bluuebunny/crossref_metadata_2025_split huggingface dataset:
iPSC culture expansion selects against putatively actionable mutations in the mitochondrial genome
Authors: Kosanke Maike , Davenport Colin , Szepes Monika , Wiehlmann Lutz , Kohrn Tim , Dorda Marie , Gruber Jonas , Menge Kaja , Sievert Maike , Melchert Anna , Gruh Ina , Martin Ulrich 
Published: November 2020

AbstractWhile human induced pluripotent stem cells (iPSCs) offer fascinating prospects for research and clinics, evaluating their genomic stability before applications is of utmost importance. During reprogramming, clonal hiPSC lines derived from the same parental cell population were observed to harbor different mitochondrial DNA (mtDNA) variants and variant heteroplasmy levels. It is unknown to date to which extent this unequal segregation of heteroplasmies between cells arises from mosaicism in the parental cell population, selection on mutated mtDNA molecules on the cellular or organelle level, genetic drift during reduction of mtDNA during reprogramming (genetic bottleneck), or de novo mutations. We analyzed mtDNA variants in 26 clonal iPSC lines by mtDNA sequencing. We did not observe a strong bottleneck or any selection for cells with specific mtDNA variants (clonal eliteness) during reprogramming. iPSC culture expansion, however, selects against putatively actionable mutations in the mitochondrial genome that may affect mitochondrial function and cell metabolism. In contrast, heteroplasmy levels of neutral variants remained stable or increased within clonal iPSC lines during culture expansion. Interestingly, the mtDNA copy number per cell got transiently reduced during targeted differentiation of iPSCs into cardiomyocytes, but mtDNA heteroplasmy levels were not affected. Altogether, our results point towards a scenario in which intra-cellular selection on mtDNA during culture expansion, but not during reprogramming or differentiation, pivotally shapes the mutational landscape of the mitochondrial genome in iPSCs. Other mechanisms such as inter-cellular selection, genetic bottleneck, and genetic drift exert minor impact.
Disturbed intramitochondrial phosphatidic acid transport impairs cellular stress signaling
Authors: Eiyama Akinori , Aaltonen Mari J , Nolte Hendrik , Tatsuta Takashi , Langer Thomas 
Published: November 2020

AbstractLipid transfer proteins of the Ups1/PRELID1 family facilitate the transport of phospholipids across the intermembrane space of mitochondria in a lipid-specific manner. Heterodimeric complexes of yeast Ups1/Mdm35 or human PRELID1/TRIAP1 shuttle phosphatidic acid (PA) synthesized in the endoplasmic reticulum (ER) to the inner membrane, where it is converted to cardiolipin (CL), the signature phospholipid of mitochondria. Loss of Ups1/PRELID1 proteins impairs the accumulation of CL and broadly affects mitochondrial structure and function. Unexpectedly and unlike yeast cells lacking the cardiolipin synthase Crd1, Ups1 deficient yeast cells exhibit glycolytic growth defects, pointing to functions of Ups1-mediated PA transfer beyond CL synthesis. Here, we show that the disturbed intramitochondrial transport of PA inups1Δ cells leads to altered phospholipid composition of the ER membrane, independent of disturbances in CL synthesis. The impaired flux of PA into mitochondria is associated with the increased synthesis of phosphatidylcholine (PC) and a reduced phosphatidylethanolamine (PE)/PC ratio in the ER ofups1Δ cells which suppresses the unfolded protein response (UPR). Moreover, we observed inhibition of TORC1 signaling in these cells. Activation of either UPR by ER protein stress or of TORC1 signaling by disruption of its negative regulator, the SEACIT complex, increased cytosolic protein synthesis and restored glycolytic growth ofups1Δ cells. These results demonstrate that PA influx into mitochondria is required to preserve ER membrane homeostasis and that its disturbance is associated with impaired glycolytic growth and cellular stress signaling.
Memory shapes microbial populations
Authors: Gokhale Chaitanya S. , Giaimo Stefano , Remigi Philippe 
Published: November 2020

AbstractCorrect decision making is fundamental for all living organisms to thrive under environmental changes. The patterns of environmental variation and the quality of available information define the most favourable strategy among multiple options, from randomly adopting a phenotypic state to sensing and reacting to environmental cues. Memory – a phenomenon often associated with, but not restricted to, higher multicellular organisms – can help when temporal correlations exist. How does memory manifest itself in unicellular organisms? Through a combination of deterministic modelling and stochastic simulations, we describe the population-wide fitness consequences of phenotypic memory in microbial populations. Moving beyond binary switching models, our work highlights the need to consider a broader range of switching behaviours when describing microbial adaptive strategies. We show that multiple cellular states capture the empirical observations of lag time distributions, overshoots, and ultimately the phenomenon of phenotypic heterogeneity. We emphasise the implications of our work in understanding antibiotic tolerance, and, in general, survival under fluctuating environments.
The outcome of neutrophil-T cell contact differs depending on activation status of both cell types
Authors: Minns Danielle , Smith Katie J , Hardisty Gareth , Rossi Adriano , Findlay Emily Gwyer 
Published: November 2020

AbstractNeutrophils and T cells exist in close proximity in lymph nodes and inflamed tissues during health and disease. They are able to form stable interactions, with profound effects on the phenotype and function of the T cells. However, the outcome of these effects are frequently contradictory; in some systems neutrophils suppress T cell proliferation, in others they are activatory or present antigen directly. Published protocols modelling these interactionsin vitrodo not reflect the full range of interactions foundin vivo; they do not examine how activated and naïve T cells differentially respond to neutrophils, or whether de-granulating or resting neutrophils induce different outcomes. Here, we established a culture protocol to ask these questions with human T cells and autologous neutrophils. We find that resting neutrophils suppress T cell proliferation, activation and cytokine production but that de-granulating neutrophils do not, and neutrophil released intracellular contents are pro-activatory. Strikingly, we also demonstrate that T cells early in the activation process are susceptible to suppression by neutrophils, while later-stage T cells are not, and naïve T cells do not respond at all. Our protocol therefore allows nuanced analysis of the outcome of interaction of these cells and may explain contradictory results observed previously.
Aurora Kinase A proximity interactome reveals centriolar satellites as regulators of its function during primary cilium biogenesis
Authors: Arslanhan Melis D. , Rauniyar Navin , Yates John R. , Firat-Karalar Elif N. 
Published: November 2020

AbstractAurora kinase A (AURKA) is a conserved kinase that plays crucial roles in numerous cellular processes. Although AURKA overexpression is frequent in human cancers, its pleiotropic functions and complex spatiotemporal regulation have presented challenges in its therapeutic targeting. An essential step to overcome these challenges is the identification of the full range of AURKA regulators and substrates, which are often weak and transient. Previous proteomic studies were limited in monitoring dynamic and non-mitotic AURKA interactions. Here, we generated the firstin vivoproximity interactome of AURKA, which consisted of over 100 proteins involving multiple biological processes and cellular compartments. Importantly, AURKA had extensive proximity interactions to centriolar satellites, key regulators of the primary cilium. Affinity pulldown and phosphoproteomics experiments confirmed this proximity relationship at the physical level. Loss-of-function experiments defined satellites as negative regulators of AURKA activity, abundance and localization in quiescent cells. Notably, loss of satellites increased AURKA activation at the basal body and resulted in defective cilium assembly and enhanced cilium disassembly. Collectively, our results provide a powerful resource for dissecting AURKA function and regulation and uncover proteostatic regulation of AURKA by centriolar satellites as a new regulatory mechanism for its non-mitotic functions.
Fine-scale coexistence between Mediterranean mesocarnivores is mediated by spatial, temporal and trophic resource partitioning
Authors: Ferreiro-Arias Iago , Isla Jorge , Jordano Pedro , Benítez-López Ana 
Published: November 2020

AbstractThe partition of the ecological niche can enhance the coexistence of predators due to differences in how they exploit three main resources: food, space, and time, the latter being an axis that often remains unexplored.We studied niche segregation in a Mediterranean mesocarnivore community composed byVulpes vulpes, Genetta genetta, Meles melesandHerpestes ichneumon, addressing simultaneously different niche axes: the temporal, trophic and spatial axes.We assessed temporal segregation between mesopredators and prey and between potential competitors, using camera trap data between 2018-2020 in a Mediterranean landscape in Southern Spain. We deployed camera traps in 35 stations in three sites with varying vegetation cover within Doñana National Park. We further examined the spatial overlap in activity centers and trophic preferences between potential competitors using diet information from studies performed in the study area.We found an overall temporal segregation between trophic generalist species, with species showing higher temporal overlap differing in their trophic preferences and/or showing limited spatial overlap. Furthermore, we observed an overall high overlap between the activity patterns of predators and their major prey in the area (the common genet vs small mammals and the red fox vs European rabbit).Our study suggests that coexistence of the different species that compose the mesocarnivore assemblage in Mediterranean landscapes can be facilitated by subtle differences along the three main niche axes, with temporal segregation being a most pronounced mechanism. Our findings reinforce the idea that the coexistence mechanisms underlying community structure are multidimensional.
The interplay between entrepreneurial orientation and control mechanisms on decision-making and new product performance
Authors: Leckie Civilai , McDonald Heath 
Published: November 2020

PurposeThis study aims to investigate whether an organization that is entrepreneurial oriented can benefit from having a formal control structure and process in new product development (NPD). This study investigates two well-known control mechanisms in NPD, namely, stage-gate system (SGS) and project management (PM), as well as decision-making comprehensiveness (DMC), reflecting the amount of information processing and investigative activities undertaken.Design/methodology/approachSurvey data were collected from 238 Australian small and medium enterprises. Structural equation modeling was used to test the hypotheses.FindingsThe findings of this study suggest that entrepreneurial orientation (EO) directly impacts new product performance and indirectly does so through DMC. While both control mechanisms positively impact DMC, they affect the EO–DMC relationship differently. While SGS positively moderates the EO–DMC relationship, PM negatively does so. However, the use of SGS and PM enhances the effect of EO on DMC.Practical implicationsThis research provides managers with insights into the design of structure and process in NPD to support interfunctional coordination and firm strategy. The findings of this study suggest that managers should be amenable to the application of control mechanisms and DMC. The calibration of the right mix of control systems is required to ensure that EO can contribute to decision-making in the NPD process.Originality/valueOn the surface, the implementation of EO requires flexibility while the control mechanisms and extensive information processing are seen as restricted structures for NPD activities. However, rather than viewing EO and control structure as counterintuitive elements in NPD, the results suggest that appropriate use of control structure can support organizational strategy and decision-making activities, which subsequently enhance NPD outcomes.
A review of the strategic planning process in the Hong Kong Police Force
Authors: Cheung Hoi-yan , Yu Eddie 
Published: November 2020

PurposeThe purpose of this paper is to review the strategic planning process of the Hong Kong Police Force (the Force) and its outcomes for the planning cycle of 2019-2021.Design/methodology/approachBased on an insider's perspective drawn from documentation, internal reports and field observation, this study is an analysis of the five-step strategic planning process of the Force as a case study over the two-year period by using the 3-H (Heart-Head-Hand) framework and futures studies.FindingsThis study demonstrates the Force's strategic management in practice. The 3-H framework and the Six Pillars Foresight Process are found to be useful tools in strategic planning. When the Heart, Head and Hand elements are developed and integrated as a mindset during the process, they help theorise the practice and experience of police officers towards a holistic and effective strategic management. Coupled with the foresight process, the Force will be more agile and outward focused in the Volatile, Uncertain, Complex and Ambiguous (VUCA) world.Originality/valueThis is the first study to apply the 3-H framework and futures thinking in analysing the process in a police organisation in Hong Kong. While strategic planning is an important process to set directions for an organisation to move forward, this study describes the process in terms of relevant practice and theoretical concepts. It is hoped that such experience can serve as reference for practitioners in other government departments and police organisations.
Inter‐regional digital forensic knowledge management: needs, challenges, and solutions
Authors: Casey Eoghan , Zehnder Anna 
Published: November 2020

AbstractIncreasing demand for digital evidence in criminal investigations is driving decentralization of forensic capabilities closer to the crime scene. Law enforcement agencies are struggling to keep pace with technological developments, cybercrime growth, and scientific advances. In federated environments, digital forensic knowledge and practices vary widely across regions. To reduce delays, wasted resources, missed opportunities, mistakes, and misinterpretations, there is a pressing need to balance the democratization of digital forensic capabilities with knowledge management and sharing between decentralized regions. There are multiple forms of knowledge to be managed, including procedural, technical, investigative, scientific, behavioral, crime analysis, and forensic intelligence. In addition, there are multiple knowledge producers and consumers, including police investigators, digital forensic practitioners, criminal intelligence analysts, attorneys, and judges. Knowledge management becomes even more challenging when multiple interdependent regions are involved, speaking different languages. Taking all of these factors into consideration, this work presents an inter‐regional knowledge management solution for improving the quality, consistency, reliability, efficiency, cost‐effectiveness, and return on investment of digital forensic capabilities. The basis of this work is a community‐driven initiative of Swiss regional police authorities. Interviews were conducted with 15 digital forensic units to determine their current knowledge management practices and needs. The results were then generalized into a prioritized set of requirements for inter‐regional digital forensic knowledge management that may be applicable in other countries. These requirements were used to evaluate knowledge management platforms, and one was selected. Implementation, operations, and maintenance challenges of an inter‐regional digital forensic knowledge management platform are discussed.
CLP gene family, a new gene family of Cotesia vestalis bracovirus inhibits melanization of Plutella xylostella hemolymph
Authors: Wang Ze‐Hua , Zhou Yue‐Nan , Ye Xi‐Qian , Wu Xiao‐Tong , Yang Pei , Shi Min , Huang Jian‐Hua , Chen Xue‐Xin 
Published: November 2020

AbstractPolydnaviruses (PDVs) are obligatory symbionts of parasitoid wasps and play an important role in suppressing host immune defenses. Although PDV genes that inhibit host melanization are known in Microplitis bracovirus, the functional homologs in Cotesia bracoviruses remain unknown. Here, we find that Cotesia vestalis bracovirus (CvBV) can inhibit hemolymph melanization of its host, Plutella xylostella larvae, during the early stages of parasitization, and that overexpression of highly expressed CvBV genes reduced host phenoloxidase activity. Furthermore, CvBV‐7‐1 in particular reduced host phenoloxidase activity within 12 h, and the injection of anti‐CvBV‐7‐1 antibody increased the melanization of parasitized host larvae. Further analyses showed that CvBV‐7‐1 and three homologs from other Cotesia bracoviruses possessed a C‐terminal leucine/isoleucine‐rich region and had a similar function in inhibiting melanization. Therefore, a new family of bracovirus genes was proposed and named as C‐terminal Leucine/isoleucine‐rich Protein (CLP). Ectopic expression of CvBV‐7‐1 in Drosophila hemocytes increased susceptibility to bacterial repression of melanization and reduced the melanotic encapsulation of parasitized D. melanogaster by the parasitoid Leptopilina boulardi. The formation rate of wasp pupae and the eclosion rate of C. vestalis were affected when the function of CvBV‐7‐1 was blocked. Our findings suggest that CLP genes from Cotesia bracoviruses encoded proteins that contain a C‐terminal leucine/isoleucine‐rich region and function as melanization inhibitors during the early stage of parasitization, which is important for successful parasitization.
Ruminal and post‐ruminal barley grain digestion and starch granule morphology under three heat methods
Authors: Shirmohammadi Shahram , Taghizadeh Akbar , Hosseinkhani Ali , Moghaddam Gholam Ali , Salem Abdelfattah Z. M. , Pliego Alberto Barbabosa 
Published: November 2020

AbstractThis study was designed to investigate the effect of three heating methods on the ruminal and post‐ruminal nutrient degradability and starch granule morphology of barley grain (BG ‐ Hordeum vulgare). Treatments were Control (CG): without processing; Roasted (RG): roasted BG for 300 s at 130°C; Microwaved (MG): irradiated BG for 120 s at 1200 W; and Steam flaked (SG): BG misted for 30 min under steam flow of boiling water and flaked. Gas production and in situ techniques were used to evaluate the ruminal degradability of treatments, and a modified three‐step method was utilised to estimate the total‐tract digestibility. Morphological changes of starch granules were determined by field emission scanning electron microscopy (FESEM). Ruminal gas production and dry matter disappearance were increased (p < .05) in SG vs. CG. Heat processing had different effects on starch and crude protein degradability; however, starch degradability increased (p < .05) from CG to SG. Post‐ruminal disappearance of dry matter in CG was greater (p < .05) than other treatments. These results validated by FESEM images that explained high barley grain degradability in relation to the number of holes on the surface of starch granules. Heat processing can enhance ruminal and post‐ruminal utilisation efficiency of barley grain, resulting in improvement of total‐tract digestibility.
Cannabis use‐related working memory deficit mediated by lower left hippocampal volume
Authors: Paul Subhadip , Bhattacharyya Sagnik 
Published: November 2020

AbstractThe association between cannabis exposure and working memory impairment and its neural substrates remain unclear. In this cross‐sectional observational study, we investigated this by examining the relationship between frequency of exposure to cannabis, working memory performance and regional brain volumes and tested whether lower volumes of cortical and subcortical structures mediate the association between cannabis exposure and working memory deficit using the Human Connectome Project data from 234 individuals with self‐reported cannabis exposure and 174 individuals unexposed to cannabis. We tested the relationship between self‐reported frequency of cannabis exposure and list‐sorting working memory task performance (total number of correct responses), between T1 weighted MRI‐derived regional grey‐matter volumes and working memory task performance as well as between frequency of cannabis exposure and brain volumes after controlling for potential confounders. Finally, mediation analysis was carried out to test whether deficit in working memory performance associated with cannabis use was mediated by its association with lower grey‐matter volume. Participants who reported higher frequency of cannabis use tended to have lower number of correct responses in the list‐sorting working memory task and lower bilateral hippocampal volumes. Association between severity of cannabis exposure as indexed by frequency of cannabis use and impairment in working memory was mediated by lower left hippocampal volume in cannabis users. We report evidence in support of the left hippocampus volume‐mediated working memory impairment associated with recreational cannabis exposure. Future studies employing prospective longitudinal design are necessary to examine the cause–effect relationships of cannabis exposure on working memory and brain volumes.
Antibody microarray analysis of amniotic fluid proteins associated with subsequent ruptured membranes in women with threatened preterm labor
Authors: Hong Subeen , Park Yehyon , Kim Yu Mi , Lee Ji Eun , Kim Hyeon Ji , Park Kyo Hoon 
Published: November 2020

AbstractProblemWe aimed to identify amniotic fluid (AF) proteins associated with the subsequent rupture of membranes (ROM) occurring in the absence of active labor in women with threatened preterm labor (PTL) using an antibody microarray.Method of the studyThis retrospective cohort study included 183 singleton pregnant women with PTL (24–33 weeks) who underwent amniocentesis. A nested case‐control study was conducted using AF samples from 20 women with subsequent ROM within 7 days of sampling (case subjects) and 20 gestational age‐matched women with term delivery (TD) without ROM (control subjects), via protein‐antibody microarray analysis. Seven candidate proteins of interest were validated via ELISA in the total cohort.ResultsSeventeen proteins displayed significant intergroup differences. ELISA validation confirmed that the levels of EN‐RAGE, Fas, IL‐8, IP‐10, MMP‐8, and MMP‐9 were significantly higher, whereas IGFBP‐3 levels were significantly lower in the AF of women with subsequent ROM within 7 days of sampling than in that of women with TD without ROM. Moreover, the time interval from sampling to membrane rupture was significantly correlated with the expression levels of AF proteins, except for IL‐10.ConclusionUsing an antibody microarray, we identified various inflammatory, angiogenic, matrix‐degrading, and apoptosis‐related proteins in the AF that were associated with subsequent ROM occurring in the absence of active labor in women with threatened PTL. These findings provide novel insights into the molecular mechanisms underlying membrane rupture without active labor in threatened PTL.