bluuebunny/crossref_metadata_2025_split huggingface dataset:
The role of antifreeze glycopeptides (AFGP) and polyvinyl alcohol/polyglycerol (X/Z-1000) cocktails as ice modulators during partial freezing of rat livers
Authors: Tessier Shannon N. , Haque Omar , Pendexter Casie A. , Cronin Stephanie E.J. , Weng Lindong , Yeh Heidi , Markmann James F. , Taylor Michael J. , Fahy Gregory M. , Toner Mehmet , Uygun Korkut 
Published: August 2021

AbstractThe current liver organ shortage has pushed the field of liver transplantation to develop new methods to prolong the preservation time of livers from the current clinical standard of static cold storage. Our approach, termed partial freezing, aims to induce a thermodynamically stable frozen state at deeper storage temperatures (−10°C to −15°C) than can be achieved with supercooling, while simultaneously maintaining a sufficient unfrozen fraction to limit dehydration and ice damage. This research first demonstrated that partially frozen glycerol treated rat livers were functionally similar after thawing from either −10 or −15°C with respect to subnormothermic machine perfusion metrics and histology. Next, we assessed the effect of adding either of two ice modulators, antifreeze glycoprotein (AFGP) and a polyvinyl alcohol/polyglycerol combination (X/Z-1000), on the viability and structural integrity of partially frozen rat livers compared to glycerol-only control livers. Results showed that AFGP livers had high levels of ATP and the least edema but suffered from significant endothelial cell damage. X/Z-1000 livers had the highest levels of ATP and energy charge (EC) but also demonstrated endothelial damage and post-thaw edema. Glycerol-only control livers exhibited the least DNA damage on Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining but also had the lowest levels of ATP and EC. Further research is necessary to optimize the ideal ice modulator cocktail for our partial-freezing protocol. Modifications to cryoprotective agent (CPA) combinations, as well as improvements to machine perfusion CPA loading and unloading, can help improve the viability of these partially frozen organs.
Intercontinental comparison of ferns community assemblages in Malaysian and Nigerian tropical forests
Authors: Akomolafe Gbenga F. , Rosazlina Rusly Binti , Rahmad Zakaria , Oloyede Fatai A. 
Published: August 2021

AbstractResearch on ferns ecology has gained attention in the last decade, yet there is paucity of information on the intercontinental comparison of ferns community across two continents. This study focused on comparing the ferns community assemblages in tropical forests of Malaysia and Nigeria, thereby assessing the patterns of the species richness and diversity across the two continents. The diversity and taxonomic compositions of ferns were assessed using 180 plots of size 10 m x 10 m in each country. The species richness and other diversity indices were determined using the combined forests data for each country and for the individual forests. The observed and rarefied–extrapolated fern species richness are significantly higher in Malaysian forests than Nigerian forests. Also, the other diversity indices (Simpson index, Margalef index, and Fisher’s alpha) are significantly higher in Malaysian forests except Shannon index which showed no significant difference between the two biogeographic regions. There is a very low similarity in the taxonomic composition of ferns between the two biogeographic areas, although the similarity in composition increased with increasing taxonomic levels (genus and family levels). Terrestrial and epiphytic ferns are more dominant than the other life forms in the two countries. Since the two countries receive varying degrees of environmental factors, we then hypothesize that these observed differences are due to climatic differences as well as historical and evolutionary processes.
Height-diameter allometry for tropical forest in northern Amazonia
Authors: de Lima Robson Borges , Görgens Eric Bastos , Elias Fernando , de Abreu Jadson Coelho , Baia Aldine Luiza , de Oliveira Cinthia Pereira , da Silva Diego Armando Silva , Batista Anderson Pedro Bernardina , Lima Robson Carmo , Sotta Eleneide Doff 
Published: August 2021

AbstractHeight measurements are essential to manage and monitor forest biomass and carbon stocks. However, accurate estimation of this variable in tropical ecosystems is still difficult due to species heterogeneity and environmental variability. In this article, we compare and discuss six nonlinear allometric models parameterized at different scales (local, regional and pantropical). We also evaluate the height measurements obtained in the field by the hypsometer when compared with the true tree height. We used a dataset composed of 180 harvested trees in two distinct areas located in the Amapá State. The functional form of the Weibull model was the best local model, showing similar performance to the pantropical model. The inaccuracy detected in the hypsometer estimates reinforces the importance of incorporating new technologies in measuring individual tree heights. Establishing accurate allometric models requires knowledge of ecophysiological and environmental processes that govern vegetation dynamics and tree height growth. It is essential to investigate the influence of different species and ecological gradients on the diameter/height ratio.
Sex- and age- dependent effect of pre-gestational chronic stress and mirtazapine treatment on neurobehavioral development of offspring
Authors: Mireia Viñas-Noguera , Kristína Csatlósová , Eva Šimončičová , Ezster Bögi , Eduard Ujházy , Michal Dubovický , Kristína Belovičová 
Published: August 2021

ABSTRACTHormonal fluctuations, such as the perinatal period, may increase susceptibility of women to depression, which in turn exert a negative impact on child’s neurodevelopment, becoming a risk factor in development of neuropsychiatric disorders. Moreover, the use of antidepressants during this critical period presents a serious health concern for both the mother and the child, due to the consequences of treatment in terms of the reliability and safety for the proper neurodevelopment of the organism being not well known. Atypical antidepressants, such as mirtazapine, that targets both serotonergic and noradrenergic systems in the central nervous system (CNS), represent a novel focus of research due to its unique pharmacological profile. The aim of this work was to study the effects of maternal depression and/or perinatal antidepressant mirtazapine treatment on the neurobehavioral development of the offspring. Pre-gestationally chronically stressed or non-stressed Wistar rat dams were treated with either mirtazapine (10 mg/kg/day) or vehicle during pregnancy and lactation followed by analysis of offspring’s behavior at juvenile and adolescent age. We found mirtazapine induced alterations of nursing behavior. In offspring, pregestational stress (PS) had an anxiogenic effect on adolescent males and increased their active behavior in forced swim test. Interaction between pregestational stress and mirtazapine treatment variously induced anxiolytic changes of juvenile and adolescent females and impairment of spatial memory in adolescent females as well. Hippocampal density of synaptophysin, pre-synaptic protein marker, was decreased mainly by mirtazapine treatment. In conclusion, our results show mirtazapine induced alterations in maternal behavior and several sex- and age-dependent changes in neurobehavioral development of offspring caused by both prenatal mirtazapine treatment and/or chronic pregestational stress.
Utility of Occupancy Models with Environmental DNA (eDNA) from Olympic Coast National Marine Sanctuary
Authors: Paight Christopher , Waddell Jenny , Galaska Matthew P 
Published: August 2021

AbstractAdjacent to the spectacular, rugged coastline bordering the Olympic Peninsula of Washington State, Olympic Coast National Marine Sanctuary (OCNMS) encompasses 8257 km2 of coastal waters that support one of North America’s most productive marine ecosystems. These rich waters support important recreational, commercial and subsistence fisheries for Washington state and four sovereign tribal governments: the Quinault Indian Nation and the Makah, Quileute and Hoh Tribes. Given its ecological, cultural and economic significance, managers from OCNMS are tasked with monitoring and management towards conserving the area’s ecological integrity. The development of metabarcoding with environmental DNA (eDNA) as an effective freshwater monitoring tool has potential applications in marine systems, but the statistical analysis and the interpretation of those eDNA results are still under development. One promising strategy to analyze eDNA is through the use of occupancy models. Occupancy models enable us to calculate probabilities of detection from each taxon sequenced and are designed to work with presence-absence data. To inform our long term monitoring design of this coastal ecosystem, we collected 44 eDNA samples at nine of OCNMS’ long term mooring sites in 2019 and tested four different molecular markers for species reported and taxonomic richness. Additionally, we assessed occupancy models for use with eDNA to estimate the number of samples required to accurately predict the presence of a species. Occupancy models show great promise for use in eDNA studies provided there is sufficient replication; additionally, the choice of molecular marker strongly influences a taxa’s probability of detection.Author SummaryWe show the utility of using occupancy models with eDNA in Olympic Coast National Marine Sanctuary for monitoring near-shore marine biological communities. Based on probabilities of detection, long term coastal monitoring projects using eDNA would benefit from designs prioritizing sample number (10-20 samples per site) over sites sampled. With proper study design, occupancy models provide a statistical framework for comparisons between sites and over time. By accounting for simple non-detection vs true absence, occupancy models help to eliminate noise from eDNA studies, increasing detection of true shifts in community composition. We also demonstrate that marker choice is an important study design consideration not only for the types of taxa recovered, but also for consistency between samples and timepoints.
Kdm6a Deficiency Restricted to Mouse Hematopoietic Cells Causes an Age- and Sex-dependent Myelodysplastic Syndrome-Like Phenotype
Authors: Tian Ling , Chavez Monique , Chang Gue Su , Helton Nichole M. , Katerndahl Casey D.S. , Miller Christopher A. , Wartman Lukas D. 
Published: August 2021

AbstractKdm6a/Utx, a gene on the X chromosome, encodes a histone K27me3 demethylase that has an orthologue on the Y chromosome (Uty)[1]. We previously identified inactivating mutations of Kdm6a in approximately 50% of mouse acute promyelocytic leukemia samples; however, somatic mutations of KDM6A are more rare in human AML samples, ranging in frequency from 2-15% in different series of patients, where their role in pathogenesis is not yet clear. In this study, we show that female Kdm6aflox/flox mice (with allele inactivation initiated by Vav1-Cre in hematopoietic stem and progenitor cells (HSPCs) have a sex-specific phenotype that emerges with aging, with features resembling a myelodysplastic syndrome (MDS). Female Kdm6a-knockout (KO) mice have an age-dependent expansion of their HSPCs with aberrant self-renewal, but they did not differentiate normally into downstream progeny. These mice became mildly anemic and thrombocytopenic, but did not develop overt leukemia, or die from these cytopenias. ChIP-seq and ATAC-seq studies showed only minor changes in H3K27me3, H3K27ac, H3K4me, H3K4me3 and chromatin accessibility between Kdm6a-WT and Kdm6a-KO mice. Utilizing scRNA-seq, Kdm6a loss was linked to the transcriptional repression of genes that mediate hematopoietic cell fate determination. These data demonstrate that Kdm6a plays an important role in normal hematopoiesis, and that its inactivation may contribute to AML pathogenesis by altering the epigenetic state of HSPCs.
Default Mode Network Connectivity Predicts Individual Differences in Long-Term Forgetting: Evidence for Storage Decay, not Retrieval Failure
Authors: Xu Yinan , Prat Chantel , Sense Florian , van Rijn Hedderik , Stocco Andrea 
Published: August 2021

AbstractDespite the importance of memories in everyday life and the progress made in understanding how they are encoded and retrieved, the neural processes by which declarative memories are maintained or forgotten remain elusive. Part of the problem is that it is empirically difficult to measure the rate at which memories fade, even between repeated presentations of the source of the memory. Without such a ground-truth measure, it is hard to identify the corresponding neural correlates. This study addresses this problem by comparing individual patterns of functional connectivity against behavioral differences in forgetting speed derived from computational phenotyping. Specifically, the individual-specific values of the speed of forgetting in long-term memory (LTM) were estimated for 33 participants using a formal model fit to accuracy and response time data from an adaptive fact learning task. Individual speeds of forgetting were then used to examine participant-specific patterns of resting-state fMRI connectivity, using machine learning techniques to identify the most predictive and generalizable features. Our results show that individual speeds of forgetting are associated with resting-state connectivity within the default mode network (DMN) as well as between the DMN and cortical sensory areas. Cross-validation showed that individual speeds of forgetting were predicted with high accuracy (r= .78) from these connectivity patterns alone. These results support the view that DMN activity and the associated sensory regions are actively involved in maintaining memories and preventing their decline, suggesting that forgetting is better understood as a result of storage decay, rather than retrieval failure.
Contribution of single mutations to selected SARS-CoV-2 emerging variants Spike antigenicity
Authors: Gong Shang Yu , Chatterjee Debashree , Richard Jonathan , Prévost Jérémie , Tauzin Alexandra , Gasser Romain , Bo Yuxia , Vézina Dani , Goyette Guillaume , Gendron-Lepage Gabrielle , Medjahed Halima , Roger Michel , Côté Marceline , Finzi Andrés 
Published: August 2021

ABSTRACTTowards the end of 2020, multiple variants of concern (VOCs) and variants of interest (VOIs) have arisen from the original SARS-CoV-2 Wuhan-Hu-1 strain. Mutations in the Spike protein are highly scrutinized for their impact on transmissibility, pathogenesis and vaccine efficacy. Here, we contribute to the growing body of literature on emerging variants by evaluating the impact of single mutations on the overall antigenicity of selected variants and their binding to the ACE2 receptor. We observe a differential contribution of single mutants to the global variants phenotype related to ACE2 interaction and antigenicity. Using biolayer interferometry, we observe that enhanced ACE2 interaction is mostly modulated by a decrease in off-rate. Finally, we made the interesting observation that the Spikes from tested emerging variants bind better to ACE2 at 37°C compared to the D614G variant. Whether improved ACE2 binding at higher temperature facilitates emerging variants transmission remain to be demonstrated.
BET inhibitors synergize with anti-PD1 by rescuing TCF1+ progenitor exhausted CD8+ T cells in Acute Myeloid Leukemia
Authors: Romine Kyle A. , Cho Hyun-jun , Kosaka Yoko , Byrd Kaelan H. , Coy Jesse L. , Flynn Patrick A. , Newman Matthew T. , Loo Christopher , Scott Jaime , Lind Evan F. 
Published: August 2021

AbstractMany acute myeloid leukemia (AML) patients exhibit hallmarks of immune exhaustion, such as increased myeloid derived suppressor cells (MDSCs), suppressive regulatory T cells (Tregs) and dysfunctional T cells. We have developed a mouse model of AML driven by Flt3-ITD and Tet2 deficiency displays these immune-related features, including CD8+ T cells exhibiting a terminally exhausted phenotype (TEx). This T cell subset has been shown to be refractory to immune checkpoint blockade (ICB) monotherapy. Here we show that small molecule inhibitors which target bromodomain and extra-terminal domain (BET) proteins affect both tumor-intrinsic factors but also rescue T cell exhaustion and ICB resistance. Ex vivo treatment of cells from AML mice and AML patients with BET inhibitors (BETi) reversed CD8+ T cell exhaustion by restoring proliferative capacity and expansion of the more functional precursor exhausted T cells (TPEx). This reversal is enhanced by combined BETi and anti-PD1 treatment. Finally, we show that BETi synergizes with anti-PD1 in vivo, resulting in the reduction of circulating leukemia cells, enrichment of CD8+ T cells in the bone marrow, and increased expression of Tcf7, Slamf6, and Cxcr5 in CD8+ T cells. In total, we show the potential efficacy of combining BETi and ICB therapy in the treatment of AML.
Petascale neural circuit reconstruction: automated methods
Authors: Macrina Thomas , Lee Kisuk , Lu Ran , Turner Nicholas L. , Wu Jingpeng , Popovych Sergiy , Silversmith William , Kemnitz Nico , Bae J. Alexander , Castro Manuel A. , Dorkenwald Sven , Halageri Akhilesh , Jia Zhen , Jordan Chris , Li Kai , Mitchell Eric , Mondal Shanka Subhra , Mu Shang , Nehoran Barak , Wong William , Yu Szi-chieh , Bodor Agnes L. , Brittain Derrick , Buchanan JoAnn , Bumbarger Daniel J. , Cobos Erick , Collman Forrest , Elabbady Leila , Fahey Paul G. , Froudarakis Emmanouil , Kapner Daniel , Kinn Sam , Mahalingam Gayathri , Papadopoulos Stelios , Patel Saumil , Schneider-Mizell Casey M. , Sinz Fabian H. , Takeno Marc , Torres Russel , Yin Wenjing , Pitkow Xaq , Reimer Jacob , Tolias Andreas S. , Reid R. Clay , Costa Nuno Maçarico da , Seung H. Sebastian 
Published: August 2021

Abstract3D electron microscopy (EM) has been successful at mapping invertebrate nervous systems, but the approach has been limited to small chunks of mammalian brains. To scale up to larger volumes, we have built a computational pipeline for processing petascale image datasets acquired by serial section EM, a popular form of 3D EM. The pipeline employs convolutional nets to compute the nonsmooth transformations required to align images of serial sections containing numerous cracks and folds, detect neuronal boundaries, label voxels as axon, dendrite, soma, and other semantic categories, and detect synapses and assign them to presynaptic and postsynaptic segments. The output of neuronal boundary detection is segmented by mean affinity agglomeration with semantic and size constraints. Pipeline operations are implemented by leveraging distributed and cloud computing. Intermediate results of the pipeline are held in cloud storage, and can be effortlessly viewed as images, which aids debugging. We applied the pipeline to create an automated reconstruction of an EM image volume spanning four visual cortical areas of a mouse brain. Code for the pipeline is publicly available, as is the reconstructed volume.
Retinal degeneration: Multilevel protection of photoreceptor and ganglion cell viability and function with the novel PKG inhibitor CN238
Authors: Tolone Arianna , Haq Wadood , Fachinger Alexandra , Rentsch Andreas , Herberg Friedrich W. , Schwede Frank , Paquet-Durand François 
Published: August 2021

AbstractHereditary retinal degeneration (RD) is often associated with excessive cGMP-signaling in photoreceptors. Previous research has shown that inhibition of cGMP-dependent protein kinase G (PKG) can slow down the loss of photoreceptors in different RD animal models. In this study, we identified a novel PKG inhibitor, the cGMP analogue CN238, with strong protective effects on photoreceptors in retinal degenerationrd1andrd10mutant mice. In long-term organotypic retinal explants, CN238 preservedrd1andrd10photoreceptor viability and function. Surprisingly, in explanted retinae CN238 also protected retinal ganglion cells from axotomy induced retrograde degeneration and preserved their functionality. Together, these results confirm the strong neuroprotective capacity of PKG inhibitors for both photoreceptors and retinal ganglion cells, thereby significantly broadening their potential applications for the treatment of retinal diseases and possibly neurodegenerative diseases in general.
Size-scaling promotes senescence-like changes in proteome and organelle content
Authors: Cheng Ling , Chen Jingyuan , Kong Yidi , Tan Ceryl , Kafri Ran , Björklund Mikael 
Published: August 2021

AbstractSenescent cells typically have an enlarged cell size but the reason for this has not been fully elucidated. As abnormal cell size may alter protein concentrations and cellular functionality, we used proteomic data from 59 unperturbed human cell lines to systematically characterize cell-size dependent changes in intracellular protein concentrations and organelle content. Increase in cell size leads to ubiquitous transcriptionally and post-transcriptionally regulated reorganization and dilution of the proteome. Many known senescence proteins display disproportionate size-scaling consistent with their altered expression in senescent cells, while lysosomes and the endoplasmic reticulum expand in larger cells contributing to the senescence phenotype. Analysis of organelle proteome expression identifies p53 and retinoblastoma pathways as mediators of size-scaling, consistent with their role in senescence. Taken together, cell size can alter cellular fitness and function through cumulative reorganization of the proteome and organelle content. An extreme consequence of this pervasive size-scaling appears to be senescence.
Autophagy suppression by TORC1 maintains epithelial plasma membrane integrity and inhibits syncytium formation
Authors: Kakanj Parisa , Bhide Sourabh , Moussian Bernard , Leptin Maria 
Published: August 2021

AbstractEpithelial wound healing inDrosophilainvolves the formation of multinucleate cells surrounding the wound. We show that autophagy, a cellular degradation process often deployed in stress responses, is required for the formation of a multinucleated syncytium during wound healing. In addition, uncontrolled autophagy in the unwounded epidermis leads to the degradation of endo-membranes and the lateral plasma membrane, while the apical and basal membranes and the epithelial barrier function remain intact. Proper functioning of TORC1 is needed to prevent autophagy from destroying the larval epidermis, which depends on membrane isolation and phagophore expansion, but does not require the fusion of autophagosomes to lysosomes. Our findings reveal a function for TORC1-mediated regulation of autophagy in maintaining membrane integrity and homeostasis in the epidermis and during wound healing. Finally, autophagy can counteract experimentally induced nuclear defects resembling laminopathies.Key findingsA novel role for TORC1/autophagy pathway to control plasma membrane integrity and homeostasis.Autophagy as the only known necessary and sufficient inducer of syncytium formation in the epithelium and during wound healing.