bluuebunny/crossref_metadata_2025_split huggingface dataset:
The evolutionary origins of extreme halophilic Archaeal lineages
Authors: Feng Yutian , Neri Uri , Gosselin Sean , Louyakis Artemis S. , Thane Papke R. , Gophna Uri , Peter Gogarten J. 
Published: December 2019

AbstractInterest and controversy surrounding the evolutionary origins of extremely halophilic Archaea has increased in recent years, due to the discovery and characterization of the Nanohaloarchaea and the Methanonatronarchaeia. Initial attempts in explaining the evolutionary placement of the two new lineages in relation to the classical Halobacteria (also referred to as Haloarchaea) resulted in hypotheses that imply the new groups share a common ancestor with the Haloarchaea. However, more recent analyses have led to a shift: the Nanohaloarchaea have been largely accepted as being a member of the DPANN superphylum, outside of the euryarchaeota; while the Methanonatronarchaeia have been placed near the base of the Methanotecta (composed of the class II methanogens, the Halobacteriales, and Archaeoglobales). These opposing hypotheses have far-reaching implications on the concepts of convergent evolution (unrelated groups evolve similar strategies for survival), genome reduction, and gene transfer. In this work, we attempt to resolve these conflicts with phylogenetic and phylogenomic data. We provide a robust taxonomic sampling of Archaeal genomes that spans the Asgardarchaea, TACK Group, euryarchaeota, and the DPANN superphylum. In addition, we assembled draft genomes from seven new representatives of the Nanohaloarchaea from distinct geographic locations. Phylogenies derived from these data imply that the highly conserved ATP synthase catalytic/non-catalytic subunits of Nanohaloarchaea share a sisterhood relationship with the Haloarchaea. We also employ a novel gene family distance clustering strategy which shows this sisterhood relationship is not likely the result of a recent gene transfer. In addition, we present and evaluate data that argue for and against the monophyly of the DPANN superphylum, in particular, the inclusion of the Nanohaloarchaea in DPANN.Significance StatementMany recent analyses have considered large groups of Bacteria and Archaea composed exclusively of environmentally assembled genomes as deep branching taxonomic groups in their respective domains. These groups display characteristics distinct from other members of their domain, which can attract unrelated lineages into those groups. This manuscript evaluates the case of the Nanohaloarchaea, and their inclusion in the DPANN Archaea, through careful analysis of the genes that compose the core of the Nanohaloarchaea. Analyses without inspection of the genes that compose a phylogenomic marker set increases the potential for the inclusion of artifacts and confuses the tree/web of life. Due to horizontal gene transfer and phylogenetic reconstruction artifacts, the placement of divergent archaeal classes into larger groups remains uncertain.
Peripheral nerve resident macrophages are microglia-like cells with tissue-specific programming
Authors: Wang Peter L , Yim Aldrin KY , Kim Kiwook , Avey Denis , Czepielewski Rafael S. , Colonna Marco , Milbrandt Jeffrey , Randolph Gwendalyn J ,   The Immunological Genome Project
Published: December 2019

SummaryWhereas microglia are recognized as fundamental players in central nervous system (CNS) development and function, much less is known about macrophages of the peripheral nervous system (PNS). Here we show that self-maintaining PNS macrophages share unique features with CNS microglia. By comparing gene expression across neural and conventional tissue-resident macrophages, we identified transcripts that were shared among neural resident macrophages as well as selectively enriched in PNS macrophages. Remarkably, PNS macrophages constitutively expressed genes previously identified to be upregulated by activated microglia during aging or neurodegeneration. Several microglial activation-associated and PNS macrophage-enriched genes were also expressed in spinal cord microglia at steady state. While PNS macrophages arose from both embryonic and hematopoietic precursors, their expression of activation-associated genes did not differ by ontogeny. Collectively, these data uncover shared and unique features between neural resident macrophages and emphasize the role of nerve environment for shaping PNS macrophage identity.
Geometry of Ranked Nearest Neighbour Interchange Space of Phylogenetic Trees
Authors: Collienne Lena , Elmes Kieran , Fischer Mareike , Bryant David , Gavryushkin Alex 
Published: December 2019

AbstractIn this paper we study the graph of ranked phylogenetic trees where the adjacency relation is given by a local rearrangement of the tree structure. Our work is motivated by tree inference algorithms, such as maximum likelihood and Markov Chain Monte Carlo methods, where the geometry of the search space plays a central role for efficiency and practicality of optimisation and sampling. We hence focus on understanding the geometry of the space (graph) of ranked trees, the so-called ranked nearest neighbour interchange (RNNI) graph. We find the radius and diameter of the space exactly, improving the best previously known estimates. Since the RNNI graph is a generalisation of the classical nearest neighbour interchange (NNI) graph to ranked phylogenetic trees, we compare geometric and algorithmic properties of the two graphs. Surprisingly, we discover that both geometric and algorithmic properties of RNNI and NNI are quite different. For example, we establish convexity of certain natural subspaces in RNNI which are not convex is NNI. Our results suggest that the complexity of computing distances in the two graphs is different.
Persistence as an optimal hedging strategy
Authors: Browning Alexander P , Sharp Jesse A , Mapder Tarunendu , Baker Christopher M , Burrage Kevin , Simpson Matthew J 
Published: December 2019

AbstractBacteria invest in a slow-growing subpopulation, called persisters, to ensure survival in the face of uncertainty. This hedging strategy is remarkably similar to financial hedging, where diversifying an investment portfolio protects against economic uncertainty. We provide a new theoretical foundation for understanding cellular hedging by unifying the study of biological population dynamics and the mathematics of financial risk management through optimal control theory. Motivated by the widely accepted role of volatility in the emergence of persistence, we consider several novel models of environmental volatility described by continuous-time stochastic processes. This allows us to study an emergent cellular hedging strategy that maximizes the expected per-capita growth rate of the population. Analytical and simulation results probe the optimal persister strategy, revealing results that are consistent with experimental observations and suggest at new opportunities for experimental investigation and design. Overall, we provide a new way of conceptualising and modelling cellular decision-making in volatile environments by explicitly unifying theory from mathematical biology and finance.
Enzyme capacity-based genome scale modelling of CHO cells
Authors: Yeo Hock Chuan , Hong Jongkwang , Lakshmanan Meiyappan , Lee Dong-Yup 
Published: December 2019

ABSTRACTChinese hamster ovary (CHO) cells are most prevalently used for producing recombinant therapeutics in biomanufacturing. Recently, more rational and systems approaches have been increasingly exploited to identify key metabolic bottlenecks and engineering targets for cell line engineering and process development based on the CHO genome-scale metabolic model which mechanistically characterizes cell culture behaviours. However, it is still challenging to quantify plausible intracellular fluxes and discern metabolic pathway usages considering various clonal traits and bioprocessing conditions. Thus, we newly incorporated enzyme kinetic information into the updated CHO genome-scale model (iCHO2291) and added enzyme capacity constraints within the flux balance analysis framework (ecFBA) to significantly reduce the flux variability in biologically meaningful manner, as such improving the accuracy of intracellular flux prediction. Interestingly, ecFBA could capture the overflow metabolism under the glucose excess condition where the usage of oxidative phosphorylation is limited by the enzyme capacity. In addition, its applicability was successfully demonstrated via a case study where the clone- and media-specific lactate metabolism was deciphered, suggesting that the lactate-pyruvate cycling could be beneficial for CHO cells to efficiently utilize the mitochondrial redox capacity. In summary,iCHO2296 with ecFBA can be used to confidently elucidate cell cultures and effectively identify key engineering targets, thus guiding bioprocess optimization and cell engineering efforts as a part of digital twin model for advanced biomanufacturing in future.
Temporal specificity and heterogeneity of the fly immune cells’ transcriptional landscape
Authors: Cattenoz Pierre B. , Sakr Rosy , Pavlidaki Alexia , Delaporte Claude , Riba Andrea , Molina Nacho , Hariharan Nivedita , Mukherjee Tina , Giangrande Angela 
Published: December 2019

SummaryImmune cells provide defense against the non-self, however recent data suggest roles well beyond innate immunity, in processes as diverse as development, metabolism and tumor progression. Nevertheless, the heterogeneity of these cells remains an open question. Using bulk RNA sequencing we find that theDrosophilaimmune cells (hemocytes) display distinct features in the embryo, a closed and rapidly developing system, compared to the larva, which is exposed to environmental and metabolic challenges. Through single cell RNA sequencing we identify fourteen hemocyte clusters present in unchallenged larvae and associated with distinct cellular processes e.g. proliferation, phagocytosis, metabolic homeostasis and humoral response. Finally, we characterize the changes occurring in the hemocyte clusters upon wasp infestation that triggers the differentiation of a novel cell type, the lamellocyte. This first molecular atlas provides precious insights and paves the way to study the biology of theDrosophilaimmune cells in physiological and pathological conditions.
Perceptual weighting of binaural lateralization cues across frequency bands
Authors: Ahrens Axel , Joshi Suyash Narendra , Epp Bastian 
Published: December 2019

AbstractThe auditory system uses interaural time- and level differences (ITD and ILD) as cues to localize and lateralize sounds. The availability of ITDs and ILDs in the auditory system is limited by neural phase-locking and by the head size, respectively. Although the frequency-specific limitations are well known, the relative contribution of ITDs and ILDs in individual frequency bands in broad-band stimuli are unknown. To determine these relative contributions, or spectral weights, listeners were asked to judge the lateralization of stimuli consisting of eleven simultaneously presented 1-ERB-wide noise bands centered between 442 Hz and 5544 Hz and separated by 1-ERB-wide gaps. Interaural disparities were applied to each noise band and were roved independently on every trial. The weights were obtained using a multiple linear regression analysis. In a second experiment the effect of temporal context on the spectral weights was investigated. Ten of the noise bands were used as pre- and postcursors and listeners were asked to lateralize the stimuli. Results show that only the lowest- or highest frequency band received highest weight for ITD and ILD, respectively. Temporal context led to significantly enhanced weights given to the band without the pre- and postcursor. The weight enhancement could only be observed at low frequencies, when determined with ITD cues and for low and high frequencies for ILDs. Hence, the auditory system seems to be able to change the spectral weighting of binaural information depending on the information content.PACS43.64.-q·43.64.+r·87.19.lt·43.66.-x·43.66.+y·43.64.Bt
The Low-Cost, Semi-Automated Shifter Microscope Stage Transforms Speed and Robustness of Manual Protein Crystal Harvesting
Authors: Wright Nathan David , Collins Patrick , Talon Romain , Nelson Elliot , Koekemoer Lizbé , Ye Mingda , Nowak Radosław , Newman Joseph , Ng Jia Tsing , Mitrovich Nick , Wiggers Helton , von Delft Frank 
Published: December 2019

AbstractDespite the tremendous success of x-ray cryocrystallography over recent decades, the transfer of crystals from the drops where they grow to diffractometer sample mounts, remains a manual process in almost all laboratories. Here we describe the Shifter, a semi-automated microscope stage that offers an accessible and scalable approach to crystal mounting that exploits on the strengths of both humans and machines. The Shifter control software manoeuvres sample drops beneath a hole in a clear protective cover, for human mounting under a microscope. By allowing complete removal of film seals the tedium of cutting or removing the seal is eliminated. The control software also automatically captures experimental annotations for uploading to the user’s data repository, removing the overhead of manual documentation. The Shifter facilitates mounting rates of 100-240 crystals per hour, in a more controlled process than manual mounting, which greatly extends the lifetime of drops and thus allows for a dramatic increase in the number of crystals retrievable from any given drop, without loss of X-ray diffraction quality. In 2015 the first in a series of three Shifter devices was deployed as part of the XChem fragment screening facility at Diamond Light Source (DLS), where they have since facilitated the mounting of over 100,000 crystals. The Shifter was engineered to be simple, allowing for a low-cost device to be commercialised and thus potentially transformative as many research initiatives as possible.SynopsisA motorised X/Y microscope stage is presented that combines human fine motor control with machine automation and automated experiment documentation, to transform productivity in protein crystal harvesting.
Inferring the Demographic History of Inbred Species From Genome-Wide SNP Frequency Data
Authors: Blischak Paul D. , Barker Michael S. , Gutenkunst Ryan N. 
Published: December 2019

AbstractDemographic inference using the site frequency spectrum (SFS) is a common way to understand historical events affecting genetic variation. However, most methods for estimating demography from the SFS assume random mating within populations, precluding these types of analyses in inbred populations. To address this issue, we developed a model for the expected SFS that includes inbreeding by parameterizing individual genotypes using beta-binomial distributions. We then take the convolution of these genotype probabilities to calculate the expected frequency of biallelic variants in the population. Using simulations, we evaluated the model’s ability to co-estimate demography and inbreeding using one- and two-population models across a range of inbreeding levels. We also applied our method to two empirical examples, American pumas (Puma concolor) and domesticated cabbage (Brassica oleraceavar.capitata), inferring models both with and without inbreeding to compare parameter estimates and model fit. Our simulations showed that we are able to accurately co-estimate demographic parameters and inbreeding even for highly inbred populations (F= 0.9). In contrast, failing to include inbreeding generally resulted in inaccurate parameter estimates in simulated data and led to poor model fit in our empirical analyses. These results show that inbreeding can have a strong effect on demographic inference, a pattern that was especially noticeable for parameters involving changes in population size. Given the importance of these estimates for informing practices in conservation, agriculture, and elsewhere, our method provides an important advancement for accurately estimating the demographic histories of these species.
A neuronal thermostat controls membrane fluidity inC. elegans
Authors: Chauve L , Murdoch S , Masoudzadeh F. , Hodge F. , Lopez-Clavijo A. , Okkenhaug H. , West G. , Segonds-Pichon A. , Wingett S. , Wakelam M. , Kienberger K. , Kleigrewe K. , Casanueva O 
Published: December 2019

SummaryAn organisms’ ability to adapt to heat can be key to its survival. Cells adapt to temperature shifts by adjusting lipid desaturation levels and the fluidity of membranes in a process that is thought to be controlled cell autonomously. We have discovered that subtle, step-wise increments in ambient temperature can lead to the conserved heat shock response being activated in head neurons ofC. elegans. This response is exactly opposite to the expression of the lipid desaturase FAT-7 in the worm’s gut. We find that the over-expression of the master regulator of this response, Hsf-1, in head neurons, causes extensive fat remodeling to occur across tissues. These changes include a decrease in FAT-7 expression and a shift in the levels of unsaturated fatty acids in the plasma membrane. These shifts are in line with membrane fluidity requirements to survive in warmer temperatures. We have identified that the cGMP receptor, TAX-2/TAX-4, as well as TGF-β/BMP signaling, as key players in the transmission of neuronal stress to peripheral tissues. This is the first study to suggest that a thermostat-based mechanism can centrally coordinate membrane fluidity in response to warm temperatures across tissues in multicellular animals.
A New Ultradian Rhythm Linked to Protein Degradation and Synthesis in Mammalian Cells
Authors: Ghenim L. , Allier C. , Obeid P. , Hervé L. , Fortin J-Y. , Balakirev M. , Gidrol X. 
Published: December 2019

AbstractWe describe a new ultradian rhythm that occurs during the interphase of the cell cycle in a wide range of mammalian cells, including both primary and transformed cells. The rhythm was detected by holographic lens-free microscopy that follows the individual histories of the dry mass of thousands of live cells simultaneously, each at a resolution of five minutes. Importantly, the rhythm was observed in inherently heterogeneous cell populations, thus eliminating synchronization and labeling bias. The rhythm is independent of circadian rhythm, has a period of 4 hours and is temperature-compensated. We demonstrated that the 4 hr rhythm is suppressed by proteostasis disruptors and is detected only in proliferating cells, suggesting that it represents the periodic dynamics of protein mass in growing cells.Brief teaserWe have revealed a 4 hr rhythm in cell dry mass dynamics that seems to be general in proliferating mammalian cells.
Biasing HER4 Tyrosine Kinase Signaling with Antibodies: Induction of Cell Death by Antibody-Dependent HER4 Intracellular Domain Trafficking
Authors: Lanotte Romain , Garambois Véronique , Gaborit Nadège , Larbouret Christel , Musnier Astrid , Martineau Pierre , Pèlegrin André , Chardès Thierry 
Published: December 2019

AbstractHER4 isoforms have oncogenic or tumor suppressor functions depending on their susceptibility to proteolytic cleavage and HER4 Intracellular Domain (4ICD) translocation. Here, we report that the NRG1 tumor suppressor mechanism through the HER4 JMa/CYT1 isoform can be mimicked by the agonist anti-HER4 antibody C6. NRG1 induced cleavage of poly(ADP-ribose) polymerase (PARP) and sub-G1 DNA fragmentation, and also reduced the metabolic activity of HER3-negative/HER4-positive cervical (C-33A) and ovarian (COV318) cancer cells. This effect was confirmed in HER4 JMa/CYT1-, but not JMa/CYT2-transfected BT549 triple-negative breast cancer cells. NRG1 favored 4ICD cleavage and retention in mitochondria in JMa/CYT1-transfected BT549 cells, leading to Reactive Oxygen Species (ROS) production through mitochondrial depolarization. Similarly, the anti-HER4 antibody C6, which binds to a conformational epitope located on aa 575-592 and 605-620 of HER4 domain IV, induced 4ICD cleavage and retention in mitochondria, and mimicked NRG1-mediated effects on PARP cleavage, ROS production, and mitochondrial membrane depolarization in cancer cells.In vivo, C6 reduced growth of COV434 and HCC187 tumor cell xenografts in nude mice. Biasing 4ICD trafficking to mitochondria with anti-HER4 antibodies to mimic NRG1 suppressor functions could be an alternative anti-cancer strategy.
The role of the anterior intraparietal sulcus and the lateral occipital cortex in fingertip force scaling and weight perception during object lifting
Authors: van Polanen Vonne , Rens Guy , Davare Marco 
Published: December 2019

ABSTRACTSkillful object lifting relies on scaling fingertip forces according to the object’s weight. When no visual cues about weight are available, force planning relies on recent lifting experience. Recently, we showed that previously lifted objects also affect weight estimation, as objects are perceived to be lighter when lifted after heavy objects compared to light ones. Here, we investigated the underlying neural mechanisms mediating these effects. We asked participants to lift objects and estimate their weight. Simultaneously, we applied transcranial magnetic stimulation (TMS) during the dynamic loading or static holding phase. Two subject groups received TMS of either the anterior intraparietal sulcus (aIPS) or lateral occipital area (LO), known to be important nodes in object grasping and perception. We hypothesized that TMS-induced disruption of aIPS and LO would alter force scaling and weight perception. Contrary to our hypothesis, we did not find effects of aIPS or LO stimulation on force planning or weight estimation caused by previous lifting experience. However, we found that TMS of both areas increased grip forces, but only when applied during dynamic loading, and decreased weight estimation, but only when applied during static holding, suggesting time-specific effects. Interestingly, our results also indicate that TMS over LO, but not aIPS, affected load force scaling specifically for heavy objects, which further indicates that planning of load and grip forces might be controlled differently. These findings provide new insights on the interactions between brain networks mediating action and perception during object manipulation.NEW & NOTEWORTHYThis article provides new insights into the neural mechanisms underlying object lifting and perception. Using transcranial magnetic stimulation during object lifting, we show that effects of previous experience on force scaling and weight perception are not mediated by the anterior intraparietal sulcus nor the lateral occipital cortex (LO). In contrast, we highlight a unique role for LO in load force scaling, suggesting different brain processes for grip and load force scaling in object manipulation.