bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mechanisms of spontaneous Ca2+ release-mediated arrhythmia in a novel 3D human atrial myocyte model: II. Ca2+-handling protein variation
Authors: Zhang X. , Smith C.E.R. , Morotti S. , Edwards A.G. , Sato D. , Louch W.E. , Ni H. , Grandi E. 
Published: July 2022

AbstractDisruption of the transverse-axial tubule system (TATS) in diseases such as heart failure and atrial fibrillation occurs in combination with changes in the expression and distribution of key Ca2+- handling proteins. Together this ultrastructural and ionic remodeling is associated with aberrant Ca2+ cycling and electrophysiological instabilities that underly arrhythmic activity. However, due to the concurrent changes in TATs and Ca2+-handling protein expression and localization that occur in disease it is difficult to distinguish their individual contributions to the arrhythmogenic state. To investigate this, we applied our novel 3D human atrial myocyte model with spatially detailed Ca2+ diffusion and TATS to investigate the isolated and interactive effects of changes in expression and localization of key Ca2+-handling proteins and variable TATS density on Ca2+- handling abnormality driven membrane instabilities. We show that modulating the expression and distribution of the sodium-calcium exchanger, ryanodine receptors, and the sarcoplasmic reticulum (SR) Ca2+ buffer calsequestrin have varying pro and anti-arrhythmic effects depending on the balance of opposing influences on SR Ca2+ leak-load and Ca2+-voltage relationships. Interestingly, the impact of protein remodeling on Ca2+-driven proarrhythmic behavior varied dramatically depending on TATS density, with intermediately tubulated cells being more severely affected compared to detubulated and densely tubulated myocytes. This work provides novel mechanistic insight into the distinct and interactive consequences of TATS and Ca2+-handling protein remodeling that underlies dysfunctional Ca2+ cycling and electrophysiological instability in disease.Key PointsIn our companion paper we developed a 3D human atrial myocyte model, coupling electrophysiology and Ca2+ handling with subcellular spatial details governed by the transverse-axial tubule system (TATS).Here we utilize this model to mechanistically examine the impact of TATS loss and changes in the expression and distribution of key Ca2+-handling proteins known to be remodeled in disease on Ca2+ homeostasis and electrophysiological stability.We demonstrate that varying the expression and localization of these proteins has variable pro- and anti-arrhythmic effects with outcomes displaying dependence on TATS density.Whereas detubulated myocytes typically appear unaffected and densely tubulated cells seem protected, the arrhythmogenic effects of Ca2+ handling protein remodeling are profound in intermediately tubulated cells.Our work shows the interaction between TATS and Ca2+-handling protein remodeling that underlies the Ca2+-driven proarrhythmic behavior observed in AF and may help to predict the effects of antiarrhythmic strategies at varying stages of ultrastructural remodeling.
Impact of the extinct megaherbivore Steller’s sea cow (Hydrodamalis gigas) on kelp forest resilience
Authors: Roopnarine Peter D. , Banker Roxanne M. W. , Sampson Scott 
Published: July 2022

AbstractGiant kelp forests off the west coast of North America are maintained primarily by sea otter (Enhydra lutris) and sunflower sea star (Pycnopodia helianthoides) predation of sea urchins. Human hunting of sea otters in historic times, together with a marine heat wave and sea star wasting disease epidemic in the past decade, have devastated these predators, leading to widespread occurrences of urchin barrens. Since the late Neogene, species of the megaherbivorous sirenian Hydrodamalis ranged throughout North Pacific giant kelp forests. The last species, H. gigas, was driven to extinction by human hunting in the mid-18th century. H. gigas was an obligate kelp canopy browser, and its body size implies that it would have had a significant impact on the system. Here we hypothesize that sea cow browsing would have promoted a denser understory algal assemblage than is typical today, thereby providing an alternative food resource for urchins, resulting in enhanced forest resilience. We tested this hypothesis with a mathematical model, comparing historical and modern community responses to marine heat waves, sea star wasting disease, and the presence of sea otters. We found that forest communities were highly resistant to marine heat waves, yet susceptible to sea star wasting disease, and to disease in combination with warming. Resistance was greatest among systems with both sea cows and sea otters present. Most simulations that transitioned to barrens did so temporarily, recovering after about 10 years. Historical communities, however, exhibited delayed transitions after perturbation relative to modern communities and faster recovery times. Sea cow browsing facilitated denser algal understories, enhancing resilience against modern perturbations. We propose that operationalizing these findings by mimicking the ecological impact of sea cow herbivory could enhance kelp forest resilience.
Genomic characterization of viruses associated with the parasitoid Anagyrus vladimiri (Hymenoptera: Encyrtidae)
Authors: Izraeli Yehuda , Lepetit David , Atias Shir , Mozes-Daube Netta , Wodowski Gal , Lachman Oded , Luria Neta , Steinberg Shimon , Varaldi Julien , Zchori-Fein Einat , Chiel Elad 
Published: July 2022

AbstractThe knowledge on symbiotic microorganisms of insects has increased in recent years, yet relatively little data is available on non-pathogenic viruses. Here we studied the virome of the parasitoid wasp Anagyrus vladimiri (Hymenoptera: Encyrtidae), a biocontrol agent of mealybugs. By high-throughput sequencing of viral nucleic acids, we revealed three novel viruses, belonging to the families Reoviridae (provisionally termed AnvRV [Anagyrus vladimiri reovirus]), Iflaviridae (AnvIFV) and Dicistroviridae (AnvDV). Phylogenetic analysis further classified the AnvRV in the genus Idnoreovirus, and the AnvDV in the genus Triatovirus. The genome of AnvRV is comprised of 10 distinct genomic segments ranging in length from 1.5 to 4.2 Kbp, but only two out of the 10 open reading frames (ORFs) have a known function. AnvIFV and AnvDV each have one polypeptide ORF, which is typical to iflaviruses but very un-common among dicistroviruses. AnvRV was found to be fixed in a mass-reared population of A. vladimiri, whereas it’s prevalence in field-collected wasps was ~15%. Similarly, the prevalence of AnvIFV and AnvDV were much higher in the mass rearing population than in the field population. Transmission electron micrographs of females’ ovaries revealed clusters and viroplasms of Reovirus-like particles in follicle cells. AnvRV was not detected in the mealybugs, suggesting that this virus is truly associated with the wasps. The possible effects of these viruses on A. vladimiri’s biology, and on biocontrol agents in general are discussed. Our findings identify RNA viruses as potential players involved in the multitrophic system of mealybugs, their parasitoids and other members of the holobiont.ImportanceDifferent biological control approaches use industrially mass-reared natural enemy insects to reduce damage of arthropod pests. Such mass-reared cultures may be positively and/or negatively affected by various microorganisms, including viruses. Yet, current knowledge on virus diversity, especially in arthropods, is limited. Here, we provide the first virome characterization of a member of the wasps family Encyrtidae - the member being the parasitoid Anagyrus vladimiri - a commercially important natural enemy of mealybug pests. We describe the genome of three previously unknown RNA viruses, co-inhabiting this parasitoid, and elaborate on the prevalence of those viruses in individual wasps of both mass-reared and environmental origins. Microscopy images suggest that at least one of the viruses is transmitted maternally via the ovaries. We discuss the genomic structure of the viruses and the possible relationship between those viruses and the A. vladimiri host, with implications on improvement of biocontrol of mealybug pests.
Finding Functionality: Rasch Analysis of the Functionality Appreciation Scale in community-dwelling adults including adults with spinal cord injury and neuropathic pain in the US
Authors: Feng Sarah , McDaniel Sydney , Van de Winckel Ann 
Published: July 2022

AbstractThe Functionality Appreciation Scale (FAS) measures an individual’s appreciation for the functions their body can perform, regardless of the individual’s physical limitations. To facilitate the use of this tool by researchers and clinicians, it is necessary to understand what ‘normal’ scoring looks like in healthy adults, as well as validate the scoring of this scale. We analyzed the FAS using Rasch Measurement Theory. FAS responses, demographic data, and clinical questionnaires were collected by the Brain Body Mind Lab (University of Minnesota) from 567 community-dwelling adults recruited at the Minnesota State Fair, including 14 adults with spinal cord injury. We evaluated item and person fit, targeting, unidimensionality, person separation reliability (PSR), local item dependence (LID), and differential item functioning (DIF) for demographic and clinical characteristics. We found a significant ceiling effect (26.98%) and a positive person mean location of 3.28±2.10 logits, indicating the FAS is too easy for the community-dwelling adults in the US. PSR was 0.79, indicating a capacity to differentiate groups of people according to their ability level of functional appreciation. We also compared the person mean location of adults who did or did not participate in body awareness training. Adults who practiced body awareness training had a higher person mean location (4.28, Interquartile Range [IQR] = 3.96 logits) than those who did not (2.73, IQR = 3.34), indicating a higher functionality appreciation. Overall, FAS demonstrated good item and person fit, but the current version of FAS will require more difficult items to be added to improve the targeting of the scale for use in a general population.
The association of typical and atypical symptoms on in-hospital mortality of older adults with COVID-19: a multicentre cohort study
Authors: Wong Eric Kai-Chung , Watt Jennifer , Zou Hanyan , Chandraraj Arthana , Zhang Alissa Wenyue , Brookes Jahnel , Verduyn Ashley , Berall Anna , Norman Richard , Piggott Katrina , Izukawa Terumi , Straus Sharon E. , Liu Barbara 
Published: July 2022

AbstractAtypical disease presentations are common in older adults with COVID-19. The objective of this study was to determine the prevalence of atypical and typical symptoms in older adults with COVID-19 through progressive pandemic waves and the association of these symptoms with in-hospital mortality. This retrospective cohort study included consecutive adults aged over 65 years with confirmed COVID-19 infection who were admitted to seven hospitals in Toronto, Canada from March 1, 2020 to June 30, 2021. The median age for the 1786 patients was 78.0 years and 847 (47.5%) were female. Atypical symptoms (as defined by geriatric syndromes) occurred in 1187 patients (66.5%), but rarely occurred in the absence of other symptoms (n=106, 6.2%). The most common atypical symptoms were anorexia (n=598, 33.5%), weakness (n=519, 23.9%), and delirium (n=449, 25.1%). Dyspnea (adjusted odds ratio [aOR] 2.05, 95% confidence interval [CI] 1.62–2.62), tachycardia (aOR 1.87, 95% CI 1.14–3.04), and delirium (aOR 1.52, 95% CI 1.18–1.96) were independently associated with in-hospital mortality. In a cohort of older adults hospitalized with COVID-19 infection, atypical presentations frequently overlapped with typical symptoms. Further research should be directed at understanding the cause and clinical significance of atypical presentations in older adults.
GIS-based approach and multivariate statistical analysis for identifying sources of heavy metals in marine sediments from the coast of Hong Kong
Authors: Huang Fengwen , Chen Chen 
Published: July 2022

AbstractMultiple methods consisting of geographic information system (GIS) technique, enrichment factor (EF), potential ecological risk index (PEI) and multivariate statistical methods was developed to identify anthropogenic heavy metal sources in marine sediments of Hong Kong. The distributions of heavy metals in sediments have been analyzed, and their pollution degrees, corresponding potential ecological risks and source identifications have been studied using geo-accumulation index, potential ecological risk index and integrated multivariate statistical methods, respectively. Three different types of anthropogenic inputs could be identified via multivariate analysis. Acoording to the findings, the first principal component might originate from the industrial discharges and shipping activities. The second principal component were identified from the natural sources. The third component mainly from the municipal discharges and industrial wastewater. These results provide baseline information for both the coastal environment management and the worldwide heavy metal distribution and assessment.
Phylogenetic Biodiversity Metrics Should Account for Both Accumulation and Attrition of Evolutionary Heritage
Authors: Rosindell James , Manson Kerry , Gumbs Rikki , Pearse William D. , Steel Mike 
Published: July 2022

AbstractPhylogenetic metrics are essential tools used in the study of ecology, evolution and conservation. Phylogenetic diversity (PD) in particular is one of the most prominent measures of biodiversity, and is based on the idea that biological features accumulate along the edges of phylogenetic trees that are summed. We argue that PD and many other phylogenetic biodiversity metrics fail to capture an essential process that we term attrition. Attrition is the gradual loss of features through causes other than extinction. Here we introduce ‘EvoHeritage’, a generalisation of PD that is founded on the joint processes of accumulation and attrition of features. We argue that whilst PD measures evolutionary history, EvoHeritage is required to capture a more pertinent subset of evolutionary history including only components that have survived attrition. We show that EvoHeritage is not the same as PD on a tree with scaled edges; instead, accumulation and attrition interact in a more complex non-monophyletic way that cannot be captured by edge lengths alone. This leads us to speculate that the one dimensional edge lengths of classic trees may be insufficiently flexible to capture the nuances of evolutionary processes. We derive a measure of EvoHeritage and show that it elegantly reproduces species richness and PD at opposite ends of a continuum based on the intensity of attrition. We demonstrate the utility of EvoHeritage in ecology as a predictor of community productivity compared with species richness and PD. We also show how EvoHeritage can quantify living fossils and resolve their associated controversy. We suggest how the existing calculus of PD-based metrics and other phylogenetic biodiversity metrics can and should be recast in terms of EvoHeritage accumulation and attrition.Candidate cover imageArtistic cover image prepared for this manuscript. The central tree depicts the gain and loss of Evolutionary Heritage (EvoHeritage) along each edge with its many coloured sections. EvoHeritage is proposed as an expansion of the concept of phylogenetic diversity. Around the outside of the tree are species that feature in our two practical applications of the EvoHeritage calculus: mammals identified as ‘living fossils’ and plants included in our study of community productivity. The cover image was generated by James Rosin-dell following discussions with co-authors. The Caenolestes outline (representing shrew opossums) and Dromiciops outline (monito del monte) used as components of this image are credited to Sarah Werning and provided under a CC BY 3.0 license; both images were recoloured in brown and placed over a shaded circle. All other images used as components are from the public domain. We thank Mina Mincheva for useful feedback on earlier drafts of the cover image.
Adipocyte differentiation of 3T3-L1 cells under TAF, TDF and INSTIs selective challenge: an in vitro model
Authors: Perna A. , Carleo M.A. , Mascolo S. , Guida A. , Contieri M. , Sellitto C , Hay E. , De Blasiis P. , Lucariello A. , Guerra G. , Baldi A. , De Luca A. , Maggi P. , Esposito V. 
Published: July 2022

ABSTRACTIntegrase strand transfer inhibitors (INSTI) are a recently available class of antiretroviral therapy (ART) medications with a good tolerability profile and a high genetic barrier to HIV drug resistance. However, several studies report more significant weight gain among persons receiving INSTI-based ART regimens for initial therapy compared to protease inhibitors (PIs) and nucleoside reverse transcriptase inhibitors (NNRTI)-based regimens. In our experimental setting, we used the in vitro model of adipogenesis of 3T3-L1 cells to investigate the effects of the NRTIs tenofovir disoproxil fumarate (TDF) and tenofovir alafenamide (TAF), alone or in combination with four integrase strand transfer inhibitors: raltegravir (RAL), elvitegravir (ELV), dolutegravir (DTG) and bictegravir (BIC) on adipose differentiation. In addition, protein expression levels of PPARɣ and C/EBPα, and the intracellular lipid accumulation by Red Oil staining, were used to monitor adipocyte differentiation. Compared to control, RAL, ELV, DTG, and BIC were all able to increase adipogenesis, being in this, RAL and ELV more efficient. On the other hand, TAF and TDF inhibited adipogenesis. Moreover, when used in combination with the other INSTI molecules, TAF and TDF were able to reduce the adipogenic effects of all four drugs. This ability was more evident when TAF was used in combination with DTG and BIC. All these data suggest that TAF and TDF have an inhibitory effect on adipogenesis in vitro and that they could also effectively counteract the increased adipogenesis caused by the treatment with INSTIs. Finally, to evaluate if the 3T3-L1 cell could express fibroblast-like features following INSTIs treatment, we evaluated the immunohistochemical expression of ER-TR7, a well-known fibroblastic marker. This last assay showed that treatment with INSTIs increased the expression of ER-TR7 compared to control and to cells treated with TAF o TDF.In conclusion, our experimental data support the evidence that in vitro challenge of 3T3-L1 cells with INSTIs is able to increase adipocytic differentiation and to drive a number of these cells toward the expression of fibroblastic features, with a different degree according to the various drugs used, while TAF and TDF have an antagonistic role on this phenomenon.
Plap-1/Aspn lineage tracing and single-cell transcriptomics reveals cellular dynamics in the periodontal ligament
Authors: Iwayama Tomoaki , Iwashita Mizuho , Miyashita Kazuya , Sakashita Hiromi , Matsumoto Shuji , Tomita Kiwako , Bhongsatiern Phan , Kitayama Tomomi , Ikegami Kentaro , Shimbo Takashi , Tamai Katsuto , Murayama Masanori A , Ogawa Shuhei , Iwakura Yoichiro , Yamada Satoru , Olson Lorin E , Takedachi Masahide , Murakami Shinya 
Published: July 2022

SummaryPeriodontal tissue supports teeth in the alveolar bone socket via fibrous attachment of the periodontal ligament (PDL). The PDL contains periodontal fibroblasts and stem/progenitor cells, collectively known as PDL cells (PDLCs), on top of osteoblasts and cementoblasts on the surface of alveolar bone and cementum, respectively. However, the characteristics and lineage hierarchy of each cell type remain poorly defined. This study identified periodontal ligament associated Protein-1 (Plap-1/Aspn) as a PDL-specific extracellular matrix. We generated knock-in mice expressing CreERT2 and GFP specifically in Plap-1-positive PDLCs. Genetic lineage tracing confirmed the long-standing hypothesis that PDLCs differentiated into osteoblasts and cementoblasts. A PDL single-cell atlas defined cementoblasts and osteoblasts as Plap-1-Ibsp+Sparcl1+ and Plap-1-Ibsp+Col11a2+, respectively. Other populations such as Nes+ mural cells, S100B+ Schwann cells, and other non-stromal cells were also identified. RNA velocity analysis suggested that Plap-1highLy6a+ cell population was the source of PDLCs. Lineage tracing of Plap-1+ PDLCs during the periodontal injury model showed periodontal tissue regeneration by PDLCs. Our study defines diverse cell populations in PDL and clarifies the role of PDLCs in periodontal tissue homeostasis and repair.
Automation of yeast spot assays using an affordable liquid handling robot
Authors: Taguchi Shodai , Suda Yasuyuki , Irie Kenji , Ozaki Haruka 
Published: July 2022

AbstractThe spot assay of the budding yeastSaccharomyces cerevisiaeis an experimental method that is used to evaluate the effect of genotypes, medium conditions, and environmental stresses on cell growth and survival. Automation of the spot assay experiments from preparing a dilution series to spotting to observing spots continuously has been implemented based on large laboratory automation devices and robots, especially for high-throughput functional screening assays. However, there has yet to be an affordable solution for the automated spot assays suited to researchers in average laboratories and with high customizability for end-users. To make reproducible spot assay experiments widely available, we have automated the plate-based yeast spot assay of budding yeast using Opentrons OT-2 (OT-2), an affordable liquid-handling robot, and a flatbed scanner. We prepared a 3D-printed mount for the Petri dish to allow for precise placement of the Petri dish inside the OT-2. To account for the uneven height of the agar plates, which were made by human hands, we devised a method to adjust the z-position of the pipette tips which is based on the weight of each agar plate. During the incubation of the agar plates, a flatbed scanner was used to automatically take images of the agar plates over time, allowing researchers to quantify and compare the cell density within the spots at optimal time pointsa posteriori. Furthermore, the accuracy of the newly developed automated spot assay was verified by performing spot assays with human experimenters and the OT-2 and quantifying the yeast-grown area of the spots. This study will contribute to the introduction of automated spot assays and the automated acquisition of growth processes in conventional laboratories that are not adapted for high-throughput laboratory automation.