bluuebunny/crossref_metadata_2025_split huggingface dataset:
A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts
Authors: Goldstein Irwin , Komisaruk Barry R. , Rubin Rachel S. , Goldstein Sue W. , Elliott Stacy , Kissee Jennifer , Kim Choll W. 
Published: July 2017

Abstract

Introduction
Since 14 years of age, the patient had experienced extreme penile pain within seconds of initial sexual arousal through masturbation. Penile pain was so severe that he rarely proceeded to orgasm or ejaculation. After 7 years of undergoing multiple unsuccessful treatments, he was concerned for his long-term mental health and for his future ability to have relationships.

Aim
To describe a novel collaboration among specialists in sexual medicine, neurophysiology, and spine surgery that led to successful management.

Methods
Collaborating health care providers conferred with the referring physician, patient, and parents and included a review of all medical records.

Main Outcome Measure
Elimination of postpubertal intense penile pain during sexual arousal.

Results
The patient presented to our sexual medicine facility at 21 years of age. The sexual medicine physician identifying the sexual health complaint noted a pelvic magnetic resonance imaging report of an incidental sacral Tarlov cyst. A subsequent sacral magnetic resonance image showed four sacral Tarlov cysts, with the largest measuring 18 mm. Neuro-genital testing result were abnormal. The neurophysiologist hypothesized the patient's pain at erection was produced by Tarlov cyst-induced neuropathic irritation of sensory fibers that course within the pelvic nerve. The spine surgeon directed a diagnostic injection of bupivacaine to the sacral nerve roots and subsequently morphine to the conus medullaris of the spinal cord. The bupivacaine produced general penile numbness; the morphine selectively decreased penile pain symptoms during sexual arousal without blocking penile skin sensation. The collaboration among specialties led to the conclusion that the Tarlov cysts were pathophysiologically mediating the penile pain symptoms during arousal. Long-term follow-up after surgical repair showed complete symptom elimination at 18 months after treatment.

Conclusion
This case provides evidence that (i) Tarlov cysts can cause sacral spinal nerve root radiculitis through sensory pelvic nerve and (ii) there are management benefits from collaboration among sexual medicine, neurophysiology, and spine surgery subspecialties.
Goldstein I, Komisaruk BR, Rubin RS, et al. A Novel Collaborative Protocol for Successful Management of Penile Pain Mediated by Radiculitis of Sacral Spinal Nerve Roots From Tarlov Cysts. Sex Med 2017;5:e203–e211.
Dollars for Dixie
Authors: Jewell Katherine Rye 
Published: July 2017

Organized in 1933, the Southern States Industrial Council&apos;s (SSIC) adherence to the South as a unique political and economic entity limited its members&apos; ability to forge political coalitions against the New Deal. The SSIC&apos;s commitment to regional preferences, however, transformed and incorporated conservative thought in the post-World War II era, ultimately complementing the emerging conservative movement in the 1940s and 1950s. In response to New Dealers&apos; attempts to remake the southern economy, the New South industrialists - heirs of C. Vann Woodward&apos;s &apos;new men&apos; of the New South - effectively fused cultural traditionalism and free market economics into a brand of southern free enterprise that shaped the region&apos;s reputation and political culture. Dollars for Dixie demonstrates how the South emerged from this refashioning and became a key player in the modern conservative movement, with new ideas regarding free market capitalism, conservative fiscal policy, and limited bureaucracy.
The future of subsidence modelling: compaction and subsidence due to gas depletion of the Groningen gas field in the Netherlands
Authors: van Thienen-Visser Karin , Fokker Peter A. 
Published: July 2017

AbstractThe Groningen gas field has shown considerable compaction and subsidence since starting production in the early 1960s. The behaviour is understood from the geomechanical response of the reservoir pressure depletion. By integrating surface movement measurements and modelling, the model parameters can be constrained and understanding of the subsurface behaviour can be improved. Such a procedure has been employed to formulate new compaction and subsidence forecasts. The results are put into the context of an extensive review of the work performed in this field, both in Groningen and beyond. The review is used to formulate a way forward designed to integrate all knowledge in a stochastic manner.
Functional characterization of single-domain cystatin-like cysteine proteinase inhibitors expressed by the trematodeFasciola hepatica
Authors: CANCELA MARTÍN , CORVO ILEANA , DA SILVA EDILEUZA , TEICHMANN ALINE , ROCHE LEDA , DÍAZ ALVARO , TORT JOSÉ FRANSISCO , FERREIRA HENRIQUE B. , ZAHA ARNALDO 
Published: July 2017

SUMMARYCystatins are small, phylogenetically conserved proteins that are tight-binding inhibitors of cysteine proteinases. The liver flukeFasciola hepaticauses a diverse set of cysteine proteinases of the papain superfamily for host invasion, immune evasion and nutrition, but little is known about the regulation of these enzymes. The aim of this work is to characterize the cystatin repertoire ofF. hepatica. For this purpose, we first surveyed the available sequence databases, identifying three differentF. hepaticasingle-domain cystatins. In agreement with thein silicopredictions, at least three small proteins with cysteine proteinase binding activity were identified. Phylogenetic analyses showed that the three cystatins (named FhStf-1, -2 and -3) are members of the I25A subfamily (stefins). Whereas FhStf-1 grouped with classical stefins, FhStf-2 and 3 fell in a divergent stefin subgroup unusually featuring signal peptides. Recombinant rFhStf-1, -2 and -3 had potent inhibitory activity againstF. hepaticacathepsinLcysteine proteinases but differed in their capacity to inhibit mammalian cathepsinB,LandC. FhStf-1 was localized in theF. hepaticareproductive organs (testes and ovary), and at the surface lamella of the adult gut, where it may regulate cysteine proteinases related with reproduction and digestion, respectively. FhStf-1 was also detected amongF. hepaticaexcretion–secretion (E/S) products of adult flukes. This suggests that it is secreted by non-classical secretory pathway and that it may interact with host lysosomal cysteine proteinases.
The First Jewish Astronomers: Lunar Theory and Reconstruction of a Dead Sea Scroll
Authors: Ratzon Eshbal 
Published: July 2017

ArgumentThe Astronomical Book of Enoch describes the passage of the moon through the gates of heaven, which stand at the edges of the earth. In doing so, the book describes the position of the rising and setting of the moon on the horizon. Otto Neugebauer, the historian of ancient science, suggested using the detailed tables found in later Ethiopic texts in order to reconstruct the path of the moon through the gates. This paper offers a new examination of earlier versions of the Astronomical Book, using a mathematical analysis of the figures and astronomical theories presented throughout the Aramaic Astronomical Book; the results fit both the data preserved in the scrolls and the mathematical approach and religious ideology of the scroll's authors better than the details found in the late Ethiopic texts. Among other new insights, this alternate theory also teaches about the process of the composition of the Astronomical Book in the first centuries of its composition.
Reversal of cancer gene expression correlates with drug efficacy and reveals therapeutic targets
Authors: Chen Bin , Ma Li , Paik Hyojung , Sirota Marina , Wei Wei , Chua Mei-Sze , So Samuel , Butte Atul J. 
Published: July 2017

AbstractThe decreasing cost of genomic technologies has enabled the molecular characterization of large-scale clinical disease samples and of molecular changes upon drug treatment in various disease models. Exploring methods to relate diseases to potentially efficacious drugs through various molecular features is critically important in the discovery of new therapeutics. Here we show that the potency of a drug to reverse cancer-associated gene expression changes positively correlates with that drug’s efficacy in preclinical models of breast, liver and colon cancers. Using a systems-based approach, we predict four compounds showing high potency to reverse gene expression in liver cancer and validate that all four compounds are effective in five liver cancer cell lines. The in vivo efficacy of pyrvinium pamoate is further confirmed in a subcutaneous xenograft model. In conclusion, this systems-based approach may be complementary to the traditional target-based approach in connecting diseases to potentially efficacious drugs.
Capicua deficiency induces autoimmunity and promotes follicular helper T cell differentiation via derepression of ETV5
Authors: Park Sungjun , Lee Seungwon , Lee Choong-Gu , Park Guk Yeol , Hong Hyebeen , Lee Jeon-Soo , Kim Young Min , Lee Sung Bae , Hwang Daehee , Choi Youn Soo , Fryer John D. , Im Sin-Hyeog , Lee Seung-Woo , Lee Yoontae 
Published: July 2017

AbstractHigh-affinity antibody production through the germinal centre (GC) response is a pivotal process in adaptive immunity. Abnormal development of follicular helper T (TFH) cells can induce the GC response to self-antigens, subsequently leading to autoimmunity. Here we show the transcriptional repressor Capicua/CIC maintains peripheral immune tolerance by suppressing aberrant activation of adaptive immunity. CIC deficiency induces excessive development of TFH cells and GC responses in a T-cell-intrinsic manner. ETV5 expression is derepressed in Cic null TFH cells and knockdown of Etv5 suppresses the enhanced TFH cell differentiation in Cic-deficient CD4+ T cells, suggesting that Etv5 is a critical CIC target gene in TFH cell differentiation. Furthermore, we identify Maf as a downstream target of the CIC–ETV5 axis in this process. These data demonstrate that CIC maintains T-cell homeostasis and negatively regulates TFH cell development and autoimmunity.
Scalable variable-index elasto-optic metamaterials for macroscopic optical components and devices
Authors: Shin Dongheok , Kim Junhyun , Kim Changwook , Bae Kyuyoung , Baek Seunghwa , Kang Gumin , Urzhumov Yaroslav , Smith David R. , Kim Kyoungsik 
Published: July 2017

AbstractOptical metamaterials with an artificial subwavelength structure offer new approaches to implement advanced optical devices. However, some of the biggest challenges associated with the development of metamaterials in the visible spectrum are the high costs and slow production speeds of the nanofabrication processes. Here, we demonstrate a macroscale (>35 mm) transformation-optics wave bender (293 mm2) and Luneburg lens (855 mm2) in the broadband white-light visible wavelength range using the concept of elasto-optic metamaterials that combines optics and solid mechanics. Our metamaterials consist of mesoscopically homogeneous chunks of bulk aerogels with superior, broadband optical transparency across the visible spectrum and an adjustable, stress-tuneable refractive index ranging from 1.43 down to nearly the free space index (∼1.074). The experimental results show that broadband light can be controlled and redirected in a volume of >105λ × 105λ × 103λ, which enables natural light to be processed directly by metamaterial-based optical devices without any additional coupling components.
Acetylation-induced TDP-43 pathology is suppressed by an HSF1-dependent chaperone program
Authors: Wang Ping , Wander Connor M. , Yuan Chao-Xing , Bereman Michael S. , Cohen Todd J. 
Published: July 2017

AbstractTDP-43 pathology marks a spectrum of multisystem proteinopathies including amyotrophic lateral sclerosis, frontotemporal lobar degeneration, and sporadic inclusion body myositis. Surprisingly, it has been challenging to recapitulate this pathology, highlighting an incomplete understanding of TDP-43 regulatory mechanisms. Here we provide evidence supporting TDP-43 acetylation as a trigger for disease pathology. Using cultured cells and mouse skeletal muscle, we show that TDP-43 acetylation-mimics promote TDP-43 phosphorylation and ubiquitination, perturb mitochondria, and initiate degenerative inflammatory responses that resemble sporadic inclusion body myositis pathology. Analysis of functionally linked amyotrophic lateral sclerosis proteins revealed recruitment of p62, ubiquilin-2, and optineurin to TDP-43 aggregates. We demonstrate that TDP-43 acetylation-mimic pathology is potently suppressed by an HSF1-dependent mechanism that disaggregates TDP-43. Our study illustrates bidirectional TDP-43 processing in which TDP-43 aggregation is targeted by a coordinated chaperone response. Thus, activation or restoration of refolding mechanisms may alleviate TDP-43 aggregation in tissues that are uniquely susceptible to TDP-43 proteinopathies.
Plasmonically Enhanced Reflectance of Heat Radiation from Low-Bandgap Semiconductor Microinclusions
Authors: Tang Janika , Thakore Vaibhav , Ala-Nissila Tapio 
Published: July 2017

AbstractIncreased reflectance from the inclusion of highly scattering particles at low volume fractions in an insulating dielectric offers a promising way to reduce radiative thermal losses at high temperatures. Here, we investigate plasmonic resonance driven enhanced scattering from microinclusions of low-bandgap semiconductors (InP, Si, Ge, PbS, InAs and Te) in an insulating composite to tailor its infrared reflectance for minimizing thermal losses from radiative transfer. To this end, we compute the spectral properties of the microcomposites using Monte Carlo modeling and compare them with results from Fresnel equations. The role of particle size-dependent Mie scattering and absorption efficiencies, and, scattering anisotropy are studied to identify the optimal microinclusion size and material parameters for maximizing the reflectance of the thermal radiation. For composites with Si and Ge microinclusions we obtain reflectance efficiencies of 57–65% for the incident blackbody radiation from sources at temperatures in the range 400–1600 °C. Furthermore, we observe a broadbanding of the reflectance spectra from the plasmonic resonances due to charge carriers generated from defect states within the semiconductor bandgap. Our results thus open up the possibility of developing efficient high-temperature thermal insulators through use of the low-bandgap semiconductor microinclusions in insulating dielectrics.
Antiplasmodial Ealapasamines A-C,‘Mixed’ Naphthylisoquinoline Dimers from the Central African Liana Ancistrocladus ealaensis
Authors: Tshitenge Dieudonné Tshitenge , Feineis Doris , Mudogo Virima , Kaiser Marcel , Brun Reto , Bringmann Gerhard 
Published: July 2017

AbstractThree unusual heterodimeric naphthylisoquinoline alkaloids, named ealapasamines A-C (1–3), were isolated from the leaves of the tropical plant Ancistrocladus ealaensis J. Léonard. These ‘mixed’, constitutionally unsymmetric dimers are the first stereochemically fully assigned cross-coupling products of a 5,8′- and a 7,8′-coupled naphthylisoquinoline linked via C-6′ in both naphthalene portions. So far, only two other West and Central Ancistrocladus species were known to produce dimers with a central 6,6″-axis, yet, in contrast to the ealapasamines, usually consisting of two 5,8′-coupled monomers, like e.g., in michellamine B. The new dimers 1–3 contain six elements of chirality, four stereogenic centers and the two outer axes, while the central biaryl axis is configurationally unstable. The elucidation of the complete stereostructures of the ealapasamines was achieved by the interplay of spectroscopic methods including HRESIMS, 1D and 2D NMR (in particular ROESY measurements), in combination with chemical (oxidative degradation) and chiroptical (electronic circular dichroism) investigations. The ealapasamines A-C display high antiplasmodial activities with excellent half-maximum inhibition concentration values in the low nanomolar range.
Chemical inhibitors of Candida albicans hyphal morphogenesis target endocytosis
Authors: Bar-Yosef Hagit , Vivanco Gonzalez Nora , Ben-Aroya Shay , Kron Stephen J. , Kornitzer Daniel 
Published: July 2017

AbstractCandida albicans is an opportunistic pathogen, typically found as a benign commensal yeast living on skin and mucosa, but poised to invade injured tissue to cause local infections. In debilitated and immunocompromised individuals, C. albicans may spread to cause life-threatening systemic infections. Upon contact with serum and at body temperature, C. albicans performs a regulated switch to filamentous morphology, characterized by emergence of a germ tube from the yeast cell followed by mold-like growth of branching hyphae. The ability to switch between growth morphologies is an important virulence factor of C. albicans. To identify compounds able to inhibit hyphal morphogenesis, we screened libraries of existing drugs for inhibition of the hyphal switch under stringent conditions. Several compounds that specifically inhibited hyphal morphogenesis were identified. Chemogenomic analysis suggested an interaction with the endocytic pathway, which was confirmed by direct measurement of fluid-phase endocytosis in the presence of these compounds. These results suggest that the activity of the endocytic pathway, which is known to be particularly important for hyphal growth, represents an effective target for hyphae-inhibiting drugs.
Molecular tools for GABAA receptors: High affinity ligands for β1-containing subtypes
Authors: Simeone Xenia , Siebert David C. B. , Bampali Konstantina , Varagic Zdravko , Treven Marco , Rehman Sabah , Pyszkowski Jakob , Holzinger Raphael , Steudle Friederike , Scholze Petra , Mihovilovic Marko D. , Schnürch Michael , Ernst Margot 
Published: July 2017

Abstractγ-Aminobutyric acid type A (GABAA) receptors are pentameric GABA-gated chloride channels that are, in mammalians, drawn from a repertoire of 19 different genes, namely α1-6, β1-3, γ1-3, δ, ε, θ, π and ρ1-3. The existence of this wide variety of subunits as well as their diverse assembly into different subunit compositions result in miscellaneous receptor subtypes. In combination with the large number of known and putative allosteric binding sites, this leads to a highly complex pharmacology. Recently, a novel binding site at extracellular α+/β− interfaces was described as the site of modulatory action of several pyrazoloquinolinones. In this study we report a highly potent ligand from this class of compounds with pronounced β1-selectivity that mainly lacks α-subunit selectivity. It constitutes the most potent β1-selective positive allosteric modulatory ligand with known binding site. In addition, a proof of concept pyrazoloquinolinone ligand lacking the additional high affinity interaction with the benzodiazepine binding site is presented. Ultimately, such ligands can be used as invaluable molecular tools for the detection of β1-containing receptor subtypes and the investigation of their abundance and distribution.
SNAP-tagged Chikungunya Virus Replicons Improve Visualisation of Non-Structural Protein 3 by Fluorescence Microscopy
Authors: Remenyi Roland , Roberts Grace C. , Zothner Carsten , Merits Andres , Harris Mark 
Published: July 2017

AbstractChikungunya virus (CHIKV), a mosquito-borne alphavirus, causes febrile disease, muscle and joint pain, which can become chronic in some individuals. The non-structural protein 3 (nsP3) plays essential roles during infection, but a complete understanding of its function is lacking. Here we used a microscopy-based approach to image CHIKV nsP3 inside human cells. The SNAP system consists of a self-labelling enzyme tag, which catalyses the covalent linking of exogenously supplemented synthetic ligands. Genetic insertion of this tag resulted in viable replicons and specific labelling while preserving the effect of nsP3 on stress granule responses and co-localisation with GTPase Activating Protein (SH3 domain) Binding Proteins (G3BPs). With sub-diffraction, three-dimensional, optical imaging, we visualised nsP3-positive structures with variable density and morphology, including high-density rod-like structures, large spherical granules, and small, low-density structures. Next, we confirmed the utility of the SNAP-tag for studying protein turnover by pulse-chase labelling. We also revealed an association of nsP3 with cellular lipid droplets and examined the spatial relationships between nsP3 and the non-structural protein 1 (nsP1). Together, our study provides a sensitive, specific, and versatile system for fundamental research into the individual functions of a viral non-structural protein during infection with a medically important arthropod-borne virus (arbovirus).
Mapping and characterization of G-quadruplexes in Mycobacterium tuberculosis gene promoter regions
Authors: Perrone Rosalba , Lavezzo Enrico , Riello Erika , Manganelli Riccardo , Palù Giorgio , Toppo Stefano , Provvedi Roberta , Richter Sara N. 
Published: July 2017

AbstractMycobacterium tuberculosisis the causative agent of tuberculosis (TB), one of the top 10 causes of death worldwide in 2015. The recent emergence of strains resistant to all current drugs urges the development of compounds with new mechanisms of action. G-quadruplexes are nucleic acids secondary structures that may form in G-rich regions to epigenetically regulate cellular functions. Here we implemented a computational tool to scan the presence of putative G-quadruplex forming sequences in the genome ofMycobacterium tuberculosisand analyse their association to transcription start sites. We found that the most stable G-quadruplexes were in the promoter region of genes belonging to definite functional categories. Actual G-quadruplex folding of four selected sequences was assessed by biophysical and biomolecular techniques: all molecules formed stable G-quadruplexes, which were further stabilized by two G-quadruplex ligands. These compounds inhibitedMycobacterium tuberculosisgrowth with minimal inhibitory concentrations in the low micromolar range. These data support formation ofMycobacterium tuberculosisG-quadruplexesin vivoand their potential regulation of gene transcription, and prompt the use of G4 ligands to develop original antitubercular agents.
Predicting susceptibility to tuberculosis based on gene expression profiling in dendritic cells
Authors: Blischak John D. , Tailleux Ludovic , Myrthil Marsha , Charlois Cécile , Bergot Emmanuel , Dinh Aurélien , Morizot Gloria , Chény Olivia , Platen Cassandre Von , Herrmann Jean-Louis , Brosch Roland , Barreiro Luis B. , Gilad Yoav 
Published: July 2017

AbstractTuberculosis (TB) is a deadly infectious disease, which kills millions of people every year. The causative pathogen, Mycobacterium tuberculosis (MTB), is estimated to have infected up to a third of the world’s population; however, only approximately 10% of infected healthy individuals progress to active TB. Despite evidence for heritability, it is not currently possible to predict who may develop TB. To explore approaches to classify susceptibility to TB, we infected with MTB dendritic cells (DCs) from putatively resistant individuals diagnosed with latent TB, and from susceptible individuals that had recovered from active TB. We measured gene expression levels in infected and non-infected cells and found hundreds of differentially expressed genes between susceptible and resistant individuals in the non-infected cells. We further found that genetic polymorphisms nearby the differentially expressed genes between susceptible and resistant individuals are more likely to be associated with TB susceptibility in published GWAS data. Lastly, we trained a classifier based on the gene expression levels in the non-infected cells, and demonstrated reasonable performance on our data and an independent data set. Overall, our promising results from this small study suggest that training a classifier on a larger cohort may enable us to accurately predict TB susceptibility.