bluuebunny/crossref_metadata_2025_split huggingface dataset:
Procoagulant platelets: generation, function, and therapeutic targeting in thrombosis
Authors: Agbani Ejaife O. , Poole Alastair W. 
Published: October 2017

AbstractCurrent understanding of how platelets localize coagulation to wound sites has come mainly from studies of a subpopulation of activated platelets. In this review, we summarize data from the last 4 decades that have described these platelets with a range of descriptive titles and attributes. We identify striking overlaps in the reported characteristics of these platelets, which imply a single subpopulation of versatile platelets and thus suggest that their commonality requires unification of their description. We therefore propose the term procoagulant platelet as the unifying terminology. We discuss the agonist requirements and molecular drivers for the dramatic morphological transformation platelets undergo when becoming procoagulant. Finally, we provide perspectives on the biomarker potential of procoagulant platelets for thrombotic events as well as on the possible clinical benefits of inhibitors of carbonic anhydrase enzymes and the water channel Aquaporin-1 for targeting this subpopulation of platelets as antiprocoagulant antithrombotics.
Hematopoietic stem cell transplantation rescues the hematological, immunological, and vascular phenotype in DADA2
Authors: Hashem Hasan , Kumar Ashish R. , Müller Ingo , Babor Florian , Bredius Robbert , Dalal Jignesh , Hsu Amy P. , Holland Steven M. , Hickstein Dennis D. , Jolles Stephen , Krance Robert , Sasa Ghadir , Taskinen Mervi , Koskenvuo Minna , Saarela Janna , van Montfrans Joris , Wilson Keith , Bosch Barbara , Moens Leen , Hershfield Michael , Meyts Isabelle 
Published: October 2017

Key Points
HSCT represents an effective and definitive treatment of DADA2. HSCT can cure the immunological, hematological, and vascular phenotype of DADA2 with 100% survival at median follow-up of 18 months.
Giving and Gambling
Authors: Delalande Nicolas 
Published: October 2017

AbstractIn 1933 a national lottery was created in France on a temporary basis. It was intended to fund in part the war veterans' pensions. Although lotteries had been forbidden and despised since 1836, this institution soon became a strong pillar of the fiscal system in France and in other European countries. This article explores the origins of this story and shows how, in the early 1930s, a small association of war veterans, the Gueules Cassées, were instrumental in shifting the boundaries among the gift, gambling, and solidarity. Looking for new resources in the midst of a deep economic crisis, the state found inspiration in this private experiment. The lottery's success depended on its appeal to charity, the players' greed, and fierce competition between public and private actors. This study highlights the contradictory and forgotten origins of the French welfare state, at the crossroads of philanthropy, market, and public sphere.En 1933 fut créée, de façon d'abord temporaire, une loterie nationale destinée à financer les pensions des anciens combattants. En quelques années, cette institution décriée, interdite depuis 1836, devint un levier essentiel du financement de l'Etat, aussi bien en France que dans d'autres pays européens. Cet article explore les origines de cette histoire en montrant comment, au début des années 1930, une opération lancée par une petite association, les Gueules cassées, contribua à déplacer les frontières entre le don, le jeu et la solidarité. En pleine crise économique, l'Etat s'inspira de cette initiative pour trouver de nouvelles ressources et honorer ses promesses. Le succès de la loterie s'appuya sur les appels à la bienfaisance, l'appât du gain et la mise en concurrence des acteurs publics et privés. Cette étude met ainsi en évidence les origines paradoxales et méconnues de l'Etat social français, au carrefour de la philanthropie, du marché et de la sphère publique.
Bone Mass Assessment in a Cohort of Adults With Down Syndrome: A Cross-Sectional Study
Authors: Costa Ramón , De Miguel Rosa , García Clara , de Asúa Diego Real , Castañeda Santos , Moldenhauer Fernando , Suárez Carmen 
Published: October 2017

Abstract
Differences in bone mineral density (BMD) have been observed between adults with Down syndrome (DS) and the general population. The purpose of this article is to describe the prevalence of bone mass disorders in a cohort of adults with DS and their predisposing factors. We performed a cross-sectional study of 104 consecutively recruited adults with DS from an outpatient clinic of a tertiary care hospital in Madrid, Spain. We recorded epidemiological and anthropometric data, nutritional variables, coexisting clinical conditions, and laboratory variables. BMD was measured at the lumbar spine, total hip, and femoral neck using dual-energy X-ray absorptiometry. The prevalence of osteopenia ranged from 48% to 52%, and that of osteoporosis ranged from 19% to 22% depending on the site of measurement (femoral neck or lumbar spine, respectively). Age was the greatest risk factor associated for lower BMD, with similar bone mass accrual curve but with lower peak of BMD than the general population. We conclude that low bone mass is an extremely prevalent condition in adult patients with DS.
User comments about research findings: How conflictual information in online science journalistic articles influences laypeople’s understanding of scientific tentativeness
Authors: Flemming Danny , Feinkohl Insa , Cress Ulrike , Kimmerle Joachim 
Published: October 2017

AbstractThis study investigated whether conflictual information about novel medical findings in online newspaper articles affected laypeople’s perception of tentativeness, their attitude toward, and fear of, the medical procedure in question. For this purpose, we rated the user comments from all available online newspaper articles about Deep Brain Stimulation (DBS). Multilevel regressions revealed that higher levels of conflictual information in the articles were associated with higher levels of expressed tentativeness and a more negative attitude toward DBS expressed in the user comments. No significant relationship with expressed fear of DBS was found. We conclude that journalistic preparation and style is directly associated with readers’ perception of tentativeness and opinion formation and discuss suggestions for journalistic presentation of scientific information.
Controlled Release of Salidroside Microspheres Prepared Using a Chitosan and Methylcellulose Interpenetrating Polymer Network
Authors: Chen Zhenlin , Ning Fangjian , He Xingcun , Peng Hailong , Xiong Hua 
Published: October 2017

Abstract
In this work, salidroside, a functional food agent, was incorporated into novel interpenetrating polymer network microspheres (IPN-Ms) prepared by chitosan (CS) and methylcellulose (MC) for controlled release and stabilization. IPN-Ms were characterized using scanning electron microscopy, Fourier transform infrared spectroscopy (FT-IR), differential scanning calorimetry and X-ray diffraction. The result indicated that salidroside-loaded IPN-Ms (S-IPN-Ms) are hollow and highly spherical, with a coarse pleated surface and a particle size ranging from 5 to 30 µm. Schiff base formation and the hemiacetal reaction are the primary mechanisms underlying the interpenetrating network cross-linking of IPN-Ms. In S-IPN-Ms, the CS and MC were homogeneously blended, and the salidroside was molecularly and amorphously dispersed. The encapsulation efficiency of the salidroside within the S-IPN-Ms was up to 75.64 %. In the S-IPN-M complex, the release of salidroside by S-IPN-Ms was governed by burst and sustained release, and Fickian diffusion was the primary release mechanism for the entire release process. Thus, controlled release and stabilization of salidroside were achieved through incorporation of salidroside into IPN-Ms prepared by chitosan (CS) and methylcellulose.
Distinct Laterality in Forelimb-Movement Representations of Rat Primary and Secondary Motor Cortical Neurons with Intratelencephalic and Pyramidal Tract Projections
Authors: Soma Shogo , Saiki Akiko , Yoshida Junichi , Ríos Alain , Kawabata Masanori , Sakai Yutaka , Isomura Yoshikazu 
Published: October 2017

Two distinct motor areas, the primary and secondary motor cortices (M1 and M2), play crucial roles in voluntary movement in rodents. The aim of this study was to characterize the laterality in motor cortical representations of right and left forelimb movements. To achieve this goal, we developed a novel behavioral task, the Right-Left Pedal task, in which a head-restrained male rat manipulates a right or left pedal with the corresponding forelimb. This task enabled us to monitor independent movements of both forelimbs with high spatiotemporal resolution. We observed phasic movement-related neuronal activity (Go-type) and tonic hold-related activity (Hold-type) in isolated unilateral movements. In both M1 and M2, Go-type neurons exhibited bias toward contralateral preference, whereas Hold-type neurons exhibited no bias. The contralateral bias was weaker in M2 than M1. Moreover, we differentiated between intratelencephalic (IT) and pyramidal tract (PT) neurons using optogenetically evoked spike collision in rats expressing channelrhodopsin-2. Even in identified PT and IT neurons, Hold-type neurons exhibited no lateral bias. Go-type PT neurons exhibited bias toward contralateral preference, whereas IT neurons exhibited no bias. Our findings suggest a different laterality of movement representations of M1 and M2, in each of which IT neurons are involved in cooperation of bilateral movements, whereas PT neurons control contralateral movements.SIGNIFICANCE STATEMENTIn rodents, the primary and secondary motor cortices (M1 and M2) are involved in voluntary movements via distinct projection neurons: intratelencephalic (IT) neurons and pyramidal tract (PT) neurons. However, it remains unclear whether the two motor cortices (M1 vs M2) and the two classes of projection neurons (IT vs PT) have different laterality of movement representations. We optogenetically identified these neurons and analyzed their functional activity using a novel behavioral task to monitor movements of the right and left forelimbs separately. We found that contralateral bias was reduced in M2 relative to M1, and in IT relative to PT neurons. Our findings suggest that the motor information processing that controls forelimb movement is coordinated by a distinct cell population.
Submillisecond Optogenetic Control of Neuronal Firing with Two-Photon Holographic Photoactivation of Chronos
Authors: Ronzitti Emiliano , Conti Rossella , Zampini Valeria , Tanese Dimitrii , Foust Amanda J. , Klapoetke Nathan , Boyden Edward S. , Papagiakoumou Eirini , Emiliani Valentina 
Published: October 2017

Optogenetic neuronal network manipulation promises to unravel a long-standing mystery in neuroscience: how does microcircuit activity relate causally to behavioral and pathological states? The challenge to evoke spikes with high spatial and temporal complexity necessitates further joint development of light-delivery approaches and custom opsins. Two-photon (2P) light-targeting strategies demonstrated in-depth generation of action potentials in photosensitive neurons bothin vitroandin vivo, but thus far lack the temporal precision necessary to induce precisely timed spiking events. Here, we show that efficient current integration enabled by 2P holographic amplified laser illumination of Chronos, a highly light-sensitive and fast opsin, can evoke spikes with submillisecond precision and repeated firing up to 100 Hz in brain slices from Swiss male mice. These results pave the way for optogenetic manipulation with the spatial and temporal sophistication necessary to mimic natural microcircuit activity.SIGNIFICANCE STATEMENTTo reveal causal links between neuronal activity and behavior, it is necessary to develop experimental strategies to induce spatially and temporally sophisticated perturbation of network microcircuits. Two-photon computer generated holography (2P-CGH) recently demonstrated 3D optogenetic control of selected pools of neurons with single-cell accuracy in depth in the brain. Here, we show that exciting the fast opsin Chronos with amplified laser 2P-CGH enables cellular-resolution targeting with unprecedented temporal control, driving spiking up to 100 Hz with submillisecond onset precision using low laser power densities. This system achieves a unique combination of spatial flexibility and temporal precision needed to pattern optogenetically inputs that mimic natural neuronal network activity patterns.
CaMKII Regulates Synaptic NMDA Receptor Activity of Hypothalamic Presympathetic Neurons and Sympathetic Outflow in Hypertension
Authors: Li De-Pei , Zhou Jing-Jing , Zhang Jixiang , Pan Hui-Lin 
Published: October 2017

NMDAR activity in the hypothalamic paraventricular nucleus (PVN) is increased and critically involved in heightened sympathetic vasomotor tone in hypertension. Calcium/calmodulin-dependent protein kinase II (CaMKII) binds to and modulates NMDAR activity. In this study, we determined the role of CaMKII in regulating NMDAR activity of PVN presympathetic neurons in male spontaneously hypertensive rats (SHRs). NMDAR-mediated EPSCs and puff NMDA-elicited currents were recorded in spinally projecting PVN neurons in SHRs and male Wistar-Kyoto (WKY) rats. The basal amplitude of evoked NMDAR-EPSCs and puff NMDA currents in retrogradely labeled PVN neurons were significantly higher in SHRs than in WKY rats. The CaMKII inhibitor autocamtide-2-related inhibitory peptide (AIP) normalized the increased amplitude of NMDAR-EPSCs and puff NMDA currents in labeled PVN neurons in SHRs but had no effect in WKY rats. Treatment with AIP also normalized the higher frequency of NMDAR-mediated miniature EPSCs of PVN neurons in SHRs. CaMKII-mediated phosphorylation level of GluN2B serine 1303 (S1303) in the PVN, but not in the hippocampus and frontal cortex, was significantly higher in SHRs than in WKY rats. Lowering blood pressure with celiac ganglionectomy in SHRs did not alter the increased level of phosphorylated GluN2B S1303 in the PVN. In addition, microinjection of AIP into the PVN significantly reduced arterial blood pressure and lumbar sympathetic nerve discharges in SHRs. Our findings suggest that CaMKII activity is increased in the PVN and contributes to potentiated presynaptic and postsynaptic NMDAR activity to elevate sympathetic vasomotor tone in hypertension.SIGNIFICANCE STATEMENTHeightened sympathetic vasomotor tone is a major contributor to the development of hypertension. Although glutamate NMDA receptor (NMDAR)-mediated excitatory drive in the hypothalamus plays a critical role in increased sympathetic output in hypertension, the molecular mechanism involved in potentiated NMDAR activity of hypothalamic presympathetic neurons remains unclear. Here we show that the activity of calcium/calmodulin-dependent protein kinase II (CaMKII) is increased and plays a key role in the potentiated presynaptic and postsynaptic NMDAR activity of hypothalamic presympathetic neurons in hypertension. Also, the inhibition of CaMKII in the hypothalamus reduces elevated blood pressure and sympathetic nerve discharges in hypertension. This new knowledge extends our understanding of the mechanism of synaptic plasticity in the hypothalamus and suggests new strategies to treat neurogenic hypertension.
Activity Patterns Elicited by Airflow in the Olfactory Bulb and Their Possible Functions
Authors: Wu Ruiqi , Liu Yue , Wang Li , Li Bo , Xu Fuqiang 
Published: October 2017

Olfactory sensory neurons (OSNs) can sense both odorants and airflows. In the olfactory bulb (OB), the coding of odor information has been well studied, but the coding of mechanical stimulation is rarely investigated. Unlike odor-sensing functions of OSNs, the airflow-sensing functions of OSNs are also largely unknown. Here, the activity patterns elicited by mechanical airflow in male rat OBs were mapped using fMRI and correlated with local field potential recordings. In an attempt to reveal possible functions of airflow sensing, the relationship between airflow patterns and physiological parameters was also examined. We found the following: (1) the activity pattern in the OB evoked by airflow in the nasal cavity was more broadly distributed than patterns evoked by odors; (2) the pattern intensity increases with total airflow, while the pattern topography with total airflow remains almost unchanged; and (3) the heart rate, spontaneous respiratory rate, and electroencephalograph power in the β band decreased with regular mechanical airflow in the nasal cavity. The mapping results provide evidence that the signals elicited by mechanical airflow in OSNs are transmitted to the OB, and that the OB has the potential to code and process mechanical information. Our functional data indicate that airflow rhythm in the olfactory system can regulate the physiological and brain states, providing an explanation for the effects of breath control in meditation, yoga, and Taoism practices.SIGNIFICANCE STATEMENTPresentation of odor information in the olfactory bulb has been well studied, but studies about breathing features are rare. Here, using blood oxygen level-dependent functional MRI for the first time in such an investigation, we explored the global activity patterns in the rat olfactory bulb elicited by airflow in the nasal cavity. We found that the activity pattern elicited by airflow is broadly distributed, with increasing pattern intensity and similar topography under increasing total airflow. Further, heart rate, spontaneous respiratory rate in the lung, and electroencephalograph power in the β band decreased with regular airflow in the nasal cavity. Our study provides further understanding of the airflow map in the olfactory bulbin vivo, and evidence for the possible mechanosensitivity functions of olfactory sensory neurons.
Fremanezumab—A Humanized Monoclonal Anti-CGRP Antibody—Inhibits Thinly Myelinated (Aδ) But Not Unmyelinated (C) Meningeal Nociceptors
Authors: Melo-Carrillo Agustin , Strassman Andrew M. , Nir Rony-Reuven , Schain Aaron J. , Noseda Rodrigo , Stratton Jennifer , Burstein Rami 
Published: October 2017

Calcitonin gene-related peptide (CGRP), the most abundant neuropeptide in primary afferent sensory neurons, is strongly implicated in the pathophysiology of migraine headache, but its role in migraine is still equivocal. As a new approach to migraine treatment, humanized anti-CGRP monoclonal antibodies (CGRP-mAbs) were developed to reduce the availability of CGRP, and were found effective in reducing the frequency of chronic and episodic migraine. We recently tested the effect of fremanezumab (TEV-48125), a CGRP-mAb, on the activity of second-order trigeminovascular dorsal horn neurons that receive peripheral input from the cranial dura, and found a selective inhibition of high-threshold but not wide-dynamic range class of neurons. To investigate the basis for this selective inhibitory effect, and further explore the mechanism of action of CGRP-mAbs, we tested the effect of fremanezumab on the cortical spreading depression-evoked activation of mechanosensitive primary afferent meningeal nociceptors that innervate the cranial dura, using single-unit recording in the trigeminal ganglion of anesthetized male rats. Fremanezumab pretreatment selectively inhibited the responsiveness of Aδ neurons, but not C-fiber neurons, as reflected in a decrease in the percentage of neurons that showed activation by cortical spreading depression. These findings identify Aδ meningeal nociceptors as a likely site of action of fremanezumab in the prevention of headache. The selectivity in its peripheral inhibitory action may partly account for fremanezumab's selective inhibition of high-threshold, as a result of a predominant A-δ input to high-threshold neurons, but not wide dynamic-range dorsal horn neurons, and why it may not be effective in all migraine patients.SIGNIFICANCE STATEMENTRecently, we reported that humanized CGRP monoclonal antibodies (CGRP-mAbs) prevent activation and sensitization of high-threshold (HT) but not wide-dynamic range trigeminovascular neurons by cortical spreading depression (CSD). In the current paper, we report that CGRP-mAbs prevent the activation of Aδ but not C-type meningeal nociceptors by CSD. This is the first identification of an anti-migraine drug that appears to be selective for Aδ-fibers (peripherally) and HT neurons (centrally). As the main CGRP-mAb site of action appears to be situated outside the brain, we conclude that the initiation of the headache phase of migraine depends on activation of meningeal nociceptors, and that for selected patients, activation of the Aδ-HT pain pathway may be sufficient for the generation of headache perception.
Integument Development in Arabidopsis Depends on Interaction of YABBY Protein INNER NO OUTER with Coactivators and Corepressors
Authors: Simon Marissa K , Skinner Debra J , Gallagher Thomas L , Gasser Charles S 
Published: October 2017

Abstract
Arabidopsis thaliana INNER NO OUTER (INO) is a YABBY protein that is essential for the initiation and development of the outer integument of ovules. Other YABBY proteins have been shown to be involved in both negative and positive regulation of expression of putative target genes. YABBY proteins have also been shown to interact with the corepressor LEUNIG (LUG) in several systems. In support of a repressive role for INO, we confirm that INO interacts with LUG and also find that INO directly interacts with SEUSS (SEU), a known corepressive partner of LUG. Further, we find that INO can directly interact with ADA2b/PROPORZ1 (PRZ1), a transcriptional coactivator that is known to interact with the histone acetyltransferase GENERAL CONTROL NONREPRESSIBLE PROTEIN 5 (GCN5, also known as HAG1). Mutations in LUG, SEU, and ADA2b/PRZ1 all lead to pleiotropic effects including a deficiency in the extension of the outer integument. Additive and synergistic effects of ada2b/prz1 and lug mutations on outer integument formation indicate that these two genes function independently to promote outer integument growth. The ino mutation is epistatic to both lug and ada2b/prz1 in the outer integument, and all three proteins are present in the nuclei of a common set of outer integument cells. This is consistent with a model where INO utilizes these coregulator proteins to activate and repress separate sets of target genes. Other Arabidopsis YABBY proteins were shown to also form complexes with ADA2b/PRZ1, and have been previously shown to interact with SEU and LUG. Thus, interaction with these corepressors and coactivator may represent a general mechanism to explain the positive and negative activities of YABBY proteins in transcriptional regulation. The LUG, SEU, and ADA2b/PRZ1 proteins would also separately be recruited to targets of other transcription factors, consistent with their roles as general coregulators, explaining the pleiotropic effects not associated with YABBY function.