bluuebunny/crossref_metadata_2025_split huggingface dataset:
A nuclear pore complex‐associated regulation of SUMOylation in meiosis
Authors: Yang Hui‐Ju , Asakawa Haruhiko , Li Fu‐An , Haraguchi Tokuko , Shih Hsiu‐Ming , Hiraoka Yasushi 
Published: December 2022

AbstractThe nuclear pore complex (NPC) provides a permeable barrier between the nucleoplasm and cytoplasm. In a subset of NPC constituents that regulate meiosis in the fission yeast Schizosaccharomyces pombe, we found that nucleoporin Nup132 (homolog of human Nup133) deficiency resulted in transient leakage of nuclear proteins during meiosis I, as observed in the nup132 gene‐deleted mutant. The nuclear protein leakage accompanied the liberation of the small ubiquitin‐like modifier (SUMO)‐specific ubiquitin‐like protease 1 (Ulp1) from the NPC. Ulp1 retention at the nuclear pore prevented nuclear protein leakage and restored normal meiosis in a mutant lacking Nup132. Furthermore, using mass spectrometry analysis, we identified DNA topoisomerase 2 (Top2) and RCC1‐related protein (Pim1) as the target proteins for SUMOylation. SUMOylation levels of Top2 and Pim1 were altered in meiotic cells lacking Nup132. HyperSUMOylated Top2 increased the binding affinity at the centromeres of nup132 gene‐deleted meiotic cells. The Top2‐12KR sumoylation mutant was less localized to the centromeric regions. Our results suggest that SUMOylation of chromatin‐binding proteins is regulated by the NPC‐bound SUMO‐specific protease and is important for the progression of meiosis.
Understanding support systems for Parkinson's disease management in community settings: A cross‐national qualitative study
Authors: Soilemezi Dia , Palmar‐Santos Ana , Navarta‐Sánchez M. Victoria , Roberts Helen C. , Pedraz‐Marcos Azucena , Haahr Anita , Sørensen Dorthe , Bragstad Line K. , Hjelle Ellen G. , Haavaag Silje Bjørnsen , Portillo Mari Carmen 
Published: December 2022

AbstractBackgroundHealth and social care systems face difficulties in managing multimorbidity, disease burden and complex needs in long‐term conditions such as Parkinson's disease.ObjectiveThis study aimed to develop a European understanding of how health and social care professionals can collaborate with stakeholders from different organizations and sectors to enhance the management of Parkinson's disease in a community setting by identifying the existing gaps in this process and how people with Parkinson's disease and their family carers could benefit from these partnerships.MethodsA mixed‐methods sequential study was conducted in Denmark, Norway, Spain and the United Kingdom. The findings from the qualitative phase are presented. Individual semistructured interviews were analysed using Braun's and Clarke's thematic analysis. A meta‐ethnography approach was used to analyse and synthesize cross‐national findings.ResultsA total of 41 healthcare professionals and 39 stakeholders from different disciplines and sectors were interviewed in the four countries. The participants acknowledged a lack of awareness of available resources and poor communication between the different support systems in the management of Parkinson's disease. To promote multiagency collaborations, the participants highlighted the need to organize services along the Parkinson's disease journey, patient involvement and strategic involvement of carers in organizing resources and Parkinson's disease care pathways. According to the participants, the benefits from multiagency partnerships could lead to an enhanced continuity of care and specialized knowledge, mobilization of resources in the community, personalized support and improved access to services.ConclusionsPolicymakers are called upon to create formal structures that facilitate multisectoral collaborations to promote an integrated system of care for the management of Parkinson's disease in the community. To address this challenge, we propose five strategies showing how organizations can work together to optimize the use of resources and enhance the management of Parkinson's disease throughout the illness trajectory.Patient or Public ContributionPatient and Public Involvement groups made up of stakeholders, healthcare professionals, patients with Parkinson's disease and family carers participated in the design of the study, the development of the interview guides and the validation of the findings.
Research on the corrosion behavior of low carbon mold flux on submerged nozzle refractory
Authors: Yang Xin , Zhang Liguo , Han Xiao , Cao Dong , Zhu Xiaolei , Zhang Junkai , He Zhijun 
Published: December 2022

AbstractIn this paper, the wetting and corrosion behavior between medium and low carbon mold flux and Al2O3‐ZrO2‐C nozzle refractory were studied through a high‐temperature wetting experiment. Combined with microstructure analysis, the corrosion mechanism of low carbon mold flux on nozzle slag line material was clarified. The results show that the wettability of low‐carbon mold flux and Al2O3‐ZrO2‐C nozzle refractory is better, compared with the traditional medium carbon mold flux, the contact angle between low‐carbon mold flux and Al2O3‐ZrO2‐C material is smaller and the mold flux spreads faster on the nozzle surface at the same temperature range. According to the microstructure analysis, the corrosion degree of low‐carbon protective slag on the ZrO2‐C material of the nozzle slag line is serious, and the corrosion depth is large. Due to the influence of carbon content, the wettability between low‐carbon mold flux and ZrO2‐C material of the nozzle slag line is better, which provides favorable kinetic conditions for the dissolution and penetration of low‐carbon mold flux into the nozzle. In addition, compared with medium carbon slag, the carbon concentration difference between low‐carbon mold flux and nozzle material is larger, resulting in greater diffusion driving force of carbon atoms, which affects the wetting, dissolution, and chemical reaction of the interface between the two phases.
Treatment of Out-of-Hospital Status Epilepticus
Authors: Carl Bazil 
Published: December 2022

A Comparison of Lorazepam, Diazepam, and Placebo for the Treatment of Out-of-Hospital Status Epilepticus Alldredge BK, Gelb AM, Isaacs SM, Corry MD, Allen F, Ulrich S, Gottwald MD, O'Neil N, Neuhaus JM, Segal MR, Lowenstein DH N Engl J Med 2001;345:631–637 Background It is uncertain whether the administration of benzodiazepines by paramedics is an effective and safe treatment for out-of-hospital status epilepticus. Methods We conducted a randomized, double-blind trial to evaluate intravenous benzodiazepines administered by paramedics for the treatment of out-of-hospital status epilepticus. Adults with prolonged (lasting five minutes or more) or repetitive generalized convulsive seizures received intravenous diazepam (5 mg), lorazepam (2 mg), or placebo. An identical second injection was given if needed. Results Of the 205 patients enrolled, 66 received lorazepam, 68 received diazepam, and 71 received placebo. Status epilepticus had been terminated on arrival at the emergency department in more patients treated with lorazepam (59.1 percent) or diazepam (42.6 percent) than patients given placebo (21.1 percent) (P=0.001). After adjustment for covariates, the odds ratio for termination of status epilepticus by the time of arrival in the lorazepam group as compared with the placebo group was 4.8 (95 percent confidence interval, 1.9 to 13.0). The odds ratio was 1.9 (95 percent confidence interval, 0.8 to 4.4) in the lorazepam group as compared with the diazepam group and 2.3 (95 percent confidence interval, 1.0 to 5.9) in the diazepam group as compared with the placebo group. The rates of respiratory or circulatory complications (indicated by bag valve-mask ventilation or an attempt at intubation, hypotension, or cardiac dysrhythmia) after the study treatment was administered were 10.6 percent for the lorazepam group, 10.3 percent for the diazepam group, and 22.5 percent for the placebo group (P=0.08). Conclusions Benzodiazepines are safe and effective when administered by paramedics for out-of-hospital status epilepticus in adults. Lorazepam is likely to be a better therapy than diazepam.
Functional MRI of Interictal EEG Activity
Authors: Lesser Ronald P. 
Published: December 2022

Simultaneous EEG and Functional MRI of Epileptic Activity: A Case Report Baudewig J, Bittermann HJ, Paulus W, Frahm J Clin Neurophysiol 2001;112:1196–1200 Objectives Attempts to localize the source of epileptic activity by linking electroencephalographic (EEG) abnormalities to blood oxygenation level-dependent (BOLD) magnetic resonance imaging (MRI) signal alterations are hampered mainly by EEG distortions during MRI, subject motion, and unknown hemodynamic response characteristics. Methods Using T2*-weighted echo-planar imaging at 2.0 T (2 s temporal resolution, 2 × 2 × 4 mm(3) spatial resolution), this work demonstrates strategies to alleviate some of these problems while studying a patient who had idiopathic generalized epilepsy with poly-spike and slow-wave complexes. Results Continuous EEG recordings during dynamic MRI (500 ms scanning, 1500 ms delay) and post-examination derivation of an EEG reference function for MRI analysis revealed positive BOLD MRI responses with temporal characteristics similar to those obtained for functional challenges. Conclusions The ability to map focal epileptic activity and/or associated cognitive processing provides new potential for both epilepsy research and clinical patient management. Spatio-Temporal Imaging of Focal Interictal Epileptiform Activity Using EEG-Triggered Functional MRI Krakow K, Lemieux L, Messina D, Scott CA, Symms MR, Duncan JS, Fish DR Epileptic Disord 2001;3:67–74 EEG-triggered, blood oxygen level-dependent functional MRI (BOLD-fMRI) was used in 24 patients with localization-related epilepsy and frequent interictal epileptiform discharges (spikes) to identify those brain areas involved in generating the spikes, and to study the evolution of the BOLD signal change over time. The location of the fMRI activation was compared with the scalp EEG spike focus and the structural MR abnormality. Twelve patients (50%) had an fMRI activation concordant with the EEG focus and structural brain abnormalities where present (n = 7). In 2 other patients, the fMRI activation was non-concordant with electroclinical findings. The remaining 10 patients (41.7%) showed no significant fMRI activation. These patients had significantly lower mean spike amplitudes compared to those with positive fMRI results (p = 0.03). The time course of the BOLD response was studied in 3 patients and this revealed a maximum signal change 1.5 to 7.5 sec after the spike. In conclusion, EEG-triggered fMRI can directly identify the generators of interictal epileptiform activity, with high spatial resolution, in selected patients with frequent spikes. The superior spatial resolution obtainable through EEG-triggered fMRI may provide an additional non-invasive tool in the presurgical evaluation of patients with intractable focal seizures.
Gabaergic Interneuron Reorganization during the Late Period May Contribute to Hippocampal Epileptogenesis
Authors: Benardo Larry S. 
Published: December 2022

Alterations of Hippocampal GABAergic System Contribute to Development of Spontaneous Recurrent Seizures in the Rat Lithium-Pilocarpine Model of Temporal Lobe Epilepsys Andre V, Marescaux C, Nehlig A, Fritschy JM Hippocampus 2001;11:452–468 Reorganization of excitatory and inhibitory circuits in the hippocampal formation following seizure-induced neuronal loss has been proposed to underlie the development of chronic seizures in temporal lobe epilepsy (TLE). Here, we investigated whether specific morphological alterations of the GABAergic system can be related to the onset of spontaneous recurrent seizures (SRS) in the rat lithium-pilocarpine model of TLE. Immunohistochemical staining for markers of interneurons and their projections, including parvalbumin (PV), calretinin (CR), calbindin (CB), glutamic acid decarboxylase (GAD), and type 1 GABA transporter (GAT1), was performed in brain sections of rats treated with lithium-pilocarpine and sacrificed after 24 h, during the silent phase (6 and 12 days), or after the onset of SRS (10–18 days after treatment). Semiquantitative analysis revealed a selective loss of interneurons in the stratum oriens of CA1, associated with a reduction of GAT1 staining in the stratum radiatum and stratum oriens. In contrast, interneurons in CA3 were largely preserved, although GAT1 staining was also reduced. These changes occurred within 6 days after treatment and were therefore insufficient to cause SRS. In the dentate gyrus, extensive cell loss occurred in the hilus. The pericellular innervation of granule cells by PV-positive axons was markedly reduced, although the loss of PV-interneurons was only partial. Most strikingly, the density of GABAergic axons, positive for both GAD and GAT1, was dramatically increased in the inner molecular layer. This change emerged during the silent period, but was most marked in animals with SRS. Finally, supernumerary CB-positive neurons were detected in the hilus, selectively in rats with SRS. These findings suggest that alterations of GABAergic circuits occur early after lithium-pilocarpine-induced status epilepticus and contribute to epileptogenesis. In particular, the reorganization of GABAergic axons in the dentate gyrus might contribute to synchronize hyperexcitability induced by the interneuron loss during the silent period, leading to the onset of chronic seizures.
New Evidence Supporting a Role for T-Type Ca2+ Channels in Absence Epilepsy and in the Action of Ethosuximide
Authors: Rogawski Michael A. 
Published: December 2022

Lack of the Burst Firing of Thalamocortical Relay Neurons and Resistance to Absence Seizures in Mice Lacking α1G T-Type Ca2+ Channels Kim D, Song I, Keum S, Lee T, Jeong MJ, Kim SS, McEnery MW, Shin HS Neuron 2001;31:35–45 T-type Ca2+ currents have been proposed to be involved in the genesis of spike-and-wave discharges, a sign of absence seizures, but direct evidence in vivo to support this hypothesis has been lacking. To address this question, we generated a null mutation of the α1G subunit of T-type Ca2+ channels. The thalamocortical relay neurons of the α1G-deficient mice lacked the burst mode firing of action potentials, whereas they showed the normal pattern of tonic mode firing. The α1G-deficient thalamus was specifically resistant to the generation of spike-and-wave discharges in response to GABAB receptor activation. Thus, the modulation of the intrinsic firing pattern mediated by α1G T-type Ca2+ channels plays a critical role in the genesis of absence seizures in the thalamocortical pathway. Block of Cloned Human T-Type Calcium Channels by Succinimide Antiepileptic Drugs Gomora JC, Daud AN, Weiergraber M, Perez-Reyes E Mol Pharmacol 2001;60:1121–1132 Inhibition of T-type Ca2+ channels has been proposed to play a role in the therapeutic action of succinimide antiepileptic drugs. Despite the widespread acceptance of this hypothesis, recent studies using rat and cat neurons have failed to confirm inhibition of T-type currents at therapeutically relevant concentrations. The present study re-examines this issue using the three cloned human channels that constitute the T-type family: α1G, α1H, and α1I. The cloned cDNAs were stably transfected and expressed into mammalian cells, leading to the appearance of typical T-type currents. The results demonstrate that both ethosuximide and the active metabolite of methsuximide, α-methyl-α-phenylsuccinimide (MPS), block human T-type channels in a state-dependent manner, with higher affinity for inactivated channels. In contrast, succinimide analogs that are not anticonvulsive were relatively poor blockers. The apparent affinity of MPS for inactivated states of the three channels was estimated using two independent measures: K1 for α1G and α1I was 0.3 to 0.5 mM and for α1H was 0.6 to 1.2 mM. T-type channels display current at the end of long pulses (persistent current), and this current was especially sensitive to block (ethosuximide IC50 = 0.6 mM). These drugs also reduced both the size of the T-type window current region and the currents elicited by a mock low threshold spike. We conclude that succinimide antiepileptic drugs are capable of blocking human T-type channels at therapeutically relevant concentrations.
Negative Symptoms in Temporal Lobe Epilepsy
Authors: Kanner Andres M. 
Published: December 2022

Negative Symptoms in Temporal Lobe Epilepsy Getz K, Hermann B, Seidenberg M, Bell B, Dow C, Jones J, Woodard A, Rutecki P, Sheth R, O'Leary D, Magnotta V. Am J Psychiatry 2002;159:644–651 Objective This study examined the frequency of negative and positive symptoms in nonpsychotic patients with temporal lobe epilepsy and the relationship of negative and positive symptoms to cognition, quantitative magnetic resonance imaging (MRI) volumetrics, and depression. Method Eighty-four patients with temporal lobe epilepsy and 74 healthy comparison subjects were evaluated for negative and positive symptoms and underwent comprehensive neuropsychological evaluation, quantitative MRI volumetrics, and assessment of mood state and depression. Results Negative symptoms were significantly more prevalent in the patients with temporal lobe epilepsy (31%) than in the comparison subjects (8%). There was no difference between groups in the rate of positive symptoms. Although the epilepsy patients as a group exhibited generalized cognitive impairment relative to the comparison subjects, the epilepsy patients with negative symptoms performed significantly worse than patients without negative symptoms and comparison subjects across measures of nonverbal intelligence, visuoperception, speeded visuomotor processing, and memory. The epilepsy patients with negative symptoms exhibited significantly greater diffuse atrophy than the healthy comparison subjects and higher CSF volumes than the epilepsy patients without negative symptoms. The epilepsy patients with and without negative symptoms had statistically equivalent Beck Depression Inventory scores and lifetime history of mood disorders, including major depression. Conclusions Negative but not positive symptoms were more prevalent in temporal lobe epilepsy patients than in healthy comparison subjects. Negative symptoms were independent of current and past depression and were associated with neuropsychological deficits exceeding the general cognitive morbidity associated with temporal lobe epilepsy and with quantitative MRI indices, suggesting greater cerebral atrophy.
Functional MRI for Language Localization
Authors: Cascino Gregory 
Published: December 2022

Language Dominance in Partial Epilepsy Patients Identified with an fMRI Reading Task Gaillard WD, Balsamo L, Xu B, Grandin CB, Braniecki SH, Papero PH, Weinstein S, Conry J, Pearl PL, Sachs B, Sato S, Jabbari B, Vezina LG, Frattali C, Theodore WH Neurology 2002;59(2):256–265 Background Functional magnetic resonance imaging (fMRI) language tasks readily identify frontal language areas; temporal activation has been less consistent. No studies have compared clinical visual judgment with quantitative region-of-interest (ROI) analysis. Objective To identify temporal language areas in patients with partial epilepsy by using a reading paradigm with clinical and ROI interpretation. Methods Thirty patients with temporal lobe epilepsy, aged 8 to 56 years, had 1.5-T fMRI. Patients silently named an object described by a sentence compared with a visual control. Data were analyzed with ROI analysis from t-maps. Regional asymmetry indices (AIs) were calculated ([L-R]/[L+R]), and language dominance defined as >0.20. t-Maps were visually rated by three readers at three t thresholds. Twenty-one patients had the intracarotid amobarbital test (IAT). Results The fMRI reading task provided evidence of language lateralization in 27 of 30 patients with ROI analysis. Twenty-five were left dominant, two right, one bilateral, and two were nondiagnostic; IAT and fMRI agreed in most patients; three had partial agreement, and none overtly disagreed. Interrater agreement ranged between 0.77 to 0.82 (Cramer V; p < 0.0001); agreement between visual and ROI reading with IAT was 0.71 to 0.77 (Cramer V; p < 0.0001). Viewing data at lower thresholds added interpretation to 12 patients on visual analysis and eight with ROI analysis. Conclusions An fMRI reading paradigm can identify language dominance in frontal and temporal areas. Clinical visual interpretation is comparable to quantitative ROI analysis.
The “Reel” Pathology of Temporal Lobe Epilepsy
Authors: Scharfman Helen 
Published: December 2022

Role for Reelin in the Development of Granule Cell Dispersion in Temporal Lobe Epilepsy Haas C, Dudeck O, Kirsch M, Huszka C, Kann G, Pollak S, Zentner J, Frotscher M J Neurosci 2002;22:5797–5802 The reelin signaling pathway plays a crucial role during the development of laminated structures in the mammalian brain. Reelin, which is synthesized and secreted by Cajal–Retzius cells in the marginal zone of the neocortex and hippocampus, is proposed to act as a stop signal for migrating neurons. Here we show that a decreased expression of reelin messenger RNA (mRNA) by hippocampal Cajal–Retzius cells correlates with the extent of migration defects in the dentate gyrus of patients with temporal lobe epilepsy. These results suggest that reelin is required for normal neuronal lamination in humans, and that deficient reelin expression may be involved in migration defects associated with temporal lobe epilepsy.
Synaptic Reorganization in an Experimental Model of Posttraumatic Epilepsy
Authors: Dudek F. Edward , Shao Li-Rong 
Published: December 2022

Synaptic Activity in Chronically Injured, Epileptogenic Sensorimotor Neocortex Li H, Prince D J Neurophysiol 2002;88:2–12 We recorded spontaneous and evoked synaptic currents in pyramidal neurons of layer V in chronically injured, epileptogenic neocortex to assess changes in the efficacy of excitatory and inhibitory neurotransmission that might promote cortical hyperexcitability. Partial sensory-motor neocortical isolations with intact blood supply (“undercuts”) were made in 20 rats on postnatal day 21–25 and examined 2–6 weeks later in standard brain slice preparations by using whole-cell patch-clamp techniques. Age-matched, uninjured naive rats (n = 20) were used as controls. Spontaneous and miniature excitatory and inhibitory postsynaptic currents (s- and mEPSCs; s- and mIPSCs) were recorded by using patch-clamp techniques. The average frequency of s- and mEPSCs was significantly higher, whereas that of s- and mIPSCs was significantly lower in neurons of undercuts versus controls. The increased frequency of excitatory events was due to an increase in both s- and mEPSC frequency, suggesting an increased number of excitatory contacts and/or increased release probability at excitatory terminals. No significant difference was observed in 10–90% rise time of these events. The input-output slopes of fast, short-latency, α-amino-3-hydroxy-5-methylisoxazole-4-propionic acid/kainate (AMPA/KA) receptor-mediated components of evoked EPSCs were steeper in undercuts than in controls. The peak amplitude of the AMPA/KA component of EPSCs evoked by suprathreshold stimuli was significantly greater in the partially isolated neocortex. In contrast, the N-methyl-d-aspartate receptor-mediated component of evoked EPSCs was not significantly different in neurons of injured versus control cortex, suggesting that the increased AMPA/KA component was due to postsynaptic alterations. Results support the conclusion that layer V pyramidal neurons receive increased AMPA/KA receptor-mediated excitatory synaptic drive and decreased γ-aminobutyric acid type A (GABAA) receptor-mediated inhibition in this chronically injured, epileptogenic cortex. This shift in the balance of excitatory and inhibitory synaptic activation of layer V pyramidal cells toward excitation might be maladaptive and play a critical role in epileptogenesis.