bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tonic Inhibitory Control of Dentate Gyrus Granule Cells by α5-Containing GABAAReceptors Reduces Memory Interference
Authors: Engin Elif , Zarnowska Ewa D. , Benke Dietmar , Tsvetkov Evgeny , Sigal Maksim , Keist Ruth , Bolshakov Vadim Y. , Pearce Robert A. , Rudolph Uwe 
Published: October 2015

Interference between similar or overlapping memories formed at different times poses an important challenge on the hippocampal declarative memory system. Difficulties in managing interference are at the core of disabling cognitive deficits in neuropsychiatric disorders. Computational models have suggested that, in the normal brain, the sparse activation of the dentate gyrus granule cells maintained by tonic inhibitory control enables pattern separation, an orthogonalization process that allows distinct representations of memories despite interference. To test this mechanistic hypothesis, we generated mice with significantly reduced expression of the α5-containing GABAA(α5-GABAARs) receptors selectively in the granule cells of the dentate gyrus (α5DGKO mice). α5DGKO mice had reduced tonic inhibition of the granule cells without any change in fast phasic inhibition and showed increased activation in the dentate gyrus when presented with novel stimuli. α5DGKO mice showed impairments in cognitive tasks characterized by high interference, without any deficiencies in low-interference tasks, suggesting specific impairment of pattern separation. Reduction of fast phasic inhibition in the dentate gyrus through granule cell-selective knock-out of α2-GABAARs or the knock-out of the α5-GABAARs in the downstream CA3 area did not detract from pattern separation abilities, which confirms the anatomical and molecular specificity of the findings. In addition to lending empirical support to computational hypotheses, our findings have implications for the treatment of interference-related cognitive symptoms in neuropsychiatric disorders, particularly considering the availability of pharmacological agents selectively targeting α5-GABAARs.SIGNIFICANCE STATEMENTInterference between similar memories poses a significant limitation on the hippocampal declarative memory system, and impaired interference management is a cognitive symptom in many disorders. Thus, understanding mechanisms of successful interference management or processes that can lead to interference-related memory problems has high theoretical and translational importance. This study provides empirical evidence that tonic inhibition in the dentate gyrus (DG), which maintains sparseness of neuronal activation in the DG, is essential for management of interference. The specificity of findings to tonic, but not faster, more transient types of neuronal inhibition and to the DG, but not the neighboring brain areas, is presented through control experiments. Thus, the findings link interference management to a specific mechanism, proposed previously by computational models.
Primary Cilia on Horizontal Basal Cells Regulate Regeneration of the Olfactory Epithelium
Authors: Joiner Ariell M. , Green Warren W. , McIntyre Jeremy C. , Allen Benjamin L. , Schwob James E. , Martens Jeffrey R. 
Published: October 2015

The olfactory epithelium (OE) is one of the few tissues to undergo constitutive neurogenesis throughout the mammalian lifespan. It is composed of multiple cell types including olfactory sensory neurons (OSNs) that are readily replaced by two populations of basal stem cells, frequently dividing globose basal cells and quiescent horizontal basal cells (HBCs). However, the precise mechanisms by which these cells mediate OE regeneration are unclear. Here, we show for the first time that the HBC subpopulation of basal stem cells uniquely possesses primary cilia that are aligned in an apical orientation in direct apposition to sustentacular cell end feet. The positioning of these cilia suggests that they function in the detection of growth signals and/or differentiation cues. To test this idea, we generated an inducible, cell type-specificIft88knock-out mouse line (K5rtTA;tetOCre;Ift88fl/fl) to disrupt cilia formation and maintenance specifically in HBCs. Surprisingly, the loss of HBC cilia did not affect the maintenance of the adult OE but dramatically impaired the regeneration of OSNs following lesion. Furthermore, the loss of cilia during development resulted in a region-specific decrease in neurogenesis, implicating HBCs in the establishment of the OE. Together, these results suggest a novel role for primary cilia in HBC activation, proliferation, and differentiation.SIGNIFICANCE STATEMENTWe show for the first time the presence of primary cilia on a quiescent population of basal stem cells, the horizontal basal cells (HBCs), in the olfactory epithelium (OE). Importantly, our data demonstrate that cilia on HBCs are necessary for regeneration of the OE following injury. Moreover, the disruption of HBC cilia alters neurogenesis during the development of the OE, providing evidence that HBCs participate in the establishment of this tissue. These data suggest that the mechanisms of penetrance for ciliopathies in the OE extend beyond that of defects in olfactory sensory neurons and may include alterations in OE maintenance and regeneration.
Morphological Abnormalities of Thalamic Subnuclei in Migraine: A Multicenter MRI Study at 3 Tesla
Authors: Magon Stefano , May Arne , Stankewitz Anne , Goadsby Peter J. , Tso Amy R. , Ashina Messoud , Amin Faisal Mohammad , Seifert Christian L. , Chakravarty M. Mallar , Müller Jannis , Sprenger Till 
Published: October 2015

The thalamus contains third-order relay neurons of the trigeminal system, and animal models as well as preliminary imaging studies in small cohorts of migraine patients have suggested a role of the thalamus in headache pathophysiology. However, larger studies using advanced imaging techniques in substantial patient populations are lacking. In the present study, we investigated changes of thalamic volume and shape in a large multicenter cohort of patients with migraine. High-resolution T1-weighted MRI data acquired at 3 tesla in 131 patients with migraine (38 with aura; 30.8 ± 9 years old; 109 women; monthly attack frequency: 3.2 ± 2.5; disease duration: 14 ± 8.4 years) and 115 matched healthy subjects (29 ± 7 years old; 81 women) from four international tertiary headache centers were analyzed. The thalamus and thalamic subnuclei, striatum, and globus pallidus were segmented using a fully automated multiatlas approach. Deformation-based shape analysis was performed to localize surface abnormalities. Differences between patients with migraine and healthy subjects were assessed using an ANCOVA model. After correction for multiple comparisons, performed using the false discovery rate approach (p< 0.05 corrected), significant volume reductions of the following thalamic nuclei were observed in migraineurs: central nuclear complex (F(1,233)= 6.79), anterior nucleus (F(1,237)= 7.38), and lateral dorsal nucleus (F(1,238)= 6.79). Moreover, reduced striatal volume (F(1,238)= 6.9) was observed in patients. This large-scale study indicates structural thalamic abnormalities in patients with migraine. The thalamic nuclei with abnormal volumes are densely connected to the limbic system. The data hence lend support to the view that higher-order integration systems are altered in migraine.SIGNIFICANCE STATEMENTThis multicenter imaging study shows morphological thalamic abnormalities in a large cohort of patients with episodic migraine compared with healthy subjects using state-of-the-art MRI and advanced, fully automated multiatlas segmentation techniques. The results stress that migraine is a disorder of the CNS in which not only is brain function abnormal, but also brain structure is undergoing significant remodeling.
Giant myelolipomas and inadvertent bilateral adrenalectomy in classic congenital adrenal hyperplasia
Authors: Kale Geetanjali , Pelley Elaine M , Davis Dawn Belt 
Published: October 2015

Summary
Myelolipomas have been reported in patients with congenital adrenal hyperplasia (CAH). ACTH excess, as seen with non-adherence to glucocorticoid therapy, may be responsible for tumor development. We report a case of a 51-year-old man with classic salt-wasting CAH managed on prednisone 7.5 mg daily and fludrocortisone who presented with chronic back pain and was found to have giant bilateral retroperitoneal masses. On computed tomography (CT) imaging, the masses were heterogeneous, but contained predominantly low-density fat attenuation. The tumors were resected due to concern for malignancy and mass symptoms. Pathologic examination identified both retroperitoneal masses as myelolipomas. The left tumor was 34×20×13 cm and weighed 4.7 kg and the right tumor was 20 cm in the largest dimension. Adrenal tissue was present in the specimen. The patient reported long-term compliance with glucocorticoid treatment. However, no biochemical monitoring of ACTH levels had occurred. Therefore, it is unclear if ACTH excess contributed to the development of these large tumors in this patient. It was presumed that both adrenal glands were inadvertently removed during surgery and the patient was treated with physiologic replacement doses of hydrocortisone and fludrocortisone postoperatively. In this case, the bilateral adrenalectomy was inadvertent. However, adrenalectomy can be considered as a treatment option in patients with classical CAH under certain circumstances to avoid complications of glucocorticoid excess.

Learning points

Myelolipomas should be considered in the differential diagnosis of adrenal or retroperitoneal masses in patients with CAH.

On CT imaging, myelolipomas are seen as heterogeneous masses with low-density mature fat interspersed with more dense myeloid tissue.

Myelolipomas are usually unilateral and measure <4 cm; however, very large and bilateral tumors have been reported.

Treatment of CAH typically involves using supraphysiologic doses of glucocorticoid to suppress adrenal hyperandrogenism. Bilateral adrenalectomy is an alternative treatment option in patients with CAH.

There is an association between ACTH excess and increased incidence of adrenal myelolipoma but the direct causal link remains to be established.
Transmission, Development, and Plasticity of Synapses
Authors: Harris Kathryn P , Littleton J Troy 
Published: October 2015

AbstractChemical synapses are sites of contact and information transfer between a neuron and its partner cell. Each synapse is a specialized junction, where the presynaptic cell assembles machinery for the release of neurotransmitter, and the postsynaptic cell assembles components to receive and integrate this signal. Synapses also exhibit plasticity, during which synaptic function and/or structure are modified in response to activity. With a robust panel of genetic, imaging, and electrophysiology approaches, and strong evolutionary conservation of molecular components, Drosophila has emerged as an essential model system for investigating the mechanisms underlying synaptic assembly, function, and plasticity. We will discuss techniques for studying synapses in Drosophila, with a focus on the larval neuromuscular junction (NMJ), a well-established model glutamatergic synapse. Vesicle fusion, which underlies synaptic release of neurotransmitters, has been well characterized at this synapse. In addition, studies of synaptic assembly and organization of active zones and postsynaptic densities have revealed pathways that coordinate those events across the synaptic cleft. We will also review modes of synaptic growth and plasticity at the fly NMJ, and discuss how pre- and postsynaptic cells communicate to regulate plasticity in response to activity.
Fitness Assays Reveal Incomplete Functional Redundancy of the HoxA1 and HoxB1 Paralogs of Mice
Authors: Ruff James S , Saffarini Raed B , Ramoz Leda L , Morrison Linda C , Baker Shambralyn , Laverty Sean M , Tvrdik Petr , Potts Wayne K 
Published: October 2015

Abstract
Gene targeting techniques have led to the phenotypic characterization of numerous genes; however, many genes show minimal to no phenotypic consequences when disrupted, despite many having highly conserved sequences. The standard explanation for these findings is functional redundancy. A competing hypothesis is that these genes have important ecological functions in natural environments that are not needed under laboratory settings. Here we discriminate between these hypotheses by competing mice (Mus musculus) whose Hoxb1 gene has been replaced by Hoxa1, its highly conserved paralog, against matched wild-type controls in seminatural enclosures. This Hoxb1A1 swap was reported as a genetic manipulation resulting in no discernible embryonic or physiological phenotype under standard laboratory tests. We observed a transient decline in first litter size for Hoxb1A1 homozygous mice in breeding cages, but their fitness was consistently and more dramatically reduced when competing against controls within seminatural populations. Specifically, males homozygous for the Hoxb1A1 swap acquired 10.6% fewer territories and the frequency of the Hoxb1A1 allele decreased from 0.500 in population founders to 0.419 in their offspring. The decrease in Hoxb1A1 frequency corresponded with a deficiency of both Hoxb1A1 homozygous and heterozygous offspring. These data suggest that Hoxb1 and Hoxa1 are more phenotypically divergent than previously reported and support that sub- and/or neofunctionalization has occurred in these paralogous genes leading to a divergence of gene function and incomplete redundancy. Furthermore, this study highlights the importance of obtaining fitness measures of mutants in ecologically relevant conditions to better understand gene function and evolution.
In the Eye of the Beholder: Archives Administration from the User's Point of View
Authors: Freeman Elsie 
Published: October 2015

The author proposes that we learn systematically, not impressionistically, who our users are and might be, what kinds of projects they pursue, and, most important, how they approach records. We must begin to think of archives administration as being centered on our clients, not on materials.
Freeman presents a series of misassumptions on which archivists operate and thereby render their work with users far less effective than it might be. The misassumptions are that: as a profession we are oriented toward users; we know who these users are; we understand the nature of research; and we provide adequate help in doing it. She discusses three of these misassumptions at length and examines the changing nature of research, the problems inherent in our finding aids, and the likelihood of a useful connection between how the researcher approaches information and the development of realistic appraisal standards. She then proposes a series of national, regional, and local efforts intended to retrain our thinking about the place of users in archives administration. These include a nationally initiated study of usership, national recognition for exemplary outreach programs, local programs that will elicit information from users, a reexamination of our descriptive and reference practices, and a restructuring of our archival training programs.
Appraisal Guidelines for Reprint Collections
Authors: Day Deborah 
Published: October 2015

Appraisal of reprint collections or large series of reprints within manuscript and archival collections is of particular interest to archivists working with voluminous contemporary scientific collections. They have sought to identify and eliminate from collections material that is not unique and has little research value. A dozen articles and books in the archival literature have discussed the collection and appraisal of ephemera, near-print material, and reprints. While several authors have suggested that reprints be appraised closely, they have failed to provide appraisal guidelines.
A review of the existing literature and a set of questions to ask in appraising reprint collections are provided in this article.
The Epic Struggle: Subject Retrieval from Large Bibliographic Databases
Authors: Tibbo Helen 
Published: October 2015

Archivists have talked at length about the virtue of contributing records to a national bibliographic utility to provide enhanced access to collections. There has been little discussion, however, of the difficulties of finding materials in such large database environments. This article discusses a retrieval study that focused on collection-level archival records in the OCLC Online Union Catalog, made accessible through the EPIC search system. Data were also collected from the local OPAC at the University of North Carolina-Chapel Hill (UNC-CH) in which UNC-CH-produced OCLC records are loaded. The chief objective was to explore the retrieval environments in which a random sample of USMARC AMC records produced at UNC-Chapel Hill were found—specifically, to obtain a picture of the density of these databases in regard to each subject heading applied and, more generally, for each record. Key questions were (1) how many records would be retrieved for each subject heading attached to each of the records and (2) what was the nature of these subject headings vis-à-vis the number of hits associated with them. Findings show that large retrieval sets are a potential problem with national bibliographic utilities and that the local and national retrieval environments can vary greatly. The need for specificity in indexing is emphasized.
This article is based on a paper given at the Society of American Archivists' 1992 annual meeting in Montreal. OCLC supported this research. The author wishes to thank Patricia Haberkern, who did much of the searching.
Bayesian cross‐validation for model evaluation and selection, with application to the North American Breeding Bird Survey
Authors: Link William A. , Sauer John R. 
Published: October 2015

AbstractThe analysis of ecological data has changed in two important ways over the last 15 years. The development and easy availability of Bayesian computational methods has allowed and encouraged the fitting of complex hierarchical models. At the same time, there has been increasing emphasis on acknowledging and accounting for model uncertainty. Unfortunately, the ability to fit complex models has outstripped the development of tools for model selection and model evaluation: familiar model selection tools such as Akaike's information criterion and the deviance information criterion are widely known to be inadequate for hierarchical models. In addition, little attention has been paid to the evaluation of model adequacy in context of hierarchical modeling, i.e., to the evaluation of fit for a single model. In this paper, we describe Bayesian cross‐validation, which provides tools for model selection and evaluation. We describe the Bayesian predictive information criterion and a Bayesian approximation to the BPIC known as the Watanabe‐Akaike information criterion. We illustrate the use of these tools for model selection, and the use of Bayesian cross‐validation as a tool for model evaluation, using three large data sets from the North American Breeding Bird Survey.
Impact of Shale-Gas Apparent Permeability on Production: Combined Effects of Non-Darcy Flow/Gas Slippage, Desorption, and Geomechanics
Authors: Wang HanYi , Marongiu-Porcu Matteo 
Published: October 2015

Summary
Permeability is one of the most fundamental reservoir-rock properties required for modeling hydrocarbon production. Many shale-gas and ultralow-permeability tight gas reservoirs can have matrix-permeability values in the range of tens to hundreds of nanodarcies. The ultrafine pore structure of these rocks can cause violation of the basic assumptions behind Darcy's law. Depending on a combination of pressure-temperature conditions, pore structure and gas properties, non-Darcy flow mechanisms such as Knudsen diffusion, and/or gas-slippage effects will affect the matrix apparent permeability.
Even though numerous theoretical and empirical models were proposed to describe the increasing apparent permeability caused by non-Darcy flow/gas-slippage behavior in nanopore space, few literature sources have investigated the impact of formation compaction and the release of the adsorption gas layer upon shale-matrix apparent permeability during reservoir depletion.
In this article, we first present a thorough review on gas flow in shale nanopore space and discuss the factors that can affect shale-matrix apparent permeability, besides the well-studied non-Darcy flow/gas-slippage behavior. Then, a unified shale-matrix apparent-permeability model is proposed to bridge the effects of non-Darcy flow/gas-slippage, geomechanics (formation compaction), and the release of the adsorption gas layer into a single, coherent equation. In addition, a mathematical framework for an unconventional reservoir simulator that was developed for this study is also presented.
Different matrix apparent-permeability models are implemented in our numerical simulator to examine how the various factors affect matrix apparent permeability within the simulated reservoir volume. Finally, the impact of a natural-fracture network on matrix apparent-permeability evolution is investigated. The results indicate that, even though the conductive fracture network plays a vital role in shale-gas production, the matrix apparent-permeability evolution during pressure depletion cannot be neglected for accurate production modeling.
Nodal Analysis by Use of ESP Intake and Discharge Pressure Gauges
Authors: Bruijnen P. M. 
Published: October 2015

Summary
Electrical submersible pumps (ESPs) are often not only equipped with bottomhole-pressure gauges, but more frequently contain discharge pressure gauges as well. This combination of gauges can be used to extend the classical nodal-analysis approach with an extra component. Inclusion of an additional discharge pressure gauge allows for the construction of two sets of inflow and outflow equations: one set where the selected node is the pump intake and one set where the selected node is the pump discharge. A graphical method demonstrates how to evaluate these two sets of equations simultaneously. This graphical method is then further condensed into a few simple and easy to use guidelines.
Six possible situations can be faced during operation of an ESP: improving/decreasing performance upstream of the intake pressure gauge, improving/decreasing performance between the intake and the discharge pressure gauges, and improving/decreasing performance downstream of the discharge pressure gauge. Analysis of the changes in intake and discharge pressures can quickly identify which one of these six scenarios is affecting the production performance, thus enabling the breakdown of the production system into the reservoir performance, ESP performance, and tubing performance. Several field examples of oil wells completed with ESPs that contain intake and discharge pressure gauges illustrate the benefit of this procedure.
This method is applicable for any downhole pump with intake and discharge pressure gauges. Even if pump maps are not available, or when the well's liquid-flow rates are not (accurately) known, it is a reliable method to localize downhole production problems. This approach makes full use of the advantages of multiple downhole gauges; nodal analysis in combination with intake and discharge pressure gauges is a quick, inexpensive, and powerful method to determine the location of production problems, so appropriate actions can be taken to maximize well performance.