bluuebunny/crossref_metadata_2025 huggingface dataset:
14-helical β-peptides Elicit Toxicity againstC. albicansby Forming Pores in the Cell Membrane and Subsequently Disrupting Intracellular Organelles
Authors: Lee Myung-Ryul , Raman Namrata , Ortiz-Bermudez Patricia , Lynn David M. , Palecek Sean P.
Published: September 2018

Synthetic peptidomimetics of antimicrobial peptides are promising as antimicrobial drug candidates because they promote membrane disruption and exhibit greater structural and proteolytic stability. We previously reported selective antifungal 14-helical β-peptides, but the mechanism of antifungal toxicity of β-peptides remains unknown. To provide insight into the mechanism, we studied antifungal β-peptide binding to artificial membranes and livingCandida albicanscells. We investigated the ability of β-peptides to interact with and permeate small unilamellar vesicle models of fungal and bacterial membranes. The partition coefficient supported a pore-mediated mechanism characterized by the existence of a critical β-peptide concentration separating low and high partition coefficient regimes. Live cell intracellular tracking of β-peptides showed that β-peptides translocated into the cytoplasm, and then disrupted the nucleus and vacuole sequentially, leading to cell death. This understanding of the mechanisms of antifungal activity will facilitate design and development of peptidomimetic AMPs, including 14-helical β-peptides, for antifungal applications.

Graphical Abstract
Ethanol decreases Pseudomonas aeruginosa flagellar motility through a cyclic-di-GMP- and stator-dependent pathway
Authors: Lewis Kimberley A. , Baker Amy E. , Chen Annie I. , Harty Colleen E. , Kuchma Sherry L. , O’Toole George A. , Hogan Deborah A.
Published: September 2018

Pseudomonas aeruginosa frequently encounters microbes that produce bioactive metabolites including ethanol. At concentrations that do not affect growth, we found that ethanol reduces P. aeruginosa motility by 30% in a swim agar assay and this decrease is accompanied by a 2.5-fold increase in levels of cyclic diguanylate (c-di-GMP), a second messenger that represses motility, in planktonic cells. A screen of mutants lacking genes involved in c-di-GMP metabolism identified SadC and GcbA as diguanylate cyclases involved in swim zone reduction by ethanol and ethanol-induced c-di-GMP production. The reduction of swimming in response to ethanol also required the stator set, MotAB, two PilZ-domain proteins (FlgZ and PilZ), PilY1-a proposed surface-sensing protein, and PilMNOP, which comprises the pilus alignment complex and these proteins have been previously implicated in the control of motility on agar surfaces. Microscopic analysis of the fraction of quiescent cells in swim medium showed that ethanol decreased the portion of motile cells in the wild type, but had opposite effects in the ∆pilY1, ∆pilMNOP, ∆motAB, and ∆pilZ∆flgZ mutants. Together, these data indicate ethanol induces a regulated change in motility in planktonic cells at concentrations similar to those produced by other microbes. We propose that this ethanol-responsiveness may contribute to the co-localization of P. aeruginosa with ethanol-producing microbes.
Induction of Sertoli cells from human fibroblasts by NR5A1 and GATA4
Authors: Liang Jianlin , Wang Nan , He Jing , Du Jian , Guo Yahui , Li Lin , Kee Kehkooi
Published: September 2018

Sertoli cells are essential nurse cells in the testis that regulate the process of spermatogenesis and establish the immune-privileged environment of the blood-testis-barrier (BTB). The induction of human Sertoli cells from fibroblasts could provide cellular sources for fertility and transplantation treatments. Here, we report thein vitroreprogramming of human fibroblasts to Sertoli cells and characterize these human induced Sertoli cells (hiSCs). Initially, five transcriptional factors (NR5A1, GATA4, WT1, SOX9 and DMRT1) and a gene reporter carrying the AMH promoter were utilized to obtain the hiSCs. We further reduce the number of reprogramming factors to two, i.e., NR5A1 and GATA4, and show that these hiSCs have transcriptome profiles that are similar to those of primary human Sertoli cells. Consistent with the known cellular properties of Sertoli cells, hiSCs attract endothelial cells and exhibit high number of lipid droplets in the cytoplasm. More importantly, hiSCs can sustain the viability of spermatogonia cells harvested from mouse seminiferous tubules. In addition, hiSCs suppress the production of IL-2 and proliferation of human T lymphocytes. When hiSCs were cotransplanted with human embryonic kidney cells, these xenotransplanted human cells survived longer in mice with normal immune systems. hiSCs also allow us to determine a gene associated with Sertoli-only syndrome (SCO),CX43, is indeed important in regulating the maturation of Sertoli cells.
Investigation of putative regulatory acetylation sites in Fas2p ofSaccharomyces cerevisiae
Authors: Bergman Alexandra , Wenning Leonie , Siewers Verena , Nielsen Jens
Published: September 2018

Yeast metabolism is highly regulated, in part via coordinated reprogramming of metabolism on a transcriptional level, for example in response to environmental changes. Furthermore, regulation occurs on the protein level via posttranslational modifications directly affecting enzymatic activity – a mode of regulation that has the benefit of being very fast in response to environmental changes. One group of posttranslational modification that has been suggested to have a high impact on regulation of metabolism are acetylations. Around 4000 distinct protein acetylation sites have been found inSaccharomyces cerevisiae, many of which are located in central metabolic enzymes. However, reports on the verification of regulatory roles of specific acetylation sites on these metabolic enzymes have yet to emerge. This study investigates putative regulatory acetylation sites on Fas2p, which in concert with Fas1p is responsible for cytosolic fatty acid (FA) biosynthesis inS. cerevisiae. Fas2p stands out as one of the most highly acetylated proteins in yeast and is located at a branchpoint of acetyl-CoA metabolism. The amino acids (AAs) glutamine (Q) and arginine (R) were introduced to mimic a constitutively acetylated or non-acetylatable state at three separate lysine sites (K) (K83, K173 and K1551) confirmed to be acetylated in two independent studies, either separately or simultaneously. The results suggest that the residue replacement system in the specific case interferes with the enzymatic function of the fatty acid synthase (FAS), as QQQ and RRR triple mutants both reduce the amount of secreted free fatty acids (FFAs) in afaa1Δfaa4Δ yeast deletion mutant. The K173Q substitution significantly decreased C16 FA species at the expense of C18 FAs, while no such change could be observed for the corresponding K173R modification.
A molecular mechanism for salt stress-induced microtubule array formation in Arabidopsis
Authors: Kesten Christopher , Wallmann Arndt , Schneider René , McFarlane Heather E. , Diehl Anne , Abbas Khan Ghazanfar , van Rossum Barth-Jan , Lampugnani Edwin , Cremer Nils , Schmieder Peter , Ford Kristina L. , Seiter Florian , Heazlewood Joshua L. , Sanchez-Rodriguez Clara , Oschkinat Hartmut , Persson Staffan
Published: September 2018

Microtubules are filamentous structures necessary for cell division, motility and morphology, with dynamics critically regulated by microtubule-associated proteins (MAPs). We outline the molecular mechanism by which the MAP, COMPANION OF CELLULOSE SYNTHASE1 (CC1), controls microtubule bundling and dynamics to sustain plant growth under salt stress. CC1 contains an intrinsically disordered N-terminus that links microtubules at evenly distributed distances through four conserved hydrophobic regions. NMR analyses revealed that two neighboring residues in the first hydrophobic binding motif are crucial for the microtubule interaction, which we confirmed through live cell analyses. The microtubule-binding mechanism of CC1 is remarkably similar to that of the prominent neuropathology-related protein Tau, indicating evolutionary convergence of MAP functions across animal and plant cells.
Enspara: Modeling molecular ensembles with scalable data structures and parallel computing
Authors: Porter J.R. , Zimmerman M.I. , Bowman G.R.
Published: September 2018

Markov state models (MSMs) are quantitative models of protein dynamics that are useful for uncovering the structural fluctuations that proteins undergo, as well as the mechanisms of these conformational changes. Given the enormity of conformational space, there has been ongoing interest in identifying a small number of states that capture the essential features of a protein. Generally, this is achieved by making assumptions about the properties of relevant features—for example, that the most important features are those that change slowly. An alternative strategy is to keep as many degrees of freedom as possible and subsequently learn from the model which of the features are most important. In these larger models, however, traditional approaches quickly become computationally intractable. In this paper, we present enspara, a library for working with MSMs that provides several novel algorithms and specialized data structures that dramatically improve the scalability of traditional MSM methods. This includes ragged arrays for minimizing memory requirements, MPI-parallelized implementations of compute-intensive operations, and a flexible framework for model estimation.
Par protein localization during the early development ofMnemiopsis leidyisuggests different modes of epithelial organization in Metazoa
Authors: Salinas-Saavedra Miguel , Martindale Mark Q
Published: September 2018

In bilaterians and cnidarians, embryonic and epithelial cell-polarity are regulated by the interactions between Par proteins, Wnt/PCP signaling pathway, and cell-cell adhesion. Par proteins are highly conserved across Metazoa, including ctenophores. But strikingly, ctenophore genomes lack components of the Wnt/PCP pathway and cell-cell adhesion complexes; raising the question if ctenophore cells are polarized by mechanisms involving Par proteins. Here, by using immunohistochemistry and live-cell imaging overexpression of specific mRNAs, we describe for the first time the subcellular localization of selected Par proteins in blastomeres and epithelial cells during the embryogenesis of the ctenophoreMnemiopsis leidyi. We show that these proteins distribute differently compared to what has been described for other animals, even though they segregate in a host-specific fashion when expressed in cnidarian embryos. This differential localization might be related to the emergence of different junctional complexes during metazoan evolution. Data obtained here challenge the ancestry of the apicobasal cell polarity and raise questions about the homology of epithelial tissue across the Metazoa.
Everyday taxi drivers: Do better navigators have larger hippocampi?
Authors: Weisberg Steven M. , Newcombe Nora S. , Chatterjee Anjan
Published: September 2018

Work with non-human animals and human navigation experts (London taxi drivers) suggests that the size of the hippocampus, particularly the right posterior hippocampus in humans, relates to navigation expertise. Similar observations, sometimes implicating other sections of the hippocampus, have been made for aging populations and for people with neurodegenerative diseases that affect the hippocampus. These data support the hypothesis that hippocampal volume relates to navigation ability. However, the support for this hypothesis is mixed in healthy, young adults, who range widely in their navigation ability. Here, we administered a naturalistic navigation task that measures cognitive map accuracy to a sample of 90 healthy, young adults who also had MRI scans. Using a sequential analysis design with a registered analysis plan, we did not find that navigation ability related to hippocampal volume (total, right only, right posterior only). We conclude that navigation ability in a typical population does not correlate with variations in hippocampal size, and consider possible explanations for this null result.
Linking YAP to Müller glia quiescence exit in the degenerative retina
Authors: Hamon Annaïg , Ail Divya , García-García Diana , Bitard Juliette , Dalkara Deniz , Locker Morgane , Roger Jérôme , Perron Muriel
Published: September 2018

Contrasting with fish or amphibian, retinal regeneration from Müller glial cells is largely limited in mammals. In our quest towards the identification of molecular cues that may boost their stemness potential, we investigated the involvement of the Hippo pathway effector YAP, which we previously found to be upregulated in Müller cells following retinal injury. We report that conditionalYapdeletion in Müller cells prevents the upregulation of cell cycle genes that normally accompanies reactive gliosis upon photoreceptor cell death. This occurs as a consequence of defective EGFR signaling. Consistent with a function of YAP in triggering Müller glia cell cycle re-entry, we further show that inXenopus, a species endowed with efficient regenerative capacity, YAP is required for their injury-dependent proliferative response. Finally, and noteworthy, we reveal that YAP overactivation in mouse Müller cells is sufficient to induce their reprogramming into highly proliferative cells. Overall, we unravel a pivotal role for YAP in tuning Müller cell response to injury and highlight a novel YAP-EGFR axis by which Müller cells exit their quiescence state, a critical step towards regeneration.
The inherent multidimensionality of temporal variability: How common and rare species shape stability patterns
Authors: Arnoldi Jean-François , Loreau Michel , Haegeman Bart
Published: September 2018

Empirical knowledge of ecosystem stability and diversity-stability relationships is mostly based on the analysis of temporal variability of population and ecosystem properties. Variability, however, often depends on external factors that act as disturbances, making it difficult to compare its value across systems and relate it to other stability concepts. Here we show how variability, when viewed as a response to stochastic perturbations, can reveal inherent stability properties of ecological communities, with clear connections with other stability notions. This requires abandoning one-dimensional representations, in which a single variability measurement is taken as a proxy for how stable a system is, and instead consider the whole set of variability values associated to a given community, reflecting the whole set of perturbations that can generate variability. Against the vertiginous dimensionality of the perturbation set, we show that a generic variability-abundance pattern emerges from community assembly, which relates variability to the abundance of perturbed species. As a consequence, the response to stochastic immigration is governed by rare species while common species drive the response to environmental perturbations. In particular, the contrasting contributions of different species abundance classes can lead to opposite diversity-stability patterns, which can be understood from basic statistics of the abundance distribution. Our work shows that a multidimensional perspective on variability allows one to better appreciate the dynamical richness of ecological systems and the underlying meaning of their stability patterns.
StPOPA, encoding an anionic peroxidase in Solanum tuberosum, enhances resistance against Phytophthora infestans
Authors: Yang Yu , Jiang Rui , Wang Hongyang , Tian Zhendong , Xie Conghua
Published: September 2018

Potato late blight, caused by Phytophthora infestans, is one of the major threats affecting the quality and output of potato all over the world. Reactive oxygen species (ROS) acted as a signal molecule to transmit signals in plants at the early stage of disease infection, and it could induce disease resistance of the plant, including potato late blight. Anionic peroxidases in many plants were reported to be involved in defense to disease. However, limited information about anionic peroxidase genes is available for the potato. Here, we reported that the expression of the StPOPA, a gene encoding a suberization-associated anionic peroxidase, was associated with resistance in potato against P. infestans. The StPOPA gene was induced by P. infestans infection, mechanical damage, jasmonic acid and ethylene treatment. Overexpression of the StPOPA gene in potato enhanced the resistance against P. infestans via promoting the accumulation of callose in the cell wall and ROS in the cytoplasm, which restricted the infection and spreading of the disease possibly by purposeful programmed cell death. Taken together, our results suggested that the StPOPA gene contributed to potato immunity against P. infestans and this gene could be used for the genetic improvement of resistance against potato late blight.
Interaction of taste and place coding in the hippocampus
Authors: Herzog Linnea E. , Pascual Leila May , Scott Seneca J. , Mathieson Elon R. , Katz Donald B. , Jadhav Shantanu P.
Published: September 2018

An animal’s survival depends on finding food, and the memory of food and contexts are often linked. Given that the hippocampus is required for spatial and contextual memory, it is reasonable to expect related coding of space and food stimuli in hippocampal neurons. However, relatively little is known about how the hippocampus responds to tastes, the most central sensory property of food. In this study, we examined the taste-evoked responses and spatial firing properties of single units in the dorsal CA1 hippocampal region as male rats received a battery of taste stimuli differing in both chemical composition and palatability within a specific spatial context. We identified a subset of hippocampal neurons that responded to tastes, some of which were place cells. These taste and place responses had a distinct interaction: taste-responsive cells tended to have less spatially specific firing fields, and place cells only responded to tastes delivered inside their place field. Like neurons in the amygdala and lateral hypothalamus, hippocampal neurons discriminated between tastes predominantly on the basis of palatability, with taste-selectivity emerging concurrently with palatability-relatedness; these responses did not reflect movement or arousal. However, hippocampal taste responses emerged several hundred msec later than responses in other parts of the taste system, suggesting that the hippocampus does not influence real-time taste decisions, instead associating the hedonic value of tastes with a particular context. This incorporation of taste responses into existing hippocampal maps could be one way that animals use past experience to locate food sources.

Significance statement

Finding food is essential for animals’ survival, and taste and context memory are often linked. While hippocampal responses to space and contexts have been well characterized, little is known about how the hippocampus responds to tastes. Here, we identified a subset of hippocampal neurons that discriminated between tastes based on palatability. Cells with stronger taste responses typically had weaker spatial responses, and taste responses were confined to place cells’ firing fields. Hippocampal taste responses emerged later than in other parts of the taste system, suggesting that the hippocampus does not influence taste decisions, but rather, associates the hedonic value of tastes consumed within a particular context. This could be one way that animals use past experience to locate food sources.
Internal bias controls dopamine perceptual decision-related responses
Authors: Sarno Stefania , Beirán Manuel , Vergara José , Rossi-Pool Román , Romo Ranulfo , Parga Néstor
Published: September 2018

Dopamine neurons produce reward-related signals that regulate learning and guide behavior. Prior expectations about forthcoming stimuli and internal biases can alter perception and choices and thus could influence dopamine signaling. We tested this hypothesis studying dopamine neurons recorded in monkeys trained to discriminate between two tactile frequencies separated by a delay period, a task affected by the contraction bias. The bias greatly controlled the animals’ choices and confidence on their decisions. During decision formation the phasic activity reflected bias-induced modulations and simultaneously coded reward prediction errors. In contrast, the activity during the delay period was not affected by the bias, was not tuned to the value of the stimuli but was temporally modulated, pointing to a role different from that of the phasic activity.
Improved Pathogenic Variant Localization using a Hierarchical Model of Sub-regional Intolerance
Authors: Hayeck Tristan J. , Stong Nicholas , Wolock Charles J. , Copeland Brett , Kamalakaran Sitharthan , Goldstein David , Allen Andrew
Published: September 2018

Different parts of a gene can be of differential importance to development and health. This regional heterogeneity is also apparent in the distribution of disease mutations which often cluster in particular regions of disease genes. The ability to precisely estimate functionally important sub-regions of genes will be key in correctly deciphering relationships between genetic variation and disease. Previous methods have had some success using standing human variation to characterize this variability in importance by measuring sub-regional intolerance, i.e., the depletion in functional variation from expectation within a given region of a gene. However, the ability to precisely estimate local intolerance was restricted by the fact that only information within a given sub-region is used, leading to instability in local estimates, especially for small regions. We show that borrowing information across regions using a Bayesian hierarchical model, stabilizes estimates, leading to lower variability and improved predictive utility. Specifically, our approach more effectively identifies regions enriched for ClinVar pathogenic variants. We also identify significant correlations between sub-region intolerance and the distribution of pathogenic variation in disease genes, with AUCs for classifying de novo missense variants in Online Mendelian Inheritance in Man (OMIM) genes of up to 0.86 using exonic sub-regions and 0.91 using sub-regions defined by protein domains. This result immediately suggests that considering the intolerance of regions in which variants are found may improve diagnostic interpretation. We also illustrate the utility of integrating regional intolerance into gene-level disease association tests with a study of known disease genes for epileptic encephalopathy.
Pooled functional genomic screens for intracellular calcium effectors
Authors: Rao Anjali , Kralj Joel M.
Published: October 2018

Cytoplasmic calcium transients relay cellular signals on timescales from milliseconds to hours, and the dynamic nature of calcium signals has slowed functional genomic screening for cellular calcium effectors. Here, we present a new strategy to identify calcium handling genes via a pooled knockdown employing the calcium-sensitive photo-switchable fluorescent protein, CaMPARI. This assay, cal-Seq, enabled identification of regulators for both cellular desensitization and histamine induced calcium signaling including GPR99, a leukotriene binding receptor, with implications in asthma treatment.
Stylometric analysis of classical Arabic texts for genre detection
Authors: Al-Yahya Maha
Published: October 2018

Purpose

In the context of information retrieval, text genre is as important as its content, and knowledge of the text genre enhances the search engine features by providing customized retrieval. The purpose of this study is to explore and evaluate the use of stylometric analysis, a quantitative analysis for the linguistics features of text, to support the task of automated text genre detection for Classical Arabic text.

Design/methodology/approach

Unsupervised clustering and supervised classification were applied on the King Saud University Corpus of Classical Arabic texts (KSUCCA) using the most frequent words in the corpus (MFWs) as stylometric features. Four popular distance measures established in stylometric research are evaluated for the genre detection task.

Findings

The results of the experiments show that stylometry-based genre clustering and classification align well with human-defined genre. The evidence suggests that genre style signals exist for Classical Arabic and can be used to support the task of automated genre detection.

Originality/value

This work targets the task of genre detection in Classical Arabic text using stylometric features, an approach that has only been previously applied to Arabic authorship attribution. The study also provides a comparison of four distance measures used in stylomtreic analysis on the KSUCCA, a corpus with over 50 million words of Classical Arabic using clustering and classification.
The relationship between leadership style and employee performance
Authors: Ohemeng Frank L.K. , Amoako-Asiedu Emelia , Obuobisa Darko Theresa
Published: October 2018

Purpose

The purpose of this paper is to advance critical theoretical insights into the idea of “relational bureaucratic leadership” and its implications for public administration in developing countries (DCs). In doing so, the paper sets out new agendas for public service governance in DCs that recognizes the changing nature and emerging complexities of both the public service and society.

Design/methodology/approach

This is an exploratory study which synthesises literature in management, human resources, leadership studies and public administration, to understand the limitations of mainstream approaches to bureaucratic leadership in DCs, particularly SSA, with a view of identifying alternative practices.

Findings

Findings from this paper suggest that public service governance in DCs are embedded in complex dynamics between power relations, complexity and social norms, and bureaucratic leaders should, therefore, focus on building relationships as a means of deepening trust and enhancing cooperation among critical actors. The case for a shift in focus to “relationality” reflects changes in the broader global political economy, including emerging wicked and multi-faceted policy problems that require heterodox and context-sensitive responses from governments and greater collaboration among key stakeholders.

Originality/value

The analysis of the limitations of traditional approaches to public service governance in this essay reveals the importance of a shift from a preoccupation with conventional organizational forms and functions, to place greater emphasis on social networks and relationships, as a way of improving leadership efficiency in the public services of DCs.
Low leverage policy: a boon or bane for Indian shareholders
Authors: Deb Soumya G. , Banerjee Pradip
Published: October 2018

Purpose

This paper aims to explore whether following an apparently sub-optimal “almost zero leverage (AZL)” policy by some Indian firms actually creates incremental value for their shareholders or is detrimental for them.

Design/methodology/approach

The paper investigates the relative equity market and operating performance of a sample of Indian firms adopting an AZL policy between 1998 and 2014,vis-a-vis, their leveraged peers from the same industry. The authors also look at the dynamic time variability of patterns, if any, in such relative performance and explore whether such patterns are explained primarily by investor perceptions or there are other factors to it.

Findings

The study show that Indian firms following post AZL policy exhibit superior equity performance compared to their leveraged counterparts, particularly during market downturns. The authors also find that this superior equity market performance is not merely because of the positive investor perception about the potential benefits of a robust debt-free balance sheet. The authors’ results show that the AZL firms register higher business risk and significantly superior operating performance, post being low leverage. The results hold even after using several robustness checks.

Practical implications

The study concludes that the managers of AZL firms take full advantage of the increased financial flexibility available with them and venture into riskier but more rewarding avenues and actually create incremental value for their shareholders.

Originality/value

The study highlights an apparently counterintuitive pattern in Indian context, counterintuitive particularly because choosing an AZL policy leads to forgo the availability of significant tax shield for firms. The results, the authors believe, can have significant implications for lenders and investors in the Indian capital markets in particular and emerging markets in general.
Convergence of management practices in India’s IT sector with ana priorivalidation
Authors: Mahesh Jayashree , Bhat Anil K.
Published: October 2018

Purpose

The purpose of this paper is to document similarities and differences between management practices of different types of organizations in India’s IT sector through an empirical survey. The authors expected these differences to be significant enough for us to be able to groupa priorithis set of companies meaningfully through cluster analysis on the basis of the similarity of their management practices alone.

Design/methodology/approach

Using a mixed-methods approach, 73 senior-level executives of companies working in India’s IT sector were approached with a pretested questionnaire to find out differences on eighteen management practices in the areas of operations management, monitoring management, targets management and talent management. The different types of organizations surveyed were small and amp; medium global multinationals, large global multinationals, small and medium Indian multinationals, large Indian multinationals and small and medium local Indian companies. The differences and similarities found through statistical testing were further validateda priorithrough cluster analysis and qualitative interviews with senior-level executives.

Findings

The management practices of multinationals in India are moving toward Western management practices, indicating that management practices converge as the organizations grow in size. Though the practices of large Indian multinationals were not significantly different from those of global multinationals, the surprising finding was that large Indian multinationals scored better than global multinationals on a few practices. The practices of small and medium Indian companies differed significantly from those of other types of organizations and hence they formed a cluster.

Practical implications

The finding that large Indian IT multinationals have an edge over global multinationals in certain people management practices is a confirmation of the role of human resource practices in their current success and their continuing competitive advantage.

Originality/value

This is perhaps the first study of its kind to document state of specific management practices across different types of organizations in India’s IT sector and then use measures on these practices to group a priori these organizations for validation.
Creating an X Window Terminal‐based Information Technology Center
Authors: Klassen Tim W.
Published: October 2018

The last decade has seen a dramatic jump in the amount of online electronic resources available to library patrons. With this change has come the need for libraries to create environments for providing access to this text and graphical information. The experiences of the University of Oregon Science Library's Information Technology Center may help other academic libraries as they plan for, and customize, high‐end workstations to meet user needs. This paper explores how SLITC could aid in this.
Assessing bottom trawling impacts based on the longevity of benthic invertebrates
Authors: Hiddink Jan Geert , Jennings Simon , Sciberras Marija , Bolam Stefan G. , Cambiè Giulia , McConnaughey Robert A. , Mazor Tessa , Hilborn Ray , Collie Jeremy S. , Pitcher C. Roland , Parma Ana M. , Suuronen Petri , Kaiser Michel J. , Rijnsdorp Adriaan D.
Published: September 2018

Bottom trawling is the most widespread human activity directly affecting seabed habitats. Assessment and effective management of the effects of bottom trawling at the scale of fisheries requires an understanding of differences in sensitivity of biota to trawling. Responses to disturbance are expected to depend on the intrinsic rate of increase in populations (r), which is expected to be linearly related to the reciprocal of longevity.

We examine the relationship between the longevity of benthic invertebrates and their response to bottom trawling; both in terms of the immediate mortality following a trawl pass and their subsequent rates of recovery. We collate all available data from experimental and comparative trawling studies, and test how longevity influences these aspects of sensitivity.

The shortest lived organisms (<1 year) increased in abundance shortly after experimental trawling but showed no response to trawling in long‐term comparative studies. Conversely, the abundance of biota with a life span >1 year decreased by ~9% immediately following a trawl pass. The effect of bottom trawling in comparative studies increased with longevity, with a 2–3× larger effect on biota living >10 years than on biota living 1–3 years. We attribute this difference to the slower recovery rates of the long‐lived biota.

The observed relationship between the intrinsic rate of population increase (r, our metric of recovery rate) and the reciprocal of longevity matches theoretical expectation and predicts that the sensitivity of habitats to bottom trawling is higher in habitats with higher proportions of long‐lived organisms.

Synthesis and applications. Where the longevity of a species or the longevity distribution of a community is known or can be inferred, our estimates of depletion and intrinsic rate of increase can be combined with high‐resolution maps of trawling intensity to assess trawling impacts at the scale of the fishery or other defined unit of assessment. Our estimates ofrmay also be used to estimate recovery times following other forms of seabed disturbance.
Korean elementary school teachers’ implementation of mathematics instruction for students struggling to learn mathematics in inclusive settings
Authors: Shin Mikyung , Ok Min Wook , Kang Eun Young , Bryant Diane P.
Published: September 2018

In this study, the researchers used a researcher‐developed online survey to examine the beliefs of elementary school general and special education teachers regarding inclusion and their implementation of mathematics instructional practices. Participants were 55 general and 38 special education teachers. The data analysis was performed using frequency analyses, crosstabs statistics (Fisher's exact test) and independent t‐tests. Results indicated that both general and special education teachers recognised the importance of and need for inclusive education. Further, the most frequently used instructional groupings were a whole class and an individualised grouping for general and special education teachers respectively. The two groups’ responses about the use of instructional materials and practices varied considerably. Finally, both groups reported a relatively high level of confidence in mathematics topics in general. Limitations, recommendations for future research and instructional practices are discussed.
Staphylococcus aureus from atopic dermatitis skin accumulates in the lysosomes of keratinocytes with induction of IL‐1α secretion via TLR9
Authors: Moriwaki Masaya , Iwamoto Kazumasa , Niitsu Yoshie , Matsushima Ayako , Yanase Yuhki , Hisatsune Junzo , Sugai Motoyuki , Hide Michihiro
Published: September 2018

Background

Staphylococcus aureus (S. aureus) is frequently detected in the skin of patients with atopic dermatitis (AD), and involved in the flare of AD. There are some evidence‐specific strains of S. aureus affect the severity of AD. However, the mechanism of predominant colonization and the aggravation of dermatitis by certain strains of S. aureus in the patients with AD are still unknown.

Objective

To reveal the characteristics of S. aureus from patients with AD (S. aureus‐AD), we analyzed the interaction of S. aureus‐AD and keratinocytes in comparison with those of S. aureus laboratory strains (S. aureus‐stand.).

Methods

We stimulated HaCaT cells, keratinocyte cell line, and human epidermal keratinocytes by heat‐killed S. aureus strains, then evaluated immune response of keratinocytes by ELISA, immunofluorescence staining, and flow cytometry.

Results

Upon incubation with keratinocytes, three out of four strains of heat‐killed S. aureus‐AD were strongly agglutinated inside the cytoplasm. In the cells, they are located in lysosomes and promoted the secretion of interleukin‐1α (IL‐1α). These reactions were not observed by any of four strains of S. aureus‐stand. and S. epidermidis and were abolished by the treatment of S. aureus with proteinase K. Moreover, the IL‐1α secretion was diminished by the inhibition of Toll‐like receptor 9 (TLR9).

Conclusion

S. aureus‐AD accumulates in lysosome of keratinocytes by means of bacterial cell wall proteins and induces IL‐1α via TLR9.
The circadian clock regulates the diurnal levels of microbial short‐chain fatty acids and their rhythmic effects on colon contractility in mice
Authors: Segers Anneleen , Desmet Louis , Thijs Theo , Verbeke Kristin , Tack Jan , Depoortere Inge
Published: September 2018

Aim

The microbiota shows diurnal oscillations that are synchronized by the host's circadian clock and feeding rhythms. Short‐chain fatty acids (SCFAs) produced by the microbiota are possible synchronizers of peripheral circadian clocks. We aimed to investigate whether faecal SCFAs show a diurnal rhythm that regulates the rhythm of SCFA receptor expression (FFAR2/3, OLFR78, HCAR2) and SCFA‐induced colonic contractility. The role of the circadian clock was studied in mice lacking the core clock gene Bmal1.

Methods

Mice were sacrificed at 4‐hour intervals. Faecal SCFA concentrations and SCFA receptor expression were determined. The effect of increasing concentrations of a SCFA mix on electrical field‐induced neural responses in colon strips was measured isometrically.

Results

Diurnal fluctuations in faecal SCFA concentrations (peak 4 hours after lights on) were observed that were in phase with the rhythm of Ffar2/3 expression in the colonic muscle layer. Olfr78 expression was not diurnal and Hcar2 was not detectable. The inhibitory effect of a SCFA mix on neural contractions in colonic smooth muscle strips showed a diurnal rhythm and oscillated in phase with faecal SCFA concentrations and Ffar2/3 expression. In contrast, neither excitatory neural responses nor acetylcholine‐induced smooth muscle contractions showed a diurnal rhythm. In Bmal1−/− mice, no fluctuations in faecal SCFA levels, Ffar3 expression and neural responses to SCFAs were observed.

Conclusion

Diurnal microbial SCFA levels regulate the rhythm of Ffar3 expression in the colonic myenteric plexus, which causes rhythmicity in SCFA‐induced colonic motility. Deletion of Bmal1 abolishes rhythmicity of SCFA levels and their downstream effects.
Diagnosis and management of central diabetes insipidus in adults
Authors: Garrahy Aoife , Moran Carla , Thompson Christopher J.
Published: September 2018

Central diabetes insipidus (CDI) is characterized by hypotonic polyuria due to impairment of AVP secretion from the posterior pituitary. In clinical practice, it needs to be distinguished from renal resistance to the antidiuretic effects of AVP (nephrogenic DI), and abnormalities of thirst appreciation (primary polydipsia). As nephrogenic diabetes insipidus is rare in adults, unless they are treated with lithium salts, the practical challenge is how to differentiate between CDI and clinical disorders of excess thirst. The differential diagnosis is usually straight forward, but the recommended gold standard test, the water deprivation test, is not without interpretative pitfalls. The addition of the measurement of plasma AVP concentrations improves diagnostic accuracy, but the radioimmunoassay for AVP is technically difficult, and is only available in a few specialized centres. More recently, the measurement of plasma copeptin concentrations has been claimed to provide a reliable alternative to measurement of plasma AVP, without the sampling handling challenges. In addition, the measurement of thirst ratings can help the differentiation between CDI and primary polydipsia. Once the diagnosis of CDI is biochemically certain, investigations to determine the cause of AVP deficiency are needed. In this review, we will outline the diagnostic approach to polyuria, revisit the caveats of the water deprivation test and review recent data on value of adding AVP/copeptin measurement. We will also discuss treatment strategies for CDI, with analysis of potential complications of treatment.
Circadian and photic modulation of daily rhythms in diurnal mammals
Authors: Yan Lily , Smale Laura , Nunez Antonio A.
Published: September 2018

The temporal niche that an animal occupies includes a coordinated suite of behavioral and physiological processes that set diurnal and nocturnal animals apart. The daily rhythms of the two chronotypes are regulated by both the circadian system and direct responses to light, a process called masking. Here we review the literature on circadian regulations and masking responses in diurnal mammals, focusing on our work using the diurnal Nile grass rat (Arvicanthis niloticus) and comparing our findings with those derived from other diurnal and nocturnal models. There are certainly similarities between the circadian systems of diurnal and nocturnal mammals, especially in the phase and functioning of the principal circadian oscillator within the hypothalamic suprachiasmatic nucleus (SCN). However, the downstream pathways, direct or indirect from the SCN, lead to drastic differences in the phase of extra‐SCN oscillators, with most showing a complete reversal from the phase seen in nocturnal species. This reversal, however, is not universal and in some cases the phases of extra‐SCN oscillators are only a few hours apart between diurnal and nocturnal species. The behavioral masking responses in general are opposite between diurnal and nocturnal species, and are matched by differential responses to light and dark in several retinorecipient sites in their brain. The available anatomical and functional data suggest that diurnal brains are not simply a phase‐reversed version of nocturnal ones, and work with diurnal models contribute significantly to a better understanding of the circadian and photic modulation of daily rhythms in our own diurnal species.
Pharmacological insights into impulsive‐compulsive spectrum disorders associated with dopaminergic therapy
Authors: Napier T. Celeste , Persons Amanda L.
Published: September 2018

Impulsive‐compulsive spectrum disorders are associated with dopamine agonist therapy in some patients. These untoward outcomes occur with direct‐acting, full and partial agonists at D2 dopamine family receptors. The disorders typically emerge during chronic treatment, and exhibit common features that are independent of the neurological or psychiatric pathology for which the initial therapy was indicated. It is well‐documented that the brain is ‘plastic’, changing in response to alterations to internal factors (e.g., disease processes), as well as external factors (e.g., therapies). The complexities of these clinical scenarios have eluded a clear depiction of the neurobiology for impulsive‐compulsive spectrum disorders and engendered considerable debate regarding the mechanistic underpinnings of the disorders. In this opinion, we use pharmacological concepts related to homeostatic compensation subsequent to chronic receptor activation to provide a unifying construct. This construct helps explain the occurrence of impulsive‐compulsive spectrum disorders across disease states, and during therapy with full and partial agonists.
Flies as models for circadian clock adaptation to environmental challenges
Authors: Helfrich‐Förster Charlotte , Bertolini Enrico , Menegazzi Pamela
Published: September 2018

Life on earth is assumed to have developed in tropical regions that are characterized by regular 24 hr cycles in irradiance and temperature that remain the same throughout the seasons. All organisms developed circadian clocks that predict these environmental cycles and prepare the organisms in advance for them. A central question in chronobiology is how endogenous clocks changed in order to anticipate very different cyclical environmental conditions such as extremely short and long photoperiods existing close to the poles. Flies of the family Drosophilidae can be found all over the world—from the tropics to subarctic regions—making them unprecedented models for studying the evolutionary processes that underlie the adaptation of circadian clocks to different latitudes. This review summarizes our current understanding of these processes. We discuss evolutionary changes in the clock genes and in the clock network in the brain of different Drosophilids that may have caused behavioural adaptations to high latitudes.
Copper in the suprachiasmatic circadian clock: A possible link between multiple circadian oscillators
Authors: Yamada Yukihiro , Prosser Rebecca A.
Published: September 2018

The mammalian circadian clock in the suprachiasmatic nucleus (SCN) is very robust, able to coordinate our daily physiological and behavioral rhythms with exquisite accuracy. Simultaneously, the SCN clock is highly sensitive to environmental timing cues such as the solar cycle. This duality of resiliency and sensitivity may be sustained in part by a complex intertwining of three cellular oscillators: transcription/translation, metabolic/redox, and membrane excitability. We suggest here that one of the links connecting these oscillators may be forged from copper (Cu). Cellular Cu levels are highly regulated in the brain and peripherally, and Cu affects cellular metabolism, redox state, cell signaling, and transcription. We have shown that both Cu chelation and application induce nighttime phase shifts of the SCN clock in vitro and that these treatments affect glutamate, N‐methyl‐D‐aspartate receptor, and associated signaling processes differently. More recently we found that Cu induces mitogen‐activated protein kinase‐dependent phase shifts, while the mechanisms by which Cu removal induces phase shifts remain unclear. Lastly, we have found that two Cu transporters are expressed in the SCN, and that one of these transporters (ATP7A) exhibits a day/night rhythm. Our results suggest that Cu homeostasis is tightly regulated in the SCN, and that changes in Cu levels may serve as a time cue for the circadian clock. We discuss these findings in light of the existing literature and current models of multiple coupled circadian oscillators in the SCN.