bluuebunny/crossref_metadata_2025_split huggingface dataset:
Guiding Irregular Nuclear Morphology on Nanopillar Array for Malignancy Differentiation in Tumor cells
Authors: Zeng Yongpeng , Zhuang Yinyin , Mitra Aninda , Chen Peng , Saggio Isabella , Shivashankar G. V. , Gao Weibo , Zhao Wenting 
Published: February 2022

AbstractFor more than a century, abnormal nuclei in tumor cells, presenting subnuclear invaginations and folds on the nuclear envelope, have been known to be associated with high malignancy and poor prognosis. However, current nuclear morphology analysis focuses on the features of the entire nucleus, overlooking the malignancy-related subnuclear features in nanometer scale. The main technical challenge is to probe such tiny and randomly distributed features inside cells. We here employ nanopillar arrays to guide subnuclear features into ordered patterns enabling their quantification as a strong indicator of cell malignancy. Both breast and liver cancer cells were validated, as well as the quantification of nuclear abnormality heterogeneity. The alterations of subnuclear patterns were also explored as effective readouts for drug treatment. We envision this nanopillar-enabled quantification of subnuclear abnormal features in tumor cells opens a new angle in characterizing malignant cells and studying the unique nuclear biology in cancer.TeaserA nanopillar-based assay quantifying the abnormal nuclear morphology in tumor cells at single-cell level.
Adaptive scans allow 3D-targeted laser-dissection to probe the mechanics of cell sheets
Authors: Meng Huicheng , Nuzhdin Dmitry , Sison Miguel , Galland Frédéric , LeGoff Loïc 
Published: February 2022

The mechanical actuation of cells by active forces from the cytoskeleton drives tissue morphogenesis. To understand these forces, multicellular laser dissection has become an essential tool for severing tissue locally and inferring tension from the recoil of surrounding structures. However, conventional laser dissection is limited by 2D steering, which is inadequate for embryos and developing tissues that are intrinsically 3D structures. In this study, we introduce a flexible near-infrared (NIR) fs-pulsed laser dissection system that allows for dissection trajectories to proceed in 3D and adapt to the curved surfaces of cell sheets, which are prominent structures in embryos. Trajectories are computed through an unsupervised search for the surface of interest. Using this technique, we demonstrate sectioning of multicellular domains on curved tissue, which was not possible with regular NIR laser scanning.We apply the developed strategy to map mechanical stresses in the imaginal disc of the developing Drosophila wing. Our targeted, adaptive scans can be used in other non-linear processes, such as two-photon fluorescence imaging or optogenetics. Overall, this new laser dissection system offers an innovative solution for studying complex 3D structures and their mechanical properties.
Effects of global change on animal biodiversity in boreal forest landscape: an assemblage dissimilarity analysis
Authors: Bouderbala Ilhem , Labadie Guillemette , Béland Jean-Michel , Boulanger Yan , Hébert Christian , Desrosiers Patrick , Allard Antoine , Fortin Daniel 
Published: February 2022

AbstractDespite an increasing number of studies highlighting the impacts of climate change on boreal species, the main factors that will drive changes in species assemblages remain ambiguous. We quantify two climate-induced pathways based on direct and indirect effects on species occupancy and assemblage dis-similarity under different harvest management scenarios. The direct climate effects illustrate the impact of climate variables while the indirect effects are reflected through the changes in land cover composition. To understand the main causes in assemblage dissimilarity, we analyze the regional and the latitudinal species assemblage dissimilarity by decomposing it into balanced variation in species occupancy and occurrence and occupancy and occurrence gradient. We develop empirical models to predict the distribution of more than 100 bird and beetle species in the Côte-Nord region of Québec over the next century. Our results show that the two pathways are complementary and alter biodiversity, mainly caused by balanced variation in species occupancy and occurrence. At the regional scale, both effects have an impact on decreasing the number of winning species. Yet, responses are much larger in magnitude under mixed climate effects (a mixture of direct and indirect effects). Regional assemblage dissimilarity reached 0.77 and 0.69 under mixed effects versus 0.09 and 0.10 under indirect effects for beetles and birds, respectively, between RCP8.5 and baseline climate scenarios when considering harvesting. Therefore, inclusion of climatic variables considers aspects other than just those related to forest landscapes, such as life cycles of animal species. Latitudinally, assemblage dissimilarity increased following the climate conditions pattern. Our analysis contributes to the understanding of how climate change alters biodiversity by reshaping community composition and highlights the importance of climate variables in biodiversity prediction.
Bimodally oriented cellulose fibers and reticulated homogalacturonan networks - A direct visualization of Allium cepa primary cell walls
Authors: Nicolas William J , Fäßler Florian , Dutka Przemysław , Schur Florian KM , Jensen Grant , Meyerowitz Elliot 
Published: February 2022

AbstractOne hallmark of plant cells is their pecto-cellulosic cell walls. They protect cells against the environment and high turgor and mediate morphogenesis through the dynamics of their mechanical and chemical properties. The walls are a complex polysaccharidic structure. Although their biochemical composition is well known, how the different components organize in the volume of the cell wall and interact with each other is not well understood and yet is key to the wall’s mechanical properties. To investigate the ultrastructure of the plant cell wall, we imaged the walls of onion (Allium cepa) bulbs in a near-native state via cryo-Focused Ion Beam milling (cryo-FIB-milling) and cryo-Electron Tomography (cryo-ET). This allowed the high-resolution visualization of cellulose fibers in situ (in muro). We reveal the coexistence of dense fiber fields bathed in a reticulated matrix we termed “meshing,” which is more abundant at the inner surface of the cell wall. The fibers adopted a regular bimodal angular distribution at all depths in the cell wall and bundled according to their orientation, creating layers within the cell wall. Concomitantly, employing homogalacturonan (HG)-specific enzymatic digestion, we observed changes in the meshing, suggesting that it is at least in part composed of HG pectins. We propose the following model for the construction of the abaxial epidermal primary cell wall: The cell deposits successive layers of cellulose fibers at −45° and +45° relative to the cell’s long axis and secretes the surrounding HG-rich meshing proximal to the plasma membrane, which then migrates to more distal regions of the cell wall.
Whole-Genome Sequence of African Swine Fever Virus isolate from India provides insights into diversity and evolution
Authors: Mahajan Sonalika , Doley Juwar , Subramaniam Saravanan , Yadav Ajay K. , Pegu Seema Rani , Mohan Narayana H. , Chander Vishal , Mathesh Karikalan , Nandi Sukdeb , Singh Karam Pal , Gupta Vivek Kumar , Sharma Gaurav Kumar 
Published: February 2022

AbstractAfrican swine fever (ASF) was first reported in 1921, and since then has posed a major threat to the world pig industry and still remains a major challenge as there is no vaccine or therapy available. In May 2020, the first incidence of ASF was recorded in India, followed by a number of outbreaks in the north eastern part of India. In this study, we report the first whole genome of an Indian isolate of ASF virus (ASF/IND/20/CAD/543) using next generation sequencing and compared with the other ASFV complete genome. On phylogenetic analysis, the virus was assigned to genotype II on the basis of p72 genotyping. However, the whole genome based phylogeny distinguished it from other genotype II isolates of clade 1.1.1. This study adds to our understanding of ASFV’s genetic diversity and molecular evolution.
Revisiting degron motifs in human AURKA required for its targeting by APC/C-FZR1
Authors: Abdelbaki Ahmed , Ascanelli Camilla , Okoye Cynthia N. , Akman Begum , Janson Giacomo , Min Mingwei , Marcozzi Chiara , Hagting Anja , Grant Rhys , De Luca Maria , Asteriti Italia Anna , Guarguaglini Giulia , Paiardini Alessandro , Lindon Catherine 
Published: February 2022

AbstractMitotic kinase Aurora A (AURKA) diverges from other kinases in its multiple active conformations that may explain its interphase roles and association with cancer, and the limited efficacy of drugs targeting the kinase pocket. Regulation of AURKA activity by the cell is critically dependent on destruction mediated by the Anaphase-Promoting Complex (APC/CFZR1) during mitotic exit and G1 phase and requires an atypical N-terminal degron in AURKA called the ‘A-box’ in addition to a reported canonical D-box degron in the C-terminus. Here we find that the proposed C-terminal D-box of AURKA does not act as a degron and instead mediates essential structural features of the protein. In living cells, as previously reported in vitro, the N-terminal intrinsically disordered region (IDR) of AURKA containing the A-box is sufficient to confer FZR1-dependent mitotic degradation. Both in silico and in cellulo assays predict the QRVL Short Linear Interacting Motif (SLiM) of the A-box to be a phospho-regulated D-box. We propose that degradation of full-length AURKA additionally depends on an intact C-terminal domain because of critical conformational parameters permissive for both activity and mitotic degradation of AURKA.Summary blurbAURKA degron motifs are redefined to show that the so-called N-terminal ‘A-box’ is in fact a D-box, and the so-called ‘D-box’ in the C-terminus is not a degron but a motif critical for the active, degradable conformation of AURKA
A genomic snapshot of demographic and cultural dynamism in Upper Mesopotamia during the Neolithic Transition
Authors: Altınışık N. Ezgi , Kazancı Duygu Deniz , Aydoğan Ayça , Gemici Hasan Can , Erdal Ömür Dilek , Sarıaltun Savaş , Vural Kıvılcım Başak , Koptekin Dilek , Gürün Kanat , Sağlıcan Ekin , Çakan Gökhan , Koruyucu Meliha Melis , Lagerholm Vendela Kempe , Karamurat Cansu , Özkan Mustafa , Kılınç Gülşah Merve , Sevkar Arda , Sürer Elif , Götherström Anders , Atakuman Çiğdem , Erdal Yılmaz Selim , Özer Füsun , Erim Özdoğan Aslı , Somel Mehmet 
Published: February 2022

AbstractUpper Mesopotamia played a key role in the Neolithic Transition in Southwest Asia through marked innovations in symbolism, technology, and foodways. We present thirteen ancient genomes (c.8500-7500 calBCE) from Pre-Pottery Neolithic Çayönü in the Tigris basin together with bioarchaeological and material culture data. Our findings reveal that Çayönü was a genetically diverse population, carrying a mixed ancestry from western and eastern Fertile Crescent, and that the community received immigrants. Our results further suggest that the community was organised along biological family lines. We document bodily interventions such as head-shaping and cauterization among the individuals examined, reflecting Çayönü’s cultural ingenuity. Finally, we identify Upper Mesopotamia as the likely source of eastern gene flow into Neolithic Anatolia, in line with material culture evidence. We hypothesise that Upper Mesopotamia’s cultural dynamism during the Neolithic Transition was the product not only of its fertile lands but also of its interregional demographic connections.
Non canonical scaffold-type ligase complex mediates protein UFMylation
Authors: Peter Joshua J. , Magnussen Helge M. , DaRosa Paul Anthony , Millrine David , Matthews Stephen P , Lamoliatte Frederic , Sundaramoorthy Ramasubramanian , Kopito Ron R , Kulathu Yogesh 
Published: February 2022

AbstractProtein UFMylation is emerging as a posttranslational modification essential for endoplasmic reticulum and cellular homeostasis. Despite its biological importance, we have a poor understanding of how UFM1 is conjugated onto substrates. Here, we use a rebuilding approach to define the minimal requirements of protein UFMylation. We find that the reported E3 ligase UFL1 is inactive on its own and identify UFBP1 to bind UFL1 to form an active E3 ligase complex. While UFC1 is an intrinsically Cys-reactive E2, we do not identify any catalytic cysteines on UFL1/UFBP1, suggesting a scaffold-type E3 ligase mechanism. Interestingly, the E3 ligase complex consists of winged-helix (WH) domain repeats that activate UFC1 for aminolysis. We identify the adaptor protein CDK5RAP3 to bind to and regulate E3 ligase activity potentially by preventing off-target UFMylation. In summary, our work identifies the minimal requirements for UFMylation and reveals regulatory principles of this atypical E3 ligase complex.
Extracellular vesicle microRNA cargo engineering reveals critical mechanisms underlying therapeutic efficacy
Authors: Euscher Lindsey M. , Mentkowski Kyle I. , Tarvirdizadeh Touba , Julian Isabella , Bhatt Karan , Eagler Lisa , Lang Jennifer K. 
Published: February 2022

AbstractBackgroundExtracellular vesicles (EVs) are key mediators of intercellular communication and function to transfer biological cargo, including microRNA (miR), from donor to recipient cells. EVs isolated from cardiosphere-derived cells (CDCs) have demonstrated therapeutic efficacy in pre-clinical models of ischemic heart disease, highlighting them as promising vectors for the treatment of CVD. Importantly, it has not yet been established whether miR cargo is necessary for the observed therapeutic benefit of CDC-EVs following acute MI (AMI).MethodsCDCs were transfected with siRNA against Drosha, the initial endonuclease in the miRNA biogenesis pathway, to generate miR depleted DROSHA-EVs. EVs were characterized by size, morphology, and protein/miR expression. The role of EV miRNA on cardiac target cell apoptosis, proliferation and angiogenesis was examined using a series of in vitro assays. Mice with acute MI underwent delivery of human CDC EVs, DROSHA-EVs and placebo in a double-blind study. LVEF was assessed by echo at 1- and 28-days post-MI and tissue samples processed for assessment of histological endpoints. In vitro sufficiency assays were performed using a combinatorial approach with individual candidate miRs to identify clusters exhibiting synergistic efficacy.ResultsDROSHA-EVs exhibited global downregulation of miRNA cargo but were otherwise indistinguishable from wild-type CDC-EVs. miR cargo was responsible for mediating the beneficial effects of human CDC-EV treatment on cardiomyocyte apoptosis, fibroblast proliferation and angiogenesis in vitro. DROSHA-EVs were unable to promote recovery following AMI on a functional or histological level, highlighting the critical role of EV miRNAs in cardioprotection following ischemic injury. A potentially therapeutic miR cluster, miR-146a-370-126a, was identified which acted synergistically to reduce cardiomyocyte apoptosis and was sufficient to render inert EVs into therapeutic vectors.ConclusionsThese results demonstrate for the first time that miRNAs are required for the regenerative potential of CDC-EVs following AMI and identify a novel miR cluster with therapeutic implications.
LAG3 regulates antibody responses in a murine model of kidney transplantation
Authors: Nicosia Michael , Fan Ran , Lee Juyeun , Gorbacheva Victoria , Valenzuela José I. , Yamamoto Yosuke , Beavers Ashley , Dvorina Nina , Chuluyan Eduardo , Araki Motoo , Baldwin William M. , Fairchild Robert L. , Min Booki , Valujskikh Anna 
Published: February 2022

AbstractLymphocyte activation gene-3 (LAG3) is a coinhibitory receptor expressed by a range of immune cells. While immunomodulatory potential of LAG3 is being actively explored in cancer and autoimmunity fields, there is no information on how this pathway affects alloreactive immune responses following organ transplantation. The goal of this study was to investigate the functions of recipient LAG3 in a mouse model of renal allograft rejection. We found that mice deficient in LAG3 expression have elevated heterologous immunity against a panel of alloantigens prior to transplantation. Recipient LAG3 deficiency results in rapid rejection of MHC-mismatched renal allografts that are spontaneously accepted by WT recipients, with graft histology characteristic of antibody mediated rejection (ABMR). Depletion of recipient B cells but not CD8+T cells significantly extended kidney allograft survival in LAG3-/-recipients further supporting ABMR as the main mechanism of graft loss. Treatment of WT recipients with an antagonistic LAG3 antibody enhanced anti-donor immune responses and induced kidney damage associated with chronic rejection. The experiments using conditional LAG3 knockout recipients demonstrated that LAG3 expression on either T or B cells is sufficient to regulate anti-donor humoral immunity. These results are the first to identify LAG3 as a regulator of both T and B cell responses to kidney allografts and a potential therapeutic target for ABMR prevention and treatment.
Glia of C. elegans coordinate the heat shock response independent of the neuronal thermosensory circuit and serotonin
Authors: Gildea Holly K. , Frankino Phillip A. , Tronnes Sarah U. , Pender Corinne L. , Choi Hyun Ok , Hunter Tayla D. , Cheung Shannon S. , Frakes Ashley E , Sukarto Edward , Dillin Andrew 
Published: February 2022

AbstractAs organisms age, they lose the ability to induce appropriate stress responses, becoming vulnerable to protein toxicity and tissue damage. Neurons can signal to peripheral tissues to induce protective organelle-specific stress responses. Recent work has demonstrated a novel and independent role of glia in inducing such responses. Here, we show that overexpression of heat shock factor 1 (hsf-1) in the four astrocyte-like cephalic sheath cells of C. elegans is sufficient to induce a non-cell autonomous cytosolic unfolded protein response (UPR), also known as the heat shock response (HSR), in distal cells. These animals upregulate the HSR in peripheral cells and have increased lifespan and resistance to heat stress. This glial HSR regulation is independent of the canonical neuronal thermosensory circuit and of known neurotransmitters but is dependent on the small clear vesicle release protein UNC-13. Additionally, HSF-1 and the FOXO transcription factor DAF-16 are partially required in peripheral tissues for increase of non-autonomous HSR, lifespan, and thermotolerance. We find that cephalic sheath glial hsf-1 over-expression leads to increased pathogen resistance, which suggests a role for this signaling pathway in immune function.
Fungal community dynamics and carbon mineralization in coarse woody debris across decay stage, tree species, and stand development stage in northern boreal forests
Authors: Hart Saskia C. , Porter Teresita M. , Basiliko Nathan , Venier Lisa , Hajibabaei Mehrdad , Morris Dave 
Published: February 2022

AbstractFungi are primary agents of coarse woody debris (CWD) decay in forests, playing an essential role in nutrient cycling and carbon storage. Characterizing fungal communities within CWD will promote further understanding of the fungal controls on CWD decomposition. We compared fungal community assemblages using alpha and beta diversity metrics, carbon mineralization, and physical and chemical properties of CWD across 3 tree species (trembling aspen [Populus tremuloides], black spruce [Picea mariana], and jack pine [Pinus banksiana]), 5 decay classes, and 2 stand development stages, differing in time-since-stand replacing disturbance (i.e., young/self-thinning and mature/steady-state) in Ontario’s boreal forest region. In total, we sampled 180 individual CWD logs from 6 independent stands, with 3 replicates per each species × decay class combination at each site. We found that fungal community structure significantly differed across tree species, decay stage, and stand age. Higher proportions of white rot fungi were found in trembling aspen CWD, whereas higher proportions of brown rot fungi were found in black spruce and jack pine CWD. Proportions of specialized wood decay fungi increased with decay stage and were higher in CWD located in mature forest stands. Fungal diversity was highest in decay class 4 CWD. We found that Mn and K concentrations, total carbon, C/N ratio, carbon mineralization (mg CO2 g dry CWD-1 d-1), and moisture content were important predictors of fungal composition across CWD species and/or decay stage, though how CWD chemistry influences fungal species composition (and vice versa) is unknown. Carbon mineralization was highest in trembling aspen CWD and increased with decay stage, perhaps facilitated by increased N concentrations. This study suggests that forest management guidelines that consider both deadwood quantity and quality will support a broader range of fungal species and communities through post-disturbance stand development, thereby conserving biodiversity over the longer-term in our managed forest systems.
Rapid stem cell spreading induced by high affinity α5β1 integrin-selective bicyclic RGD peptide in biomimetic hydrogels
Authors: Liu Kaizheng , Vandaele Johannes , Bernhagen Dominik , van Erp Merijn , Oosterwijk Egbert , Timmerman Peter , Rocha Susana , Kouwer Paul H. J. 
Published: February 2022

AbstractCell-matrix interactions form a crucial parameter for the design of a synthetic extracellular matrix (ECM), as they ultimately dictate cell fate and functions. Universally, synthetic biomaterials are conjugated with a linear or cyclic Arg-Gly-Asp (RGD) peptide to establish a direct link of the ECM with the cell. These peptides, however, present low binding affinities and lack selectivity towards integrin subtypes presented on the cell membrane. Here, a highly biomimetic synthetic ECM based on polyisocyanides (PIC) that has been decorated with bicyclic peptides that show a high affinity towards specific integrin subtypes is presented. 3D cell studies show that human adipose-derived stem cells (hASCs) in matrices carrying the optimized bicyclic α5β1 -integrin binder, spread within 24 hours, which is much faster than in other PIC gels, including the default RGD-decorated gel, but also much faster than in the positive Matrigel control. YAP/TAZ staining shows that the rapid morphological change in the 3D microenvironments is YAP independent. The data highlights that the design of synthetic matrices with appropriate, optimized guiding signals is key to guide cells towards a predetermined outcome.