bluuebunny/crossref_metadata_2025 huggingface dataset:
Uncovering Interpretable Fine-Grained Phenotypes of Subcellular Dynamics through Unsupervised Self-Training of Deep Neural Networks
Authors: Wang Chuangqi , Choi Hee June , Woodbury Lucy , Lee Kwonmoo
Published: May 2021

Live cell imaging provides unparallel insights into dynamic cellular processes across spatiotemporal scales. Despite its potential, the inherent spatiotemporal heterogeneity within live cell imaging data often obscures critical mechanical details underlying cellular dynamics. Uncovering fine-grained phenotypes of live cell dynamics is pivotal for precise understandings of the heterogeneity of physiological and pathological processes. However, this endeavor introduces formidable technical challenges to unsupervised machine learning, demanding the extraction of features that can faithfully preserve heterogeneity, effectively discriminate between different molecularly perturbed states, and provide interpretability. While deep learning shows promise in extracting useful features from large datasets, it often falls short in producing such high-fidelity features, especially in unsupervised learning settings. To tackle these challenges, we present DeepHACX (Deep phenotyping of Heterogeneous Activities of Cellular dynamics with eXplanations), a self-training deep learning framework designed for fine-grained and interpretable phenotyping. This framework seamlessly integrates an unsupervised teacher model with interpretable features to facilitate feature learning in a student deep neural network (DNN). Significantly, it incorporates an autoencoder-based regularizer, termed SENSER (SENSitivity-enhancing autoEncoding Regularizer), designed to prompt the student DNN to maximize the heterogeneity associated with molecular perturbations. This approach enables the acquisition of features that not only discriminate between different molecularly perturbed states but also faithfully preserve the heterogeneity linked to these perturbations. In our study, DeepHACX successfully delineated fine-grained phenotypes within the heterogeneous protrusion dynamics of migrating epithelial cells, uncovering specific responses to pharmacological perturbations. Remarkably, DeepHACX adeptly captured a minimal number of highly interpretable features uniquely linked to these fine-grained phenotypes, each corresponding to specific temporal intervals crucial for their manifestation. This unique capability positions DeepHACX as a valuable tool for investigating diverse cellular dynamics and comprehensively studying their heterogeneity.
Longitudinal immune dynamics of mild COVID-19 define signatures of recovery and persistence
Authors: Talla Aarthi , Vasaikar Suhas V. , Lemos Maria P. , Moodie Zoe , Lee Pebworth Mark-Phillip , Henderson Kathy E. , Cohen Kristen W. , Czartoski Julie L. , Lai Lilin , Suthar Mehul S. , Heubeck Alexander T , Genge Palak C. , Roll Charles R. , Weiss Morgan , Reading Julian , Kondza Nina , MacMillan Hugh , Fong Olivia C. , Thomson Zachary James , Graybuck Lucas T. , Okada Lauren Y. , Newell Evan W. , Coffey Ernest M. , Meijer Paul , Becker Lynne A. , De Rosa Stephen C. , Skene Peter J. , Torgerson Troy R. , Li Xiao-jun , Szeto Gregory Lee , McElrath M. Juliana , Bumol Thomas F.
Published: May 2021

SARS-CoV-2 has infected over 200 million and caused more than 4 million deaths to date. Most individuals (>80%) have mild symptoms and recover in the outpatient setting, but detailed studies of immune responses have focused primarily on moderate to severe COVID-19. We deeply profiled the longitudinal immune response in individuals with mild COVID-19 beginning with early time points post-infection (1-15 days) and proceeding through convalescence to >100 days after symptom onset. We correlated data from single cell analyses of peripheral blood cells, serum proteomics, virus-specific cellular and humoral immune responses, and clinical metadata. Acute infection was characterized by vigorous coordinated innate and adaptive immune activation that differed in character by age (young vs. old). We then characterized signals associated with recovery and convalescence to define and validate a new signature of inflammatory cytokines, gene expression, and chromatin accessibility that persists in individuals with post-acute sequelae of SARS-CoV-2 infection (PASC).
How do symbiotic associations in lecideoid lichens respond to different environmental conditions along the Transantarctic Mountains, Ross Sea region, Antarctica?
Authors: Wagner Monika , Brunauer Georg , Bathke Arne C. , Cary S. Craig , Fuchs Roman , Sancho Leopoldo G. , Türk Roman , Ruprecht Ulrike
Published: May 2021

Lecideoid lichens as dominant vegetation-forming organisms in the climatically harsh areas of the southern part of continental Antarctica show clear preferences in relation to environmental conditions (i.e. macroclimate). 306 lichen samples were included in the study, collected along the Ross Sea coast (78°S–85.5°S) at six climatically different sites. The species compositions as well as the associations of their two dominant symbiotic partners (myco- and photobiont) were set in context with environmental conditions along the latitudinal gradient. Diversity values were nonlinear with respect to latitude, with the highest alpha diversity in the milder areas of the McMurdo Dry Valleys (78°S) and the most southern areas (Durham Point, 85.5°S; Garden Spur, 84.5°S), and lowest in the especially arid and cold Darwin Area (~79.8°S). Furthermore, the specificity of mycobiont species towards their photobionts decreased under more severe climate conditions. The generalist lichen speciesLecanora fuscobrunneaandLecidea cancriformiswere present in almost all habitats, but were dominant in climatically extreme areas.Carbonea vorticosa, Lecidella greeniiandRhizoplaca macleaniiwere confined to milder areas.

In summary, the macroclimate is considered to be the main driver of species distribution, making certain species useful as bioindicators of climate conditions and, consequently, for detecting climate change.
Systemic infection with highly pathogenic H5N8 of avian origin produces encephalitis and mortality in wild mammals at a UK rehabilitation centre
Authors: Floyd Tobias , Banyard Ashley C. , Lean Fabian Z. X. , Byrne Alexander M. P. , Fullick Edward , Whittard Elliot , Mollett Benjamin C. , Bexton Steve , Swinson Vanessa , Macrelli Michele , Lewis Nicola S. , Reid Scott M. , Núñez Alejandro , Duff J. Paul , Hansen Rowena , Brown Ian H.
Published: May 2021

Europe has experienced extensive outbreaks of highly pathogenic avian influenza (HPAI) during the autumn/winter 2020/21 season. These avian influenza A viruses are highly transmissible and have infected over 1000 commercial and backyard poultry premises in Europe in this period causing high mortality. The impact on wild bird populations has also been significant, with over 400 detections in at least 47 different species reported across Europe as being positive with the H5N8 virus. Although different H5Nx combinations within the H5 clade 2.3.4.4b have been detected, the H5N8 subtype has predominated both in wild birds and domestic poultry outbreaks. In the UK there have been 22 outbreaks of H5N8 in domestic poultry and captive birds and more than 300 wild bird detections involving H5N8 over the autumn/winter 2020/21 period to April 2021. Here we detail the series of events surrounding the detection of an H5N8 influenza A virus of avian origin in five swans, a fox and three seals in a wildlife rehabilitation centre.
Fibronectin meshwork controls epithelial stem cell fate
Authors: Estrach Soline , Tosello Lionel , Tissot Floriane S. , Cailleteau Laurence , Cervera Ludovic , Jensen Kim B , Féral Chloé C.
Published: May 2021

Adult stem cell fate is tightly balanced by the local microenvironment called niche and sustain tissue regeneration1–4. How niche signals are integrated and regulate regeneration remains largely unexplored. The extracellular matrix and integrin ligand fibronectin is a crucial and well-characterized wound healing actor that has never been involved in skin regeneration. Here, we show that fibronectin displays a highly specific enrichment in hair follicle stem cells (HFSC) at the onset of regeneration. Conditional deletion of fibronectin in HFSC compartment (Lrig1, K19) leads to hair regeneration blockade, impaired stem cell location and fate. Dermal injection of exogenous fibronectin rescues these phenotypes. To elucidate molecular mechanism underlying fibronectin function, we used conditional deletion models of SLC3A2, the main integrin coreceptor. We show that, via its role in integrin-dependent assembly of fibronectin matrix, SLC3A2 acts as molecular relay of niche signals. Thus, fibronectin-integrin-SLC3A2 cascade finely tunes HFSC fate and tissue regenerative power.
Molecular programming in utero modulates hepatic lipid metabolism and adult metabolic risk in obese mother offspring in a sex-specific manner
Authors: Savva Christina , Helguero Luisa A. , González-Granillo Marcela , Melo Tânia , Couto Daniela , Angelin Bo , Rosário Domingues Maria , Li Xidan , Kutter Claudia , Korach-André Marion
Published: May 2021

Male and female offspring of obese mothers are known to differ significantly in their metabolic adaptation and later development of complications. We investigated the sex-dependent responses in obese offspring of mice with maternal obesity, focusing on changes in liver glucose and lipid metabolism. Maternal obesity prior to and during gestation led to hepatic insulin resistance and inflammation in male offspring, while female offspring were protected. These sex differences were explained by more efficient transcriptional and posttranscriptional reprogramming of metabolic pathways to prevent the damaging effects of maternal obesity in females compared to males. These differences were sustained later in life, resulting in a better metabolic balance in female offspring. In conclusion, sex and maternal obesity drive transcriptional and posttranscriptional regulation of major metabolic processes in offspring liver differently, explaining the sexual dimorphism in obesity-associated metabolic risk.
Genome-wide screening in human kidney organoids identifies novel aspects of nephrogenesis
Authors: Ungricht Rosemarie , Guibbal Laure , Lasbennes Marie-Christine , Orsini Vanessa , Beibel Martin , Waldt Annick , Cuttat Rachel , Carbone Walter , Basler Anne , Roma Guglielmo , Nigsch Florian , Tchorz Jan , Hoepfner Dominic , Hoppe Philipp S.
Published: May 2021

Human organoids allow studying proliferation, lineage specification, and three-dimensional tissue development. Due to the inherent multicellular complexity, interrogation by systematic genetic methodologies is challenging. Here, we present the first genome-wide CRISPR screen in iPSC-derived kidney organoids. The combination of genome editing, longitudinal sampling and sorting of specific cell populations enabled us to uncover novel biology from development to tubular morphogenesis. We validated the high quality of our screen by individual hit follow up and comparisons to kidney disease datasets. The discovery of a novel regulatory mechanism which controls epithelial proliferation via a trans-activating but cis-inhibitory effect of the Notch ligand Jagged1 proves how mosaic knockouts generated by pooled CRISPR screening in organoids can identify novel ways of communication between heterogeneous cell populations in complex tissues. Collectively, these data demonstrate the feasibility of using complex iPSC- derived organoids for genome-scale screening and serves as a benchmark for future organoid CRISPR screens.
SARS-CoV-2 Nsp14 activates NF-κB signaling and induces IL-8 upregulation
Authors: Li Taiwei , Kenney Adam D. , Liu Helu , Fiches Guillaume N. , Zhou Dawei , Biswas Ayan , Que Jianwen , Santoso Netty , Yount Jacob S. , Zhu Jian
Published: May 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection leads to NF-κB activation and induction of pro-inflammatory cytokines, though the underlying mechanism for this activation is not fully understood. Our results reveal that the SARS-CoV-2 Nsp14 protein contributes to the viral activation of NF-κB signaling. Nsp14 caused the nuclear translocation of NF-κB p65. Nsp14 induced the upregulation of IL-6 and IL-8, which also occurred in SARS-CoV-2 infected cells. IL-8 upregulation was further confirmed in lung tissue samples from COVID-19 patients. A previous proteomic screen identified the putative interaction of Nsp14 with host Inosine-5’-monophosphate dehydrogenase 2 (IMPDH2) protein, which is known to regulate NF-κB signaling. We confirmed the Nsp14-IMPDH2 protein interaction and found that IMPDH2 knockdown or chemical inhibition using ribavirin (RIB) and mycophenolic acid (MPA) abolishes Nsp14-mediated NF-κB activation and cytokine induction. Furthermore, IMDPH2 inhibitors (RIB, MPA) efficiently blocked SARS-CoV-2 infection, indicating that IMDPH2, and possibly NF-κB signaling, is beneficial to viral replication. Overall, our results identify a novel role of SARS-CoV-2 Nsp14 in causing the activation of NF-κB.
The complete sequence of a human genome
Authors: Nurk Sergey , Koren Sergey , Rhie Arang , Rautiainen Mikko , Bzikadze Andrey V. , Mikheenko Alla , Vollger Mitchell R. , Altemose Nicolas , Uralsky Lev , Gershman Ariel , Aganezov Sergey , Hoyt Savannah J. , Diekhans Mark , Logsdon Glennis A. , Alonge Michael , Antonarakis Stylianos E. , Borchers Matthew , Bouffard Gerard G. , Brooks Shelise Y. , Caldas Gina V. , Cheng Haoyu , Chin Chen-Shan , Chow William , de Lima Leonardo G. , Dishuck Philip C. , Durbin Richard , Dvorkina Tatiana , Fiddes Ian T. , Formenti Giulio , Fulton Robert S. , Fungtammasan Arkarachai , Garrison Erik , Grady Patrick G.S. , Graves-Lindsay Tina A. , Hall Ira M. , Hansen Nancy F. , Hartley Gabrielle A. , Haukness Marina , Howe Kerstin , Hunkapiller Michael W. , Jain Chirag , Jain Miten , Jarvis Erich D. , Kerpedjiev Peter , Kirsche Melanie , Kolmogorov Mikhail , Korlach Jonas , Kremitzki Milinn , Li Heng , Maduro Valerie V. , Marschall Tobias , McCartney Ann M. , McDaniel Jennifer , Miller Danny E. , Mullikin James C. , Myers Eugene W. , Olson Nathan D. , Paten Benedict , Peluso Paul , Pevzner Pavel A. , Porubsky David , Potapova Tamara , Rogaev Evgeny I. , Rosenfeld Jeffrey A. , Salzberg Steven L. , Schneider Valerie A. , Sedlazeck Fritz J. , Shafin Kishwar , Shew Colin J. , Shumate Alaina , Sims Yumi , Smit Arian F. A. , Soto Daniela C. , Sović Ivan , Storer Jessica M. , Streets Aaron , Sullivan Beth A. , Thibaud-Nissen Françoise , Torrance James , Wagner Justin , Walenz Brian P. , Wenger Aaron , Wood Jonathan M. D. , Xiao Chunlin , Yan Stephanie M. , Young Alice C. , Zarate Samantha , Surti Urvashi , McCoy Rajiv C. , Dennis Megan Y. , Alexandrov Ivan A. , Gerton Jennifer L. , O’Neill Rachel J. , Timp Winston , Zook Justin M. , Schatz Michael C. , Eichler Evan E. , Miga Karen H. , Phillippy Adam M.
Published: May 2021

In 2001, Celera Genomics and the International Human Genome Sequencing Consortium published their initial drafts of the human genome, which revolutionized the field of genomics. While these drafts and the updates that followed effectively covered the euchromatic fraction of the genome, the heterochromatin and many other complex regions were left unfinished or erroneous. Addressing this remaining 8% of the genome, the Telomere-to-Telomere (T2T) Consortium has finished the first truly complete 3.055 billion base pair (bp) sequence of a human genome, representing the largest improvement to the human reference genome since its initial release. The new T2T-CHM13 reference includes gapless assemblies for all 22 autosomes plus Chromosome X, corrects numerous errors, and introduces nearly 200 million bp of novel sequence containing 2,226 paralogous gene copies, 115 of which are predicted to be protein coding. The newly completed regions include all centromeric satellite arrays and the short arms of all five acrocentric chromosomes, unlocking these complex regions of the genome to variational and functional studies for the first time.
Impaired function and delayed regeneration of dendritic cells in COVID-19
Authors: Winheim Elena , Rinke Linus , Lutz Konstantin , Reischer Anna , Leutbecher Alexandra , Wolfram Lina , Rausch Lisa , Kranich Jan , Wratil Paul R. , Huber Johanna E. , Baumjohann Dirk , Rothenfußer Simon , Hellmuth Johannes C. , Scherer Clemens , Muenchhoff Maximilian , Bergwelt-Baildon Michael von , Stark Konstantin , Straub Tobias , Brocker Thomas , Keppler Oliver T. , Subklewe Marion , Krug Anne B.
Published: May 2021

Disease manifestations in COVID-19 range from mild to severe illness associated with a dysregulated innate immune response. Alterations in function and regeneration of dendritic cells (DC) and monocytes may contribute to immunopathology and influence adaptive immune responses in COVID-19 patients. We analyzed circulating DC and monocyte subsets in 65 hospitalized COVID-19 patients with mild/moderate or severe disease from acute disease to recovery and in healthy controls. Persisting reduction of all DC subpopulations was accompanied by an expansion of proliferating Lineage- HLADR+ cells lacking DC markers. Increased frequency of the recently discovered CD163+ CD14+ DC3 subpopulation in patients with more severe disease was associated with systemic inflammation, activated T follicular helper cells, and antibody-secreting cells. Persistent downregulation of CD86 and upregulation of PD-L1 in conventional DC (cDC2 and DC3) and classical monocytes associated with a reduced capacity to stimulate naïve CD4+ T cells correlated with disease severity. Long-lasting depletion and functional impairment of DCs and monocytes may have consequences for susceptibility to secondary infections and therapy of COVID-19 patients.
Comparison of linear combination modeling strategies for GABA-edited MRS at 3T
Authors: Zöllner Helge J. , Tapper Sofie , Hui Steve C. N. , Barker Peter B. , Edden Richard A. E. , Oeltzschner Georg
Published: May 2021

Purpose

J-difference-edited spectroscopy is a valuable approach for the in vivo detection of γ-aminobutyric-acid (GABA) with MRS. A recent expert consensus article recommends linear combination modeling (LCM) of edited MRS but does not give specific details of implementation. This study explores different modeling strategies to adapt LCM for GABA-edited MRS.

Methods

61 medial parietal lobe GABA-edited MEGA-PRESS spectra from a recent 3T multi-site study were modeled using 102 different strategies combining six different approaches to account for co-edited macromolecules, three modeling ranges, three baseline knot spacings, and the use of basis sets with or without homocarnosine. The resulting GABA and GABA+ estimates (quantified relative to total creatine), the residuals at different ranges, SDs and CVs, and Akaike information criteria, were used to evaluate the models’ performance.

Results

Significantly different GABA+ and GABA estimates were found when a well-parameterized MM3cobasis function was included in the model. The mean GABA estimates were significantly lower when modeling MM, while the CVs were similar. A sparser spline knot spacing led to lower variation in the GABA and GABA+ estimates, and a narrower modeling range – only including the signals of interest – did not substantially improve or degrade modeling performance. Additionally, results suggest that LCM can separate GABA and the underlying co-edited MM3co. Incorporating homocarnosine into the modeling did not significantly improve variance in GABA+ estimates.

Conclusion

GABA-edited MRS is most appropriately quantified by LCM with a well-parameterized co-edited MM3cobasis function with a constraint to the non-overlapped MM0.93, in combination with a sparse spline knot spacing (0.55 ppm) and a modeling range between 0.5 and 4 ppm.

Graphical Abstract

102 strategies to model GABA-edited MRS with linear combination modeling were evaluated to quantify GABA and GABA+ in Osprey. Significantly different GABA and GABA+ estimates were found when a well-parameterized macro-molecule at 3 ppm was included. The findings suggest that linear combination modeling needs to be adapted for quantification of GABA-edited MRS.
PGC1α Regulates the Endothelial Response to Fluid Shear Stress via Telomerase Reverse Transcriptase Control of Heme Oxygenase-1
Authors: Kant Shashi , Tran Khanh-Van , Kvandova Miroslava , Caliz Amada D. , Yoo Hyung-Jin , Learnard Heather , Craige Siobhan M. , Hall Joshua D. , Jiménez Juan M. , Hilaire Cynthia St. , Schulz Eberhard , Kröller-Schön Swenja , Keaney John F.
Published: May 2021

Fluid shear stress (FSS) is known to mediate multiple phenotypic changes in the endothelium. Laminar FSS (undisturbed flow) is known to promote endothelial alignment to flow that is key to stabilizing the endothelium and rendering it resistant to atherosclerosis and thrombosis. The molecular pathways responsible for endothelial responses to FSS are only partially understood. Here we have identified peroxisome proliferator gamma coactivator-1α (PGC-1α) as a flow-responsive gene required for endothelial flow alignment in vitro and in vivo. Compared to oscillatory FSS (disturbed flow) or static conditions, laminar FSS (undisturbed flow) increased PGC-1α expression and its transcriptional co-activation. PGC-1α was required for laminar FSS-induced expression of telomerase reverse transcriptase (TERT) in vitro and in vivo via its association with ERRα and KLF4 on the TERT promoter. We found that TERT inhibition attenuated endothelial flow alignment, elongation, and nuclear polarization in response to laminar FSS in vitro and in vivo. Among the flow-responsive genes sensitive to TERT status was heme oxygenase-1 (HMOX1), a gene required for endothelial alignment to laminar FSS. Thus, these data suggest an important role for a PGC-1α-TERT-HMOX1 axis in the endothelial stabilization response to laminar FSS.
Interactions of surfactants with the bacterial cell wall and inner membrane: Revealing the link between aggregation and antimicrobial activity
Authors: Sharma Pradyumn , Vaiwala Rakesh K. , Parthasarathi Srividhya , Patil Nivedita , Waskar Morris , Raut Janhavi S. , Basu Jaydeep K. , Ayappa K. Ganapathy
Published: May 2021

Surfactants with their intrinsic ability to solubilize lipids are widely used as antibacterial agents. Interaction of surfactants with the bacterial cell envelope is complicated due to their propensity to aggregate. It is important to discern the interactions of micellar aggregates and single surfactants on the various components of the cell envelope to improve selectivity and augment the efficacy of surfactant-based products. In this study, we present a combined experimental and molecular dynamics investigation to unravel the molecular basis for the superior kill efficacy of laurate over oleate observed in contact time assays with liveE. coli. To gain a molecular understanding of these differences, we performed all-atom molecular dynamics simulations to observe the interactions of surfactants with the periplasmic peptidoglycan layer and the inner membrane of Gram-negative bacteria. The peptidoglycan layer allows a greater number of translocation events for laurate when compared with oleate molecules. More interestingly, aggregates did not translocate the peptidoglycan layer, thereby revealing an intrinsic sieving property of the bacterial cell wall to effectively modulate the surfactant concentration at the inner membrane. The molecular dynamics simulations exhibit greater thinning of the inner membrane in the presence of laurate when compared with oleate, and laurate induced greater disorder and decreased the bending modulus of the inner membrane to a greater extent. The enhanced antimicrobial efficacy of laurate over oleate was further verified by experiments with giant unilamellar vesicles, which revealed that laurate induced vesicle rupture at lower concentrations in contrast to oleate. The novel molecular insights gained from our study uncovers hitherto unexplored pathways to rationalize the development of antimicrobial formulations and therapeutics.
Hydrophobic mismatch is a key factor in protein transport on the Tat pathway
Authors: Hao Binhan , Zhou Wenjie , Theg Steven M.
Published: May 2021

The twin-arginine translocation (Tat) pathway transports folded proteins across membranes in bacteria, thylakoid, plant mitochondria, and archaea. In most species, the active Tat machinery consists of three independent subunits, TatA, TatB and TatC. TatA and TatB from all bacterial species possess short transmembrane alpha-helices (TMHs), both of which are only fifteen residues long in E. coli. Such short TMHs cause a hydrophobic mismatch between Tat subunits and the membrane bilayer. Here, by modifying the length of the TMHs of E. coli TatA and TatB, we assess the functional importance of the hydrophobic mismatch in the Tat transport mechanism. Surprisingly, both TatA and TatB with as few as 11 residues in their respective TMHs are still able to insert into the membrane bilayer, albeit with a decline in membrane integrity. Three different assays, both qualitative and quantitative, were conducted to evaluate the Tat activity of the TMH length mutants. Our experiments indicate that the TMHs of TatA and TatB appear to be evolutionarily tuned to 15 amino acids, with activity dropping off with any modification of this length. We believe our study supports a model of Tat transport utilizing localized toroidal pores that form when the membrane bilayer is thinned to a critical threshold. In this context, the 15-residue length of the TatA and TatB TMHs can be seen as a compromise between the need for some hydrophobic mismatch to allow the membrane to reversibly reach the threshold thinness required for toroidal pore formation, and the permanently destabilizing effect of placing even shorter helices into these energy-transducing membranes.
Microtubules Promote the Non-cell Autonomy of MicroRNAs by Inhibiting their Cytoplasmic Loading into ARGONAUTE1 inArabidopsis
Authors: Fan Lusheng , Zhang Cui , Zhang Yong , Stewart Ethan , Jez Jakub , Nakajima Keiji , Chen Xuemei
Published: May 2021

Mobile microRNAs (miRNAs) serve as local and long-distance signals in developmental patterning and stress responses in plants. However, mechanisms governing the non-cell autonomous activities of miRNAs remain elusive. Here, we show that mutations that disrupt microtubule dynamics are specifically defective for the non-cell autonomous actions of mobile miRNAs, including miR165/6 that is produced in the endodermis and moves to the vasculature to pattern xylem cell fates inArabidopsisroots. We show that KTN1, a subunit of a microtubule-severing enzyme, is required in source and intermediary cells to inhibit the loading of miR165/6 into ARGONUATE1 (AGO1), which is cell-autonomous, to enable the miRNA‟s cell exit. Microtubule disruption enhances the association of miR165/6 with AGO1 in the cytosol. These findings suggest that, while cell-autonomous miRNAs load into AGO1 in the nucleus, cytoplasmic AGO1 loading of mobile miRNAs is a key step regulated by microtubules to promote the range of miRNA‟s cell-to-cell movement.
Histone acetyltransferase activity of CREB-binding protein is essential for synaptic plasticity in Lymnaea
Authors: Hatakeyama Dai , Sunada Hiroshi , Totani Yuki , Watanabe Takayuki , Felletár Ildikó , Fitchett Adam , Eravci Murat , Anagnostopoulou Aikaterini , Miki Ryosuke , Kuzuhara Takashi , Kemenes Ildikó , Ito Etsuro , Kemenes György
Published: May 2021

In eukaryotes, CREB-binding protein (CBP), a coactivator of CREB, functions both as a platform for recruiting other components of the transcriptional machinery and as a histone acetyltransferase (HAT) that alters chromatin structure. We previously showed that the transcriptional activity of cAMP-responsive element binding protein (CREB) plays a crucial role in neuronal plasticity in the pond snail Lymnaea stagnalis. However, there is no information on the role CBP plays in CREB-initiated plastic changes in Lymnaea. In this study, we characterized the Lymnaea CBP (LymCBP) gene and investigated the roles it plays in synaptic plasticity involved in regulating feeding behaviors. Similar to CBPs of other species, LymCBP possesses functional domains, such as KIX domain, which is essential for interaction with CREB and was shown to regulate long-term memory (LTM). In situ hybridization showed that the staining patterns of LymCBP mRNA in the central nervous system were very similar to those of Lymnaea CREB1 (LymCREB1). A particularly strong LymCBP mRNA signal was observed in the Cerebral Giant Cell (CGC), an identified extrinsic modulatory interneuron of the feeding circuit, key to both appetitive and aversive LTM for taste. Biochemical experiments using the recombinant protein of LymCBP HAT domain showed that its enzymatic activity was blocked by classical HAT inhibitors such as curcumin, anacardic acid and garcinol. Preincubation of Lymnaea CNSs with these HAT inhibitors blocked cAMP-induced long-term potentiation between the CGC and the follower B1 motoneuron. We therefore suggest that HAT activity of LymCBP in the CGCs is a key factor in synaptic plasticity contributing to LTM after classical conditioning.
An altered metabolism in leukocytes showing in vitro igG memory from SARS-CoV-2-infected patients
Authors: Fanelli G. , Gevi F. , Zarletti G. , Tiberi M. , De Molfetta V. , Scapigliati G. , Timperio A.M.
Published: May 2021

Coronavirus disease 2019 (COVID 19) is a systemic infection that exerts a significant impact on cell metabolism. In this study we performed metabolomic profiling coupled with multivariate statistics analysis obtained from 43 in vitro cultures of peripheral blood mononuclear cells (PBMC), 19 of which displaying IgG memory for spike-S1 antigen 60-90 days after infection. By using mass spectrometry analysis, a significant up regulation of S-adenosyl-Homocysteine, Sarcosine and Arginine was found in leukocytes showing IgG memory. These metabolites are known to be involved in physiological recovering from viral infections and immune activities, and our findings might represent a novel and easy measure that could be of help in understanding SARS-Cov-2 effects on leukocytes.
Distinct internal states interact to shape food choice by modulating sensorimotor processing at global and local scales
Authors: Münch Daniel , Goldschmidt Dennis , Ribeiro Carlos
Published: May 2021

When deciding what to eat, animals evaluate sensory information about food quality alongside multiple ongoing internal states. How internal states interact to alter sensorimotor processing and shape decisions such as food choice remains poorly understood. Here, we use pan-neuronal volumetric activity imaging in theDrosophilabrain to investigate the neuronal basis of internal state dependent nutrient appetites. We created a functional atlas of the ventral fly brain and find that metabolic state shapes sensorimotor processing across large sections of the neuropil. Reproductive state, in contrast, acts locally to define how sensory information is translated into feeding motor output. Thereby, these two states synergistically modulate protein-specific food intake and thus food choice. Finally, using a novel computational strategy, we identify driver lines innervating state-modulated regions and show that the newly identified borboleta region is sufficient to direct food choice towards protein-rich food. We therefore identify a generalizable principle by which distinct internal states are integrated to shape decision-making and propose a strategy to uncover and functionally validate how internal states shape behavior.
Transcriptional milestones in Dictyostelium development
Authors: Katoh-Kurasawa Mariko , Hrovatin Karin , Hirose Shigenori , Webb Amanda , Ho Hsing-I , Zupan Blaž , Shaulsky Gad
Published: May 2021

Development of the social amoeba Dictyostelium discoideum begins by starvation of single cells and ends in multicellular fruiting bodies 24 hours later. These major morphological changes are accompanied by sweeping gene expression changes, encompassing nearly half of the 13,000 genes in the genome. To explore the relationships between the transcriptome and developmental morphogenesis, we performed time-series RNA-sequencing analysis of the wild type and 20 mutant strains with altered morphogenesis. These strains exhibit arrest at different developmental stages, accelerated development, or terminal morphologies that are not typically seen in the wild type. Considering eight major morphological transitions, we identified 1,371 milestone genes whose expression changes sharply between two consecutive transitions. We also identified 1,099 genes as members of 21 regulons, which are groups of genes that remain coordinately regulated despite the genetic, temporal, and developmental perturbations in the dataset. The gene annotations in these milestones and regulons validate known transitions and reveal several new physiological and functional transitions during development. For example, we found that DNA replication genes are co-regulated with cell division genes, so they are co-expressed in mid-development even though chromosomal DNA is not replicated at that time. Altogether, the dataset includes 486 transcriptional profiles, across developmental and genetic conditions, that can be used to identify new relationships between gene expression and developmental processes and to improve gene annotations. We demonstrate the utility of this resource by showing that the cycles of aggregation and disaggregation observed in allorecognition-defective mutants involve a dedifferentiation process. We also show unexpected variability and sensitivity to genetic background and developmental conditions in two commonly used genes, act6 and act15, and robustness of the coaA gene. Finally, we propose that gpdA should be used as a standard for mRNA quantitation because it is less sensitive to genetic background and developmental conditions than commonly used standards. The dataset is available for democratized exploration without the need for programming skills through the web application dictyExpress and the data mining environment Orange.
Local atomic structure analysis around Mg atom doped in GaN by X-ray absorption spectroscopy and spectrum simulations
Authors: Isomura Noritake , Kimoto Yasuji
Published: May 2021

The identification of the incorporated site of magnesium (Mg) and hydrogen (H) required for p-type formation in gallium nitride (GaN) power devices has been demonstrated by X-ray absorption spectroscopy (XAS). In this study, the fluorescence line of Mg with 3 × 1019 atoms cm−3 was successfully separated from that of Ga using a superconducting tunnel junction array detector with high sensitivity and high energy resolution, and consequently the Mg K-edge XAS spectra of such dilute samples were obtained. The site of Mg atoms incorporated into the GaN lattice was identified as the Ga substitutional site by comparing the experimental XAS spectrum with the simulated spectra calculated by density functional theory. In addition, the presence or absence of H around Mg can be determined through distinctive characteristics expected from the spectrum simulations.
Relativistic spacetime crystals
Authors: Gopalan Venkatraman
Published: May 2021

Periodic space crystals are well established and widely used in physical sciences. Time crystals have been increasingly explored more recently, where time is disconnected from space. Periodic relativistic spacetime crystals on the other hand need to account for the mixing of space and time in special relativity through Lorentz transformation, and have been listed only in 2D. This work shows that there exists a transformation between the conventional Minkowski spacetime (MS) and what is referred to here as renormalized blended spacetime (RBS); they are shown to be equivalent descriptions of relativistic physics in flat spacetime. There are two elements to this reformulation of MS, namely, blending and renormalization. When observers in two inertial frames adopt each other's clocks as their own, while retaining their original space coordinates, the observers become blended. This process reformulates the Lorentz boosts into Euclidean rotations while retaining the original spacetime hyperbola describing worldlines of constant spacetime length from the origin. By renormalizing the blended coordinates with an appropriate factor that is a function of the relative velocities between the various frames, the hyperbola is transformed into a Euclidean circle. With these two steps, one obtains the RBS coordinates complete with new light lines, but now with a Euclidean construction. One can now enumerate the RBS point and space groups in various dimensions with their mapping to the well known space crystal groups. The RBS point group for flat isotropic RBS spacetime is identified to be that of cylinders in various dimensions:mm2which is that of a rectangle in 2D, (∞/m)mwhich is that of a cylinder in 3D, and that of a hypercylinder in 4D. An antisymmetry operation is introduced that can swap between space-like and time-like directions, leading to color spacetime groups. The formalism reveals RBS symmetries that are not readily apparent in the conventional MS formulation.Mathematicascript is provided for plotting the MS and RBS geometries discussed in the work.
A small UAV tracking algorithm based on AIMM-UKF
Authors: Hou Zhiwen , Bu Fanliang
Published: May 2021

Purpose

The purpose of this study is to establish an effective tracking algorithm for small unmanned aerial vehicles (UAVs) based on interacting multiple model (IMM) to take timely countermeasures against illegal flying UAVs.

Design/methodology/approach

In this paper, based on the constant velocity model (CV), the maneuvering adaptive current statistical model (CS) and the angular velocity adaptive three-dimensional (3D) fixed center constant speed rate constant steering rate model, a small UAV tracking algorithm based on adaptive interacting multiple model (AIMM-UKF) is proposed. In addition, an adaptive robust filter is added to each model of the algorithm. The linear Kalman filter algorithm is attached to the CV model and the CS model and the unscented Kalman filter algorithm (UKF) is attached to the CSCDR model to solve the nonlinearity of the 3D turning model.

Findings

Monte-Carlo simulation comparison with the other two IMM tracking algorithms shows that in the case of different movement modes and maneuvering strength of the UAV, the AIMM-UKF algorithm makes a good trade-off between the amount of calculation and filtering accuracy, which can maintain more accurate and stable tracking and has strong robustness. At the same time, after testing the actual observation data of the UAV, the results show that the AIMM-UKF algorithm state estimation trajectory can be regarded as an actual trajectory in practical engineering applications, which has good practical value.

Originality/value

This paper presents a new small UAV tracking algorithm based on IMM and the advantages and practicability of this algorithm compared with existing algorithms are proved through experiments.
Responsible leadership and employee outcomes: a systematic literature review, integration and propositions
Authors: Haque Amlan , Fernando Mario , Caputi Peter
Published: May 2021

Purpose

The dominant view of responsible leadership (RL) has so far lacked adequate testing for employees' motivational outcomes, including presenteeism. Presenteeism, or attending work while being ill and unable to work at full capacity, causes productivity loss and imposes a significant economic burden to businesses and national economies. Applying the social identity theory of leadership (SITL), this paper aims to offer a conceptual framework supporting the relationship between RL and presenteeism and incorporating the mediating roles of organisational commitment and employees' turnover intentions.

Design/methodology/approach

This paper conducts a systematic literature review using a Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) flowchart with the existing research on RL, presenteeism, organisational commitment and employee turnover intentions covering the main contributors to this research stream. The proposed model offers eight propositions to promote the examination of RL in more insightful ways.

Findings

A shift in focus to the aspect of value-based leadership and presenteeism allows this paper to explore probable employee motivational outcomes, especially with consideration of organisational commitment and turnover intentions. While extant studies about presenteeism have tended to identify negative consequences, this paper explores different contexts in which RL could be crucial and positive. Based on a PRISMA flowchart, this paper provides a conceptual framework and directions that scholars might use to guide organisations and evaluate future research studies in RL and presenteeism.

Research limitations/implications

The implications of this paper lie first in highlighting the demand for scholars to employ RL when conducting research reviews in organisational leadership and presenteeism. Beyond this broad purpose, this paper will help researchers to develop a holistic and pragmatic research approach more systematically and coherently. It is hoped that this conceptual framework can potentially lead to higher employee productivity and retention.

Originality/value

The systematic literature review offers a novel framework that will allow future researchers to conduct and explore empirical studies in organisational leadership. The suggested propositions will direct future scholars and practitioners to explore solutions in which presenteeism can be recognised at work and managed to achieve practical application of RL within organisational settings.
How can an economic scenario generation model cope with abrupt changes in financial markets?
Authors: Lee Yi-Hsi , Hsieh Ming-Hua , Kuo Weiyu , Tsai Chenghsien Jason
Published: May 2021

Purpose

It is quite possible that financial institutions including life insurance companies would encounter turbulent situations such as the COVID-19 pandemic before policies mature. Constructing models that can generate scenarios for major assets to cover abrupt changes in financial markets is thus essential for the financial institution's risk management.

Design/methodology/approach

The key issues in such modeling include how to manage the large number of risk factors involved, how to model the dynamics of chosen or derived factors and how to incorporate relations among these factors. The authors propose the orthogonal ARMA–GARCH (autoregressive moving-average–generalized autoregressive conditional heteroskedasticity) approach to tackle these issues. The constructed economic scenario generation (ESG) models pass the backtests covering the period from the beginning of 2018 to the end of May 2020, which includes the turbulent situations caused by COVID-19.

Findings

The backtesting covering the turbulent period of COVID-19, along with fan charts and comparisons on simulated and historical statistics, validates our approach.

Originality/value

This paper is the first one that attempts to generate complex long-term economic scenarios for a large-scale portfolio from its large dimensional covariance matrix estimated by the orthogonal ARMA–GARCH model.
Dry sliding tribological properties of A356-SiCP aluminum matrix composites prepared by vacuum stir casting
Authors: Pan Jiaqi , Liu Xiaoshan , He Guoqiu , Ge Bin , Le Peiwen , Li Jingquan , Zhou Zhiqiang
Published: May 2021

Purpose

The purpose of this paper is to understand the effect of particle content, applied load and sliding speed on the tribological properties of A356-SiCP composites manufactured using a newly developed vacuum stir casting technique.

Design/methodology/approach

A356 alloy reinforced with 10, 15 and 20 vol% SiC particles was prepared by vacuum stir casting. Tribological tests were carried out on block-on-ring tribometer under dry sliding conditions, room temperature. Wear mechanism was investigated by scanning electron microscope and energy dispersion spectrum.

Findings

SiCP is homogeneously dispersed in the matrix. The increase in SiCP content decrease wear rate, but it leads to an increase in coefficient of friction. The wear rate increase and friction coefficient present different variation trends with increasing load. For A356-20%SiCP composite, when the load is less than 10 MPa, wear rate and friction coefficient under sliding speed of 400 rpm are lower than those of 200 rpm. Wear mechanism transition from abrasion, oxidation, delamination, adhesion to plastic flow as load and sliding speed increasing.

Practical implications

Results of this study will help guide the use of A356-SiCP in many automotive products such as brake rotors, brake pads, brake drums and pistons.

Originality/value

There are few paper studies the effect of particle content, applied load and sliding speed on the tribological properties of A356-SiCP composites. Aluminum matrix composites with uniform distribution of reinforcing particles were successfully prepared by using the newly developed vacuum stir casting technique.
Determinants of the use of accounting systems in microenterprises: evidence from Chile
Authors: Najera Ruiz Tonatiuh , Collazzo Pablo
Published: May 2021

Purpose

The purpose of this research is to contribute to knowledge-building on microenterprises in emerging economies, by assessing the determinants that drive their use of accounting systems.

Design/methodology/approach

A probabilistic model was developed to determine the likelihood that a micro-firm would adopt an accounting registry system as a function of a series of contingencies and personal characteristics of their owners/managers. Data from the Microentrepreneurship Survey (EME), from the National Institute of Statistics of Chile for 2017 was used.

Findings

The findings suggest that access to external funds, the size and the use of technology strongly influence micro-firms' adoption of accounting systems.

Research limitations/implications

Despite the richness and scope of the data, direct measurements of entrepreneurial orientation and environmental uncertainty, both central variables of the contingency theory, were missing. Hence, duly justified proxies were applied. It is also likely that there would be other variables that also influence the probability of using accounting tools.

Practical implications

The study contributes to a better understanding of microenterprises, and the factors that determine the use of accounting systems. The results highlight that public policies aimed at fostering microenterprises should facilitate access to technology and external funds. Consistent with previous studies, the authors’ findings highlight the importance of training owner/managers on issues related to their business.

Originality/value

This paper contributes to theory by arguably being the first study to confirm that contingency theory does explain the adoption of accounting systems in microenterprises in emerging countries.