bluuebunny/crossref_metadata_2025 huggingface dataset:
Behavioral flexibility is associated with changes in structure and function distributed across a frontal cortical network in macaques
Authors: Sallet Jérôme , Noonan MaryAnn P , Thomas Adam , O’Reilly Jill X , Anderson Jesper , Papageorgiou Georgios K , Neubert Franz X , Ahmed Bashir , Smith Jackson , Bell Andrew H , Buckley Mark J , Roumazeilles Léa , Cuell Steven , Walton Mark E , Krug Kristine , Mars Rogier B , Rushworth Matthew FS
Published: April 2019

One of the most influential accounts of central orbitofrontal cortex– that it mediates behavioral flexibility – has been challenged by the finding that discrimination reversal in macaques –the classic test of behavioral flexibility –is unaffected when lesions are made by excitotoxin injection rather than aspiration. This suggests the critical brain circuit mediating behavioral flexibility in reversal tasks lies beyond the central orbitofrontal cortex. To determine its identity a group of nine macaques were taught discrimination reversal learning tasks and its impact on grey matter was measured. Magnetic resonance imaging scans were taken before and after learning and compared with scans from two control groups each comprising ten animals. One control group learned similar discrimination tasks but which lacked any reversal component and the other control group engaged in no learning. Grey matter changes were prominent in posterior orbitofrontal cortex/anterior insula but also were found in three other frontal cortical regions: lateral orbitofrontal cortex (12o), cingulate cortex, and lateral prefrontal cortex. In a second analysis, neural activity in posterior orbitofrontal cortex/anterior insula was measured at rest and its pattern of coupling with the other frontal cortical regions was assessed. Activity coupling increased significantly in the reversal learning group in comparison to controls. In a final set of experiments we used similar structural imaging procedures and analyses to demonstrate that aspiration lesion of central orbitofrontal cortex, of the type known to affect discrimination learning, affected structure and activity in the same frontal cortical circuit. The results identify a distributed frontal cortical circuit associated with behavioral flexibility.
Quantitative proteomic alterations of human iPSC-based neuronal development indicate early onset of Rett syndrome
Authors: Varderidou-Minasian Suzy , Hinz Lisa , Hagemans Dominique , Posthuma Danielle , Altelaar Maarten , Heine Vivi M.
Published: April 2019

Rett syndrome (RTT) is a progressive neurodevelopmental disease often caused by mutations in the X-linked gene encoding methyl-CpG binding protein 2 (MeCP2). The mechanisms by which impaired MeCP2 induces the pathological abnormalities in the brain are not understood. To understand the molecular mechanisms involved in disease, we used an RTT patient induced pluripotent stem cell (iPSC)-based model and applied an in-depth high-resolution quantitative mass spectrometry-based analysis during early stages of neuronal development. Our data provide evidence of proteomic alteration at developmental stages long before the phase that symptoms of RTT syndrome become apparent. Differences in expression profiles became more pronounced from early to late neural stem cell phases, although proteins involved in immunity, metabolic processes and calcium signaling were already affected at initial stages. These results can help development of new biomarkers and therapeutic approaches by selectively target the affected proteins in RTT syndrome.
Comparing infiltration rates in soils managed with conventional and alternative farming methods: a meta-analysis
Authors: Basche Andrea D. , DeLonge Marcia S.
Published: April 2019

Identifying agricultural practices that enhance water cycling is critical, particularly with increased rainfall variability and greater risks of droughts and floods. Soil infiltration rates offer useful insights to water cycling in farming systems because they affect both yields (through soil water availability) and other ecosystem outcomes (such as pollution and flooding from runoff). For example, conventional agricultural practices that leave soils bare and vulnerable to degradation are believed to limit the capacity of soils to quickly absorb and retain water needed for crop growth. Further, it is widely assumed that farming methods such as no-till and cover crops can improve infiltration rates. Despite interest in the impacts of agricultural practices on infiltration rates, this effect has not been systematically quantified across a range of practices. To evaluate how conventional practices affect infiltration rates relative to select alternative practices (no-till, cover crops, crop rotation, introducing perennials, crop and livestock systems), we performed a meta-analysis that included 89 studies with field trials comparing at least one such alternative practice to conventional management. We found that introducing perennials (grasses, agroforestry, managed forestry) or cover crops led to the largest increases in infiltration rates (mean responses of 59.2 ± 20.9% and 34.8 ± 7.7%, respectively). Also, although the overall effect of no-till was non-significant (5.7 ± 9.7%), the practice led to increases in wetter climates and when combined with residue retention. The effect of crop rotation on infiltration rate was non-significant (18.5 ± 13.2%), and studies evaluating impacts of grazing on croplands indicated that this practice reduced infiltration rates (−21.3 ± 14.9%). Findings suggest that practices promoting ground cover and continuous roots, both of which improve soil structure, were most effective at increasing infiltration rates.
In the Body’s Eye: The Computational Anatomy of Interoceptive Inference
Authors: Allen Micah , Levy Andrew , Parr Thomas , Friston Karl J.
Published: April 2019

A growing body of evidence highlights the intricate linkage of exteroceptive perception to the rhythmic activity of the visceral body. In parallel, interoceptive inference theories of emotion and self-consciousness are on the rise in cognitive science. However, thus far no formal theory has emerged to integrate these twin domains; instead most extant work is conceptual in nature. Here, we introduce a formal model of cardiac active inference, which explains how ascending cardiac signals entrain exteroceptive sensory perception and confidence. Through simulated psychophysics, we reproduce the defensive startle reflex and commonly reported effects linking the cardiac cycle to fear perception. We further show that simulated ‘interoceptive lesions’ blunt fear expectations, induce psychosomatic hallucinations, and exacerbate metacognitive biases. Through synthetic heart-rate variability analyses, we illustrate how the balance of arousal-priors and visceral prediction errors produces idiosyncratic patterns of physiological reactivity. Our model thus offers the possibility to computationally phenotype disordered brain-body interaction.
Altered functional interactions between neurons in primary visual cortex of macaque monkeys with experimental amblyopia
Authors: Acar Katerina , Kiorpes Lynne , Anthony Movshon J. , Smith Matthew A.
Published: April 2019

Amblyopia, a disorder in which vision through one of the eyes is degraded, arises because of defective processing of information by the visual system. Amblyopia often develops in humans after early misalignment of the eyes (strabismus), and can be simulated in macaque monkeys by artificially inducing strabismus. In such amblyopic animals, single-unit responses in primary visual cortex (V1) are appreciably reduced when evoked by the amblyopic eye compared to the other (fellow) eye. However, this degradation in single V1 neuron responsivity is not commensurate with the marked losses in visual sensitivity and resolution measured behaviorally. Here we explored the idea that changes in patterns of coordinated activity across populations of V1 neurons may contribute to degraded visual representations in amblyopia, potentially making it more difficult to read out evoked activity to support perceptual decisions. We studied the visually-evoked activity of V1 neuronal populations in three macaques (M. nemestrina) with strabismic amblyopia and in one control. Activity driven through the amblyopic eye was diminished, and these responses also showed more interneuronal correlation at all stimulus contrasts than responses driven through the fellow eye or responses in the control. A decoding analysis showed that responses driven through the amblyopic eye carried less visual information than other responses. Our results suggest that part of the reduced visual capacity of amblyopes may be due to changes in the patterns of functional interaction among neurons in V1.

New and noteworthy

Amblyopia is a developmental disorder of visual processing that reduces visual function and changes the visual responses of cortical neurons in macaque monkeys. The neuronal and behavioral changes are not always well correlated. We found that the interactions among neurons in the visual cortex of monkeys with amblyopia are also altered. These changes may contribute to amblyopic visual deficits by diminishing the amount of information relayed by neuronal populations driven by the amblyopic eye.
Poorer auditory sensitivity is related to stronger visual enhancement of the human auditory mismatch negativity (MMNm)
Authors: Møller Cecilie , Højlund Andreas , Bærentsen Klaus B. , Hansen Niels Chr. , Skewes Joshua C. , Vuust Peter
Published: April 2019

Multisensory processing facilitates perception of our everyday environment and becomes particularly important when sensory information is degraded or close to the discrimination threshold. Here, we used magnetoencephalography and an audiovisual oddball paradigm to assess the complementary role of visual information in subtle pitch discrimination at the neural level of participants with varying levels of pitch discrimination abilities, i.e., musicians and nonmusicians. The amplitude of the auditory mismatch negativity (MMNm) served as an index of sensitivity. The gain in amplitude resulting from compatible audiovisual information was larger in participants whose MMNm amplitude was smaller in the condition deviating only in the auditory dimension, in accordance with the multisensory principle of inverse effectiveness. These findings show that discrimination of even a sensory-specific feature as pitch is facilitated by multisensory information at a pre-attentive level, and they highlight the importance of considering inter-individual differences in uni-sensory abilities when assessing multisensory processing.
Scalable data analysis in proteomics and metabolomics using BioContainers and workflows engines
Authors: Perez-Riverol Yasset , Moreno Pablo
Published: April 2019

The recent improvements in mass spectrometry instruments and new analytical methods are increasing the intersection between proteomics and big data science. In addition, the bioinformatics analysis is becoming an increasingly complex and convoluted process involving multiple algorithms and tools. A wide variety of methods and software tools have been developed for computational proteomics and metabolomics during recent years, and this trend is likely to continue. However, most of the computational proteomics and metabolomics tools are targeted and design for single desktop application limiting the scalability and reproducibility of the data analysis. In this paper we overview the key steps of metabolomic and proteomics data processing including main tools and software use to perform the data analysis. We discuss the combination of software containers with workflows environments for large scale metabolomics and proteomics analysis. Finally, we introduced to the proteomics and metabolomics communities a new approach for reproducible and large-scale data analysis based on BioContainers and two of the most popular workflows environments: Galaxy and Nextflow.
Microbial community dynamics and coexistence in a sulfide-driven phototrophic bloom
Authors: Bhatnagar Srijak , Cowley Elise S. , Kopf Sebastian H. , Castro Sherlynette Pérez , Kearney Sean , Dawson Scott C. , Hanselmann Kurt , Ruff S. Emil
Published: April 2019

Phototrophic microbial mats commonly contain multiple phototrophic lineages that coexist based on their light, oxygen and nutrient preferences. Here we show that similar coexistence patterns and ecological niches can occur in suspended phototrophic blooms of an organic-rich estuary. The water column showed steep gradients of oxygen, pH, sulfate, sulfide, and salinity. The upper part of the bloom was dominated by aerobic phototrophicCyanobacteria, the middle and lower parts were dominated by anoxygenic purple sulfur bacteria (Chromatiales) and green sulfur bacteria (Chlorobiales), respectively. We found multiple uncultured phototrophic lineages and present metagenome-assembled genomes of two uncultured organisms within theChlorobiales. Apparently, thoseChlorobialespopulations were affected byMicroviridaeviruses. We suggest a sulfur cycle within the bloom in which elemental sulfur produced by phototrophs is reduced to sulfide byDesulfuromonas sp. These findings improve our understanding of the ecology and ecophysiology of phototrophic blooms and their impact on biogeochemical cycles.
Bats dynamically change echolocation parameters in response to acoustic playback
Authors: Beetz M. Jerome , Kossl Manfred , Hechavarria Julio C.
Published: April 2019

Animals extract behaviorally relevant signals from 'noisy' environments. To investigate signal extraction, echolocating provides a rich system testbed. For orientation, bats broadcast calls and assign each echo to the corresponding call. When orienting in acoustically enriched environments or when approaching targets, bats change their spectro-temporal call design. Thus, to assess call adjustments that are exclusively meant to facilitate signal extraction in 'noisy' environments, it is necessary to control for distance-dependent call changes. By swinging bats in a pendulum, we tested the influence of acoustic playback on the echolocation behavior of Carollia perspicillata. This paradigm evokes reproducible orientation behavior and allows a precise definition of the influence of the acoustic context. Our results show that bats dynamically switch between different adaptations to cope with sound-based navigation in acoustically contaminated environments. These dynamics of echolocation behavior may explain the large variety of adaptations that have been reported in the bat literature.
Yeast Sup35 prion structure: two types, four parts, many variants
Authors: Dergalev Alexander A. , Alexandrov Alexander I. , Ivannikov Roman I. , Ter-Avanesyan Michael D. , Kushnirov Vitaly V.
Published: April 2019

The yeast [PSI+] prion, formed by the Sup35 (eRF3) protein, can exist as multiple structural variants exhibiting phenotypic variation in the strength of nonsense suppression and mitotic stability. Structure of [PSI+] and its variation is only partly characterized. Here, we mapped the Sup35 proteinase K-resistant amyloid cores of 26 [PSI+] prions of different origin, isolated from yeast cells. In all cases the Sup35 amino acid residues 2-32 were fully resistant and the region up to residue 72 was partially resistant. Proteinase K-resistant structures were also found within regions 73-124, 125-153 and 154-221, but their presence differed between [PSI+] isolates. The [PSI+] phenotype depended mainly, if not solely, on the structure in region 2-72. Structures in region 73-221 were in some cases mitotically unstable and heterogenous. Two distinct digestion patterns were observed for the 2-72 fragment, which correlated with the “strong” and “weak” [PSI+] nonsense-suppressor phenotypes. All [PSI+] with a weak pattern were eliminated by multicopyHSP104gene and were not toxic when combined with multicopySUP35.[PSI+] with a strong pattern showed opposite properties, being resistant to multicopyHSP104and lethal in the presence of multicopySUP35. Thus, our data suggest existence of two distinct and reliably distinguishable structural classes of [PSI+] rather than a continuum of prions with gradually altering phenotype.

Importance

Prions and amyloids are relatively novel and incompletely characterized structures. To understand them better, we mapped amyloid cores of 26 isolates of the Sup35 yeast prion using proteinase K digestion and mass spectrometry. We found that these cores are composed of up to four proteinase K-resistant elements spanning almost the whole length of Sup35 region inessential for viability. However, only the N-terminal element was present in all structures. There are many variants of the Sup35 prion, and these are usually roughly combined into two groups, “strong” and “weak”, based on the strength of their nonsense-suppressor phenotype. However, it was not clear whether such groups could be distinguished by any reliable qualitative criteria. Our data indicate that these groups do exist and can be reliably distinguished based on the N-terminal element digestion pattern and the effects of the multicopySUP35andHSP104genes on these prion variants.
Fecal short-chain fatty acids are not predictive of colonic tumor status and cannot be predicted based on bacterial community structure
Authors: Sze Marc A. , Topçuoğlu Begüm D. , Lesniak Nicholas A. , Ruffin Mack T. , Schloss Patrick D.
Published: April 2019

Colonic bacterial populations are thought to have a role in the development of colorectal cancer with some protecting against inflammation and others exacerbating inflammation. Short-chain fatty acids (SCFAs) have been shown to have anti-inflammatory properties and are produced in large quantities by colonic bacteria which produce SCFAs by fermenting fiber. We assessed whether there was an association between fecal SCFA concentrations and the presence of colonic adenomas or carcinomas in a cohort of individuals using 16S rRNA gene and metagenomic shotgun sequence data. We measured the fecal concentrations of acetate, propionate, and butyrate within the cohort and found that there were no significant associations between SCFA concentration and tumor status. When we incorporated these concentrations into random forest classification models trained to differentiate between people with normal colons and those with adenomas or carcinomas, we found that they did not significantly improve the ability of 16S rRNA gene or metagenomic gene sequence-based models to classify individuals. Finally, we generated random forest regression models trained to predict the concentration of each SCFA based on 16S rRNA gene or metagenomic gene sequence data from the same samples. These models performed poorly and were able to explain at most 14% of the observed variation in the SCFA concentrations. These results support the broader epidemiological data that questions the value of fiber consumption for reducing the risks of colorectal cancer. Although other bacterial metabolites may serve as biomarkers to detect adenomas or carcinomas, fecal SCFA concentrations have limited predictive power.

Importance

Considering colorectal cancer is the third leading cancer-related cause of death within the United States, it is important to detect colorectal tumors early and to prevent the formation of tumors. Short-chain fatty acids (SCFAs) are often used as a surrogate for measuring gut health and for being anti-carcinogenic because of their anti-inflammatory properties. We evaluated the fecal SCFA concentration of a cohort of individuals with varying colonic tumor burden who were previously analyzed to identify microbiome-based biomarkers of tumors. We were unable to find an association between SCFA concentration and tumor burden or use SCFAs to improve our microbiome-based models of classifying people based on their tumor status. Furthermore, we were unable to find an association between the fecal community structure and SCFA concentrations. Our results indicate that the association between fecal SCFAs, the gut microbiome, and tumor burden is weak.
Sustained visual priming effects can emerge from attentional oscillation and temporal expectation
Authors: Wang Muzhi , Huang Yan , Luo Huan , Zhang Hang
Published: April 2019

Priming refers to the influence that a previously encountered object exerts on future responses to similar objects. For many years, visual priming has been known as a facilitation and sometimes an inhibition effect that lasts for an extended period of time. It contrasts with the recent finding of an oscillated priming effect where facilitation and inhibition alternate over time periodically. Here we developed a computational model of visual priming that combines rhythmic sampling of the environment (attentional oscillation) with active preparation for future events (temporal expectation). Counterintuitively, it shows both the sustained and oscillated priming effects can emerge from an interaction between attentional oscillation and temporal expectation. The interaction also leads to novel predictions such as the change of visual priming effects with temporal expectation and attentional oscillation. Reanalysis of two published datasets and the results of two new experiments of visual priming tasks with male and female human participants provide support for the model’s relevance to human behavior. More generally, our model offers a new perspective that may unify the increasing findings of behavioral and neural oscillations with the classic findings in visual perception and attention.

Significance Statement

There is increasing behavioral and neural evidence that visual attention is a periodic process that sequentially samples different alternatives in the theta frequency range. It contrasts with the classic findings of sustained facilitatory or inhibitory attention effects. How can an oscillatory perceptual process give rise to sustained attention effects? Here we make this connection by proposing a computational model for a “fruit fly” visual priming task and showing both the sustained and oscillated priming effects can have the same origin: an interaction between rhythmic sampling of the environment and active preparation for future events. One unique contribution of our model is to predict how temporal contexts affects priming. It also opens up the possibility of reinterpreting other attention-related classic phenomena.
The level of workaholism and its relation to positive and negative perfectionism
Authors: Ali Aldahadha Basim Mohammad
Published: April 2019

The present study aimed to test how common workaholism is and which groups are most targeted in the workplace among Jordanian employees. Additionally, the roles of positive and negative perfectionism in workaholism were investigated. The sample consisted of 686 employees. All of them completed the study instruments. The results showed that the mean of workaholism, positive perfectionism, and negative perfectionism were respectively 2.60, 4.04, and 3.53. Additionally, multivariate tests showed that the results of post hoc differences for positive perfectionism were in favor of males, subordinates, those with a bachelor’s degree, those with less than 5 years of experience, and those aged less than 30 years. Furthermore, the differences for negative perfectionism were in favor of those with a bachelor’s degree and subordinates. For workaholism, the differences were in favor of subordinates, public sector employees, married persons, and those with a diploma degree. Finally, the results of hierarchical regression analysis found that positive and negative perfectionism and some demographic variables predicted 129% of the variability in workaholism, and the typical hierarchical regression model included positive and negative perfectionism without other demographic variables.
Measuring the impact of an interdisciplinary learning project on nursing, architecture and landscape design students’ empathy
Authors: Donnelly Samantha , Dean Suzanne J , Razavy Shohreh , Levett-Jones Tracy
Published: April 2019

In Australia and internationally, domestic violence is a major cause of homelessness for women and children. When designing emergency accommodation, the concerns, preferences, and perspectives of individuals who access refuge services must be sought in order to create spaces that are conducive to the needs of this diverse and vulnerable group. An empathic ‘lens’ can provide meaningful insights that can inform the design of refuge services specifically targeted at addressing these needs.

This paper describes an authentic interdisciplinary learning experience for nursing, architecture and landscape students’, and presents the results of a study designed to measure the impact of this initiative on participants’ empathy towards women and children who access refuge services as a result of homelessness and/or domestic violence. Empathy levels were measured using the Comprehensive State Empathy Scale.

The learning experience consisted of collaborative meetings with stakeholders from the refuge sector, fieldwork, individual research, exchanging ideas and problem-solving in teams. Students then developed design guides for refuges that demonstrated their emerging understanding of the specific needs and perspectives of the issues faced by women and children who were homeless.

A convenience sample of 48 students (nursing n = 22; architecture n = 11; and landscape n = 13) participated in the study. Participants were aged from 19 to 37 years with an average of 23.8 years (SD= 3.65). Pre-post Comprehensive State Empathy Scale results indicated that the empathy levels of nursing and landscape students increased and those of architecture students decreased, however, these results were not statistically significant.

In Australia, one in six women have experienced domestic violence and domestic violence remains the single largest cause of homelessness for women. Yet reports suggest that these women frequently encounter discrimination, both in the community and when accessing services. As empathy is one of the strongest negative correlates of prejudice, authentic teaching and learning activities, such as the one described in this paper, have the potential to positively impact the lived experience of these women.
Pelleted-hay alfalfa feed increases sheep wether weight gain and rumen bacterial richness over loose-hay alfalfa feed
Authors: Ishaq Suzanne L. , Lachman Medora M. , Wenner Benjamin A. , Baeza Amy , Butler Molly , Gates Emily , Olivo Sarah , Geddes Julie Buono , Hatfield Patrick , Yeoman Carl J.
Published: April 2019

Diet composed of smaller particles can improve feed intake, digestibility, and animal growth or health, but in ruminant species can reduce rumination and buffering – the loss of which may inhibit fermentation and digestibility. However, the explicit effect of particle size on the rumen microbiota remains untested, despite their crucial role in digestion. We evaluated the effects of reduced particle size on rumen microbiota by feeding long-stem (loose) alfalfa hay compared to a ground and pelleted version of the same alfalfa in yearling sheep wethers.In situdigestibility of the pelleted diet was greater at 48 h compared with loose hay; however, distribution of residual fecal particle sizes in sheep did not differ between the dietary treatments at any time point. Both average daily gain and feed efficiency were greater for the wethers consuming the pelleted diet. Observed bacterial richness was very low at the end of the adaptation period and increased over the course of the study, suggesting the rumen bacterial community was still in flux after two weeks of adaptation. The pelleted-hay diet group had a greater increase in bacterial richness, including common fibrolytic rumen inhabitants. The pelleted diet was positively associated with severalSucciniclasticum, a Prevotella, and uncultured taxa in the Ruminococcaceae and Rickenellaceae families and Bacteroidales order. Pelleting an alfalfa hay diet for sheep does shift the rumen microbiome, though the interplay of diet particle size, retention and GI transit time, microbial fermentative and hydrolytic activity, and host growth or health is still largely unexplored.
Tuberculosis at farmer-cattle interface in the rural villages of South Gondar Zone of northwest Ethiopia
Authors: Alelign Amir , Zewude Aboma , Petros Beyene , Ameni Gobena
Published: April 2019

Background

Tuberculosis (TB) has been an important public health concern in Ethiopia, particularly at areas of human-animal intersection. However, limited epidemiological information is available in this respect in the country. Therefore, the present study was conducted to investigate the transmission of TB at human-cattle interface, associated risk factors and public awareness about the disease at South Gondar Zone, northwest Ethiopia.

Methods

A cross sectional study was conducted between March 2015 and April 2018 on 186 farmers and 476 cattle in South Gondar Zone, northwest Ethiopia. Bacteriological examination, region of difference (RD) 9 based polymerase chain reaction (PCR), single intradermal comparative tuberculin test (SIDCTT) and questionnaire were used for undertaking this study.

Results

Culture positivity in farmers was 59.7% (111/186) and all the culture positive isolates wereM. tuberculosis. About 68% (74/111) of culture positive respondents did not know about the transmission of TB from cattle to human or vice versa. The animal and herd prevalence of bovine TB were 1.5% (7/476) and 7.4% (7/95) respectively. The odd of bovine TB in cattle owned by TB positive households was slightly higher than those owned by TB free households (adjusted odds ratio, AOR=1.39; 95% CI: 0.31-7.10; p = 0.76).

Conclusion

Although SIDCTT reactivity was slightly higher in cattle owned by TB positive households, all the human isolates wereM. tuberculosisand noM. boviswas isolated from farmers, which could be due to the low prevalence of bovine TB in the area.
Identification and Characterization of the First Fragment Hits for SETDB1 Tudor Domain
Authors: Mader Pavel , Mendoza-Sanchez Rodrigo , Iqbal Aman , Dong Aiping , Dobrovetsky Elena , Corless Victoria B. , Liew Sean K. , Houliston Scott R. , De Freitas Renato Ferreira , Smil David , Dela Sena Carlo C. , Kennedy Steven , Diaz Diego B. , Wu Hong , Dombrovski Ludmila , Allali-Hassani Abdellah , Min Jinrong , Schapira Matthieu , Vedadi Masoud , Brown Peter J. , Santhakumar Vijayaratnam , Yudin Andrei K. , Arrowsmith Cheryl H.
Published: April 2019

SET domain bifurcated protein 1 (SETDB1) is a human histone-lysine methyltransferase, which is amplified in human cancers and was shown to be crucial in the growth of non-small and small cell lung carcinoma. In addition to its catalytic domain, SETDB1 harbors a unique tandem tudor domain which recognizes histone sequences containing both methylated and acetylated lysines, and likely contributes to its localization on chromatin. Using X-ray crystallography and NMR spectroscopy fragment screening approaches, we have identified the first small molecule fragment hits that bind to histone peptide binding groove of the TTD of SETDB1. Herein, we describe the binding modes of these fragments and analogues and the biophysical characterization of key compounds. These confirmed small molecule fragments will inform the development of potent antagonists of SETDB1 interaction with histones.
Methamphetamine learning induces persistent nonmuscle myosin II-dependent spine motility in the basolateral amygdala
Authors: Young Erica J. , Lin Hua , Kamenecka Theodore M. , Rumbaugh Gavin , Miller Courtney A.
Published: April 2019

Nonmuscle myosin II inhibition (NMIIi) in the basolateral amygdala (BLA) selectively disrupts memories associated with methamphetamine (METH) days after learning, without retrieval. However, the molecular mechanisms underlying this selective vulnerability remain poorly understood. A known function of NMII is to transiently activate dendritic spine actin dynamics with learning. Therefore, we hypothesized that METH-associated learning perpetuates NMII-driven actin dynamics in dendritic spines, leading to an extended window of vulnerability for memory disruption. Two-photon imaging of actin-mediated spine motility in neurons from memory-related structures, BLA and CA1, revealed a persistent increase in spine motility after METH-associated learning that was restricted to BLA neurons. METH-induced changes to BLA spine dynamics were reversed by a single systemic injection of an NMII inhibitor. Thus, a perpetual form of NMII-driven spine actin dynamics in BLA neurons may contribute to the unique susceptibility of METH-associated memories.
Comparative genomics groups phages of Negativicutes and classical Firmicutes despite different Gram-staining properties
Authors: Rands Chris M , Brüssow Harald , Zdobnov Evgeny M
Published: April 2019

Negativicutes are Gram-Negative bacteria characterized by two cell membranes, but they are phylogenetically a side-branch of Gram-Positive Firmicutes that contain only a single membrane. We asked whether viruses (phages) infecting Negativicutes were horizontally acquired from Gram-Negative Proteobacteria, given the shared outer cell structure of their bacterial hosts, or if Negativicute phages co-evolved vertically with their hosts and thus resemble Gram-Positive Firmicute prophages. We predicted and characterised 485 prophages from Gram-Negative Firmicute genomes plus 2,977 prophages from other bacterial clades, and we used virome sequence data from 183 human stool samples to provide independent evidence for our predictions. The majority of the identified Negativicute prophages were lambdoids closer related to prophages from other Firmicutes than Proteobacteria by sequence relationship and genome organization (position of the lysis module). Only a single Mu-like candidate prophage and no clear P2-like prophages were identified in Negativicutes, both commonly found in Proteobacteria. Therefore, it is unlikely that Negativicute phages were acquired from Proteobacteria. Sequence-related prophages were identified in two distinct Negativicute orders (Veillonellales and Acidaminococcales) possibly suggesting horizontal cross-order phage infection between human gut commensals. Phages infecting these Negativicute orders occasionally harboured putative antibiotic resistance genes.
Differential Metabolic Sensitivity of Insulin-like-response- and mTORC1-Dependent Overgrowth in Drosophila Fat Cells
Authors: Devilliers Maelle , Garrido Damien , Poidevin Mickael , Rubin Thomas , Le Rouzic Arnaud , Montagne Jacques
Published: April 2019

The glycolytic/lipogenic axis promotes the synthesis of energetic molecules and building blocks necessary to support cell growth, although the absolute requirement of this metabolic axis must be deeply investigated. Here, we used Drosophila genetics and focus on the mTOR signaling network that controls cell growth and homeostasis. mTOR is present in two distinct complexes, mTORC1 and mTORC2. The former directly responds to amino acids and energetic levels, whereas the latter is required to sustain the signaling response downstream of insulin-like-peptide (Ilp) stimulation. Either signaling branch can be independently modulated in most Drosophila tissues. We confirm this independency in the fat tissue. We show that ubiquitous over-activation of mTORC1 or Ilp signaling affects carbohydrate and lipid metabolism, supporting the use of Drosophila as a powerful model to study the link between growth and metabolism. We show that cell-autonomous restriction of glycolysis or lipogenesis in fat cells impedes overgrowth dependent on Ilp-but not mTORC1-signaling. Additionally, ubiquitous deficiency of lipogenesis (FASN mutants) results in a drop in mTORC1 but not Ilp signaling, whereas, at the cell-autonomous level, lipogenesis deficiency affects none of these signals in fat cells. These findings thus, reveal differential metabolic sensitivity of mTORC1- and Ilp-dependent overgrowth. Furthermore, they suggest that local metabolic defects may elicit compensatory pathways between neighboring cells, whereas enzyme knockdown in the whole organism results in animal death. Importantly, our study weakens the use of single inhibitors to fight mTOR-related diseases and strengthens the use of drug combination and selective tissue-targeting.
The histone chaperone CAF-1 cooperates with the DNA methyltransferases to maintain Cd4 silencing in cytotoxic T cells
Authors: Ng Charles , Aichinger Martin , Nguyen Tung , Au Christy , Najar Tariq , Wu Lin , Mesa Kai R. , Liao Will , Quivy Jean-Pierre , Hubert Benjamin , Almouzni Genevieve , Zuber Johannes , Littman Dan R.
Published: April 2019

The transcriptional repression of alternative lineage genes is critical for cell fate commitment. Mechanisms by which locus-specific gene silencing is initiated and heritably maintained during cell division are not clearly understood. To study the maintenance of silent gene states, we investigated how the Cd4 gene is stably repressed in CD8+ T cells. Through CRISPR and shRNA screening, we identified the histone chaperone CAF-1 as a critical component for Cd4 repression. We found that the large subunit of CAF-1, Chaf1a, requires the N-terminal KER domain to associate with the histone deacetylases HDAC1/2 and the histone demethylase LSD1, enzymes that also participate in Cd4 silencing. When CAF-1 was lacking, Cd4 derepression was markedly enhanced in the absence of the de novo DNA methyltransferase Dnmt3a but not the maintenance DNA methyltransferase Dnmt1. In contrast to Dnmt1, Dnmt3a deficiency did not significantly alter levels of DNA methylation at the Cd4 locus. Instead, Dnmt3a deficiency sensitized CD8+ T cells to Cd4 derepression mediated by compromised functions of histone-modifying factors, including the enzymes associated with CAF-1. Thus, we propose that the heritable silencing of the Cd4 gene in CD8+ T cells exploits cooperative functions among the DNA methyltransferases, CAF-1, and histone-modifying enzymes.
Processes of hybridization and de-hybridization: organizing and the task at hand
Authors: Kastberg Gustaf , Lagström Cristian
Published: April 2019

Purpose

The problematization indicates the need for enhancing the understanding of hybrid settings as potentially dynamic, changing and fragile. The purpose of this paper is to generate the knowledge through a conceptualization of the relationship between hybrid organizing and object, helping us understand how and why hybridization takes place or de-hybridizing occurs.

Design/methodology/approach

The study is based on a longitudinal qualitative case study of an attempt to introduce cost-benefit calculations as a management initiative in the social sector. In total, 18 observations of meetings and 48 interviews were done.

Findings

The main contribution is the empirically detailed description of how hybridizing must be understood in connection to a complex task at hand. A core observation is how complexity is escaped by either an intensive framing or compartmentalization – the former either leading to a disciplined hybrid allowing efficient action or to a hot and contested situation characterized by inertia. The latter, compartmentalization, presupposes less complexity with the potential of full de-hybridization into single-purpose organizing, failing to deal with the complex task at hand.

Research limitations/implications

A limitation is the one case approach and further research could focus on other settings.

Practical implications

The paper provides concepts useful for analysis of specific cooperative arrangements.

Social implications

The authors believe that the findings can bring useful insights to professionals, policy makers and others who are engaging in and addressing complex societal issues, not least within the public sector, a matter all too often overlooked by the accounting research community.

Originality/value

The originality of the paper is the focus on the organization and control in relation to the task at hand.
A sustainable perspective in wine production for common-good management
Authors: Cantino Valter , Giacosa Elisa , Cortese Damiano
Published: April 2019

Purpose

The purpose of this paper is to analyse how sustainability is crucial in maintaining and assigning value to a common good. In particular, the paper identifies several characteristics of a business model that could be adopted to manage sustainable innovation strategies that respect the balance among environmental, social and commercial goals.

Design/methodology/approach

This case study involves Fontanafredda, an internationally recognised historical Italian wine company characterised by its highly innovative business approach and sustainable business model.

Findings

Fontanafredda’s approach is connected to the broader concept of the common good the winery has internalised to become an element of its competitive advantage and differentiation. The preservation of traditional values – primarily the respect and valuing of one’s own territory – is a key asset of the winery, which attaches great symbolic and concrete importance to these values.

Research limitations/implications

The study uses a single case study approach and a qualitative method without quantifying the impact of every business choice. For theoretical implications, the study emphasises the strong connection between sustainability and innovation in the management of the common good.

Practical implications

Numerous practical implications are identified regarding several stakeholder groups, such as the management, owners, investors and the various entities linked to the regional promotion and tourism sectors.

Originality/value

This research explores how and why Fontanafredda amounts to more than simply wine production by focusing on the characteristics of its business model, which efficiently handles the link between innovation and heritage for common-good development.
Computational fluid dynamics and laminar heat transfer of water/Cu nanofluid in ribbed microchannel with a two-phase approach
Authors: Cheloii Navid Ahmadi , Akbari Omid Ali , Toghraie Davood
Published: April 2019

Purpose

This study aims to numerically investigate the heat transfer and laminar forced and two-phase flow of Water/Cu nanofluid in a rectangular microchannel with oblique ribs with angle of attacks equal to 0-45°. This simulation was conducted in the range of Reynolds numbers of 5-120 in volume fractions of 0, 2 and 4 per cent of solid nanoparticles in three-dimensional space.

Design/methodology/approach

This study investigates the effect of the changes of angle of attack of rectangular rib on heat transfer and hydrodynamics of two-phase flow. This study was done in three-dimensional space and simulation was done with finite volume method. SIMPLEC algorithm and second-order discretization of equations were used to increase the accuracy of results. The usage of nanofluid, application of rips with different angles of attacks and using the two-phase mixture method is the distinction of this paper compared with other studies.

Findings

The results of this research revealed that the changing angle of attack of ribs is an effective factor in heat transfer enhancement. On the other hand, the existence of rib on the internal surfaces of a microchannel increases friction coefficient. By increasing the volume fraction of nanoparticles, due to the augmentation of fluid density and viscosity, the pressure drop increases significantly. For all of the angle of attacks studied in this paper, the maximum rate of performance evaluation criterion has been obtained in Reynolds number of 30 and the minimum amount of performance evaluation criterion was been obtained in Reynolds numbers of 5 and 120.

Originality/value

Many studies have been done in the field of heat transfer in ribbed microchannel. In this paper, the laminar flow in the ribbed microchannel Water/Cu nanofluid in a rectangular microchannel by using two-phase mixture method is numerically investigated with different volume fractions (0-4 per cent), Reynolds numbers (5-120) and angle of attacks of rectangular rib in the indented microchannel (0-45°).
A cross-level analysis of management commitment and work ability among senior casino dealers in Macau
Authors: Li Jun (Justin) , Kim Jong-Hyeong
Published: April 2019

Purpose

This paper aims to investigate the corporate-level determinants (i.e. management commitment) of work ability. It also examined whether mid-level contextual variables intensify the relationship between management commitment and the work ability of senior casino dealers.

Design/methodology/approach

A three-level hierarchical analysis of data from 432 casino dealers from 16 casinos was performed to determine the proportion of variance in the dependent variable when the explanatory variables were at varying hierarchical levels.

Findings

The findings suggest that management commitment has a positive and significant impact on frontline dealers’ work ability. Furthermore, supervisor support and group trust have moderating effects on the relationship between management commitment and dealers’ work ability.

Research limitations/implications

The current study provides important information on how to increase the ability of aging dealer to remain active and learn new skills.

Originality/value

Work ability has received substantial attention from recent studies of human resources because of its close relationship to employee job skills and competencies. However, to the best of the authors’ knowledge, no conceptual model explains the role of work ability role in promoting and updating human resources management practices and policies.
Heterogeneous adoption of quality standards in the hotel industry: drivers and effects
Authors: Tarí Juan José , Pereira-Moliner Jorge , Molina-Azorín José F. , López-Gamero María D.
Published: April 2019

Purpose

This paper aims to examine the impact of external and internal drivers on the dimensions of internalization (daily practices and continuous improvement) of quality standards, the relationship between the dimensions of internalization and their effects on customer, employee, society and organizational results in hotels.

Design/methodology/approach

The study applies a structural equations analysis to test these relationships using empirical data from 176 quality-certified hotels.

Findings

Hotels need internal drivers to internalize a quality system because the external drivers themselves are not able to explain significantly the quality internalization process. This paper shows the significant relationship between the dimensions of internalization (daily practices and continuous improvement) and the importance of continuous improvement (e.g. innovations from quality standards and reflection on how to improve the current work processes) for improved customer, employees, society and organizational results.

Originality/value

To the best of the authors’ knowledge, there are no empirical studies jointly analyzing the drivers of internalization, the relationship between the dimensions of internalization and their effects on different dimensions of results (customers, employees and society) in hotels.