bluuebunny/crossref_metadata_2025 huggingface dataset:
Discovery of novel endogenous viral elements in Aedes spp. mosquitoes
Authors: Pischedda Elisa , Palatini Umberto , Crava Maria Cristina , Mattia Annamaria , Bonizzoni Mariangela
Published: December 2019

The genomes of Aedes spp. mosquitoes contain integrated sequences from nonretroviral RNA viruses that are enriched in piRNA clusters, are embedded next to transposable elements (TEs) and produce piRNAs. The parallelism between TEs and viral integrations led to the hypothesis that viral integrations may constitute an archive of past viral infections and potentially have an immunity impact on novel infection with cognate viruses, similarly to how the piRNA pathway interacts with TEs. A corollary of this hypothesis is that the landscape of viral integrations should be variable across populations depending on their viral exposure. The highly repetitive nature of Aedes spp. genomes make the discovery of viral integrations from whole genome sequencing data of wild mosquitoes a daunting task.

Here we describe a novel bioinformatic pipeline to rigorously identify viral integrations using Next Generation Sequencing (NGS) data. Libraries from single or pools of mosquitoes, reference genome statistics, the landscape of TEs and the geographic origin of the analyzed samples are the actors of the analysis.

This pipeline has been tested in Ae. aegypti and Ae. albopictus mosquitoes, allowing to compare the performance of the analyses on genome assemblies of different completeness. We identified novel viral integrations in both genomes. Additionally, we show that the landscape of viral integrations is dynamic, with a population-specific behavior that we can leverage to formulate hypothesis on mechanisms of integration and the biological role of viral integrations.
Concerted cutting by Spo11 illuminates DNA break mechanisms and initiates gap repair during meiosis
Authors: Johnson Dominic , Crawford Margaret , Cooper Tim , Bouuaert Corentin Claeys , Keeney Scott , Llorente Bertrand , Garcia Valerie , Neale Matthew J.
Published: December 2019

Genetic variation arises during meiosis via repair of DNA double-strand breaks (DSBs) created by the topoisomerase-like Spo11 protein. These DSBs are thought to always occur sparsely across the genome, with isolated DSBs generating discrete recombination events. We challenge this view, demonstrating that hyper-localised coincident DSBs frequently form within hotspots in bothS. cerevisiaeand mouse—a process suppressed by the DNA damage response kinase Tel1/ATM. Remarkably, the distances separating coincident DSBs vary with ∼10.5 bp periodicity, invoking a model where adjacent Spo11 molecules have a fixed orientation relative to the DNA helix. Deep sequencing of meiotic progeny identifies recombination scars consistent with gap repair initiated by adjacent DSBs. Our results revise current thinking about how genetic recombination initiates, reviving original concepts of meiotic recombination as double-strand gap repair.
Tracking self-citations in academic publishing
Authors: Kacem Ameni , Flatt Justin W. , Mayr Philipp
Published: December 2019

Citation metrics have value because they aim to make scientific assessment a level playing field, but urgent transparency-based adjustments are necessary to ensure that measurements yield the most accurate picture of impact and excellence. One problematic area is the handling of self-citations, which are either excluded or inappropriately accounted for when using bibliometric indicators for research evaluation. Here, in favor of openly tracking self-citations we report on self-referencing behavior among various academic disciplines as captured by the curated Clarivate Analytics Web of Science database. Specifically, we examined the behavior of 385,616 authors grouped into 15 subject areas like Biology, Chemistry, Science & Technology, Engineering, and Physics. These authors have published 3,240,973 papers that have accumulated 90,806,462 citations, roughly five percent of which are self-citations. Up until now, very little is known about the buildup of self-citations at the author-level and in field-specific contexts. Our view is that hiding self-citation data is indefensible and needlessly confuses any attempts to understand the bibliometric impact of one’s work. Instead we urge academics to embrace visibility of citation data in a community of peers, which relies on nuance and openness rather than curated scorekeeping.
Human tauopathies are not associated with an activated unfolded protein response
Authors: Pitera A. P. , Hartnell I. J. , Boche D. , O’Connor V. , Deinhardt K.
Published: December 2019

Tauopathies are the neurodegenerative diseases associated with the accumulation of misfolded tau protein. Despite many years of investigation, the mechanisms underpinning tau dependent proteinopathy remains to be elucidated. A protein quality control pathway within the endoplasmic reticulum (ER), called unfolded protein response (UPR), has been suggested as a possible response implicated in the misfolded tau-mediated neurodegeneration. However, the question arose: how does the cytosolic protein tau that does not enter the ER induce a response stemming from this compartment? In this study we investigated three different human tauopathies to establish whether these diseases are associated with the activation of UPR. We probed for the modulation of several reliable UPR markers in mRNA and proteins extracted from 20 brain samples from Alzheimer’s disease (AD) patients, 11 from Pick’s disease (PiD) and 10 from Progressive Supranuclear Palsy (PSP) patients coupled to equal numbers of age-matched non-demented controls. This showed that different markers of UPR are not changed in any of the human tauopathies investigated. Interestingly, UPR signatures were often observed in non-demented controls. These data from human tissue further support the emerging evidence that the accumulation of misfolded cytosolic tau does not drive a diseased associated activation of UPR.
EM-seq: Detection of DNA Methylation at Single Base Resolution from Picograms of DNA
Authors: Vaisvila Romualdas , Ponnaluri V. K. Chaithanya , Sun Zhiyi , Langhorst Bradley W. , Saleh Lana , Guan Shengxi , Dai Nan , Campbell Matthew A. , Sexton Brittany S. , Marks Katherine , Samaranayake Mala , Samuelson James C. , Church Heidi E. , Tamanaha Esta , Corrêa Ivan R. , Pradhan Sriharsa , Dimalanta Eileen T. , Evans Thomas C. , Williams Louise , Davis Theodore B.
Published: December 2019

Bisulfite sequencing is widely used to detect 5mC and 5hmC at single base resolution. However, bisulfite treatment damages DNA resulting in fragmentation, loss of DNA and biased sequencing data. To overcome this, we developed Enzymatic Methyl-seq (EM-seq), an enzymatic based approach that uses as little as 100 pg of DNA. EM-seq outperformed bisulfite converted libraries in all metrics examined including coverage, duplication, sensitivity and nucleotide composition. EM-seq libraries displayed even GC distribution, improved correlation across input amounts as well as increased representation of genomic features. These data indicate that EM-seq is more accurate and reliable than whole genome bisulfite sequencing (WGBS).
Sympatric ecological divergence with coevolution of niche preference
Authors: Payne Pavel , Polechová Jitka
Published: December 2019

Reinforcement, the increase of assortative mating driven by selection against unfit hybrids, is conditional on pre-existing divergence. Yet, for ecological divergence to precede the evolution of assortment, strict symmetries between fitnesses in niches must hold, and/or there must be low gene flow between the nascent species. It has thus been argued that conditions favouring sympatric speciation are rarely met in nature. Indeed, we show that under disruptive selection, violating symmetries in niche sizes and increasing strength of the trade-off in selection between the niches quickly leads to loss of genetic variation, instead of evolution of specialists. The region of the parameter space where polymorphism is maintained further narrows with increasing number of loci encoding the diverging trait and the rate of recombination between them. Yet, evolvable assortment and pre-existing assortment both substantially broaden the parameter space within which polymorphism is maintained. Notably, pre-existing niche preference speeds up further increase of assortment, thus facilitating reinforcement in the later phases of speciation. We conclude that in order for sympatric ecological divergence to occur, niche preference must co-evolve throughout the divergence process. Even if populations come into secondary contact, having diverged in isolation, niche preference substantially broadens the conditions for coexistence in sympatry and completion of the speciation process.
HIV Care Prioritization using Phylogenetic Branch Length
Authors: Moshiri Niema , Smith Davey M. , Mirarab Siavash
Published: December 2019

Abstract

In HIV epidemics, the structure of the transmission network can be dictated by just a few individuals. Public health intervention, such as ensuring people living with HIV adhere to antiretroviral therapy (ART) and are continually virally-suppressed, can help control the spread of the virus. However, such intervention requires utilizing the limited public health resource allocations. As a result, the ability to determine which individuals are most at-risk of transmitting HIV could allow public health officials to focus their limited resources on these individuals. Molecular epidemiology suggests an approach: prioritizing people living with HIV based on patterns of transmission inferred from their sampled viral sequences. In this paper, we introduce ProACT (Prioritization usingAnCesTral edge lengths), a phylogenetic approach for prioritizing individuals living with HIV. ProACT uses a simple idea: ordering individuals by their terminal branch length in the phylogeny of their virus. In simulations and also on a dataset of HIV-1 subtype Bpolsequences obtained in San Diego, we show that this simple strategy improves the effectiveness of prioritization compared to state-of-the-art methods that rely on monitoring the growth of transmission clusters defined based on genetic distance.
Novel instrumented insole algorithm accurately approximates plantar flexor loading
Authors: Hullfish Todd J. , Baxter Josh R.
Published: December 2019

Plantar flexor loading is critical for ambulatory function but there are few wearable solutions to monitor loading. The purpose of this study was to develop and validate a method to quantify plantar flexor loading using a commercially-available instrumented insole. Seven healthy young adults completed a battery of functional activities to characterize a range of plantar flexor loading which included single leg heel raise, step down, and drop jump as well as walking and running at comfortable speeds. Lower extremity trajectories were captured using motion capture and ground reaction forces were recorded with embedded force plates as well as the instrumented insole. Measurements of plantar flexor loading quantified by the instrumented insole were compared to ‘gold standard’ inverse dynamics. We found that the insole loading calculation of plantar flexor moment was accurate to within 4.2% on average compared to inverse dynamics across all activities. Additionally, the calculated wave forms were strongly correlated with inverse dynamics (Rxy> 0.928). Our findings demonstrate the utility and fidelity of a new method for measuring plantar flexor loading using a commercially available instrumented insole. By leveraging this new methodology, it is now feasible to prospectively track and eventually prescribe plantar flexor loading outside of the clinic to improve patient outcomes.
Conformational state switching and pathways of chromosome dynamics in cell cycle
Authors: Chu Xiakun , Wang Jin
Published: December 2019

Cell cycle is a process and function of a cell with different phases essential for cell growth, proliferation, and replication. Cell cycle depends on the structure and dynamics of the underlying DNA molecule, which underpins the genome function. A microscopic structural-level understanding of how genome or its functional module chromosome performs the cell cycle in terms of large-scale conformational transformation between different phases such as the interphase and the mitotic phase is still challenging. Here, we develop a non-equilibrium excitation-relaxation energy landscape-switching model to quantify the underlying chromosome conformational transitions through (de-)condensation for a complete microscopic understanding of the cell cycle. We show that the chromosome conformational transition mechanism from the interphase to the mitotic phase follows a two-stage scenario, in good agreement with the experiments. In contrast, the mitotic exit pathways show the existence of an over-expanded chromosome that recapitulates the chromosome in the experimentally identified intermediate state at the telophase. We find the conformational pathways are heterogeneous and irreversible, as a result of the non-equilibrium dynamics of the cell cycle from both structural and kinetic perspectives. We suggest that the irreversibility is mainly due to the distinct participation of the ATP-dependent structural maintenance of chromosomal protein complexes during the cell cycle. Our findings provide crucial insights into the microscopic molecular structural and dynamical physical mechanism for the cell cycle beyond the previous more macroscopic descriptions. Our non-equilibrium landscape framework is general and applicable to study diverse non-equilibrium physical and biological processes such as active matter, differentiation/development and cancer.
broadcontrols leg imaginal disc morphogenesis in Drosophila via regulation of cell shape changes and remodeling of extracellular matrix
Authors: Rice Clinton , Macdonald Stuart , Wang Xiaochen , Ward Robert E
Published: December 2019

Imaginal disc morphogenesis during metamorphosis inDrosophila melanogasterprovides an excellent model to uncover molecular mechanisms by which hormonal signals effect physical changes during development. Thebroad(br)Z2isoform encodes a transcription factor required for disc morphogenesis in response to 20-hydroxyecdysone, yet how it accomplishes this remains largely unknown. Here, we show that amorphicbr5mutant discs fail to remodel their basal extracellular matrix (ECM) after puparium formation and do not undergo necessary cell shape changes. RNA sequencing of wild type and mutant leg discs identified 717 genes differentially regulated bybr; functional studies reveal that several are required for adult leg formation, particularly those involved in remodeling the ECM. Additionally,br Z2expression is abruptly shut down at the onset of metamorphosis, and expressing it beyond this time results in failure of leg development during the late prepupal and pupal stages. Taken together, our results suggest thatbr Z2is required to drive ECM remodeling, change cell shape, and maintain metabolic activity through the mid prepupal stage, but must be switched off to allow expression of pupation genes.

Summary Statement

TheDrosophila melanogasterecdysone-responding transcription factorbroadcontrols morphogenetic processes in leg imaginal discs during metamorphosis through regulation of genes involved in extracellular matrix remodeling, metabolism, and cell shape changes and rearrangements.
Population Responses Represent Vocalization Identity, Intensity, and Signal-to-Noise Ratio in Primary Auditory Cortex
Authors: Ni Ruiye , Bender David A. , Barbour Dennis L.
Published: December 2019

The ability to process speech signals under challenging listening environments is critical for speech perception. Great efforts have been made to reveal the underlying single unit encoding mechanism. However, big variability is usually discovered in single-unit responses, and the population coding mechanism is yet to be revealed. In this study, we are aimed to study how a population of neurons encodes behaviorally relevant signals subjective to change in intensity and signal-noise-ratio (SNR). We recorded single-unit activity from the primary auditory cortex of awake common marmoset monkeys (Callithrix jacchus) while delivering conspecific vocalizations degraded by two different background noises: broadband white noise (WGN) and vocalization babble (Babble). By pooling all single units together, the pseudo-population analysis showed the population neural responses track intra- and inter-trajectory angle evolutions track vocalization identity and intensity/SNR, respectively. The ability of the trajectory to track the vocalizations attribute was degraded to a different degree by different noises. Discrimination of neural populations evaluated by neural response classifiers revealed that a finer optimal temporal resolution and longer time scale of temporal dynamics were needed for vocalizations in noise than vocalizations at multiple different intensities. The ability of population responses to discriminate between different vocalizations were mostly retained above the detection threshold.

Significance Statement

How our brain excels in the challenge of precise acoustic signal encoding against noisy environment is of great interest for scientists. Relatively few studies have strived to tackle this mystery from the perspective of neural population responses. Population analysis reveals the underlying neural encoding mechanism of complex acoustic stimuli based upon a pool of single units via vector coding. We suggest the spatial population response vectors as one important way for neurons to integrate multiple attributes of natural acoustic signals, specifically, marmots’ vocalizations.
Natural Zeitgebers cannot compensate for the loss of a functional circadian clock in timing of a vital behaviour inDrosophila
Authors: Ruf Franziska , Mitesser Oliver , Mungwa Simon Tii , Horn Melanie , Rieger Dirk , Hovestadt Thomas , Wegener Christian
Published: December 2019

The adaptive significance of adjusting behavioural activities to the right time of the day is intuitive. Laboratory studies have implicated an important role of circadian clocks in behavioural timing and rhythmicity. Yet, recent studies on clock-mutant animals questioned this importance under more naturalistic settings, as various clock mutants showed nearly normal diel activity rhythms under semi-natural Zeitgeber conditions.

We here report evidence that proper timing of eclosion, a vital behaviour of the fruit flyDrosophila melanogaster, requires a functional molecular clock even under quasi-natural conditions. In contrast to wildtype flies,period01mutants with a defective molecular clock eclose mostly arrhythmically in a temperate environment even in the presence of a full complement of abiotic Zeitgebers. Moreover,period01mutants eclose during a much larger portion of the day, and peak eclosion time becomes more susceptible to variable day-to-day changes of light and temperature. Under the same conditions, flies with impaired peptidergic inter-clock signalling (pdf01andhan5304mutants) stayed largely rhythmic with normal gate sizes. Our results suggest that the presence of natural Zeitgebers can mitigate a loss of peptide-mediated phasing between central clock neuron groups, but cannot substitute for the lack of a functional molecular clock under natural temperate conditions.
Mitochondrial-Encoded Peptide MOTS-c is an Exercise-Induced Regulator of Aging Metabolic Homeostasis and Physical Capacity
Authors: Reynolds Joseph C. , Lai Rochelle W. , Woodhead Jonathan S.T. , Joly James H. , Mitchell Cameron J. , Cameron-Smith David , Lu Ryan , Cohen Pinchas , Graham Nicholas A. , Benayoun Bérénice A. , Merry Troy L. , Lee Changhan
Published: December 2019

Healthy aging can be promoted by enhancing metabolic fitness and physical capacity (1, 2). Mitochondria are chief metabolic organelles with strong implications in aging (3–8). In addition to their prominent role in bioenergetics, mitochondria also coordinate broad physiological functions by communicating to other cellular compartments or distal cells using multiple factors (9, 10), including peptides that are encoded within their own independent genome (11, 12). However, it is unknown if aging is actively regulated by factors encoded in the mitochondrial genome. MOTS-c is a mitochondrial-encoded peptide that regulates metabolic homeostasis (13, 14), in part, by translocating to the nucleus to regulate adaptive nuclear gene expression in response to cellular stress (15–17). Here, we report that MOTS-c is an exercise-induced mitochondrial-encoded peptide that significantly enhanced physical performance when administered to young (2 mo.), middle-aged (12 mo.), and old (22 mo.) mice. In humans, we found that endogenous MOTS-c levels significantly increased in response to exercise in skeletal muscle (11.9-fold) and in circulation (1.5-fold). Systemic MOTS-c treatment in mice significantly enhanced the performance on a treadmill of all age groups (~2-fold). MOTS-c regulated (i) nuclear genes, including those related to metabolism and protein homeostasis, (ii) glucose and amino acid metabolism in skeletal muscle, and (iii) myoblast adaptation to metabolic stress. Late-life (23.5 mo.) initiated intermittent MOTS-c treatment (3x/week) improved physical capacity and trended towards increasing lifespan. Our data indicate that aging is regulated by genes that are encoded not only in the nuclear genome (18, 19), but also in the mitochondrial genome. Considering that aging is the major risk factor for multiple chronic diseases (20, 21), our study provides new grounds for further investigation into mitochondrial-encoded regulators of healthy lifespan.
Aerobic heterotrophy and RuBisCO-mediated CO2metabolism in marineThaumarchaeota
Authors: Reji Linta , Francis Christopher A.
Published: December 2019

Thaumarchaeotaconstitute an abundant and ubiquitous phylum of Archaea that play critical roles in the global nitrogen and carbon cycles. Most well-characterized members of the phylum are chemolithoautotrophic ammonia-oxidizing archaea (AOA), which comprise up to 5 and 20 % of the total single-celled life in soil and marine systems, respectively. Using two high-quality metagenome-assembled genomes (MAGs), here we describe a divergent marine thaumarchaeal clade that is devoid of the ammonia-oxidation machinery and the AOA-specific carbon-fixation pathway. Phylogenomic analyses placed these genomes within the uncultivated and largely understudied marine pSL12-like thaumarchaeal clade. The predominant mode of nutrient acquisition appears to be aerobic heterotrophy, evidenced by the presence of respiratory complexes and various organic carbon degradation pathways. Unexpectedly, both genomes encoded a form III RuBisCO. Genomic composition of the MAGs is consistent with the role of RuBisCO in nucleotide salvage, as has been proposed previously for archaea harboring the form III variant. Metabolic reconstructions revealed a complete nonoxidative pentose phosphate pathway (PPP) and gluconeogenesis, which can cyclize the RuBisCO-mediated carbon metabolic pathway. We conclude that these genomes represent a hitherto unrecognized evolutionary link between predominantly anaerobic basal thaumarchaeal lineages and mesophilic marine AOA, with important implications for diversification within the phylumThaumarchaeota.
Innovation in solitary bees is driven by exploration, shyness and activity levels
Authors: Collado Miguel Á. , Menzel Randolf , Sol Daniel , Bartomeus Ignasi
Published: December 2019

Behavioural innovation is widely considered an important mechanism by which animals respond to novel environmental challenges, including those induced by human activities. Despite its functional and ecological relevance, much of our current understanding of the innovation process comes from studies in vertebrates. Understanding innovation processes in insects has lagged behind partly because they are not perceived to have the cognitive machinery required to innovate. This perception is however challenged by recent evidence demonstrating sophisticated cognitive capabilities in insects despite their small brains. Here, we study the innovation capacity of a solitary bee (Osmia cornuta) in the laboratory by exposing naïve individuals to an obstacle removal task. We also studied the underlying cognitive and non-cognitive mechanisms through a battery of experimental tests designed to measure learning, exploration, shyness and activity levels. We found that solitary bees can innovate, with 11 of 29 individuals (38%) being able to solve a new task consisting in lifting a lid to reach a reward. The propensity to innovate was uncorrelated with learning capacities, but increased with exploration, boldness and activity. These results provide solid evidence that non-social insects can innovate, and highlight the importance of interpreting innovation in the light of non-cognitive processes.
Fronto-temporal coupling dynamics during spontaneous activity and auditory processing
Authors: García-Rosales Francisco , Lopez-Jury Luciana , Gonzalez-Palomares Eugenia , Cabral-Calderín Yuranny , Hechavarría Julio C.
Published: December 2019

Most mammals rely on the extraction of acoustic information from the environment in order to survive. However, the mechanisms that support sound representation in auditory neural networks involving sensory and association brain areas remain underexplored. In this study, we address the functional connectivity between an auditory region in frontal cortex (the frontal auditory field, FAF) and the auditory cortex (AC) in the batCarollia perspicillata. The AC is a classic sensory area central for the processing of acoustic information. On the other hand, the FAF belongs to the frontal lobe, a brain region involved in the integration of sensory inputs, modulation of cognitive states, and in the coordination of behavioural outputs. The FAF-AC network was examined in terms of oscillatory coherence (local-field potentials, LFPs), and within an information theoretical framework linking FAF and AC spiking activity. We show that in the absence of acoustic stimulation, simultaneously recorded LFPs from FAF and AC are coherent in low frequencies (1-12 Hz). This “default” coupling was strongest in deep AC layers and was unaltered by acoustic stimulation. However, presenting auditory stimuli did trigger the emergence of coherent auditory-evoked gamma-band activity (>25 Hz) between the FAF and AC. In terms of spiking, our results suggest that FAF and AC engage in distinct coding strategies for representing artificial and natural sounds. Taken together, our findings shed light onto the neuronal coding strategies and functional coupling mechanisms that enable sound representation at the network level in the mammalian brain.
Measuring energy-dependent photoelectron escape in microcrystals
Authors: Storm Selina L. S. , Crawshaw Adam D. , Devenish Nicholas E. , Bolton Rachel , Hall David R. , Tews Ivo , Evans Gwyndaf
Published: December 2019

With the increasing trend of using microcrystals and intense microbeams at synchrotron X-ray beamlines, radiation damage becomes a more pressing problem. Theoretical calculations show that the photoelectrons that primarily cause damage can escape microcrystals. This effect would become more pronounced with decreasing crystal size as well as at higher energies. To prove this effect, data from cryocooled lysozyme crystals of dimensions 5 × 3 × 3 and 20 × 8 × 8 µm mounted on cryo-transmission electron microscopy (cryo-TEM) grids were collected at 13.5 and 20.1 keV using a PILATUS CdTe 2M detector, which has a similar quantum efficiency at both energies. Accurate absorbed doses were calculated through the direct measurement of individual crystal sizes using scanning electron microscopy after the experiment and characterization of the X-ray microbeam. The crystal lifetime was then quantified based on the D
1/2 metric. In this first systematic study, a longer crystal lifetime for smaller crystals was observed and crystal lifetime increased at higher X-ray energies, supporting the theoretical predictions of photoelectron escape. The use of detector technologies specifically optimized for data collection at energies above 20 keV allows the theoretically predicted photoelectron escape to be quantified and exploited, guiding future beamline-design choices.
Characterization and functionality of fibre-rich pomaces from the tropical fruit pulp industry
Authors: Medeiros Igor Ucella Dantas de , Aquino Jailane de Souza , Cavalcanti Natália Sufiatti de Holanda , Campos Ana Regina Nascimento , Cordeiro Angela Maria Tribuzy de Magalhães , Damasceno Karla Suzanne Florentino da Silva Chaves , Hoskin Roberta Targino
Published: December 2019

Purpose

The purpose of this paper is to evaluate the chemical and functional composition of acerola, guava and cashew freeze-dried pomaces.

Design/methodology/approach

Fruit pomaces were obtained from the pulp juice industrial sector and submitted to freeze-drying. Samples were analysed for composition (macronutrients, micronutrients, moisture and ash), technological attributes (morphological, hygroscopicity, retention of oil and water and solubility), bioactive compounds (total phenolics, flavonoids, proanthocyanins, anthocyanins, carotenoids and ascorbic acid), antioxidant and antimicrobial properties. Total phenolics, brown pigments and antioxidant activity of thermally treated samples were evaluated. Results were presented as mean and standard deviation, and submitted to Shapiro–Wilk normality test, and ANOVA statistical significance follows by Tukey’s post hoc test (p<0.05). Also, Pearson correlation coefficients were used to test the relationship between selected parameters.

Findings

Guava pomace had the highest insoluble fibre (40.6 per cent), protein (13.8 per cent) and lipid (9.3 per cent) contents and acerola higher soluble fibre (14.2 per cent) and water and oil holding capacity (12 and 5.4 g/g, respectively). Cashew pomace had higher solubility (45.3 per cent) and hygroscopicity (11.2 per cent). Acerola pomace had the highest phenolic content (5,331.7 mg AGE/100 g), DPPH and oxygen radical absorbance capacity antioxidant activity (63.3 and 756.6 µmol TE/g). Despite of that none of extracts showed antibacterial activity. All pomaces presented good antioxidant activity retention after thermal treatments (> 70 per cent), which might be correlated to thermally induced brown pigments.

Originality/value

This investigation was motivated by the large amounts of pomaces produced by the fruit pulp and juice processing industries, which represents a waste of residual phytochemicals and cause potential environmental problems. Overall, it was demonstrated that freeze-dried acerola, guava and cashew pomaces are promising ingredients for multiple food applications.
Upgrading at work: employee disposition and cynicism about organizational changes
Authors: Fauzan Rizky
Published: December 2019

Purpose

The purpose of this study is to examine potential predictors and moderating relationships involving one type of organizational cynicism – cynicism about organizational transformation (CAOC).

Design/methodology/approach

A total of 137 subjects participated in this study. The participants had been in their current positions at work for an average of 4.77 years and had been with their current organization an average of 7.28 years. CAOC was measured using the 12-item scale (α = 0.86) from Wanous et al.’s (2000) study. The response scale had five points ranging from “strongly disagree” to “strongly agree.”

Findings

CAOC and negative affectivity were positively correlated, thus supporting H1. H2 was not supported, i.e. subjective change was not related to CAOC, and objective change was actually correlated negatively with CAOC. H3 was not supported, i.e. individuals with a higher organizational commitment will not have a less positive relationship between CAOC and organizational transformation (subjective and objective) than individuals with lower organizational commitment. H4 was not supported, i.e. individuals who perceive a higher degree of petty tyranny will not have a stronger relationship between CAOC and organizational transformation (subjective and objective) than individuals who perceive a lower degree of petty tyranny. H5 was not supported, i.e. individuals who perceive a higher degree of perceived organizational support (POS) will not have a weaker relationship between CAOC and organizational transformation (subjective and objective) than individuals who perceive a lower degree of POS.

Originality/value

The intent of the present study is to examine potential causes of CAOC and potential moderators of the relationships between those antecedents and CAOC. In particular, two variables are proposed as antecedents (negative affectivity with past organizational transformations) and three as moderators (organizational commitment, petty tyranny by supervisors and POS).
Stress and work motivation of primary and secondary school teachers
Authors: Kongcharoen Jinda , Onmek Nutthajit , Jandang Panaya , Wangyisen Sukanya
Published: December 2019

Purpose

The purpose of this paper is to explore the levels of stress and work motivation of primary and secondary school teachers, investigate factors affecting stress of teachers and validate the consistency of the model and empirical data.

Design/methodology/approach

The sample consisted of 400 teachers of primary and secondary schools. Questionnaire was implemented as the instrument and the data were analyzed byt-test, ANOVA and confirmatory factor analysis.

Findings

The results indicated that teachers of secondary schools have higher overall stress than teachers of primary schools for many reasons, such as financial issues and work obligations. Stress was found to be significantly positively associated with work motivation in secondary school teachers. The study revealed that demographic and work motivation factors influence teacher stress. The validation of a goodness of fitted model demonstrated an acceptable model fit with empirical data (χ2test/df = 1.913, GFI = 0.934, CFI = 0.965, NFI = 0.930, AGFI = 0.893).

Originality/value

Teachers under stress could negatively influence their students’ academic performance and might be more vulnerable to occupational diseases. Therefore, the teachers should find favorite activities that reduce stress and thereby contribute to effective teaching. This study would be beneficial for anyone who works to support teachers and wants to reduce turnover among teachers.
Combination therapy of apremilast and biologics in patients with psoriasis showing biologic fatigue
Authors: Takamura Saori , Sugai Sora , Taguchi Ryokichi , Teraki Yuichi
Published: December 2019

Biologics have been shown to constitute a highly effective treatment for patients with psoriasis. However, a significant number of patients treated with biologics will discontinue them due to loss of efficacy over time, a phenomenon known as biologic fatigue or secondary failure. Combination therapy of biologics with other agents can be considered as a treatment option in such cases. Information regarding the efficacy and safety of adding apremilast to biologic therapy in patients with psoriasis is limited. In the present study, we retrospectively evaluated the efficacy and safety of apremilast combined with biologics in 14 patients with psoriasis showing biologic fatigue at a single hospital. Before the addition of apremilast, the mean Psoriasis Area and Severity Index (PASI) score was 3.2 ± 0.4. At week 24 following the addition of apremilast, the mean PASI score decreased to 1.6 ± 0.3, and four (29%) and seven (50%) patients had achieved 75% and 50% reduction in PASI score, respectively. During the 24 weeks of treatment, diarrhea was observed in four patients, and diarrhea and nausea were observed in one patient. Weight loss of more than 5% bodyweight was observed in two patients. None of the patients discontinued therapy because of these side‐effects. These results suggest that the combination therapy of apremilast and biologics could be a safe, effective option for the management of patients with psoriasis showing biologic fatigue.
Effect of imidazoline‐1 receptor agonists on renal dysfunction in rats associated with chronic, sequential fructose and ethanol administration
Authors: Elkomy Nesreen M. I. M. , Ibrahim Islam A. A. E. ‐H. , El‐Fayoumi Hassan M. , Elshazly Shimaa M.
Published: December 2019

Insulin resistance and chronic alcoholism are risk factors for renal dysfunction. This study investigated the therapeutic effects of two imidazoline‐1 receptor (I1R) agonists on renal dysfunction in rats after chronic, sequential fructose and ethanol administration. Daily drinking water was supplemented with fructose (10%, w/v) for 12 weeks and then with ethanol (20%, v/v) for another 8 weeks. Rats were treated with rilmenidine and clonidine in the last two weeks of the study. Blood glucose and serum insulin (sIns) levels, lipid profiles, kidney function and renal histopathology were evaluated at the end of the experiment. Additionally, renal gene expression of nischarin, phosphatidylcholine‐specific phospholipase C (PC‐PLC) and prostaglandin E2 (PGE2) were measured. Renal levels of superoxide dismutase (SOD), malondialdehyde (MDA), myeloperoxidase (MPO), inducible nitric oxide synthase (iNOS) and total NO (tNO) were detected, and we determined the relative renal gene expression levels of alpha smooth muscle actin (α‐SMA), hydroxyproline, interleukin 10 (IL‐10), tumour necrosis factor alpha (TNF‐α) and caspase‐3. The results showed significant deterioration of blood glucose, sIns, lipid profiles, kidney function and renal histopathology in fructose/ethanol‐fed rats. Additionally, markers of inflammation, fibrosis, apoptosis and oxidative stress were upregulated. The administration of rilmenidine or clonidine significantly improved blood glucose and sIns levels and reduced renal dysfunction. Our work showed that chronic, sequential fructose and ethanol administration induced fasting hyperglycaemia and renal impairment, and these effects were ameliorated by I1R agonists.
Cathelicidin deficiency exacerbates cardiac dysfunction in lipopolysaccharide‐induced endotoxaemic mice
Authors: Zhai Tingting , Zhang Jie , Zhang Yacheng , Wu Yan
Published: December 2019

The therapeutic potential of the antimicrobial peptide cathelicidin (Camp) administration in sepsis has been widely investigated. However, little is known about the pathophysiological roles of cathelicidin in septic cardiomyopathy. In a lipopolysaccharide (LPS)‐induced endotoxaemic model, we found that the mRNA and protein expression of cardiac cathelicidin were induced in C57BL/6J wild‐type (WT) mice upon LPS challenge, accompanied by increased circulating cathelicidin levels. We showed that this peptide was mainly derived from neutrophils and monocytes/macrophages. Camp deficiency exacerbated LPS‐induced myocardial depression, while the administration of CRAMP (the mature form of mouse cathelicidin) decreased the LPS‐induced mortality in a D‐galactosamine hydrochloride (D‐GalN)‐sensitized endotoxin shock model. In vivo, LPS‐treated Camp knockout mice had a significant higher protein level of myocardial and circulating tumour necrosis factor‐alpha (TNF‐α), a major contributing factor to septic cardiomyopathy, compared to LPS‐treated WT mice, while CRAMP administration inhibited LPS‐induced TNF‐α production in the heart and plasma in D‐GalN‐sensitized endotoxaemic mice. In vitro, CRAMP treatment suppressed LPS‐induced Tnf‐α mRNA expression in cultured neonatal mouse cardiomyocytes and reduced TNF‐α secretion in the culture supernatant. The inhibitory effects of CRAMP on TNF‐α production may be related to its neutralizing ability of LPS, since CRAMP application had no effects on another toll‐like receptor 4 ligand paclitaxel‐induced Tnf‐α mRNA expression in cardiomyocytes. These findings suggest that LPS‐induced cathelicidin protects the heart against myocardial depression partly through the inhibition of TNF‐α production via neutralizing LPS.
MicroRNA‐378‐3p/5p represses proliferation and induces apoptosis of oral squamous carcinoma cells via targeting KLK4
Authors: Cui Zhi , Bao Xingfu , Liu Qilin , Li Qianpeng , Huang Lei , Wang Hanchi , Jiao Kun
Published: December 2019

Oral squamous cell carcinoma (OSCC) is one of the most common types of head and neck neoplasm. Down‐regulation of hsa‐microRNA‐378 (miR‐378) has been proved in OSCC tissues, suggesting that miR‐378 might play crucial roles in the progression of OSCC. The present study aimed to evaluate the effect of miR‐378‐3p/5p on the proliferation and apoptosis of OSCC in vitro and in vivo. According to the results, lentivirus‐mediated overexpression of miR‐378 lowered the colony formation efficiency, blocked cell cycle progression, and decreased the percentage of Ki‐67 positive cells, whereas knockdown of miR‐378‐3p/5p led to the opposite results. Furthermore, the apoptosis of OSCC cells was induced by the overexpression of miR‐378 as evidenced by decreasing Bcl‐2/Bax ratio, increasing cleaved caspase‐9, cleaved caspase‐3, and cleaved PARP levels, and promoting the release of cytochrome c into the cytoplasm. However, the above results were reversed by miR‐378‐3p/5p silencing. In addition, the overexpression of miR‐378 inhibited the activation of PI3K/AKT signalling pathway. Conversely, miR‐378‐3p/5p knockdown resulted in the inactivation of PI3K/AKT signalling pathway. Mechanically, we validated that miR‐378‐3p/5p could target kallikrein‐related peptidase 4 (KLK4), and enforced overexpression of KLK4 counteracted miR‐378 overexpression‐induced apoptosis. Finally, tumourigenesis in nude mice was suppressed by the overexpression of miR‐378, which was promoted by miR‐378‐3p/5p silencing. Taken together, these results suggest that miR‐378 may be a potential target in the diagnoses and treatment of OSCC.
Postprandial microvascular blood flow in skeletal muscle: Similarities and disparities to the hyperinsulinaemic‐euglycaemic clamp
Authors: Roberts‐Thomson Katherine M. , Betik Andrew C. , Premilovac Dino , Rattigan Stephen , Richards Stephen M. , Ross Renee M. , Russell Ryan D. , Kaur Gunveen , Parker Lewan , Keske Michelle A.
Published: December 2019

Skeletal muscle contributes to ~40% of total body mass and has numerous important mechanical and metabolic roles in the body. Skeletal muscle is a major site for glucose disposal following a meal. Consequently, skeletal muscle plays an important role in postprandial blood glucose homeostasis. Over the past number of decades, research has demonstrated that insulin has an important role in vasodilating the vasculature in skeletal muscle in response to an insulin infusion (hyperinsulinaemic‐euglycaemic clamp) or following the ingestion of a meal. This vascular action of insulin is pivotal for glucose disposal in skeletal muscle, as insulin‐stimulated vasodilation increases the delivery of both glucose and insulin to the myocyte. Notably, in insulin‐resistant states such as obesity and type 2 diabetes, this vascular response of insulin in skeletal muscle is significantly impaired. Whereas the majority of work in this field has focussed on the action of insulin alone on skeletal muscle microvascular blood flow and myocyte glucose metabolism, there is less understanding of how the consumption of a meal may affect skeletal muscle blood flow. This is in part due to complex variations in glucose and insulin dynamics that occurs postprandially—with changes in humoral concentrations of glucose, insulin, amino acids, gut and pancreatic peptides—compared to the hyperinsulinaemic‐euglycaemic clamp. This review will address the emerging body of evidence to suggest that postprandial blood flow responses in skeletal muscle may be a function of the nutritional composition of a meal.
Investigating the effectiveness of idiom intervention for 9–16‐year‐olds with developmental language disorder
Authors: Benjamin Lucy , Newton Caroline , Ebbels Susan
Published: December 2019

Background

Idiom skills are essential for children to access age‐appropriate media, curriculum resources and teaching. Children with developmental language disorder (DLD) require support to develop the ability to understand and define idioms. However, research investigating one‐to‐one and classroom‐based idiom skill intervention for children with DLD is limited.

Aims

To investigate the effectiveness of one‐to‐one speech and language therapist (SLT) and classroom‐based interventions to develop and maintain progress of the idiom skills of 9–16‐year‐olds with DLD.

Methods & Procedures

Forty‐nine 9–16‐year‐olds from a specialist school for children with DLD received 20 intervention sessions to develop idiom skills during two school terms. Following a baseline period, 24 participants (aged 11–16) received ten 30‐min one‐to‐one SLT intervention sessions once per week for the first term and classroom‐based intervention for the second term. A total of 25 participants (aged 9–16) received the same intervention in the reverse order. Classroom‐based intervention was delivered collaboratively by English teachers and SLTs during English lessons. All participants were assessed on their ability to identify, interpret, explain and use idioms 3 months before, directly before and after each intervention and 3 months post‐intervention, using a bespoke assessment including 48 idioms randomly assigned to three sets: one‐to‐one intervention, classroom‐based intervention and control idioms.

Outcomes & Results

Participants made significantly more progress during the intervention blocks than during the baseline period (block 1:d= 1.91; block 2:d= 1.01) and post‐intervention levels were maintained 3 months post‐intervention. Idiom skills showed significant progress when targeted through both one‐to‐one (d= 2.18) and classroom‐based intervention (d= 0.91) but one‐to‐one intervention was significantly more effective than classroom‐based intervention (d= 0.63). Examination of the specific idiom skills targeted revealed that although idiom identification and interpretation skills did not progress significantly more during intervention blocks than the baseline period, idiom explanation (block 1:d= 1.02; block 2:d= 0.97); and use did (block 1:d= 0.94; block 2:d= 0.81). One‐to‐one intervention was more effective than classroom‐based intervention for developing idiom explanation (d= 1.32) and use (d= 0.65). Progress on control items was not significantly different during intervention blocks than during the baseline period overall or for any of the individual idiom skills.

Conclusions & Implications

Both one‐to‐one SLT and classroom‐based intervention are effective (although one‐to‐one is more effective) for teaching and maintaining idiom skills, particularly explanation and use. This means that SLTs and English teachers can help children to develop idiom skills which may enable better access to the curriculum and popular media.
Small RNA coaR contributes to intestinal colonization in Vibrio cholerae via the two‐component system EnvZ/OmpR
Authors: Xi Daoyi , Li Yujia , Yan Junxiang , Li Yuehua , Wang Xiaochen , Cao Boyang
Published: December 2019

Vibrio cholerae is a waterborne bacterium responsible for worldwide outbreaks of acute and fatal cholera. Recently, small regulatory RNAs (sRNAs) have become increasingly recognized as important regulators of virulence gene expression in response to environmental signals. In this study, we determined that two‐component system EnvZ/OmpR was required for intestinal colonization in V. cholerae O1 EI Tor strain E12382. Analysis of the characteristics of OmpR revealed a potential binding site in the intergenic region between vc1470 and vc1471, and qRT‐PCR showed that expression of the intergenic region increased 5.3‐fold in the small intestine compared to LB medium. Race and northern blot assays were performed and demonstrated a new sRNA, coaR (cholerae osmolarity and acidity related regulatory RNA). A ΔcoaR mutant showed a deficient colonization ability in small intestine with CI of 0.15. We identified a target of coaR, tcpI, a negative regulator of the major pilin subunit of TcpA. The ΔtcpI mutant has an increased colonization with CI of 3.16. The expression of coaR increased 2.8‐fold and 3.3‐fold under relative acidic and hypertonic condition. In summary, coaR was induced under the condition of high osmolarity and acid stress via EnvZ/OmpR and explained that tcpI relieves pH‐mediated repression of toxin co‐regulated pilus synthesis.