bluuebunny/crossref_metadata_2025_split huggingface dataset:
Stem-cell niche self-restricts the signaling range via receptor-ligand degradation
Authors: Ladyzhets Sophia , Antel Matthew , Simao Taylor , Gasek Nathan , Inaba Mayu 
Published: September 2018

AbstractStem-cell niche signaling is short-range in nature, such that only stem cells but not their differentiating progeny experience self-renewing signals. At the apical tip of the Drosophila testes, 8 to 10 germline stem cells (GSCs) surround the hub, a cluster of somatic cells that function as the major component of the stem cell niche. We have shown that GSCs form microtubule-based nanotubes (MT-nanotubes), which project into the hub cells, serving as the platform for niche signal reception: the receptor Tkv expressed by GSCs localizes to the surface of MT-nanotubes, where it receives the hub-derived ligand Decapentaplegic (Dpp), ensuring the reception of the ligand specifically by stem cells but not by differentiating cells.Here we show that receptor (Tkv)-ligand (Dpp) interaction at the surface of MT-nanotubes serves a second purpose of dampening the niche signaling: we found that the receptor Tkv and the ligand Dpp are internalized into hub cells and are degraded in the hub cell lysosomes. Perturbation of hub lysosomal function or MT-nanotube formation leads to excess receptor retention within germ cells as well as excess Dpp that diffuses out of the hub, leading to ectopic activation of niche signal in differentiating germ cells. Our results demonstrate that MT-nanotubes plays dual roles in ensuring the short-range nature of the niche signaling by 1) providing exclusive interphase of the niche ligand-receptor interaction and 2) limiting the amount of available ligand-receptor via their degradation.
The zebrafish orthologue of familial Alzheimer’s disease genePRESENILIN2 is required for normal adult melanotic skin pigmentation
Authors: Jiang Haowei , Newman Morgan , Lardelli Michael 
Published: September 2018

AbstractAlzheimer’s disease is the most common form of age-related dementia. At least 15 mutations in the human genePRESENILIN 2(PSEN2) have been found to cause familial Alzheimer’s disease (fAD). Zebrafish possess an orthologous gene,psen2, and present opportunities for investigation ofPRESENILINfunction related to Alzheimer’s disease. The most prevalent and best characterized fAD mutation inPSEN2isN141I. The equivalent codon in zebrafishpsen2is N140. We used genome editing technology in zebrafish to target generation of mutations to the N140 codon. We isolated two mutations:psen2N140fs, (hereafter “N140fs”), causing truncation of the coding sequence, andpsen2T141_L142delinsMISLISV, (hereafter “T141_L142delinsMISLISV”), that deletes the two codons immediately downstream of N140 and replaces them with seven codons coding for amino acid residues MISLISV. Thus, like almost every fAD mutation in thePRESENILINgenes, this latter mutation does not truncate the gene’s open reading frame. Both mutations are homozygous viable althoughN140fstranscripts are subject to nonsense-mediated decay and lack any possibility of coding for an active γ-secretase enzyme.N140fshomozygous larvae initially show grossly normal melanotic skin pigmentation but subsequently lose this as they grow while retaining pigmentation in the retinal pigmented epithelium.T141_L142delinsMISLISVhomozygotes retain faint skin melanotic pigmentation as adults, most likely indicating that the protein encoded by this allele retains weak γ-secretase activity. Null mutations in the humanPRESENILINgenes do not cause Alzheimer’s disease so these two mutations may be useful for future investigation of the differential effects of null and fAD-likePRESENILINmutations on brain aging.Financial Disclosure StatementThis research was supported by grants from the National Health and Medical Research Council of Australia, GNT1061006 and GNT1126422, and by funds from the School of Biological Sciences of the University of Adelaide. HJ is supported by an Adelaide Scholarship International from the University of Adelaide.Conflict of Interest StatementThe authors declare no conflict of interest.
Axenic Biofilm Formation and Aggregation bySynechocystisPCC 6803 is Induced by Changes in Nutrient Concentration, and Requires Cell Surface Structures
Authors: Allen Rey , Rittmann Bruce E. , Curtiss Roy 
Published: September 2018

AbstractPhototrophic biofilms are key to nutrient cycling in natural environments and bioremediation technologies, but few studies describe biofilm formation by pure (axenic) cultures of a phototrophic microbe. The cyanobacteriumSynechocystissp. PCC 6803 (hereafterSynechocystis) is a model micro-organism for the study of oxygenic photosynthesis and biofuel production. We report here that wild-type (WT)Synechocystiscaused extensive biofilm formation in a 2000 liter outdoor non-axenic photobioreactor under conditions attributed to nutrient limitation. We developed a biofilm assay and found that axenicSynechocystisforms biofilms of cells and extracellular material, but only when induced by an environmental signal, such as by reducing the concentration of growth medium BG11. Mutants lacking cell surface structures, namely type IV pili and the S-layer, do not form biofilms.To further characterize the molecular mechanisms of cell-cell binding bySynechocystis, we also developed a rapid (8 hour) axenic aggregation assay. Mutants lacking Type IV pili were unable to aggregate, but mutants lacking a homolog to Wza, a protein required for Type 1 exopolysaccharide export inEscherichia coli, had a super-binding phenotype. In WT cultures, 1.2x BG11 induced aggregation to the same degree as 0.8x BG11. Overall, our data support that Wza-dependant exopolysaccharide is essential to maintain stable, uniform suspensions of WTSynechocystiscells in unmodified growth medium, and this mechanism is counter-acted in a pili-dependent manner under altered BG11 concentrations.ImportanceMicrobes can exist as suspensions of individual cells in liquids, and also commonly form multicellular communities attached to surfaces. Surface-attached communities, called biofilms, can confer antibiotic resistance to pathogenic bacteria during infections, and establish food webs for global nutrient cycling in the environment. Phototrophic biofilm formation is one of the earliest phenotypes visible in the fossil record, dating back over 3 billion years. Despite the importance and ubiquity of phototrophic biofilms, most of what we know about the molecular mechanisms, genetic regulation, and environmental signals of biofilm formation comes from studies of heterotrophic bacteria. We aim to help bridge this knowledge gap by developing new assays forSynechocystis, a phototrophic cyanobacterium used to study oxygenic phototsynthesis and biofuel production. With the aid of these new assays, we contribute to the development ofSynechocystisas a model organism for the study of axenic phototrophic biofilm formation.
Inhibitor of the spindle assembly checkpoint surpasses apoptosis sensitizer in synergy with taxanes
Authors: Han Teng-Long , Jiang Zhi-Xin , Li Yun-Tian , Wu Deng-Shan , Ji Jun , Lin Hu , Hu Bin , Sha Hang 
Published: September 2018

AbstractThe antitumor effect of taxanes have been attributed to their ability to induce mitotic arrest through activation of the spindle assembly checkpoint. Cell death following prolonged mitotic arrest is mediated by the intrinsic apoptosis pathway. Thus, apoptosis sensitizers which inhibit antiapoptotic Bcl-2 family proteins has been shown to enhance taxanes-induced cell death. By contrast, spindle checkpoint disruption facilitates mitotic slippage and is thought to promote taxanes resistance. Notably, other modes of cell death also contribute to treatment outcomes. Here we show that inhibition of the spindle checkpoint suppresses taxanes induced apoptosis but increases terminal growth arrest of tumor cells with features of cellular senescence. By using clonogenic assay which measures the net result of multiple forms of cell death and is more reflective of therapeutic response, our finding suggests apoptosis is not a major determinant of antitumor efficacy of taxanes, whereas spindle checkpoint inhibitor displays a long-term advantage over apoptosis sensitizer in blocking colony outgrowth of tumor cells when combined with different microtubule toxins, therefore represents a superior therapeutic strategy.SIGNIFICANCEApoptosis has long been regarded as the primary mechanism of anti-cancer efficacy of taxanes, while the role of the spindle assembly checkpoint (SAC) in treatment response to taxanes has been controversial. Either apoptosis sensitizer or inhibitor of SAC has been reported to synergize with taxanes. While inhibitor of antiapoptotic proteins potentiates taxanes induced apoptosis, inhibitor of SAC suppresses apoptosis by facilitating mitotic slippage, that is why it is implicated in taxanes resistance. By demonstrating that apoptotic rates are not associate with long-term treatment response, not only do we find that inhibitor of SAC displays a long-term advantage over apoptosis sensitizer in combination with taxanes, but we also resolve the dispute around the role of SAC in cellular response to taxanes.
Chronic Staphylococcus aureus lung infection correlates with proteogenomic and metabolic adaptations leading to an increased intracellular persistence
Authors: Tan Xin , Coureuil Mathieu , Ramond Elodie , Euphrasie Daniel , Dupuis Marion , Tros Fabiola , Meyer Julie , Nemanzny Ivan , Chhuon Cerina , Guerrera Ida Chiara , Ferroni Agnes , Sermet-Gaudelus Isabelle , Nassif Xavier , Charbit Alain , Jamet Anne 
Published: September 2018

AbstractBackgroundChronic lung infection of cystic fibrosis (CF) patients by Staphylococcus aureus is a well-established epidemiological fact. Indeed, S. aureus is the most commonly identified pathogen in the lungs of CF patients. Strikingly the molecular mechanisms underlying S. aureus persistency are not understood.MethodsWe selected pairs of sequential S. aureus isolates from 3 patients with CF and from one patient with non-CF chronic lung disease. We used a combination of genomic, proteomic and metabolomic approaches with functional assays for in-depth characterization of S. aureus long-term persistence.ResultsFor the first time, we show that late S. aureus isolates from CF patients have an increased ability for intracellular survival in CFBE-F508del cells compared to ancestral early isolates. Importantly, the increased ability to persist intracellularly was confirmed for S. aureus isolates within the own patient F508del epithelial cells. An increased ability to form biofilm was also demonstrated.Furthermore, we identified the underlying genetic modifications inducing altered protein expression profiles and notable metabolic changes. These modifications affect several metabolic pathways and virulence regulators that could constitute therapeutic targets.ConclusionsOur results strongly suggest that the intracellular environment might constitute an important niche of persistence and relapse necessitating adapted antibiotic treatments.SummaryS. aureus persists for years in the lungs of patients with cystic fibrosis despite antibiotic therapies. We demonstrate that S. aureus adaptation leads to increased intracellular persistence suggesting a key role for intracellular niche during S. aureus chronic lung infection.
Hippocampal-entorhinal transformations in abstract frames of reference
Authors: Kaplan Raphael , Friston Karl J 
Published: September 2018

AbstractKnowing how another’s preferences relate to our own is a central aspect of everyday decision-making, yet how the brain performs this transformation is unclear. Here, we ask whether the putative role of the hippocampal-entorhinal system in transforming relative and absolute spatial coordinates during navigation extends to transformations in abstract decision spaces. During fMRI scanning, subjects learned a stranger’s preference for an everyday activity – relative to one of three personally known individuals – and subsequently decided how the stranger’s preference relates to the other two individuals’ preferences. We found that entorhinal cortex/subiculum signals exhibited reference frame-sensitive responses to the absolute distance between the ratings of the stranger and the familiar choice options. In contrast, striatal signals increased when accurately determining the ordinal position of choice options in relation to the stranger. Paralleling its role in navigation, these data implicate the entorhinal/subicular region in assimilating relatively coded knowledge within abstract metric spaces.
New Drosophila long-term memory genes revealed by assessing computational function prediction methods
Authors: Kacsoh Balint Z. , Barton Stephen , Jiang Yuxiang , Zhou Naihui , Mooney Sean D. , Friedberg Iddo , Radivojac Predrag , Greene Casey S. , Bosco Giovanni 
Published: September 2018

ABSTRACTA major bottleneck to our understanding of the genetic and molecular foundation of life lies in the ability to assign function to a gene and, subsequently, a protein. Traditional molecular and genetic experiments can provide the most reliable forms of identification, but are generally low-throughput, making such discovery and assignment a daunting task. The bottleneck has led to an increasing role for computational approaches. The Critical Assessment of Functional Annotation (CAFA) effort seeks to measure the performance of computational methods. In CAFA3 we performed selected screens, including an effort focused on long-term memory. We used homology and previous CAFA predictions to identify 29 keyDrosophilagenes, which we tested via a long-term memory screen. We identify 11 novel genes that are involved in long-term memory formation and show a high level of connectivity with previously identified learning and memory genes. Our study provides first higher-order behavioral assay and organism screen used for CAFA assessments and revealed previously uncharacterized roles of multiple genes as possible regulators of neuronal plasticity at the boundary of information acquisition and memory formation.
Population structure, genetic connectivity, and adaptation in the Olympia oyster (Ostrea lurida) along the west coast of North America
Authors: Silliman Katherine 
Published: September 2018

ABSTRACTEffective management of threatened and exploited species requires an understanding of both the genetic connectivity among populations and local adaptation. The Olympia oyster (Ostrea lurida), patchily distributed from Baja California to the central coast of Canada, has a long history of population declines due to anthropogenic stressors. For such coastal marine species, population structure could follow a continuous isolation-by-distance model, contain regional blocks of genetic similarity separated by barriers to gene flow, or be consistent with a null model of no population structure. To distinguish between these hypotheses inO. lurida, 13,444 single-nucleotide polymorphisms (SNPs) were used to characterize rangewide population structure, genetic connectivity, and adaptive divergence. Samples were collected across the species range on the west coast of North America, from southern California to Vancouver Island. A conservative approach for detecting putative loci under selection identified 288 SNPs across 129 GBS loci, which were functionally annotated and analyzed separately from the remaining neutral loci. While strong population structure was observed on a regional scale in both neutral and outlier markers, neutral markers had greater power to detect fine-scale structure. Geographic regions of reduced gene flow aligned with known marine biogeographic barriers, such as Cape Mendocino, Monterey Bay, and the currents around Cape Flattery. The outlier loci identified as under putative selection included genes involved in developmental regulation, sensory information processing, energy metabolism, immune response, and muscle contraction. These loci are excellent candidates for future research and may provide targets for genetic monitoring programs. Beyond specific applications for restoration and management of the Olympia oyster, this study lends to the growing body of evidence for both population structure and adaptive differentiation across a range of marine species exhibiting the potential for panmixia. Computational notebooks are available to facilitate reproducibility and future open-sourced research on the population structure ofO. lurida.
Miro ubiquitination is critical for efficient damage-induced PINK1/Parkin-mediated mitophagy
Authors: López-Doménech Guillermo , Covill-Cooke Christian , Howden Jack H. , Birsa Nicol , Morfill Corinne , Brandon Nicholas J. , Kittler Josef T. 
Published: September 2018

AbstractClearance of mitochondria following damage is critical for neuronal homeostasis. Here, we investigate the role of Miro proteins in mitochondrial turnover by the PINK1 / Parkin mitochondrial quality control systemin vitroandin vivo. We find that upon mitochondrial damage, Miro is promiscuously ubiquitinated on multiple lysine residues. Combined knockout of both Miro1 and Miro2 or block of Miro ubiquitination and subsequent degradation, lead to slowed mitophagy. In cultured neurons, Miro1 knockout also leads to delayed Parkin translocation onto damaged mitochondria and reduced mitochondrial clearance.In vivo, postnatal knockout of Miro1 in hippocampus and cortex disrupts mitophagy and leads to a dramatic age dependent upregulation of the mitofusin mitochondrial fusion machinery. Fluorescence imaging of aged neurons conditionally knocked out for Miro1 and expressing mitoDendra to label mitochondriain vivo, reveals that Mfn1 / Mfn2 upregulation leads to enlarged and hyperfused somatic mitochondria. Our results provide new insights into the role of Miro in PINK1/Parkin dependent mitophagy and further suggest that disruption of this regulation may be implicated in human neurological pathology.
Capturing value-based leadership in practice
Authors: Bäckström Ingela , Ingelsson Pernilla , Snyder Kristen , Hedlund Christer , Lilja Johan 
Published: September 2018

PurposeThe purpose of this paper is to present and discuss the results from the appreciative inquiry (AI)-inspired interviews to explore the underlying values held by top managers and to identify soft aspects of leadership.Design/methodology/approachTop managers were interviewed as a part of a research project with the aim to support the development of value-based leadership that integrates company values, organizational culture, customer needs and sustainable development. A structured interview guide, inspired by AI, was developed and used to pinpoint their motivation and vision of a good organization to understand the values that the managers had and to identify soft aspects of leadership. The interviews were analyzed in workshops with the whole research team and structured and visualized through affinity diagrams.FindingsThe results showed the underlying values held by top managers and identified soft aspects of leadership.Practical implicationsThe presented interview guide can be used to identify the top managers’ underlying values, and the presented results from the interviews can be used to inspire other managers and leaders to develop their leadership in their striving of good leadership and effective organizations.Originality/valueThe paper explains how to apply an AI-inspired interview guide in finding out value-based leadership and soft aspects of leadership for enhancing organizational culture.
Tribological characteristics of SCM 440 bearing steel under gas and oil lubricant in the cylinder block tractor engine
Authors: Adiyanto Okka , Pratama Pandu Sandi , Choi Wonsik 
Published: September 2018

Purpose
This paper aims to examine the friction coefficient and wear rate characteristics of SCM 440 bearing steel used in the cylinder block of a tractor engine with gas lubrication and oil lubrication.

Design/methodology/approach
Friction tests were performed using a pin-on-disc tester with loads of 2 to 10 N and sliding velocities of 0.06 to 0.34 m/s. The experiment was done with and without nitrogen, and paraffin oil lubricant was used to prevent wear during process.

Findings
The nondimensional characteristic number from the Stribeck curves indicated that the lubrication regime is hydrodynamic. As the velocity and load increased, the friction coefficient of the SCM 440 increased and greater applied load resulted in a smaller friction coefficient. The range of the friction coefficient was 0.017001 to 0.092904 with paraffin oil lubrication and 0.01614 to 0.4555 with nitrogen lubrication. Nitrogen is effective in reducing the friction coefficient of materials that are in contact and subjected to a load and velocity.

Originality/value
The experiments confirm that nitrogen is effective for reducing the friction coefficient of SCM 440 materials that are in contact with each other and subjected to a load and velocity.
Developing and deploying marketing agility in an emerging economy: the case of Blue Skies
Authors: Osei Collins , Amankwah-Amoah Joseph , Khan Zaheer , Omar Maktoba , Gutu Mavis 
Published: September 2018

PurposeIn almost every large business, there is a growing recognition of the importance of organisational agility in improving their marketing responsiveness and business survival. However, limited insights have been offered by scholars on multinational enterprises and their marketing agility in emerging markets context. The purpose of this paper is to examine the various manifestations of agility and the various strategies adopted to sustain agility by an emerging economy multinational enterprise (EMNE) which started in the late 1990s as a small firm operating within the fresh fruit and juice industry in Africa.Design/methodology/approachThe authors utilised empirical qualitative data from an emerging African economy to develop a three-stage model of how agility manifests overtime.FindingsThe authors find that successful development and deployment of international marketing agility strategy adopted by an EMNE from emerging markets hinge on building relationships, being socially responsible and being innovative in standardisation and adaptation in response to, and in anticipation of, the rapidly changing business environment.Research limitations/implicationsThis research is based on data from one organisation. Future research can consider using multiple cases from different countries to further understand marketing agility in emerging markets and when such firms internalise into developed markets.Originality/valueThis paper extends research on standardisation/adaptation debate and research on agility, to address the gap on international marketing agility. Hitherto, there was no significant research on marketing agility in emerging markets which focused on highly perishable products such as fruits. This research provides unique insight into how marketing agility could be developed, deployed and sustained in emerging African markets.