bluuebunny/crossref_metadata_2025 huggingface dataset:
Intra-species transcriptional profiling reveals key regulators ofCandida albicanspathogenic traits
Authors: Wang Joshua M. , Woodruff Andrew L. , Dunn Matthew J , Fillinger Robert J. , Bennett Richard J. , Anderson Matthew Z.
Published: March 2021

The human commensal and opportunistic fungal pathogenCandida albicansdisplays extensive genetic and phenotypic variation across clinical isolates. Here, we performed RNA sequencing on 21 well-characterized isolates to examine how genetic variation contributes to gene expression differences, and to link these differences to phenotypic traits.C. albicansadapts primarily through clonal evolution and yet hierarchical clustering of gene expression profiles in this set of isolates did not reproduce their phylogenetic relationship. Strikingly, strain-specific gene expression was prevalent in some strain backgrounds. Association of gene expression with phenotypic data by differential analysis, linear correlation, and assembly of gene networks connected both previously characterized and novel genes with 23C. albicanstraits. Construction ofde novogene modules produced a gene atlas incorporating 67% ofC. albicansgenes and revealed correlations between expression modules and important phenotypes such as systemic virulence. Furthermore, targeted investigation of two modules that have novel roles in growth and filamentation supported our bioinformatic predictions. Together, these studies reveal widespread transcriptional variation acrossC. albicansisolates and identify genetic and epigenetic links to phenotypic variation based on co-expression network analysis.

Importance

Infectious fungal species are often treated uniformly despite clear evidence of genotypic and phenotypic heterogeneity being widespread across strains. Identifying the genetic basis for this phenotypic diversity is extremely challenging because of the tens or hundreds of thousands of variants that may distinguish two strains. Here we use transcriptional profiling to determine differences in gene expression that can be linked to phenotypic variation among a set of 21Candida albicansisolates. Analysis of this transcriptional dataset uncovered clear tends in gene expression characteristics for this species and new genes and pathways that associated with variation in pathogenic processes. Direct investigation confirmed functional predictions for a number of new regulators associated with growth and filamentation, demonstrating the utility of these approaches in linking genes to important phenotypes.
NPEPPS is a novel and druggable driver of platinum resistance
Authors: Jones Robert T. , Scholtes Mathijs , Goodspeed Andrew , Akbarzadeh Maryam , Mohapatra Saswat , Feldman Lily Elizabeth , Vekony Hedvig , Jean Annie , Tilton Charlene B. , Orman Michael V. , Romal Shahla , Deiter Cailin , Kan Tsung Wai , Xander Nathaniel , Araki Stephanie , Joshi Molishree , Javaid Mahmood , Layer Ryan , Laajala Teemu D. , Parker Sarah , Mahmoudi Tokameh , Zuiverloon Tahlita , Theodorescu Dan , Costello James C.
Published: March 2021

There is an unmet need to improve efficacy of platinum-based cancer chemotherapy. Using multi-omic assessment of cisplatin-responsive and -resistant human bladder cancer cell lines and whole-genome CRISPR screens, we identified Puromycin-Sensitive Aminopeptidase, NPEPPS, as a novel driver of cisplatin resistance. NPEPPS depletion sensitizes resistant bladder cancer cells to cisplatinin vitroandin vivo. Conversely, overexpression of NPEPPS in sensitive cells increased cisplatin resistance. We show that NPEPPS affects treatment response by regulating intracellular cisplatin concentrations. Patient-derived organoids (PDOs) generated from bladder cancer samples before and after cisplatin-based treatment, and from patients who did not receive cisplatin, were evaluated for sensitivity to cisplatin and they were found to be concordant with clinical response. In PDOs, shRNA depletion or pharmacologic inhibition of NPEPPS led to increased cisplatin sensitivity, while NPEPPS overexpression had the opposite effect. Our data present NPEPPS as a novel and druggable driver of cisplatin resistance by regulating intracellular cisplatin concentrations, along with providing the preclinical data to support clinical trials combining NPEPPS inhibition with cisplatin.
Intraspecific variation in elemental accumulation and its association with salt tolerance inPaspalum vaginatum
Authors: Goad David M. , Kellogg Elizabeth A. , Baxter Ivan , Olsen Kenneth M.
Published: March 2021

Most plant species, including most crops, perform poorly in salt-affected soils because high sodium levels are cytotoxic and can disrupt uptake of water and important nutrients. Halophytes are species that have evolved adaptations to overcome these challenges and may be a useful source of knowledge for salt tolerance mechanisms and genes that may be transferable to crop species. The salt content of saline habitats can vary dramatically by location, providing ample opportunity for different populations of halophytic species to adapt to their local salt concentrations; however, the extent of this variation, and the physiology and polymorphisms that drive it, remain poorly understood. Differential accumulation of inorganic elements between genotypes or populations may play an important role in local salinity adaptation. To test this, we investigated the relationships between population structure, tissue ion concentrations (i.e., ionomic profiles) and salt tolerance in 17 “fine-textured” genotypes of the halophytic turfgrass seashore paspalum (Paspalum vaginatumSwartz). A high-throughput ionomics pipeline was used to quantify the shoot concentration of 18 inorganic elements across three salinity treatments. We found a significant relationship between population structure and ion accumulation, with strong correlations between principal components derived from genetic and ionomic data. Additionally, genotypes with higher salt tolerance accumulated more K and Fe and less Ca than less tolerant genotypes. Together these results indicate that differences in ion accumulation betweenP. vaginatumpopulations may reflect locally adapted salt stress responses.
Deep learning: step forward to high-resolution in vivo shortwave infrared imaging
Authors: Baulin Vladimir A. , Usson Yves , Guével Xavier Le
Published: March 2021

Shortwave infrared window (SWIR: 1000-1700 nm) represents a major improvement compared to the NIR-I region (700-900 nm) in terms of temporal and spatial resolutions in depths down to 4 mm. SWIR is a fast and cheap alternative to more precise methods such as X-ray and opto-acoustic imaging. Main obstacles in SWIR imaging are the noise and scattering from tissues and skin that reduce the precision of the method. We demonstrate that the combination of SWIR in vivo imaging in the NIRIIb region (1500-1700 nm) with advanced deep learning image analysis allows to overcome these obstacles and making a large step forward to high resolution imaging: it allows to precisely segment vessels from tissues and noise, provides morphological structure of the vessels network, with learned pseudo-3D shape, their relative position, dynamic information of blood vascularization in depth in small animals and distinguish the vessels types: artieries and veins. For demonstration we use neural network IterNet that exploits structural redundancy of the blood vessels, which provides a useful analysis tool for raw SWIR images.
Evaluation of protein kinase D auto-phosphorylation as biomarker for NLRP3 inflammasome activation
Authors: Heiser Diane , Rubert Joëlle , Unterreiner Adeline , Maurer Claudine , Kamke Marion , Bodendorf Ursula , Farady Christopher J. , Roediger Ben , Bornancin Frédéric
Published: March 2021

Background

The NLRP3 inflammasome is a critical component of sterile inflammation, which is involved in many diseases. However, there is currently no known proximal biomarker for measuring NLRP3 activation in pathological conditions. Protein kinase D (PKD) has emerged as an important NLRP3 kinase that catalyzes the release of a phosphorylated NLRP3 species that is competent for inflammasome complex assembly.

Methods

To explore the potential for PKD activation to serve as a selective biomarker of the NLRP3 pathway, we tested various stimulatory conditions in THP-1 and U937 cell lines, probing the inflammasome space beyond NLRP3. We analyzed the correlation between PKD activation (monitored by its auto-phosphorylation) and functional inflammasome readouts.

Results

PKD activation/auto-phosphorylation always preceded cleavage of caspase-1 and gasdermin D, and treatment with the PKD inhibitor CRT0066101 could block NLRP3 inflammasome assembly and interleukin-1β production. Conversely, blocking NLRP3 either genetically or using the MCC950 inhibitor prevented PKD auto-phosphorylation, indicating a bidirectional functional crosstalk between NLRP3 and PKD. Further assessments of the pyrin and NLRC4 pathways, however, revealed that PKD auto-phosphorylation can be triggered by a broad range of stimuli unrelated to NLRP3 inflammasome assembly.

Conclusion

Although PKD and NLRP3 become functionally interconnected during NLRP3 activation, the promiscuous reactivity of PKD challenges its potential use for tracing the NLRP3 inflammasome pathway.
Homothorax Controls a Binary Rhodopsin Switch inDrosophilaOcelli
Authors: Mishra Abhishek Kumar , Fritsch Cornelia , Voutev Roumen , Mann Richard S. , Sprecher Simon G.
Published: March 2021

Visual perception of the environment is mediated by specialized photoreceptor (PR) neurons of the eye. Each PR expresses photosensitive opsins, which are activated by a particular wavelength of light. In most insects, the visual system comprises a pair of compound eyes that are mainly associated with motion detection, color or polarized light perception and a triplet of ocelli that are thought to be critical during flight to detect horizon and movements. It is widely believed that evolutionary diversification of compound eye and ocelli in insects occurred from an ancestral visual organ around 500 million years ago. Concurrently, opsin genes were also duplicated to provide distinct spectral sensitivities to different PRs of compound eye and ocelli. In the fruit flyDrosophila melanogaster, Rhodopsin1 (Rh1) and Rh2 are closely related opsins that are originated from the duplication of a single ancestral gene. However, in the visual organs, Rh2 is uniquely expressed in ocelli whereas Rh1 is uniquely expressed in outer PRs of the compound eye. It is currently unknown how this differential expression of Rh1 and Rh2 in the two visual organs is controlled to provide unique spectral sensitivities to ocelli and compound eyes. Here, we show that Homothorax (Hth) is expressed in ocelli and confers properrhodopsinexpression. We find that Hth controls a binary Rhodopsin switch in ocelli to promote Rh2 expression and repress Rh1 expression. Genetic and molecular analysis ofrh1andrh2supports that Hth acts through their promoters to regulate Rhodopsin expression in the ocelli. Finally, we also show that when ectopically expressed in the retina,hthis sufficient to induce Rh2 expression only at the outer PRs in a cell autonomous manner. We therefore propose that the diversification ofrhodpsinsin the ocelli and retinal outer PRs occurred by duplication of an ancestral gene, which is under the control of Homothorax.
Basement membrane proteins as a substrate for efficientTrypanosoma bruceidifferentiation in vitro
Authors: Rojas Federico , Cayla Mathieu , Matthews Keith R.
Published: March 2021

The ability to reproduce the developmental events of trypanosomes that occur in their mammalian hostin vitrooffers significant potential to assist in understanding of the underlying biology of the process. For example, the transition from bloodstream slender to bloodstream stumpy forms is a quorum-sensing response to the parasite-derived peptidase digestion products of environmental proteins. As an abundant physiological substratein vivo, we studied the ability of a basement membrane matrix enriched gel (BME) in the culture medium to support differentiation of pleomorphicTrypanosoma bruceito stumpy forms. BME comprises extracellular matrix proteins, which are among the most abundant proteins found in connective tissues in mammals and known substrates of parasite-released peptidases. We previously showed that two of these released peptidases are involved in generating a signal that promotes slender-to-stumpy differentiation. Here, we tested the ability of basement membrane extract to enhance parasite differentiation through its provision of suitable substrates to generate the quorum sensing signal, namely oligopeptides. Our results show that when grown in the presence of BME,T. bruceipleomorphic cells arrest at the G0/1 phase of the cell cycle and express the differentiation marker PAD1, the response being restricted to differentiation-competent parasites. Further, the stumpy forms generated in BME medium are able to efficiently proceed onto the next life cycle stagein vitro, procyclic forms, when incubated with cis-aconitate, further validating thein vitroBME differentiation system. Hence, BME provides a suitablein vitrosubstrate able to accurately recapitulate physiological parasite differentiation without the use of experimental animals.

Author summary

African trypanosome parasites responsible for human and animal trypanosomiasis, live extracellularly in their mammalian host and exploit environmental information to regulate their virulence and transmissibility. Morphological slender forms that proliferate in the mammalian host transform into the non-proliferative stumpy forms by receiving an extracellular signal generated by the accumulating parasites. Parasites secrete peptidases into the host that degrade extracellular matrix (ECM) proteins. In this study, we evaluated the capacity to generate stumpy formsin vitroby including a basement membrane extract into the culture medium. We show that cells exposed to ECM proteins are able to differentiate efficiently into cell-cycle arrested stumpy forms and that the generated differentiation signal depends on the stumpy induction signalling pathway. This method can be used to generate stumpy formsin vitro, these being suitable for experimental analysis, thereby reducing the use of mice.
Intestine-enrichedapolipoprotein borthologs are required for stem cell differentiation and regeneration in planarians
Authors: Wong Lily L. , Bruxvoort Christina G. , Cejda Nicholas I. , Otero Jannette Rodriguez , Forsthoefel David J.
Published: March 2021

Lipid metabolism plays an instructive role in regulating stem cell state and differentiation. However, the roles of lipid mobilization and utilization in stem cell-driven regeneration are unclear. Planarian flatworms readily restore missing tissue due to injury-induced activation of pluripotent somatic stem cells called neoblasts. Here, we identify two intestine-enriched orthologs ofapolipoprotein b, apob-1andapob-2,which mediate transport of neutral lipid stores from the intestine to target tissues including neoblasts, and are required for tissue homeostasis and regeneration. Inhibition ofapobfunction by RNAi causes head regression and lysis in uninjured animals, and delays body axis re-establishment and regeneration of multiple organs in amputated fragments. Furthermore,apobRNAi causes expansion of the population of differentiating neoblast progeny and dysregulates expression of genes enriched in differentiating and mature cells in eight major cell type lineages. We conclude that intestine-derived lipids serve as a source of metabolites required for neoblast differentiation.
Young chicks rely on perceptual grouping to discriminate prime numbers
Authors: Loconsole Maria , De Agrò Massimo , Regolin Lucia
Published: March 2021

Grouping sets of elements into smaller, equal-sized, subsets constitutes a perceptual strategy employed by humans and other animals to enhance cognitive performance. We hypothesized that asymmetrical grouping, a characteristic of prime numbers, could provide visual cues enabling discrimination of prime from non-prime numerosities. Newborn chicks were habituated to even numerosities (as sets of elements presented on a screen), and then tested for their spontaneous choice among a prime and a non-prime odd numerosity. Chicks discriminated and preferred the prime over the composite set of elements. We discuss this result in terms of novelty preference. By employing different contrasts (i.e., 7vs.9, 11vs.9, and 13vs.15) we investigated the limits of such mechanism showing that induced grouping positively affects chicks’ performance.
Positional SHAP (PoSHAP) for Interpretation of Machine Learning Models Trained from Biological Sequences
Authors: Dickinson Quinn , Meyer Jesse G.
Published: March 2021

Machine learning with multi-layered artificial neural networks, also known as “deep learning,” is effective for making biological predictions. However, model interpretation is challenging, especially for sequential input data used with recurrent neural network architectures. Here, we introduce a framework called “Positional SHAP” (PoSHAP) to interpret models trained from biological sequences by utilizing SHapely Additive exPlanations (SHAP) to generate positional model interpretations. We demonstrate this using three long short-term memory (LSTM) regression models that predict peptide properties, including binding affinity to major histocompatibility complexes (MHC), and collisional cross section (CCS) measured by ion mobility spectrometry. Interpretation of these models with PoSHAP reproduced MHC class I (rhesus macaque Mamu-A1*001 and human A*11:01) peptide binding motifs, reflected known properties of peptide CCS, and provided new insights into interpositional dependencies of amino acid interactions. PoSHAP should have widespread utility for interpreting a variety of models trained from biological sequences.
Haplotype-aware variant calling enables high accuracy in nanopore long-reads using deep neural networks
Authors: Shafin Kishwar , Pesout Trevor , Chang Pi-Chuan , Nattestad Maria , Kolesnikov Alexey , Goel Sidharth , Baid Gunjan , Eizenga Jordan M. , Miga Karen H. , Carnevali Paolo , Jain Miten , Carroll Andrew , Paten Benedict
Published: March 2021

Long-read sequencing has the potential to transform variant detection by reaching currently difficult-to-map regions and routinely linking together adjacent variations to enable read based phasing. Third-generation nanopore sequence data has demonstrated a long read length, but current interpretation methods for its novel pore-based signal have unique error profiles, making accurate analysis challenging. Here, we introduce a haplotype-aware variant calling pipeline PEPPER-Margin-DeepVariant that produces state-of-the-art variant calling results with nanopore data. We show that our nanopore-based method outperforms the short-read-based single nucleotide variant identification method at the whole genome-scale and produces high-quality single nucleotide variants in segmental duplications and low-mappability regions where short-read based genotyping fails. We show that our pipeline can provide highly-contiguous phase blocks across the genome with nanopore reads, contiguously spanning between 85% to 92% of annotated genes across six samples. We also extend PEPPER-Margin-DeepVariant to PacBio HiFi data, providing an efficient solution with superior performance than the current WhatsHap-DeepVariant standard. Finally, we demonstratede novoassembly polishing methods that use nanopore and PacBio HiFi reads to produce diploid assemblies with high accuracy (Q35+ nanopore-polished and Q40+ PacBio-HiFi-polished).
Induction ofBdnffrom promoter I following electroconvulsive seizures contributes to structural plasticity in neurons of the piriform cortex
Authors: Ramnauth Anthony D. , Maynard Kristen R. , Kardian Alisha S. , Phan BaDoi , Tippani Madhavi , Rajpurohit Sumita , Hobbs John W. , Page Stephanie Cerceo , Jaffe Andrew E. , Martinowich Keri
Published: March 2021

The efficacy of electroconvulsive therapy (ECT) as a treatment for psychiatric disorders, including major depressive disorder (MDD) is hypothesized to depend on induction of molecular and cellular events that trigger structural plasticity in neurons. Electroconvulsive seizures (ECS) in animal models can help to inform our understanding of how electroconvulsive therapy (ECT) impacts the brain. ECS induces structural plasticity in neuronal dendrites in many brain regions, including the piriform cortex, a highly epileptogenic region that has also been implicated in depression. ECS-induced structural plasticity is associated with differential expression of unique isoforms encoding the neurotrophin, brain-derived neurotrophic factor (BDNF), but the functional significance of these transcripts in dendritic plasticity is not clear. Here, we demonstrate that differentBdnfisoforms are expressed non-stochastically across neurons of the piriform cortex following ECS. Specifically, cells expressingBdnfexon 1-containing transcripts show a unique spatial recruitment pattern in response to ECS. We further demonstrate thatBdnfEx1 expression in these cells is necessary for ECS-induced dendritic spine plasticity.
IgM+and IgM-memory B cells represent heterogeneous populations capable of producing class-switched antibodies and germinal center B cells upon re-challenge withP. yoelii
Authors: Brown Susie L. , Bauer Jonathan J. , Lee Juhyung , Ntirandekura Enatha , Stumhofer Jason S.
Published: March 2021

Memory B cells (MBCs) are essential for maintaining long-term humoral immunity to infectious organisms, includingPlasmodium. MBCs are a heterogeneous population whose function can be dictated by isotype or expression of particular surface proteins. Here, aided by antigen-specific B-cell tetramers, MBC populations were evaluated to discern their phenotype and function in response to infection with a non-lethal strain ofP. yoelii. Infection of mice withP. yoelii17X resulted in the production of two predominant MBC populations: somatically hypermutated isotype-switched (IgM-) and IgM+MBCs that co-expressed CD73 and CD80 that produced antigen-specific antibodies in response to secondary infection. Re-challenge experiments indicated that IgG-producing cells dominated the recall response over the induction of IgM-secreting cells, with both populations expanding with similar timing during the secondary response. Furthermore, using ZsGreen1 expression as a surrogate for activation-induced cytidine deaminase expression alongside CD73 and CD80 co-expression, ZsGreen1+CD73+CD80+IgM+MBCs gave rise to class-switched IgG-producing plasmablasts that induced comparable titers of Ag-specific Abs as their IgM-counterparts after adoptive transfer and infection withP. yoelii. Moreover, ZsGreen1+CD73+CD80+IgM+and IgM-MBCs differentiated into B cells with a germinal center phenotype after adoptive transfer. A third population of B cells (ZsGreen1-CD73-CD80-IgM-) that emerges after infection responded poorly to reactivation in vitro and in vivo, indicating that these cells do not represent a population of MBCs. Together these data indicated that MBC function is not defined by immunoglobulin isotype, nor does co-expression of key surface markers limit the potential fate of MBCs after recall.

IgM+and IgM-MBCs that co-express CD73 and CD80 can differentiate into plasmablasts and GC B cells after re-challenge withP. yoelii.
Structural insights into plasticity and discovery of remdesivir metabolite GS-441524 binding in SARS-CoV-2 macrodomain
Authors: Ni Xiaomin , Schröder Martin , Olieric Vincent , Sharpe May E. , Olmos Victor , Proschak Ewgenij , Merk Daniel , Knapp Stefan , Chaikuad Apirat
Published: March 2021

The nsP3 macrodomain is a conserved protein interaction module that plays essential regulatory roles in host immune response by recognizing and removing posttranslational ADP-ribosylation sites during SARS-CoV-2 infection. Thus, targeting this protein domain may offer a therapeutic strategy to combat the current and future virus pandemics. To assist inhibitor development efforts, we report here a comprehensive set of macrodomain crystal structures complexed with diverse naturally-occurring nucleotides, small molecules as well as nucleotide analogues including GS-441524 and its phosphorylated analogue, active metabolites of remdesivir. The presented data strengthen our understanding of the SARS-CoV-2 macrodomain structural plasticity and it provides chemical starting points for future inhibitor development.
Large-scale placenta DNA methylation mega-analysis reveals fetal sex-specific differentially methylated CpG sites and regions
Authors: Andrews Shan V. , Yang Irene J. , Froehlich Karolin , Oskotsky Tomiko , Sirota Marina
Published: March 2021

Although male-female differences in placental structure and function have been observed, little is understood about their molecular underpinnings. Here, we present a mega-analysis of 14 publicly available placenta DNA methylation (DNAm) microarray datasets to identify individual CpGs and regions associated with fetal sex. In the discovery dataset of placentas from full term pregnancies (N = 532 samples), 5,212 CpGs met genome-wide significance (p < 1E-8) and were enriched in pathways such as keratinization (FDR p-value = 7.37E-14), chemokine activity (FDR p-value = 1.56E-2), and eosinophil migration (FDR p-value = 1.83E-2). Nine differentially methylated regions were identified (fwerArea < 0.1) including a region in the promoter ofZNF300that showed consistent differential DNAm in samples from earlier timepoints in pregnancy and appeared to be driven predominately by effects in the trophoblast cell type. We describe the largest study of fetal sex differences in placenta DNAm performed to date, revealing genes and pathways characterizing sex-specific placenta function and health outcomes later in life.
A genetic screen for regulators of muscle morphogenesis inDrosophila
Authors: Ou Tiffany , Huang Gary , Wilson Beth , Gontarz Paul , Skeath James B. , Johnson Aaron N.
Published: March 2021

The mechanisms that determine the final topology of skeletal muscles remain largely unknown. We have been developingDrosophilabody wall musculature as a model to identify and characterize the pathways that control muscle size, shape, and orientation during embryogenesis (Johnson et al., 2013; Williams et al., 2015; Yang et al., 2020a; Yang et al., 2020b). Our working model argues muscle morphogenesis is regulated by (1) extracellular guidance cues that direct muscle cells toward muscle attachment sites, and (2) contact dependent interactions between muscles and tendons. While we have identified several pathways that regulate muscle morphogenesis, our understanding is far from complete. Here we report the results of a recent EMS-based forward genetic screen that identified a myriad of loci not previously associated with muscle morphogenesis. We recovered new alleles of known muscle morphogenesis genes, includingbsd, kon, ths, andtum, arguing our screening strategy was effective and efficient. We also identified and sequenced new alleles ofsalm,barr, andptcthat presumably disrupt independent pathways directing muscle morphogenesis. Equally as important, our screen shows that at least 11 morphogenetic loci remain to be identified. This screen has developed exciting new tools to study muscle morphogenesis, which may provide future insights into the mechanisms that determine skeletal muscle topology.
Localised expression ofOsIAA29suggests a key role for auxin in regulating development of the dorsal aleurone of early rice grains
Authors: Basunia Mafroz A. , Nonhebel Heather M. , Backhouse David , McMillan Mary
Published: March 2021

Endosperm of rice and other cereals accumulates high concentrations of the predominantin plantaauxin, indole-3-acetic acid (IAA) during early grain development. However, IAA signalling and function during endosperm development are poorly understood. Here, we report thatOsYUC12(an auxin biosynthesis gene) andOsIAA29(encoding a non-canonical AUX/IAA) are both expressed exclusively in grains, reaching a maximum 5 to 6 days after pollination.OsYUC12expression is localized in the aleurone, sub-aleurone and embryo, whereasOsIAA29expression is restricted to a narrow strip in the dorsal aleurone, directly under the vascular bundle. Although rice has been reported to lack endosperm transfer cells (ETCs), this region of the aleurone is enriched with sugar transporters and is likely to play a key role in apoplastic nutrient transfer, analogous to ETCs in other cereals.OsIAA29has orthologues only in grass species; expression of which is also specific to early grain development.OsYUC12andOsIAA29are temporally co-expressed with two genes(AL1andOsPR602)previously linked to the development of dorsal aleurone or ETCs. Also up regulated at the same time are a cluster of MYB-related genes (designatedOsMRPLs)homologous toZmMRP-1,which regulates maize ETC development. Wheat homologues ofZmMRP-1are also expressed in ETCs. Although previous work has suggested that other cereals do not have orthologues of ZmMRP-1, our work suggests OsIAA29 and OsMRPLs and their homologues in other grasses are part of an auxin-regulated, conserved signalling network involved in the differentiation of cells with ETC-like function in developing cereal grains.

Main Conclusion

Non-canonical AUX/IAA protein, OsIAA29, and ZmMPR-1 homologues, OsMRPLs, are part of an auxin-related signalling cascade operating in the dorsal aleurone during early rice grain development.
Compound- and fiber type-selective requirement of AMPKγ3 for insulin-independent glucose uptake in skeletal muscle
Authors: Rhein Philipp , Desjardins Eric M. , Rong Ping , Ahwazi Danial , Bonhoure Nicolas , Stolte Jens , Santos Matthieu D. , Ovens Ashley J. , Ehrlich Amy M. , Garcia José L. Sanchez , Ouyang Qian , Kjolby Mads F. , Membrez Mathieu , Jessen Niels , Oakhill Jonathan S. , Treebak Jonas T. , Maire Pascal , Scott John W. , Sanders Matthew J. , Descombes Patrick , Chen Shuai , Steinberg Gregory R. , Sakamoto Kei
Published: March 2021

Objective:The metabolic master-switch AMP-activated protein kinase (AMPK) mediates insulin-independent glucose uptake in muscle and regulates the metabolic activity of brown and beige adipose tissue (BAT). The regulatory AMPKγ3 isoform is uniquely expressed in skeletal muscle and also potentially in BAT. Here, we investigated the role that AMPKγ3 plays in mediating skeletal muscle glucose uptake and whole-body glucose clearance in response to small-molecule activators that act on AMPK via distinct mechanisms. We also assessed if γ3 plays a role in adipose thermogenesis and browning.

Methods:Global AMPKγ3 knockout (KO) mice were generated. A systematic whole-body, tissue and molecular phenotyping linked to glucose homeostasis was performed in γ3 KO and wild type (WT) mice. Glucose uptake in glycolytic and oxidative skeletal muscleex vivo,as well as blood glucose clearance in response to small molecule AMPK activators that target nucleotide-binding domain of γ subunit (AICAR) and allosteric drug and metabolite (ADaM) site located at the interface of the α and β subunit (991, MK-8722) were assessed. Oxygen consumption, thermography, and molecular phenotyping with a β3-adrenergic receptor agonist (CL-316,243) treatment were performed to assess BAT thermogenesis, characteristics and function.

Results:Genetic ablation of γ3 did not affect body weight, body composition, physical activity, and parameters associated with glucose homeostasis under chow or high fat diet. γ3 deficiency had no effect on fiber-type composition, mitochondrial content and components, or insulin-stimulated glucose uptake in skeletal muscle. Glycolytic muscles in γ3 KO mice showed a partial loss of AMPKα2 activity, which was associated with reduced levels of AMPKα2 and β2 subunit isoforms. Notably, γ3 deficiency resulted in a selective loss of AICAR-, but not MK-8722-induced blood glucose-loweringin vivoand glucose uptake specifically in glycolytic muscleex vivo. We detected γ3 in BAT and found that it preferentially interacts with α2 and β2. We observed no differences in oxygen consumption, thermogenesis, morphology of BAT and inguinal white adipose tissue (iWAT), or markers of BAT activity between WT and γ3 KO mice.

Conclusions:These results demonstrate that γ3 plays a key role in mediating AICAR- but not ADaM site binding drug-stimulated blood glucose clearance and glucose uptake specifically in glycolytic skeletal muscle. We also showed that γ3 is dispensable for thermogenesis and browning of iWAT.
Crystal structures of 4-bromo-2-formyl-1-tosyl-1H-pyrrole, (E)-4-bromo-2-(2-nitrovinyl)-1-tosyl-1H-pyrrole and 6-(4-bromo-1-tosylpyrrol-2-yl)-4,4-dimethyl-5-nitrohexan-2-one
Authors: Kingsbury Christopher J. , Sample Harry C. , Senge Mathias O.
Published: March 2021

The crystal structures of three intermediate compounds in the synthesis of 8-bromo-2,3,4,5-tetrahydro-1,3,3-trimethyldipyrrin are reported; 4-bromo-2-formyl-1-tosyl-1H-pyrrole, C12H10BrNO3S, (E)-4-bromo-2-(2-nitrovinyl)-1-tosyl-1H-pyrrole, C13H11BrN2O4S, and 6-(4-bromo-1-tosylpyrrol-2-yl)-4,4-dimethyl-5-nitrohexan-2-one, C19H23BrN2O5S. The compounds show multitudinous intermolecular C—H...O interactions, with bond distances and angle consistent in the series and within expectations, as well as varied packing types. The merits of collecting data beyond the standard resolution usually reported for small molecules are discussed.
Open space and sense of community of older adults: a study in a residential area in Hong Kong
Authors: Yu Andrew
Published: March 2021

Purpose

This study examines the relationship between quality and quantity of open space in residential areas and the sense of community of Chinese older adults in Hong Kong.

Design/methodology/approach

A survey was conducted with 257 adults aged 55 and over in Kwun Tong, Hong Kong. The quality of open space was assessed from four dimensions: social and recreational facilities, entrance, location and environment. Geographic information system (GIS) was used to evaluate the quantity of open space in terms of size and amount.

Findings

The result shows that the environment has a strong influence on the sense of community, while the quantity of open space does not. The results provide urban planners with evidence for open space planning in the future. Urban planners should consider building more people-oriented environment; such as green areas instead of merely increasing the size, amount and facilities of open space. The Hong Kong Government also needs to review the current standardised planning guideline in order to maximise the social connection of older adults.

Originality/value

This cross-sectional study tried to understand the relationship between the quality and quantity of open spaces and sense of community in Chinese older adults in Hong Kong. It is one of the few studies to simultaneously examine both the quality and quantity of open spaces when studying its relationship with sense of community.
Identification and ordering of safety performance indicators using fuzzy TOPSIS: a case study in Indian construction company
Authors: Singh Arpit , Misra Subhas C. , Kumar Vinod , Kumar Uma
Published: March 2021

Purpose

The purpose of this paper is to propose a practical framework to measure the safety performance of workers in the Indian construction industry. The key safety performance indicators are identified and ordered on the premise that the higher order assignment of an indicator implies a strong indication of an effective safety performance.

Design/methodology/approach

Various indicators of safety performance in the construction industry were identified from extant literature review combined with author's personal viewpoint. The identified variables were inquired for appropriateness for the Indian construction scenario by consultation with experts. Fuzzy Technique for order preference by similarity to ideal solution (TOPSIS) technique was considered for the ranking of the indicators from most to least important.

Findings

The most important highlight of the study was the importance of the role of management by participating in informing workers about the safety rules and compliance toward safety measures. Proper and timely safety training to the workers and equipping them with sophisticated safety equipment for daily activities is perceived to be highly important in ensuring a safe and healthy workplace environment. Controlling the absenteeism rate reduces the burden of extra work on the employees, thereby, encouraging safe work-related behavior.

Originality/value

Senior management should make safety induction programs compulsory at the time of joining of the employees. The guidelines for safety practices, rules and information about the safety equipment should be properly documented and arranged in safety manuals. Periodical drills involving visual demonstration of the safety practices should be followed to ensure safety at workplace.
Occupational choices in art and agriculture – a mixed-method web scraping approach
Authors: Mann Stefan
Published: March 2021

Purpose

Empirical studies on occupational choice have typically concentrated on a specific sector. The purpose of this study is to compare two sectors wherein there are grounds to hypothesise that lifestyle reasons play a key role for occupational choice.

Design/methodology/approach

Arguing that the potential for qualitative web scraping is still underused, the hypothesis is tested through qualitative web scraping for occupational choices.

Findings

It is shown that incomes for farmers are both documented in a better way and higher than in arts. The central roles played by farmers in the provision of basic needs and in powerful value chains are possible reasons for this difference. As a common factor between the sectors, two-thirds of both farmers and artists choose their profession for reasons of self-realisation or societal motives.

Originality/value

This study is the first to show both common grounds and differences in occupational choices of two different sectors.
Failure learning and entrepreneurial resilience: the moderating role of firms’ knowledge breadth and knowledge depth
Authors: Yao Kai , Li Xiaolin , Liang Bang
Published: March 2021

Purpose

Drawing on the knowledge-based view, the purpose of this study is to investigate the differential effects of failure normalization (FN) and failure analysis (FA) on entrepreneurial resilience (ER) and examines how firms’ knowledge breadth (KB) and knowledge depth (KD) moderate these effects in distinctive ways.

Design/methodology/approach

The study uses a mixed-methods approach, including a two-wave survey study among 226 entrepreneurial high-tech firms in China and a qualitative study.

Findings

The findings reveal that FA has a stronger positive effect on ER than FN. KB enhances the effect of FA on ER, whereas KD enhances the effect of FN on ER but buffers the effect of FA on ER.

Practical implications

The study advocates that entrepreneurs need to be aware of the importance of ER and strengthen the reflection on failure. Additionally, the study suggests that entrepreneurs should match FN and FA with firms’ knowledge characteristics. With this match, KB and KD can exert greater impacts on the effect of failure learning on ER.

Originality/value

Knowledge can influence the effect of learning on firm capability. However, such an effect in entrepreneurial firms linking to ER remains to be explored. This study contributes to ER from the failure learning perspective and extends knowledge management theory in the entrepreneurship context.
The Challenges of Implementing Anti‐Money Laundering Regulation: An Empirical Analysis
Authors: Zavoli Ilaria , King Colin
Published: March 2021

For over three decades, money laundering has been an area of concern for policymakers and law enforcement, with significant efforts undertaken at national and international levels to combat it. Recently, laundering of criminal proceeds using real property has attracted increased attention amongst policymakers. Various efforts are now being undertaken to tackle money laundering in the UK property market, but there are still significant difficulties in its practical implementation. Drawing upon semi‐structured interviews with estate agents and compliance officials, this study identifies critical aspects of AML compliance that are particularly problematic for those involved in it. In so doing, this article delivers a new perspective, by analysing data gathered with the first empirical study on the implementation of AML obligations in practice (in the UK property market) since the introduction of the 2017 Money Laundering Regulations.
Macroscopic fat containing renal cell carcinoma
Authors: Kirkinis Maria , Sutherland Tom
Published: March 2021

Renal masses containing macroscopic fat traditionally are pathognomonic for angiomyolipoma, a benign tumour. We describe two cases contrary to this axiom, the first being initially referred for angioembolisation, but subsequently biopsied when it was angiographically occult, whilst the second case showed a small macroscopic fat component and arterial enhancement prompting biopsy. Neither of these two cases demonstrated calcification which would usually suggest a more sinister lesion requiring further workup. The results demonstrated renal cell carcinoma for both lesions. Our multidisciplinary meeting approach to renal masses with a small amount of macroscopic fat and no calcifications has now changed.
Abstinence Among Alcohol Use Disorder Patients During the COVID‐19 Pandemic: Insights From Spain
Authors: Barrio Pablo , Baldaquí Nuria , Andreu Magalí , Kilian Carolin , Rehm Jürgen , Gual Antoni , Manthey Jakob
Published: March 2021

Background

Patients with alcohol use disorder (AUD) are likely to suffer disproportionate harms related to the COVID‐19 pandemic and related policy measures. While many surveys have been conducted, most are focused on drinking changes in the general population and validation with biological markers is lacking.

Method

We performed a retrospective cohort study among patients with AUD attending a urine drug screening program. With mixed‐effects logistic regression models, we assessed the probability of screening positive for ethyl glucuronide according to patients’ main clinical characteristics and time of analysis (either prior to or after a lockdown was implemented in Spain).

Results

A total of 362 patients provided 2,040 urine samples (1,295 prior to lockdown, 745 during lockdown). The mean age of participants was 52.0 years (SD 12.6), and 69.2% were men. Of the 43% of patients tested for other drugs 22% screened positive. After adjusting for all covariates, the odds of screening positive for ethyl glucuronide during lockdown almost doubled (OR = 1.99, 95% CI 1.20 to 3.33, p = 0.008). Other significant covariates included testing positive for other drugs (OR = 10.79, 95% CI 4.60 to 26.97) and length of treatment (OR = 0.59, 95% CI 0.47 to 0.74).

Conclusions

Our data support an association between the lockdown due to COVID‐19 and increased alcohol use in patients with AUD. Thus, addiction healthcare systems could face significant challenges ahead. In light of these findings, it is essential to evaluate prospectively how patients with AUD are affected by the pandemic and how health systems respond to their needs.
COVID‐19's Lockdown and Crime Victimization: The State of Emergency under the Abe Administration
Authors: Shen Yichen , Fu Rong , Noguchi Haruko
Published: March 2021

COVID‐19 has led many governments to impose lockdowns in efforts to reduce the spread of the virus. One of the many consequences of the lockdown is a reduction in crime. We apply a difference‐in‐differences approach to the 2018–2020 Crime Statistics to investigate the effect of the 2020 lockdown on crime victimization in Japan. We find that the 2020 lockdown leads to 12.7% and 20.9% declines in violent and property crime victimization rates per 100,000 people, respectively. Moreover, we observe that premeditated crimes, such as breaking‐and‐entering and sexual assault, decline more than non‐premeditated crimes, such as homicide. We also explore the heterogeneous effects of the lockdown by age groups. We observe that there is a significant decline in sexual assault victimization for those between the ages of 0 and 29, and there are significant declines in overall violent and property crime victimizations and their subtypes for those between ages of 30 and 59. Finally, we show that there is an improvement in suicide rates, which suggests that better mental health is the mechanism partially mediating the relationship between lockdown and crime victimization.
Socio‐economic status in families affected by childhood cataract
Authors: Al‐Bakri Moug , Bach‐Holm Daniella , Larsen Dorte Ancher , Siersma Volkert , Kessel Line
Published: March 2021

Purpose

To investigate the socio‐economic status of families affected by childhood cataract and to assess how the socio‐economic status is affected by cataract diagnosis.

Materials and methods

Children born between 2000 and 2017, seen between the age 0 and 10 years in the same period at Rigshospitalet or Aarhus University Hospital for cataract (N = 485), were included and compared to a matched children group without cataract (N = 4358). Socio‐economic status was evaluated by the parents’ income, employment, education, marital status and family structure.

Results

Parents of children with cataract were more likely to have a low yearly income (OR = 1.60, 95% CI (1.12–2.27)), be out of work (OR = 1.74, 95% CI (1.34–2.26)) and have basic education as the highest attained education (OR = 1.64, 95% CI (1.27–2.13)) prior to diagnosis. This social gradient was not affected by the diagnosis. In addition, a higher number of children with cataract lived in multi‐family residencies (13.8% versus 8% in group of children without cataract) and they had a greater number of siblings (6.2% had ≥4 siblings versus 2.1% in group of children without cataract).

Conclusion

Families affected by childhood cataract have a lower socio‐economic status and educational background even before cataract is diagnosed but the diagnosis does not aggravate the differences between these families and the background population. The lower socio‐economic status and parental educational background should be taken into consideration in the management of these families.