bluuebunny/crossref_metadata_2025_split huggingface dataset:
Tremor in motor neuron disease may be central rather than peripheral in origin
Authors: Latorre A. , Rocchi L. , Stamelou M. , Batla A. , Ciocca M. , Balint B. , Sidle K. , Berardelli A. , Rothwell J. C. , Bhatia K. P. 
Published: June 2018

Background and purposeMotor neuron disease (MND) refers to a spectrum of degenerative diseases affecting motor neurons. Recent clinical and post‐mortem observations have revealed considerable variability in the phenotype. Rhythmic involuntary oscillations of the hands during action, resembling tremor, can occur in MND, but their pathophysiology has not yet been investigated.MethodsA total of 120 consecutive patients with MND were screened for tremor. Twelve patients with action tremor and no other movement disorders were found. Ten took part in the study. Tremor was recorded bilaterally using surface electromyography (EMG) and triaxial accelerometer, with and without a variable weight load. Power spectra of rectified EMG and accelerometric signal were calculated. To investigate a possible cerebellar involvement, eyeblink classic conditioning was performed in five patients.ResultsAction tremor was present in about 10% of our population. All patients showed distal postural tremor of low amplitude and constant frequency, bilateral with a small degree of asymmetry. Two also showed simple kinetic tremor. A peak at the EMG and accelerometric recordings ranging from 4 to 12 Hz was found in all patients. Loading did not change peak frequency in either the electromyographic or accelerometric power spectra. Compared with healthy volunteers, patients had a smaller number of conditioned responses during eyeblink classic conditioning.ConclusionsOur data suggest that patients with MND can present with action tremor of a central origin, possibly due to a cerebellar dysfunction. This evidence supports the novel idea of MND as a multisystem neurodegenerative disease and that action tremor can be part of this condition.
Perampanel: Does it have broad‐spectrum potential?
Authors: Potschka Heidrun , Trinka Eugen 
Published: June 2018

SummaryThis article reviews the profile of perampanel, a novel noncompetitive α‐amino‐3‐hydroxyl‐5‐methyl‐4‐isoxazole‐propionate (AMPA) receptor antagonist, and its role as a potential broad‐spectrum antiepileptic drug in the treatment of epilepsy. For this narrative review, data were collected using specified search criteria. Articles reporting the evidence for perampanel's efficacy from preclinical models, phase 3 clinical studies, observational studies, and descriptive evidence were included. AMPA receptors play a key role in mediating the action of glutamate at the excitatory synapse. Preclinical research showed the AMPA receptor blockade to constitute a promising target for antiepileptic drug therapy. In animal models, perampanel proved to be protective against seizures and reduce seizure severity and duration. Four phase‐3 randomized controlled trials (3 in patients with focal seizures and one in primary generalized tonic–clonic seizures in idiopathic generalized epilepsy) have been completed. In focal (partial) onset seizures, perampanel (4, 8, and 12 mg) significantly reduced seizure frequency per 28 days (23.3%‐28.8% vs 12.8%; P < .01) and responder rates (≥50% reduction in seizures) (28.5%‐35.3% vs 19.3%; P < .05) compared with placebo. In primary generalized tonic–clonic seizures, perampanel 8 mg resulted in greater reduction in seizure frequency per 28 days (−76.5% vs −38.4%; P < .0001) and responder rate (64.2% vs 39.5%; P = .0019) than placebo. The efficacy, safety, and tolerability of perampanel have been reproduced in real‐world clinical practice, and the agent has been shown to be effective in other epilepsy syndromes. Perampanel is a potentially broad‐spectrum antiepileptic drug with a novel mechanism of action that may be a useful addition for patients with epilepsy with various seizure types. The availability of novel antiepileptic drugs for epilepsy treatment enables more individualized treatment for these patients.
Quantitative positron emission tomography–guided magnetic resonance imaging postprocessing in magnetic resonance imaging–negative epilepsies
Authors: Lin Yicong , Fang Yu‐Hua Dean , Wu Guiyun , Jones Stephen E. , Prayson Richard A. , Moosa Ahsan N. V. , Overmyer Margit , Bena James , Larvie Mykol , Bingaman William , Gonzalez‐Martinez Jorge A. , Najm Imad M. , Alexopoulos Andreas V. , Wang Z. Irene 
Published: June 2018

SummaryObjectiveDetection of focal cortical dysplasia (FCD) is of paramount importance in epilepsy presurgical evaluation. Our study aims at utilizing quantitative positron emission tomography (QPET) analysis to complement magnetic resonance imaging (MRI) postprocessing by a morphometric analysis program (MAP) to facilitate automated identification of subtle FCD.MethodsWe retrospectively included a consecutive cohort of surgical patients who had a negative preoperative MRI by radiology report. MAP was performed on T1‐weighted volumetric sequence and QPET was performed on PET/computed tomographic data, both with comparison to scanner‐specific normal databases. Concordance between MAP and QPET was assessed at a lobar level, and the significance of concordant QPET‐MAP+ abnormalities was confirmed by postresective seizure outcome and histopathology. QPET thresholds of standard deviations (SDs) of −1, −2, −3, and −4 were evaluated to identify the optimal threshold for QPET‐MAP analysis.ResultsA total of 104 patients were included. When QPET thresholds of SD = −1, −2, and −3 were used, complete resection of the QPET‐MAP+ region was significantly associated with seizure‐free outcome when compared with the partial resection group (P = 0.023, P < 0.001, P = 0.006) or the no resection group (P = 0.002, P < 0.001, P = 0.001). The SD threshold of −2 showed the best combination of positive rate (55%), sensitivity (0.68), specificity (0.88), positive predictive value (0.88), and negative predictive value (0.69). Surgical pathology of the resected QPET‐MAP+ areas revealed mainly FCD type I. Multiple QPET‐MAP+ regions were present in 12% of the patients at SD = −2.SignificanceOur study demonstrates a practical and effective approach to combine quantitative analyses of functional (QPET) and structural (MAP) imaging data to improve identification of subtle epileptic abnormalities. This approach can be readily adopted by epilepsy centers to improve postresective seizure outcomes for patients without apparent lesions on MRI.
Effects of eslicarbazepine on slow inactivation processes of sodium channels in dentate gyrus granule cells
Authors: Holtkamp Dominik , Opitz Thoralf , Hebeisen Simon , Soares‐da‐Silva Patrício , Beck Heinz 
Published: June 2018

SummaryObjectivePharmacoresistance is a problem affecting ∼30% of chronic epilepsy patients. An understanding of the mechanisms of pharmacoresistance requires a precise understanding of how antiepileptic drugs interact with their targets in control and epileptic tissue. Although the effects of (S)‐licarbazepine (S‐Lic) on sodium channel fast inactivation are well understood and have revealed maintained activity in epileptic tissue, it is not known how slow inactivation processes are affected by S‐Lic in epilepsy.MethodsWe have used voltage clamp recordings in isolated dentate granule cells (DGCs) and cortical pyramidal neurons of control versus chronically epileptic rats (pilocarpine model of epilepsy) and in DGCs isolated from hippocampal specimens from temporal lobe epilepsy patients to examine S‐Lic effects on sodium channel slow inactivation.ResultsS‐Lic effects on entry into and recovery from slow inactivation were negligible, even at high concentrations of S‐Lic (300 μmol/L). Much more pronounced S‐Lic effects were observed on the voltage dependence of slow inactivation, with significant effects at 100 μmol/L S‐Lic in DGCs from control and epileptic rats or temporal lobe epilepsy patients. For none of these effects of S‐Lic could we observe significant differences either between sham‐control and epileptic rats, or between human DGCs and the two animal groups. S‐Lic was similarly effective in cortical pyramidal neurons from sham‐control and epileptic rats. Finally, we show in expression systems that S‐Lic effects on slow inactivation voltage dependence are only observed in Nav1.2 and Nav1.6 subunits, but not in Nav1.1 and Nav1.3 subunits.SignificanceFrom these data, we conclude that a major mechanism of action of S‐Lic is an effect on slow inactivation, primarily through effects on slow inactivation voltage dependence of Nav1.2 and Nav1.6 channels. Second, we demonstrate that this main effect of S‐Lic is maintained in both experimental and human epilepsy and applies to principal neurons of different brain areas.
Lung histopathology of non‐infectious pulmonary complications after allogeneic haematopoietic stem cell transplantation
Authors: Meignin Veronique , Thivolet‐Bejui Francoise , Kambouchner Marianne , Hussenet Claire , Bondeelle Louise , Mitchell Andrew , Chagnon Karine , Begueret Hugues , Segers Valerie , Cottin Vincent , Tazi Abdellatif , Chevret Sylvie , Danel Claire , Bergeron Anne 
Published: June 2018

AimsNon‐infectious pulmonary complications (NIPCs) occur frequently following allogeneic haematopoietic stem cell transplantation (HSCT). As there is no consensus on the description of the related pulmonary pathological lesions, pathologist reports and clinical conclusions are largely inconsistent in routine practice. The aim of our study was to provide an accurate overview of post‐allogeneic HSCT NIPCs from a large number of lung biopsies.Methods and resultsWe reviewed 61 lung biopsies in patients with an NIPC, including 51 surgical lung biopsies, four post‐mortem biopsies and six lung explants. We found both bronchiolar (n = 59) and alveolar/interstitial pathologies (n = 27). We describe two types of bronchiolar lesions: bronchiolectasies (n = 37) and fibrous and cellular lesions with luminal narrowing (n = 43). We found a wide spectrum of airway/interstitial pathologies that were labelled using the terminology of the 2013 American Thoracic Society and European Respiratory Society (ATS/ERS) classification of idiopathic interstitial pneumonias (IIPs), including the following: organising pneumonia (OP, n = 8), non‐specific interstitial pneumonia (NSIP, n = 9), diffuse alveolar damage (DAD, n = 6), lymphoid interstitial pneumonia (LIP, n = 1) and pleuroparenchymal fibroelastosis (PPFE, n = 2), as well as one instance of associated PPFE and NSIP.ConclusionsInterstitial pathology was associated with bronchiolar lesions in 41% of the cases reviewed (n = 25). Lung airway and interstitial inflammation was still present in lung explants from patients who underwent lung transplantation for post‐allogeneic HSCT end‐stage respiratory insufficiency. Herein, we describe a wide spectrum of pathological lung lesions encountered in post‐allogeneic HSCT NIPCs.
Importance of contextual variables related to cavitated lesions in 5‐year‐old children
Authors: Gomes Monalisa Cesarino , Neves Érick Tássio Barbosa , Perazzo Matheus França , Paiva Saul Martins , Ferreira Fernanda Morais , Granville‐Garcia Ana Flávia 
Published: June 2018

BackgroundDental caries have a high prevalence in children and need to evaluate their individual and contextual determinants.AimTo evaluate the importance of individual and contextual determinants on the occurrence of cavitated lesions in 5‐year‐old children.DesignA cross‐sectional study was conducted with 769 preschoolers in a city in northeastern Brazil. Parents/caregivers answered questionnaires addressing psychological aspects, socio‐demographic characteristics and the child's oral health. The diagnosis of dental caries (cavitated lesion) was performed using the ICDAS‐II. Variables related to the context were collected at the preschools and official municipal publications. Unadjusted and adjusted multilevel Poisson regression models with robust variance correction were used.ResultsThe prevalence of cavitated lesions was 58.8%. In the analysis adjusted by individual determinants, low household income (PR = 1.61; 95%CI:1.27–2.05), lower parent's/caregiver's schooling (PR = 1.57; 95%CI:1.20–2.05), not visited to the dentist (PR = 0.77; 95%CI:0.62–0.94), brushing frequency under 2 times per day (PR = 2.17; 95%CI:1.35–3.51) and weak parent's/caregiver's SOC (PR = 1.30; 95%CI:1.09–1.56) were associated with cavitated lesions. However, after the incorporation of the contextual determinants, parent's/caregiver's schooling and SOC lost their association. Considering contextual factors, children attending public preschools (PR = 1.66; 95%CI:1.34–2.05) and/or smaller preschools (PR = 1.001; 95%CI:1.001–1.002) had a greater probability of exhibiting cavitated lesions.ConclusionContextual variables were more important to the occurrence cavitated lesions than individual socioeconomic variables.
Increased leaf tocopherol and β‐carotene content is associated with the tolerance of winter wheat cultivars to frost
Authors: Janeczko Anna , Dziurka Michał , Pociecha Ewa 
Published: June 2018

AbstractComparative studies in winter wheat cultivars have so far been focused on the content of tocopherols in the grains as tocopherols are an important source of vitamin E in the human diet. Our approach was to verify the following main hypothesis—whether a higher accumulation of nonenzymatic antioxidants (tocopherol, tocotrienols, β‐carotene) in the leaves of winter wheat during cold acclimation is accompanied by a higher frost tolerance of winter wheat cultivars. Seedlings of winter wheat cultivars—frost susceptible (Bystra) and frost tolerant (Nutka and Smuga)—were cold acclimated for a period of 3 weeks. To analyse the antioxidants (tocotrienols, tocopherols, β‐carotene), leaf samples were taken on the final day of the exposure to cold. Moreover, samples were also taken to estimate the content of abscisic acid, jasmonic acid and salicylic acid. After leaf chlorophyllafluorescence measurements, the plants were exposed to frost (−8 to −14°C) and left to regrow to estimate their survival. Cultivars of winter wheat with higher accumulation of tocopherols in leaves had higher frost tolerance than cultivar with fewer tocopherols in leaves. α‐tocopherol was accumulated in cv. Bystra in the amount of 137 μg gDW−1. The content of α‐tocopherol was about 26% and 90% higher in cv. Nutka and cv. Smuga, respectively. The β‐carotene content was also higher in cv. Nutka and cv. Smuga compared to cv. Bystra. This work indicates a need for further and more detailed studies on the role of tocopherols and carotenoids in the acclimation process of cereals (winter wheat) to low temperatures. The accumulation of nonenzymatic antioxidants in the cold acclimation process will be discussed against the background of the accumulation of the stress hormones and changes in the photosynthetic efficiency in the tested cultivars.
Systemic research of plant growth and stress in a specially designed climatic hydroponics system
Authors: Šimkūnas Alvydas , Denisov Vitalij , Valašinaitė Sandra 
Published: June 2018

AbstractModern plant physiology deals with a plant at different hierarchical levels, from the ecosystem to molecular ones, so there is a demand to integrate the knowledge obtained at these levels. Examining plant growth and cold resistance, namely the intermediate levels (organism, organs, tissues, multicellular) often reveals the peculiarities of the functional–structural organization of the entire plant. The paper presents an integrated climatic hydroponic system, designed to implement a physical‐holistic experiment, accompanied by a particular methodology of systemic research. It covers the following main steps, which are the verification of the experimental system, production of high‐quality experimental material, including direct measurements and mathematical data analysis. The latter involves the decomposition of the phenomena under study, synthesis of data and the extraction of non‐linear components. The studies on the growth and stress of Poaceae plants (Lolium multiflorum, Festuca pratensis, Festulolium braunii) have already provided some significant results. A new boundary of the leaf meristem was proposed, adaptive growth bifurcations were discovered in the meristem, and a cells rounding phenomenon was detected. Using this top‐down approach, further research directions are delineated towards the lower hierarchical levels. Finally, the presented approach allows for the integration of data obtained at different plant investigation levels.
Do Holarctic ant species exist? Trans‐Beringian dispersal and homoplasy in the Formicidae
Authors: Schär Sämi , Talavera Gerard , Espadaler Xavier , Rana Jignasha D. , Andersen Andersen Anne , Cover Stefan P. , Vila Roger 
Published: June 2018

AbstractAimContinents harbour unique faunas, and only a small percentage of species naturally inhabit more than a single continent. This pattern is most evident in the insects, a morphologically small and extremely diverse group. Nevertheless, 12 species of ants have traditionally been recognized as native to both North America and Eurasia, the Holarctic region. Since intercontinental dispersal is presumably rare in ants, allopatric speciation in the absence of gene flow can be expected over evolutionary time. Here, we reassess the existence of Holarctic ant species and reconstruct their biogeographical history.LocationThe Holarctic.TaxonAll known ant species with purportedly Holarctic distributions.MethodsWe reconstructed the phylogenetic relationships, biogeographical history and reassessed the taxonomic status of all known ants with Holarctic distributions using genetic data based on one mitochondrial and three nuclear genes and an ancestral area reconstruction of 310 specimens and 73 species (the 12 Holarctic species plus outgroup taxa).ResultsContrary to the currently accepted hypothesis, only three ant species have Holarctic native ranges, while six taxa separate into distinct Palearctic and Nearctic species. Four species are shown to be recent introductions from Europe to North America by human activity, one of which was thought to be native. Genetic diversity is considerably higher within the North American than within European species as currently defined.Main conclusionsThe Formicidae have repeatedly dispersed through Beringia, during and after land bridge formation, and in both directions between the Palearctic and Nearctic regions. However, only three cold‐tolerant species crossed the Bering Strait in relatively recent time. Our results highlight the potential existence of many unknown Nearctic ant taxa. Reliance on an evolutionarily labile morphological character, erect hairs, seems to have obscured species delimitation in these ant taxa. Based on our investigation, the typical time for speciation in allopatry for ants is 2–5 Ma.
The genetic architecture of genome‐wide recombination rate variation in allopolyploid wheat revealed by nested association mapping
Authors: Jordan Katherine W. , Wang Shichen , He Fei , Chao Shiaoman , Lun Yanni , Paux Etienne , Sourdille Pierre , Sherman Jamie , Akhunova Alina , Blake Nancy K. , Pumphrey Michael O. , Glover Karl , Dubcovsky Jorge , Talbert Luther , Akhunov Eduard D. 
Published: June 2018

SummaryRecombination affects the fate of alleles in populations by imposing constraints on the reshuffling of genetic information. Understanding the genetic basis of these constraints is critical for manipulating the recombination process to improve the resolution of genetic mapping, and reducing the negative effects of linkage drag and deleterious genetic load in breeding. Using sequence‐based genotyping of a wheat nested association mapping (NAM) population of 2,100 recombinant inbred lines created by crossing 29 diverse lines, we mapped QTL affecting the distribution and frequency of 102 000 crossovers (CO). Genome‐wide recombination rate variation was mostly defined by rare alleles with small effects together explaining up to 48.6% of variation. Most QTL were additive and showed predominantly trans‐acting effects. The QTL affecting the proximal COs also acted additively without increasing the frequency of distal COs. We showed that the regions with decreased recombination carry more single nucleotide polymorphisms (SNPs) with possible deleterious effects than the regions with a high recombination rate. Therefore, our study offers insights into the genetic basis of recombination rate variation in wheat and its effect on the distribution of deleterious SNPs across the genome. The identified trans‐acting additive QTL can be utilized to manipulate CO frequency and distribution in the large polyploid wheat genome opening the possibility to improve the efficiency of gene pyramiding and reducing the deleterious genetic load in the low‐recombining pericentromeric regions of chromosomes.
Role of GhHDA5 in H3K9 deacetylation and fiber initiation in Gossypium hirsutum
Authors: Kumar Verandra , Singh Babita , Singh Sunil K. , Rai Krishan M. , Singh Surendra P. , Sable Anshulika , Pant Poonam , Saxena Gauri , Sawant Samir V. 
Published: June 2018

SummaryCotton fibers are single‐celled trichomes that initiate from the epidermal cells of the ovules at or before anthesis. Here, we identified that the histone deacetylase (HDAC) activity is essential for proper cotton fiber initiation. We further identified 15 HDACs homoeologs in each of the A‐ and D‐subgenomes of Gossypium hirsutum. Few of these HDAC homoeologs expressed preferentially during the early stages of fiber development [−1, 0 and 6 days post‐anthesis (DPA)]. Among them, GhHDA5 expressed significantly at the time of fiber initiation (−1 and 0 DPA). The in vitro assay for HDAC activity indicated that GhHDA5 primarily deacetylates H3K9 acetylation marks. Moreover, the reduced expression of GhHDA5 also suppresses fiber initiation and lint yield in the RNA interference (RNAi) lines. The 0 DPA ovules of GhHDA5RNAi lines also showed alterations in reactive oxygen species homeostasis and elevated autophagic cell death in the developing fibers. The differentially expressed genes (DEGs) identified through RNA‐seq of RNAi line (DEP12) and their pathway analysis showed that GhHDA5 modulates expression of many stress and development‐related genes involved in fiber development. The reduced expression of GhHDA5 in the RNAi lines also resulted in H3K9 hyper‐acetylation on the promoter region of few DEGs assessed by chromatin immunoprecipitation assay. The positively co‐expressed genes with GhHDA5 showed cumulative higher expression during fiber initiation, and gene ontology annotation suggests their involvement in fiber development. Furthermore, the predicted protein interaction network in the positively co‐expressed genes indicates HDA5 modulates fiber initiation‐specific gene expression through a complex involving reported repressors.