bluuebunny/crossref_metadata_2025 huggingface dataset:
scPNMF: sparse gene encoding of single cells to facilitate gene selection for targeted gene profiling
Authors: Song Dongyuan , Li Kexin Aileen , Hemminger Zachary , Wollman Roy , Li Jingyi Jessica
Published: February 2021

Single-cell RNA sequencing (scRNA-seq) captures whole transcriptome information of individual cells. While scRNA-seq measures thousands of genes, researchers are often interested in only dozens to hundreds of genes for a closer study. Then a question is how to select those informative genes from scRNA-seq data. Moreover, single-cell targeted gene profiling technologies are gaining popularity for their low costs, high sensitivity, and extra (e.g., spatial) information; however, they typically can only measure up to a few hundred genes. Then another challenging question is how to select genes for targeted gene profiling based on existing scRNA-seq data. Here we develop the single-cell Projective Non-negative Matrix Factorization (scPNMF) method to select informative genes from scRNA-seq data in an unsupervised way. Compared with existing gene selection methods, scPNMF has two advantages. First, its selected informative genes can better distinguish cell types. Second, it enables the alignment of new targeted gene profiling data with reference data in a low-dimensional space to facilitate the prediction of cell types in the new data. Technically, scPNMF modifies the PNMF algorithm for gene selection by changing the initialization and adding a basis selection step, which selects informative bases to distinguish cell types. We demonstrate that scPNMF outperforms the state-of-the-art gene selection methods on diverse scRNA-seq datasets. Moreover, we show that scPNMF can guide the design of targeted gene profiling experiments and cell-type annotation on targeted gene profiling data.
Sub-diffraction error mapping for localization microscopy images
Authors: Marsh Richard J. , Costello Ishan , Gorey Mark-Alexander , Ma Donghan , Huang Fang , Gautel Mathias , Parsons Maddy , Cox Susan
Published: February 2021

Assessing the quality of localization microscopy images is highly challenging due to difficulty in reliably detecting errors in experimental data, with artificial sharpening being a particularly common failure mode of the technique. Here we use Haar wavelet kernel analysis (HAWK), a localization microscopy data analysis method which is known to give results without artificial sharpening, to generate a reference image. This enables the mapping and quantification of this common artefact. By suppressing intensity information, we are able to map sharpening errors in a way which is not influenced by nonlinearity in the localisation imaging process. The HAWK Method for the Assessment of Nanoscopy (HAWKMAN) is a general approach which allows the reliability of localization information to be assessed.
Single paternal Dexamethasone challenge programs offspring metabolism and reveals circRNAs as novel candidates in RNA-mediated inheritance
Authors: Gapp Katharina , Parada Guillermo , Gross Fridolin , Corcoba Alberto , Grau Evelyn , Hemberg Martin , Bohacek Johannes , Miska Eric A.
Published: February 2021

Single traumatic events that elicit an exaggerated stress response can lead to the development of neuropsychiatric conditions. Studies in mice suggests germline RNA as a mediator of effects of chronic environmental exposures to the progeny. The effects of an acute paternal stress exposure on the germline and their potential consequences on offspring remain unknown. We find that acute administration of an agonist for the stress- sensitive Glucocorticoid receptor, using the common corticosteroid Dexamethasone, affects the RNA payload of post-meiotic transcriptionally silent, mature sperm as soon as 3 hours post exposure. It further impacts early embryonic transcriptional trajectories, as determined by single embryo sequencing, and metabolism in the offspring. Importantly, we show persistent regulation of tRNA fragments in sperm and the descendant 2-cell- embryos, suggesting actual transmission from sperm to embryo. Lastly, we unravel environmentally induced alterations in the previously underconsidered class of sperm circRNAs, and their targets in the early embryo, highlighting this class as a novel candidate in RNA-mediated inheritance.
Identification and mechanistic analysis of an inhibitor of the CorC Mg2+transporter
Authors: Huang Yichen , Mu Kaijie , Teng Xinyu , Zhao Yimeng , Funato Yosuke , Miki Hiroaki , Zhu Weiliang , Xu Zhijian , Hattori Motoyuki
Published: February 2021

The CorC/CNNM family of Na+-dependent Mg2+transporters is ubiquitously conserved from bacteria to humans. CorC, the bacterial member of the CorC/CNNM family of proteins, is involved in resistance to antibiotic exposure and in the survival of pathogenic microorganisms in their host environment. The CorC/CNNM family proteins possess a cytoplasmic region containing the regulatory ATP-binding site. While CorC and CNNM have attracted interest as therapeutic targets, inhibitors targeting the ir regulatory ATP-binding site have not yet been identified.

Here, we performed a virtual screening of CorC by targeting its regulatory ATP-binding site, identified a chemical compound named IGN95a with inhibitory effects on both ATP binding and Mg2+export, and determined the cytoplasmic domain structure in complex with IGN95a. Furthermore, a chemical cross-linking experiment indicated that with ATP bound to the cytoplasmic domain, the conformational equilibrium of CorC was shifted more towards the inward-facing state of the transmembrane domain. In contrast, IGN95a did not induce such a shift. Our results provide a structural basis for the further design and optimization of chemical compounds targeting the regulatory ATP-binding site of CorC as well as mechanistic insights into how ATP and chemical compounds modulate the transport activity of CorC.
Characterisation of immune cell subsets of tumour infiltrating lymphocytes in brain metastases
Authors: Croft Priyakshi Kalita-de , Chittoory Haarika , Nguyen Tam , Saunus Jodi M , Kim Woo Gyeong , Reed Amy McCart , Lim Malcolm , De Luca Xavier M , Ferguson Kaltin , Niland Colleen , Mazzieri Roberta , Dolcetti Riccardo , Simpson Peter T , Lakhani Sunil R
Published: February 2021

The heterogeneity of tumor infiltrating lymphocytes is not well characterized in brain metastasis. To address this, we performed a targeted analysis of immune cell subsets in brain metastasis tissues to test which immunosuppressive routes are involved in brain metastasis. We performed multiplex immunofluorescence (mIF), using commercially available validated antibodies on twenty formalin-fixed paraffin embedded whole sections. We quantitated the subsets of immune cells utilizing a targeted panel of proteins including PanCK, CD8, CD4, VISTA and Iba1, and analyzed an average of 15000 cells per sample. We classified tumours as either high (>30%) or low (<30%) tumour infiltrating lymphocytes (TILs) and found that increased TILs density correlated with survival. We next sought out to phenotype these TILs using mIF. The tumours with low TILs (n=9) had significantly higher expression of the immune-checkpoint molecule VISTA in tumor cells (p<0.01) as well as in their microenvironment (p<0.001). Contrastingly, the brain metastatic tumours with high TILs (n=8) displayed higher levels of activated microglia, as measured by Iba1 expression. Low TILs-tumours displayed CD8+ T-cells that co-express VISTA (p<0.01) significantly more compared to high TILs group, where CD8+ T-cells significantly co-express Iba1 (p<0.05). Interestingly, no definite phenotypes of CD4+ subsets were observed. These results were supported by RNA analysis of a publicly available, independent cohort. In conclusion, our work contributes to a growing understanding of the immune surveillance escape routes active in brain metastasis.

Graphical Abstract

Graphical abstract:

Brain metastasis patients with low TILs have high VISTA expression and patients with high TILs have significantly more activated microglia
Fasting reverses drug-resistance in hepatocellular carcinoma through p53-dependent metabolic synergism
Authors: Krstic Jelena , Reinisch Isabel , Schindlmaier Katharina , Galhuber Markus , Berger Natascha , Kupper Nadja , Moyschewitz Elisabeth , Auer Martina , Michenthaler Helene , Nössing Christoph , Depaoli Maria R. , Ramadani-Muja Jeta , Stryeck Sarah , Pichler Martin , Rinner Beate , Deutsch Alexander J.A. , Reinisch Andreas , Madl Tobias , Chiozzi Riccardo Zenezini , Heck Albert J.R. , Huch Meritxell , Malli Roland , Prokesch Andreas
Published: February 2021

Cancer cells voraciously consume nutrients to support their growth, exposing a metabolic vulnerability that can be therapeutically exploited. Here we show in hepatocellular carcinoma (HCC) cells, xenografts, and in patient-derived HCC organoids that fasting can synergistically sensitize resistant HCC to sorafenib. Mechanistically, sorafenib acts non-canonically as an inhibitor of mitochondrial respiration, causing resistant cells to depend on glycolysis for survival. Fasting, through reduction in glucose and impeded AKT/mTOR-signaling, prevents this Warburg shift. Regulating glucose transporter and pro-apoptotic protein expression, p53 is necessary and sufficient for the sorafenib-sensitizing effect of fasting. p53 is also crucial for fasting-mediated improvement of sorafenib efficacy in an orthotopic HCC mouse model. Together, our data suggest intermittent fasting and sorafenib as rational combination therapy for HCC with intact p53 signaling. As HCC therapy is currently severely limited by resistance, these results should instigate clinical studies aimed at improving therapy response in advanced-stage, and possibly even early-stage, HCC.

HIGHLIGHTS

Fasting sensitizes resistant HCC xenografts and patient-derived organoids to sorafenib

Sorafenib-mediated Warburg shift is prevented by glucose limitation upon fasting

Fasting synergistically improves sorafenib efficacy in non-resistant models

p53 is required for synergism by regulating glucose uptake and apoptosis

GRAPHICAL ABSTRACT
Evidence of stock connectivity, hybridization and misidentification in white anglerfish support the need of a genetics-informed fisheries management framework
Authors: Aguirre-Sarabia Imanol , Díaz-Arce Natalia , Pereda-Agirre Iker , Mendibil Iñaki , Urtizberea Agurtzane , Gerritsen Hans D. , Burns Finlay , Holmes Ian , Landa Jorge , Coscia Ilaria , Quinconces Iñaki , Santurtún Marina , Zanzi Antonella , Martinsohn Jann T. , Rodríguez-Ezpeleta Naiara
Published: February 2021

Understanding population connectivity within a species as well as potential interactions with its close relatives is crucial to define management units and to derive efficient management actions. However, although genetics can reveal mismatches between biological and management units and other relevant but hidden information such as species misidentification or hybridization, the uptake of genetic methods by the fisheries management process is far from having been consolidated. Here, we have assessed the power of genetics to better understand the population connectivity of white angelfish (Lophius piscatorius) and its interaction with its sister species, the black anglerfish (L. budegassa). Our analyses, based on thousands of genome-wide single nucleotide polymorphisms, show three findings that are crucial for white anglerfish management. We found i) that white anglerfish is likely composed of a single panmictic population throughout the Northeast Atlantic, challenging the three-stock based management, ii) that a fraction of specimens classified as white anglerfish using morphological characteristics are genetically identified as black anglerfish (L. budegassa) and iii) that the twoLophiusspecies naturally hybridize leading to a population of hybrids of up to 20% in certain areas. Our results set the basics for a genetics-informed white anglerfish assessment framework that accounts for stock connectivity, revises and establishes new diagnostic characters forLophiusspecies identification and evaluates the effect of hybrids in the current and future assessments of the white anglerfish. Furthermore, our study contributes to provide additional evidence of the potentially negative consequences of ignoring genetic data for assessing fisheries resources.
A pilot study on the home range and movement patterns of the Andean FoxLycalopex culpaeus(Molina, 1782) in Cotopaxi National Park, Ecuador
Authors: Castellanos Armando , Castellanos Francisco X. , Kays Roland , Brito Jorge
Published: February 2021

This study reports movement patterns and home range estimates of an Andean fox (Lycalopex culpaeus) in Cotopaxi National Park in Ecuador, representing the first GPS-tagging of the species. The GPS functioned well during the 197-day tracking period. Home range sizes ranged between 4.9 - 8.1 km2, depending on the estimation method. Movement speeds averaged 0.17 km/hr at day vs. 0.87 km/hr. at night, and distance traveled averaged 0.23 km at day vs. 0.89 km at night. These preliminary results highlight the importance of collecting unbiased, high-quality data which enables an enhanced understanding on mammal behavior and human/animal interaction.
The integration of continuous audio and visual speech in a cocktail-party environment depends on attention
Authors: Ahmed Farhin , Nidiffer Aaron R. , O’Sullivan Aisling E. , Zuk Nathaniel J. , Lalor Edmund C.
Published: February 2021

In noisy, complex environments, our ability to understand audio speech benefits greatly from seeing the speaker’s face. This is attributed to the brain’s ability to integrate audio and visual information, a process known as multisensory integration. In addition, selective attention to speech in complex environments plays an enormous role in what we understand, the so-called cocktail-party phenomenon. But how attention and multisensory integration interact remains incompletely understood. While considerable progress has been made on this issue using simple, and often illusory (e.g., McGurk) stimuli, relatively little is known about how attention and multisensory integration interact in the case of natural, continuous speech. Here, we addressed this issue by analyzing EEG data recorded from subjects who undertook a multisensory cocktail-party attention task using natural speech. To assess multisensory integration, we modeled the EEG responses to the speech in two ways. The first assumed that audiovisual speech processing is simply a linear combination of audio speech processing and visual speech processing (i.e., an A+V model), while the second allows for the possibility of audiovisual interactions (i.e., an AV model). Applying these models to the data revealed that EEG responses to attended audiovisual speech were better explained by an AV model than an A+V model, providing evidence for multisensory integration. In contrast, unattended audiovisual speech responses were best captured using an A+V model, suggesting that multisensory integration is suppressed for unattended speech. Follow up analyses revealed some limited evidence for early multisensory integration of unattended AV speech, with no integration occurring at later levels of processing. We take these findings as evidence that the integration of natural audio and visual speech occurs at multiple levels of processing in the brain, each of which can be differentially affected by attention.
Evaluating Wayfinding Designs in Healthcare Settings through EEG Data and Virtual Response Testing
Authors: Kalantari Saleh , Tripathi Vidushi , Rounds James D. , Mostafavi Armin , Snell Robin , Cruz-Garza Jesus G.
Published: February 2021

Wayfinding difficulties in healthcare facilities have been shown to increase anxiety among patients and visitors and reduce staff operational efficiency. Wayfinding-oriented interior design features have proven beneficial, but the evaluation of their performance is hindered by the unique nature healthcare facilities and the expense of testing different navigational aids. This study implemented a virtual-reality testing platform to evaluate the effects of different signage and interior hospital design conditions during navigational tasks; evaluated through behavioral responses and mobile EEG. The results indicated that using color to highlight destinations and increase the contrast of wayfinding information yielded significant benefits when combined with wayfinding-oriented environmental affordances. Neural dynamics from the occipital cortex showed beta-band desynchronization with enhanced color condition and additional theta-band desynchronization with enhanced environmental affordance. This multimodal testing platform has the potential to establish a robust body of evidence for future wayfinding design strategies.
Gene dosage effects of polyA track engineered hypomorphs
Authors: Powell Geralle , Pavlovic-Djuranovic Slavica , Djuranovic Sergej
Published: February 2021

The manipulation of gene activity through the creation of hypomorphic mutants has been a long-standing tool in examining gene function. Our previous studies have indicated that hypomorphic mutants could be created by inserting cis-regulatory sequences composed of consecutive adenosine nucleotides called polyA tracks. Here we use polyA tracks to create hypomorphic mutants and functional characterization of membrane, secretory and endogenous proteins. Insertion of polyA tracks into the sequences of interleukin-2 and membrane protein CD20 results in a programmable reduction of mRNA stability and attenuation of protein expression regardless of the presence of signaling sequence. Likewise, CRISPR/Cas9 targeted insertion of polyA tracks in the coding sequence of endogenous human genesAUF1andTP53results in a programmable reduction of targeted protein and mRNA levels. Functional analyses of AUF1 engineered hypomorphs indicate a direct correlation betweenAUF1gene levels and the stability of AUF1-regulated mRNAs. Hypomorphs of TP53 affect the expression of the target genes differentially depending upon the severity of the hypomorphic mutation. Finally, decreases in TP53 protein affect the same cellular pathways in polyA track engineered cells as in cancer cells, indicating these variants’ biological relevance. These results highlight this technology’s power to create predictable, stable hypomorphs in recombinant or endogenous genes in combination with CRISPR/Cas9 engineering tools.
Bfimpute: A Bayesian factorization method to recover single-cell RNA sequencing data
Authors: Wen Zi-Hang , Langsam Jeremy L. , Zhang Lu , Shen Wenjun , Zhou Xin
Published: February 2021

Single-cell RNA-seq (scRNA-seq) offers opportunities to study gene expression of tens of thousands of single cells simultaneously, to investigate cell-to-cell variation, and to reconstruct cell-type-specific gene regulatory networks. Recovering dropout events in a sparse gene expression matrix for scRNA-seq data is a long-standing matrix completion problem. We introduce Bfimpute, a Bayesian factorization imputation algorithm that reconstructs two latent gene and cell matrices to impute final gene expression matrix within each cell group, with or without the aid of cell type labels or bulk data. Bfimpute achieves better accuracy than other six publicly notable scRNA-seq imputation methods on simulated and real scRNA-seq data, as measured by several different evaluation metrics. Bfimpute can also flexibly integrate any gene or cell related information that users provide to increase the performance. Availability: Bfimpute is implemented in R and is freely available athttps://github.com/maiziezhoulab/Bfimpute.
TemplateFlow: FAIR-sharing of multi-scale, multi-species brain models
Authors: Ciric Rastko , Thompson William H. , Lorenz Romy , Goncalves Mathias , MacNicol Eilidh , Markiewicz Christopher J. , Halchenko Yaroslav O. , Ghosh Satrajit S. , Gorgolewski Krzysztof J. , Poldrack Russell A. , Esteban Oscar
Published: February 2021

Reference anatomies of the brain and corresponding atlases play a central role in experimental neuroimaging workflows and are the foundation for reporting standardized results. The choice of such references —i.e., templates— and atlases is one relevant source of methodological variability across studies, which has recently been brought to attention as an important challenge to reproducibility in neuroscience. TemplateFlow is a publicly available framework for human and nonhuman brain models. The framework combines an open database with software for access, management, and vetting, allowing scientists to distribute their resources under FAIR —findable, accessible, interoperable, reusable— principles. TemplateFlow supports a multifaceted insight into brains across species, and enables multiverse analyses testing whether results generalize across standard references, scales, and in the long term, species, thereby contributing to increasing the reliability of neuroimaging results.
Material-mediated histogenesis using mechano-chemically microstructured cell niches
Authors: Newman Peter L. H. , Yip Queenie , Osteil Pierre , Anderson Tim A. , Sun Jane Q. J. , Kempe Daryan , Biro Maté , Shin Jae-Won , Tam Patrick P.L. , Zreiqat Hala
Published: February 2021

Stem-cell derived tissue models are commonly cultured under globally-delivered stimuli that trigger histogenesis via self-organizing activity. However, the culture of such tissue models is prone to stochastic behavior, limiting the reproducibility of cellular composition and resulting in non-physiological architectures. To overcome these shortcomings, we developed a method for printing cell niche microenvironments with microstructured cues that mediate local histogenic processes, including mechanosensing and differentiation of selected cell types. Microstructured cues include independently tunable mechano-chemical properties, with conjugated peptides, proteins, and morphogens across a range of Young’s moduli. By rationally designing niches, we mediate the structure of tissues derived from stem-cell-progenitor sources, including a bone-fat assembly from stromal mesenchyme, and embryonic tissues derived from hiPSC. We show that microstructured cues can recapitulate mechano-chemical signals resembling early embryonic histogenesis. This outcome includes a role for niche mechanics in human embryonic organization, where soft niche mechanics bias markers of mesendodermal differentiation and epithelial-to-mesenchymal-transition (EMT), as well as a demonstration of a material-mediated morphogen signaling centers able to induce foci of mesenchymal and EMT differentiation. Thus, microstructured materials can mediate local histogenic processes to enhance the structure and composition of tissue models.
Optimized CRISPR tools and site-directed transgenesis inCulex quinquefasciatusmosquitoes for gene drive development
Authors: Feng Xuechun , Del Amo Víctor López , Mameli Enzo , Lee Megan , Bishop Alena L. , Perrimon Norbert , Gantz Valentino M.
Published: February 2021

Culexmosquitoes are a global vector for multiple human and animal diseases, including West Nile virus, lymphatic filariasis, and avian malaria, posing a constant threat to public health, livestock, companion animals, and endangered birds. While rising insecticide resistance has threatened the control ofCulexmosquitoes, advances in CRISPR genome-editing tools have fostered the development of alternative genetic strategies such as gene drive systems to fight disease vectors. However, though gene-drive technology has quickly progressed in other mosquitoes, advances have been lacking inCulex. Here, we developed aCulex-specific Cas9/gRNA expression toolkit and used site-directed homology-based transgenesis to generate and validate aCulex quinquefasciatusCas9-expressing line. We showed that gRNA scaffold variants improve transgenesis efficiency in bothCulexandDrosophilaand boost gene-drive performance in the fruit fly. These findings support future technology development to controlCulexmosquitoes and provide valuable insight for improving these tools in other species.
Bacterial diversity of chronic middle ear lesions revealed by high-throughput sequencing
Authors: Gu Xingzhi , Cheng Xiuqing , Abulajiang Tuoheti , Huang Xiaoban
Published: February 2021

Chronic otitis media is a common middle ear disease in otolaryngology and head and neck surgery. Bacterial infection is considered the main cause of disease, but relying on conventional bacterial cultures can be problematic for identification of specific pathogens. Current research suggests that bacteria in microbial communities can only be identified by rDNA sequencing of bacteria.This prospective study utilized broad-range PCR amplification of 16S rRNA genes with clone analysis to compare bacterial diversity in lesions from 6 patients with chronic suppurative otitis media (CSOM) and 10 patients with cholesteatoma of middle ear lesions. Bacteria were analyzed at the phylum, order, family, genus, and species levels. Bacterial species abundance and species diversity were greater in cholesteatoma of the middle ear lesions than in CSOM lesions. At all bacterial taxonomic levels, the epithelial tissue of middle ear cholesteatoma was complex in terms of bacterial diversity, covering a large number of Gram-positive and Gram-negative bacteria, likely related to bacterial microbiome formation. In contrast, bacteriology of the CSOM lesions was relatively simple at all taxonomic levels, with all sequences characterized as belonging to Gram-negative bacteria. These results suggest that persistent infection of middle ear cholesteatoma may be a microbial flora disorder, which is related to conditional pathogenic bacteria, rather than a single bacterial infectious disease. Findings from the study may have implications in the selection of antimicrobial agents for the treatment of chronic otitis media.
Comparative proteome signatures of trace samples by multiplexed Data-Independent Acquisition
Authors: Ctortecka Claudia , Krššáková Gabriela , Stejskal Karel , Penninger Josef M. , Mendjan Sasha , Mechtler Karl , Stadlmann Johannes
Published: February 2021

Single cell transcriptomics has revolutionized our understanding of basic biology and disease. Since transcript levels often do not correlate with protein expression, it is crucial to complement transcriptomics approaches with proteome analyses at single cell resolution. Despite continuous technological improvements in sensitivity, mass spectrometry-based single cell proteomics ultimately faces the challenge of reproducibly comparing the protein expression profiles of thousands of individual cells. Here, we combine two hitherto opposing analytical strategies, DIA and Tandem-Mass-Tag (TMT)-multiplexing, to generate highly reproducible, quantitative proteome signatures from ultra-low input samples. While conventional, data-dependent shotgun proteomics (DDA) of ultra-low input samples critically suffers from the accumulation of missing values with increasing sample-cohort size, data-independent acquisition (DIA) strategies do usually not take full advantage of isotope-encoded sample multiplexing. We developed a novel, identification-independent proteomics data-analysis pipeline that allows to quantitatively compare DIA-TMT proteome signatures across hundreds of samples independent of their biological origin, and to identify cell types and single protein knockouts. We validate our approach using integrative data analysis of different human cell lines and standard database searches for knockouts of defined proteins. These data establish a novel and reproducible approach to markedly expand the numbers of proteins one detects from ultra-low input samples, such as single cells.
The geometry of cortical representations of touch in rodents
Authors: Nogueira Ramon , Rodgers Chris C. , Bruno Randy M. , Fusi Stefano
Published: February 2021

Neural responses are often highly heterogeneous non-linear functions of multiple task variables, a signature of a high-dimensional geometry of the neural representations. We studied the representational geometry in the somatosensory cortex of mice trained to report the curvature of objects using their whiskers. High-speed videos of the whisker movements revealed that the task can be solved by linearly integrating multiple whisker contacts over time. However, the neural activity in somatosensory cortex reflects a process of non-linear integration of spatio-temporal features of the sensory inputs. Although the responses at first appear disorganized, we could identify an interesting structure in the representational geometry: different whisker contacts are disentangled variables represented in approximately, but not fully, orthogonal subspaces of the neural activity space. The observed geometry allows linear readouts to perform a broad class of tasks of different complexities without compromising the ability to generalize to novel situations.
Cholinergic calcium responses in cultured antennal lobe neurons of the migratory locust
Authors: Bergmann Gregor A. , Bicker Gerd
Published: February 2021

Locusts are advantageous organisms to elucidate mechanisms of olfactory coding at the systems level. Sensory input is provided by the olfactory receptor neurons of the antenna, which send their axons into the antennal lobe. So far, cellular properties of neurons isolated from the circuitry of the olfactory system, such as transmitter-induced calcium responses, have not been studied. Biochemical and immunocytochemical investigations have provided evidence for acetylcholine as classical transmitter of olfactory receptor neurons. Here, we characterize cell cultured projection and local interneurons of the antennal lobe by cytosolic calcium imaging to cholinergic stimulation. We bulk loaded the indicator dye Cal-520 AM in dissociated culture and recorded calcium transients after applying cholinergic agonists and antagonists. The majority of projection and local neurons respond with increases in calcium levels to activation of both nicotinic and muscarinic receptors. In local interneurons, we reveal interactions lasting over minutes between intracellular signaling pathways, mediated by muscarinic and nicotinic receptor stimulation. The present investigation is pioneer in showing that Cal-520 AM readily loadsLocusta migratorianeurons, making it a valuable tool for future research in locust neurophysiology, neuropharmacology, and neurodevelopment.
BMP signaling interferes with optic chiasm formation and retinal ganglion cell pathfinding in zebrafish
Authors: Knickmeyer Max D. , Mateo Juan L. , Heermann Stephan
Published: February 2021

Decussation of axonal tracts is an important hallmark of vertebrate neuroanatomy resulting in one brain hemisphere controlling the contralateral side of the body and also computing the sensory information originating from that respective side. Here, we show that BMP interferes with optic chiasm formation and RGC pathfinding in zebrafish.

Experimental induction of BMP4 at 15 hpf results in a complete ipsilateral projection of RGC axons and failure of commissural connections of the forebrain in part being the result of an interaction with shh signaling, transcriptional regulation of midline guidance cues and an affected optic stalk morphogenesis.

Experimental induction of BMP4 at 24 hpf, resulting in only a mild repression of forebrain shh ligand expression but in a broad expression of pax2a in the diencephalon, does not per se prevent RGC axons from crossing the midline. It nevertheless shows severe pathologies of RGC projections e.g. the fasciculation of RGC axons with the ipsilateral optic tract resulting in the innervation of one tectum by two eyes or the projection of RGC axons in the direction of the contralateral eye.
Molecular principles of Piwi-mediated cotranscriptional silencing through the dimeric SFiNX complex
Authors: Schnabl Jakob , Wang Juncheng , Hohmann Ulrich , Gehre Maja , Batki Julia , Andreev Veselin I. , Purkhauser Kim , Fasching Nina , Duchek Peter , Novatchkova Maria , Mechtler Karl , Plaschka Clemens , Patel Dinshaw J. , Brennecke Julius
Published: February 2021

Nuclear Argonaute proteins, guided by their bound small RNAs to nascent target transcripts, mediate cotranscriptional silencing of transposons and repetitive genomic loci through heterochromatin formation. The molecular mechanisms involved in this process are incompletely understood. Here, we show that the SFiNX complex, a silencing mediator downstream from nuclear Piwi-piRNA complexes in Drosophila, facilitates cotranscriptional silencing as a homodimer. The dynein light chain protein Cut up/LC8 mediates SFiNX dimerization, and its function can be bypassed by a heterologous dimerization domain, arguing for a constitutive SFiNX dimer. Dimeric, but not monomeric SFiNX, is capable of forming molecular condensates in a nucleic acid-stimulated manner. Mutations that prevent SFiNX dimerization result in loss of condensate formation in vitro and the inability of Piwi to initiate heterochromatin formation and silence transposons in vivo. We propose that multivalent SFiNX-nucleic acid interactions are critical for heterochromatin establishment at piRNA target loci in a cotranscriptional manner.
Enhancing CRISPR deletion via pharmacological delay of DNA-PKcs
Authors: Bosch-Guiteras Núria , Uroda Tina , Guillen-Ramirez Hugo A. , Riedo Rahel , Gazdhar Amiq , Esposito Roberta , Pulido-Quetglas Carlos , Zimmer Yitzhak , Medová Michaela , Johnson Rory
Published: February 2021

CRISPR-Cas9 deletion (CRISPR-del) is the leading approach for eliminating DNA from mammalian cells and underpins a variety of genome-editing applications. Target DNA, defined by a pair of double-strand breaks (DSBs), is removed during nonhomologous end-joining (NHEJ). However, the low efficiency of CRISPR-del results in laborious experiments and false-negative results. By using an endogenous reporter system, we show that repression of the DNA-dependent protein kinase catalytic subunit (DNA-PKcs)—an early step in NHEJ—yields substantial increases in DNA deletion. This is observed across diverse cell lines, gene delivery methods, commercial inhibitors, and guide RNAs, including those that otherwise display negligible activity. We further show that DNA-PKcs inhibition can be used to boost the sensitivity of pooled functional screens and detect true-positive hits that would otherwise be overlooked. Thus, delaying the kinetics of NHEJ relative to DSB formation is a simple and effective means of enhancing CRISPR-deletion.
A sociological view toward the economic and technological development zones in China
Authors: Yan Zheng Joseph , Zámborský Peter , Liang Hongji
Published: February 2021

Purpose

This paper aims to introduce a sociological view to analyze the Economic and Technological Development Zones (ETDZs) in China. The ETDZs are established to foster concentrated regional economic development. Currently, there are 219 national level ETDZs throughout the country, and they account for more than 10% of China’s total GDP. Given the scale of the Chinese economy, the economic significance of the ETDZs indicates an important phenomenon for better understanding.

Design/methodology/approach

This paper conceptualizes the Chinese ETDZs with sociology concepts of place, institutional logics and habitus.

Findings

The sociological view centers on how the ETDZs can naturally evolve with the participation of firms. The authors show that firms operating in the ETDZs can unintentionally alter the dynamics of the policy environment. A process model of place, logics and practice is developed to encapsulate these ideas.

Originality/value

Conventional research on the connections between Chinese Government policies and business operations has been largely conducted under a political economy view which outlines a top-down logic (policymaking, followed by firms’ strategic response). The authors move away from this dogma by introducing a sociological view of the ETDZs. This new view highlights that a government-initiated policy environment in China can also evolve when firms are seeking to blend into the regulatory system, instead of trying to shape the coercive arrangements to suit their best interests.
Responsiveness of residential construction-production progress to house price dynamics
Authors: Ma Le , Liu Henry , Sing Michael
Published: February 2021

Purpose

This study aims to address the gap by empirically exploring how residential construction-production progress, which includes project commencement, under-construction and project completion, responds dynamically to fluctuations in house prices.

Design/methodology/approach

A vector autoregressive model and an impulse response function are applied to simulate and analyse the circle of the stage-responsiveness of residential construction to residential property price dynamics in the state of Victoria, Australia. The quarterly numbers of dwelling units commenced, under-construction and completed are used as the proxy for the residential construction activities at three stages over the construction progress.

Findings

The analysis indicates that the dynamics are essentially transmitted throughout the construction process and can substantially impact the pace of production progress. The findings from this study provide an empirical base that should be useful in developing price-elasticity and production theories applicable to the context of residential property construction.

Research limitations/implications

The findings described above have been generated basically by examining the case of Victoria, Australia at a macro level. The generalisation of the research output needs to be verified further by future researchers using data collected from other regions/countries. Nevertheless, the reliability of the conclusions with particular practical implications can be substantially improved by future researchers by analysing more markets and production proxies at the activity level.

Practical implications

Based on new empirical findings, this research argues that building activity (i.e. under construction) played as a gateway between the construction and housing sectors, via which the inter-responsiveness of the housing supply in terms of construction activities and housing prices are transmitted.

Originality/value

This research firstly attempts to explore the inter-responsiveness between the real estate and construction sectors. A simulated circle of the stage-responsiveness of residential construction to residential property price dynamics is proposed, which can serve as a significant foundation for developing the theory of construction production.
Application of Lean Six Sigma framework for improving manufacturing efficiency: a case study in Indian context
Authors: Sharma Astha , Bhanot Neeraj , Gupta Ajay , Trehan Rajeev
Published: February 2021

Purpose

This study aims to utilize DMAIC methodology along with value stream mapping and other Lean Six Sigma tools in a major automobile light manufacturing industry to reduce defect rates and increase production capacity in their manufacturing line. The study also proposes a modified framework based on lean principles and FlexSim to identify and reduce waste in the selected industry.

Design/methodology/approach

A Lean Six Sigma modified framework has been deployed with DMAIC to reduce the defect rate and increase the production rate. Various tools like value stream mapping, brainstorming, Pareto charts, 5S, kanban, etc. have been used at different phases of DMAIC targeting wastes and inventory in the production line. Also, a simulation model has been utilized for the automobile light manufacturing industry to improve the machine utilization time with varying batch sizes.

Findings

The results of the study indicated a 53% reduction in defect rates. Thus, there would be an expected improvement in sigma value from 3.78 to 3.89 and a reduction in defects per million opportunities (DPMO) from 11,244 to 8,493. Additionally, simulation model using FlexSim was developed, and the optimum ordering batch size of raw material was obtained. It was also analyzed that idle time for various stations could be reduced by up to 30%.

Practical implications

The utilized framework helps identify defects for managers to increase production efficiency. The workers, operators and supervisors on the production line also need to be trained regularly for identifying the areas of improvement.

Originality/value

The modified Lean Six Sigma framework used in this study includes FlexSim simulation to make the framework robust, which has not been used with LSS tools in the literature studied. Also, the LSS finds very less application in the manufacturing domain, considering which this study tends to add value in existing literature taking a case of an automobile light manufacturing industry.
Firm capability assessment via the BSC and DEA
Authors: Lin Chinho , Ting Shu-Fang , Lee Leslie , Lin Sheng-Tun
Published: February 2021

Purpose

This study proposes an objective assessment model to evaluate the performance of internal and external capabilities of firms. It facilitates firms to invest appropriate resources to cultivate the organizational capability necessary to meet the requirements of the performance indicators.

Design/methodology/approach

This study integrates the concepts of resource-based theory, the organizational capability concept, and conduct a performance analysis to the four perspectives of the BSC by implementing the fuzzy set theory and data employment analysis.

Findings

The findings show that the appropriate strategies help allocate available resources and capabilities during the different product life cycle, which provides practical guidelines for firms to achieve sustaining competitive advantage.

Research limitations/implications

The selected factors were focused on four resources and capabilities rather than all possible factors.

Originality/value

An objective assessment model was created based on internal and external competitive performance efficiency in this research field. This model facilitates the ability of the top management to make decisions for resource allocation that will enhance firm's performance.
Crime linkage practice in New Zealand
Authors: Tonkin Matt , Weeks Martin Joseph
Published: February 2021

Purpose

The purpose of this paper is to understand (i) how crime linkage is currently performed with residential burglaries in New Zealand, (ii) the factors that promote/hinder accurate crime linkage and (iii)whether computerised decision-support tools might assist crime linkage practice.

Design/methodology/approach

A total of 39 New Zealand Police staff completed a questionnaire/interview/focus group relating to the process, challenges, products and uses of crime linkage with residential burglary in New Zealand. These data (alongside four redacted crime linkage reports) were subjected to thematic analysis.

Findings

The data clearly indicated wide variation in crime linkage process, methods and products (Theme 1). Furthermore, a number of factors were identified that impacted on crime linkage practice (Theme 2).

Research limitations/implications

Future research should develop computerised crime linkage decision-support tools and evaluate their ability to enhance crime linkage practice. Also, researchers should explore the use of crime linkage in court proceedings.

Practical implications

To overcome the barriers identified in the current study, greater training in and understanding of crime linkage is needed. Moreover, efforts to enhance the quality of crime data recorded by the police will only serve to enhance crime linkage practice.

Social implications

By enhancing crime linkage practice, opportunities to reduce crime, protect the public and deliver justice for victims will be maximised.

Originality/value

The practice of crime linkage is under-researched, which makes it difficult to determine if/how existing empirical research can be used to support ongoing police investigations. The current project fills that gap by providing a national overview of crime linkage practice in New Zealand, a country where crime linkage is regularly conducted by the police, but no published linkage research exists.
Risk-adjusted banks' resource-utilization and investment efficiencies: does intellectual capital matter?
Authors: Kweh Qian Long , Lu Wen-Min , Tone Kaoru , Nourani Mohammad
Published: February 2021

Purpose

The purpose of this study is twofold. First, this research estimates banks' efficiencies from the perspectives of resource utilization and investment after incorporating risk measures as an exogenous input in the investment-efficiency stage. Second, the current study examines the relationship between intellectual capital (IC) and banks' efficiencies.

Design/methodology/approach

First, this study uses a dynamic network data envelopment analysis approach in investigating the efficiencies of 24 Taiwanese banks in 2007–2018 from two perspectives. Second, this research utilizes various regression techniques, namely, ordinary least squares (OLS), robust least squares and truncated regression, to gauge the impact of IC on banks' efficiencies. Typically, IC is determined based on a monetary value-based measure and value-added intellectual coefficient (VAICTM).

Findings

Resource-utilization (investment) efficiencies were observed as 0.941 (0.964), thereby contributing to the mean overall efficiency of the sample banks at 0.952. However, the related efficiency changes decline over the sample period, thereby suggesting that the average banks' efficiencies hardly increase. Regression analyses show a significantly positive relationship between IC and banks' overall resource-utilization and investment efficiencies.

Research limitations/implications

Overall, this study suggests that researchers should consider risks when estimating banks' efficiencies owing to their connection to banks' investment performance. From banks' dynamic two-stage efficiencies, this study demonstrated that investments in IC will bring improved future economic benefits.

Originality/value

Different from prior studies, this study improves banks' efficiency evaluation models by incorporating risk measures and assuming weighted periods for the 2007–2008 global financial crisis. Moreover, the use of monetary value-based measure of IC provides consistent results as the commonly-used VAICTM does.
Intellectual capital and supply chain resilience
Authors: Mubarik Muhammad Shujaat , Bontis Nick , Mubarik Mobasher , Mahmood Tarique
Published: February 2021

Purpose

The main objective of this study is to test whether firms with a higher level of intellectual capital (IC) perform better in terms of their supply chain resilience compared to those with lower levels of IC. Likewise, the study also examines the impact of IC (characterized by human capital, relational capital and structural capital) on supply chain resilience directly and through supply chain learning.

Design/methodology/approach

Data were collected from the 159 processed-food sector firms using a close-ended questionnaire during the corona virus 2019 (COVID-19) pandemic. Partial least squares structural equation modelling (PLS-SEM), partial least squares multigroup analysis (PLS-MGA) and one-way analysis of variance (ANOVA) were used to test a set of hypotheses emanating from a conceptual model of IC and supply chain resilience.

Findings

Empirical results revealed a significant influence of all dimension of IC on a firm's supply chain learning and supply chain resilience. Likewise, findings also exhibit a momentous role of supply chain learning in reinforcing the impact of IC on supply chain resilience. Cross-firm size comparison reveals that supply chain resilience of firms with a higher level of IC performed significantly better than those with lower levels of IC. Firms with a higher level of structural capital had a highly resilient supply chain.

Practical implications

Findings of the study imply that IC and supply chain learning should be considered as a strategic tool and should be strategically developed for uplifting a supply chain performance of a firm. The development of IC and supply chain learning (SCL) not only improves the supply chain resilience of a firm but also can help to integrate the internal and external knowledge for harnessing supply chain resilience.

Originality/value

This research study was conducted during the COVID-19 pandemic which provides a unique setting to examine resiliency and learning.