bluuebunny/crossref_metadata_2025 huggingface dataset:
Boosting the toolbox for live imaging of translation
Authors: Bellec Maelle , Chen Ruoyu , Dhayni Jana , Trullo Antonello , Avinens Damien , Karaki Hussein , Mazzarda Flavia , Lenden-Hasse Helene , Favard Cyril , Lehmann Ruth , Bertrand Edouard , Lagha Mounia , Dufourt Jeremy
Published: February 2023

Live imaging of translation based on tag recognition by a single chain antibody is a powerful technique to assess translation regulation in living cells. However, especially in a multicellular organism, this approach is challenging and requires optimization in terms of expression level and detection sensitivity of the system. Here, we improved existing fluorescent tools and developed new ones to image and quantify nascent translation in the livingDrosophilaembryo and in mammalian cells. We tested and characterized five different Green Fluorescent Protein variants fused to the single chain fragment variable (scFv) and uncover photobleaching, aggregation and intensity disparities. Using different strengths of germline and somatic drivers, we determined that the availability of the scFv is critical in order to detect translation throughout development. We introduced a new translation imaging method based on a nanobody/tag system named ALFA-array, allowing the sensitive and simultaneous detection of the translation of several distinct mRNA species. Finally, we developed a largely improved RNA imaging system based on an MCP-tdStaygold fusion.
Evaluation of non-modified wireframe DNA origami for acute toxicity and biodistribution in mice
Authors: Wamhoff Eike-Christian , Knappe Grant A. , Burds Aurora A. , Du Rebecca R. , Neun Barry W. , Difilippantonio Simone , Sanders Chelsea , Edmondson Elijah F. , Matta Jennifer L. , Dobrovolskaia Marina A. , Bathe Mark
Published: February 2023

Wireframe DNA origami can be used to fabricate virus-like particles for a range of biomedical applications, including the delivery of nucleic acid therapeutics. However, the acute toxicity and biodistribution of these wireframe nucleic acid nanoparticles (NANPs) have not previously been characterized in animal models. In the present study, we observed no indications of toxicity in BALB/c mice following therapeutically relevant dosage of unmodified DNA-based NANPs via intravenous administration, based on liver and kidney histology, liver biochemistry, and body weight. Further, the immunotoxicity of these NANPs was minimal, as indicated by blood cell counts and type-I interferon and pro-inflammatory cytokines. In an SJL/J model of autoimmunity, we observed no indications of NANP-mediated DNA-specific antibody response or immune-mediated kidney pathology following the intraperitoneal administration of NANPs. Finally, biodistribution studies revealed that these NANPs accumulate in the liver within one hour, concomitant with substantial renal clearance. Our observations support the continued development of wireframe DNA-based NANPs as next-generation nucleic acid therapeutic delivery platforms.
A Gold Standard for Transcription Factor Regulatory Interactions inEscherichia coliK-12: Architecture of Evidence Types
Authors: Lara Paloma , Gama-Castro Socorro , Salgado Heladia , Rioualen Claire , Tierrafría Víctor H. , Muñiz-Rascado Luis J. , Bonavides-Martínez César , Collado-Vides Julio
Published: February 2023

Post-genomic implementations have expanded the experimental strategies to identify elements involved in the regulation of transcription initiation. As new methodologies emerge, a natural step is to compare their results with those from established methodologies, such as the classic methods of molecular biology used to characterize transcription factor binding sites, promoters, or transcription units.

In the case ofEscherichia coliK-12, the best-studied microorganism, for the last 30 years we have continuously gathered such knowledge from original scientific publications, and have organized it in two databases, RegulonDB and EcoCyc. Furthermore, since RegulonDB version 11.0 (1), we offer comprehensive datasets of binding sites from chromatin immunoprecipitation combined with sequencing (ChIP-seq), ChIP combined with exonuclease digestion and next-generation sequencing (ChIP-exo), genomic SELEX screening (gSELEX), and DNA affinity purification sequencing (DAP-seq) HT technologies, as well as additional datasets for transcription start sites, transcription units and RNA sequencing (RNA-seq) expression profiles.

Here, we present for the first time an analysis of the sources of knowledge supporting the collection of transcriptional regulatory interactions (RIs) ofE. coliK-12. An RI is formed by the transcription factor, its positive or negative effect on a promoter, a gene or transcription unit. We improved the evidence codes so that the specific methods are described, and we classified them into seven independent groups. This is the basis for our updated computation of confidence levels, weak, strong, or confirmed, for the collection of RIs. We compare the confidence levels of the RI collection before and after adding HT evidence illustrating how knowledge will change as more HT data and methods appear in the future. Users can generate subsets filtering out the method they want to benchmark and avoid circularity, or keep for instance only the confirmed interactions.

The comparison of different HT methods with the available datasets indicate that ChIP-seq recovers the highest fraction (>70%) of binding sites present in RegulonDB followed by gSELEX, DAP-seq and ChIP-exo. There is no other genomic database that offers this comprehensive high-quality anatomy of evidence supporting a corpus of transcriptional regulatory interactions.
Improvement of thermostability and activity of PET-degrading enzyme Cut190 towards a detailed understanding and application of the enzymatic reaction mechanism
Authors: Numoto Nobutaka , Kamiya Narutoshi , Oda Masayuki
Published: February 2023

Enzymes capable of hydrolyzing polyethylene terephthalate (PET) and other plastics are attractive catalysts for application to the recycling of plastic waste due to their generally low environmental impact. Cut190 is a cutinase from a thermophilic actinomycete and shows PET-degrading activity and high thermal stability. We developed a series of Cut190 mutants exhibiting further improvements in thermal stability and activity, and showed that the unique stabilization and activation mechanism was dependent on Ca2+ions. Two of these mutants, Cut190** and Cut190*SS, differed from the previous mutant Cut190* by deletion of the three C-terminal residues and introduction of five substitutions, including two cysteines forming a disulfide-bond, respectively. These mutants exhibit higher thermal stability and activity, which are often mutually exclusive characteristics. Crystallographic studies of these mutants and their inactivated derivatives demonstrated that they could have a novel ejecting form that would be responsible for releasing products. We also determined the crystal structures of ligand-bound complexes, which revealed the molecular mechanisms of the aromatic-ring recognition and the tetrahedral intermediate during the substrate cleaving, although the ligands had no aromatic ring but a cyclic group. This structural information provides insights into the mechanism of the Ca2+-dependent PET-cleaving activity of Cut190 and provides a useful basis for further mutant design and computational studies.
FOXP3+regulatory T cells use heparanase to access IL-2 bound to ECM in inflamed tissues
Authors: Martinez Hunter A. , Koliesnik Ievgen , Kaber Gernot , Reid Jacqueline K. , Nagy Nadine , Barlow Graham , Falk Ben A. , Medina Carlos O. , Hargil Aviv , Vlodavsky Israel , Li Jin-Ping , Pérez-Cruz Magdiel , Tang Sai-Wen , Meyer Everett H. , Wrenshall Lucile E. , Lord James D. , Garcia K. Christopher , Palmer Theo D. , Steinman Lawrence , Nepom Gerald T. , Wight Thomas N. , Bollyky Paul L. , Kuipers Hedwich F.
Published: February 2023

FOXP3+regulatory T cells (Treg) depend on exogenous IL-2 for their survival and function, but circulating levels of IL-2 are low, making it unclear how Treg access this critical resourcein vivo. Here, we show that Treg use heparanase (HPSE) to access IL-2 sequestered by heparan sulfate (HS) within the extracellular matrix (ECM) of inflamed central nervous system tissue. HPSE expression distinguishes human and murine Treg from conventional T cells and is regulated by the availability of IL-2. HPSE-/-Treg have impaired stability and functionin vivo, including the experimental autoimmune encephalomyelitis (EAE) mouse model of multiple sclerosis. Conversely, endowing Treg with HPSE enhances their ability to access HS-sequestered IL-2 and their tolerogenic functionin vivo. Together, these data identify novel roles for HPSE and the ECM in immune tolerance, providing new avenues for improving Treg-based therapy of autoimmunity.

One-Sentence Summary

Regulatory T cells use heparanase to strip IL-2 bound to extracellular matrix within inflamed tissues, thereby supporting their homeostasis and function.
Structural homology screens reveal poxvirus-encoded proteins impacting inflammasome-mediated defenses
Authors: Boys Ian N. , Johnson Alex G. , Quinlan Meghan , Kranzusch Philip J. , Elde Nels C.
Published: February 2023

Viruses acquire host genes via horizontal gene transfer and can express them to manipulate host biology during infections. Some viral and host homologs retain sequence identity, but evolutionary divergence can obscure host origins. We used structural modeling to compare vaccinia virus proteins with metazoan proteomes. We identified vacciniaA47Las a homolog of gasdermins, the executioners of pyroptosis. An X-ray crystal structure of A47 confirmed this homology and cell-based assays revealed that A47 inhibits pyroptosis. We also identified vacciniaC1Las the product of a cryptic gene fusion event coupling a Bcl-2 related fold with a pyrin domain. C1 associates with components of the inflammasome, a cytosolic innate immune sensor involved in pyroptosis, yet paradoxically enhances inflammasome activity, suggesting a benefit to poxvirus replication in some circumstances. Our findings demonstrate the potential of structural homology screens to reveal genes that viruses capture from hosts and repurpose to benefit viral fitness.
Whole-genome sequencing of ethnolinguistic diverse northwestern Chinese Hexi Corridor people from the 10K_CPGDP project suggested the differentiated East-West genetic admixture along the Silk Road and their biological adaptations
Authors: He Guanglin , Yao Hongbing , Sun Qiuxia , Duan Shuhan , Tang Renkuan , Chen Jing , Wang Zhiyong , Sun Yuntao , Li Xiangping , Wang Shaomei , Hu Liping , Yun Libing , Yang Junbao , Yan Jiangwei , Nie Shengjie , Zhu Yanfeng , Liu Chao , Wang Mengge
Published: February 2023

The ancient Silk Road served as the main connection between East and West Eurasia for several centuries. At any rate, the genetic exchange between populations along the ancient Silk Road was likely to leave traces on the contemporary gene pool of local people in Northwest China, which was the passage of the Northern Silk Road. However, genetic sources from northwestern China are under-represented in the current population-scale genomic database. To characterize the genetic architecture and adaptative history of the Northern Silk Road ethnic populations, we performed whole-genome sequencing on 126 individuals from six ethnolinguistic groups (Tibeto-Burman (TB)-speaking Tibetan, Mongolic (MG)-speaking Dongxiang/Tu/eastern Yugur, and Turkic (TK)-speaking Salar/western Yugur) living in Gansu and Qinghai in the 10K Chinese people Genomic Diversity Project (10K_CPGDP). We observed ethnicity-related differentiated population structures among these geographically close Northwest Chinese populations, that is, Salar and Tu people showed a close affinity with southwestern TB groups, and other studied populations shared more alleles with MG and Tungusic groups. Overall, the patterns of genetic clustering were not consistent with linguistic classifications. We estimated that Dongxiang, Tibetan, and Yugur people inherited more than 10% West Eurasian ancestry, much higher than that of Salar and Tu people (<7%). Hence, the difference in the proportion of West Eurasian ancestry has primarily contributed to the genetic divergence of geographically close Northwest Chinese populations. The signatures of natural selection were identified in genes associated with cardiovascular system diseases or lipid metabolism related to triglyceride levels (e.g.,PRIM2, PDE4DIP, NOTCH2, DDAH1, GALNT2, andMLIP) and developmental and neurogenetic diseases (e.g.,NBPFs 8/9/20/25P, etc.). Moreover, theEPAS1gene, a transcription factor regulating hypoxia response, showed relatively high PBS values in our studied groups. The sex-biased admixture history, in which the West Eurasian ancestry was introduced primarily by males, was identified in Dongxiang, Tibetan, and Yugur populations. We determined that the eastern-western admixture occurred ∼783–1131 years ago, coinciding with the intensive economic and cultural exchanges during the historic Trans-Eurasian cultural exchange era.
Cure of congenital purpura fulminans via expression of engineered protein C through neonatal genome editing in mice
Authors: Togashi Tomoki , Baatartsogt Nemekhbayar , Nagao Yasumitsu , Kashiwakura Yuji , Hayakawa Morisada , Kamoshita Nobuhiko , Hiramoto Takafumi , Fujiwara Takayuki , Morishita Eriko , Nureki Osamu , Ohmori Tsukasa
Published: February 2023

Protein C (PC) is a plasma anticoagulant encoded byPROC; mutation in bothPROCalleles results in neonatal purpura fulminans—a fatal systemic thrombotic disorder. In the present study, we aimed to develop a genome editing treatment to cure congenital PC deficiency. First, we generated an engineered activated PC to insert a self-cleaving peptide sequence between light and heavy chains. The engineered PC could be released in its activated form and significantly prolonged the plasma coagulation time independent of the cofactor activity of protein Sin vitro. The adeno-associated virus (AAV) vector-mediated expression of the engineered PC, but not wild-type PC, prolonged coagulation time owing to the inhibition of activated coagulation factor V in a dose-dependent manner and abolished pathological thrombus formationin vivoin C57BL/6 mice. The insertion ofEGFPsequence conjugated with self-cleaving peptide sequence atAlblocus via neonatalin vivogenome editing using AAV vector resulted in the expression of EGFP in 7% of liver cells, mainly via homology-directed repair, in mice. Finally, we succeeded in improving the survival of PC-deficient mice by expressing the engineered PC via neonatal genome editingin vivo. These results suggest that the expression of the engineered PC via neonatal genome editing is a potential cure for severe congenital PC deficiency.

One Sentence Summary

Ectopic expression of an engineered protein C via genome editing cures protein C deficiency in mice.
The IRE1α-endonuclease regulates PD-1 expression through a novel XBP1/miRNA-34a axis within Natural Killer cells
Authors: Bednarska Karolina , Thillaiyampalam Gayathri , Mujaj Sally , Nourse Jamie , Gunawardana Jay , Sabdia Muhammed B. , Cui Qingyan , de Long Lilia M. , Vari Frank , Gandhi Maher K. , Cristino Alexandre S.
Published: February 2023

Activation of the IRE1α-endonuclease is critical for Natural Killer (NK)-cell function. We describe a novel regulatory role for IRE1α-endonuclease in fine-tuning NK-cell effector functions through an inter-connected activation of the transcription factor XBP1s and inhibition of microRNA-34a-5p (miR-34a-5p) to modulate PD-1 immune checkpoint expression. NK-cells, when exposed to cancer cells, activate IRE1α-endonuclease mediated decay of miR-34a-5p. This reduces miR-34a-5p and consequently increases the expression of the target genes XBP1 and PD-1. IRE1α-endonuclease activation not only enhances NK-cell effector function but also promotes PD-1 expression. PD-1 is itself directly regulated by miR-34a-5p, which binds to the 3’UTR of PD-1 messenger RNA to repress PD-1 protein at the NK-cell surface. IRE1α-pathway activation is impaired in the NK-cells of patients with Hodgkin Lymphoma, and miR-34a-5p and PD-1 expression are inversely correlated. The IRE1α-pathway plays a dual role in regulating the XBP1/miRNA-34a axis and PD-1 expression within NK-cells, that is disrupted in cancer patients.
Immediate targeting of host ribosomes by jumbo phage encoded proteins
Authors: Gerovac Milan , Chihara Kotaro , Wicke Laura , Böttcher Bettina , Lavigne Rob , Vogel Jörg
Published: February 2023

Bacteriophages must seize control of the host gene expression machinery to promote their own protein synthesis. Since the bacterial hosts are armed with numerous anti-phage defence systems, it is essential that mechanisms of host take-over act immediately upon infection. Although individual proteins that modulate components of the bacterial gene expression apparatus have been described in several different phages, systematic approaches which capture the phage’s arsenal for immediate targeting of host transcription and translation processes have been lacking. In particular, there are no known phage factors that associate directly with host ribosomes to modulate protein synthesis. Here, we take an integrative high-throughput approach to uncover numerous new proteins encoded by the jumbo phage ΦKZ that target the gene expression machinery of the Gram-negative human pathogenPseudomonas aeruginosaimmediately upon infection. By integrating biochemical and structural analyses, we identify a conserved phage factor that associates with the large ribosomal subunit by binding the 5S ribosomal RNA. This highly abundant factor is amongst the earliest ΦKZ proteins expressed after infection and stays bound to ribosomes during the entire translation cycle. Our study provides a general strategy to decipher molecular components of phage-mediated host take-over and argues that phage genomes represent a large discovery space for proteins that modulate the host gene expression machinery.
Bacterial histone HBb fromBdellovibrio bacteriovoruscompacts DNA by bending
Authors: Hu Yimin , Schwab Samuel , Deiss Silvia , Escudeiro Pedro , van Heesch Thor , Joiner Joe D. , Vreede Jocelyne , Hartmann Marcus D. , Lupas Andrei N. , Alvarez Birte Hernandez , Alva Vikram , Dame Remus T.
Published: February 2023

Histones are essential for genome compaction and transcription regulation in eukaryotes, where they assemble into octamers to form the nucleosome core. In contrast, archaeal histones assemble into dimers that form hypernucleosomes upon DNA binding. Although histone homologs have been identified in bacteria recently, their DNA-binding characteristics remain largely unexplored. Our study reveals that the bacterial histone HBb (Bd0055) is indispensable for the survival ofBdellovibrio bacteriovorus, suggesting critical roles in DNA organization and gene regulation. By determining crystal structures of free and DNA-bound HBb, we unveil its distinctive dimeric assembly, diverging from those of eukaryotic and archaeal histones, while also elucidating how it binds and bends DNA through interaction interfaces reminiscent of eukaryotic and archaeal histones. Building on this, by employing various biophysical and biochemical approaches, we further substantiated the ability of HBb to bind and compact DNA by bending in a sequence-independent manner. Finally, using DNA affinity purification and sequencing, we reveal that HBb binds along the entire genomic DNA ofB. bacteriovoruswithout sequence specificity. These distinct DNA-binding properties of bacterial histones, showcasing remarkable similarities yet significant differences from their archaeal and eukaryotic counterparts, highlight the diverse roles histones play in DNA organization across all domains of life.

Histones, traditionally known for organizing and regulating DNA in eukaryotes and archaea, have recently been discovered in bacteria, opening up a new frontier in our understanding of genome organization across the domains of life. Our study investigates the largely unexplored DNA-binding properties of bacterial histones, focusing on HBb inBdellovibrio bacteriovorus. We reveal that HBb is essential for bacterial survival and exhibits DNA-binding properties similar to archaeal and eukaryotic histones. However, unlike eukaryotic and archaeal histones, which wrap DNA, HBb bends DNA without sequence specificity. This work not only broadens our understanding of DNA organization across different life forms but also suggests that bacterial histones may have diverse roles in genome organization.
Integrated analysis of gene expression and protein-protein interaction with tensor decomposition
Authors: Taguchi Y-H. , Turki Turki
Published: February 2023

Motivation

Integration of gene expression (GE) and protein-protein interaction (PPI) is not straightforward because the former is provided as a matrix, whereas the latter is provided as a network. In many cases, genes processed with GE analysis are refined further based on a PPI network or vice versa. This is hardly regarded as a true integration of GE and PPI. To address this problem, we proposed a tensor decomposition (TD) based method that can integrate GE and PPI prior to any analyses where PPI is also formatted as a matrix to which singular value decomposition (SVD) is applied.

Results

Integrated analyses with TD improved the coincidence between vectors attributed to samples and class labels over 27 cancer types retrieved from The Cancer Genome Atlas Program (TCGA) toward five class labels. Enrichment using genes selected with this strategy were also improved with the integration using TD. The PPI network associated with the information on the strength of the PPI can improve the performance than PPI that stores only if the interaction exists in individual pairs. In addition, even restricting genes to the intersection of GE and PPI can improve coincidence and enrichment.

Availability and implementation

The R source code used to perform this analyses is in the supplementary file.
Mobile brain imaging in butoh dancers: from rehearsals to public performance
Authors: Theofanopoulou Constantina , Paez Sadye , Huber Derek , Todd Eric , Ramírez-Moreno Mauricio A. , Khaleghian Badie , Sánchez Alberto Muñoz , Barceló Leah , Gand Vangeline , Contreras-Vidal José L.
Published: February 2023

Dissecting the neurobiology of dance would shed light on a complex, yet ubiquitous, form of human communication. In this experiment, we sought to study, via mobile electroencephalography (EEG), the brain activity of five experienced dancers while dancing butoh, a postmodern dance that originated in Japan. We report the experimental design, methods, and practical execution of a highly interdisciplinary project that required the collaboration of dancers, engineers, neuroscientists, musicians, and multimedia artists, among others. We explain in detail how we technically validated all our EEG procedures (e.g., via impedance value monitoring) and how we minimized potential artifacts in our recordings (e.g., via electrooculography and inertial measurement units). We also describe the engineering details and hardware that enabled us to achieve synchronization between signals recorded in different sampling frequencies, and a signal preprocessing and denoising pipeline that we have used to re-sample our data and remove power line noise. As our experiment culminated in a live performance, where we generated a real-time visualization of the dancers’ interbrain synchrony on a screen via an artistic brain-computer interface, we outline all the methodology (e.g., filtering, time-windows, equation) we used for online bispectrum estimations. We also share all the raw EEG data and codes we used in our recordings. We, lastly, describe how we envision that the data could be used to address several hypotheses, such as that of interbrain synchrony or the motor theory of vocal learning. Being, to our knowledge, the first study to report synchronous and simultaneous recording from five dancers, we expect that our findings will inform future art-science collaborations, as well as dance-movement therapies.
A generalizable Cas9/sgRNA prediction model using machine transfer learning with small high-quality datasets
Authors: Ham Dalton T. , Browne Tyler S. , Banglorewala Pooja N. , Wilson Tyler , Michael Richard , Gloor Gregory B. , Edgell David R.
Published: February 2023

The CRISPR/Cas9 nuclease fromStreptococcus pyogenes(SpCas9) can be used with single guide RNAs (sgRNAs) as a sequence-specific antimicrobial agent and as a genome-engineering tool. However, current bacterial sgRNA activity models poorly predict SpCas9/sgRNA activity and are not generalizable, possibly because the underlying datasets used to train the models do not accurately measure SpCas9/sgRNA cleavage activity and cannot distinguish cleavage activity from toxicity. We solved this problem by using a two-plasmid positive selection system to generate high-quality biologically-relevant data that more accurately reports on SpCas9/sgRNA cleavage activity and that separates activity from toxicity. We developed a new machine transfer learning architecture (crisprHAL) that can be trained on existing datasets and that shows marked improvements in sgRNA activity prediction accuracy when transfer learning is used with small amounts of high-quality data. The crisprHAL model recapitulates known SpCas9/sgRNA-target DNA interactions and provides a pathway to a generalizable sgRNA bacterial activity prediction tool.
Mass spectrometric profiling of HLA-B44 peptidomes provides evidence for tapasin-mediated tryptophan editing
Authors: Kaur Amanpreet , Surnilla Avrokin , Zaitouna Anita J. , Basrur Venkatesha , Mumphrey Michael B. , Grigorova Irina , Cieslik Marcin , Carrington Mary , Nesvizhskii Alexey I. , Raghavan Malini
Published: February 2023

Activation of CD8+T cells against pathogens and cancers involves the recognition of antigenic peptides bound to human leukocyte antigen (HLA) class-I proteins. Peptide binding to HLA class I proteins is coordinated by a multi-protein complex called the peptide loading complex (PLC). Tapasin, a key PLC component, facilitates the binding and optimization of HLA class I peptides. However, different HLA class I allotypes have variable requirements for tapasin for their assembly and surface expression. HLA-B*44:02 and HLA-B*44:05, which differ only at residue 116 of their heavy chain sequences, fall at opposite ends of the tapasin-dependency spectrum. HLA-B*44:02 (D116) is highly tapasin-dependent, whereas HLA-B*44:05 (Y116) is highly tapasinindependent. Mass spectrometric comparisons of HLA-B*4405 and HLA-B*44:02 peptidomes were undertaken to better understand the influences of tapasin upon HLA-B44 peptidome compositions. Analyses of the HLA-B*44:05 peptidomes in the presence and absence of tapasin reveal that peptides with the C-terminal tryptophan residues and those with higher predicted binding affinities are selected in the presence of tapasin. Additionally, when tapasin is present, C-terminal tryptophans are also more highly represented among peptides unique to B*44:02 and those shared between B*44:02 and B*44:05, compared with peptides unique to B*44:05. Overall, our findings demonstrate that tapasin influences the C-terminal composition of HLA class I-bound peptides and favors the binding of higher affinity peptides. For the HLA-B44 family, the presence of tapasin or high tapasin-dependence of an allotype results in better binding of peptides with C-terminal tryptophans, consistent with a role for tapasin in stabilizing an open conformation to accommodate bulky C-terminal residues.
Odor modality is transmitted to cortical brain regions from the olfactory bulb
Authors: Craft Michelle F. , Barreiro Andrea K. , Hari Gautam Shree , Shew Woodrow L. , Ly Cheng
Published: February 2023

Odor perception is the impetus for important animal behaviors with two predominate modes of processing: odors pass through the front of the nose (orthonasal) while inhaling and sniffing, or through the rear (retronasal) during exhalation and while eating. Despite the importance of olfaction for an animal’s well-being and that ortho and retro naturally occur, it is unknown how the modality (ortho versus retro) is even transmitted to cortical brain regions, which could significantly affect how odors are processed and perceived. Using multi-electrode array recordings in tracheotomized anesthetized rats, which decouples ortho-retro modality from breathing, we show that mitral cells in rat olfactory bulb can reliably and directly transmit ortho versus retronasal modality with ethyl butyrate, a common food odor. Drug manipulations affecting synaptic inhibition via GABAAlead to worse decoding of ortho versus retro, independent of whether overall inhibition increases or decreases, suggesting that the olfactory bulb circuit may naturally favor encoding this important aspect of odors. Detailed data analysis paired with a firing rate model that captures population trends in spiking statistics shows how this circuit can encode odor modality. We have not only demonstrated that ortho/retro information is encoded to downstream brain regions, but also use modeling to demonstrate a plausible mechanism for this encoding: due to synaptic adaptation, it is the slower time course of the retronasal stimulation that causes retronasal responses to be stronger and less sensitive to inhibitory drug manipulations than orthonasal responses.

New and Noteworthy

Whether ortho (sniffing odors) versus retro (exhalation and eating) is encoded from the olfactory bulb to other brain areas is not completely known. Using multi-electrode array recordings in anesthetized rats, we show that the olfactory bulb transmits this information downstream via spikes. Altering inhibition degrades ortho/retro information on average. We use theory and computation to explain our results, which should have implications on cortical processing considering that only food odors occur retronasally.
Protein embeddings improve phage-host interaction prediction
Authors: Gonzales Mark Edward M. , Ureta Jennifer C. , Shrestha Anish M.S.
Published: February 2023

With the growing interest in using phages to combat antimicrobial resistance, computational methods for predicting phage-host interactions have been explored to help shortlist candidate phages. Most existing models consider entire proteomes and rely on manual feature engineering, which poses difficulty in selecting the most informative sequence properties to serve as input to the model. In this paper, we framed phage-host interaction prediction as a multiclass classification problem, which takes as input the embeddings of a phage’s receptor-binding proteins, which are known to be the key machinery for host recognition, and predicts the host genus. We explored different protein language models to automatically encode these protein sequences into dense embeddings without the need for additional alignment or structural information. We show that the use of embeddings of receptor-binding proteins presents improvements over handcrafted genomic and protein sequence features. The highest performance was obtained using the transformer-based protein language model ProtT5, resulting in a 3% to 4% increase of weighted F1 scores across different prediction confidence threshold,compared to using selected handcrafted sequence features.

Author summary

Antimicrobial resistance is among the major global health issues at present. As alternatives to the usual antibiotics, drug formulations based on phages (bacteria-infecting viruses) have received increased interest, as phages are known to attack only a narrow range of bacterial hosts and antagonize the target pathogen with minimal side effects. The screening of candidate phages has recently been facilitated through the use of machine learning models for inferring phage-host pairs. The performance of these models relies heavily on the transformation of raw biological sequences into a collection of numerical features. However, since a wide array of potentially informative features can be extracted from sequences, selecting the most relevant ones is challenging. Our approach eliminates the need for this manual feature engineering by employing protein language models to automatically generate numerical representations for specific subsets of tail proteins known as receptor-binding proteins. These proteins are responsible for a phage’s initial contact with the host bacterium and are thus regarded as important determinants of host specificity. Our results show that this approach presents improvements over using handcrafted genomic and protein sequence features in predicting phage-host interaction.
Repurposing of Anti-infectives for the Management of Onchocerciasis using Machine Learning and Protein Docking Studies
Authors: Tetteh Cyril Nii Okai-Kommey , Ampomah Bernice , Oppong Mahmood Brobbey , Lartey Michael , Donkor Paul Owusu , Opuni Kwabena Frimpong-Manso , Adutwum Lawrence Asamoah
Published: February 2023

The discovery of new drugs for the treatment of neglected tropical diseases (NTDs) is hampered by the lack of financial reward associated with their development. A combination of exploratory data analysis, machine learning (ML) and molecular docking studies were used to evaluate 58 anti-infective agents to identify those with the potential to be repurposed for the management of onchocerciasis, an NTD. Out of the 58 test drugs, 14 were predicted by at least five ML models to be useful in managing onchocerciasis. Molecular docking studies using glycine receptor subunit α-3, gamma-aminobutyric acid receptor subunit β-3 and glutamate-gated chloride channel of the 14 drugs showed binding affinities comparable to that of doramectin and pyrvinium which are known onchocerciasis drugs. Diminazine, trimetinib, triclabendazole, cridanimod, vandetinib and trametinib were the top agents showing high binding affinities from the molecular docking studies. The binding affinities of diminazine and cridanimod are similar to doramectin and pyrvinium which have demonstrated activity against onchocerciasis. The outcome of this study shows the potential of using these 14 drugs to manage onchocerciasis.
Intra-prostatic tumour evolution, steps in metastatic spread and histogenomic associations revealed by integration of multi-region whole genome sequencing with histopathological features
Authors: Rao Srinivasa , Verrill Clare , Cerundolo Lucia , Alham Nasullah Khalid , Kaya Zeynep , O’Hanlon Miriam , Hayes Alicia , Lambert Adam , James Martha , Tullis Iain D. C. , Niederer Jane , Lovell Shelagh , Omer Altan , Lopez Francisco , Leslie Tom , Buffa Francesca , Bryant Richard J. , Lamb Alastair D. , Vojnovic Boris , Wedge David C. , Mills Ian G. , Woodcock Dan J. , Tomlinson Ian , Hamdy Freddie C.
Published: February 2023

Extension of prostate cancer beyond the primary site into the surrounding organs by local invasion or nodal metastasis is associated with poor prognosis. The emergence and evolution of cancer clones at this early stage of expansion and spread has not been studied in detail. We performed whole genome sequencing on 42 prostate cancer samples from the prostate, seminal vesicles and regional lymph nodes of five treatment-naive patients with locally advanced disease who underwent radical prostatectomy. Using cancer cell fractions computed from single nucleotide variants and copy number alterations, we reconstructed the tumour phylogenies, which in turn allowed us to infer key molecular steps in the progression of prostate cancer in these individuals. We mapped the clonal composition of cancer sampled across the prostate in each individual and inferred the routes of spread of cancer cells within the prostate and to seminal vesicles and lymph nodes. Based on these data, we delineated the route of tumour progression and metastasis following the transformation of adenocarcinoma to amphicrine morphology, the molecular events leading to whole genome duplication associated with a single clonal expansion and identified putative driver events associated with local invasion and lymph node metastasis. We also correlated genomic changes associated with differences in morphology and identified putative driver events associated with spread to seminal vesicle invasion and lymph node metastasis. Taken together, these findings have implications for diagnosis and risk stratification, in addition to providing a rationale for further studies to characterise the genetic changes associated with morphological transformation. Our results demonstrate the value of integrating multi-region sequencing with histopathological data to study tumour evolution and identify mechanisms of prostate cancer spread.
Parallelohedra, old and new
Authors: Senechal Marjorie , Taylor Jean E.
Published: February 2023

It is shown that from a skewed, skeletal (edges and vertices), truncated octahedron, skewed skeletons can be derived of the other four convex parallelohedra found by Fedorov in 1885. In addition, three new nonconvex parallelohedra are produced, a counterexample to a statement by Grünbaum. This opens several new ways to view atomic positions in crystals, and new avenues in geometry.
Does corporate governance affect the performance and stability of Islamic banks?
Authors: Mamatzakis Emmanuel , Alexakis Christos , Yahyaee Khamis Al , Pappas Vasileios , Mobarek Asma , Mollah Sabur
Published: February 2023

Purpose

This paper aims to investigate the impact of corporate governance practices on cost efficiency and financial stability for a sample of Islamic and conventional banks. In the analysis, the author uses a set of corporate governance variables that include, the board size, board independence, director gender, board meetings, board attendance, board committees, chair independence and CEO characteristics.

Design/methodology/approach

The author uses corporate governance data of Islamic banks that is unique in this field. In the analysis, the author also uses stochastic frontier analysis and panel vector autoregression models to quantify long-run and short-run statistical relationships between the operational efficiency of Islamic Banks and corporate governance practices.

Findings

According to the results, Islamic and conventional banks exhibit important differences in the effects of corporate governance practices on cost efficiency and financial stability. Results show that with a blind general adoption of corporate governance practices, Islamic banks may suffer a loss in their value since the adoption of the third layer of binding practices, over and above the already existing ones, imposed by the Sharia Board and the Board of Directors, may lead to cumbersome business operations. This conclusion is of importance to Islamic Banks since they struggle to survive in a very competitive international environment.

Practical implications

The author believes that the results may be of a certain value to regulators, policymakers and managers of Islamic banks. Based on the results, the author postulate that Islamic banks should select carefully international corporate governance practices.

Social implications

Islamic banks should not adopt additional third layer of binding practices as that would result lower performance and instability that would be damaging for the economy

Originality/value

This study employs a unique sample of Islamic banks that includes corporate governance data hand collected. Our findings of the corporate governance impact on Islamic banks performance and stability are therefore unique in the literature.
Co-creating values for the transformation of scientific and technological achievements: research on the structural hole filling behavior of stakeholders
Authors: Liu Jiayuan
Published: February 2023

Purpose

This study aims to explore how stakeholders leverage theirguanxiand structural holes to promote knowledge mobilization to increase the performance of sci-tech achievement transformation.

Design/methodology/approach

This study conducted questionnaires, a social network analysis and semistructured interviews to examine its hypotheses by gathering data from a university and an enterprise in China.

Findings

Structural holes impede knowledge mobilization among stakeholders in their network, butguanximoderates this impeding effect. In addition, knowledge mobilization promotes transformation performance.

Originality/value

By developing a mechanism to illustrate how stakeholders strategically leverage theirguanxiand structural holes to affect the efficacy of knowledge mobilization to increase transformation performance, we reveal how stakeholders interact to co-create values for innovation, thereby contributing to the innovation and knowledge management literature.
Dual solutions on three-dimensional nanofluid flow and heat transfer over a permeable non-linearly shrinking surface with second-order velocity slips
Authors: Roşca Natalia C. , Roşca Alin V. , Pop Ioan
Published: February 2023

Purpose

This paper aims to present the steady dual solutions on three-dimensional flow and heat transfer of nanofluid over a permeable non-linearly shrinking surface with two-order velocity slips conditions. Boundary layer assumption is considered in the mathematical modelling. Authors comprehend from previous studies and papers that the shrinking surfaces are extremely important in current engineering and environmental systems.

Design/methodology/approach

Using appropriate similarity variables, the full partial differential equations (PDF) are modified into a specific set of ordinary (similar) differential equations (ODE). The resulting non-linear ordinary differential system is then solved both analytically for some particular cases and numerically for the general case using the function bvp4c from MATLAB for characteristic values of the parameters which govern the equations. The transformed mathematical model is analysed using the bvp4c procedure. Based on the given assumptions, this study is able to produce multiple solutions of the problem.

Findings

The ordinary (similarity) differential equations have two branches solutions, upper and lower branch solutions, given some interval of shrinking and velocity slip parameters. The authors consider here a temporal stability analysis, as they want to establish which of the solutions are stable and which are not. In a distinct paragraph, the authors discuss in detail and present in a graphical manner the effects of shrinking and second-order slip flow model on the skin friction coefficient, surface wall heat flux and dimensionless velocity and temperature profiles. The analysis reveals that the second order slip has a big influence on the flow and heat transfer characteristics.

Originality/value

The present discoveries are unique and truly new for the research of the three-dimensional stretching/shrinking forced convection flow and heat transfer nanofluids. The nanofluid is a water-based nanofluid (H2O), which contains one type of nanoparticles, namely, copper (Cu). Of course, the analysis can be further extended considering other types of nanoparticles such as alumina (Al2O3). The authors assume that the thermal equilibrium is reached for the base fluid together with the suspended nanoparticles and that the nanoparticles are uniform in dimension and form.
Strategic management accounting revisited: building on insights from the business model field
Authors: Roslender Robin , Hart Susan , Nielsen Christian
Published: February 2023

Purpose

This paper aims to identify and discuss insights from the business model field on the creation and delivery of value to customers that provide new thinking in relation to the strategic management accounting field.

Design/methodology/approach

The customer emphases exhibited in parts of the extant strategic management accounting literature are highlighted and amplified using insights from the business model literature, including those relating to value propositions, customer value creation and delivery and meeting customers’ value expectations.

Findings

The paper demonstrates that in addition to providing valuable insights for accounting to management, an extended strategic management accounting concept enables accounting and reporting to customers, now identified as major stakeholders, in the context of integrated reporting.

Practical implications

Through its customer resonances, the paper affirms strategic management accounting’s practical utility for organisations seeking a strong position in highly competitive marketplaces, via the addition of a focus on accounting to customers.

Originality/value

The paper’s use of insights from the business model literature further reinforces the view that strategic management accounting potentially constitutes a pivotal development within both managerial and financial accounting and reporting.
Citizens' perceptions of World Heritage values: the case of Cuenca, Ecuador
Authors: Molina Barbara , Eljuri Gabriela , Roigé Ventura Xavier
Published: February 2023

Purpose

This paper aims to study possible differences between the Outstanding Universal Value (OUV) defined in the designation of Cuenca as a World Heritage (WH) site and its inhabitants' perceptions of heritage value. The study is based on research conducted in the historic centre of Cuenca in Ecuador, which was accorded WH status in 1999.

Design/methodology/approach

The research employs both quantitative and qualitative methodologies, providing a complementary approach to the research subject. Quantitative research involved a probability survey of 400 informants randomly selected from the population of the canton of Cuenca, while qualitative research included 40 semi-structured interviews with residents and traders in the historic centre and 150 further written consultations with residents of the city.

Findings

Following the introduction, methodology and description, the paper presents the data gathered from the survey and interviews. These indicate inhabitants' perceptions of the meaning, values, and uses of WH in Cuenca and reveal differences between their perceptions and those of the official OUV.

Originality/value

Although there are several studies on WH residents' perceptions of UNESCO OUV, few highlight the mismatch between local community views of heritage and those established by UNESCO. This study reflects critically on the concept of OUV, which is based on technical and political criteria rather than social participation. The study employs methodologies that could be applied in other case studies and used to improve heritage management. This is the only study on local perceptions of Cuenca's OUV.
You can't shop with us: how US-based, value- and mid-market online clothing retailers position their plus-size female clothing sections
Authors: Shelton Summer Suzanne , Bradshaw Amanda S. , Cretul Matthew , Treise Debbie
Published: February 2023

Purpose

Plus-size women represent a large consumer segment that has grown in popularity with the fashion industry, retailers and advertisers. Despite advancements in clothing availability for plus-sized women, the shopping experience for these women (compared with that of straight-size women) often still falls short. The current experience leaves plus-sized women feel like a second-class, minority group despite the fact that the majority of women in USA are considered plus-size. The purpose of this study was to assess how US-based, value- and mid-market online clothing retailers position their plus-size female clothing sections in their site navigation.

Design/methodology/approach

This study assessed the websites of N = 68 popular plus- and straight-sized US-based, value- and mid-market retailers to evaluate the placement of, and options available in, their plus-sized clothing sections.

Findings

Findings revealed that the majority of retailers completely separated out the plus-sized section from the straight-sized section and that the language used to describe plus-size clothing was body-focused (versus clothing-focused for straight-size clothing sections). Theoretical and practical implications for marketers, advertisers and retailers are discussed.

Originality/value

This is the first study to assess the separation of plus- and straight-sized clothing sections in online retail spaces. As brands begin to consider combining plus- and straight-sized clothing sections (see Old Navy), it is important to assess how wide-spread the separation of sections currently is in online retail environments.