bluuebunny/crossref_metadata_2025_split huggingface dataset:
Multiomic Analysis of Adult Diapause inDrosophila melanogasterIdentifies Hallmarks of Cellular Quiescence
Authors: Hutfilz Corinne 
Published: December 2022

AbstractAge is a fundamental aspect of biology that underlies the efficacy of a broad range of functions. Identifying determinants for how quickly or slowly we age will contribute greatly to our understanding of age as a modifier of overall health, particularly to the advancement of therapeutic interventions designed to mitigate or delay age-associated disorders. While much work has been devoted to the study of genetic or pharmacological interventions that extend lifespan, this approach does not necessarily recapitulate the physiological profile of naturally long-lived individuals. Diapause and diapause-like states constitute natural, inducible and evolutionarily conserved examples of lifespan plasticity that are well-suited to serve as physiologically accurate models of longevity. Here, we leveraged a metabolically critical signaling organ in Drosophila, the fat body, to examine diapause-associated transcription in the context of chromatin accessibility and the regulation of lifespan. Through a combination of ATAC-seq and RNA-seq, our observations suggest chromatin is globally reorganized in diapause and may assume a poised conformation to facilitate the rapid transcription of pro-development genes upon diapause termination. We found particular significance of GAF, NELF, and RNA polymerase III in this context. Congruently, transcription during diapause appears to favor many processes supporting the maintenance of cellular quiescence and the inhibition of differentiation. Our data are consistent with a model wherein diapause induces cellular quiescence in the fat body, as was additionally supported through fluorescent microscopy and comparison with public ChIP-seq data for developmentally juvenile files. This work opens the possibility that longevity in diapause may be partially determined through a lack of mitogenic signaling from the quiescent niche, concurrent with changes to the hormonal and immunological profiles that skew metabolism towards tissue maintenance.
The miR156-targetedSlSBP15represses tomato shoot branching via modulating auxin transport and interacting withGOBLETandBRANCHED1b
Authors: Barrera-Rojas Carlos Hernán , Vicente Mateus Henrique , Pinheiro Brito Diego Armando , Silva Eder M. , Lopez Aitor Munoz , Ferigolo Leticia F. , do Carmo Rafael Monteiro , Silva Carolina M. S. , Silva Geraldo F.F. , Correa Joao P. O. , Notini Marcela M. , Freschi Luciano , Cubas Pilar , Nogueira Fabio T.S. 
Published: December 2022

AbstractThe microRNA156 (miR156)/SQUAMOSA PROMOTER-BINDING PROTEIN-LIKE(SPL/SBP) regulatory hub is highly conserved among phylogenetically distinct species, but how it interconnects multiple pathways to converge to common integrators controlling shoot architecture is still unclear. Here, we demonstrated that the miR156/SlSBP15hub modulates tomato shoot branching (SB) by connecting phytohormones with important genetic pathways regulating both axillary bud (AB) development and outgrowth. We verified that plants overexpressing the miR156 (156-OE plants) display high SB, whereas plants overexpressing a miR156-resistant SlSBP15 alelle (rSBP15 plants) display arrested SB and are able to partially restore the wild-type (WT) phenotype in156-OE background. Although rSBP15 plants showed ABs smaller than MT, its activation is dependent on shoot apex-derived auxin transport inhibition. Additionally, hormonal measurements reveal that IAA and ABA concentrations were lower in 156-OE and higher in rSBP15-OE plants. SlSBP15 regulates AB development and outgrowth by inhibiting auxin transport and the activity ofGOBLET(GOB), and by interacting with BRANCHED1b (SlBRC1b) at the protein level to control abscisic acid (ABA) levels within ABs. Our data provide a new mechanism by which the miR156/SPL/SBPhub regulates SB, and suggest thatSlSBP15has potential applications in improving tomato architecture.
Activated gliosis, accumulation of amyloid β and hyperphosphorylation of tau in aging canines with and without cognitive decline
Authors: Hines Amelia D. , McGrath Stephanie , Latham Amanda S. , Kusick Breonna , Mulligan Lisa , Richards McKenzie L. , Moreno Julie A. 
Published: December 2022

AbstractCanine cognitive dysfunction (CCD) syndrome is a well-recognized naturally occurring disease in aged dogs, with a remarkably similar disease course, both in its clinical presentation and neuropathological changes, as humans with Alzheimer’s disease (AD). Similar to human AD patients this naturally occurring disease is found in the aging canine population however, there is little understanding of how the canine brain ages pathologically. It is well known that in neurodegenerative diseases, there is an increase in inflamed glial cells as well as an accumulation of hyperphosphorylation of tau (P-tau) and amyloid beta (Aβ1-42). These pathologies increase neurotoxic signaling and eventual neuronal loss. We assessed these brain pathologies in aged canines and found an increase in the number of glial cells, both astrocytes and microglia, and the activation of astrocytes indicative of neuroinflammation. A rise in the aggregated protein Aβ1-42and hyperphosphorylated tau, at Threonine 181 and 217, in the cortical brain regions of aging canines is seen. We then asked if any of these aged canines had CCD utilizing the only current diagnostic, owner questionnaires, verifying positive or severe CCD had pathologies of gliosis and accumulation of Aβ1-42like their aged matched controls. However uniquely the CCD dogs had P-tau at T217. Therefore, this phosphorylation site of tau at threonine 217 may be a predictor for CCD.
Transcriptomic and functional analysis ofANGPTL4overexpression in pancreatic cancer nominates targets that reverse chemoresistance
Authors: Gordon Emily R. , Wright Carter A. , James Mikayla , Cooper Sara J. 
Published: December 2022

ABSTRACTBackgroundPancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers based on five-year survival rates. Genes contributing to chemoresistance represent novel therapeutic targets that can improve treatment response. Increased expression ofANGPTL4in tumors correlates with poor outcomes in pancreatic cancer.MethodsWe used statistical analysis of publicly available gene expression data (TCGA-PAAD) to test whether expression ofANGPTL4and its downstream targets, ITGB4andAPOL1, were correlated with patient survival. We measured the impact ofANGPTL4overexpression in a common pancreatic cancer cell line, MIA PaCa-2 cells, using CRISPRa for overexpression and DsiRNA for knockdown. We characterized global gene expression changes associated with high levels ofANGPTL4and response to gemcitabine treatment using RNA-sequencing. Gemcitabine dose response curves were calculated on modified cell lines by measuring cell viability with CellTiter-Glo (Promega). Impacts on cell migration were measured using a time course scratch assay.ResultsWe show thatANGPTL4overexpression leads toin vitroresistance to gemcitabine and reduced survival times in patients. Overexpression ofANGPTL4induces transcriptional signatures of tumor invasion and metastasis, proliferation and differentiation, and inhibition of apoptosis. Analyses revealed an overlapping signature of genes associated with bothANGPTL4activation and gemcitabine response. Increased expression of the genes in this signature in patient PDAC tissues was significantly associated with shorter patient survival. We identified 42 genes that were both co-regulated withANGPTL4and were responsive to gemcitabine treatment.ITGB4andAPOL1were among these genes. Knockdown of either of these genes in cell lines overexpressingANGPTL4reversed the observed gemcitabine resistance and inhibited cellular migration associated with epithelial to mesenchymal transition (EMT) andANGPTL4overexpression.ConclusionsThese data suggest thatANGPTL4promotes EMT and regulates the genesAPOL1andITGB4. Importantly, we show that inhibition of both targets reverses chemoresistance and decreases migratory potential. Our findings have revealed a novel pathway regulating tumor response to treatment and suggest relevant therapeutic targets in pancreatic cancer.
Soft multimodal opto-electric biointerfaces for co-localized optical and electrical recording of cell function
Authors: Obaid Sofian N. , Quirion Nathaniel , Balansag Jade , Daza Nicolas , Shi Xinyu , Chen Zhiyuan , Lu Luyao 
Published: December 2022

ABSTRACTOptical fluorescence and electrical monitoring of cell activity are two powerful approaches to study organ functions. Simultaneous recording of optical and electrical data types will provide complementary information from and take advantage of each approach. However, devices that can concurrently record optical signals from the same cell population underneath the microelectrodes have not been widely explored and remain a grand technical challenge. This work presents an innovative flexible opto-electric device that monolithically integrates transparent gold nanogrid microelectrodes directly above microscale light-emitting diodes, photodetectors, and optical filters to achieve co-localized crosstalk-free optical fluorescence and electrical recording. The optimized gold nanogrid microelectrodes show excellent optical transparency (>81%) and low normalized 1 kHz electrochemical impedance (6.3 Ω cm2). The optical recording subsystem offers high wavelength selectivity (>1,300) and linearity (R2>0.99) for exciting and capturing green fluorescence from various fluorescent reporters in measurement ranges relevant toin vivoapplications with minimal thermal effects. The opto-electric device exhibits remarkable durability under soaking for 40 days and repetitive mechanical bending for 5,000 cycles. The work may provide a versatile approach for constructing mechanically compliant biointerfaces containing crosstalk-free optical and electrical modalities with widespread application potentials in basic and clinical research.
Language models generalize beyond natural proteins
Authors: Verkuil Robert , Kabeli Ori , Du Yilun , Wicky Basile I. M. , Milles Lukas F. , Dauparas Justas , Baker David , Ovchinnikov Sergey , Sercu Tom , Rives Alexander 
Published: December 2022

AbstractLearning the design patterns of proteins from sequences across evolution may have promise toward generative protein design. However it is unknown whether language models, trained on sequences of natural proteins, will be capable of more than memorization of existing protein families. Here we show that language models generalize beyond natural proteins to generatede novoproteins. We focus on two protein design tasks: fixed backbone design where the structure is specified, and unconstrained generation where the structure is sampled from the model. Remarkably although the models are trained only on sequences, we find that they are capable of designing structure. A total of 228 generated proteins are evaluated experimentally with high overall success rates (152/228 or 67%) in producing a soluble and monomeric species by size exclusion chromatography. Out of 152 experimentally successful designs, 35 have no significant sequence match to known natural proteins. Of the remaining 117, sequence identity to the nearest sequence match is at median 27%, below 20% for 6 designs, and as low as 18% for 3 designs. For fixed backbone design, the language model generates successful designs for each of eight experimentally evaluated artificially created fixed backbone targets. For unconstrained generation, sampled proteins cover diverse topologies and secondary structure compositions, and have high experimental success rate (71/129 or 55%). The designs reflect deep patterns linking sequence and structure, including motifs that occur in related natural structures, and motifs that are not observed in similar structural contexts in known protein families. The results show that language models, though only trained on sequences, learn a deep grammar that enables the design of protein structure, extending beyond natural proteins.
Senescent response in inner annulus fibrosus cells in response to TNFα, H2O2, and TNFα-induced nucleus pulposus senescent secretome
Authors: Montgomery-Song Aaryn , Ashraf Sajjad , Santerre Paul , Kandel Rita 
Published: December 2022

AbstractSenescence, particularly in the nucleus pulposus (NP) cells, has been implicated in the pathogenesis of disc degeneration, however, the mechanism(s) of annulus fibrosus (AF) cell senescence is still not well understood. Both TNFα and H2O2, have been implicated as contributors to the senescence pathways, and their levels are increased in degenerated discs when compared to healthy discs. Thus the objective of this study is to identify factor(s) that induces inner AF (iAF) cell senescence. Under TNFα exposure, at a concentration that can induce senescence in NP cells, bovine iAF cells did not undergo senescence, indicated by their ability to continue to proliferate as demonstrated by Ki67 staining and growth curves and lack of expression of the senescent markers, p16 and p21. Unlike iAF cells, NP cells treated with TNFα accumulated more intracellular ROS and secreted more H2O2. Following TNFα treatment, only iAF cells had increased expression of the superoxide scavengersSOD1andSOD2whereas NP cells had increasedNOX4gene expression, an enzyme that can generate H2O2. Treating iAF cells with low dose H2O2(50 μM) induced senescence, however unlike TNFα, H2O2did not induce degenerative-like changes as there was no difference inCOL2, ACAN, MMP13, orIL6gene expression or number of COL2 and ACAN immunopositive cells compared to untreated controls. The latter result suggests that iAF cells have distinct degenerative and senescent phenotypes. To evaluate paracrine signalling, iAF and TNFα-treated NP cells were co-cultured. In contact co-culture the NP cells did induce iAF senescence. Thus, senescent NP cells may secrete soluble factors that induce degenerative and senescent changes within the iAF. This may contribute to a positive feedback loop of disc degeneration. It is possible these factors may include H2O2and cytokines (TNFα). Further studies will investigate if human disc cells respond similarly.
Proteomic landscape of tunneling nanotubes reveals CD9 and CD81 tetraspanins as key regulators
Authors: Manzano Roberto Notario , Chaze Thibault , Rubinstein Eric , Penard Esthel , Matondo Mariette , Zurzolo Chiara , Brou Christel 
Published: December 2022

SummaryTunneling nanotubes (TNTs) are open actin- and membrane-based channels, connecting remote cells and allowing direct transfer of cellular material (e.g. vesicles, mRNAs, protein aggregates) from cytoplasm to cytoplasm. Although they are important especially in pathological conditions (e.g., cancers, neurodegenerative diseases), their precise composition and their regulation were still poorly described. Here, using a biochemical approach allowing to separate TNTs from cell bodies and from extracellular vesicles and particles (EVPs), we obtained the full composition of TNTs compared to EVPs. We then focused to two major components of our proteomic data, the CD9 and CD81 tetraspanins, and further investigated their specific roles in TNT formation and function. We show that these two tetraspanins have distinct non-redundant functions: CD9 participates in stabilizing TNTs, whereas CD81 expression is required to allow the functional transfer of vesicle in the newly formed TNTs, possibly by regulating docking to or fusion with the opposing cell.
Modelling of outbreaks of SARS-CoV-2 Omicron variants after easing Dynamic Zero-COVID strategy in mainland China
Authors: Song Fujian , Bachmann Max O. 
Published: December 2022

AbstractBackgroundChina lifted strict non-pharmacological interventions (NPIs) to prevent outbreaks of SARS-CoV-2 Omicron variants in December 2022. Relatively low levels of immunity and of vaccine booster coverage in the Chinese population raise concerns that future outbreaks will rapidly result in high rates of death and severe illness and will overwhelm health services.MethodsThis was a compartmental, discrete-time population dynamic model. It compared projected deaths and hospitalisation under various scenarios, including booster vaccine coverage and strictness of NPIs.ResultsWe projected between 268,300 to 398,700 COVID-19 deaths, and peak numbers of hospitalised severe/critical cases between 3.2 to 6.4 per 10,000 population, before the outbreak wave recedes by February 2023. The COVID-19 deaths are reduced by 8% and 30%, respectively, under the weak and strict NPI scenarios, compared with the scenario without NPI measures. Early achievement of high coverage of three vaccine doses will further reduce COVID-19 deaths.ConclusionWe projected fewer COVID-19 deaths and hospitalisations than some other models have. Rapid expansion of booster vaccine coverage will only be effective if combined with strict NPIs and/or the high coverage of booster vaccination could be achieved early.
An unsupervised map of excitatory neurons’ dendritic morphology in the mouse visual cortex
Authors: Weis Marissa A. , Papadopoulos Stelios , Hansel Laura , Lüddecke Timo , Celii Brendan , Fahey Paul G. , Wang Eric Y. , Bae J. Alexander , Bodor Agnes L. , Brittain Derrick , Buchanan JoAnn , Bumbarger Daniel J. , Castro Manuel A. , Collman Forrest , da Costa Nuno Maçarico , Dorkenwald Sven , Elabbady Leila , Halageri Akhilesh , Jia Zhen , Jordan Chris , Kapner Dan , Kemnitz Nico , Kinn Sam , Lee Kisuk , Li Kai , Lu Ran , Macrina Thomas , Mahalingam Gayathri , Mitchell Eric , Mondal Shanka Subhra , Mu Shang , Nehoran Barak , Popovych Sergiy , Reid R. Clay , Schneider-Mizell Casey M. , Seung H. Sebastian , Silversmith William , Takeno Marc , Torres Russel , Turner Nicholas L. , Wong William , Wu Jingpeng , Yin Wenjing , Yu Szi-chieh , Reimer Jacob , Berens Philipp , Tolias Andreas S. , Ecker Alexander S. 
Published: December 2022

AbstractNeurons in the neocortex exhibit astonishing morphological diversity which is critical for properly wiring neural circuits and giving neurons their functional properties. However, the organizational principles underlying this morphological diversity remain an open question. Here, we took a data-driven approach using graph-based machine learning methods to obtain a low-dimensional morphological “bar code” describing more than 30,000 excitatory neurons in mouse visual areas V1, AL and RL that were reconstructed from the millimeter scale MICrONS serial-section electron microscopy volume. Contrary to previous classifications into discrete morphological types (m-types), our data-driven approach suggests that the morphological landscape of cortical excitatory neurons is better described as a continuum, with a few notable exceptions in layers 5 and 6. Dendritic morphologies in layers 2–3 exhibited a trend towards a decreasing width of the dendritic arbor and a smaller tuft with increasing cortical depth. Inter-area differences were most evident in layer 4, where V1 contained more atufted neurons than higher visual areas. Moreover, we discovered neurons in V1 on the border to layer 5 which avoided deeper layers with their dendrites. In summary, we suggest that excitatory neurons’ morphological diversity is better understood by considering axes of variation than using distinct m-types.
Conservation agriculture reduces climate change impact of a popcorn and wheat crop rotation
Authors: Guidoboni Maria Vittoria , Duparque Annie , Boissy Joachim , Mouny Jean-Christophe , Auberger Julie , van der Werf Hayo M.G. 
Published: December 2022

AbstractUrgent action is needed to ensure humanity’s future under climate change. Agriculture faces major challenges as it is both influenced by and contributes to climate change. Conservation agriculture reduces greenhouse gas (GHG) emissions and sequesters carbon (C) in the soil due to practices such as reduced tillage and planting of cover crops. This study assessed effects of an innovative conservation agriculture popcorn (Zea mays) and wheat (Triticum aestivum) crop rotation in south-western France on soil C sequestration, GHG emissions and several environmental impacts. Two complementary approaches were used: i) a comparison based on field data and expert judgement to assess short-term effects and ii) modelling of three scenarios to quantify long-term outcomes. In both approaches Life cycle assessment (LCA) was used to compare popcorn and wheat rotations. The conventional rotation used ploughing, and its soil was bare between wheat harvest and popcorn sowing. Conservation agriculture used reduced tillage, cover crops, and compost of green waste. Impacts of compost production were allocated mainly to its waste treatment function, based on waste treatment cost and compost price. Simulation modelling of soil C was used to estimate the amount of C sequestered by the conservation and conventional crop rotations. LCA was combined with soil C modelling over 100 years to assess the long-term climate change impact of three scenarios for the popcorn and wheat rotation. Mean annual C sequestration and net climate change impact were -0.24 t/ha and 3867 kg CO2-eq./ha, respectively, for the conventional rotation and 0.91 t/ha and 434 kg CO2-eq./ha, respectively, for the conservation rotation. The climate change impact of the conservation rotation depended strongly on the allocation of composting impacts between the waste treatment and compost production functions. Compared to the conventional rotation, the conservation rotation had a lower marine eutrophication impact (−7%) but higher impacts for terrestrial acidification (+9%), land competition (+3%), and cumulative energy demand (+2%). Modelling over 100 years revealed that at near soil C equilibrium, a conventional scenario lost 9% of soil C, whereas conservation agriculture scenarios gained 14% (only cover crop) and 26% of soil C (cover crop + compost). Conservation agriculture resulted in soil C sequestration over several decades, until a new soil C equilibrium was reached.HighlightsConservation and conventional popcorn and wheat crop rotations were comparedCoupling of LCA and soil carbon modelling allowed for comprehensive assessmentConservation agriculture sequestered carbon in the soilConservation agriculture strongly reduced climate change impactCompost impact-allocation choices strongly influenced potential impacts
16s rRNA gene sequence analysis of the microbial community on microplastic samples from the North Atlantic and Great Pacific Garbage Patches
Authors: Tora Dkawlma , Hentschel Ute , Lips Stefan , Schmitt-Jansen Mechthild , Borchert Erik 
Published: December 2022

ABSTRACTThe exponential increase in plastic production has led to their accumulation in the environment, particularly in oceans, polluting these environments from the shore to the open ocean and even sea ice in the pole regions. We compared microbial communities on plastic particles, known as “Plastisphere”, collected from the Atlantic and Pacific oceans gyres in the Summer of 2019 and subsequently looked for potential plastic degraders. We applied a 16S rRNA amplicon sequencing approach to decipher differences and similarities in colonization behaviour between these two gyres. Two polymer types include plastics: polyethylene (PE) and polypropylene (PP). We found that microbes differed significantly between the two oceans and identified thirty-two differentially abundant taxa at the class level. Proteobacteria, Cyanobacteria and Bacteroidota were the most prominent relative abundant phyla in the two oceans. Finally, according to the current literature, we found 40 genera documented as potential plastic degraders. This study highlights the importance of the biogeographical location with respect to microbial colonization patterns of marine plastic debris, differing even in the open oceans. Furthermore, the wide distribution of potential plastic-degrading bacteria was shown.