bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mobility in Osteogenesis Imperfecta: A Multicenter North American Study
Authors: Kruger Karen M. , Caudill Angela , Rodriguez Celin Mercedes , Nagamani Sandesh CS , Shapiro Jay R , Steiner Robert D , Bober Michael B , Hart Tracy , Cuthbertson M.S. David , Krischer Jeff , Byers Peter H , Durigova Michaela , Glorieux Francis H , Rauch Frank , Sutton V Reid , Lee Brendan , Rush Eric T , Smith Peter A. , Harris Gerald F. 
Published: July 2018

BackgroundOsteogenesis imperfecta (OI) is a genetic connective tissue disorder characterized by increased bone fragility and recurrent fractures. The phenotypic severity of OI has a significant influence on the ability to walk but little is known about the ambulatory characteristics, strength, or functional abilities in individuals with OI, especially in the more severe forms. To advance clinical research in OI, the Linked Clinical Research Centers, network of clinical centers in North America with significant experience in treating patients with OI, was established in 2009. The purpose of this work was to characterize mobility in OI using standard clinical assessment tools. and determine if any patient characteristics could be used to predict mobility outcomes.MethodsData were collected at five clinical sites and included age, gender, ethnicity, height, weight, use of assistive device, and bisphosphonate use and mobility metrics (age at first walk, Gillette Functional Assessment Questionnaire, Functional Mobility Scale, and distance walked in the 6 minute walk test). Linear mixed models were developed to explore the relationships between subject demographics and mobility metrics.ResultsThe study identified 491 individuals age 3 and older. In general, the results showed minor limitations in the type I group while the more severe types showed more significant limitations in all mobility metrics analyzed. Height and weight were shown to be the most significant predictors of mobility metrics. Relationships with mobility and bisphosphonates varied with OI type and whether oral or IV was used.ConclusionThis paper is the most comprehensive report of mobility in individuals with OI to date. These results are vital to understanding the mobility limitations of specific types of OI and beneficial when developing rehabilitation protocols for this population. It is important for physicians, patients, and caregivers to gain insight into severity and classification of the disease and the influence of disease-related characteristics on the prognosis for mobility.
Disentangling the Role of Face Typicality and Affect in Emotional Face Processing: Self-reported and Electrophysiological Evidence
Authors: Pereira Mariana R. , Paiva Tiago O. , Barbosa Fernando , Almeida Pedro R. , Martins Eva C. , Baldeweg Torsten , de Haan Michelle , Ferreira-Santos Fernando 
Published: July 2018

AbstractTypicality, or averageness, is one of the key features that influences face evaluation, but the role of this property in the perception of facial expressions of emotions is still not fully understood. Typical faces are usually considered more pleasant and trustworthy, and neuroimaging results suggest typicality modulates amygdala and fusiform activation, influencing face perception. At the same time, there is evidence that arousal is a key affective feature that modulates neural reactivity to emotional expressions. In this sense, it remains unclear whether the neural effects of typicality depend on altered perceptions of affect from facial expressions or if the effects of typicality and affect independently modulate face processing. The goal of this work was to dissociate the effects of typicality and affective properties, namely valence and arousal, in electrophysiological responses and self-reported ratings across several facial expressions of emotion. Two ERP components relevant for face processing were measured, the N170 and Vertex Positive Potential (VPP), complemented by subjective ratings of typicality, valence, and arousal, in a sample of 30 healthy young adults (21 female). The results point out to a modulation of the electrophysiological responses by arousal, regardless of the typicality or valence properties of the face. These findings suggest that previous findings of neural responses to typicality may be better explained by accounting for the subjective perception of arousal in facial expressions.
Targeting Wnt Signaling To Overcome PARP Inhibitor Resistance
Authors: Yamamoto Tomomi M. , McMellen Alexandra , Watson Zachary L. , Aguilera Jennifer , Sikora Matthew J. , Ferguson Rebecca , Nurmemmedov Elmar , Thakar Tanay , Moldovan George-Lucian , Kim Hyunmin , Cittelly Diana M. , Wilson Heidi , Behbakht Kian , Bitler Benjamin G. 
Published: July 2018

ABSTRACTEpithelial ovarian cancer (EOC) has one of the highest deaths to incidence ratios. High grade serous ovarian carcinoma (HGSOC) is the most common and deadliest EOC histotype because of the lack of secondary therapeutic options following debulking surgery and platinum/taxane-based chemotherapies. For recurrent chemosensitive HGSOC, poly(ADP)-ribose polymerase inhibitors (PARPi; olaparib, rucaparib, or niraparib) represent an emerging treatment strategy. While PARPi are most effective in homologous recombination DNA repair-deficient (HRD) HGSOCs, more recent studies have observed a significant clinical benefit in non-HRD HGSOCs. However, all HGSOC patients are likely to acquire resistance to PARPi. Therefore, there is an urgent clinical need to better understand PARPi resistance, and to introduce novel combinatorial therapies to overcome PARPi resistance and extend HGSOC disease-free intervals. Utilizing a two BRCA2-mutated and one BRCA-wildtype HGSOC cell lines that are olaparib sensitive, we established resistant cells. Transcriptome analysis of the matched olaparib-sensitive versus resistant cells did not detect BRCA2 reversion mutations, but revealed activation of Wnt/TCF signaling pathway, as TCF transcriptional activity was significantly increased in PARPi-resistant cells. In parallel, forced activation of Wnt signaling in PARPi-sensitive cells via WNT3A stimulation reduced response to PARPi. In a recurrent-HGSOC PARPi insensitive patient-derived xenograft model there was an increase in a Wnt/TCF transcriptional target. PARPi resistant cells were sensitive to inhibition of Wnt signaling using the FDA-approved compound, pyrvinium pamoate, which has been shown to inhibit Wnt signaling. We observed that combining pyrvinium pamoate with olaparib resulted in a significant decrease in tumor burden and number of tumor nodules. This study demonstrates that Wnt signaling can mediate PARPi resistance in HGSOC and provides a clinical rationale for combining PARPi and Wnt inhibitors.
Proximal recolonization by self-renewing microglia reestablishes microglial homeostasis in the adult mouse brain
Authors: Zhan Lihong , Krabbe Grietje , Du Fei , Jones Ian , Reichert Meredith C. , Telpoukhovskaia Maria , Kodama Lay , Wang Chao , Cho Seo-hyun , Sayed Faten , Li Yaqiao , Le David , Zhou Yungui , Shen Yin , West Brian , Gan Li 
Published: July 2018

AbstractMicroglia are resident immune cells that play critical roles in maintaining normal physiology of the central nervous system. Remarkably, microglia have intrinsic capacity to replenish after being acutely ablated. However, the underlying mechanisms that drive such microglial restoration remain elusive. Here, we removed microglia via CSF1R inhibitor PLX5622 and characterized repopulation both spatially and temporally. We also investigated the cellular origin of repopulated microglia and report that microglia are replenished via self-renewal, with little contribution from non-microglial lineage progenitors, including nestin+ progenitors and the circulating myeloid population. Interestingly, spatial analyses with multi-color labeling reveal that newborn microglia recolonize the parenchyma by forming distinctive clusters that maintain stable territorial boundaries over time, indicating proximal expansion nature of adult microgliogenesis and stability of microglia tiling. Temporal transcriptome profiling from newborn microglia at different repopulation stages revealed that the adult newborn microglia gradually regain steady-state maturity from an immature state that is reminiscent of neonatal stage and follow a series of maturation programs that include NF-κB activation, interferon immune activation and apoptosis, etc. Importantly, we show that the restoration of microglial homeostatic density requires NF-κB signaling as well as apoptotic egress of excessive cells. In summary, our study reports key events that take place from microgliogenesis to homeostasis re-establishment.
Topological segregation of functional networks increases in developing brains
Authors: He Wei , Sowman Paul F. , Brock Jon , Etchell Andrew C. , Stam Cornelis J. , Hillebrand Arjan 
Published: July 2018

AbstractA growing literature conceptualises human brain development from a network perspective, but it remains unknown how functional brain networks are refined during the preschool years. The extant literature diverges in its characterisation of functional network development, with little agreement between haemodynamic- and electrophysiology-based measures. In children aged from 4 to 12 years, as well as adults, age appropriate magnetoencephalography was used to estimate unbiased network topology, using minimum spanning tree (MST) constructed from phase synchrony between beamformer-reconstructed time-series. During childhood, network topology becomes increasingly segregated, while cortical regions decrease in centrality. We propose a heuristic MST model, in which a clear developmental trajectory for the emergence of complex brain networks is delineated. Our results resolve topological reorganisation of functional networks across temporal and special scales in youth and fill a gap in the literature regarding neurophysiological mechanisms of functional brain maturation during the preschool years.
Out of Africa by spontaneous migration waves
Authors: Bons Paul D. , Bauer Catherine C. , Bocherens Hervé , de Riese Tamara , Drucker Dorothée G. , Francken Michael , Menéndez Lumila , Uhl Alexandra , van Milligen Boudewijn P. , Wiβing Christoph 
Published: July 2018

AbstractHominin evolution is characterized by progressive regional differentiation, as well as migration waves, leading to anatomically modern humans that are assumed to have emerged in Africa and spread over the whole world. Why or whether Africa was the source region of modern humans and what caused their spread remains subject of ongoing debate. We present a spatially explicit, stochastic numerical model that includes ongoing mutations, demic diffusion, assortative mating and migration waves. Diffusion and assortative mating alone result in a structured population with relatively homogeneous regions bound by sharp clines. The addition of migration waves results in a power-law distribution of wave areas: for every large wave, many more small waves are expected to occur. This suggests that one or more out-of-Africa migrations would probably have been accompanied by numerous smaller migration waves across the world. The migration waves are considered “spontaneous”, as the current model excludes environmental or other factors. Large waves preferentially emanate from the central areas of large, compact inhabited areas. During the Pleistocene, Africa was the largest such area most of the time, making Africa the statistically most likely origin of anatomically modern humans, without a need to invoke additional environmental or ecological drivers.
The cap size and shape of Arabidopsis thaliana primary roots impact the root responses to an increase in medium strength
Authors: Roué J. , Chauvet H. , Brunel-Michac N. , Bizet F. , Moulia B. , Badel E. , Legué V. 
Published: July 2018

AbstractDuring root progression in soil, root cap cells are the first to encounter obstacles. The root cap is known to sense environmental cues, making it a relevant candidate for a mechanosensing site. An original two-layer medium was developed in order to study root responses to growth medium strength and the importance of the root cap in the establishment of these responses. Root growth and trajectory of primary roots of Arabidopsis thaliana seedlings were investigated using in vivo image analysis. After contact with the harder layer, the root either penetrated it or underwent rapid curvature, enabling reorientation of the root primary growth. The role of the root cap in tip reorientation was investigated by analyzing the responses of Arabidopsis mutant roots with altered caps. The primary root of fez-2 mutant lines, which has fewer root cap cell layers than wild-type roots, showed impaired penetration ability. Conversely, smb-3 roots of mutant lines, which display a higher number of root cap cells, showed enhanced penetration abilities. This work highlights that alterations in root cap shape and size affect the root responses to medium strength.HighlightThe analysis of the growth and orientation of Arabidopsis thaliana mutant roots affected in root cap size and shape showed that properly formed root cap is required to trigger the root responses to medium strength.AbbreviationsCOLcolumella;LRCLateral Root Cap;SISharpness Index;SMBSOMBRERO.
Step-wise evolution of temperature-mediated phenotypic plasticity in eyespot size across nymphalid butterflies
Authors: Bhardwaj Shivam , Jolander Lim Si-Hui , Wenk Markus R. , Oliver Jeffrey C. , Nijhout H. Frederik , Monteiro Antónia 
Published: July 2018

AbstractThere are two disparate views regarding phenotypic plasticity. One regards plasticity as a derived adaptation to help organisms survive in variable environments1, 2while the other views plasticity as the outcome of flexible, non-canalized, developmental processes, ancestrally present in most organisms, that helps them colonize or adapt to novel environments3–5e.g., a pre-adaptation. Both views of plasticity currently lack a rigorous, mechanistic examination of ancestral and derived states and direction of change2. Here we show that the origin of phenotypic plasticity in eyespot size in response to environmental temperature observed inBicyclus anynanabutterflies is a derived adaptation of this lineage. Eyespot size is regulated by temperature-mediated changes in levels of a steroid hormone, 20E, that affects proliferation of eyespot central cells expressing the 20E receptor (EcR)6, 7. By estimating the origin of the known physiological and molecular components of eyespot size plasticity in a comparative framework, we showed that 20E titer plasticity in response to temperature is a pre-adaptation shared by all butterfly species examined, whereas the origin of expression of EcR in eyespot centers, and the origin of eyespot sensitivity to the hormone-receptor complex are both derived traits found only in a subset of species with eyespots. The presence of all three molecular components required to produce a plastic response is only observed inB. anynana. This gradual, step-wise, physiological/molecular response to temperature is a likely adaptation to temperature variation experienced across wet and dry seasons in the habitat of this species. This work supports, thus, the first view of plasticity as a derived adaptation.
Comprehensive analysis of retinal development at single cell resolution identifies NFI factors as essential for mitotic exit and specification of late-born cells
Authors: Clark Brian S. , Stein-O’Brien Genevieve L. , Shiau Fion , Cannon Gabrielle H. , Davis Emily , Sherman Thomas , Rajaii Fatemeh , James-Esposito Rebecca E. , Gronostajski Richard M. , Fertig Elana J. , Goff Loyal A. , Blackshaw Seth 
Published: July 2018

SUMMARYPrecise temporal control of gene expression in neuronal progenitors is necessary for correct regulation of neurogenesis and cell fate specification. However, the extensive cellular heterogeneity of the developing CNS has posed a major obstacle to identifying the gene regulatory networks that control these processes. To address this, we used single cell RNA-sequencing to profile ten developmental stages encompassing the full course of retinal neurogenesis. This allowed us to comprehensively characterize changes in gene expression that occur during initiation of neurogenesis, changes in developmental competence, and specification and differentiation of each of the major retinal cell types. These data identify transitions in gene expression between early and late-stage retinal progenitors, as well as a classification of neurogenic progenitors. We identify here the NFI family of transcription factors (Nfia, Nfib, and Nfix) as genes with enriched expression within late RPCs, and show they are regulators of bipolar interneuron and Müller glia specification and the control of proliferative quiescence.
Memory sequencing reveals heritable single cell gene expression programs associated with distinct cellular behaviors
Authors: Shaffer Sydney M. , Emert Benjamin L. , Reyes-Hueros Raul , Coté Christopher , Harmange Guillaume , Sizemore Ann E. , Gupte Rohit , Torre Eduardo , Singh Abhyudai , Bassett Danielle S. , Raj Arjun 
Published: July 2018

AbstractNon-genetic factors can cause individual cells to fluctuate substantially in gene expression levels over time. Yet it remains unclear whether these fluctuations can persist for much longer than the time of one cell division. Current methods for measuring gene expression in single cells mostly rely on single time point measurements, making the duration of gene expression fluctuations or cellular memory difficult to measure. Here, we report a method combining Luria and Delbrück’s fluctuation analysis with population-based RNA sequencing (MemorySeq) for identifying genes transcriptome-wide whose fluctuations persist for several cell divisions. MemorySeq revealed multiple gene modules that are expressed together in rare cells within otherwise homogeneous clonal populations. Further, we found that these rare cell subpopulations are associated with biologically distinct behaviors, such as the ability to proliferate in the face of anti-cancer therapeutics, in different cancer cell lines. The identification of non-genetic, multigenerational fluctuations has the potential to reveal new forms of biological memory at the level of single cells and suggests that non-genetic heritability of cellular state may be a quantitative property.
Migration and Differentiation of Osteoclast Precursors under Gradient Fluid Shear Stress
Authors: Gao Y , Li T. Y , Sun Q. , Ye C. Y , Guo M. M. , Chen Z. B. , Chen J. , Huo B. 
Published: July 2018

AbstractThe skeleton is able to adapt to mechanical loading through bone remodeling, i.e. bone resorption followed by bone formation. The osteoclasts close to microdamages are believed to initiate bone resorption, but whether local mechanical loading such as fluid flow regulates recruitment and differentiation of osteoclast precursors at the site of bone resorption has yet to be investigated. In the present study, finite element analysis first revealed that there exists low fluid shear stress (FSS) field inside microdamage. Basing on a custom-made device of cone-and-plate fluid chamber, finite element analysis and particle image velocimetry measurement were performed to verify the formation of gradient FSS flow field. Furthermore, the effects of gradient FSS on the migration, aggregation, and fusion of osteoclast precursors were observed. Results showed that osteoclast precursor RAW264.7 cells migrate along radial direction toward the region with lower FSS during exposure to gradient FSS stimulation for 40 min, obviously deviating from the direction of actual fluid flow indicated by fluorescent particles. When inhibiting calcium signaling pathway with gadolinium and thapsigargin, cell migration toward low-FSS region was significantly reduced. For other cell lines, MC3T3-E1, PDLF, rMSC and MDCK, gradient FSS stimulation did not lead to the low-FSS-inclined migration. After being cultured under gradient FSS stimulation for 6 days, the density of RAW264.7 cells and the ratio of TRAP-positive multinucleated osteoclasts in low-FSS region were significantly higher than those in high-FSS region. Therefore, osteoclast precursor cells may have special ability to sense FSS gradient and tend to actively migrate toward low-FSS region, which is regulated by calcium signaling pathway.
Prospects for enhancing leaf photosynthetic capacity by manipulating mesophyll cell morphology
Authors: Ren Tao , Weraduwage Sarathi M , Sharkey Thomas D. 
Published: July 2018

AbstractLeaves are beautifully specialized organs designed to maximize the use of light and CO2 for photosynthesis. Engineering leaf anatomy therefore brings great potential to enhance photosynthetic capacity. Here we review the effect of the dominant leaf anatomical traits on leaf photosynthesis and confirm that a high chloroplast surface area exposed to intercellular airspace per unit leaf area (Sc) is critical for efficient photosynthesis. The possibility of improving Sc through appropriately increasing mesophyll cell density is further analyzed. The potential influences of modifying mesophyll cell morphology on CO2 diffusion, light distribution within the leaf, and other physiological processes are also discussed. Some potential target genes regulating leaf mesophyll cell proliferation and expansion are explored. Indeed, more comprehensive research is needed to understand how manipulating mesophyll cell morphology through editing the potential target genes impact leaf photosynthetic capacity and related physiological processes. This will pinpoint the targets for engineering leaf anatomy to maximize photosynthetic capacity.HighlightCell morphology in leaves affects photosynthesis by controlling CO2 diffusion and light distribution. Recent work has uncovered genes that control cell size, shape, and number paving the way improved photosynthesis.
Dynamic recovery from depression enables rate encoding in inhibitory synapses
Authors: Huang Shiyong , Bridi Morgan S. , Kirkwood Alfredo 
Published: July 2018

SummaryFast-spiking parvalbumin positive interneurons (PV-INs) are essential for controlling network firing and the gain of the cortical response to sensory stimulation. Crucial for these functions, PV-INs can sustain high frequency firing with no accommodation. However, PV-INs also exhibit short-term depression (STD) during sustained activation, which is largely due to the depletion of synaptic resources (vesicles). In most synapses the rate of replenishment of depleted vesicles is constant, determining an inverse relationship between the STD level and the activation rate, which theoretically, severely limits rate coding capabilities. We examined STD of the PV-IN to pyramidal cell synapse in the mouse visual cortex, and found that in these synapses the recovery of depleted resources is not constant but increases linearly with the frequency of use. By combining modeling, dynamic clamp and optogenetics, we demonstrated that this dynamic regulation of recovery enables PV-INs to reduce pyramidal cell firing in a linear manner, which, theoretically, is crucial for controlling the gain of cortical visual responses.