bluuebunny/crossref_metadata_2025_split huggingface dataset:
Neurophysiological correlates of residual inhibition in tinnitus: Hints for trait-like EEG power spectra
Authors: Schoisswohl S. , Schecklmann M. , Langguth B. , Schlee W. , Neff P. 
Published: December 2020

AbstractMagneto- and electroencephalography (M/EEG) investigations in tinnitus patients demonstrated anomalous oscillatory brain activity patterns compared to healthy controls. A well-established phenomenon in tinnitus is the possibility to temporary suppress tinnitus following acoustic stimulation, which is termed residual inhibition (RI). The few former neurophysiological investigations of RI reported partly conflicting results hampering consensus on tinnitus-specific brain activity and basic neural models.Hence, our objective was to investigate RI-specific oscillatory brain activity changes and whether these changes can be associated with behavioral measures of tinnitus loudness. Further, contrasts between acoustic stimulation responders and non-responders provide further insights in RI-related spontaneous brain activity.Three different types of noise stimuli were administered for acoustic stimulation in 45 tinnitus patients. Subjects resting state brain activity was recorded before and during RI via EEG alongside with subjective measurements of tinnitus loudness.On the whole-group level, tinnitus-unspecific changes were observed which fit established knowledge about basic neural responses after acoustic stimulation. Responder non-responder contrasts revealed differences in alpha and gamma band activity in line with the proposed neural models for oscillatory brain activity in tinnitus. Further analysis of sample characteristics demonstrated divergences between responders and nonresponders notably for tinnitus duration. During RI, distinct differences between responders and non-responders were exclusively observed for alpha band activity in auditory cortical areas. Neither correlations of behavioral tinnitus measures nor differences between stimulus-induced changes in ongoing brain activity could be detected.Taken together, our observations might be indicative of trait-specific forms of oscillatory signatures in different subsets and chronification grades of the tinnitus population possibly related to acoustic tinnitus suppression. Results and insights are not only useful to understand basic neural mechanisms behind RI but are also valuable for general neural models of tinnitus.HighlightsResidual inhibition provides a key method to study the basic mechanisms of tinnitus.We compared residual inhibition EEG activity between responders and non-responders.In responders, the alpha activity in auditory areas was increased during tinnitus suppression.Results and insights are valuable for understanding the neural mechanisms behind acoustic tinnitus suppression.
Modeling intrahippocampal effects of anterior hippocampal hyperactivity relevant to schizophrenia using chemogenetic excitation of long axis-projecting mossy cells in the mouse dentate gyrus
Authors: Bauer James P. , Rader Sarah L. , Joffe Max E. , Kwon Wooseok , Quay Juliana , Seanez Leann , Zhou Chengwen , Conn P. Jeffrey , Lewis Alan S. 
Published: December 2020

ABSTRACTBackgroundThe anterior hippocampus of individuals with early psychosis or schizophrenia is hyperactive, as is the ventral hippocampus in rodent models for schizophrenia risk. Hyperactive ventral hippocampal projections to extrahippocampal brain regions contribute to schizophrenia symptoms, but less is known about the functional effects of hyperactive projections within the hippocampal formation long axis. We approached this question by testing whether hyperactivation of ventral dentate gyrus (DG) mossy cells (MCs), which densely project intrahippocampally to the dorsal DG, influences spatial memory, a cognition dependent on intact dorsal DG function.MethodsIn CD-1 mice, we targeted dorsal DG-projecting ventral DG MCs using an adeno-associated virus intersectional strategy. In vivo fiber photometry recording of ventral DG MCs was performed during exploratory behaviors. We targeted excitatory chemogenetic constructs to ventral DG MCs and tested whether their hyperactivation impaired encoding in a spatial memory task.ResultsVentral DG MCs were activated during behavior related to environmental information gathering (rearing) but not during non-exploratory motor behaviors. Ventral DG MCs made functional monosynaptic inputs to dorsal DG granule cells, with chemogenetic activation of ventral DG MCs leading to increased activity of dorsal DG granule cells. Finally, chemogenetic activation of ventral DG MCs during the encoding phase of an object location memory task impaired retrieval 24 hours later, without effects on locomotion or other exploratory behaviors.ConclusionsThese data suggest that localized hippocampal hyperactivity may have longitudinal intrahippocampal functional consequences, supporting study of longitudinal circuits as targets to mitigate cognitive deficits associated with schizophrenia.
Integration of Cell Growth and Asymmetric Division During Lateral Root Initiation InArabidopsis thaliana
Authors: Schütz Lilli Marie , Louveaux Marion , Barro Amaya Vilches , Bouziri Sami , Cerrone Lorenzo , Wolny Adrian , Kreshuk Anna , Hamprecht Fred A. , Maizel Alexis 
Published: December 2020

AbstractLateral root formation determines to a large extent the ability of plants to forage their environment and thus their growth. InArabidopsis thalianaand other angiosperms, lateral root initiation requires radial cell expansion and several rounds of anticlinal cell divisions that give rise to a central core of small pericycle cells, which express different markers than the larger surrounding cells. These small central cells then switch their plane of divisions to periclinal, and give rise to seemingly morphologically similar daughter cells that have different identities and establish the different cell types of the new root. Although the execution of these two types of divisions is tightly regulated and essential for the correct development of the lateral root, we know little about their geometrical features. Here we analyse a four-dimensional reconstruction of the first stages of lateral root formation and analyze the geometric features of the anticlinal and periclinal divisions. We identify that the periclinal divisions of the small central cells are morphologically dissimilar and asymmetric. We show that mother cell volume is different when looking at anticlinal versus periclinal divisions and the repeated anticlinal divisions do not lead to reduction in cell volume although cells are shorter. Finally, we show that cells undergoing a periclinal division are characterized by a strong cell expansion. Our results indicate that cells integrate growth and division to precisely partition their volume upon division during the first two stages of lateral root formation.
The GPIbα intracellular tail - role in transducing VWF- and Collagen/GPVI-mediated signaling
Authors: Constantinescu-Bercu Adela , Wang Yuxiao Alice , Woollard Kevin J , Mangin Pierre , Vanhoorelbeke Karen , Crawley James TB , Salles-Crawley Isabelle I. 
Published: December 2020

AbstractSynergy between GPIbα and GPVI signaling machineries has been suggested previously, however its molecular mechanism remains unclear. We generated a novelGPIbαtransgenic mouse (GPIbαΔsig/Δsig) by CRISPR-Cas9 technology to delete the last 24 residues of the GPIbα intracellular tail important for VWF-mediated signaling.GPIbαΔsig/Δsigplatelets bound VWF normally under flow but formed fewer filopodia on VWF/botrocetin, demonstrating that the deleted region does not affect ligand binding but appreciably impairs VWF-dependent signaling. Notably, while haemostasis was normal inGPIbαΔsig/Δsigmice,GPIbαΔsig/Δsigplatelets exhibited defective responses after collagen-related-peptide stimulation and formed smaller aggregates on collagen-coated microchannels at low and high shears. Flow assays performed with plasma-free blood or in the presence of αIIbβ3-or GPVI-blockers suggested reduced αIIbβ3activation contributes to the phenotype of theGPIbαΔsig/Δsigplatelets. Together, these results reveal a new role for the intracellular tail of GPIbα in transducing both VWF-GPIbα and collagen-GPVI signaling events in platelets.Summary statementGPIbα and GPVI are two key receptors on the platelet surface. Using a novel transgenic mouse (GPIbαΔsig/Δsig) that lacks the last 24 amino acids of the GPIbα intracellular tail, we demonstrate the importance of this region not only in transducing signals in response to GPIbα binding to VWF, but also for collagen-GPVI-mediated platelet responses revealing previously underappreciated receptor crosstalk between GPIbα and GPVI.
DDI2 protease activity controls embryonic development and inflammation via TCF11/NRF1
Authors: Siva Monika , Haberecht-Müller Stefanie , Prochazkova Michaela , Prochazka Jan , Sedlak Frantisek , Chawengsaksophak Kallayanee , Kasparek Petr , Sedlacek Radislav , Konvalinka Jan , Krüger Elke , Saskova Klara Grantz 
Published: December 2020

SUMMARYDDI2 is an aspartic protease that cleaves polyubiquitinated substrates. Upon proteotoxic stress, DDI2 activates the ER-bound transcription factor TCF11/NRF1 (NFE2L1), a master regulator of proteostasis maintenance in mammalian cells, and ensures the expression of rescue factors including proteasome subunits. Here we describe the consequences of DDI2 ablation bothin vivoand in cells. Knock-out of DDI2 in mice resulted in embryonic lethality at E12.5 with severe developmental failure. Molecular characterization of the embryos and surrogateDDI2knock-out cell lines showed insufficient proteasome expression with proteotoxic stress, accumulation of high molecular weight ubiquitin conjugates, and induction of the unfolded protein and integrated stress responses. We also show thatDDI2KO-induced proteotoxic stress causes the cell-autonomous innate immune system to induce a type I interferon signature. These results indicate an important role for DDI2 in the proteostasis network of cells and tissues and in the maintenance of a balanced immune response.HighlightsDDI2-deficiency in mice causes severe developmental failure and embryonic lethality at mid-late gestationDDI2-deficiency causes severe proteotoxic stress and proteasome impairmentDDI2-deficiency induces the UPR and ISR signaling pathwaysDDI2-deficient cells survive via STAT3-dependent interferon signaling
Nucleolar TFIIE plays a role in ribosomal biogenesis and performance
Authors: Phan Tamara , Maity Pallab , Ludwig Christina , Streit Lisa , Michaelis Jens , Scharffetter-Kochanek Karin , Iben Sebastian 
Published: December 2020

AbstractRibosome biogenesis is a highly energy-demanding process in eukaryotes which requires the concerted action of all three RNA polymerases. In RNA polymerase II transcription, the general transcription factor TFIIH is recruited by TFIIE to the initiation site of protein-coding genes. Distinct mutations in TFIIH and TFIIE give rise to the degenerative disorder trichothiodystrophy (TTD). Here we uncovered an unexpected role of TFIIE in ribosomal RNA synthesis by RNA polymerase I. With high resolution microscopy we detected TFIIE in the nucleolus where TFIIE binds to actively transcribed rDNA. Mutations in TFIIE affects gene-occupancy of RNA polymerase I, rRNA maturation, ribosomal assembly and performance. In consequence, the elevated translational error rate with imbalanced protein synthesis and turnover results in an increase in heat-sensitive proteins. Collectively, mutations in TFIIE – due to impaired ribosomal biogenesis and translational accuracy – lead to a loss of protein homeostasis (proteostasis) which can partly explain the clinical phenotype in TTD.
URL normalization and assessing website structures in higher education websites
Authors: Richardson Brian 
Published: December 2020

Purpose
This study aims to explore the character and attainment of an effective URL system by expanding the concept of URL normalization, originally connected to machine-reading access of web pages, to form a broader understanding of URL systematization that includes user-focused cognitive and practical elements.

Design/methodology/approach
A revised understanding of URL normalization will be used to critically analyzed URLs of main admissions pages from M1 universities, as designated by the Carnegie Foundation.

Findings
The study found that very few institutions implemented well-organized systems of Uniform Resource Locators (URLs) and redirects and that many included unintelligible and impractical URLs that would hinder the effective use of their websites.

Practical implications
A broader understanding of URL systematization will result in more effective website design. URLs must serve an indexical function pointing to a unique web resource, whatever the URL's format. However, URLs should also consider human usability issues and strive to be simple, short, communicable, intelligible and ultimately useful as part of social interactions. Poorly designed URLs create frustration, if not failure, by being difficult to use, confusing or interminable. An effective URL system should also include redirects to anticipate alternate, meaningful URLs that are different from the canonical path. The framework and recommendations arising from this study are applicable to many website structures.

Originality/value
The expanded understanding of the concept of URL normalization and subsequent evaluation principles can be used to assess the overall coherence and completeness of the website in general, thus improving website usability.
Astaxanthin ameliorates oxidative stress and neuronal apoptosis via SIRT1/NRF2/Prx2/ASK1/p38 after traumatic brain injury in mice
Authors: Zhang Xiang‐Sheng , Lu Yue , Li Wen , Tao Tao , Peng Lei , Wang Wei‐Han , Gao Sen , Liu Cang , Zhuang Zong , Xia Da‐Yong , Hang Chun‐Hua , Li Wei 
Published: December 2020

Background and PurposeOxidative stress and neuronal apoptosis play key roles in traumatic brain injury. We investigated the protective effects of astaxanthin against traumatic brain injury and its underlying mechanisms of action.Experimental ApproachA weight‐drop model of traumatic brain injury in vivo and hydrogen peroxide exposure in vitro model were established. Brain oedema, behaviour tests, western blot, biochemical analysis, lesion volume, histopathological study and cell viability were performed.Key ResultsAstaxanthin significantly reduced oxidative insults on Days 1, 3 and 7 after traumatic brain injury. Neuronal apoptosis was also ameliorated on Day 3. Additionally, astaxanthin improved neurological functions up to 3 weeks after traumatic brain injury. Astaxanthin treatment dramatically enhanced the expression of peroxiredoxin 2 (Prx2), nuclear factor‐erythroid 2‐related factor 2 (NRF2/Nrf2) and sirtuin 1 (SIRT1), while it down‐regulated the phosphorylation of apoptosis signal‐regulating kinase 1 (ASK1) and p38. Inhibition of Prx2 by siRNA injection reversed the beneficial effects of astaxanthin against traumatic brain injury. Additionally, Nrf2 knockout prevented the neuroprotective effects of astaxanthin in traumatic brain injury. In contrast, overexpression of Prx2 in Nrf2 knockout mice attenuated the secondary brain injury after traumatic brain injury. Moreover, inhibiting SIRT1 by EX527 dramatically inhibited the neuroprotective effects of astaxanthin and suppressed SIRT1/Nrf2/Prx2/ASK1/p38 pathway both in vivo and in vitro.Conclusion and ImplicationsAstaxanthin improved the neurological functions and protected the brain from injury after traumatic brain injury, primarily by reducing oxidative stress and neuronal death via SIRT1/Nrf2/Prx2/ASK1/p38 signalling pathway and might be a new candidate to ameliorate traumatic brain injury.
Initial experience with percutaneous mitral valve repair in patients with cardiac amyloidosis
Authors: Volz Martin J. , Pleger Sven T. , Weber Andreas , Geis Nicolas A. , Hamed Sonja , Mereles Derliz , Hegenbart Ute , Katus Hugo A. , Frey Norbert , Raake Philip W. , Kreusser Michael M. 
Published: December 2020

AbstractBackgroundPercutaneous mitral valve repair (PMVR) is a therapeutic option for severe mitral regurgitation (MR) in patients with heart failure due to differential aetiologies. However, only little is known about the safety and efficacy of this procedure in patients with amyloid cardiomyopathy.MethodsFive patients with cardiac amyloidosis and moderate to severe or severe MR undergoing PMVR were analysed retrospectively and compared to seven patients with cardiac amyloidosis and severe MR without intervention. Clinical and functional data, renal function and cardiac biomarkers as well as established risk scores for cardiac amyloidosis were assessed. Primary endpoint was the reduction in MR one year after PMVR. Secondary endpoints were safety, overall mortality after 12 months compared with the control group, as well as changes in clinical and functional parameters.ResultsAmyloidosis risk assessment documented amyloid cardiomyopathy at an advanced stage in all patients. Procedural, technical and device success of PMVR were all 100% and residual MR remained mild to moderate at 12 months follow‐up (P = .038 vs before PMVR). Differences in survival compared with the control (no PMVR) group pointed to a possible survival benefit in the PMVR group (P = .02).ConclusionPMVR is a feasible and safe procedure in patients with cardiac amyloidosis and might carry a possible survival benefit in this patient group.
Assessing the experience of the quality of care of patients living with multiple sclerosis and their caregivers: The MusiCare questionnaire
Authors: Veillard David , Baumstarck Karine , Edan Gilles , Debouverie Marc , Wiertlewski Sandrine , De Sèze Jérôme , Clavelou Pierre , Pelletier Jean , Verny Christophe , Chauvin Karine , Cosson Marie Elisabeth , Loundou Anderson , Auquier Pascal 
Published: December 2020

AbstractBackground and purposePatients with a chronic illness, such as multiple sclerosis (MS), and their natural caregivers have a specific experience of healthcare and health services. These experiences need to be assessed to evaluate the quality of care. Our objective was to develop a French‐language questionnaire to evaluate the quality of care as experienced by MS patients and their natural caregivers.MethodsEligible patients had been diagnosed with MS according to the McDonald criteria. Eligible caregivers were individuals designated by the patients. The MusiCare questionnaire was developed in two standard phases: (i) item generation, based on interviews with patients and caregivers; and (ii) validation, consisting of validity, reliability, external validity, reproducibility, and responsiveness measures.ResultsIn total, 1088 patients (n = 660) and caregivers (n = 488) were recruited. The initial 64‐item version of MusiCare was administered to a random subsample (n = 748). The validation process generated a 35‐item questionnaire. Internal consistency and scalability were satisfactory. Testing of the external validity revealed expected associations between MusiCare scores and sociodemographic and clinical data. The questionnaire showed good reproducibility and responsiveness.ConclusionsThe availability of a reliable and validated French‐language self‐report questionnaire probing the experience of the quality of care for MS will allow the feedback of patients and caregivers to be incorporated into a continuous healthcare quality‐improvement strategy.
Phylogenetic regionalization of tree assemblages reveals novel patterns of evolutionary affinities in the Atlantic Forest
Authors: Rezende Vanessa Leite , Pontara Vanessa , Bueno Marcelo Leandro , van den Berg Eduardo , Silva de Miranda Pedro Luiz , de Oliveira‐Filho Ary Teixeira , Dexter Kyle G. 
Published: December 2020

AbstractAimWe used a phylogenetic approach to group assemblages of woody plant into major vegetation units in the Atlantic Forest, thus for the first time incorporating information on species evolutionary relationships into a bioregionalization of this critical hotspot. A phylogenetic regionalization will provide a spatially explicit framework for answering many basic and applied questions in biogeography, ecology and conservation.LocationAtlantic Forest.TaxonAngiospermsMethodsOur data set comprises 614 genera and 116 families, spread over 1,755 assemblages. To place assemblages in a multivariate evolutionary composition space, we used a phylogenetically informed ordination analysis, and to determine what the main phylogenetic groups of assemblages were, we used K‐means clustering based on phylogenetic dissimilarity of assemblages. To quantify how well environmental variables distinguish the phylogenetic groups found, we implemented classification tree approaches. Then, to explore the evolutionary turnover between the phylogenetic groups, we calculated phylogenetic beta diversity. Finally, we determined the lineages that are most strongly associated with individual phylogenetic groups using an indicator analysis for lineages.ResultsOur analyses suggest that there are seven principal groups, in terms of evolutionary lineage composition, in the Atlantic Forest. The greatest turnover of phylogenetic lineage composition separates tropical evergreen rain forest and semideciduous assemblages from subtropical and highland assemblages. The mixed subtropical forest showed the lowest phylogenetic compositional similarity values with other groups. Tropical rain forest had the highest number of significant indicator lineages, and the highest values of the indicator statistic for lineages.Main conclusionsWe found that the most pronounced evolutionary division separates southern and highland tree assemblages from those occurring under more tropical climates and at lower elevations. Our phylogenetic analyses point to an environmentally driven compositional division, likely based on the regular occurrence of freezing versus non‐freezing temperatures. Precipitation and edaphic regimes that assemblages experience had less definitive effects on their evolutionary lineage composition.
Photoperiod integration in C3H rd1 mice
Authors: Leclercq Bastien , Hicks David , Laurent Virginie 
Published: December 2020

AbstractIn mammals, the suprachiasmatic nuclei (SCN) constitute the main circadian clock, receiving input from the retina which allows synchronization of endogenous biological rhythms with the daily light/dark cycle. Over the year, the SCN encodes photoperiodic variations through duration of melatonin secretion, with abundant nocturnal levels in winter and lower levels in summer. Thus, light information is critical to regulate seasonal reproduction in many species and is part of the central photoperiodic integration. Since intrinsically photosensitive retinal ganglion cells (ipRGCs) are vital for circadian photoentrainment and other nonvisual functions, we studied the contribution of ipRGCs in photoperiod integration in C3H retinal degeneration 1 (rd1) mice. We assessed locomotor activity and melatonin secretion in mice exposed to short or long photoperiods. Our results showed that rd1 mice are still responsive to photoperiod variations in term of locomotor activity, melatonin secretion, and regulation of the reproductive axis. In addition, retinas of animals exposed to short photoperiod exhibit higher melanopsin labeling intensity compared with the long photoperiod condition, suggesting seasonal‐dependent changes within this photoreceptive system. These results show that ipRGCs in rd1 mice can still measure photoperiod and suggest a key role of melanopsin cells in photoperiod integration and the regulation of seasonal physiology.