bluuebunny/crossref_metadata_2025_split huggingface dataset:
DendritesIn VitroandIn VivoContain Microtubules of Opposite Polarity and Axon Formation Correlates with Uniform Plus-End-Out Microtubule Orientation
Authors: Yau Kah Wai , Schätzle Philipp , Tortosa Elena , Pagès Stéphane , Holtmaat Anthony , Kapitein Lukas C. , Hoogenraad Casper C. 
Published: January 2016

In cultured vertebrate neurons, axons have a uniform arrangement of microtubules with plus-ends distal to the cell body (plus-end-out), whereas dendrites contain mixed polarity orientations with both plus-end-out and minus-end-out oriented microtubules. Rather than non-uniform microtubules, uniparallel minus-end-out microtubules are the signature of dendrites inDrosophilaandCaenorhabditis elegansneurons. To determine whether mixed microtubule organization is a conserved feature of vertebrate dendrites, we used live-cell imaging to systematically analyze microtubule plus-end orientations in primary cultures of rat hippocampal and cortical neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neurons in the somatosensory cortex of living mice.In vitroandin vivo, all microtubules had a plus-end-out orientation in axons, whereas microtubules in dendrites had mixed orientations. When dendritic microtubules were severed by laser-based microsurgery, we detected equal numbers of plus- and minus-end-out microtubule orientations throughout the dendritic processes. In dendrites, the minus-end-out microtubules were generally more stable and comparable with plus-end-out microtubules in axons. Interestingly, at early stages of neuronal development in nonpolarized cells, newly formed neurites already contained microtubules of opposite polarity, suggesting that the establishment of uniform plus-end-out microtubules occurs during axon formation. We propose a model in which the selective formation of uniform plus-end-out microtubules in the axon is a critical process underlying neuronal polarization.SIGNIFICANCE STATEMENTLive-cell imaging was used to systematically analyze microtubule organization in primary cultures of rat hippocampal neurons, dentate granule cells in mouse organotypic slices, and layer 2/3 pyramidal neuron in somatosensory cortex of living mice.In vitroandin vivo, all microtubules have a plus-end-out orientation in axons, whereas microtubules in dendrites have mixed orientations. Interestingly, newly formed neurites of nonpolarized neurons already contain mixed microtubules, and the specific organization of uniform plus-end-out microtubules only occurs during axon formation. Based on these findings, the authors propose a model in which the selective formation of uniform plus-end-out microtubules in the axon is a critical process underlying neuronal polarization.
Resolution of High-Frequency Mesoscale Intracortical Maps Using the Genetically Encoded Glutamate Sensor iGluSnFR
Authors: Xie Yicheng , Chan Allen W. , McGirr Alexander , Xue Songchao , Xiao Dongsheng , Zeng Hongkui , Murphy Timothy H. 
Published: January 2016

Wide-field-of-view mesoscopic cortical imaging with genetically encoded sensors enables decoding of regional activity and connectivity in anesthetized and behaving mice; however, the kinetics of most genetically encoded sensors can be suboptimal forin vivocharacterization of frequency bands higher than 1–3 Hz. Furthermore, existing sensors, in particular those that measure calcium (genetically encoded calcium indicators; GECIs), largely monitor suprathreshold activity. Using a genetically encoded sensor of extracellular glutamate andin vivomesoscopic imaging, we demonstrate rapid kinetics of virally transduced or transgenically expressed glutamate-sensing fluorescent reporter iGluSnFR. In both awake and anesthetized mice, we imaged an 8 × 8 mm field of view through an intact transparent skull preparation. iGluSnFR revealed cortical representation of sensory stimuli with rapid kinetics that were also reflected in correlation maps of spontaneous cortical activities at frequencies up to the alpha band (8–12 Hz). iGluSnFR resolved temporal features of sensory processing such as an intracortical reverberation during the processing of visual stimuli. The kinetics of iGluSnFR for reporting regional cortical signals were more rapid than those for Emx-GCaMP3 and GCaMP6s and comparable to the temporal responses seen with RH1692 voltage sensitive dye (VSD), with similar signal amplitude. Regional cortical connectivity detected by iGluSnFR in spontaneous brain activity identified functional circuits consistent with maps generated from GCaMP3 mice, GCaMP6s mice, or VSD sensors. Viral and transgenic iGluSnFR tools have potential utility in normal physiology, as well as neurologic and psychiatric pathologies in which abnormalities in glutamatergic signaling are implicated.SIGNIFICANCE STATEMENTWe have characterized the usage of virally transduced or transgenically expressed extracellular glutamate sensor iGluSnFR to perform wide-field-of-view mesoscopic imaging of cortex in both anesthetized and awake mice. Probes for neurotransmitter concentration enable monitoring of brain activity and provide a more direct measure of regional functional activity that is less dependent on nonlinearities associated with voltage-gated ion channels. We demonstrate functional maps of extracellular glutamate concentration and that this sensor has rapid kinetics that enable reporting high-frequency signaling. This imaging strategy has utility in normal physiology and pathologies in which altered glutamatergic signaling is observed. Moreover, we provide comparisons between iGluSnFR and genetically encoded calcium indicators and voltage-sensitive dyes.
Regulation of ATP13A2 via PHD2-HIF1α Signaling Is Critical for Cellular Iron Homeostasis: Implications for Parkinson's Disease
Authors: Rajagopalan Subramanian , Rane Anand , Chinta Shankar J. , Andersen Julie K. 
Published: January 2016

We previously reported that pharmacological inhibition of a class of enzymes known as prolyl hydroxylase domain proteins (PHDs) has neuroprotective effects in variousin vitroandin vivomodels of Parkinson's disease (PD). We hypothesized that this was due to inhibition of the PHD2 isoform, preventing it from hydroxylating the transcription factor hypoxia inducible factor 1 α (HIF1α), targeting it for eventual proteasomal degradation. HIF1α itself induces the transcription of various cellular stress genes, including several involved in iron metabolism. Although all three isoforms of PHD are expressed within vulnerable dopaminergic (DAergic) substantia nigra pars compacta neurons, only select downregulation of the PHD2 isoform was found to protect againstin vivoneurodegenerative effects associated with the mitochondrial neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine. These findings were corroborated in induced pluripotent stem cell-derived neurons, providing validation in a pertinent human cell model. PHD2 inhibition was found to result in increased expression ofATP13A2, mutation of which is responsible for a rare juvenile form of PD known as Kufor-Rakeb syndrome. Knockdown ofATP13A2expression within human DAergic cells was found to abrogate restoration of cellular iron homeostasis and neuronal cell viability elicited by inhibition of PHD2 under conditions of mitochondrial stress, likely via effects on lysosomal iron storage. These data suggest that regulation of ATP13A2 by the PHD2-HIF1α signaling pathway affects cellular iron homeostasis and DAergic neuronal survival. This constitutes a heretofore unrecognized process associated with loss ofATP13A2function that could have wide-ranging implications for it as a therapeutic target for PD and other related conditions.SIGNIFICANCE STATEMENTReductions in PHD2 activity within dopaminergic neuronsin vivoand in cultured human induced pluripotent stem cell-derived neurons protects against mitochondrial stress-induced neurotoxicity. Protective effects are dependent on downstreamHIF-1α expression. Knockdown ofATP13A2, a gene linked to a rare juvenile form of Parkinson's disease and recently identified as a novel HIF1α target, was found to abrogate maintenance of cellular iron homeostasis and neuronal viability elicited by PHD2 inhibitionin vivoand in cultured dopaminergic cells under conditions of mitochondrial stress. Mechanistically, this was due toATP13A2's role in maintaining lysosomal iron stores. This constitutes a novel mechanism by which alterations inATP13A2activity may be driving PD-related neuropathology.
Female-Specific Intergenerational Transmission Patterns of the Human Corticolimbic Circuitry
Authors: Yamagata Bun , Murayama Kou , Black Jessica M. , Hancock Roeland , Mimura Masaru , Yang Tony T. , Reiss Allan L. , Hoeft Fumiko 
Published: January 2016

Parents have large genetic and environmental influences on offspring's cognition, behavior, and brain. These intergenerational effects are observed in mood disorders, with particularly robust association in depression between mothers and daughters. No studies have thus far examined the neural bases of these intergenerational effects in humans. Corticolimbic circuitry is known to be highly relevant in a wide range of processes, including mood regulation and depression. These findings suggest that corticolimbic circuitry may also show matrilineal transmission patterns. Therefore, we examined human parent–offspring association in this neurocircuitry and investigated the degree of association in gray matter volume between parent and offspring. We used voxelwise correlation analysis in a total of 35 healthy families, consisting of parents and their biological offspring. We found positive associations of regional gray matter volume in the corticolimbic circuit, including the amygdala, hippocampus, anterior cingulate cortex, and ventromedial prefrontal cortex between biological mothers and daughters. This association was significantly greater than mother–son, father–daughter, and father–son associations. The current study suggests that the corticolimbic circuitry, which has been implicated in mood regulation, shows a matrilineal-specific transmission patterns. Our preliminary findings are consistent with what has been found behaviorally in depression and may have clinical implications for disorders known to have dysfunction in mood regulation such as depression. Studies such as ours will likely bridge animal work examining gene expression in the brains and clinical symptom-based observations and provide promising ways to investigate intergenerational transmission patterns in the human brain.SIGNIFICANCE STATEMENTParents have large genetic and environmental influences on the offspring, known as intergenerational effects. Specifically, depression has been shown to exhibit strong matrilineal transmission patterns. Although intergenerational transmission patterns in the human brain are virtually unknown, this would suggest that the corticolimbic circuitry relevant to a wide range of processes including mood regulation may also show matrilineal transmission patterns. Therefore, we examined the degree of association in corticolimbic gray matter volume (GMV) between parent and offspring in 35 healthy families. We found that positive correlations in maternal corticolimbic GMV with daughters were significantly greater than other parent–offspring dyads. Our findings provide new insight into the potential neuroanatomical basis of circuit-based female-specific intergenerational transmission patterns in depression.
Orthogonal intercellular signaling for programmed spatial behavior
Authors: Grant Paul K , Dalchau Neil , Brown James R , Federici Fernan , Rudge Timothy J , Yordanov Boyan , Patange Om , Phillips Andrew , Haseloff Jim 
Published: January 2016

AbstractBidirectional intercellular signaling is an essential feature of multicellular organisms, and the engineering of complex biological systems will require multiple pathways for intercellular signaling with minimal crosstalk. Natural quorum‐sensing systems provide components for cell communication, but their use is often constrained by signal crosstalk. We have established new orthogonal systems for cell–cell communication using acyl homoserine lactone signaling systems. Quantitative measurements in contexts of differing receiver protein expression allowed us to separate different types of crosstalk between 3‐oxo‐C6‐ and 3‐oxo‐C12‐homoserine lactones, cognate receiver proteins, and DNA promoters. Mutating promoter sequences minimized interactions with heterologous receiver proteins. We used experimental data to parameterize a computational model for signal crosstalk and to estimate the effect of receiver protein levels on signal crosstalk. We used this model to predict optimal expression levels for receiver proteins, to create an effective two‐channel cell communication device. Establishment of a novel spatial assay allowed measurement of interactions between geometrically constrained cell populations via these diffusible signals. We built relay devices capable of long‐range signal propagation mediated by cycles of signal induction, communication and response by discrete cell populations. This work demonstrates the ability to systematically reduce crosstalk within intercellular signaling systems and to use these systems to engineer complex spatiotemporal patterning in cell populations.
As patients get older, we should be aware of salt levels in factor products
Authors: Alavian Sharon , Hutchinson Wendy 
Published: January 2016

Abstract
Hypertension is a well-known risk factor for ischaemic heart disease and cerebrovascular events. Globally, there is a drive to try to reduce salt intake. In an older population, where hypertension is likely to have a high prevalence, are health care professionals aware of the sodium content in replacement factor?
Management of an uncommon form of type 2M VWD: a single centre experience
Authors: Rashid Sabia , Bignell Patricia , Keeling David , Curry Nicola 
Published: January 2016

Abstract
We report a single centre’s experience of the diagnosis and management of an uncommon form of type 2 von Willebrand disease (VWD) in members of two unrelated families. The affected patients presented with mild to moderate bleeding phenotypes and accompanying MCMDM-1 VWD bleeding assessment tool scores of 5 or less. Genetic analysis in both families confirmed a missense mutation in exon 30 of the von Willebrand factor (VWF) gene, a single base substitution T>A at nucleotide 5282 which led to change at codon 1761 from methionine to lysine (M1761K). This mutation lies within the A3 domain of the VWF protein, a region that is important for collagen binding. All affected patients were found to have normal coagulation profiles, normal VWF multimers and normal VWF assays except the VWF collagen-binding (VWF: CB) assay levels, which were significantly reduced. Desmopressin effected a good response in all treated patients, with a 3- to 5-fold rise of VWF:CB levels. However, there was variability in the degree to which VWF:CB levels remained elevated. Surgical procedures, including the delivery of one patient, were able to be managed with either desmopressin and/or tranexamic acid alone, with little need for recourse to VWF factor concentrate therapy.
Lumbar Microdiscectomy
Authors: Truumees Eeric , Geck Matthew , Stokes John K. , Singh Devender 
Published: January 2016

In most patients, the radiculopathy associated with lumbar disc herniation resolves nonoperatively. For patients in whom nonsurgical management has failed, microdiscectomy can be considered. Today, an operating microscope is preferred because of the collinear light and magnification offered. Alternatively, loupes and a headlight may be employed. The major steps of the procedure are (1) making a 2-cm vertical incision and then developing the corridor to the lamina subperiosteally or by using serial dilation techniques; (2) confirming the level of surgery radiographically prior to incision and once the lamina has been reached and then detaching the lateral attachments of the flavum; (3) making a small laminotomy, resecting any superior facet osteophytes, then mobilizing the compressed traversing nerve root, and, in some cases, making a small annulotomy; and (4) removing loose disc fragments and performing wound closure.
Most outcomes reports after microdiscectomy have been favorable for radicular symptoms. Associated back pain typically decreased as well. Common complications include recurrent disc herniation or disc herniation at another level, wound infections, and durotomy with spinal headache.
Mechanistic Modeling of Low-Salinity Waterflooding Through Coupling a Geochemical Package With a Compositional Reservoir Simulator
Authors: Korrani Aboulghasem Kazemi , Jerauld Gary R. , Sepehrnoori Kamy 
Published: January 2016

SummaryLow-salinity waterflooding is an emerging enhanced-oil-recovery (EOR) technique in which the salinity of the injected water is substantially reduced to improve oil recovery over conventional higher-salinity waterflooding. Although there are many low-salinity experimental results reported in the literature, publications on modeling this process are rare. Although there remains some debate regarding the mechanisms of low salinity waterflooding process (LoSal EOR®)*, the geochemical reactions that control the wetting of crude oil on the rock are likely to be central to a detailed description of the process. Because no comprehensive geochemical-based modeling has been applied in this area, it was decided to couple a state-of-the-art geochemical package, IPhreeqc (Charlton and Parkhurst 2011), developed by the US Geological Survey, with UTCOMP (Chang 1990), the compositional reservoir simulator developed by The University of Texas at Austin.A step-by-step algorithm is presented for integrating IPhreeqc with UTCOMP. Through this coupling, we are able to simulate homogeneous and heterogeneous (mineral dissolution/precipitation), irreversible, and ion-exchange reactions under nonisothermal, nonisobaric, and both local-equilibrium (away from the wellbore) and kinetic (near wellbore) conditions. Consistent with the literature, there are significant effects of water-soluble hydrocarbon components—e.g., carbon dioxide (CO2), methane (CH4), and acidic/basic components of the crude—on buffering the aqueous pH value and more generally, on the crude oil, brine, and rock reactions. Thermodynamic constraints are used to explicitly include the effect of these water-soluble hydrocarbon components. Hence, this combines the geochemical power of IPhreeqc with the important aspects of hydrocarbon flow and compositional effects to produce a robust, flexible, and accurate integrated tool capable of including the reactions needed to mechanistically model low-salinity waterflooding.Different geochemical-based approaches to modeling wettability change in sandstones (e.g., interpolation on the basis of total ionic strength and multicomponent ion exchange through surface complexation of the organometallic components) were implemented in UTCOMP-IPhreeqc, and the integrated tool is then used to match and interpret a low-salinity experiment published by Kozaki (2012) and the field trial performed by BP at the Endicott field.
Low Solids Shear Dependent Fluid System to Plug Zones for Preventing Fluid Influx and Loss
Authors: Javier Urdaneta , Krishna Ravi , Jaime Pacheco , Oscar Jaramillo , John Patiño 
Published: January 2016

Abstract
Lost circulation and influx from sections of high-pressure zones is a recurrent challenge and high-cost event within the oil industry, particularly in mature fields or weak-fracture-gradient zones. These can significantly increase operational costs, non-productive time (NPT), the possibility of stuck pipe, and well integrity challenges. Lost circulation can be defined in a variety of ways, from partial to total loss, and in a variety of formations, including highly-permeable, fractured, or cavernous formations. Loss circulation materials, such as particulates, have been successfully used to plug smaller fractures and permeable zones. Challenges arise when the losses cannot be stopped using particulates because of the loss magnitude. The industry has used various chemical solutions to overcome this challenge with mixed results. Particulates are usually unsuccessful in terms of plugging high-pressure zones to help prevent fluid influx.
This paper presents a low-solids loss circulation solution that develops rapid gel strength when shear rate decreases. The gel strength buildup is based on polymers and nanomaterials in the fluid system. This helps prevent fluid from continuously flowing into the zone or being expelled from the zone. Once gel strength has developed, the system develops nominal compressive strength to adhere to the formation and thus helps prevent displacement during subsequent well operations. The fluid is shear thinning and hence easily enters the formation zone and does not flow continuously, as it gels upon entering the formation. The low solids and low rheology under shear means that it can be easily pumped through the drill bit without having to pull out of the hole (POOH).
This paper describes a system that was pumped into a high-pressure zone to isolate an unconsolidated sand formation. Initial attempts to isolate the zone included a bradenhead squeeze operation, which was unsuccessful, and fluid influx from the zone was observed during subsequent well operations. The fluid system and process described in this paper should help the industry in terms of shutting off streaks of high-pressure zones and curing fluid lost into the formation.
Size Degradation Studies of Lost Circulation Materials in a Flow Loop
Authors: Grant Patrick , Lassus Laurent , Savari Sharath , Whitfill Donald L. 
Published: January 2016

Abstract
Recently, there has been significant interest in understanding the material properties of lost circulation materials (LCM), including size degradation studies from mechanical compression tests and from shear flow. These types of tests are currently of particular importance because of increased drilling activity in mature fields, which often require LCMs as a background material. The objective of this work is to present the size degradation of LCMs from flow loop tests.
A flow loop test was performed to study the size degradation of LCMs, mainly ground marble (GM) and resilient graphitic carbon (RGC). A predetermined amount of GM and RGC was added to an 80-bbl synthetic-oil-based drilling fluid. The flow loop consisted of 3-in. diameter flow lines. One circulation through this flow loop required approximately 8 minutes, which is equivalent to one circulation in the actual field application. The fluid with LCM was circulated through the flow loop at a 400-gal/min flow rate. Fluid samples were collected at different stages, and a wet sieve analysis was performed to determine the amount of material in the drilling fluid retained on each sieve. Comparing the amount after the flow with the amount before flow allowed estimations of the LCM size degradation. This provided the size degradation the LCM would experience as a result of flow through the loop.
Another objective was to study the effect of a turbine, which was anticipated to be part of the bottomhole assembly (BHA) on the size degradation rate of LCMs. To evaluate this, a turbine was incorporated in the flow loop, and the fluid with LCM was again circulated at a 400-gal/min flow rate. Again, samples were collected at different times, with a wet sieve analysis performed to determine the size degradation of LCMs when flowing through the turbine and the flow loop.
GM was subjected to a 35% size reduction resulting from the flow loop alone, compared to only a 16% size reduction of the RGC. When the turbine was added to the flow loop, GM was almost completely degraded (a total of 75% reduction) to a smaller size after only one circulation through the loop. Concurrently, the RGC experienced only a 20% reduction in size even after 160 minutes of flow (20 circulations) through the loop and the turbine.
Size degradation studies of LCMs were conducted for the first time in a flow loop at a 400-gal/min circulation rate. The results show the importance of using a resilient LCM, such as RGC as part of a LCM background package when drilling lost circulation problem zones in mature fields.