bluuebunny/crossref_metadata_2025_split huggingface dataset:
Asgard ESCRT-III and VPS4 reveal conserved chromatin binding properties of the ESCRT machinery
Authors: Nachmias Dikla , Melnikov Nataly , Zorea Alvah , Sharon Maya , Yemini Reut , De-picchoto Yasmin , Tsirkas Ioannis , Aharoni Amir , Frohn Bela , Schwille Petra , Zarivach Raz , Mizrahi Itzhak , Elia Natalie 
Published: October 2022

Abstract
The archaeal Asgard superphylum currently stands as the most promising prokaryotic candidate, from which eukaryotic cells emerged. This unique superphylum encodes for eukaryotic signature proteins (ESP) that could shed light on the origin of eukaryotes, but the properties and function of these proteins is largely unresolved. Here, we set to understand the function of an Asgard archaeal protein family, namely the ESCRT machinery, that is conserved across all domains of life and executes basic cellular eukaryotic functions, including membrane constriction during cell division. We find that ESCRT proteins encoded in Loki archaea, express in mammalian and yeast cells, and that the Loki ESCRT-III protein, CHMP4-7, resides in the eukaryotic nucleus in both organisms. Moreover, Loki ESCRT-III proteins associated with chromatin, recruited their AAA-ATPase VPS4 counterpart to organize in discrete foci in the mammalian nucleus, and directly bind DNA. The human ESCRT-III protein, CHMP1B, exhibited similar nuclear properties and recruited both human and Asgard VPS4s to nuclear foci, indicating interspecies interactions. Mutation analysis revealed a role for the N terminal region of ESCRT-III in mediating these phenotypes in both human and Asgard ESCRTs. These findings suggest that ESCRT proteins hold chromatin binding properties that were highly preserved through the billion years of evolution separating Asgard archaea and humans. The conserved chromatin binding properties of the ESCRT membrane remodeling machinery, reported here, may have important implications for the origin of eukaryogenesis.
Nephrons, podocytes and chronic kidney disease: Strategic antihypertensive therapy for renoprotection
Authors: Haruhara Kotaro , Kanzaki Go , Tsuboi Nobuo 
Published: October 2022

AbstractChronic kidney disease (CKD) is one of the strongest risk factors for hypertension, and hypertension can exacerbate the progression of CKD. Thus, the management of CKD and antihypertensive therapy are inextricably linked. Research over the past decades has shown that the human kidney is more diverse than initially thought. Subjects with low nephron endowment are at increased risk of developing CKD and hypertension, which is consistent with the theory of the developmental origins of health and disease. Combined with other lifetime risks of CKD, hypertension may lead to a vicious cycle consisting of podocyte injury, glomerulosclerosis and further loss of nephrons. Of note, recent studies have shown that the number of nephrons correlates well with the number of podocytes, suggesting that these two components are intrinsically linked and may influence each other. Both nephrons and podocytes have no or very limited regenerative capacity and are destined to decrease throughout life. Therefore, one of the best strategies to slow the progression of CKD is to maintain the “numbers” of these essential components necessary to preserve renal function. To this end, both the achievement of an optimal blood pressure and a maximum reduction in urinary protein excretion are essential. Lifestyle modifications and antihypertensive drug therapy must be carefully individualized to address the potential diversity of the kidneys.
A single transcription factor facilitates an insect host combating Bacillus thuringiensis infection while maintaining fitness
Authors: Guo Zhaojiang , Guo Le , Qin Jianying , Ye Fan , Sun Dan , Wu Qingjun , Wang Shaoli , Crickmore Neil , Zhou Xuguo , Bravo Alejandra , Soberón Mario , Zhang Youjun 
Published: October 2022

AbstractMaintaining fitness during pathogen infection is vital for host survival as an excessive response can be as detrimental as the infection itself. Fitness costs are frequently associated with insect hosts countering the toxic effect of the entomopathogenic bacterium Bacillus thuringiensis (Bt), which delay the evolution of resistance to this pathogen. The insect pest Plutella xylostella has evolved a mechanism to resist Bt toxins without incurring significant fitness costs. Here, we reveal that non-phosphorylated and phosphorylated forms of a MAPK-modulated transcription factor fushi tarazu factor 1 (FTZ-F1) can respectively orchestrate down-regulation of Bt Cry1Ac toxin receptors and up-regulation of non-receptor paralogs via two distinct binding sites, thereby presenting Bt toxin resistance without growth penalty. Our findings reveal how host organisms can co-opt a master molecular switch to overcome pathogen invasion with low cost, and contribute to understanding the underlying mechanism of growth-defense tradeoffs during host-pathogen interactions in P. xylostella.
Targeting EGFR-dependent tumors by disrupting an ARF6-mediated sorting system
Authors: Guo Huiling , Wang Juan , Ren Su , Zheng Lang-Fan , Zhuang Yi-Xuan , Li Dong-Lin , Sun Hui-Hui , Liu Li-Ying , Xie Changchuan , Wu Ya-Ying , Wang Hong-Rui , Deng Xianming , Li Peng , Zhao Tong-Jin 
Published: October 2022

AbstractAberrant activation of EGFR due to overexpression or mutation is associated with poor prognosis in many types of tumors. Here we show that blocking the sorting system that directs EGFR to plasma membrane is a potent strategy to treat EGFR-dependent tumors. We find that EGFR palmitoylation by DHHC13 is critical for its plasma membrane localization and identify ARF6 as a key factor in this process. N-myristoylated ARF6 recognizes palmitoylated EGFR via lipid-lipid interaction, recruits the exocyst complex to promote EGFR budding from Golgi, and facilitates EGFR transporting to plasma membrane in a GTP-bound form. To evaluate the therapeutic potential of this sorting system, we design a cell-permeable peptide, N-myristoylated GKVL-TAT, and find it effectively disrupts plasma membrane localization of EGFR and significantly inhibits progression of EGFR-dependent tumors. Our findings shed lights on the underlying mechanism of how palmitoylation directs protein sorting and provide an potential strategy to manage EGFR-dependent tumors.
Experimental reconstructions of 3D atomic structures from electron microscopy images using a Bayesian genetic algorithm
Authors: De Backer Annick , Van Aert Sandra , Faes Christel , Arslan Irmak Ece , Nellist Peter D. , Jones Lewys 
Published: October 2022

AbstractWe introduce a Bayesian genetic algorithm for reconstructing atomic models of monotype crystalline nanoparticles from a single projection using Z-contrast imaging. The number of atoms in a projected atomic column obtained from annular dark field scanning transmission electron microscopy images serves as an input for the initial three-dimensional model. The algorithm minimizes the energy of the structure while utilizing a priori information about the finite precision of the atom-counting results and neighbor-mass relations. The results show promising prospects for obtaining reliable reconstructions of beam-sensitive nanoparticles during dynamical processes from images acquired with sufficiently low incident electron doses.
Immunogenicity of SARS-CoV-2 spike antigens derived from Beta & Delta variants of concern
Authors: Akache Bassel , Renner Tyler M. , Stuible Matthew , Rohani Nazanin , Cepero-Donates Yuneivy , Deschatelets Lise , Dudani Renu , Harrison Blair A. , Gervais Christian , Hill Jennifer J. , Hemraz Usha D. , Lam Edmond , Régnier Sophie , Lenferink Anne E. G. , Durocher Yves , McCluskie Michael J. 
Published: October 2022

AbstractUsing our strongly immunogenic SmT1 SARS-CoV-2 spike antigen platform, we developed antigens based on the Beta & Delta variants of concern (VOC). These antigens elicited higher neutralizing antibody activity to the corresponding variant than comparable vaccine formulations based on the original reference strain, while a multivalent vaccine generated cross-neutralizing activity in all three variants. This suggests that while current vaccines may be effective at reducing severe disease to existing VOC, variant-specific antigens, whether in a mono- or multivalent vaccine, may be required to induce optimal immune responses and reduce infection against arising variants.
Immunogenicity of MultiTEP platform technology-based Tau vaccine in non-human primates
Authors: Hovakimyan Armine , Zagorski Karen , Chailyan Gor , Antonyan Tatevik , Melikyan Levon , Petrushina Irina , Batt Dash G. , King Olga , Ghazaryan Manush , Donthi Aashrit , Foose Caitlynn , Petrovsky Nikolai , Cribbs David H. , Agadjanyan Michael G. , Ghochikyan Anahit 
Published: October 2022

AbstractPathological forms of Tau protein are directly associated with neurodegeneration and correlate with Alzheimer’s Disease (AD) symptoms, progression, and severity. Previously, using various mouse models of Tauopathies and AD, we have demonstrated the immunogenicity and efficacy of the MultiTEP-based adjuvanted vaccine targeting the phosphatase activating domain (PAD) of Tau, AV-1980R/A. Here, we analyzed its immunogenicity in non-human primates (NHP), the closest phylogenic relatives to humans with a similar immune system, to initiate the transition of this vaccine into clinical trials. We have demonstrated that AV-1980R/A is highly immunogenic in these NHPs, activating a broad but unique to each monkey repertoire of MultiTEP-specific T helper (Th) cells that, in turn, activate B cells specific to PAD. The resulting anti-PAD IgG antibodies recognize pathological Tau tangles and Tau-positive neuritis in AD case brain sections with no staining in control non-AD cases. These published data and efficacy results support the AV-1980R/A vaccine progression to first-in-human clinical trials.
Personalizing exoskeleton assistance while walking in the real world
Authors: Slade Patrick , Kochenderfer Mykel J. , Delp Scott L. , Collins Steven H. 
Published: October 2022

AbstractPersonalized exoskeleton assistance provides users with the largest improvements in walking speed1 and energy economy2–4 but requires lengthy tests under unnatural laboratory conditions. Here we show that exoskeleton optimization can be performed rapidly and under real-world conditions. We designed a portable ankle exoskeleton based on insights from tests with a versatile laboratory testbed. We developed a data-driven method for optimizing exoskeleton assistance outdoors using wearable sensors and found that it was equally effective as laboratory methods, but identified optimal parameters four times faster. We performed real-world optimization using data collected during many short bouts of walking at varying speeds. Assistance optimized during one hour of naturalistic walking in a public setting increased self-selected speed by 9 ± 4% and reduced the energy used to travel a given distance by 17 ± 5% compared with normal shoes. This assistance reduced metabolic energy consumption by 23 ± 8% when participants walked on a treadmill at a standard speed of 1.5 m s−1. Human movements encode information that can be used to personalize assistive devices and enhance performance.
Maturation and circuit integration of transplanted human cortical organoids
Authors: Revah Omer , Gore Felicity , Kelley Kevin W. , Andersen Jimena , Sakai Noriaki , Chen Xiaoyu , Li Min-Yin , Birey Fikri , Yang Xiao , Saw Nay L. , Baker Samuel W. , Amin Neal D. , Kulkarni Shravanti , Mudipalli Rachana , Cui Bianxiao , Nishino Seiji , Grant Gerald A. , Knowles Juliet K. , Shamloo Mehrdad , Huguenard John R. , Deisseroth Karl , Pașca Sergiu P. 
Published: October 2022

AbstractSelf-organizing neural organoids represent a promising in vitro platform with which to model human development and disease1–5. However, organoids lack the connectivity that exists in vivo, which limits maturation and makes integration with other circuits that control behaviour impossible. Here we show that human stem cell-derived cortical organoids transplanted into the somatosensory cortex of newborn athymic rats develop mature cell types that integrate into sensory and motivation-related circuits. MRI reveals post-transplantation organoid growth across multiple stem cell lines and animals, whereas single-nucleus profiling shows progression of corticogenesis and the emergence of activity-dependent transcriptional programs. Indeed, transplanted cortical neurons display more complex morphological, synaptic and intrinsic membrane properties than their in vitro counterparts, which enables the discovery of defects in neurons derived from individuals with Timothy syndrome. Anatomical and functional tracings show that transplanted organoids receive thalamocortical and corticocortical inputs, and in vivo recordings of neural activity demonstrate that these inputs can produce sensory responses in human cells. Finally, cortical organoids extend axons throughout the rat brain and their optogenetic activation can drive reward-seeking behaviour. Thus, transplanted human cortical neurons mature and engage host circuits that control behaviour. We anticipate that this approach will be useful for detecting circuit-level phenotypes in patient-derived cells that cannot otherwise be uncovered.
Coral community data Heron Island Great Barrier Reef 1962–2016
Authors: Tanner Jason E. , Connell Joseph H. 
Published: October 2022

AbstractHere we describe benthic composition data derived from benthic photoquadrats collected over 41 surveys between 1962 and 2016 at four sites on Heron reef, at the southern end of Australia’s Great Barrier Reef, to assess change in coral composition over time. Surveys have often been annual, in a few years sub-annual, and the longest gap is six years. A subset of the data from two sites with the most complete records has been fully processed to allow the size of all individual colonies, and changes in species composition and cover, to be tracked over time. The taxonomy in these quadrats has been carefully checked for internal consistency, and is generally at the species level. A second subset has been processed, but has not been through full quality control, while a third subset exists as images only. This is the longest, 56 years, regular photographic record of coral cover in existence, and provides a valuable temporal contrast dating back in time to more recent studies of greater geographic extent and/or resolution.
Factors determining the dorsal coloration pattern of aposematic salamanders
Authors: Barzaghi Benedetta , Melotto Andrea , Cogliati Paola , Manenti Raoul , Ficetola Gentile Francesco 
Published: October 2022

AbstractAposematic bright colors have a key role for animal defense and can be expressed through metabolic production or by acquiring pigments from diet. Aposematic coloration can be related to both local adaptations and availability of trophic resources. The European fire salamander (Salamandra salamandra) shows significant color variability and occurs across a broad range of habitats. Here we combined field observations with common rearing experiments to disentangle the role of environmental conditions and local adaptations in determining aposematic coloration of salamander populations. We assessed color variation and measured habitat features and food availability in adults from 25 populations. Furthermore, we reared newborn larvae from 10 populations under different food availability and analyzed color of metamorphs. To assess color pattern, we measured the percentage of yellow covering the body, and the Hue, Saturation and Value of yellow coloration. Adult showed strong variation of color pattern; variation was strongly related to the individual's size, to habitat productivity and to food availability. Under common garden conditions, differences between populations were not anymore evident, and coloration was only affected by resource availability during larval development. Our results suggest that environmental conditions and food availability are more important than local adaptations in determining differences in aposematic color pattern.
The future of Viscum album L. in Europe will be shaped by temperature and host availability
Authors: Walas Łukasz , Kędziora Wojciech , Ksepko Marek , Rabska Mariola , Tomaszewski Dominik , Thomas Peter A. , Wójcik Roman , Iszkuło Grzegorz 
Published: October 2022

AbstractViscum album L. is a plant of great importance due to its influence on the host trees and, by extension, entire ecosystems. The species is also significant to humans—on the one hand, because of its use in medicine, and on the other, because of the growing threat it poses to the stability of conifer stands. Therefore, it is important to recognize the future range of three mistletoe subspecies (Viscum album subsp. album, V. album subsp. austriacum, and V. album subsp. abietis). Modelling of the potential range of these subspecies was performed using MAXENT software. Locations were collected from literature and databases. A total number of 3335 stands were used. Bioclimatic data for the current conditions and three future scenarios (SSP 1.26, SSP 3.70, SSP 5.85) were downloaded from the CHELSA database. The results confirmed that the temperature is the key variable on the potential range of the analysed subspecies. V. album subsp. abietis is withdrawing from its range according to all scenarios. In the case of V. album subsp. austriacum, a slight range shift is visible. Only the V. album subsp. album will expand non-directionally. The reason is most likely a very large number of host species and greater genetic variability compared to the subspecies found on conifers.
Nonlinear seepage erosion model of water inrush considering particle size distribution of karst collapse column and its engineering applications
Authors: Yang Bin , Shi Wenhao , Yang Xin 
Published: October 2022

AbstractWater inrush through karst collapse column is one of the great disasters which threaten coal mine safety production. The particle size distribution of karst collapse column is one of its most basic physical properties, which has a strong correlation with particle migration, and is an important basis for evaluating the water inrush risk of collapse column. The nonlinear flow tests of broken rock under different gradation conditions were carried out by a custom-built apparatus, and the relationship equation between nonlinear flow parameters (permeability and non-Darcy factor) and Talbol power exponent n were constructed. A nonlinear flow model with variable mass of water inrush from karst collapse column was established. The spatio-temporal evolution law of pressure, velocity, porosity and concentration under particle loss and the influence of particle gradation on the water inrush risk of karst collapse column at Fan gezhuang mine were discussed. During the water inrush, the flow state of fluids in karst collapse column gradually transitions from a weak inertial flow to a strong one, eventually becoming a turbulent flow. The flow model based on single flow state cannot reflect the essence of flow regime transition in water inrush. The larger n is, the stronger the water permeability of the karst collapse column, the faster the particles migrate and are lost, the faster the flow channel with high porosity develops, the shorter the time for the water inflow to reach its peak value, and the greater the risk of water inrush.
Tumor immune cell infiltration score based model predicts prognosis in multiple myeloma
Authors: Chen Can , Li Yiwei , Miao Peiwen , Xu Ying , Xie Yaping , Chen Zhenzhen , Qian Shenxian 
Published: October 2022

AbstractThe tumor microenvironment plays an important role in various processes, including tumorigenesis, cancer progression, and metastasis. Immune signatures have been identified and verified for use in diagnosis and prognosis prediction. We used single-sample Gene Set Enrichment Analysis to evaluate tumor immune cell infiltration score (TIICs) and verify their prognostic significance in both training and validation cohorts and using this information to build a prognostic model. A total of 1281 samples were obtained for further evaluation of the immune enrichment scores of 28 immune cells, showing that Th17 cell contributed most significantly to survival. Using the median TIICs as a cutoff to divide the samples into two groups, we found that the high-TIICs group was associated with favorable outcomes in both the training and validation sets. We then constructed a prognostic model to predict the 6, 8, and 10-year survival outcomes. Further analysis showed that immune score and tumor purity were higher in the high-TIICs group, while the matrix score was lower in this group. Forty-two differentially expressed genes were identified between the two groups. This new prognostic model based on immune cell infiltration indicates the potential for TIICs in predicting prognosis and as targets for treatment.
In vitro inhibition of SARS-CoV-2 Infection by dry algae powders
Authors: Garcia-Ruiz Daniel , Villalobos-Sánchez Erendira , Alam-Escamilla David , Elizondo-Quiroga Darwin 
Published: October 2022

AbstractChlorella spp., Spirulina spp., and fucoidan dry powders, are commercialized as food supplements and are considered safe for human consumption. Their broad-spectrum antiviral properties have been studied, however, their effect against SARS-CoV-2 remains unknown. We investigated the potential antiviral activity of three algae powders: Chlorella vulgaris, Arthrospira maxima (Spirulina) and fucoidan purified from marine brown algae Sargassum spp. against SARS-CoV-2 infection in vitro. Vero cells were incubated with 70 μg/ml of each algae powder and either 50 or 100 TCID50/ml of SARS-CoV-2, in two types of experiments (pretreatment and simultaneous) and comparing two kinds of solvents (DMEM and DMSO). Chlorella vulgaris powder, inhibited SARS-CoV-2 infection in all assays; viral RNA was significantly reduced in supernatants at 24, 48, 72, and 96 h post-infection, the highest difference in viral load (8000-fold) was observed after 96 h. Arthrospira maxima powder inhibited SARS-CoV-2 infection using 50 TCID50/ml for both experimental schemes, but protection percent was lower when viral inoculum was increase to 100 TCID50/ml; viral RNA decreased 48 h after infection, reaching a 250-fold difference at 72 h. Fucoidan powder partially inhibited SARS-CoV-2 infection since no CPE was observed in 62.5% of trated cultures in DMEM, but the antiviral activity was increased to 100% of protection when DMSO was used as solvent. All the algae samples showed high antiviral activity against SARS-CoV-2 with a SI above of 18. These results suggest that all three algae samples are potential therapeutic candidates for the treatment of COVID-19.