bluuebunny/crossref_metadata_2025 huggingface dataset:
Individual variability in structural brain development from late childhood to young adulthood
Authors: Mills Kathryn L. , Siegmund Kimberly D. , Tamnes Christian K. , Ferschmann Lia , Wierenga Lara M. , Bos Marieke G. N. , Luna Beatriz , Herting Megan M.
Published: February 2021

A fundamental task in neuroscience is to characterize the brain’s developmental course. While replicable group-level models of structural brain development from childhood to adulthood have recently been identified, we have yet to quantify and understand individual differences in structural brain development. The present study examined individual variability and sex differences in changes in brain structure, as assessed by anatomical MRI, across ages 8.0–26.0 years in 269 participants (149 females) with three time points of data (807 scans), drawn from three longitudinal datasets collected in the Netherlands, Norway, and USA. We further investigated the relationship between overall brain size and developmental changes, as well as how females and males differed in change variability across development. There was considerable individual variability in the magnitude of changes observed for all included brain measures. However, distinct developmental patterns of change were observed for total brain and cortical gray matter, cortical thickness, and white matter surface area, with individuals demonstrating either stability or decreases in early adolescence, then almost universal decreases during mid-to-late adolescence, before returning to more variable patterns in early adulthood. White matter volume demonstrated a similar developmental pattern of variability, but with individuals shifting from increases to a majority stabilizing during mid-to-late adolescence. We observed sex differences in these patterns, and also an association between an individual’s brain size and their overall rate of change. The present study provides new insight as to the amount of individual variance in changes in structural morphometrics from late childhood to early adulthood in order to obtain a more nuanced picture of brain development. The observed individual- and sex-differences in brain changes also highlight the importance of further studying individual variation in developmental patterns in healthy, at-risk, and clinical populations.
A protein-based biosensor for detecting calcium by magnetic resonance imaging
Authors: Ozbakir Harun F. , Miller Austin D.C. , Fishman Kiara B. , Martins André F. , Kippin Tod E. , Mukherjee Arnab
Published: February 2021

Calcium-responsive contrast agents for magnetic resonance imaging (MRI) offer an attractive approach to noninvasively image neural activity with wide coverage in deep brain regions. However, current MRI sensors for calcium are based on synthetic architectures fundamentally incompatible with genetic technologies forin vivodelivery and targeting. Here, we present a protein-based MRI sensor for calcium, derived from a calcium-binding protein known as calprotectin. Calcium-binding causes calprotectin to sequester manganese. We demonstrate that this mechanism allows calprotectin to alter T1and T2weighted contrast in response to biologically relevant calcium concentrations. Corresponding changes in relaxation times are comparable to synthetic calcium sensors and exceed those of previous protein-based MRI sensors for other neurochemical targets. The biological applicability of calprotectin was established by detecting calcium in lysates prepared from a neuronal cell line. Calprotectin thus represents a promising path towards imaging neural activity by combining the benefits of MRI and protein sensors.
The protein modifier SUMO is critical for Arabidopsis shoot meristem maintenance at warmer ambient temperatures
Authors: Hammoudi Valentin , Beerens Bas , Jonker Martijs J. , Helderman Tieme A. , Vlachakis Georgios , Giesbers Marcel , Kwaaitaal Mark , van den Burg Harrold A.
Published: February 2021

Short heat waves (>37°C) are extremely damaging to non-acclimated plants and their capacity to recover from heat stress is key for their survival. To acclimate, the HEAT SHOCK TRANSCRIPTION FACTOR A1 (HSFA1) subfamily activates a transcriptional response that resolves incurred damages. In contrast, little is known how plants acclimate to sustained non-detrimental warm periods at 27-28°C. Plants respond to this condition with a thermomorphogenesis response. In addition, HSFA1 is critical for plant survival during these warm periods. We find that SUMO, a protein modification whose conjugate levels rise sharply during acute heat stress in eukaryotes, is critical too for plant longevity during warm periods, in particular for normal shoot meristem development. The known SUMO ligases were not essential to endure these warm periods, alone or in combination. Thermo-lethality was also not seen when plants lacked certain SUMO proteases or when SUMO chain formation was blocked. The SUMO-dependent thermo-resilience was as well independent of the autoimmune phenotype of the SUMO mutants. As acquired thermotolerance was normal in thesumo1/2knockdown mutant, our data thus reveal a role for SUMO in heat acclimation that differs from HSFA1 and SIZ1. We conclude that SUMO is critical for shoot meristem integrity during warm periods.

Highlight

The protein modifier SUMO governs shoot meristem maintenance in Arabidopsis allowing sustained rosette development when plants endure a sustained warm non-detrimental period of 28 degrees Celsius.
Genomic regions associated withMycoplasma ovipneumoniaepresence in nasal secretions of domestic sheep
Authors: Mousel Michelle R. , White Stephen N. , Herndon Maria K. , Herndon David R. , Taylor J. Bret , Becker Gabrielle M. , Murdoch Brenda M.
Published: February 2021

Mycoplasma ovipneumoniaecontributes to polymicrobial pneumonia in domestic sheep. Elucidation of host genetic components toM. ovipneumoniaenasal detection would have the potential to reduce the incidence of pneumonia. Nasal mucosal secretions were collected from 647 sheep from a large US sheep flock. Ewes of three breeds (Polypay n=222, Rambouillet n=321, and Suffolk n=104) ranging in age from one to seven years, were sampled at three different times of the production cycle (February, April, and September/October) over four years (2015 to 2018). The presence and quantity ofM. ovipneumoniaewas determined using a species-specific qPCR with 3 to 10 sampling times per sheep. Breed (P<0.001), age (P<0.024), sampling time (P<0.001), and year (P<0.001) of collection affected log10transformedM. ovipneumoniaeDNA copy number, where Rambouillet had the lowest (P<0.0001) compared with both Polypay and Suffolk demonstrating a possible genetic component to detection. Samples from yearlings, April, and 2018 had the highest (P<0.046) detected DNA copy number mean. Sheep genomic DNA was genotyped with the Illumina OvineHD BeadChip. Principal component analysis identified most of the variation in the dataset was associated with breed. Therefore, genome wide association analysis was conducted with a mixed model (EMMAX), with principle components 1 to 6 as fixed and a kinship matrix as random effects. Genome-wide significant (P<9×10−8) SNPs were identified on chromosomes 6 and 7 in the all-breed analysis. Individual breed analysis had genome-wide significant (P<9×10−8) SNPs on chromosomes 3, 4, 7, 9, 10, 15, 17, and 22. Annotated genes near these SNPs are part of immune (ANAPC7, CUL5, TMEM229B, PTPN13), gene translation (PIWIL4), and chromatin organization (KDM2B) pathways. Immune genes are expected to have increased expression when leukocytes encounterM. ovipneumoniaewhich would lead to chromatin reorganization. Work is underway to narrow the range of these associated regions to identify the underlying causal mutations.
AlnC: An extensive database of long non-coding RNAs in Angiosperms
Authors: Singh Ajeet , Vivek AT , Kumar Shailesh
Published: February 2021

Long non-coding RNAs (lncRNAs) play a major role in diverse biological processes that are contemplated to have diverse regulatory roles in plants. While lncRNAs have been described and annotated in major plant species, many of plant species lack annotated lncRNAs despite the availability of transcriptome data in public repositories. In this study, we have identified and annotated the lncRNAs in the transcriptomic data from the 1000 plant genome project (1KP), and developed a user-friendly, open-access database called AlnC. This can be used for the exploration of lncRNAs in 682 Angiosperm plants. The current version of AlnC offers 10,855,598 annotated lncRNA transcripts across 809 sample tissues of diverse flowering plants. To enhance the AlnC interface, we have provided the features for browsing, searching and downloading of lncRNA data, interactive graphics, and online BLAST service. In addition to these information, each lncRNA record is annotated with possible Short open reading frames (e.g. sORFs) to facilitate the study of peptides encoded within lncRNAs. With this user-friendly interface, we assume that AlnC will serve as a rich source of lncRNAs that will contribute to small-and large-scale studies in a wide range of flowering plants.
Limitations of bacterial culture, viral PCR, and tulathromycin susceptibility test methods from upper respiratory tract samples in predicting the outcome of tulathromycin control or treatment of bovine respiratory disease in high risk feeder heifers
Authors: Sarchet Jeffrey J. , Pollreisz John H. , Bechtol David T. , Blanding Mitch , Saltman Roger L. , Taube Patrick C.
Published: February 2021

A cross-sectional prospective cohort study to correlate BRD clinical outcomes for tulathromycin metaphylaxis/treatment for bovine respiratory disease (BRD) with the results of bacterial culture and tulathromycin susceptibility from isolates of deep nasopharyngeal swabs (DNS) as well as viral polymerase chain reaction (PCR) results from nasal swabs revealed poor correlation of bacterial culture and tulathromycin susceptibility with response to tulathromycin metaphylaxis or treatment. 1031 heifers, assumed to be at high-risk (>40% expected BRD morbidity rates), were procured and transported to a research feedlot in Texas. Isolation rates from DNS collected on arrival and at first treatment respectively were:Mannheimia haemolytica(10.9% & 34.1%);Pasteurella multocida(10.4% & 7.4%);Mycoplasma bovis(1.0% & 36.6%); andHistophilus somni (0.7% & 6.3%). Prevalence of BRD viral nucleic acid on nasal swabs collected at first treatment were: PI-3V (34.1%); BVDV (26.3%); BoHV-1 (10.8%); and BRSV (54.1%). Increased relative risk of treatment failure was associated with positive viral PCR results, PI-3V (1.2644), BVDV (1.3917), BHV-1 (1.5156), and BRSV (1.3474) from nasal swabs collected at first pull and culture ofM. haemolytica(1.2284) from DNS collected at arrival; however, no other statistically predictable risk of treatment outcomes were measured from DNS for bacterial isolation or tulathromycin susceptibility forM. haemolyticaorP. multocidaat arrival or first treatment. Predictive values of bacterial culture and tulathromycin susceptibility were substantially lower than the 85% level expected with susceptibility testing. These results indicate tulathromycin susceptibility testing of isolates ofM. haemolyticaorP. multocidafrom DNS collected on arrival or at first pull unreliably predict clinical efficacy of tulathromycin for BRD control or treatment most likely due to impacts of unpredictable risk factors and other viral and/or bacterial BRD comorbidities.
ATP-dependent Clp protease subunit C1, HvClpC1, is a strong candidate gene for barley variegation mutantluteostriansas revealed by genetic mapping and genomic re-sequencing
Authors: Li Mingjiu , Guo Ganggang , Pidon Hélène , Melzer Michael , Prina Alberto R. , Börner Thomas , Stein Nils
Published: February 2021

Implementation of next-generation sequencing in forward genetic screens greatly accelerated gene discovery in species with larger genomes, including many crop plants. In barley, extensive mutant collections are available, however, the causative mutations for many of the genes remains largely unknown. Here we demonstrate how a combination of low-resolution genetic mapping, whole-genome resequencing and comparative functional analyses provides a promising path towards candidate identification of genes involved in plastid biology and / or photosynthesis, even if genes are located in recombination poor regions of the genome. As a proof of concept, we simulated the prediction of a candidate gene for the recently cloned variegation mutantalbostrians(HvAST/HvCMF7) and adopted the approach for suggestingHvClpC1as candidate gene for the yellow-green variegation mutantluteostrians.

Author Summary

Forward genetics is an approach of identifying a causal gene for a mutant phenotype and has proven to be a powerful tool for dissecting the genetic control of biological processes in many species. A large number of barley mutants was generated in the 1940s to 1970s when mutation breeding programs flourished. Genetic dissection of the causative mutations responsible for the phenotype, however, lagged far behind, limited by lack of molecular markers and high-throughput genotyping platforms. Next-generation sequencing technologies have revolutionized genomics, facilitating the process of identifying mutations underlying a phenotype of interest. Multiple mapping-by-sequencing or cloning-by-sequencing strategies were established towards fast gene discovery. In this study, we used mapping-by-sequencing to identify candidate genes within coarsely delimited genetic intervals, for two variegation mutants in barley –luteostriansandalbostrians. After testing the approach using the example of the previously clonedalbostriansgeneHvAST, the geneHvClpC1could be delimited as candidate gene forluteostrians.The mapping-by-sequencing strategy implemented here is generally suited for surveying barley mutant collections for phenotypes affecting fundamental processes of plant morphology, physiology and development.
Genome-Wide CRISPR Screening Identifies BRD9 as a Druggable Component of Interferon-Stimulated Gene Expression and Antiviral Activity
Authors: Börold Jacob , Eletto Davide , Busnadiego Idoia , Mair Nina K. , Moritz Eva , Schiefer Samira , Schmidt Nora , Petric Philipp P. , Wong W. Wei-Lynn , Schwemmle Martin , Hale Benjamin G.
Published: February 2021

Transient interferon (IFN) induction of IFN-stimulated genes (ISGs) creates a formidable protective antiviral state. However, loss of appropriate control mechanisms can result in constitutive pathogenic ISG upregulation. Here, we used genome-wide loss-of-function screening to establish genes critical for IFN signaling, identifying all expected members of the JAK-STAT pathway and the previously unappreciated bromodomain-containing protein 9 (BRD9), a defining subunit of non-canonical BAF (ncBAF) chromatin remodeling complexes. Genetic knock-out or small-molecule mediated degradation of BRD9 limited IFN-induced expression of a subset of ISGs in multiple cell-types, and prevented IFN from exerting full antiviral activity against several RNA and DNA viruses. Mechanistically, BRD9 acts at the level of ISG transcription, exhibits a proximal association with STAT2 following IFN stimulation, and relies on its intact acetyl-binding bromodomain and unique ncBAF scaffolding function for activity. Given its druggability, BRD9 may be an attractive target for dampening constitutive ISG expression under certain pathogenic autoinflammatory conditions.
Microglia control cerebral blood flow and neurovascular coupling via P2Y12R-mediated actions
Authors: Császár Eszter , Lénárt Nikolett , Cserép Csaba , Környei Zsuzsanna , Fekete Rebeka , Pósfai Balázs , Balázsfi Diána , Hangya Balázs , Schwarcz Anett D. , Szöllősi Dávid , Szigeti Krisztián , Máthé Domokos , West Brian L. , Sviatkó Katalin , Brás Ana Rita , Mariani Jean-Charles , Kliewer Andrea , Lenkei Zsolt , Hricisák László , Benyó Zoltán , Baranyi Mária , Sperlágh Beáta , Menyhárt Ákos , Farkas Eszter , Dénes Ádám
Published: February 2021

Microglia, the main immunocompetent cells of the brain regulate neuronal function in health and disease, but their contribution to cerebral blood flow (CBF) remained elusive. Here we identify microglia as important modulators of CBF both under physiological conditions and during hypoperfusion. We show that microglia establish direct purinergic contacts with cells in the neurovascular unit that shape cerebral perfusion in both mice and humans. Surprisingly, the absence of microglia or blockade of microglial P2Y12 receptor (P2Y12R) substantially impairs neurovascular coupling in the barrel cortex after whisker stimulation. We also reveal that hypercapnia, which is associated with acidification, induces microglial adenosine production, while depletion of microglia reduces brain pH and impairs hypercapnia-induced vasodilation. Furthermore, the absence or dysfunction of microglia markedly impairs adaptation to hypoperfusion via P2Y12R after transient unilateral common carotid artery occlusion, which is also influenced by CX3CR1-mediated actions. Thus, our data reveal a previously unrecognized role for microglia in CBF regulation with broad implications for common neurological diseases.
Alpha-arrestins Aly1 and Aly2 regulate trafficking of the glycerophosphoinositol transporter Git1 and impact phospholipid homeostasis
Authors: Robinson Benjamin P. , Hawbaker Sarah , Chiang Annette , Jordahl Eric M. , Anaokar Sanket , Nikiforov Alexiy , Bowman Ray W. , Ziegler Philip , McAtee Ceara K. , Patton-Vogt Jana , O’Donnell Allyson F.
Published: February 2021

Phosphatidylinositol (PI) is an essential phospholipid and critical component of membrane bilayers. The complete deacylation of PI by phospholipases of the B-type leads to the production of intracellular and extracellular glycerophosphoinositol (GPI), a water-soluble glycerophosphodiester. Extracellular GPI is transported into the cell via Git1, a member of the Major Facilitator Superfamily of transporters that resides at the plasma membrane in yeast. Once internalized, GPI can be degraded to produce inositol, phosphate and glycerol, thereby contributing to reserves of these building blocks. Not surprisingly,GIT1gene expression is controlled by nutrient balance, with limitation for phosphate or inositol each increasingGIT1expression to facilitate GPI uptake. Less is known about how Git1 protein levels or localization are controlled. Here we show that the α-arrestins, an important class of protein trafficking adaptor, regulate the localization of Git1 in a manner dependent upon their association with the ubiquitin ligase Rsp5. Specifically, α-arrestin Aly2 is needed for effective Git1 internalization from the plasma membrane under basal conditions. However, in response to GPI-treatment of cells, either Aly1 or Aly2 can promote Git1 trafficking to the vacuole. Retention of Git1 at the cell surface, as occurs inaly1Δaly2Δ cells, results in impaired growth in the presences of excess exogenous GPI and results in increased uptake of radiolabeled GPI, suggesting that accumulation of this metabolite or its downstream products leads to cellular toxicity. We further show that regulation of α-arrestin Aly1 by the protein phosphatase calcineurin improves both steady-state and ligand-induced trafficking of Git1 when a mutant allele of Aly1 that mimics the dephosphorylated state at calcineurin-regulated residues is employed. Thus, calcineurin regulation of Aly1 is important for the GPI-ligand induced trafficking of Git1 by this α-arrestin, however, the role of calcineurin in regulating Git1 trafficking is much broader than can simply be explained by regulation of the α-arrestins. Finally, we find that loss of Aly1 and Aly2 leads to an increase in phosphatidylinositol-3-phosphate on the limiting membrane of the vacuole and this alteration is further exacerbated by addition of GPI, suggesting that the effect is at least partially linked to Git1 function. Indeed, loss of Aly1 and Aly2 leads to increased incorporation of inositol label from3H-inositol-labelled GPI into PI, confirming that internalized GPI influences PI synthesis and indicating a role for the α-arrestins in regulating the process.
Bronchoalveolar lavage affects thorax computed tomography of healthy and SARS-CoV-2 infected rhesus macaques (Macaca mulatta)
Authors: Maaskant Annemiek , Meijer Lisette , Bakker Jaco , van Geest Leo , Zijlmans Dian G.M. , Langermans Jan A.M. , Verschoor Ernst J. , Stammes Marieke A.
Published: February 2021

Medical imaging as method to assess the longitudinal process of a SARS-CoV-2 infection in non-human primates is commonly used in research settings. Bronchoalveolar lavage (BAL) is also regularly used to determine the local virus production and immune effects of SARS-CoV-2 in the lower respiratory tract. However, the potential interference of those two diagnostic modalities with each other is unknown in non-human primates. The current study investigated the effect and duration of BAL on computed tomography (CT) in both healthy and experimentally SARS-CoV-2-infected female rhesus macaques (Macaca mulatta). In addition, the effect of subsequent BALs was reviewed. Thorax CTs and BALs were obtained from four healthy animals and 11 experimentally SARS-CoV-2-infected animals. From all animals, CTs were obtained just before BAL, and 24 hours post-BAL. Additionally, from the healthy animals, CTs immediately after and four hours post-BAL were obtained. Thorax CTs were evaluated for alterations in lung density, measured in Hounsfield units, and a visual semi-quantitative scoring system. An increase in the lung density was observed on the immediately post-BAL CT but resolved within 24 hours in the healthy animals. In the infected animals, a significant difference in both the lung density and CT score was still found 24 hours after BAL. Furthermore, the differences between timepoints in CT score were increased for the second BAL. These results indicate that the effect of BAL on infected lungs is not completed within the first 24 hours. Therefore, it is of importance to acknowledge the interference between BAL and CT in rhesus macaques.
Modulation of SARS-CoV-2 Spike-induced Unfolded Protein Response (UPR) in HEK293T cells by selected small chemical molecules
Authors: Balakrishnan B , Lai K
Published: February 2021

Coronaviruses (CoV) exploits the endoplasmic reticulum (ER) of the host cells for replication and in doing so, increases ER stress. evokes Unfolded Protein Response (UPR) and possibly autophagy, which could all attribute to the pathophysiology of the viral infections. To date, little is known about the roles of ER stress, UPR, and autophagy in SARS-CoV-2 infection. Here we over-expressed the viral Spike (S) protein in cultured HEK293T cells, as it has been shown that such protein is largely responsible for UPR activation in other CoV-infected cells. We noticed, in the transfected cells, heightened ER stress, activation of the PERK-eIF2α arm of the UPR, induction of autophagy and cell death. When we treated the transfected cells with Tauroursodeoxycholic acid (TUDCA), 4-phenyl butyric acid (PBA), Salubrinal, Trazadone hydrochloride, and Dibenzoylmethane (DBM), we saw reduced the BiP/GRP78 levels, but only PBA and TUDCA could significantly diminish the levels of peIF2α and autophagy expression.
Ventral hippocampus mediates the context-dependence of two-way signaled avoidance in male rats
Authors: Oleksiak Cecily R. , Ramanathan Karthik R. , Miles Olivia W. , Perry Sarah J. , Maren Stephen , Moscarello Justin M.
Published: February 2021

Considerable work indicates that instrumental responding is context-dependent, but the neural mechanisms underlying this phenomenon are poorly understood. Given the important role for the hippocampal formation in contextual processing, we hypothesized that reversible inactivation of the hippocampus would impair the context-dependence of active avoidance. To test this hypothesis, we used a two-way signaled active avoidance (SAA) task that requires rats to shuttle across a divided chamber during a tone CS in order to avoid a footshock US. After training, avoidance responding was assessed in an extinction test in both the training context and a novel context in a counterbalanced order. Rats performed significantly more avoidance responses in the training context than in the novel context, demonstrating the context-dependence of shuttle avoidance behavior. To examine the role of the hippocampus in the context-dependence of SAA, we reversibly inactivated either the dorsal (DH) or ventral hippocampus (VH) prior to testing. Inactivation of the VH eliminated the context-dependence of SAA and elevated avoidance responding in the novel context to levels similar to that expressed in the training context. In contrast, DH inactivation had no effect on avoidance in either context, and neither manipulation affected freezing behavior. Therefore, the integrity of the VH, but not DH, is required for the expression context-dependence of avoidance behavior.
High Affinity Chimeric Antigen Receptor with Cross-Reactive scFv to Clinically Relevant EGFR Oncogenic Isoforms
Authors: Thokala Radhika , Binder Zev A. , Yin Yibo , Zhang Logan , Zhang Jiasi Vicky , Zhang Daniel Y. , Milone Michael C. , Ming Guo-li , Song Hongjun , O’Rourke Donald M.
Published: February 2021

Tumor heterogeneity is a key reason for therapeutic failure and tumor recurrence in glioblastoma (GBM). Our chimeric antigen receptor (CAR) T cell (2173 CAR T cells) clinical trial (NCT02209376) against Epidermal growth factor receptor (EGFR) variant III (EGFRvIII) demonstrated successful trafficking of T cells across the blood brain barrier into GBM active tumor sites. However, CAR T cell infiltration was associated only with a selective loss of EGFRvIII+ tumor, demonstrating little to no effect on EGFRvIII-tumor cells. Post-CAR T treated tumor specimens showed continued presence of EGFR amplification and oncogenic EGFR extracellular domain (ECD) missense mutations, despite loss of EGFRvIII. To address tumor escape, we generated an EGFR-specific CAR by fusing monoclonal antibody (mAb) 806 to a 4-1BB co-stimulatory domain. The resulting construct was compared to 2173 CAR T cells in GBM, using in vitro and in vivo models. 806 CAR T cells specifically lysed tumor cells and secreted cytokines in response to amplified EGFR, EGFRvIII, and EGFR-ECD mutations in U87MG cells, GBM neurosphere-derived cell lines, and patient-derived GBM organoids. 806 CAR T cells did not lyse fetal brain astrocytes or primary keratinocytes to a significant degree. They also exhibited superior antitumor activity in vivo when compared to 2173 CAR T cells. The broad specificity of 806 CAR T cells to EGFR alterations gives us the potential to target multiple clones within a tumor and reduce opportunities for tumor escape via antigen loss.
Primary tumor associated macrophages activate programs of invasion and dormancy in disseminating tumor cells
Authors: Borriello Lucia , Coste Anouchka , Sharma Ved P. , Karagiannis George S. , Lin Yu , Wang Yarong , Ye Xianjun , Duran Camille L. , Chen Xiaoming , Dalla Erica , Singh Deepak K. , Oktay Maja H. , Aguirre-Ghiso Julio A. , Condeelis John , Entenberg David
Published: February 2021

Metastases are initiated by disseminated tumor cells (DTCs) that depart from the primary tumor and colonize target organs. Growing evidence suggests that the microenvironment of the primary tumor lesion primes DTCs to display dormant or proliferative fates in target organs. However, the manner in which events taking place in the primary tumor influence DTC fate, sometimes long after dissemination, remains poorly understood. With the advent of a novel intravital imaging technique called the Window for High-Resolution Intravital Imaging of the Lung (WHRIL), we have, for the first time, been able to study the live lung longitudinally and follow the fate of individual DTCs that spontaneously disseminate from orthotopic breast tumors. We find, across several models, a high rate of success for tumor cells to complete the initial steps of the metastatic cascade in the secondary site, including retention of DTCs in the lung vasculature, speed of extravasation, and survival after extravasation. Importantly, initiation of metastatic growth was controlled primarily by a rate-limiting step that occurred post-extravasation and at the stage of the conversion of single DTCs from a dormant to a proliferative state. Detailed analysis of these events revealed that, even before dissemination, a subset of macrophages within the primary tumor induces, in tumor cells that are about to disseminate, the expression of proteins that regulate a pro- dissemination (MenaINV) and pro-dormancy (NR2F1) phenotype. Surprisingly, if cancer cells are intravenously injected, the rate limiting stages of MenaINV-associated extravasation, dormancy, and other parameters, are lost or altered in a way that impacts how DTCs progress through the metastatic cascade. Our work provides novel insight into how specific primary tumor microenvironments prime a subpopulation of cells for dissemination and dormancy. We also propose that dissecting mechanisms of metastasis, or testing anti-metastatic therapies, may yield results of limited application if derived from models that do not follow spontaneous dissemination.

SIGNIFICANCE

This study provides important insight into the contribution of primary tumor microenvironmental niches to cancer metastasis by identifying the manner in which these niches spawn subpopulations of DTCs that are primed for dissemination and dormancy in the secondary site. This study may provide novel targets that could be inhibited to prevent successful colonization of the secondary site and, hence, metastasis.
The chicken or the egg? Plastome evolution and a novel loss of the inverted repeat in papilionoid legumes
Authors: Lee Chaehee , Choi In-Su , Cardoso Domingos , de Lima Haroldo C. , de Queiroz Luciano P. , Wojciechowski Martin F. , Jansen Robert K. , Ruhlman Tracey A
Published: February 2021

The plastid genome (plastome), while surprisingly constant in gene order and content across most photosynthetic angiosperms, exhibits variability in several unrelated lineages. During the diversification history of the legume family Fabaceae, plastomes have undergone many rearrangements, including inversions, expansion, contraction and loss of the typical inverted repeat (IR), gene loss and repeat accumulation in both shared and independent events. While legume plastomes have been the subject of study for some time, most work has focused on agricultural species in the IR-lacking clade (IRLC) and the plant modelMedicago truncatula. The subfamily Papilionoideae, which contains virtually all of the agricultural legume species, also comprises most of the plastome variation detected thus far in the family. In this study 33 newly sequenced plastomes of papilionoid legumes and outgroups were evaluated, along with 34 publicly available sequences, to assess plastome structural evolution in the subfamily. In an effort to examine plastome variation across the subfamily, just ∼20% of the sampling represents the IRLC with the remainder selected to represent the early-branching papilionoid clades. A number of IR-related and repeat-mediated changes were identified and examined in a phylogenetic context. Recombination between direct repeats associated withycf2resulted in intraindividual plastome heteroplasmy. Although loss of the inverted repeat has not been reported in legumes outside of the IRLC, one genistoid taxon was found to completely lack the typical plastome IR. The role of the IR and non-IR repeats in driving plastome change is discussed.

Significance statement

Comparative genomic approaches employing plastid genomes (plastomes) have revealed that they are more variable across angiosperms than previously suggested. This study examined 64 species of Fabaceae and outgroups, including 33 newly sequenced taxa, to explore plastome structural evolution of the subfamily Papilionoideae in a phylogenetic context. Several unusual features of the inverted repeat highlight the importance of recombination in plastomic structural changes within and between individuals and species.
Plasticity of body axis polarity inHydraregeneration under constraints
Authors: Livshits Anton , Garion Liora , Maroudas-Sacks Yonit , Shani-Zerbib Lital , Keren Kinneret , Braun Erez
Published: February 2021

One of the major events in animal morphogenesis is the emergence of a polar body axis. Here, we combine classic grafting techniques with live imaging to study the emergence of body axis polarity during whole body regeneration inHydra. Composite tissues are made by fusing two rings, excised from separate animals, in different configurations that vary in the polarity and original positions of the rings along the body axes of the parent animals. Under frustrating initial configurations, body axis polarity that is otherwise stably inherited from the parent animal, can become labile and even be reversed. Importantly, the site of head regeneration exhibits a strong bias toward the edges of the tissue, even when this involves polarity reversal. In particular, we observe head formation at an originally aboral tissue edge, which is not compatible with models ofHydraregeneration based only on preexisting morphogen gradients or an injury response. Rather, we suggest that the structural bias toward head formation at the doublets’ edge is reinforced by the presence of a defect in the organization of the supra-cellular actin fibers, which invariably forms at the edge as the tissue heals. In this scenario, the defect supports head formation at the edge, even though a defect is neither required nor sufficient for head formation. Altogether, our results suggest that body axis determination is an integrated process that arises from the dynamic interplay between mechanical feedback and signaling processes.
Maize inbred line B96 is the source of large-effect loci for resistance to generalist but not specialist spider mites
Authors: Bui Huyen , Greenhalgh Robert , Gill Gunbharpur S. , Ji Meiyuan , Kurlovs Andre H. , Ronnow Christian , Lee Sarah , Ramirez Ricardo A. , Clark Richard M.
Published: February 2021

Maize (Zea mays subsp. mays) yield loss from arthropod herbivory is substantial. While the basis of resistance to major insect herbivores has been comparatively well-studied in maize, less is known about resistance to spider mite herbivores, which are distantly related to insects and feed by a different mechanism. Two spider mites, the generalist Tetranychus urticae, and the grass-specialist Oligonychus pratensis, are notable pests of maize, especially during drought conditions. We assessed the resistance to both mite species of 38 highly diverse maize lines, including several previously reported to be resistant to one or the other mite species. We found that line B96, as well as its derivatives B49 and B75, were highly resistant to T. urticae. In contrast, neither these three lines, nor any others included in our study, were notably resistant to O. pratensis. Quantitative trait locus (QTL) mapping with F2 populations from crosses of B49, B75, and B96 to susceptible B73 identified a large-effect QTL on chromosome 6 as underlying T. urticae resistance in each line, with an additional QTL on chromosome 1 in B96. Genome sequencing and haplotype analyses identified B96 as the apparent sole source of resistance haplotypes. Our study identifies loci for use in maize breeding programs for T. urticae resistance, as well as to assess if the molecular-genetic basis of spider mite resistance is shared with insect pests of maize, as B96 is also among the most resistant known maize lines to several insects, including the European corn borer, Ostrinia nubilalis.

Key message Maize

(Zea mays subsp. mays) inbred lines B49, B75, and B96 harbor large-effect loci for resistance to the generalist spider mite Tetranychus urticae, but not the specialist Oligonychus pratensis.
High-Resolution Chemical Mapping and Microbial Identification of Rhizosphere using Correlative Microscopy
Authors: Bandara Chaturanga D. , Schmidt Matthias , Davoudpour Yalda , Stryhanyuk Hryhoriy , Richnow Hans H. , Musat Niculina
Published: February 2021

During the past decades, several stand-alone and combinatory methods have been developed to investigate the chemistry (i.e. mapping of elemental, isotopic and molecular composition) and the role of microbes in soil and rhizosphere. However, none of these approaches are currently capable of characterizing soil-root-microbe interactions simultaneously in their spatial arrangement. Here we present a novel approach that allows chemical and microbial identification of the rhizosphere at micro-to nano-meter spatial resolution. Our approach includes i) a resin embedding and sectioning method suitable for simultaneous correlative characterization ofZea maysrhizosphere, ii) an analytical work flow that allows up to six instruments/techniques to be used correlatively, and iii) data and image correlation. Hydrophilic, immunohistochemistry compatible, low viscosity LR white resin was used to embed the rhizosphere sample. We employed waterjet cutting and avoided polishing the surface to prevent smearing of the sample surface at nanoscale. Embedding quality was analyzed by Helium Ion Microscopy (HIM). Bacteria in the embedded soil was identified by Catalyzed Reporter Deposition-FluorescenceIn SituHybridization (CARD-FISH) to avoid interferences from high levels of auto fluorescence emitted by soil particles and organic matter. Chemical mapping of the rhizosphere was done by Scanning Electron Microscopy (SEM) with Energy-dispersive X-ray analysis (SEM-EDX), Time-of-Flight Secondary Ion Mass Spectrometry (ToF-SIMS), nano-focused Secondary Ion mass Spectrometry (nanoSIMS), and confocal Raman spectroscopy (µ-Raman). High-resolution correlative characterization by six different techniques followed by image registration shows that this method can meet the demanding requirements of multiple characterization techniques to chemically map the rhizosphere and identify spatial organization of bacteria. Finally, we presented individual and correlative workflows for imaging and image registration to analyze data. We hope this method will be a platform to combine various 2D analytics for an ample understanding of the rhizosphere processes and their ecological significance.

Graphical Abstract
Development of the entorhinal cortex occurs via parallel lamination during neurogenesis
Authors: Liu Yong , Bergmann Tobias , Mori Yuki , Vidal Juan Miguel Peralvo , Pihl Maria , Vasistha Navneet A , Thomsen Preben Dybdahl , Seemann Stefan E , Gorodkin Jan , Hyttel Poul , Khodosevich Konstantin , Witter Menno P , Hall Vanessa Jane
Published: February 2021

The entorhinal cortex (EC) is the spatial processing center of the brain and structurally is an interface between the three layered paleocortex and six layered neocortex, known as the periarchicortex. Limited studies indicate peculiarities in the formation of the EC such as early emergence of cells in layers (L) II and late deposition of LIII, as well as divergence in the timing of maturation of cell types in the superficial layers. In this study, we examine developmental events in the entorhinal cortex using an understudied model in neuroanatomy and development, the pig and supplement the research with BrdU labeling in the developing mouse EC. We determine the pig serves as an excellent anatomical model for studying human neurogenesis, given its long gestational length, presence of a moderate sized outer subventricular zone and early cessation of neurogenesis during gestation. Immunohistochemistry identified prominent clusters of OLIG2+ oligoprogenitor-like cells in the superficial layers of the lateral EC (LEC) that are sparser in the medial EC (MEC). These are first detected in the subplate during the early second semester. MRI analyses reveal an acceleration of EC growth at the end of the second trimester. BrdU labeling of the developing MEC, shows the deeper layers form first and prior to the superficial layers, but the LV/VI emerges in parallel and the LII/III emerges later, but also in parallel. We coin this lamination pattern parallel lamination. The early-born Reln+ stellate cells in the superficial layers express the classic LV marker, Bcl11b (Ctip2) and arise from a common progenitor that forms the late deep layer LV neurons. In summary, we characterize the developing EC in a novel animal model and outline in detail the formation of the EC. We further provide insight into how the periarchicortex forms in the brain, which differs remarkably to the inside-out lamination of the neocortex.
ARGONAUTE10 is required for cell fate specification and the control of formative cell divisions in the Arabidopsis root meristem
Authors: Arbi Nabila El , Schürholz Ann-Kathrin , Schiffner Alexei , Prados Inés Hidalgo , Böhme Friedrich , Wenzl Christian , Zhao Xinai , Zeng Jian , Lohmann Jan U. , Wolf Sebastian
Published: February 2021

A key question in plant biology is how oriented cell divisions are integrated with patterning mechanisms to generate organs with adequate cell type allocation. In the root vasculature, a miRNA gradient controls the abundance of HD-ZIP III transcription factors, which in turn control cell fate and spatially restrict vascular cell proliferation to specific cells. Here, we show that a functional miRNA gradient requires an opposing gradient of ARGONAUTE10, which sequesters miRNAs to protect HD-ZIP III transcripts from degradation. In the absence of ARGONAUTE10, xylem precursor cells undergo periclinal divisions that lead to continuous strands of differentiated xylem elements at ectopic positions. Notably, periclinal daughter cells maintain xylem identity even when they are located outside of the xylem axis, resulting in disrupted tissue boundaries. We further demonstrate that ARGONAUTE10 and HD-ZIP IIIs buffer cytokinin signalling to control formative cell divisions, providing a framework for integration of phytohormone and miRNA-mediated patterning.
Pivoting authentic assessment to an accounting podcast during COVID-19
Authors: Halabi Abdel Karim
Published: February 2021

Purpose

This paper aims to describe how the COVID-19 pivot to online teaching enabled a student-produced podcast assessment to be created and substituted for the final examination in an MBA accounting course.

Design/methodology/approach

This paper provides instructors’ reflections and feedback from students on the usefulness of podcasts as an assessment tool in accounting education. Also included are the assignment instructions and a marking rubric which can be adapted as a sharing network.

Findings

The pivot to the authentic podcast assessment proved to be a very positive outcome during COVID-19 for instructors and students. The students embraced and enjoyed the task, and importantly it was an efficient learning experience that connected theory to practice, while preserving authenticity.

Originality/value

Podcasts have grown in popularity and have been widely used with students as receivers. The accounting education literature is however devoid of instances where podcasts have been used as an assessment tool. Although the assessment was changed because of the COVID-19 pandemic, it has ongoing applicability as a useful assignment in future semesters.
COVID-19: a shock to the system-reflections from practice by safeguarding adults board managers
Authors: Lloyd-Smith Walter , Bampton Lindsey , Caldwell Julia , Eader Anita , Jones Helen , Turner Steven
Published: February 2021

Purpose

This paper aims to set out to share the reflections of safeguarding adult board managers as they worked through what is likely to be just the first wave of the coronavirus COVID-19 pandemic.

Design/methodology/approach

The paper draws on the experience of small number of safeguarding adult board managers who have provided reflections from practice.

Findings

This paper illustrates just some of the responses developed by safeguarding adult board managers and their boards to continue to deliver the work of safeguarding those at risk of abuse and harm in the face of unprecedented impact of the coronavirus COVID-19 pandemic on a key aspect of the safeguarding adult system in England.

Originality/value

The reflections reported here are not intended to offer a representative commentary on the experiences of those who oversee and manage safeguarding adults’ boards. It is intention to provide a flavour of some of the challenges and dilemmas faced and some of the creative solutions to address them used by one group of adult safeguarding practitioners.
A network group booking model for airline revenue management
Authors: Venkataraman Sri Vanamalla , Kaushik Ankit , Mishra Siddharth
Published: February 2021

Purpose

Airlines use various analytical techniques to optimally control seats in its various fare classes. Most literature on inventory control does not discuss policies for group arrivals. This study aims to address the literature gap in determining an optimal booking policy which considers the dynamics of group behaviour with respect to cancellations and refunds.

Design/methodology/approach

An analytical model by which bid price control mechanism can be applied to group bookings is developed through this study.

Findings

Numerical experiments are performed to demonstrate the analytical model under various scenarios. A comparison of the model with the traditional model indicates an increase in the total revenue generated.

Originality/value

The novelty of this work is in modelling the dynamics of group behaviour in a network of flights, and it contributes to the literature on revenue management.
Microwave-assisted synthesis of disazothiazolone dyes as antibacterial agents and their application in polyester printing
Authors: Ahmed Ebtsam Abdelmowla , Elgemeie Galal , Ahmed Kawther Abd-Elzaher
Published: February 2021

Purpose

This study aims to represent a successful simple method for the synthesis of some novel dyes based on thiazole derivatives and their applications in textile printing.

Design/methodology/approach

2-(benzo[d]thiazol-2-ylmethyl)thiazol-4(5H)-one compound is prepared by convention heating and microwave technique then used as a coupling agent, which reacts with different diazonium Salt to form diazo dyes.

Findings

The synthesized diazo dyes are confirmed via spectral data (IR,1H-NMR, 13C-NMR and Mass spectra). The dyes are used to print polyester fabric. The obtained results clarified that the prints have good color strength, brilliant color and highly durable antibacterial activity.

Originality/value

The authors designed efficient synthesis for some novel thiazolone dyes. The novel procedure features short-reaction time, very good yields and a simple workup. The authors studied the antibacterial activity and their application in printing polyester fabrics.