bluuebunny/crossref_metadata_2025_split huggingface dataset:
Long‐term, dynamic synaptic reorganization after GABAergic precursor cell transplantation into adult mouse spinal cord
Authors: Llewellyn‐Smith Ida J. , Basbaum Allan I. , Bráz João M. 
Published: November 2017

AbstractTransplanting embryonic precursors of GABAergic neurons from the medial ganglionic eminence (MGE) into adult mouse spinal cord ameliorates mechanical and thermal hypersensitivity in peripheral nerve injury models of neuropathic pain. Although Fos and transneuronal tracing studies strongly suggest that integration of MGE‐derived neurons into host spinal cord circuits underlies recovery of function, the extent to which there is synaptic integration of the transplanted cells has not been established. Here, we used electron microscopic immunocytochemistry to assess directly integration of GFP‐expressing MGE‐derived neuronal precursors into dorsal horn circuitry in intact, adult mice with short‐ (5–6 weeks) or long‐term (4–6 months) transplants. We detected GFP with pre‐embedding avidin–biotin‐peroxidase and GABA with post‐embedding immunogold labeling. At short and long times post‐transplant, we found host‐derived synapses on GFP‐immunoreactive MGE cells bodies and dendrites. The proportion of dendrites with synaptic input increased from 50% to 80% by 6 months. In all mice, MGE‐derived terminals formed synapses with GFP‐negative (host) cell bodies and dendrites and, unexpectedly, with some GFP‐positive (i.e., MGE‐derived) dendrites, possibly reflecting autoapses or cross talk among transplanted neurons. We also observed axoaxonic appositions between MGE and host terminals. Immunogold labeling for GABA confirmed that the transplanted cells were GABAergic and that some transplanted cells received an inhibitory GABAergic input. We conclude that transplanted MGE neurons retain their GABAergic phenotype and integrate dynamically into host‐transplant synaptic circuits. Taken together with our previous electrophysiological analyses, we conclude that MGE cells are not GABA pumps, but alleviate pain and itch through synaptic release of GABA.
Electrochromism in Polymer‐Electrolyte‐Enabled Nanostructured WO3: Active Layer Thickness and Morphology on Device Performance
Authors: Bathe Suvarna Ravi , Illa Mr. Sivaram , Narayan Ramanuj , Basak Pratyay 
Published: November 2017

AbstractHerein, we showcase the ease and feasibility of integrating a quasi‐solid semi‐IPN electrolyte supporting Li+‐ion conduction with nanostructured WO3 to achieve a functional electrochromic device with impressive performance and stability. Co‐continuous WO3 electrodes, obtained layer‐by‐layer, reveal interesting changes in morphology from plate‐like structures to nanoparticles. The nanostructured electrodes offer a large surface area and a sufficiently open architecture for realizing effective permeation of the polymeric electrolyte. WO3 films (∼300 nm) achieved with five repetitive deposition‐spin cycles (5 L) provide best coverage, electrolyte wetting and device characteristics. Redox efficiency and reversibility >2000 cycles indicates a stable electrode‐electrolyte interface and device performance. A considerably high coloration efficiency of ∼134 cm2 C−1, an appreciably fast switching response (<2 s), full coloration/bleaching at competitive time scales of 5.9 s and 5.1 s, respectively, along with device reversibility of ≈97 % underline the viability of electrode architecture and polymer electrolyte combination.
Pharmacokinetics, Pharmacodynamics, and Safety of a Long‐Acting Human Growth Hormone (MOD‐4023) in Healthy Japanese and Caucasian Adults
Authors: Kramer William G. , Jaron‐Mendelson Michal , Koren Ronit , Hershkovitz Oren , Hart Gili 
Published: November 2017

AbstractDaily injections of growth hormone (GH) as replacement therapy in GH‐deficient (GHD) patients may cause poor compliance and inconvenience. C‐terminal peptide–modified human GH (MOD­4023) has been developed for once­weekly administration in GHD adults and children. In the present study, the pharmacokinetics (PK) and pharmacodynamics (PD) of a single subcutaneous dose of MOD­4023 were evaluated in healthy Caucasian and Japanese adults, using a phase 1 double‐blind, vehicle‐controlled, randomized study design. The study was conducted in 42 healthy Japanese (n = 21) and Caucasian (n = 21) men receiving either MOD‐4023 at a dose of 2.5, 7.5, or 15 mg or vehicle. In the 2.5‐ and 7.5‐mg cohorts, no differences in mean MOD‐4023 serum concentration were found between Japanese and Caucasian subjects. A comparison of PK parameters in the 15‐mg group suggests a slower absorption rate of MOD‐4023 in Japanese subjects. PD analysis showed no apparent differences in IGF‐1 and IGFBP‐3 plasma concentrations between the Japanese and Caucasian subjects and indicated that a dose of 15 mg achieved the maximal effect in both ethnic groups. MOD‐4023 demonstrated a favorable safety profile and local tolerance following single‐dose subcutaneous administration. This study provides additional support for the development of MOD‐4023 as a long‐acting human growth hormone formulation for once‐weekly administration.
On the Performance of Hybrid Functionals for Non‐linear Optical Properties and Electronic Excitations in Chiral Molecular Crystals: The Case of Butterfly‐Shaped Dicinnamalacetone
Authors: da Silva Pedro S. Pereira , Martín‐Ramos Pablo , Domingos Sérgio R. , Bota de Sousa Maria do Carmo , Arranja Cláudia T. , Sobral Abílio J. F. N. , Ramos Silva Manuela 
Published: November 2017

AbstractPurely organic chiral molecular assemblies in the solid state hold great potential for non‐linear optical applications. Herein, a newly synthesised molecular system is reported, namely, dicinnamalacetone, an otherwise planar molecule that crystallises in a disordered non‐centrosymmetric form with four different conformations having an overall predominance of a particular helicity. A combined experimental and theoretical approach, including single‐crystal X‐ray diffraction, Kurtz–Perry and ab initio methods, is employed to characterise the system and benchmark the performance of hybrid functionals for the prediction of non‐linear optical properties and electronic excitations. Comparison of experiment and theory points to a particular set of hybrid functionals that provides an optimal description of this molecular system.
Development and Application of a Voltammetric Biosensor Based on Polypyrrole/uricase/graphene for Uric Acid Determination
Authors: de Fátima Giarola Juliana , Mano Valdir , Pereira Arnaldo César 
Published: November 2017

AbstractIn the present paper a voltammetric biosensor based on platinum electrode and polypyrrole / uricase / graphene composite, named Pt‐PPy/UOx/Grap has been successfully prepared and validated for uric acid (UA) determination in real samples. The electrochemical behavior has been evaluated by employing cyclic voltammetric. The charge transfer coefficient, α, and the charge transfer rate constant, κs, for electron transfer between PPy/UOx/Grap and Pt were calculated as 0.71, in average, and 48.3 s−1, respectively. Under optimized conditions for the composite (2.5 U mL−1 of UOx, 0.3 mg mL−1 of Grap and 2.9 mmol L−1 of pyrrole) and for the analysis (pH 7.0 in 0.1 mol L−1 phosphate buffer) the method was validated for UA determination at human urine and showed good linearity to UA from 2 up to 24 nmol L−1 (r=0.993) with limits of detection and quantification of 0.541 and 1.805 nmol L−1, respectively. The results obtained for the UA determination at urine presented a relative error lower than 5 %, showing the good performance of the method developed and potential application in UA clinical analysis.
Recent Advances in Flexible Electrochromic Devices: Prerequisites, Challenges, and Prospects
Authors: Eh Alice Lee‐Sie , Tan Alvin Wei Ming , Cheng Xing , Magdassi Shlomo , Lee Pooi See 
Published: November 2017

AbstractElectrochromic (EC) technology has progressed tremendously in recent years. Rigid EC devices have advanced to offer additional attractive physical attributes such as flexibility, stretchability, and foldability. These features are appealing for wearable and futuristic technologies, and hence serve to revolutionize EC applications toward deformable electronics. In this review, the essential prerequisites of each component of the flexible EC devices are delineated, such that each component is mechanically flexible to maintain the structural integrity of the device. The recent progress in flexible EC performance is discussed, from flexible to stretchable and the foldable device being the latest trend in deformable electronics. Next, we address the pertinent challenges often encountered in the fabrication of flexible EC devices and outline the adopted strategies from the literature to this point. Finally, the concept of the multifunctional EC device is discussed for achieving versatile emerging applications. We envision that this review will shed light on the properties of flexible ECs and shape the new milestones to be set for realizing a more versatile multifunctional EC device.
Biofuel production and soil GHG emissions after land‐use change to switchgrass and giant reed in the U.S. Southeast
Authors: Nocentini Andrea , Field John , Monti Andrea , Paustian Keith 
Published: November 2017

AbstractUnited States mandated the production of biofuel from lignocellulosic feedstocks. Nonetheless, the cultivation of these feedstocks may produce debates, as agricultural land is scarce and it is primarily needed for food production and grazing. Thus, it is thought that biofuel production should be placed on land with low economical value (i.e., marginal land). At the same time, depending on what land is considered marginal and therefore available for lignocellulosic crops, different greenhouse gas impacts will be generated upon land use change. Here, we attempted to estimate the biomass production and soil greenhouse gas emissions of the cultivation of switchgrass (Panicum virgatum L.) and giant reed (Arundo donax L.) in the U.S. Southeast, when converting distinct former land uses. We employed the NLCD and the SSURGO databases to select grasslands, shrublands, and marginal croplands and to then allocate switchgrass and giant reed on this land basing on biophysical parameters included in the Land Capability Classification. After calibration, the DAYCENT model was employed to simulate 15‐year cultivation of both crops in the U.S. Southeast. Florida, Georgia, Mississippi and South Carolina were the States with the highest availability of land, thus the highest potential for biofuel production. Among scenarios, the one converting poor grazing land and marginal croplands yielded the greatest benefits: converting 3.6 Mha of land, 44 Mt/year of dry biomass could be produced, storing 0.05 Mt/year of soil organic C at the same time. In this scenario, considering 80‐km supply areas, nineteen biorefineries could deliver 7,124 Ml/year of advanced ethanol across the region. When minimizing giant reed invasion risks through reallocating giant reed outside flooded areas, 4,695 Ml/year of advanced ethanol could be still delivered from thirteen biorefineries, but the scenario turned in a biogenic greenhouse gas source (3.2 Mt CO2eq/year).
Origin and dynamics of oligodendrocytes in the developing brain: Implications for perinatal white matter injury
Authors: van Tilborg Erik , de Theije Caroline G. M. , van Hal Maurik , Wagenaar Nienke , de Vries Linda S. , Benders Manon J. , Rowitch David H. , Nijboer Cora H. 
Published: November 2017

AbstractInfants born prematurely are at high risk to develop white matter injury (WMI), due to exposure to hypoxic and/or inflammatory insults. Such perinatal insults negatively impact the maturation of oligodendrocytes (OLs), thereby causing deficits in myelination. To elucidate the precise pathophysiology underlying perinatal WMI, it is essential to fully understand the cellular mechanisms contributing to healthy/normal white matter development. OLs are responsible for myelination of axons. During brain development, OLs are generally derived from neuroepithelial zones, where neural stem cells committed to the OL lineage differentiate into OL precursor cells (OPCs). OPCs, in turn, develop into premyelinating OLs and finally mature into myelinating OLs. Recent studies revealed that OPCs develop in multiple waves and form potentially heterogeneous populations. Furthermore, it has been shown that myelination is a dynamic and plastic process with an excess of OPCs being generated and then abolished if not integrated into neural circuits. Myelination patterns between rodents and humans show high spatial and temporal similarity. Therefore, experimental studies on OL biology may provide novel insights into the pathophysiology of WMI in the preterm infant and offers new perspectives on potential treatments for these patients.
Systemic immune‐checkpoint blockade with anti‐PD1 antibodies does not alter cerebral amyloid‐β burden in several amyloid transgenic mouse models
Authors: Latta‐Mahieu Martine , Elmer Bradford , Bretteville Alexis , Wang Yaming , Lopez‐Grancha Mati , Goniot Philippe , Moindrot Nicolas , Ferrari Paul , Blanc Véronique , Schussler Nathalie , Brault Emmanuel , Roudières Valérie , Blanchard Véronique , Yang Zhi‐Yong , Barneoud Pascal , Bertrand Philippe , Roucourt Bart , Carmans Sofie , Bottelbergs Astrid , Mertens Liesbeth , Wintmolders Cindy , Larsen Peter , Hersley Caroline , McGathey Tyler , Racke Margaret M. , Liu Ling , Lu Jirong , O'Neill Michael J. , Riddell David R. , Ebneth Andreas , Nabel Gary J. , Pradier Laurent 
Published: November 2017

AbstractChronic inflammation represents a central component in the pathogenesis of Alzheimer's disease (AD). Recent work suggests that breaking immune tolerance by Programmed cell Death‐1 (PD1) checkpoint inhibition produces an IFN‐γ‐dependent systemic immune response, with infiltration of the brain by peripheral myeloid cells and neuropathological as well as functional improvements even in mice with advanced amyloid pathology (Baruch et al., (): Nature Medicine, 22:135–137). Immune checkpoint inhibition was therefore suggested as potential treatment for neurodegenerative disorders when activation of the immune system is appropriate. Because a xenogeneic rat antibody (mAb) was used in the study, whether the effect was specific to PD1 target engagement was uncertain. In the present study we examined whether PD1 immunotherapy can lower amyloid‐β pathology in a range of different amyloid transgenic models performed at three pharmaceutical companies with the exact same anti‐PD1 isotype and two mouse chimeric variants. Although PD1 immunotherapy stimulated systemic activation of the peripheral immune system, monocyte‐derived macrophage infiltration into the brain was not detected, and progression of brain amyloid pathology was not altered. Similar negative results of the effect of PD1 immunotherapy on amyloid brain pathology were obtained in two additional models in two separate institutions. These results show that inhibition of PD1 checkpoint signaling by itself is not sufficient to reduce amyloid pathology and that additional factors might have contributed to previously published results (Baruch et al., (): Nature Medicine, 22:135–137). Until such factors are elucidated, animal model data do not support further evaluation of PD1 checkpoint inhibition as a therapeutic modality for Alzheimer's disease.
Microglia from offspring of dams with allergic asthma exhibit epigenomic alterations in genes dysregulated in autism
Authors: Vogel Ciernia Annie , Careaga Milo , LaSalle Janine M. , Ashwood Paul 
Published: November 2017

AbstractDysregulation in immune responses during pregnancy increases the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive, and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain's resident immune cells. We therefore tested the hypothesis that epigenomic alterations to microglia may be involved in behavioral abnormalities observed in MAA offspring. We used the genome‐wide approaches of whole genome bisulfite sequencing to examine DNA methylation and RNA sequencing to examine gene expression in microglia from juvenile MAA offspring. Differentially methylated regions were enriched for immune signaling pathways and important microglial developmental transcription factor binding motifs. Differential expression analysis identified genes involved in controlling microglial sensitivity to the environment and shaping neuronal connections in the developing brain. Differentially expressed genes significantly overlapped genes with altered expression in human ASD cortex, supporting a role for microglia in the pathogenesis of ASD.
Cortical hemispheric asymmetries are present at young ages and further develop into adolescence
Authors: Yamazaki Hiroshi , Easwar Vijayalakshmi , Polonenko Melissa Jane , Jiwani Salima , Wong Daniel D. E. , Papsin Blake Croll , Gordon Karen Ann 
Published: November 2017

AbstractSpecialization of the auditory cortices for pure tone listening may develop with age. In adults, the right hemisphere dominates when listening to pure tones and music; we thus hypothesized that (a) asymmetric function between auditory cortices increases with age and (b) this development is specific to tonal rather than broadband/non‐tonal stimuli. Cortical responses to tone‐bursts and broadband click‐trains were recorded by multichannel electroencephalography in young children (5.1 ± 0.8 years old) and adolescents (15.2 ± 1.7 years old) with normal hearing. Peak dipole moments indicating activity strength in right and left auditory cortices were calculated using the Time Restricted, Artefact and Coherence source Suppression (TRACS) beamformer. Monaural click‐trains and tone‐bursts in young children evoked a dominant response in the contralateral right cortex by left ear stimulation and, similarly, a contralateral left cortex response to click‐trains in the right ear. Responses to tone‐bursts in the right ear were more bilateral. In adolescents, peak activity dominated in the right cortex in most conditions (tone‐bursts from either ear and to clicks from the left ear). Bilateral activity was evoked by right ear click stimulation. Thus, right hemispheric specialization for monaural tonal stimuli begins in children as young as 5 years of age and becomes more prominent by adolescence. These changes were marked by consistent dipole moments in the right auditory cortex with age in contrast to decreases in dipole activity in all other stimulus conditions. Together, the findings reveal increasingly asymmetric function for the two auditory cortices, potentially to support greater cortical specialization with development into adolescence.
Acyclic Cucurbit[n]uril‐type Receptors: Preparation, Molecular Recognition Properties and Biological Applications
Authors: Ganapati Shweta , Isaacs Lyle 
Published: November 2017

AbstractThis article traces the development of acyclic cucurbit[n]uril‐type receptors with a focus on work from the Isaacs group. First, we describe the synthesis of methylene bridged glycoluril dimers capped with aromatic sidewalls which allowed us to probe the interconversion of the S‐ and C‐shaped dimers which is a fundamental step in CB[n] formation. The C‐shaped compounds were found to undergo discrete self‐assembly (dimerization) in both water and organic solvents which lead us to investigate multicomponent self‐sorting systems. We supressed the self‐association of 8 by electrostatic repulsion in the putative dimer which allowed expression of its innate molecular recognition properties toward methylene blue and related planar cationic dyes. Longer glycoluril oligomers (trimer‐hexamer, acyclic decamer) were prepared by starving the CB[n]‐forming reaction of formaldehyde. The longer oligomers (e. g. 15 and 16) bind to alkylammonium ions in water ≈100‐fold weaker than macrocyclic CB[n] highlighting the high preorganization of the acyclic but polycyclic framework. We prepared a wide variety of acyclic CB[n] compounds (wall variants, solubilizing group variants, linker variants) based on glycoluril trimer and tetramer. In particular, 26 and 27 have been shown to possess a wide variety of chemically and biologically interesting functions. For example, 26 was used to formulate the insoluble drug Albendazole and treat mice bearing SK‐OV‐3 xenograft tumors. Compound 27 binds tightly to the neuromuscular blocking agents rocuronium, vecuronium, and cisatracurium and acts as an in vivo reversal agent for these compounds in anesthetized rats. Container 27 was also found to modulate the hyperlocomotive effect of rats that had been treated with methamphetamine. Finally, 38 has been used as a cross reactive component of sensor arrays that are capable of classifying and quantifying cancer related nitroamine and a range of over the counter drugs. Overall, the work demonstrates that acyclic CB[n]‐type compounds are nicely pre‐organized and therefore retain the essential aspects of the recognition properties of macrocyclic CB[n] but allow for more straightforward tailoring of structure and solubility that enables a variety of chemically and biologically important applications.
Genetic Risk Factors for Atypical Femoral Fractures (AFFs): A Systematic Review
Authors: Nguyen Hanh H , van de Laarschot Denise M , Verkerk Annemieke JMH , Milat Frances , Zillikens M Carola , Ebeling Peter R 
Published: November 2017

ABSTRACTAtypical femoral fractures (AFFs) are uncommon and have been associated particularly with long‐term antiresorptive therapy, including bisphosphonates. Although the pathogenesis of AFFs is unknown, their identification in bisphosphonate‐naïve individuals and in monogenetic bone disorders has led to the hypothesis that genetic factors predispose to AFF. Our aim was to review and summarize the evidence for genetic factors in individuals with AFF. We conducted structured literature searches and hand‐searching of conference abstracts/reference lists for key words relating to AFF and identified 2566 citations. Two individuals independently reviewed citations for (i) cases of AFF in monogenetic bone diseases and (ii) genetic studies in individuals with AFF. AFFs were reported in 23 individuals with the following 7 monogenetic bone disorders (gene): osteogenesis imperfecta (COL1A1/COL1A2), pycnodysostosis (CTSK), hypophosphatasia (ALPL), X‐linked osteoporosis (PLS3), osteopetrosis, X‐linked hypophosphatemia (PHEX), and osteoporosis pseudoglioma syndrome (LRP5). In 8 cases (35%), the monogenetic bone disorder was uncovered after the AFF occurred. Cases of bisphosphonate‐naïve AFF were reported in pycnodysostosis, hypophosphatasia, osteopetrosis, X‐linked hypophosphatemia, and osteoporosis pseudoglioma syndrome. A pilot study in 13 AFF patients and 268 controls identified a greater number of rare variants in AFF cases using exon array analysis. A whole‐exome sequencing study in 3 sisters with AFFs showed, among 37 shared genetic variants, a p.Asp188Tyr mutation in the GGPS1 gene in the mevalonate pathway, critical to osteoclast function, which is also inhibited by bisphosphonates. Two studies completed targeted ALPL gene sequencing, an ALPL heterozygous mutation was found in 1 case of a cohort of 11 AFFs, whereas the second study comprising 10 AFF cases did not find mutations in ALPL. Targeted sequencing of ALPL, COL1A1, COL1A2, and SOX9 genes in 5 cases of AFF identified a variant in COL1A2 in 1 case. These findings suggest a genetic susceptibility for AFFs. A large multicenter collaborative study of well‐phenotyped AFF cases and controls is needed to understand the role of genetics in this uncommon condition. © 2017 The Authors JBMR Plus published by Wiley Periodicals, Inc. on behalf of American Society for Bone and Mineral Research.