bluuebunny/crossref_metadata_2025_split huggingface dataset:
Transient Bilateral Central Scotoma on Awakening: A Distinct Phenomenon
Authors: Sanchez Moreno Francisco R. , Mansukhani Sasha A. , Bhatti M. Tariq , Chen John J. 
Published: October 2022

Background:
Transient vision loss can be an alarming symptom owing to potentially serious etiologies such as thromboembolism or giant cell arteritis. Transient monocular vision loss (TVML) on awakening has been recently described as a benign phenomenon (Bouffard et al, 2017). Our objective was to describe the unique phenomenon of transient binocular vision loss (TBVL) on awakening.

Methods:
Retrospective observational case series of 5 patients who experienced TBVL on awakening seen in the neuro-ophthalmology clinic at the Mayo Clinic between 2016 and 2020. Patients who described generalized blurred vision and those with monocular transient vision loss were excluded.

Results:
The median age was 81.4 years (range, 68–92 years), and all were male. Every patient described a stereotyped transient bilateral central scotoma on awakening with slightly irregular borders and mild asymmetry between the 2 eyes lasting between 15 and 90 minutes. Frequency ranged from 3 to 7 times per week, and there was a median of 319 episodes (range, 126–728 episodes) before evaluation in the neuro-ophthalmology clinic. All patients had normal optic nerves, and no plaques were noted in the retinal vessels. All 5 had macular drusen, which were predominantly extrafoveal and mild. Two patients underwent electrophysiology testing, which were both normal on full-field electroretinogram (ERG), but there was blunted central wave forms on multifocal ERG. Two patients underwent dark adaptation testing, which showed both prolong and diminished dark adaptation. Neuroimaging and thromboembolic workup were unrevealing.

Conclusions:
TBVL is a distinct phenomenon from TMVL on awakening, which has a different demographic and symptomology. The etiology is unclear but seems to be a focal macular process in conjunction with an autoregulatory failure resulting in a supply–demand mismatch during low-light conditions.
Transparent and stretchable metal nanowire composite recording microelectrode arrays
Authors: Chen Zhiyuan , Nguyen Khanh , Kowalik Grant , Shi Xinyu , Tian Jinbi , Doshi Mitansh , Alber Bridget R. , Ning Xin , Kay Matthew W. , Lu Luyao 
Published: October 2022

AbstractTransparent microelectrodes have received much attention from the biomedical community due to their unique advantages in concurrent crosstalk-free electrical and optical interrogation of cell/tissue activity. Despite recent progress in constructing transparent microelectrodes, a major challenge is to simultaneously achieve desirable mechanical stretchability, optical transparency, electrochemical performance, and chemical stability for high-fidelity, conformal, and stable interfacing with soft tissue/organ systems. To address this challenge, we have designed microelectrode arrays (MEAs) with gold coated silver nanowires (Au-Ag NWs) by combining technical advances in materials, fabrication, and mechanics. The Au coating improves both the chemical stability and electrochemical impedance of the Au-Ag NWs microelectrodes with only slight changes in optical properties. The MEAs exhibit a high optical transparency >80% at 550 nm, a low normalized 1 kHz electrochemical impedance of 1.2-7.5 Ω cm2, stable chemical and electromechanical performance after exposure to oxygen plasma for 5 minutes and cyclic stretching for 600 cycles at 20% strain, superior to other transparent microelectrode alternatives. The MEAs easily conform to curvilinear heart surfaces for co-localized electrophysiological and optical mapping of cardiac function. This work demonstrates that stretchable transparent metal nanowire MEAs are promising candidates for diverse biomedical science and engineering applications, particularly under mechanically dynamic conditions.
Phylogeography ofGeothelphusafreshwater crabs: unexpected dual dispersal routes via land and sea
Authors: Masaki Takenaka , Koki Yano , Koji Tojo 
Published: October 2022

AbstractAimDispersal is an important factor that determines the potential for colonization to pioneer sites. Most decapods employ seaward migration for reproduction with a planktonic larval phase. However, true freshwater crabs spend their entire life cycle in freshwater. Therefore, it is expected that genetic regionality can be easily detected. In this study, we focused on the genetic structures of true freshwater crabs,Geothelphusacrabs. Herein, we reveal the evolutionary history and dispersal patterns of freshwater crustaceans, for which there is limited knowledge to date.LocationJapanese IslandsTaxonGeothelphusa dehaani(Decapoda, Potamidae)MethodsWe collected and genetically analyzed 283 specimens at 138 localities from freshwater habitats across the Japanese Islands. Phylogenetic analyses were conducted on 1,796 bp of the combined dataset (mtDNA COI, 16S, and nDNA ITS1, histone H3) and 569 bp of the mtDNA COI dataset. The demographic history ofG. dehaaniwas simulated using Approximate Bayesian Computation analysis. A salt tolerance experiment was conducted to confirm the survival rate in seawater.ResultsThe resulting of phylogenetic relationships detected 10 clades that were highly likely to be monophyletic. These 10 clades genetically exhibited an explicit pattern of geographical differentiation. Also, we confirmed the salt tolerance ability of these Japanese freshwater crabs.Main conclusionsThe highlights of this study were the discovery of several cryptic species/lineages or undescribed species, and the completely different heterogeneous dual dispersal pathways detected within a single species; i.e., both land and ocean routes. As a result of phylogenetic analysis, it was concluded that Japanese crabs are basically genetically divided by straits. However, strong evidence for dispersion via ocean currents was also detected (i.e., a “sweepstake”), and it was also determined thatG. dehaanicould survive in seawater. This is the first observation of such a unique mode of expansion of a species’ distribution area.
Environment-mediated vertical transmission fostered uncoupled phylogenetic relationships between longicorn beetles and their symbionts
Authors: Sasakura Yasunori , Yuzawa Nobuhisa , Yamasako Junsuke , Mori Kazuki , Horie Takeo , Nonaka Masaru 
Published: October 2022

ABSTRACTThe Coleoptera Cerambycidae (longicorn beetles) use wood under different states (living healthy, freshly snapped, completely rot, etc.) in a species-specific manner for their larval diet. Larvae of some Cerambycidae groups have mycetomes, accessory organs associated with the midgut that harbor fungal symbiont cells. The symbionts are thought to improve nutrient conditions; however, this has yet to be shown experimentally. To deduce the evolutionary history of this symbiosis, we investigated the characteristics of the mycetomes in the larvae of longicorn beetles collected in Japan. Lepturinae, Necydalinae, and Spondylidinae are the only groups that possess mycetomes, and these three groups’ mycetomes and corresponding fungal cells exhibit different characteristics between the groups. However, the phylogenetic relationship of symbiont yeasts does not coincide with that of the corresponding longicorn beetle species, suggesting they have not co-speciated. The imperfect vertical transmission of symbiont yeasts from female to offspring is a mechanism that could accommodate the host-symbiont phylogenetic incongruence. Some Lepturinae species secondarily lost mycetomes. The loss is associated with their diet choice, suggesting that different conditions between feeding habits could have allowed species to discard this organ. We found that symbiont fungi encapsulated in the mycetomes are dispensable for larval growth if sufficient nutrients are given, suggesting that the role of symbiotic fungi could be compensated by the food larvae take.Aegosoma sinicumis a longicorn beetle classified to the subfamily Prioninae, which does not possess mycetomes. However, this species contains a restricted selection of yeast species in the larval gut, suggesting that the symbiosis between longicorn beetles and yeasts emerged before acquiring the mycetomes.
Thalamocortical networks involved in Pusher Syndrome
Authors: Rosenzopf Hannah , Klingbeil Julian , Wawrzyniak Max , Röhrig Lisa , Sperber Christoph , Saur Dorothee , Karnath Hans-Otto 
Published: October 2022

AbstractIndirect quantification of functional and structural disconnection increases the knowledge derived from focal brain lesions by inferring subsequent brain network damage from the respective lesion. We applied both measures to a sample of 124 stroke patients to investigate brain disconnection in pusher syndrome – a disorder characterized by a disturbed perception of one’s own upright body posture. Our results suggest a hub-like function of the posterior and lateral portions of the thalamus in the perception of one’s own postural upright and identified dysfunction in a thalamo-cortical network as one likely cause of pusher syndrome. Lesion network-symptom-mapping investigating functional disconnection indicated cortical diaschisis in cerebellar, frontal, parietal, occipital, and temporal areas in patients with thalamic lesions suffering from pusher syndrome, but there was no evidence for functional diaschisis in cortical stroke and no evidence for the convergence of thalamic and cortical lesions onto a common functional network. Structural disconnectivity mapping identified several thalamo-cortical disconnections. Many of the thalamic and cortical regions disconnected by lesions that lead to pusher behavior correspond to previously reported lesion sites associated with pusher syndrome. Thus, while the presence of both, isolated thalamic and cortical lesions in context with pusher behavior has been reported previously and led to the conclusion that the correct estimation of one’s own postural upright might depend on a thalamo-cortical network, our analyses offer the first evidence for a direct thalamo-cortical (or cortico-thalamic) interconnection and, more importantly, shed light on the location of the respective thalamo-cortical disconnections.
MIND Networks: Robust Estimation of Structural Similarity from Brain MRI
Authors: Sebenius Isaac , Seidlitz Jakob , Warrier Varun , Bethlehem Richard A I , Alexander-Bloch Aaron , Mallard Travis T , Garcia Rafael Romero , Bullmore Edward T , Morgan Sarah E 
Published: October 2022

AbstractStructural similarity networks are a central focus of magnetic resonance imaging (MRI) research into human brain connectomes in health and disease. We present Morphometric INverse Divergence (MIND), a robust method to estimate within-subject structural similarity between cortical areas based on the Kullback-Leibler divergence between the multivariate distributions of their structural features. Compared to the prior approach of morphometric similarity networks (MSNs) on N>10,000 data from the ABCD cohort, MIND networks were more consistent with known cortical symmetry, cytoarchitecture, and (in N=19 macaques) gold-standard tract-tracing connectivity, and were more invariant to cortical parcellation. Importantly, MIND networks were remarkably coupled with cortical gene co-expression, providing fresh evidence for the unified architecture of brain structure and transcription. Using kinship (N=1282) and genetic data (N=4085), we characterized the heritability of MIND phenotypes, identifying stronger genetic influence on the relationship between structurally divergent regions compared to structurally similar regions. Overall, MIND presents a biologically-validated lens for analyzing the structural organization of the cortex using readily-available MRI measurements.
ERK3/MAPK6 dictates Cdc42/Rac1 activity and ARP2/3-dependent actin polymerization
Authors: Bogucka-Janczi Katarzyna , Harms Gregory , May-Coissieux Mary , Bentires-Alj Mohamad , Thiede Bernd , Rajalingam Krishnaraj 
Published: October 2022

SummaryThe actin cytoskeleton is tightly controlled by RhoGTPases, actin binding proteins and nucleation-promoting factors to perform fundamental cellular functions. Here, we show that ERK3, an atypical MAPK, directly acts as a guanine nucleotide exchange factor for Cdc42 and phosphorylates the ARP3 subunit of the ARP2/3 complex at S418 to promote filopodia formation and actin polymerization, respectively. Consistently, depletion of ERK3 prevented both basal and EGF-dependent Rac1 and Cdc42 activation, maintenance of F-actin content, filopodia formation and epithelial cell migration. Further, ERK3 protein binds directly to the purified ARP2/3 complex and augments polymerization of actinin vitro. ERK3 kinase activity is required for the formation of actin-rich protrusions in mammalian cells. These findings unveil a fundamentally unique pathway employed by cells to control actin-dependent cellular functions.
Development of Multi-Bundle Virtual Ligaments to Simulate Knee Mechanics after Total Knee Arthroplasty
Authors: Vakili Samira , Lanting Brent , Getgood Alan , Willing Ryan 
Published: October 2022

AbstractPreclinical evaluation of total knee arthroplasty (TKA) components is essential to understanding their mechanical behavior and developing strategies for improving joint stability. While preclinical testing of TKA components has been useful in quantifying their effectiveness, such testing can be criticized for lacking clinical relevance, as the important contributions of surrounding soft tissues are either neglected or greatly simplified. The purpose of our study was to develop and determine if subject-specific virtual ligaments reproduce the same kinematics as native ligaments surrounding TKA joints. Five TKA knees were mounted to a motion simulator. Each was subjected to tests of anterior-posterior (AP), internal-external (IE), and varus-valgus (VV) laxity. The forces transmitted through major ligaments were measured using a sequential resection technique. By tuning the measured ligament forces and elongations to a generic non-linear elastic ligament model, virtual ligaments were designed and used to simulate the soft tissue envelope around isolated TKA components. The average root mean square error (RMSE) between the laxity results of TKA joints with native versus virtual ligaments was 2.9 mm during AP translation, 6.5° during IE rotations, and 2.0° during VV rotations, and there was no statistically significant difference between the results of both methods. Interclass correlation coefficients (ICCs) indicated a good level of reliability for AP and IE laxity (0.85 and 0.84). To conclude, a virtual ligament envelope around TKA joints can mimic natural knee behavior and is an effective method for the preclinical testing of TKA components.
Widespread enhancer co-activity identified by multimodal single cell analysis
Authors: Ziyani Chaymae , Delaneau Olivier , Ribeiro Diogo M. 
Published: October 2022

AbstractNon-coding regulatory elements such as enhancers are key in controlling the cell type-specificity and spatio-temporal expression of genes. To drive stable and precise gene transcription that is robust to genetic variation and environmental stress, genes are often targeted by multiple enhancers with redundant action. However, it is unknown whether enhancers targeting the same gene display simultaneous activity or whether some enhancer combinations are more often co-active than others. Here, we take advantage of the recent developments in single cell technology that permit assessing chromatin status (scATAC-seq) and gene expression (scRNA-seq) in the same single cells to link gene expression to the activity of multiple enhancers. Measuring activity patterns across 24,844 human lymphoblastoid single cells, we found that the majority of enhancers associated with the same gene display significant correlation in their chromatin profiles. For 6944 expressed genes associated with enhancers, we identified 89,885 significant enhancer-enhancer associations between nearby enhancers. We found that associated enhancers share similar transcription factor binding profiles and that gene essentiality is linked with higher enhancer co-activity. Our extensive enhancer co-activity maps can be used to pinpoint combinations of enhancers relevant in gene expression regulation and allow us to better predict the effect of genetic variation falling in non-coding regions.
Export of discarded splicing intermediates requires mRNA export factors and the nuclear basket
Authors: Zeng Yi , Staley Jonathan P. 
Published: October 2022

AbstractTo promote fidelity in nuclear pre-mRNA splicing, the spliceosome rejects and discards suboptimal splicing substrates after they have engaged the spliceosome. Although nuclear quality control mechanisms have been proposed to retain immature mRNPs, evidence indicates that discarded splicing substrates, including lariat intermediates, do export to the cytoplasm, as indicated by their translation and degradation by cytoplasmic nucleases. However, the mechanism for exporting these species has remained unknown. By single molecule (sm) RNA FISH in budding yeast, we have directly observed the nuclear export of lariat intermediates. Further, by crosslinking, export reporter assays, and smRNA FISH, we have demonstrated that the export of lariat intermediates requires the general mRNA export receptor Mex67p and three of its mRNA export adapter proteins, Nab2p, Yra1p, and Nlp3, establishing that mRNAs and lariat intermediates share the same export machinery. Unexpectedly, the export of lariat intermediates, but not mRNA, requires an interaction between Nab2p and Mlp1p, a nuclear basket component implicated in retaining immature mRNPs, including unspliced pre-mRNA, in the nucleus of budding yeast. Finally, the export of lariat intermediates, like mRNA, relies on the E3 ubiquitin ligase Tom1p and its target sites in Yra1p. Overall, our data indicate that the nuclear basket can promote, rather than antagonize, the export of an immature mRNP. Further, our data imply that the export of discarded lariat intermediates requires both Mlp1p-dependent docking onto the nuclear basket and subsequent Tom1p-mediated undocking, a mechanism our data suggests functions in the export of mRNA also but in a manner obscured by redundant pathways.
Chemical inhibition of PIN auxin transporters by the anti-inflammatory drug Naproxen
Authors: Xia Jing , Kong Mengjuan , Yang Zhisen , Sun Lianghanxiao , Peng Yakun , Wei Hong , Ying Wei , Gao Yongxiang , Friml Jiří , Liu Xin , Sun Linfeng , Tan Shutang 
Published: October 2022

AbstractThe phytohormone auxin plays central roles in many growth and developmental processes in plants. Development of chemical tools targeting the auxin pathway is useful for both plant biology and agriculture. Here we uncover that Naproxen, a synthetic compound with anti-inflammatory activity in humans, acts as an auxin transport inhibitor targeting PIN transporters in plants. Physiological experiments indicate that exogenous Naproxen treatment affects pleiotropic auxin-regulated developmental processes. Further cellular and biochemical evidence supports that Naproxen suppresses auxin transport, specifically PIN-mediated auxin efflux. Moreover, biochemical and structural analysis confirms that Naproxen binds directly to PIN1 protein, via the same binding cavity as the IAA substrate. Thus, by combining cellular, biochemical, and structural approaches, this study well establishes that Naproxen is a PIN inhibitor and elucidates the underlying mechanisms. Further use of the compound may advance our understanding on the molecular mechanisms of PIN-mediated auxin transport, and expand our toolkit in auxin biology and agriculture.
A stem cell zoo uncovers intracellular scaling of developmental tempo across mammals
Authors: Lázaro Jorge , Costanzo Maria , Sanaki-Matsumiya Marina , Girardot Charles , Hayashi Masafumi , Hayashi Katsuhiko , Diecke Sebastian , Hildebrandt Thomas B. , Lazzari Giovanna , Wu Jun , Petkov Stoyan , Behr Rüdiger , Trivedi Vikas , Matsuda Mitsuhiro , Ebisuya Miki 
Published: October 2022

AbstractDifferential speeds in biochemical reactions have been proposed to be responsible for the differences in developmental tempo between mice and humans. However, the underlying mechanism controlling the species-specific kinetics remains to be determined. Usingin vitrodifferentiation of pluripotent stem cells, we recapitulated the segmentation clocks of diverse mammalian species varying in body weight and taxa: marmoset, rabbit, cattle and rhinoceros. Together with the mouse and human, the segmentation clock periods of the six species did not scale with the animal body weight, but were rather grouped according to phylogeny. The biochemical kinetics of the core clock gene HES7 displayed clear scaling with the species-specific segmentation clock period. However, the cellular metabolic rates did not show an evident correlation. Instead, genes involving biochemical reactions showed an expression pattern that scales with the segmentation clock period. Altogether, our stem cell zoo uncovered general scaling laws governing species-specific developmental tempo.*
Metabolite profiling and cytotoxic activity of Andean potatoes: polyamines and glycoalkaloids as potential anticancer agents in human neuroblastoma cellsin vitro
Authors: Lanteri María Luciana , Silveyra María Ximena , Morán Mónica Mariela , Boutet Stéphanie , Solis-Gozar Deyvis-Dante , Perreau François , Andreu Adriana Balbina 
Published: October 2022

AbstractAndean potatoes (Solanum tuberosumL. ssp.andigena) are a good source of dietary antioxidant polyphenols. We have previously demonstrated that polyphenol extracts from Andean potato tubers exerted a dose-dependent cytotoxic effect in human neuroblastoma SH-SY5Y cells, being skin extracts more potent than flesh ones. In order to gain insight into the bioactivities of potato phenolics, we investigated the composition and thein vitrocytotoxic activity of total extracts and fractions of skin and flesh tubers of three Andean potato cultivars (Santa María, Waicha, and Moradita). Potato total extracts were subjected to liquid-liquid fractionation using ethyl acetate solvent in organic and aqueous fractions. We analyzed both fractions by HPLC-DAD, HPLC-ESI-MS/MS, and HPLC-HRMS. Results corroborated the expected composition of each fraction. Organic fractions were rich in hydroxycinnamic acids (principally chlorogenic acid isomers), whereas aqueous fractions contained mainly polyamines conjugated with phenolic acids, glycoalkaloids, and flavonoids. Organic fractions were not cytotoxic against SH-SY5Y cells, and indeed, some increased cellular metabolism compared to controls. Aqueous fractions were cytotoxic and even more potent than their respective total extracts. Treatment with a combination of both fractions showed a similar cytotoxic response to the corresponding extract. According to correlation studies, it is tempting to speculate that polyamines and glycoalkaloids are crucial in inducing cell death. Our findings indicate that the activity of Andean potato extracts is a combination of various compounds and contribute to the revalorization of potato as a functional food.