binary factors using the 25th percentile as the cut-off point. Results showed that the major part of the variability (as CV) comes from birth (20% to 25%) and increased only a little during lactation and 14-d post weaning. From this point onwards, CV tended to decrease, as pigs got closer to the marketing weight (down 11.5% to 12.7%). Regarding the indicators selected, RR, OR, and PAR presented similar trends in the three DS studied. Therefore, for the variables finally included, these indicators had their minimum values at the start of the cycle and then gradually increased at the end. Those results, based on an epidemiological approach, suggest that the closer to the end of the cycle the greater the probability for a light piglet of being/becoming LGS. It might be explained by the shorter available time to efficiently implement preventive measures aimed to improve the performance of delayed pigs and, thus, reducing variability.Those results, based on an epidemiological approach, make sense as the probability for a light piglet to be a LGS increases the closer to the end of the cycle, due to the short time to implement preventive measures and increase the performance of delayed pigs and reduce variability. The differential PAR associated with both, the nursery and the growing period, was 1.7% and 1.5% for DS1, 5.1% and 3.1% for DS2, and 3.7% and 2.8% for DS3. For the lactation period, the results were 4.3% for DS2 and 4.5% for DS3. Results suggest that the most critical periods, in relation to retardation of growth in swine, are lactation and nursery. Implementing measures that maintain risk factors under or above thresholds, especially in the initial phases of growth, will reduce the percentage of LGS pigs and positively affect the overall homogeneity of the batch.
Functional Balance Testing in Cervical Spondylotic Myelopathy Patients
Authors: Haddas Ram , Lieberman Isador , Boah Akwasi , Arakal Raj , Belanger Theodore , Ju Kevin L.
Published: June 2018

Study Design.

A prospective cohort study.

Objective.

The aim of this study was to quantify the amount of sway associated with maintaining a balanced posture in a group of untreated cervical spondylotic myelopathy (CSM) patients.

Summary of Background Data.

Balance is defined as the ability of the human body to maintain its center of mass (COM) within the base of support with minimal postural sway. Sway is the movement of the COM in the horizontal plane when a person is standing in a static position. CSM patients have impaired body balance and proprioceptive loss.

Methods.

Thirty-two CSM patients performed a series of functional balance tests a week before surgery. Sixteen healthy controls (HCs) performed a similar balance test. Patients are instructed to stand erect with feet together and eyes opened in their self-perceived balanced and natural position for a full minute. All test subjects were fitted to a full-body reflective markers set and surface electromyography (EMG).

Results.

CSM patients had more COM sway in the anterior-posterior (CSM: 2.87 cm vs. C: 0.74 cm; P = 0.023), right-left (CSM: 5.16 cm vs. C: 2.51 cm; P = 0.003) directions as well as head sway (anterior-posterior - CSM: 2.17 cm vs. C: 0.82 cm; P = 0.010 and right-left - CSM: 3.66 cm vs. C: 1.69 cm; P = 0.044), more COM (CSM: 44.72 cm vs. HC: 19.26 cm, p = 0.001), and head (Pre: 37.87 cm vs. C: 19.93 cm, P = 0.001) total sway in comparison to controls. CSM patients utilized significantly more muscle activity to maintain static standing, evidenced by the increased trunk and lower extremity muscle activity (multifidus, erector spinae, rectus femoris, and tibialis anterior, P < 0.050) during 1-minute standing.

Conclusion.

In symptomatic CSM patients, COM and head total sway were significantly greater than controls. Individuals with CSM exhibit more trunk and lower extremity muscle activity, and thus expend more neuromuscular energy to maintain a balanced, static standing posture. This study is the first effort to evaluate global balance as a dynamic process in this patient population.

Level of Evidence: 3
Is on-Demand HIV Pre-exposure Prophylaxis a Suitable Tool for Men Who Have Sex With Men Who Practice Chemsex? Results From a Substudy of the ANRS-IPERGAY Trial
Authors: Roux Perrine , Fressard Lisa , Suzan-Monti Marie , Chas Julie , Sagaon-Teyssier Luis , Capitant Catherine , Meyer Laurence , Tremblay Cécile , Rojas-Castro Daniela , Pialoux Gilles , Molina Jean-Michel , Spire Bruno
Published: June 2018

Background:

Chemsex—the use of psychoactive substances during sexual encounters—among men who have sex with men is a growing concern. On-demand HIV pre-exposure prophylaxis (PrEP) may be a suitable tool to prevent HIV transmission among “chemsexers.” We used the open-label extension study of the ANRS-IPERGAY trial to describe chemsexers and their PrEP use.

Methods:

Among the 361 men who have sex with men enrolled in ANRS-IPERGAY's open-label extension study, we selected the 331 with available data on drug use. A 2-monthly web questionnaire on sociobehavioral data was used to compare sexual behaviors between questionnaires where chemsex was reported and those where it was not. Using a generalized estimating equation logistic regression, we studied whether practicing chemsex was associated with correct PrEP use.

Results:

Among the 331 participants, 30% reported chemsex practice at least once during follow-up and were considered chemsexers. Chemsex was reported in 16% of all questionnaires. Chemsexers were not significantly different from nonchemsexers regarding sociodemographic characteristics, although they reported greater use of anxiolytics and more sensation-seeking. Reporting chemsex was associated with more high-risk sexual practices and a higher perception of risk. After adjustment for other potential correlates, chemsex remained associated with correct PrEP use [odds ratio (95% confidence interval) = 2.24 (1.37 to 3.66)].

Conclusions:

Our findings show that chemsexers were more likely to report high-risk sexual practices but also had a higher perception of risk. They were also more likely to use PrEP correctly when practicing chemsex. Consequently, PrEP may be a suitable tool to reduce HIV-risk transmission among chemsexers.
Orexin-1 receptor signaling in ventral pallidum regulates demand for the opioid remifentanil
Authors: Mohammdkhani Aida , Pantazis Caroline B , Bowrey Hannah E , James Morgan H , Aston-Jones Gary
Published: June 2018

Signaling at the orexin-1 receptor (Ox1R) is important for motivation for various drugs of abuse. Recently, our laboratory showed that systemic blockade of Ox1Rs decreased motivation for the potent and short-acting opioid remifentanil, as well as remifentanil consumption at null cost (Porter-Stransky et al., 2017). However, the central site(s) through which orexin acts to regulate opioid-seeking behaviors are not known. We investigated ventral pallidum (VP) as a potential site of orexin action, as VP is a known mediator of opioid reward and is densely innervated by orexin-immunoreactive fibers. We used a within-session behavioral economics (BE) paradigm in which remifentanil price (responses/ μg iv remifentanil) was sequentially increased throughout the session. Rats were implanted with bilateral cannulae into caudal VP (cVP), through which microinjections of SB334867 (SB), an Ox1R antagonist, were given prior to BE and reinstatement testing. Contrary to systemic SB treatment, intra-cVP SB preferentially reduced motivation (increased demand elasticity and reinstatement) for reminfentanil, without affecting remifentanil consumption at null cost. These effects were specific to cVP, as control microinjections of SB immediately dorsal to cVP did not affect remifentanil-seeking. Baseline demand for remifentanil predicted cued reinstatement of remifentanil seeking and the efficacy with which intra-cVP SB administration reduced motivation for remifentanil. These findings indicate a specific role for cVP Ox1R signaling in mediating the motivational properties of the opioid remifentanil, distinct from its consumption at null cost. Our findings also highlight the BE paradigm as an effective biomarker for predicting opioid addiction behaviors and treatment efficacy.
Induction and suppression of NF-kB signalling by a DNA virus ofDrosophila
Authors: Palmer William H. , Joosten Joep , Overheul Gijs J. , Jansen Pascal W. , Vermeulen Michiel , Obbard Darren J. , Van Rij Ronald P.
Published: June 2018

Interactions between the insect immune system and RNA viruses have been best studied inDrosophila, where RNA interference, NF-kB and JAK-STAT pathways underlie antiviral immunity. In response to these immune mechanisms, insect viruses have convergently evolved suppressors of RNA interference that act by diverse mechanisms to permit viral replication. However, interactions between the insect immune system and DNA viruses have received less attention, primarily because fewDrosophila-infectingDNA virus isolates are available. Here, we use a recently-isolated DNA virus ofDrosophila melanogaster, Kallithea virus, to probe known antiviral immune responses and virus evasion tactics in the context of DNA virus infection. We find that fly mutants for RNA interference and Immune deficiency (Imd), but not Toll, pathways are more susceptible to Kallithea virus infection. We identify the Kallithea virus-encoded protein gp83 as a potent inhibitor of Toll signalling, strongly suggesting that Toll mediates antiviral responses during Kallithea virus infection, but that it is suppressed by the virus. Further, we find that Kallithea gp83 inhibits Toll signalling either through NF-kB transcription factor regulation, or transcriptionally. Together, these results provide a broad description of known antiviral pathways in the context of DNA virus infection and identify the first Toll pathway inhibitor in aDrosophilavirus, extending the known diversity of insect virus-encoded immune inhibitors.
N-terminal phosphorylation of Huntingtin: A molecular switch for regulating Htt aggregation, helical conformation, internalization and nuclear targeting
Authors: DeGuire Sean M. , Ruggeri Francesco. S. , Fares Mohamed-Bilal , Chiki Anass , Cendrowska Urszula , Dietler Giovanni , Lashuel Hilal A.
Published: June 2018

Phosphorylation of exon1 of the Huntingtin protein (Httex1) has been shown to play important roles in regulating the structure, toxicity and cellular properties of N-terminal fragments and the full-length Huntingtin protein. Here, we investigated and compared the effect of bona fide phosphorylation at S13 and/or S16 on the structure, aggregation, membrane binding, and subcellular properties of mutant Httex1-Q18A. We show that serine phosphorylation at either S13 or S16 strongly disrupts the amphipathic α-helix of the N-terminus, inhibits the aggregation of mutant Httex1 and prompts the internalization and nuclear targeting of Httex1 preformed aggregates. In synthetic peptides phosphorylation at S13 and/or S16 strongly disrupted the amphipathic α-helix of the N-terminal 17 residues (Nt17) of Httex1 and Nt17 membrane binding. Our studies on peptides bearing a different combination of phosphorylation sites within Nt17 revealed a novel phosphorylation-dependent switch for regulating the structure of Httex1 involving crosstalk between phosphorylation at T3 and S13 or S16. Together, our results provide novel insights into the role of phosphorylation in regulating Httex1 structure and function in health and disease and underscore the critical importance of identifying enzymes responsible for regulating Htt phosphorylation and their potential as therapeutic targets for the treatment of Huntington’s disease.
Experimental determination of codon usage-dependent selective pressure on high copy-number genes inSaccharomyces cerevisiae
Authors: Jossé Lyne , Singh Tarun , von der Haar Tobias
Published: June 2018

One of the central hypotheses in the theory of codon usage evolution is that in highly expressed genes particular codon usage patterns arise because they facilitate efficient gene expression and are thus selected for in evolution. Here we use plasmid copy number assays and growth rate measurements to explore details of the relationship between codon usage, gene expression level, and selective pressure inSaccharomyces cerevisiae. We find that when high expression levels are required optimal codon usage is beneficial and provides a fitness advantage, consistent with evolutionary theory. However, when high expression levels are not required, optimal codon usage is surprisingly and strongly selected against. We show that this selection acts at the level of protein synthesis, and we exclude a number of molecular mechanisms as the source for this negative selective pressure including nutrient and ribosome limitations and proteotoxicity effects. These findings inform our understanding of the evolution of codon usage bias, as well as the design of recombinant protein expression systems.
Wolbachia pipientisassociated to tephritid fruit fly pests: from basic research to applications
Authors: Mateos Mariana , Martinez Humberto , Lanzavecchia Silvia B. , Conte Claudia , Guillén Karina , Morán-Aceves Brenda M. , Toledo Jorge , Liedo Pablo , Asimakis Elias D. , Doudoumis Vangelis , Kyritsis Georgios A. , Papadopoulos Nikos T. , Avgoustinos Antonios A. , Segura Diego F. , Tsiamis George , Bourtzis Kostas
Published: June 2018

Members of the true fruit flies (family Tephritidae) are among the most serious agricultural pests worldwide, whose control and management demands large and costly international efforts. The need for cost-effective and environmentally-friendly integrated pest management (IPM) has led to the development and implementation of autocidal control strategies. Autocidal approaches include the widely used sterile insect technique (SIT) and the incompatible insect technique (IIT). IIT relies on maternally transmitted bacteria (namelyWolbachia), to cause a conditional sterility in crosses between released mass-rearedWolbachia-infected males and wild females, which are either uninfected or infected with a differentWolbachiastrain (i.e., cytoplasmic incompatibility; CI). Herein, we review the current state of knowledge onWolbachia-tephritid interactions including infection prevalence in wild populations, phenotypic consequences, and their impact on life history traits. Numerous pest tephritid species are reported to harborWolbachiainfections, with a subset exhibiting high prevalence. The phenotypic effects ofWolbachiahave been assessed in very few tephritid species, due in part to the difficulty of manipulatingWolbachiainfection (removal or transinfection). Based on recent methodological advances (high-throughput DNA sequencing) and a breakthrough concerning the mechanistic basis of CI, we suggest research avenues that could accelerate generation of necessary knowledge for the potential use ofWolbachia-based IIT in area-wide integrated pest management (AW-IPM) strategies for the population control of tephritid pests.
Stress vulnerability promotes an alcohol prone phenotype in a preclinical model of sustained depression
Authors: Riga Danai , Schmitz Leanne JM , van Mourik Yvar , Hoogendijk Witte JG , De Vries Taco J , Smit August B , Spijker Sabine
Published: June 2018

Major depression and alcohol-related disorders frequently co-occur. Depression severity weighs on the magnitude and persistence of comorbid alcohol use disorder (AUD), with severe implications for disease prognosis. Here, we investigated whether depression vulnerability drives propensity to AUD at the preclinical level. We used the social defeat-induced persistent stress (SDPS) model of chronic depression in combination with operant alcohol self-administration (SA). Male Wistar rats were subjected to social defeat (5 episodes) and prolonged social isolation (~12 weeks) and subsequently classified as SDPS-prone or SDPS-resilient based on their affective and cognitive performance. Using an operant alcohol SA paradigm, acquisition, motivation, extinction and cue-induced reinstatement of alcohol-seeking were examined in the two subpopulations. SDPS-prone animals showed increased alcohol SA, excessive motivation to acquire alcohol, persistent alcohol-seeking despite alcohol unavailability, extinction resistance and increased cue-induced relapse; the latter could be blocked by the α2 adrenoreceptor agonist guanfacine. In SDPS-resilient rats, prior exposure to social defeat increased alcohol SA without affecting any other measures of alcohol-seeking and -taking. Our data revealed that depression proneness confers vulnerability to alcohol, emulating patterns of alcohol dependence seen in human addicts, and that depression resilience to a large extent protects from the development of AUD-like phenotypes. Furthermore, our data suggest that stress exposure alone, independently of depressive symptoms, alters alcohol intake in the long-term.
A computational strategy for finding novel targets and therapeutic compounds for opioid dependence
Authors: Wu Xiaojun , Xie Siwei , Wang Lirong , Fan Peihao , Ge Songwei , Xie Xiang-Qun , Wu Wei
Published: June 2018

Opioids are widely used for treating different types of pains, but overuse and abuse of prescription opioids have led to opioid epidemic in the United States. Besides analgesic effects, chronic use of opioid can also cause tolerance, dependence, and even addiction. Effective treatment of opioid addiction remains a big challenge today. Studies on addictive effects of opioids focus on striatum, a main component in the brain responsible for drug dependence and addiction. Some transcription regulators have been associated with opioid addiction, but relationship between analgesic effects of opioids and dependence behaviors mediated by them at the molecular level has not been thoroughly investigated. In this paper, we developed a new computational strategy that identifies novel targets and potential therapeutic molecular compounds for opioid dependence and addiction. We employed several statistical and machine learning techniques and identified differentially expressed genes over time which were associated with dependence-related behaviors after exposure to either morphine or heroin, as well as potential transcription regulators that regulate these genes, using time course gene expression data from mouse striatum. Moreover, our findings revealed that some of these dependence-associated genes and transcription regulators are known to play key roles in opioid-mediated analgesia and tolerance, suggesting that an intricate relationship between opioid-induce pain-related pathways and dependence may develop at an early stage during opioid exposure. Finally, we determined small compounds that can potentially target the dependence-associated genes and transcription regulators. These compounds may facilitate development of effective therapy for opioid dependence and addiction. We also built a database (http://daportals.org) for all opioid-induced dependence-associated genes and transcription regulators that we discovered, as well as the small compounds that target those genes and transcription regulators.
An activation pathway governs cell wall polymerization by a bacterial morphogenic machine
Authors: Rohs Patricia D. A. , Buss Jackson , Sim Sue , Squyres Georgia , Srisuknimit Veerasak , Smith Mandy , Cho Hongbaek , Sjodt Megan , Kruse Andrew C. , Garner Ethan , Walker Suzanne , Kahne Daniel , Bernhardt Thomas G.
Published: June 2018

Cell elongation in rod-shaped bacteria is mediated by the Rod system, a conserved morphogenic complex that spatially controls cell wall (CW) assembly. InEscherichia coli, alterations in a CW synthase component of the system called PBP2 were identified that overcome other inactivating defects. Rod system activity was stimulated in the suppressors in vivo, and purified synthase complexes with these changes showed more robust CW synthesis in vitro. Polymerization of the actin-like MreB component of the Rod system was also found to be enhanced in cells with the activated synthase. The results suggest an activation pathway governing Rod system function in which PBP2 conformation plays a central role in stimulating both CW glycan polymerization by its partner RodA and the formation of cytoskeletal filaments of MreB to orient CW assembly. An analogous activation pathway involving similar enzymatic components is likely responsible for controlling CW synthesis by the division machinery.
Anomalous diffusion in inverted variable-lengthscale fluorescence correlation spectroscopy
Authors: Stolle M. , Fradin C.
Published: June 2018

Using fluorescence correlation spectroscopy (FCS) to distinguish between different types of diffusion processes is often a perilous undertaking, as the analysis of the resulting autocorrelation data is model-dependant. Two recently introduced strategies, however, can help move towards a model-independent interpretation of FCS experiments: 1) the obtention of correlation data at different length-scales and 2) its inversion to retrieve the mean-squared displacement associated with the process under study. We use computer simulations to examine the signature of several biologically relevant diffusion processes (simple diffusion, continuous-time random walk, caged diffusion, obstructed diffusion, two-state diffusion and diffusing diffusivity) in variable-lengthscale FCS. We show that, when used in concert, lengthscale variation and data inversion permit to identify non-Gaussian processes and, regardless of Gaussianity, to retrieve their mean-squared displacement over several orders of magnitude in time. This makes unbiased discrimination between different classes of diffusion models possible.
Neural tracking of the speech envelope in cochlear implant users
Authors: Somers Ben , Verschueren Eline , Francart Tom
Published: June 2018

Objective

When listening to speech, the brain tracks the speech envelope. It is possible to reconstruct this envelope from EEG recordings. However, in people who hear using a cochlear implant (CI), the artifacts caused by electrical stimulation of the auditory nerve contaminate the EEG. This causes the decoder to produce an artifact-dominated reconstruction, which does not reflect the neural signal processing. The objective of this study is to develop and validate a method for assessing the neural tracking of speech envelope in CI users.

Approach

To obtain EEG recordings free of stimulus artifacts, the electrical stimulation is periodically in-terrupted. During these stimulation gaps, artifact-free EEG can be sampled and used to train a linear envelope decoder. Different recording conditions were used to characterize the artifacts and their influence on the envelope reconstruction.

Main results

The present study demonstrates for the first time that neural tracking of the speech envelope can be measured in response to ongoing electrical stimulation. The responses were validated to be truly neural and not affected by stimulus artifact.

Significance

Besides applications in audiology and neuroscience, the characterization and elimination of stimulus artifacts will enable future EEG studies involving continuous speech in CI users. Measures of neural tracking of the speech envelope reflect interesting properties of the listener’s perception of speech, such as speech intelligibility or attentional state. Successful decoding of neural envelope tracking will open new possibilities to investigate the neural mechanisms of speech perception with a CI.
Putting a New Spin of G4 Structure and Binding by Analytical Ultracentrifugation
Authors: Dean William L. , Gray Robert D. , DeLeeuw Lynn , Monsen Robert C. , Chaires Jonathan B.
Published: June 2018

Analytical ultracentrifugation is a powerful biophysical tool that provides information about G-quadruplex structure, stability and binding reactivity. This chapter provides a simplified explanation of the method, along with examples of how it can be used to characterize G4 formation and to monitor small-molecule binding.
A quantitative framework for motion visibility in human cortex
Authors: Birman Daniel , Gardner Justin L
Published: June 2018

Despite the central use of motion visibility to reveal the neural basis of perception, perceptual decision making, and sensory inference there exists no comprehensive quantitative framework establishing how motion visibility parameters modulate human cortical response. Random-dot motion stimuli can be made less visible by reducing image contrast or motion coherence, or by shortening the stimulus duration. Because each of these manipulations modulates the strength of sensory neural responses they have all been extensively used to reveal cognitive and other non-sensory phenomenon such as the influence of priors, attention, and choice-history biases. However, each of these manipulations is thought to influence response in different ways across different cortical regions and a comprehensive study is required to interpret this literature. Here, human participants observed random-dot stimuli varying across a large range of contrast, coherence, and stimulus durations as we measured blood-oxygen-level dependent responses. We developed a framework for modeling these responses which quantifies their functional form and sensitivity across areas. Our framework demonstrates the sensitivity of all visual areas to each parameter, with early visual areas V1-V4 showing more parametric sensitivity to changes in contrast and V3A and MT to coherence. Our results suggest that while motion contrast, coherence, and duration share cortical representation, they are encoded with distinct functional forms and sensitivity. Thus, our quantitative framework serves as a reference for interpretation of the vast perceptual literature manipulating these parameters and shows that different manipulations of visibility will have different effects across human visual cortex and need to be interpreted accordingly.
TCR/ITK signaling via mTOR tunes CD8+ T cell homeostatic proliferation, metabolism, and anti-tumor effector function
Authors: Huang Weishan , Luo Junjie , August Avery
Published: June 2018

T cell homeostatic proliferation (HP) is regulated by T cell receptor (TCR) signals and homeostatic cytokines, and suggested to be proportional to TCR signal strength. However, we show here that ITK, a positive regulator of TCR signaling, negatively tunes CD8+ T cell HP, metabolism, and effector function. Under lymphopenic environments, Itk−/− CD8+ T cells exhibit significant increase in T cell-intrinsic HP, which requires mTOR activity and can be driven by T cell-T cell interaction. TCR signals through ITK tune IL-7-mediated CD8+ T cell metabolism and HP in a mTOR-dependent manner. The lack of ITK also resulted in enhanced effector cell fate programming, antigen sensitivity and anti-tumor immunity by HP cells. Thus, TCR signaling via ITK, is a negative tuner of CD8+ T cell homeostasis, metabolism and effector function, and may be a target for clinical benefit in cancer therapy.

One Sentence Summary

TCR signal strength had been long-thought to be proportional to T cell proliferation and effector function, here we demonstrate a counterintuitive role of the TCR signaling through ITK in negatively tuning proliferation under lymphopenic conditions via regulating mTOR activity, T cell metabolism, proliferation, and effector function.
Reducing cancer health disparities among US Latinos: a Freireian approach
Authors: Rivera Yonaira M.
Published: June 2018

Purpose

The purpose of this paper is to apply Paulo Freire’s writings from Pedagogy of the Oppressed to critique current efforts to reduce cancer health disparities (CHDs) among Latinos in the USA.

Design/methodology/approach

Freire’s writings on oppression, critical consciousness, praxis and dialogical education are applied to recent efforts to reduce CHDs among Latinos in the USA through the use of promotores.

Findings

Freireian teachings can provide insight on ways to engage Latino communities in culturally sensitive conversations that respect deeply rooted beliefs, and address the political and socioeconomic inequities many continue to face. Programs must revisit Freire’s political and transformative roots to ensure efforts to reduce CHDs also promote health equity and community empowerment.

Practical implications

Public health initiatives should incorporate Freireian principles of dialogical education and critical consciousness in the development of cancer prevention and screening programs tailored to Latinos in the USA to ensure program longevity and success.

Social implications

Approaching conversations and interactions dialogically can foster critical engagement and empower collective action among Latino communities in efforts to improve their environments and reduce health disparities.

Originality/value

This is a multi-layered analysis of different social and structural factors influencing CHDs among Latinos in the USA, and is coupled with a historical overview of colonialism and oppression in Latin America. It culminates in suggestions on ways to improve future public health efforts that embrace Freireian approaches and promote health equity.