bluuebunny/crossref_metadata_2025 huggingface dataset:
A 3-dimensional molecular cartography of human cerebral organoids revealed by double-barcoded spatial transcriptomics
Authors: Lozachmeur Gwendoline , Bramoulle Aude , Aubert Antoine , Stüder François , Moehlin Julien , Madrange Lucie , Yates Frank , Deslys Jean-Philippe , Mendoza-Parra Marco Antonio
Published: January 2023

Spatially-resolved transcriptomics is revolutionizing our understanding of complex tissues, but their current use for the exploration of a few sections is not representative of their 3-dimensional architecture. In this work we present a low-cost strategy for manufacturing molecularly double-barcoded DNA arrays, enabling large-scale spatially-resolved transcriptomics studies. We applied this technique to spatially resolve gene expression in several human brain organoids, including the reconstruction of a 3-dimensional view from multiple consecutive sections, revealing gene expression divergencies throughout the tissue.
Comparative phylogeography of Ponto-Caspian amphipods throughout the invaded Baltic and native NW Black Sea donor ranges – can introduction mode affect genetic diversity?
Authors: Copilaș-Ciocianu Denis , Šidagytė-Copilas Eglė , Son Mikhail O. , Morhun Halyna , Macher Jan Niklas , Arbačiauskas Kęstutis
Published: January 2023

The Baltic countries harbor a diverse assemblage of alien amphipods of Ponto-Caspian origin. The composition of this fauna was shaped by three invasion waves: 1) pre-20thcentury dispersals via watershed-connecting canals, 2) deliberate introductions in the 1960s, and 3) new dispersals during the last decade via shipping and pre-existing canals. Given this rich invasion history, we test whether genetic diversity (mitochondrial and nuclear) differs between the native and invaded ranges and between the deliberately introduced species and the ones that dispersed on their own. Our results show a significant decrease in mitochondrial but not nuclear genetic diversity in the invaded Baltic range. We also find that in the invaded range the introduced species exhibit a higher mitochondrial and nuclear genetic diversity than the species that dispersed on their own, while in the native range only the nuclear diversity is higher in introduced species. Mitochondrial diversity was more structured geographically in the native range and the dominant invasive haplotypes were detected in the native populations of all but one species, further highlighting the utility of this marker in tracing invasion sources. Our comparative approach provides important insight into the inter-range genetic diversity of Ponto-Caspian invaders, highlighting the role of introduction mode.
Rodent ultrasonic vocal interaction resolved with millimeter precision using hybrid beamforming
Authors: Sterling M. L. , Englitz B.
Published: January 2023

Ultrasonic vocalizations (USVs) fulfill an important role in communication and navigation in many species. Because of their social and affective significance, rodent USVs are increasingly used as a behavioral measure in neurodevelopmental and neurolinguistic research. Reliably attributing USVs to their emitter during close interactions has emerged as a difficult, key challenge. If addressed, all subsequent analyses gain substantial confidence.

We present a hybrid ultrasonic tracking system, HyVL, that synergistically integrates a high-resolution acoustic camera with high-quality ultrasonic microphones. HyVL is the first to achieve millimeter precision (~3.4-4.8mm, 91% assigned) in localizing USVs, ~3x better than other systems, approaching the physical limits (mouse snout ~ 10mm).

We analyze mouse courtship interactions and demonstrate that males and females vocalize in starkly different relative spatial positions, and that the fraction of female vocalizations has likely been overestimated previously due to imprecise localization. Further, we find that male mice vocalize more intensely when interacting with two mice, an effect mostly driven by the dominant male.

HyVL substantially improves the precision with which social communication between rodents can be studied. It is also affordable, open-source, easy to set up, can be integrated with existing setups, and reduces the required number of experiments and animals.

Data & Code Availability

During the review process, reviewers can access all Data and Code via the link below:https://data.donders.ru.nl/loqin/reviewer-208072048/iJ4c-oRNlPIp3vArKiYQ0lAW9FipiHL8foxSzwt1FDAUponacceptance, these materials will be made available to the public.
A mathematical model for axonal transport of large cargo vesicles
Authors: Rahman Nizhum , Oelz Dietmar B.
Published: January 2023

In this study, we consider axonal transport of large cargo vesicles characterised by transient expansion of the axon shaft. Our goal is to formulate a mathematical model which captures the dynamic mechanical interaction of such cargo vesicles with the membrane associated periodic cytoskeletal structure (MPS). It consists of regularly spaced actin rings that are transversal to the longitudinal direction of the axon and involved in the radial contraction of the axon. A system of force balance equations is formulated by which we describe the transversal rings as visco-elastic Kelvin-Voigt elements. In a homogenisation limit, we reformulate the model as a free boundary problem for the interaction of the submembranous MPS with the large vesicle. We derive a non-linear force-velocity relation as a quasi-steady state solution. Computationally we analyse the vesicle size dependence of the transport speed and use an asymptotic approximation to formulate it as a power law that can be tested experimentally.
Recurrent phases of strict protein limitation inhibit tumor growth and restore lifespan in aDrosophilaintestinal cancer model
Authors: Pfefferkorn Roxana M. , Mortzfeld Benedikt M. , Fink Christine , von Frieling Jakob , Bossen Judith , Esser Daniela , Kaleta Christoph , Rosenstiel Philip , Heine Holger , Roeder Thomas
Published: January 2023

Diets that restrict caloric or protein intake offer a variety of benefits, including decreasing the incidence of cancer. However, whether such diets pose a substantial therapeutic benefit as auxiliary cancer treatments remains unclear. We determined the effects of severe protein depletion on tumorigenesis in aDrosophila melanogasterintestinal tumor model, using a human RAF gain-of-function allele. Severe and continuous protein restriction significantly reduced tumor growth but resulted in premature death. Therefore, we developed a diet in which short periods of severe protein restriction alternated cyclically with periods of complete feeding. This nutritional regime reduced tumor mass, restored gut functionality, and normalized the lifespan of oncogene-expressing flies to the levels observed in healthy control flies. Furthermore, this diet reduced the chemotherapy-induced stem cell activity associated with tumor recurrence. Transcriptome analysis revealed long-lasting changes in the expression of key genes involved in multiple major developmental signaling pathways. Overall, the data suggest that recurrent severe protein depletion effectively mimics the health benefits of continuous protein restriction, without undesired nutritional shortcomings. This provides seminal insights into the mechanisms of the transcriptomic memory effect required to maintain the positive effects of protein restriction throughout the phases of a full diet.
Nanovirseq: dsRNA sequencing for plant virus and viroid detection by Nanopore sequencing
Authors: Javaran Vahid J. , Poursalavati Abdonaser , Lemoyne Pierre , Ste-Croix Dave T. , Moffett Petter , Fall Mamadou L.
Published: January 2023

Worldwide, there is a need for certified clean plant materials to limit viral diseases spread. In order to design a robust and proactive viral-like disease certification, diagnostics, and management program, it is essential to have a fast, inexpensive, and user-friendly tool. The purpose of this study was to determine whether dsRNA-based nanopore sequencing can be a reliable method for the detection of viruses and viroids in grapevines or not. Compared to direct RNA sequencing from rRNA-depleted total RNA (rdTotalRNA), direct-cDNA sequencing from dsRNA (dsRNAcD) yielded more viral reads and detected all grapevine viruses and viroids detected using Illumina MiSeq sequencing (dsRNA-MiSeq). With dsRNAcD sequencing it was possible to detect low abundance viruses (e.g., Grapevine red globe virus) where rdTotalRNA sequencing failed to detect them. Indeed, even after removing rRNA, rdTotalRNA sequencing yielded low viral read numbers. rdTotalRNA sequencing was not sensitive enough to detect all the viruses detected by dsRNA-MiSeq. In addition, there was a false positive identification of a viroid in the rdTotalRNA sequencing that was due to misannotation of a host-driven read. For quick and accurate reads classification, two different taxonomical classification workflows based on protein and nucleotide homology were evaluated in this study, namely DIAMOND&MEGAND (DIA&MEG) and Centrifuge&Recentrifuge (Cent&Rec), respectively. Virome profiles from both workflows were similar except for grapevine endophyte endornavirus (GEEV), which was only detected using DIA&MEG. However, because DIA&MEG’s classification is based on protein homology, it cannot detect viroid infection despite giving more robust results. Even though Cent&Rec’s virus and viroid detection workflow was faster (30 minutes) than DIA&MEG’s (two hours), it could not provide the details and information DIA&MEG was able to provide. As demonstrated in our study, nanopore dsRNAcD sequencing and the proposed data analysis workflows are suitable and reliable for viruses and viroids detection, especially in grapevine where viral mixed infection is common.
Mapping the spatial transcriptomic signature of the hippocampus during memory consolidation
Authors: Vanrobeys Yann , Mukherjee Utsav , Langmack Lucy , Bahl Ethan , Lin Li-Chun , Michaelson Jacob J , Abel Ted , Chatterjee Snehajyoti
Published: January 2023

Memory consolidation involves discrete patterns of transcriptional events in the hippocampus. Despite the emergence of single-cell transcriptomic profiling techniques, defining learning-responsive gene expression across subregions of the hippocampus has remained challenging. Here, we utilized unbiased spatial sequencing to elucidate transcriptome-wide changes in gene expression in the hippocampus following learning, enabling us to define molecular signatures unique to each hippocampal subregion. We find that each subregion of the hippocampus exhibits distinct yet overlapping transcriptomic signatures. Although the CA1 region exhibited increased expression of genes related to transcriptional regulation, the DG showed upregulation of genes associated with protein folding. We demonstrate the functional relevance of subregion-specific gene expression by genetic manipulation of a transcription factor selectively in the CA1 hippocampal subregion, leading to long-term memory deficits. This work demonstrates the power of using spatial molecular approaches to reveal transcriptional events during memory consolidation.
Combinatorial single-cell profiling of all major chromatin types with MAbID
Authors: Lochs Silke J.A. , van der Weide Robin H. , de Luca Kim L. , Korthout Tessy , van Beek Ramada E. , Kimura Hiroshi , Kind Jop
Published: January 2023

Gene expression programs result from the collective activity of many regulatory factors. To obtain insight into the mechanisms that govern gene regulation, it is imperative to study their combined mode of action and interconnectivity. However, it has been challenging to simultaneously measure a combination of these factors within one sample. Here, we introduce MAbID, a method that combines genomic profiling of many histone modifications and chromatin-binding proteins in a single reaction. MAbID employs antibody-DNA conjugates to enable genomic barcoding of chromatin at sites of epitope occupancy. This barcoding strategy allows for the combined incubation of multiple antibodies in a single sample to reveal the genomic distributions of many epigenetic states simultaneously. We used MAbID to profile both active and inactive chromatin types in human cell lines and multiplexed measurements in the same sample without loss of data quality. Moreover, we obtained joint measurements of six epitopes covering all major chromatin types in single cells during mousein vitroneural differentiation and captured associated changes in multifactorial chromatin states. Thus, MAbID holds the potential to gain unique insights into the interplay between gene regulatory mechanisms, especially in settings with limited sample material and in single cells.
sLASER and PRESS Perform Similarly at Revealing Metabolite-Age Correlations
Authors: Hui Steve C.N. , Gong Tao , Zöllner Helge J. , Hupfeld Kathleen E. , Gudmundson Aaron T. , Murali-Manohar Saipavitra , Davies-Jenkins Christopher W. , Song Yulu , Chen Yufan , Oeltzschner Georg , Wang Guangbin , Edden Richard A. E.
Published: January 2023

Purpose

To compare the respective ability of PRESS and sLASER to reveal biological relationships, using age as a validation covariate.

Methods

MRS data were acquired from 102 healthy volunteers using PRESS and sLASER in centrum semiovale (CSO) and posterior cingulate cortex (PCC) regions. Acquisition parameters included TR/TE 2000/30 ms; 96 transients; 2048 datapoints sampled at 2 kHz.

Spectra were analyzed using Osprey. Signal-to-noise ratio (SNR), full-width-half-maximum linewidth of tCr, and metabolite concentrations were extracted. A linear model was used to compare SNR and linewidth. Paired t-tests were used to assess differences in metabolite measurements between PRESS and sLASER. Correlations were used to evaluate the relationship between PRESS and sLASER metabolite estimates, as well as the strength of each metabolite-age relationship. Coefficients of variation were calculated to assess inter-subject variability in each metabolite measurement.

Results

SNR and linewidth were significantly higher (p<0.05) for sLASER than PRESS. Paired t-tests showed significant differences between PRESS and sLASER in most metabolite measurements. Metabolite measures were significantly correlated (p<0.05) for most metabolites between the two methods except GABA, Gln and Lac in CSO and GSH, Lac and NAAG in PCC. Metabolite-age relationships were consistently identified using both PRESS and sLASER. Similar CVs were observed for most metabolites.

Conclusion

The study results suggest strong agreement between PRESS and sLASER in identifying relationships between brain metabolites and age in CSO and PCC data acquired at 3T. sLASER is technically desirable due to the reduced chemical shift displacement artifact; however, PRESS performed similarly in ‘good’ brain regions at clinical field strength.
A single dietary factor, daily consumption of a fermented beverage, can modulate the gut microbiome within the same ethnic community
Authors: Das Santanu , Özkurt Ezgi , Joishy Tulsi Kumari , Deb Dibyayan , Mukherjee Ashis K. , Hildebrand Falk , Khan Mojibur R.
Published: January 2023

In this study, the impact of traditional rice-based fermented alcoholic beverages (Apong) on the gut microbiome and health of theMishingcommunity in India was examined. Two groups that consumed one of these beverages were compared to a control group that did not consume either beverage. Gut microbial composition was analyzed by sequencing 16S rRNA of fecal metagenomes and analyzing untargeted fecal metabolites, and short-chain fatty acids (SCFAs). We also collected data on anthropometric measures and serum biochemical markers. Our results showed thatApongdrinkers had higher blood pressure, but lower blood glucose and total protein levels than other non-drinkers. Also, gut microbiome composition was found to be affected by the choice ofApong, withApongdrinkers having a more diverse and distinct microbiome compared to non-drinkers.Apongdrink type or being a non-drinker explained even a higher variation of fecal metabolome composition than microbiome composition andApongdrinkers had lower levels of the SCFA isovaleric acid than non-drinkers. Overall, this study shows that a single dietary factor can significantly impact the gut microbiome of a community and highlights the potential role of traditional fermented beverages in maintaining gut health.
Functional domain annotation by structural similarity
Authors: Mirzavand Borujeni Poorya , Salavati Reza
Published: January 2023

Traditional automated insilicofunctional annotation uses tools like Pfam that rely on sequence similarities for domain annotation. However, structural conservation often exceeds sequence conservation, suggesting an untapped potential for improved annotation through structural similarity. This approach was previously overlooked before the AlphaFold2 introduction due to the need for more high-quality protein structures. Leveraging structural information especially holds significant promise to enhance accurate annotation in diverse proteins across phylogenetic distances.

In our study, we evaluated the feasibility of annotating Pfam domains based on structural similarity. To this end, we created a database from segmented full-length protein structures at their domain boundaries, representing the structure of Pfam seeds. We usedTrypanosomabrucei, a phylogenetically distant protozoan parasite as our model organism. Its structome was aligned with our database using Foldseek, the ultra-fast structural alignment tool, and the top non-overlapping hits were annotated as domains. Our method identified over 400 new domains in the T.bruceiproteome, surpassing the benchmark set by sequence-based tools, Pfam and Pfam-N, with some predictions validated manually. We have also addressed limitations and suggested avenues for further enhancing structure-based domain annotation.
Regulation of Ebola GP conformation and membrane binding by the chemical environment of the late endosome
Authors: Jain Aastha , Govindan Ramesh , Berkman Alexander , Luban Jeremy , Díaz-Salinas Marco A. , Durham Natasha D. , Munro James B.
Published: January 2023

Interaction between the Ebola virus envelope glycoprotein (GP) and the endosomal membrane is an essential step during virus entry into the cell. Acidic pH and Ca2+have been implicated in mediating the GP-membrane interaction. However, the molecular mechanism by which these environmental factors regulate the conformational changes that enable engagement of GP with the target membrane is unknown. Here, we apply fluorescence correlation spectroscopy (FCS) and single-molecule Förster resonance energy transfer (smFRET) imaging to elucidate how the acidic pH, Ca2+and anionic phospholipids in the late endosome promote GP-membrane interaction, thereby facilitating virus entry. We find that bis(monoacylglycero)phosphate (BMP), which is specific to the late endosome, is especially critical in determining the Ca2+-dependence of the GP-membrane interaction. Molecular dynamics (MD) simulations suggested residues in GP that sense pH and induce conformational changes that make the fusion loop available for insertion into the membrane. We similarly confirm residues in the fusion loop that mediate GP’s interaction with Ca2+, which likely promotes local conformational changes in the fusion loop and mediates electrostatic interactions with the anionic phospholipids. Collectively, our results provide a mechanistic understanding of how the environment of the late endosome regulates the timing and efficiency of virus entry.

Author Summary

Ebola virus causes disease in humans with high fatality. A better understanding of how Ebola virus enters cells is critical to inform the development of novel therapeutic and preventative measures. The viral glycoprotein present on the surface of the virus mediates attachment to cells and subsequent entry through a poorly understood mechanism involving fusion of viral and cellular membranes. Here, we employ computational and experimental biophysical techniques to understand how the Ebola glycoprotein senses chemical cues in its environment, such as pH, calcium ions, and specific lipid species to ensure that entry occurs at the right time and place. Our results specify elements of the glycoprotein that control its structure under changing physiological environments.
Trajectories of COVID-19: a longitudinal analysis of many nations and subnational regions
Authors: Burg David , Ausubel Jesse H.
Published: January 2023

The COVID-19 pandemic is the first to be rapidly and sequentially measured by nation-wide PCR community testing for the presence of the viral RNA at a global scale. We take advantage of the novel “natural experiment” where diverse nations and major subnational regions implemented various policies including social distancing and vaccination at different times with different levels of stringency and adherence. Initially, case numbers expanding exponentially with doubling times of ∼1-2 weeks. In the nations where lockdowns were not implemented or ineffectual, case numbers increased exponentially but then stabilized around 102-to-103new infections (per km2built-up area per day). Dynamics under strict lockdowns were perturbed and infections decayed to low levels. They rebounded following the lifting of the policies but converged on an equilibrium setpoint. Here we deploy a mathematical model which captures this behavior, incorporates a direct measure of lockdown efficacies, and allows derivation of a maximal estimate for the basic reproductive numberRo(mean 1.6-1.8). We were able to test this approach by comparing the approximated “herd immunity” to the vaccination coverage observed that corresponded to rapid declines in community infections during 2021. The estimates reported here agree with the observed phenomena. Moreover, the decay ratesd(0.4-0.5) and rebound ratesr0(0.2- 0.3) were similar throughout the pandemic and among all the nations and regions studied. Finally, a longitudinal analysis comparing multiple national and regional results provides insights on the underlying epidemiology of SARS-CoV-2 and lockdown and vaccine efficacy, as well as evidence for the existence of an endemic steady state of COVID-19.
Evaluation of ultrasound as diagnostic tool in patients with clinical features suggestive of carpal tunnel syndrome in comparison to nerve conduction studies: study protocol for a diagnostic testing study
Authors: de la Paz Murciano Casas María , Rodríguez-Piñero Manuel , Sarmiento Aguas-Santas Jiménez , López Mercedes Álvarez , Jurado Gema Jiménez
Published: January 2023

Background

Carpal Tunnel Syndrome (CTS) is the most common compressive neuropathy, accounting for 90% of all neuropathies. Its prevalence ranges from 3.8% - 7.8% in the population. The gold standard for its diagnosis is the neurophysiological study (85% sensitivity and 95% specificity), with the disadvantage of being invasive, complex and expensive, which means an increase in cost and time for the diagnosis of the disease. The main objective of this diagnostic test evaluation study is to investigate the value of ultrasound in the diagnosis of CTS, and among the secondary objectives, to establish the ultrasound parameters that are predictors of CTS in comparison with neurophysiological studies, attempting to standardize a protocol and reference values that determine the presence or absence of CTS.

Methods

Prospective, cross-sectional study. The reference test with which we compared the ultrasound is the neurophysiological test (NPT). Patients will come consecutively from the Neurophysiology Department of the Virgen Macarena Hospital, with clinical suspicion of CTS and fulfilling the inclusion/exclusion criteria. To calculate the sample size (EPIDAT program) we proposed a sensitivity of 78% and specificity of 87% with a confidence level of 95%, requiring 438 patients (264 NPT positive, 174 NPT negative). We followed an ultrasound study protocol that included the ultrasound variables: cross-sectional area at the entrance and exit of the tunnel, range of nerve thinning, wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and the existence of adjacent wrists or masses. We propose a timeline for the study to be performed between 2020 and 2023. Finally, we propose a cost-effectiveness analysis.

Discussion

Ultrasound not only allows to objectify the alterations of the median nerve but also the underlying pathological mechanisms in CTS. A multitude of ultrasound parameters have been described that should be regarded in syndrome’s study, among which we included the cross-sectional area, the range of nerve thinning, the wrist-forearm index, flexor retinaculum bulging, power Doppler uptake and assessment of anatomical alterations. The use of ultrasound as a diagnostic tool in CTS has many advantages for both doctors and the patients, as it is a non-invasive, convenient, and fast tool increasingly accessible to professionals.

Administrative information
Long-read direct RNA sequencing of the mitochondrial transcriptome ofSaccharomyces cerevisiaereveals condition-dependent intron turnover
Authors: Koster Charlotte C. , Kleefeldt Askar , van den Broek Marcel , Luttik Marijke , Daran Jean-Marc , Daran-Lapujade Pascale
Published: January 2023

Mitochondria fulfil many essential roles and have their own genome, which is expressed as polycistronic transcripts that undergo co- or post-transcriptional processing and splicing. Due to inherent complexity and limited technical accessibility of the mitochondrial transcriptome, fundamental questions regarding mitochondrial gene expression and splicing remain unresolved, even in the model eukaryoteSaccharomyces cerevisiae. Long-read sequencing could address these fundamental questions. Therefore, a method for enrichment of mitochondrial RNA and sequencing using Nanopore technology was developed, enabling the resolution of splicing of polycistronic genes and the quantification the spliced RNA.

This method successfully captured the full mitochondrial transcriptome and resolved RNA splicing patterns with single-base resolution, and was applied to explore the transcriptome ofS. cerevisiaegrown with glucose or ethanol as sole carbon source, revealing the impact of growth conditions on mitochondrial RNA-expression and splicing. This study uncovered a remarkable difference in turn-over of group II introns between yeast grown in mostly fermentative and fully respiratory conditions. Whether this accumulation of introns in glucose medium has an impact on mitochondrial functions remains to be explored. Combined with the high tractability of the model yeastS. cerevisiae, the developed method enables to explore mitochondrial transcriptome regulation and processing in a broad range of conditions relevant in human context, including aging, apoptosis and mitochondrial diseases.
Temporal dynamics of collateral RNA cleavage by LbuCas13a in human cells
Authors: Bot Jorik F. , Zhao Zhihan , Li Mengyuan , Kammeron Darnell , Shang Peng , Geijsen Niels
Published: January 2023

CRISPR-Cas13 exclusively targets RNA. In prokaryotic cells, Cas13 cleaves both target and non-target RNA indiscriminately upon activation by a specific target RNA, but in eukaryotic cells collateral cleavage activity has been limited. To investigate collateral cleavage by Cas13 in eukaryotic cells, we first compared various Cas13 orthologs and found that specifically LbuCas13a exhibits strong collateral RNA cleavage activity in human cells when delivered as ribonucleoprotein, independent of cell line and targeting both exogenous and endogenous transcripts. Collateral RNA cleavage started within 50 minutes of ribonucleoprotein delivery resulting in major alterations to the total RNA profile. In response to the collateral RNA cleavage, cells upregulated genes associated with stress and innate immune response, ultimately leading to apoptotic cell death. This enabled us to use LbuCas13a as a flexible and repeatable target-RNA-specific cell elimination tool. Finally, we used Nanopore sequencing to explore the identity of collaterally cleaved RNAs, the nucleotide position at which they are cleaved, and the temporal dynamics of collateral RNA cleavage. This revealed that LbuCas13a activation leads to rapid and global cleavage of cytoplasmic RNAs at specific nucleotide positions. In conclusion, we here report that LbuCas13a has high collateral activity in human cells and describe the temporal dynamics of the collateral RNA cleavage, the cellular responses ultimately leading to apoptosis, how this can be exploited as a cell elimination tool, and the collateral cleavage preferences of LbuCas13a.
AlphaFold Prediction of Structural Ensembles of Disordered Proteins
Authors: Brotzakis Z. Faidon , Zhang Shengyu , Vendruscolo Michele
Published: January 2023

Deep learning methods of predicting protein structures have reached an accuracy comparable to that of high-resolution experimental methods. It is thus possible to generate accurate models of the native states of hundreds of millions of proteins. An open question, however, concerns whether these advances can be translated to disordered proteins, which should be represented as structural ensembles because of their heterogeneous and dynamical nature. Here we show that the inter-residue distances predicted by AlphaFold for disordered proteins can be used to construct accurate structural ensembles. These results illustrate the application to disordered proteins of deep learning methods originally trained for predicting the structures of folded proteins.
piRNA processing by a trimeric Schlafen-domain nuclease
Authors: Podvalnaya Nadezda , Bronkhorst Alfred W. , Lichtenberger Raffael , Hellmann Svenja , Nischwitz Emily , Falk Torben , Karaulanov Emil , Butter Falk , Falk Sebastian , Ketting René F.
Published: January 2023

Transposable elements are genomic parasites that expand within and spread between genomes1. Piwi proteins control transposon activity, notably in the germline2,3. These proteins recognize their targets through small RNA co-factors named piRNAs, making piRNA biogenesis a key specificity-determining step in this crucial genome immunity system. While the processing of piRNA precursors is an essential step in this process, many molecular details of this process remain unknown. We identify a novel endoribonuclease, PUCH, that initiates piRNA processing in the nematodeCaenorhabditis elegans. Genetic and biochemical studies show that PUCH, a trimer of Schlafen-like-domain proteins (SLFL proteins), executes 5’-end piRNA precursor cleavage. PUCH-mediated processing strictly requires an m7G-Cap and a uracil at position three. We also demonstrate how PUCH interacts with PETISCO, a complex that binds piRNA precursors4, and that this interaction enhances piRNA productionin vivo. The identification of PUCH completes the repertoire ofC. eleganspiRNA biogenesis factors and uncovers a novel type of RNA endonuclease formed by three SLFL proteins. Mammalian Schlafen (Slfn) genes have been associated with immunity responses5, exposing a thus far unknown molecular link between immune responses in mammals and deeply conserved RNA-based mechanisms that control transposable elements.
Extremely potent pan-sarbecovirus neutralizing antibodies generated by immunization of macaques with an AS03-adjuvanted monovalent subunit vaccine against SARS-CoV-2
Authors: Feng Yupeng , Yuan Meng , Powers John M. , Hu Mengyun , Munt Jennifer E. , Arunachalam Prabhu S. , Leist Sarah R. , Bellusci Lorenza , Adams Lily E. , Sundaramurthy Sumana , Shirreff Lisa M. , Mallory Michael L. , Scooby Trevor D. , Moreno Alberto , O’Hagan Derek T. , Kleanthous Harry , Villinger Francois J. , Veesler David , King Neil P. , Suthar Mehul S. , Khurana Surender , Baric Ralph S. , Wilson Ian A. , Pulendran Bali
Published: January 2023

The rapid emergence of SARS-CoV-2 variants that evade immunity to vaccination has placed a global health imperative on the development of therapeutic countermeasures that provide broad protection against SARS-CoV-2 and related sarbecoviruses. Here, we identified extremely potent pan-sarbecovirus antibodies from non-human primates vaccinated with an AS03 adjuvanted subunit vaccine against SARS-CoV-2 that recognize conserved epitopes in the receptor binding domain (RBD) with femtomolar affinities. Longitudinal analysis revealed progressive accumulation of somatic mutation in the immunoglobulin genes of antigen-specific memory B cells for at least one year following primary vaccination. 514 monoclonal antibodies (mAbs) were generated from antigen-specific memory B cells. Antibodies isolated at 5 to 12 months following vaccination displayed greater potency and breadth, relative to those identified at 1.4 months. Notably, 15 out of 338 (∼4.4%) antibodies isolated at 1.4∼6 months after the primary vaccination showed extraordinary neutralization potency against SARS-CoV-2 omicron BA.1, despite the absence of BA.1 neutralization in serum. Two of them, 25F9 and 20A7, neutralized authentic clade Ia sarbecoviruses (SARS-CoV, WIV-1, SHC014) and clade Ib sarbecoviruses (SARS-CoV-2 D614G, SARS-CoV-2 BA.1, Pangolin-GD) with half-maximal inhibition concentrations of (0.85 ng/ml, 3 ng/ml, 6 ng/ml, 6 ng/ml, 42 ng/ml, 6 ng/ml) and (13 ng/ml, 2 ng/ml, 18 ng/ml, 9 ng/ml, 6 ng/ml, 345 ng/ml), respectively. Furthermore, 20A7 and 27A12 showed potent neutralization against all SARS-CoV-2 variants of concern and multiple Omicron sublineages, including BA.1, BA.2, BA.3, BA.4/5, BQ.1, BQ.1.1 and XBB variants. X-ray crystallography studies revealed the molecular basis of broad and potent neutralization through targeting conserved RBD sites. In vivo prophylactic protection of 25F9, 20A7 and 27A12 was confirmed in aged Balb/c mice. Notably, administration of 25F9 provided complete protection against SARS-CoV-2, SARS-CoV-2 BA.1, SARS-CoV, and SHC014 challenge, underscoring that these mAbs are promising pan-sarbecovirus therapeutic antibodies.

One Sentence Summary

Extremely potent pan-sarbecovirus neutralizing antibodies
Downregulation and delayed induction of photosynthesis by coordinated transcriptomic changes induced by sink-source imbalance
Authors: Ozawa Yui , Tanaka Aiko , Suzuki Takamasa , Sugiura Daisuke
Published: January 2023

Understanding comprehensive mechanisms of the downregulation of photosynthesis induced by accumulation of non-structural carbohydrates (NSCs) is essential for the future food security.x Despite numerous studies, whether NSCs accumulation directly affects steady-state maximum photosynthesis and photosynthetic induction, as well as underlying gene expression profiles, remains unknown so far.

We evaluated the relationship between photosynthetic capacity and NSCs accumulation induced by cold-girdling, sucrose feeding, and low nitrogen treatment inGlycine maxandPhaseolus vulgaris. InG. max, changes in transcriptome profiles were further investigated focusing on physiological processes of photosynthesis and NSCs accumulation.

NSCs accumulation decreased maximum photosynthetic capacity and delayed photosynthetic induction in both species. InG. max, such photosynthetic downregulation was explained by coordinated downregulation of photosynthetic genes involved in Calvin cycle, Rubisco activase, photochemical reactions, and stomatal opening. Furthermore, sink-source imbalance may have triggered a change in the balance of sugar-phosphate translocators in chloroplast membranes, which may have promoted starch accumulation in chloroplasts.

Our findings provided an overall picture of the photosynthetic downregulation and NSCs accumulation inG. max, demonstrating that the photosynthetic downregulation is triggered by NSCs accumulation and cannot be explained simply by N deficiency.

One Sentence Summary

Accumulation of nonstructural carbohydrates directly induced both downregulation and delayed induction of photosynthesis by coordinated transcriptomic changes in photosynthetic genes inGlycine max.
Task-specific patterns of odorant receptor expression in worker antennae indicates a sensory filter regulating division of labor in ants
Authors: Caminer Marcel A. , Libbrecht Romain , Majoe Megha , Ho David V. , Baumann Peter , Foitzik Susanne
Published: January 2023

Division of labor (DOL) is a characteristic trait of insect societies, where tasks are generally performed by groups of specialized individuals. In social insects, young workers perform duties within the safety of the nest (e.g., brood care), while older ones undertake riskier tasks (e.g., foraging for food). This DOL remains dynamic, and workers may switch back and forth when colony needs require. Theoretical models propose that workers differ in their thresholds to take on certain tasks when confronted to task-related stimuli, resulting in variation in their response to such stimuli, task-specialization, and thus DOL. Such models assume that workers differ in how they respond to task-related information rather than in how they perceive such information. Here, we test the hypothesis that DOL rather stems from workers differing in their efficiency to detect task-related stimuli. We used transcriptomics to compare gene expression in the antennae and in the brain between nurses and foragers in the antTemnothorax longispinosus. We found that seven times as many genes were differentially expressed between the behavioral phenotypes in the antennae compared to the brain. Moreover, nearly half of all odorant receptors genes were differentially expressed, with an overrepresentation of the 9-exon gene subfamily upregulated in the antennae of nurses. These findings suggest that nurses and foragers differ in how they perceive their olfactory environment, and task-related signals. The results of this study support the hypothesis that a sensory filter in the antennaepredisposes workers to specialize in specific tasks, and may improve our understanding of DOL in insect societies.
Effect of nano-SiC doping on the structure and superconducting properties of Mg(B1–x
C
x
)2
Authors: Melone M. , Malachevsky M. T. , Sobrero C. E. , Troiani H. , Serquis A.
Published: January 2023

Carbon doping is studied in MgB2 pellets during one-step synthesis by solid-state reaction, employing both undoped and carbon-doped boron with and without the addition of nano-SiC. The phase formation during the synthesis as a function of time was followed using powder X-ray diffraction and Rietveld refinement. The superconducting properties were characterized with a magnetometer to investigate doping-induced changes. Mg(B1–x
C
x
)2 is obtained with nano-precipitates and different compositions depending on the synthesis temperature. It is found that the addition of nano-SiC prevents the phase formation at low temperature (700°C). Nevertheless, the best superconducting properties are obtained for the sample treated at 900°C using simultaneously C and SiC, with a critical current density of 105 A cm−2 at 3 T and 20 K, named the 900-20-C-nanoSiC sample.
Organic line extensions: do they make sense for brands?
Authors: Hernandez-Olalla Maria-Luisa , Valor Carmen , Abril Carmen
Published: January 2023

Purpose

Past work on the role of brands in the acceptance of organic products is partial and inconclusive. Research has failed to examine the consumer sense-making process underpinning fit assessment, despite the centrality of this assessment in the acceptance of line extensions. This study reconceptualizes the fit construct, showing the relationship of the fit dimensions (noncompensatory) and contributes to the literature with a deeper understanding of the role of a brand's association in the assessment process, which has been poorly examined in the past.

Design/methodology/approach

Grounded theory was used to unearth the process followed by consumers to assess the fit of organic line extensions. The study was based on 14 in-depth interviews.

Findings

The findings show that the dimensions of fit that consumers consider in assessing organic line extensions depend on the schema used in the assessment process. Moreover, it demonstrates that these dimensions have disparate structural relationships with one another, depending on consumers' previous commitment to organic products. Finally, the paper identifies three possible behavioral reactions by consumers toward organic line extensions.

Research limitations/implications

The main limitation of this research concerns the settings in which it was developed. Therefore, and as stated by Strauss and Corbin (1990) the model applies to the situation analyzed and not to others. Future research could study if there are cultural differences in the assessment process of an organic line extension. Moreover, the contribution presented in this paper needs further empirical testing; specifically, the configuration of dimensions needed to accept an organic line extension and the relationship among dimensions.

Originality/value

This paper contributes to the literature by studying the impact of brand association on assessing an organic line extension and reconceptualizing the fit construct by showing the dimensions and the relationship between them that are not additive to the overall fit, as shown in past literature. Additionally, it provides a guide to brands wishing to launch an organic product using a line extension strategy and the potential implications for the parent brand that should be considered.
An experimental investigation of BPMN-based corporate communications modeling
Authors: Polančič Gregor , Orban Boštjan
Published: January 2023

Purpose

Despite corporate communications having an immense impact on corporate success, there is a lack of dedicated techniques for their management and visualization. A potential strategy is to apply business process management (BPM) approach with business process model and notation (BPMN) modeling techniques.

Design/methodology/approach

The goal of this study was to gain empirical insights into the cognitive effectiveness of BPMN-based corporate communications modeling. To this end, experimental research was performed in which subjects tested two modeling notations – standardized BPMN conversation diagrams and a BPMN extension with corporate communications-specific concepts.

Findings

Standard conversation diagrams were demonstrated to be more time-efficient for designing and interpreting diagrams. However, the subjects made significantly fewer mistakes when interpreting the diagrams modeled in the BPMN extension. Subjects also evolved positive perceptions toward the proposed extension.

Practical implications

BPMN-based corporate communications modeling may be applied to organizations to depict how formal communications are or should be performed consistently, effectively and transparently by following and integrating with BPM approaches and modeling techniques.

Originality/value

The paper provides empirical insights into the cognitive effectiveness of corporate communications modeling based on BPMN and positions the corresponding models into typical process architecture.
Trends in knowledge management research in small businesses
Authors: Shekhar  , Valeri Marco
Published: January 2023

Purpose

This paper aims to map the knowledge management research in small businesses and suggest future actions to strengthen managerial practices. Knowledge management practices foster the growth of small businesses. They allow innovation to grow within the institutions, enhance customer satisfaction and reduce employee absenteeism and attrition.

Design/methodology/approach

The study adopts a bibliometric protocol to retrieve the 686 articles published in the Web of Science (WoS) database. The WoS database is selected to ensure only quality and peer-reviewed publications are analysed in the study. It then identifies the top contributions, and existing thematic areas, and suggests future research and policy actions for boosting economic growth through small business. The study uses VOSviewer, Science of Science (Sci2) and Gephi to conduct the bibliometric and network analysis.

Findings

The results from keyword co-occurrence and co-citation analysis helps in identifying thematic areas. The findings highlight that there exist five major themes in knowledge management research for small businesses. The dynamic co-citation analysis helps in tracing the evolution of these clusters and suggests future themes, research directions and methodological advances in the theme. PageRank analysis helps in identifying the top articles published on high-impact journals in the theme.

Research limitations/implications

The study helps researchers by summarising existing literature and identifying key thematic areas. It also assists policymakers by recommending actions to improve knowledge management practises in small businesses to gain a competitive advantage. The paper suffers from the limitations of bibliometric analysis. The sample is collected from a single data source and a single type (journal articles) and the statistical accuracy of the analysis depends on the quality of the sample.

Originality/value

The study’s originality lies in using fit-for-purpose software in clustering the research and suggesting actions. To the best of the authors’ knowledge, this study is one of its kind in applying bibliometrics in studying and covering several aspects of knowledge management in small businesses with a combination of software.
An SEM-ANN analysis of the impacts of Blockchain on competitive advantage
Authors: Leong Lai-Ying , Hew Jun-Jie , Lee Voon-Hsien , Tan Garry Wei-Han , Ooi Keng-Boon , Rana Nripendra P.
Published: January 2023

Purpose

Though Blockchain has been studied in numerous contexts, the understanding of the impacts of Blockchain in achieving competitive advantages remains unexplored. Many industries, organizations and firms are still in a “wait and see” mode. This study aims at examining the effects of the technological, organizational and environmental factors drawn from the TOE framework in generating competitive advantage.

Design/methodology/approach

A dual-staged deep learning structural equation modeling artificial neural network analysis was conducted on 211 samples of small and medium enterprises. Four neural network models were engaged to rank the normalized importance of each of the predictor variables.

Findings

The research model can expound 57.99 and 47.33% of the variance in Blockchain adoption and competitive advantage correspondingly. The study successfully identified nonlinear relationships. The theoretical and managerial contributions are useful to scholars and practitioners such as industrial players, investors, chief executive officers (CEOs), managers, decision-makers and other stakeholders that intend to use Blockchain technology.

Originality/value

Unlike the existing technological–organizational–environmental (TOE) framework that uses a linear model and theoretically assumes that all relationships are linear, this has been the first study, which has successfully validated that there exist nonlinear relationships in the TOE framework. Further, very little has been theorized on the impacts of Blockchain adoption on competitive advantage, especially in the context of SMEs. Therefore, this study is the first one to provide the necessary theoretical foundation that may further extend the current knowledge of Blockchain technology adoption and its impacts.