bluuebunny/crossref_metadata_2025 huggingface dataset:
The virulome of Streptomyces scabiei in response to cello-oligosaccharide elicitors
Authors: Deflandre Benoit , Stulanovic Nudzejma , Planckaert Sören , Anderssen Sinaeda , Bonometti Beatrice , Karim Latifa , Coppieters Wouter , Devreese Bart , Rigali Sébastien
Published: January 2022

The development of spots or lesions symptomatic of common scab on root and tuber crops is caused by few pathogenic

Streptomyces

with

Streptomyces scabiei

87–22 as the model species. Thaxtomin phytotoxins are the primary virulence determinants, mainly acting by impairing cellulose synthesis, and their production in

S. scabiei

is in turn boosted by cello-oligosaccharides released from host plants. In this work we aimed to determine which molecules and which biosynthetic gene clusters (BGCs) of the specialized metabolism of

S. scabiei

87–22 show a production and/or a transcriptional response to cello-oligosaccharides. Comparative metabolomic analyses revealed that molecules of the virulome of

S. scabiei

induced by cellobiose and cellotriose include (i) thaxtomin and concanamycin phytotoxins, (ii) desferrioxamines, scabichelin and turgichelin siderophores in order to acquire iron essential for housekeeping functions, (iii) ectoine for protection against osmotic shock once inside the host, and (iv) bottromycin and concanamycin antimicrobials possibly to prevent other microorganisms from colonizing the same niche. Importantly, both cello-oligosaccharides reduced the production of the spore germination inhibitors germicidins thereby giving the ‘green light’ to escape dormancy and trigger the onset of the pathogenic lifestyle. For most metabolites - either with induced or reduced production - cellotriose was revealed to be a slightly stronger elicitor compared to cellobiose, supporting an earlier hypothesis which suggested the trisaccharide was the real trigger for virulence released from the plant cell wall through the action of thaxtomins. Interestingly, except for thaxtomins, none of these BGCs’ expression seems to be under direct control of the cellulose utilization repressor CebR suggesting the existence of a yet unknown mechanism for switching on the virulome. Finally, a transcriptomic analysis revealed nine additional cryptic BGCs that have their expression awakened by cello-oligosaccharides, suggesting that other and yet to be discovered metabolites could be part of the virulome of

S. scabiei

.
NIMAA: an R/CRAN package to accomplish NomInal data Mining AnAlysis
Authors: Jafari Mohieddin , Chen Cheng , Mirzaie Mehdi , Tang Jing
Published: January 2022

Nominal data is data that has been “labeled” and can be designated into a number of non-overlapping unordered groups. The analysis of this type of data is often trivial because it is not feasible to conduct extensive numerical methods on this type of data. Graphs or networks, on the other hand, are comprised of sets of nodes and edges that can also be considered as nominal variables. By integrating graph theory and data mining approaches, we offer the R package NIMAA to define a nominal data-mining pipeline to explore more information. Using nominal variables in a dataset, NIMAA provides functions for constructing weighted and unweighted bipartite graphs, analysing the similarity of labels in nominal variables, clustering labels or categories to super-labels, validating clustering results, predicting bipartite edges by missing weight imputation, and providing a variety of visualization tools. Here, we also indicated the application of nominal data mining in a biological dataset with well-riched nominal variables.

Availability

NIMAA’s official release and the beta update are available on CRAN and Github, respectively. URLs: https://CRAN.R-project.org/package=NIMAA and https://github.com/jafarilab/NIMAA

Contact

mohieddin.jafari@helsinki.fi; jing.tang@helisnki.fi

Contributions

MJ conceived the study and developed the models, MJ and CC adopted and implemented the methods, MM improved the methods, JT provided the funding, MJ, CC, MM and JT wrote the paper.
Generation of novel SARS-CoV-2 variants on B.1.1.7 lineage in three patients with advanced HIV disease
Authors: Riddell Anna C. , Kele Beatrix , Harris Kathryn , Bible Jon , Murphy Maurice , Dakshina Subathira , Storey Nathaniel , Owoyemi Dola , Pade Corinna , Gibbons Joseph M. , Harrington David , Alexander Eliza , McKnight Áine , Cutino-Moguel Teresa
Published: January 2022

The emergence of new SARS-COV-2 variants is of public health concern in case of vaccine escape. Described are three patients with advanced HIV-1 and chronic SARS-CoV-2 infection in whom there is evidence of selection and persistence of novel mutations which are associated with increased transmissibility and immune escape.
A survey assessing antimicrobial prescribing at UNRWA primary health care centers in Jordan
Authors: Orubu ESF , Albeik S , Ching C , Hussein R , Mousa A , Horino M , Naqa R , Elayyan M , Saadeh R , Zaman MH
Published: January 2022

Antimicrobial resistance (AMR) is a public health emergency. There is insufficient information on AMR in the context of humanitarian settings. An understanding of behavioural and institutional level factors can strengthen antimicrobial stewardship. This study used a semi-structured questionnaire to assess both knowledge, attitudes and practices (KAP) on antimicrobial use, resistance and stewardship, and options to improving prescribing, among prescribers at the Primary Healthcare facilities of the UNRWA Jordan field office. Responses to the KAP questions were evaluated using the Capability, Opportunity, Motivation, Behaviour (COM-B) framework and Bloom’s cutoffs. For each framework component, Blooms cutoffs and interpretations were: >80%, “good”; 60-79%, “moderate”; and <60%’ “poor”. Fourteen options to improve prescribing were each assessed using 5-point Likert scales from very unhelpful to very helpful, aggregated by helpful and very helpful and ranked as: >90%, best/most acceptable; >80-90%, as acceptable; and, 70-80% as maybe acceptable/good. The questionnaire response rate was 59% (37/63) with a completion rate of 92% (34/37). Aggregate scores for real knowledge on AMR was 97%; opportunity to improve prescribing 88%; and motivation 16% - participants did not believe that there was a connection between their prescribing and AMR or that they had a key role in helping control AMR. Good options (74% aggregate score) to improving prescribing were the availability of guidelines and resistance data. There was good knowledge of AMR and good opportunities, but poor motivation for rational prescribing or behavioral change. There is a clinical need for antimicrobial resistance data to promote rational antibiotic prescribing.
Data-driven extraction of human kinase-substrate relationships from omics datasets
Authors: Maier Benjamin Dominik , Petursson Borgthor , Lussana Alessandro , Petsalaki Evangelia
Published: January 2022

Phosphorylation forms an important part of the signalling system that cells use for decision making and regulation of processes such as cell division and differentiation. To date, a large portion of identified phosphosites are not known to be targeted by any kinase. At the same time around 30% of kinases have no known target. This knowledge gap stresses the need to make large scale, data-driven computational predictions.

In this study, we have created a machine learning-based model to derive a probabilistic kinase-substrate network from omics datasets. Our methodology displays improved performance compared to other state-of-the-art kinase-substrate prediction methods, and provides predictions for more kinases. Importantly, it better captures new experimentally-identified kinase-substrate relationships. It can therefore allow the improved prioritisation of kinase-substrate pairs for illuminating the dark human cell signalling space.

Our model is integrated into a web server, SELPHI2.0, to allow unbiased analysis of phosphoproteomics data, facilitating the design of downstream experiments to uncover mechanisms of signal transduction across conditions and cellular contexts.
CNAViz: An interactive webtool for user-guided segmentation of tumor DNA sequencing data
Authors: Lalani Zubair , Chu Gillian , Hsu Silas , Kagawa Shaw , Xiang Michael , Zaccaria Simone , El-Kebir Mohammed
Published: January 2022

Copy-number aberrations (CNAs) are genetic alterations that amplify or delete the number of copies of large genomic segments. Although they are ubiquitous in cancer and, thus, a critical area of current cancer research, CNA identification from DNA sequencing data is challenging because it requires partitioning of the genome into complex segments with the same copy-number states that may not be contiguous. Existing segmentation algorithms address these challenges either by leveraging the local information among neighboring genomic regions, or by globally grouping genomic regions that are affected by similar CNAs across the entire genome. However, both approaches have limitations: overclustering in the case of local segmentation, or the omission of clusters corresponding to focal CNAs in the case of global segmentation. Importantly, inaccurate segmentation will lead to inaccurate identification of important CNAs. For this reason, most pan-cancer research studies rely on manual procedures of quality control and anomaly correction. To improve copy-number segmentation and their control, we introduce CNAViz, a web-based tool that enables the user to simultaneously perform local and global segmentation, thus overcoming the limitations of each approach. Using simulated data, we demonstrate that by several metrics, CNAViz allows the user to obtain more accurate segmentation relative to existing local and global segmentation methods. Moreover, we analyze six bulk DNA sequencing samples from three breast cancer patients. By validating with parallel singlecell DNA sequencing data from the same samples, we show that by using CNAViz, our user was able to obtain more accurate segmentation and improved accuracy in downstream copy-number calling. CNAViz is available at https://github.com/elkebir-group/cnaviz.
Sero-Prevalence of Covid-19 among workers in Malaysia
Authors: Noordin Noorliza Mohamad , Omar Aziyati binti , Isharudin Ishmah Hana , Idris Riasah , Chem Yukie , Mat Sahat Intan Surianne , Sengol Selvanesan , Aziz Zirwatul Adilah , Lim Zhuo-zhi , Lim Teck-Onn
Published: January 2022

From the beginning of the pandemic in Feb 2020, Malaysia has been through 4 waves of outbreak, the magnitude of each wave is several orders larger than the preceding one. By the end of the fourth wave in October 2021, Malaysia has among the highest death toll in Asia, cumulative incidence of confirmed cases has reached 7.0% (>30% in Klang Valley). However it remains uncertain what is the true proportion of the population infected.

We conducted a sero-survey on 1078 workers from 17 worksites in Klang Valley and Perak between July and September 2021. We tested them for SARS-CoV-2–specific antibodies using Ecotest, a lateral flow immunoassay (LFIA). The ability of antibody testing to detect prior infection depends on the assay and sero-reversion. We therefore adjusted the prevalence estimates to correct for potential misclassification bias due to the use of LFIA and sero-reversion using test sensitivity and specificity results estimated from an independent validation study.

The mean age of the workers was 32 years, 89% were male and migrant workers comprised 81% of all subjects, 59% the subjects were from Klang valley. 33% of workers had prior RT-PCR confirmed Covid-19 infections. We estimated 82.2 percent of workers had been infected by Covid-19 by July-September 2021. Prevalence was 99.9% among migrant workers and 12.1% among local workers. Klang Valley, the most industrialized region in Malaysia where most migrant workers are found, had 100% prevalence, giving an infection-to-case ratio (ICF) of ∼3.

Our sero-prevalence results show that the incidence of Covid19 is extremely high among migrant workers in Malaysia, consistent with findings from other countries such as Kuwait and Singapore which also hosted large number of migrant workers.
Pooled RNA: extraction free testing of saliva for SARS-CoV-2 detection
Authors: Allicock Orchid M. , Yolda-Carr Devyn , Todd John A. , Wyllie Anne L.
Published: January 2022

The key to limiting SARS-CoV-2 spread is to identify virus-infected individuals (both symptomatic and asymptomatic) and isolate them from the general population. Hence, routine weekly testing for SARS-CoV-2 in all asymptomatic (capturing both infected and non-infected) individuals is considered critical in situations where a large number of individuals congregate such as schools, prisons, aged care facilities and industrial workplaces. Such testing is hampered by operational issues such as cost, test availability, access to healthcare workers and throughput. We developed the SalivaDirect RT-qPCR assay to increase access to SARS-CoV-2 testing via a low-cost, streamlined protocol using self-collected saliva. To expand the single sample testing protocol, we explored multiple extraction-free pooled saliva testing workflows prior to testing with the SalivaDirect assay. A pool size of five, with or without heat inactivation at 65°C for 15 minutes prior to testing resulted in a positive agreement of 98% and 89%, respectively, and an increased Ct value shift of 1.37 and 1.99 as compared to individual testing of the positive clinical saliva specimens. Applying this shift in Ct value to 316 individual, sequentially collected, SARS-CoV-2 positive saliva specimen results reported from six clinical laboratories using the original SalivaDirect assay, 100% of the samples would have been detected (Ct value >45) had they been tested in the 1:5 pool strategy. The availability of multiple pooled testing workflows for laboratories can increase test turnaround time, permitting results in a more actionable time frame while minimizing testing costs and changes to laboratory operational flow.
Evolution of a novel left-right asymmetry involving tissue remodelling and MyoID
Authors: Lefèvre Bénédicte M. , Delvigne Marine , Vidal Josué , Courtier-Orgogozo Virginie , Lang Michael
Published: January 2022

Left-right asymmetries recurrently evolve in animals but the underlying developmental mechanisms are unknown. In mostDrosophilaspecies, the male genitalia is symmetric and undergoes a clockwise 360° rotation during development. InD. melanogaster, this tissue remodeling process is directed by class I myosins: in MyoID mutants the rotation is reversed and the genitalia remains symmetric. Males ofDrosophila pacheahave evolved unique left-right asymmetric genital organs and a characteristic right-sided copulation posture in the past 3-6 million years. To test if these asymmetries in morphology and behavior evolved via the recruitment of pre-existing directional cues controlled by MyoID, we used CRISPR to knockout MyoID inD. pachea. Strikingly, mutant males undergo a reverse genitalia rotation and develop mirror-image asymmetric genitalia, indicating that MyoID controls both the direction of genitalia rotation direction and morphological asymmetry. Although genital asymmetry is reversed, MyoID mutants still adopt a wild-type right-sided copulation posture. Our results show that MyoID and its asymmetry guidance role were recruited for the evolution of a novel left-right asymmetry inD. pacheaand that lateralized copulation behavior is determined by other mechanisms. The evolution of a new left-right organ size asymmetry inD. pacheainvolved recruitment of existing directional cues.
Topological supramolecular network enabled highly conductive and stretchable organic bioelectronics
Authors: Jiang Yuanwen , Zhang Zhitao , Wang Yi-Xuan , Li Deling , Coen Charles-Théophile , Hwaun Ernie , Chen Gan , Wu Hung-Chin , Zhong Donglai , Niu Simiao , Wang Weichen , Saberi Aref , Lai Jian-Cheng , Wang Yang , Trotsyuk Artem A. , Loh Kang Yong , Shih Chien-Chung , Xu Wenhui , Liang Kui , Zhang Kailiang , Hu Wenping , Jia Wang , Cheng Zhen , Dauskardt Reinhold H. , Gurtner Geoffrey C. , Tok Jeffery B.-H. , Deisseroth Karl , Soltesz Ivan , Bao Zhenan
Published: January 2022

Intrinsically stretchable bioelectronic devices based on soft and conducting organic materials have been regarded as the ideal interface for seamless and biocompatible integration with the human body. However, the grand challenge remains for the conducting polymer to possess both high mechanical ductility and good electrical conduction at cellular level feature sizes. This longstanding material limitation in organic bioelectronics has impeded the full exploitation of its unique benefits. Here, we introduce a new molecular engineering strategy based on rationally designed topological supramolecular networks, which allows effective decoupling of competing effects from multiple molecular building blocks to meet complex requirements. We achieve two orders of magnitude improvement in the conductivity under 100% strain in physiological environment, along with the capability for direct photopatterning down to 2 μm. These unprecedented capabilities allow us to realize previously inaccessible bioelectronic applications including high-resolution monitoring of ‘soft and malleable’ creatures, e.g., octopus, and localized neuromodulation down to single nucleus precision for controlling organ-specific activities through delicate tissues, e.g., brainstem.
Crystal Structure of Caskin1/CASK complex reveals the molecular basis of the binding specificity of CASK_CAMK domain and its binding partners
Authors: Wang Yue , Chen Qiangou , Jiang Riting , Ye Xiaoyang , Wan Jun , Li Jianchao , Liu Wei
Published: January 2022

CASK is a unique scaffold protein in the synapse system. It links numerous proteins to the pre- or post-synaptic region and is critical to the homeostasis of synaptic vesicles. The N-terminus of CASK is a calcium/calmodulin-dependent protein kinase (CAMK) domain, which has diverse functions and interacts with downstream proteins to form a scaffold platform. Caskin1 is one of the brain-specific adaptor proteins of CASK. Previous studies showed that CASK_CAMK domain interacts with Caskin1 CID domain with relatively low affinity. In this study, we re-visit this interaction by remapping the interaction boundary and solving their complex structure. Based on the structure, we systematically compared the interactions between CASK_CAMK and other binding partners. Our results showed that CAMK domain occupies the CID peptide by using its C-lobe groove (between the α1 and α2) and there is a highly conserved signature motif (ζ-x-ψ-W-ψ-x-R) in the CID domain, where ζ is acidic side chain containing residues, x is any amino acid residue, ψ is hydrophobic residues, W is for tryptophan, and R is arginine. These findings allowed us to identify several new potential cytoplasmic binding partners for CASK_CAMK.
Divergent age-related methylation patterns in long and short-lived mammals
Authors: Haghani Amin , Wang Nan , Lu Ake T. , Mozhui Khyobeni ,   Mammalian Methylation Consortium, Raj Ken , Yang X. William , Horvath Steve
Published: January 2022

Age-related changes to cytosine methylation have been extensively characterized across the mammalian family. Some cytosines that are conserved across mammals exhibit age-related methylation changes that are so consistent that they were used to successfully develop cross-species age predictors. In a similar vein, methylation levels of some conserved cytosines correlate highly with species lifespan, leading to the development of highly accurate lifespan predictors. Surprisingly, little to no commonality is found between these two sets of cytosines even though the relationship between aging and lifespan is by most measures linked. We ventured to address this conundrum by first identifying age-related cytosines whose methylation levels change in opposite directions between short and long-lived species. We hypothesized that age-related CpGs that are also associated with species lifespan would tap into biological processes that simultaneously impact aging and lifespan. To this end, we analyzed age-related cytosine methylation patterns in 82 mammalian species. For each CpG, we correlated the intra-species age correlation with maximum lifespan across mammalian species. We refer to this correlation of correlations as Lifespan Uber Correlation (LUC). This approach is unique in incorporating age and species lifespan in a single analysis. We identified 629 CpGs with opposing methylation aging patterns in long and short-lived species. Many of these are found to be near BCL11B, NPTN, and HOXC4 loci. Methylation and transcription analyses of Bcl11b knockout mice indicate that this gene partially regulates the methylation state of LUC CpGs. We developed DNAm age estimators (epigenetic clocks) based on LUC CpGs. These LUC clocks exhibited the expected behavior in benchmark aging interventions such as caloric restriction, growth hormone receptor knockout and high-fat diet. Furthermore, we found that Bcl11b heterozygous knockout mice exhibited an increased epigenetic age in the striatum. Overall, we present a bioinformatics approach that identified CpGs and their associated genes implicated both in aging and lifespan. These cytosines lend themselves to developing epigenetic clocks that are sensitive to perturbations that impact both age and lifespan.
Entamoeba histolytica EHD1 is involved in mitosome-endosome contact
Authors: Santos Herbert J. , Hanadate Yuki , Imai Kenichiro , Watanabe Haruo , Nozaki Tomoyoshi
Published: January 2022

Inter-organellar crosstalk is often mediated by membrane contact sites (MCSs), which are zones where participating membranes come within a proximity of 30 nm. MCSs have been found in organelles including the endoplasmic reticulum, Golgi bodies, endosomes, and mitochondria. Despite its seeming ubiquity, reports of MCS involving mitochondrion-related organelles (MROs) present in a few anaerobic parasitic protozoa remain lacking. Entamoeba histolytica, the etiological agent of amoebiasis, possesses an MRO called mitosome. We previously discovered several Entamoeba-specific transmembrane mitosomal proteins (ETMPs) from in silico and cell biological analyses. One of them, ETMP1 (EHI_175060), was predicted to have one transmembrane domain and two coiled-coil regions, and was demonstrated to be mitosome membrane-integrated based on carbonate fractionation and immunoelectron microscopy (IEM) data. Immunoprecipitation analysis detected a candidate interacting partner, EH-domain containing protein (EHD1, EHI_105270). We expressed HA-tagged EHD1 in E. histolytica and subsequent immunofluorescence and IEM data indicated an unprecedented MCS between the mitosome and the endosome. Live imaging of GFP-EHD1 expressing strain demonstrated that EHD1 is involved in early endosome formation, and is observed in MCS between endosomes of various sizes. In vitro assay using recombinant His-EHD1 demonstrated ATPase activity. MCSs are involved in lipid transfer, ion homeostasis, and organelle dynamics. The serendipitous discovery of the ETMP1 interacting partner EHD1, led to the observation of the mitosome-endosome contact site in E. histolytica. It opened a new view of how the relic mitochondria of Entamoeba may likewise be involved in organelle crosstalk, a conserved feature of mitochondria and other organelles in general.
An efficient simplified method for the generation of corneal epithelial cells from human pluripotent stem cells
Authors: Abdalkader Rodi , Kamei Ken-ichiro
Published: January 2022

Corneal epithelial cells derived from human pluripotent stem cells (hPSCs) are an important cell source for preclinical models to test ophthalmic drugs. However, current differentiation protocols lack instructions regarding optimal culturing conditions, which hinders the quality of cells and limits scale-up. Here, we introduce a simplified small molecule-based corneal induction method (SSM-CI) to generate corneal epithelial cells from hPSCs. SSM-CI provides the advantage of minimizing cell culturing time using two defined culturing media containing TGF-β, and Wnt/β-catenin pathway inhibitors, and bFGF growth factor over 25 days. Compared to the conventional human corneal epithelial cell line (HCE-T) and human primary corneal epithelial cells (hPCEpCs), corneal epithelial cells generated by SSM-CI are well-differentiated and express relevant maturation markers, including PAX6 and CK12. RNA-seq analysis indicated the faithful differentiation of hPSCs into corneal epithelia, with significant upregulation of corneal progenitor and adult corneal epithelial phenotypes. Furthermore, despite the initial inhibition of TGF-β and Wnt/β-catenin, upregulation of these pathway-related transcripts was observed in the later stages, indicating their necessity in the generation of mature corneal epithelial cells. Moreover, we observed a shift in gene signatures associated with the metabolic characteristics of mature corneal epithelial cells, involving a decrease in glycolysis- and an increase in fatty acid oxidation. This was also attributed to the overexpression of metabolic enzymes and transporter-related transcripts responsible for fatty acid metabolism. Thus, SSM-CI provides a comprehensive method for the generation of functional corneal epithelial cells for use in preclinical models.
Evolutionary conservation of A/T-ending codons reflects co-regulation of expression and complex formation
Authors: Benisty Hannah , Hernandez-Alias Xavier , Weber Marc , Anglada-Girotto Miquel , Mantica Federica , Radusky Leandro , Senger Gökçe , Weghorn Donate , Irimia Manuel , Schaefer Martin H. , Serrano Luis
Published: January 2022

Background

In a wide variety of organisms, synonymous codons are used with different frequencies, a phenomenon known as codon bias that plays an important role in determining expression levels. However, the importance of codon bias to facilitate the simultaneous turnover of thousands of protein-coding transcripts to bring about phenotypic changes in cellular programs such as development, has not yet been investigated in detail.

Results

Here, we discover that genes with A/T-ending codon preferences are expressed coordinately and display a high codon conservation in mammals. This feature is not observed in genes enriched in G/C-ending codons. A paradigmatic case of this phenomenon is KRAS, from the RAS family, an A/T-rich gene with a high codon conservation (95%) in comparison to HRAS (76%). Also, we find that genes with similar codon composition are more likely to be part of the same protein complex, and that genes with A/T-ending codons are more prone to form protein complexes than those rich in G/C. The codon preferences of genes with A/T-ending codons are conserved among vertebrates. We propose that codon conservation, a feature of expression-coordinated transcripts, is linked to the high expression variation and coordination of tRNA isoacceptors reading A/T-ending codons.

Conclusions

Our data indicate that cells exploit A/T-ending codons to generate coordinated, fine-tuned changes of protein-coding transcripts. We suggest that this orchestration contributes to tissue-specific and ontogenetic-specific expression, which can facilitate, for instance, timely protein complex formation.
A deep learning pipeline for segmentation of Proteus mirabilis colony patterns
Authors: Doshi Anjali , Shaw Marian , Tonea Ruxandra , Minyety Rosalía , Moon Soonhee , Laine Andrew , Guo Jia , Danino Tal
Published: January 2022

The motility mechanisms of microorganisms are critical virulence factors, enabling their spread and survival during infection. Motility is frequently characterized by qualitative analysis of macroscopic colonies, yet the standard quantification method has mainly been limited to manual measurement. Recent studies have applied deep learning for classification and segmentation of specific microbial species in microscopic images, but less work has focused on macroscopic colony analysis. Here, we advance computational tools for analyzing colonies of Proteus mirabilis, a bacterium that produces a macroscopic bullseye-like pattern via periodic swarming, a process implicated in its virulence. We present a dual-task pipeline for segmenting (1) the macroscopic colony including faint outer swarm rings, and (2) internal ring boundaries, unique features of oscillatory swarming. Our convolutional neural network for patch-based colony segmentation and U-Net with a VGG-11 encoder for ring boundary segmentation achieved test Dice scores of 93.28% and 83.24%, respectively. The predicted masks at times improved on the ground truths from our automated annotation algorithms. We demonstrate how application of our pipeline to a typical swarming assay enables ease of colony analysis and precise measurements of more complex pattern features than those which have been historically quantified.
YAP restricts renal inflammation and mitigates kidney damage in nephronothisis related kidney disease
Authors: Ferri Giulia , Goffette Valentine , Porée Esther , Braeg Simone , Carvalho Shana , Quatredeniers Marceau , Kuehn E. Wolfgang , Saunier Sophie , Viau Amandine
Published: January 2022

Nephronophthisis (NPH) is an orphan recessive kidney disease mostly caused by mutations in NPHP1 and 20 other genes encoding proteins that localize to primary cilia. To date the pathways linking altered primary cilia function to progressive kidney scarring in NPH remain poorly defined and therapeutic options allowing NPH patients to escape end-stage kidney disease are lacking.

Distinct proteins mutated in NPH interact with components of the Hippo pathway, an important regulator of cell fate. YAP (Yes-associated protein) overactivation has been shown to induce renal scarring while YAP inhibition showed protective effect in kidney diseases unrelated to NPH. Yet, the therapeutic potential of YAP inhibition in NPH has not been formerly assessed.

Here we studied the impact of both genetic and pharmacologic YAP inhibition on the NPH-like phenotype caused by a bi-allelic mutation of Lkb1, a ciliary kinase interacting with NPHP1. Contrary to non NPH renal disease, our results reveal an unexpected protective role of YAP in Lkb1 mutant kidneys. Indeed, YAP genetic disruption drastically increase kidney disease burden in Lkb1 deficient mice, while pharmacologic inhibition of YAP failed to improve their phenotype.

Collectively these results suggest that YAP inhibition is not a valid therapeutic strategy in NPH and suggest that LKB1 and YAP are parallel negative regulators of a yet uncharacterized pathway detrimental for kidney health.
Out of the blue: the independent activity of sulfur-oxidizers and diatoms mediate the sudden color shift of a tropical river
Authors: Arce-Rodríguez Alejandro , Libby Eduardo , Castellón Erick , Avendaño Roberto , Cambronero Juan Carlos , Vargas Maribel , Pieper Dietmar H. , Bertilsson Stefan , Chavarría Max , Puente-Sánchez Fernando
Published: January 2022

Río Celeste (“Sky-Blue River”) is a river located in the Tenorio National Park (Costa Rica) that has become an important hotspot for eco-tourism due to its striking sky-blue color. A previous study suggested that this color is not caused by dissolved chemical species, but by precipitation of lightscattering aluminosilicate particles at the mixing point of two colorless streams, the acidic Quebrada Agria and the neutral Río Buenavista. We now present microbiological information on Río Celeste and its two tributaries, as well as a more detailed characterization of the particles that occur at the mixing point. Our results overturn the previous belief that the light scattering particles are formed by the aggregation of smaller particles coming from Río Buenavista, and rather point to chemical formation of hydroxyaluminosilicate colloids with Quebrada Agria as the main contributor to the phenomenon, with Río Buenavista acting as a secondary source of silica to the reaction. We also show how the sky-blue color of Río Celeste arises from the tight interaction between chemical and biological processes. Sulfur-oxidizing bacteria generate an acidic environment in Quebrada Agria, which in turn cause dissolution and mobilization of aluminum and other metals, while in Río Buenavista the growth of diatoms transforms dissolved silicon into colloidal biogenic forms. The local interaction between these two well-known biological activities gives rise to the unique Río Celeste phenomenon, in what constitutes a textbook example of emergent behavior in environmental microbiology.
Meta-analysis of the black soldier fly (Hermetia illucens) microbiota based on 16S rRNA gene amplicon sequencing
Authors: IJdema Freek , De Smet Jeroen , Crauwels Sam , Lievens Bart , Van Campenhout Leen
Published: January 2022

Black soldier fly larvae (BSFL) belong to the most widely reared insect species as an alternative protein source at industrial scale. Bacteria in the larval gut can provide benefits for the animal, though some bacteria can also be pathogenic for the insect. Accurate characterization of the BSFL microbiota is important for the production of BSFL in terms of yield and microbiological safety. In this study, 16S ribosomal RNA gene sequence data sets from 11 studies were re-analysed to gain better insights in the BSFL gut microbiota, potential factors that influence their composition, and differences between the gut and the whole larvae microbiota. A core gut microbiota was found consisting of members ofEnterococcus, Klebsiella, Morganella, Providencia, andScrofimicrobium.Further, the factors “Study”, “Age” and “Feed” significantly affected the microbiota gut composition. When compared to whole larvae, a significantly lower number of observed zero-radius Operational Taxonomic Units and a lower diversity was found for gut samples, suggesting that the larvae harboured additional microbes on their cuticle or in the insect body. Universal choices in insect sample type, primer selection and bio-informatics can strengthen future meta-analyses and improve our understanding of the BSFL gut microbiota towards the optimization of insect production.
In vivo inactivation of RAD51-mediated homologous recombination leads to premature aging, but not to tumorigenesis
Authors: Matos-Rodrigues Gabriel , Barroca Vilma , Muhammad Ali-Akbar , Allouch Awatef , Koundrioukoff Stephane , Lewandowski Daniel , Despras Emmanuelle , Guirouilh-Barbat Josée , Frappart Lucien , Kannouche Patricia , Dupaigne Pauline , Cam Eric Le , Perfettini Jean-Luc , Romeo Paul-Henri , Debatisse Michelle , Jasin Maria , Livera Gabriel , Martini Emmanuelle , Lopez Bernard S.
Published: January 2022

Genetic instability is a hallmark of both cancer and aging. Homologous recombination (HR) is a prominent DNA repair pathway maintaining genomic integrity. Mutations in many HR genes lead to cancer predisposition. Paradoxically, the consequences of mutations in the pivotal HR player, RAD51, on cancer development remain puzzling. Moreover, in contrast with other HR genes, RAD51 mouse models are not available to experimentally address the role of RAD51 on aging and carcinogenesis, in vivo. Here, we engineered a mouse model with an inducible dominant negative form of RAD51 (SMRad51) that suppresses RAD51-mediated HR without stimulating alternative non-conservative repair pathways. We found that, in vivo expression of SMRad51 did not trigger tumorigenesis, but instead induced premature aging. We propose that these in vivo phenotypes result from the exhaustion of proliferating progenitors submitted to chronic endogenous replication stress resulting from RAD51-mediated HR suppression. Our data underline the importance of the RAD51 activity for progenitors homeostasis, preventing aging, and more generally for the balance between cancer and aging.
The oncogene FOXQ1 is a selective activator of Wnt/β-catenin signalling
Authors: Pizzolato Giulia , Moparthi Lavanya , Söderholm Simon , Cantù Claudio , Koch Stefan
Published: January 2022

The forkhead box transcription factor FOXQ1 is aberrantly induced in various cancers, and contributes to tumour growth and metastasis. It has been suggested that FOXQ1 exacerbates cancer by activating the oncogenic Wnt/β-catenin signalling pathway. However, the mode of action of FOXQ1 in the Wnt pathway remains to be resolved. Here, we report that FOXQ1 is a bimodal transcriptional activator of Wnt target gene expression in normal and cancer cells. Using co-immunoprecipitation, proximity proteomics, and reporter assays, we show that FOXQ1 engages the Wnt transcriptional complex to promote gene expression via TCF/LEF transcription factors. In parallel, FOXQ1 differentially regulates the expression of Wnt target genes independently of β-catenin and TCF/LEFs, which is facilitated by spatially separated activator and repressor domains. Our results suggest that FOXQ1 is a novel component of the Wnt transcriptional complex that reinforces and specifies Wnt signalling in a context-dependent manner.
Palatal morphology predicts the paleobiology of early salamanders
Authors: Jia Jia , Li Guangzhao , Gao Ke-Qin
Published: January 2022

Ecological preferences and life history strategies have enormous impacts on the evolution and phenotypic diversity of salamanders, but the yet established reliable ecological indicators hinder investigations on the paleobiology of early salamanders. Here we statistically demonstrate using geometric morphometric analysis that both the shape of the palate and many non-shape variables particularly associated with vomerine teeth are ecologically informative in early stem- and basal crown-group salamanders. The morphology of the palate is heavily impacted by convergence constrained by feeding mechanisms and also exhibits clear stepwise evolutionary patterns with alternative phenotypic designs to cope with similar functional demand. Paleoecological disparities in early salamanders had took place before the Middle Jurassic and have achieved all ecological preferences in the Early Cretaceous. Metamorphosis is significant in the expansion of ecomorphospace of the palate in early salamanders. The common ancestor of salamanders is metamorphosed and terrestrial, and share unified lifestyles with other modern amphibians.
Discrimination of edge orientation by bumblebees
Authors: Guiraud Marie , Roper Mark , Wolf Stephan , Woodgate Joseph L. , Chittka Lars
Published: January 2022

Simple feature detectors in the visual system, such as edge-detectors, are likely to underlie even the most complex visual processing, so understanding the limits of these systems is crucial for a fuller understanding of visual processing. We investigated the ability of bumblebees (Bombus terrestris) to discriminate between differently angled edges. In a multiple-choice, “meadow-like” scenario, bumblebees successfully discriminated between angled bars with 7° differences, significantly exceeding the previously reported performance of eastern honeybees (Apis cerana, limit: 15°). Neither the number of choices required to learn, nor the bees’ final discrimination performance were affected by the angular orientation of the training bars, indicating a uniform performance across the visual field. Previous work has found that, in dual-choice tests, eastern honeybees cannot reliably discriminate between angles with less than 25° difference, suggesting that performance in discrimination tasks is affected by the training regime, and doesn’t simply reflect the perceptual limitations of the visual system. We used high resolution LCD monitors to investigate the limits of bumblebees’ angular resolution in dual-choice experiments. Bumblebee could still discriminate 7° angle differences under such conditions (exceeding the previously reported limit forApis mellifera, of 10°, as well as that ofA. cerana), eventually reaching similar levels of accuracy, but required longer learning periods than under multiple-choice conditions. Bumblebees show impressive abilities to discriminate between angled edges, performing better than two previously tested species of honeybee. This high performance may, in turn, support complex visual processing in the bumblebee brain.
A quantitative analysis of the similarities and differences of the HIV/FIV gag genome
Authors: Siu Charlotte , Horn Meredith , Cheng Xiao-Wen
Published: January 2022

This manuscript has been withdrawn following erroneous duplicate posting. The appropriate version is available at 10.1101/2022.01.09.475545.
Dual specificity phosphatase 7 drives the formation of cardiac mesoderm in mouse embryonic stem cells
Authors: Sladeček Stanislava , Radaszkiewicz Katarzyna Anna , Bőhmová Martina , Gybeľ Tomáš , Radaszkiewicz Tomasz Witold , Pacherník Jiří
Published: January 2022

Dual specificity phosphatase 7 (DUSP7) is a protein belonging to a broad group of phosphatases that 14 can dephosphorylate phosphoserine/phosphothreonine as well as phosphotyrosine residues within the 15 same substrate. DUSP7 has been linked to the negative regulation of mitogen activated protein kinases 16 (MAPK), and in particular to the regulation of extracellular signal-regulated kinases 1 and 2 (ERK1/2). 17 MAPKs play an important role in embryonic development, where their duration, magnitude, and 18 spatiotemporal activity must be strictly controlled by other proteins, among others by DUSPs. In this 19 study, we focused on the effect of DUSP7 depletion on the in vitro differentiation of mouse embryonic 20 stem (ES) cells. We showed that even though DUSP7 knock-out ES cells do retain some of their basic 21 characteristics, when it comes to differentiation, they preferentially differentiate towards neural cells, 22 while the formation of early cardiac mesoderm is repressed. Therefore, our data indicate that DUSP7 23 is necessary for the correct formation of neuroectoderm and cardiac mesoderm during the in vitro 24 differentiation of ES cells.
Differential UBE2H-CTLH E2-E3 ubiquitylation modules regulate erythroid maturation
Authors: Sherpa Dawafuti , Müller Judith , Karayel Özge , Chrustowicz Jakub , Xu Peng , Gottemukkala Karthik V. , Baumann Christine , Gross Annette , Czarnezki Oliver , Zhang Wei , Gu Jun , Nilvebrant Johan , Weiss Mitchell J. , Sidhu Sachdev S. , Murray Peter J. , Mann Matthias , Schulman Brenda A. , Alpi Arno F.
Published: January 2022

The development of haematopoietic stem cells into mature erythrocytes – erythropoiesis – is a controlled process characterized by cellular reorganisation and drastic reshaping of the proteome landscape. Failure of ordered erythropoiesis is associated with anaemias and haematological malignancies. Although the ubiquitin (UB) system is a known crucial post-translational regulator in erythropoiesis, how the erythrocyte is reshaped by the UB system is poorly understood. By measuring the proteomic landscape ofin vitrohuman erythropoiesis models, we found dynamic differential expression of subunits of the CTLH E3 ubiquitin ligase complex that formed distinct maturation stage-dependent assemblies of structurally homologous RANBP9-and RANBP10-CTLH complexes. Moreover, protein abundance of CTLH’s cognate E2-conjugating enzyme UBE2H increased during terminal differentiation, which depended on catalytically active CTLH E3 complexes. CRISPR-Cas9 mediated inactivation of all CTLH E3 assemblies by targeting the catalytic subunitMAEA,orUBE2H, triggered spontaneous and accelerated maturation of erythroid progenitor cells including increased heme and haemoglobin synthesis. Thus, the orderly progression of human erythropoiesis is controlled by the assembly of distinct UBE2H-CTLH modules functioning at different developmental stages.
Formation and stabilization mechanism of mesoscale clusters in solution
Authors: Zong Shuyi , Wang Jingkang , Huang Xin , Wu Hao , Liu Qi , Hao Hongxun
Published: January 2022

To understand the existence of complex meso-sized solute-rich clusters, which challenge the understanding of phases and phase equilibria, the formation and stabilization mechanisms of clusters in solution during nucleation of crystals and the associated physico-chemical rules are studied in detail. An essential part of the mechanism is the formation of long-lived oligomers between solute molecules. By means of density functional theory simulation and nuclear magnetic resonance experiments, this work showed that the oligomers in solution tend to be π–π stacking dimers. Clusters are formed under the combined effect of diffusion and monomer–dimer reaction. The physically meaningful quantities such as the monomer–dimer reaction rate constants and the diffusion coefficients of both species were obtained by reaction-diffusion kinetics and diffusion-ordered spectroscopy results. The evolution of cluster radius as a function of time, and the qualitative spatial distributions of monomer and dimer densities under steady-state were plotted to better understand the formation process and the nature of the clusters.
A general method for searching for homometric structures
Authors: Shen Yihan , Jiang Yibin , Lin Jianhua , Wang Cheng , Sun Junliang
Published: January 2022

The discovery of the homometry of X-ray diffraction dates back to the 1930s and shows the ambiguity in structure characterization purely from diffraction technologies. Since then, there has only been limited discussion on this topic with reference to several real structures and an efficient method for finding homometric structures for a known three-dimensional structure is still lacking today. In this work, a method was developed to create a set of structures with the same interatomic distances as an original structure, which can then be identified as powder X-ray diffraction or single-crystal X-ray diffraction homometric structures. This method was applied to the Inorganic Crystal Structure Database (ICSD) and homometric structures for 37 reported structures were found. Also it was found that homometric structures are encountered frequently in solving crystal structures when building initial models with only heavy atoms, which indicates that special caution is needed in interpreting XRD data with heavy-atom methods.
Crystal structure of hexasodium tetraserinolium paratungstate B decahydrate, [Na6{(CH2OH)2CHNH3}4][W12O40(OH)2]·10H2O
Authors: Sifaki Kleanthi , Gumerova Nadiia I. , Giester Gerald , Rompel Annette
Published: January 2022

The title polyoxometalate-based organic–inorganic hybrid compound, [Na6(C3H10NO2)4][W12O40(OH)2]·10H2O, consists of a di-μ
3-hydroxido-tetra-μ
3-oxido-octadeca-μ-oxido-octadecaoxidododecatungstate (paradodecatungstate B) anion, [W12O40(OH)2]10–, and six sodium cations coordinated by the oxygen ions of the polyanions, serinol ligands protonated at the N atom, and water molecules. The centrosymmetric paratungstate B anion shows characteristic features in terms of bond lengths and angles. The three-dimensional framework structure is established by bonding of the sodium cations with oxygen ions of the paratungstate B anions and a network consisting of N—H...O and O—H...O hydrogen bonds of medium strength between the protonated serinol cations, water molecules and the paratungstate B anions. The title compound was also characterized by means of elemental analysis, IR spectroscopy and thermogravimetric analysis.