bluuebunny/crossref_metadata_2025 huggingface dataset:
Simultaneous measurement of nascent transcriptome and translatome using 4-thiouridine metabolic RNA labeling and translating ribosome affinity purification
Authors: Imai Hirotatsu , Utsumi Daisuke , Torihara Hidetsugu , Takahashi Kenzo , Kuroyanagi Hidehito , Yamashita Akio
Published: February 2023

Regulation of gene expression in response to various biological processes, including extracellular stimulation and environmental adaptation requiresde novoRNA synthesis and translation. Analysis of the coordinated and circular regulation of dynamic RNA synthesis and translation is required to determine functional protein production. However, reliable methods for the simultaneous measurement of nascent RNA synthesis and translation at the gene level are limited. Here, we developed a novel method for the simultaneous assessment of nascent RNA synthesis and translation by combining 4-thiouridine (4sU) metabolic RNA labeling and translating ribosome affinity purification (TRAP) using a monoclonal antibody against evolutionarily conserved ribosomal P-stalk proteins. The P-stalk-mediated TRAP (P-TRAP) technique recovered endogenous translating ribosomes, allowing easy translatome analysis of various eukaryotes. We validated this method in mammalian cells by demonstrating that acute unfolded protein response (UPR) in the endoplasmic reticulum (ER) induces dynamic reprograming of nascent RNA synthesis and translation. Our method can serve as a simple and powerful tool for analyzing the coordinated regulation of transcription and translation of individual genes in various eukaryotes.
De novofatty-acid synthesis protects invariant NKT cells from cell death, thereby promoting their homeostasis and pathogenic roles in airway hyperresponsiveness
Authors: Koh Jaemoon , Woo Yeon Duk , Yoo Hyun Jung , Choi Jun-Pyo , Kim Sae Hoon , Chang Yoon-Seok , Jung Kyeong Cheon , Kim Ji Hyung , Jeon Yoon Kyung , Kim Hye Young , Chung Doo Hyun
Published: February 2023

Abstract

Invariant natural-killer T (iNKT) cells play pathogenic roles in allergic asthma in murine models and possibly also humans. While many studies show that the development and functions of innate and adaptive immune cells depend on their metabolic state, the evidence for this iniNKT cells is very limited. It is also not clear whether such metabolic regulation ofiNKT cells could participate in their pathogenic activities in asthma. Here, we showed that acetyl-coA-carboxylase 1 (ACC1)-mediatedde novofatty-acid synthesis is required for the survival ofiNKT cells and their deleterious functions in allergic asthma. ACC1, which is a key fatty-acid synthesis enzyme, was highly expressed by lungiNKT cells from WT mice that were developing asthma.Cd4-CreAcc1fl/flmice failed to develop OVA-induced and HDM-induced asthma. Moreover,iNKT cell-deficient mice that were reconstituted with ACC1-deficientiNKT cells failed to develop asthma, unlike when WTiNKT cells were transferred. ACC1 deficiency iniNKT cells associated with reduced expression of fatty acid-binding proteins (FABPs) and peroxisome proliferator-activated receptor (PPAR)γ, but increased glycolytic capacity that promotediNKT-cell death. Furthermore, circulatingiNKT cells from allergic-asthma patients expressed higherACC1andPPARGlevels than the corresponding cells from non-allergic-asthma patients and healthy individuals. Thus,de novofatty-acid synthesis preventsiNKT-cell deathviaan ACC1-FABP-PPARγ axis, which contributes to their homeostasis and their pathogenic roles in allergic asthma.
Comprehensive Multi-omics Analysis Reveals the Core Role of Glycerophospholipid Metabolism in Rheumatoid Arthritis Development
Authors: Jian Congcong , Wei Lingli , Wu Tong , Li Shilin , Wang Tingting , Chen Jianghua , Chang Chengjia , Zhang Jie , He Binhan , Wu Jianhong , Su Jiang , Zhu Jing , Wu Min , Zhang Yan , Zeng Fanxin
Published: February 2023

Objectives

Rheumatoid arthritis (RA) is a chronic autoimmune disease with complex causes and recurrent attacks that can easily develop into chronic arthritis. Our study aims to elucidate potential mechanism among control, new-onset RA (NORA) and chronic RA (CRA) with multi-omics analysis.

Methods

A total of 162 subjects were included in our study, 121 subjects were used for 16S rRNA, ITS sequencing and metabolomics analysis and 41 subjects were used for transcriptomics analysis. Enrichment analysis was based on significant difference metabolites and genes. Protein-protein interaction network and correlation analyses were performed to interpret the interactions among intestinal flora, metabolites and genes. We applied three models to distinguish between NORA and CRA using computational OR values, LASSO and random forest, respectively.

Results

Our results demonstrated intestinal flora disturbance in RA development, with significantly increased abundance ofEscherichia-ShigellaandProteobacteriain NORA. We also found that the diversity was significantly reduced in CRA compared to NORA through fungi analysis. Moreover, we identified 28 differential metabolites between NORA and CRA. Pathway enrichment analysis revealed significant dysregulation of glycerophospholipid metabolism and phenylalanine metabolism pathways in RA patients. Next, we identified 40 differentially expressed genes between NORA and CRA, which acetylcholinesterase (ACHE) was the core gene and significantly enriched in glycerophospholipid metabolism pathway. Correlation analysis showed a strong negatively correlation between glycerophosphocholine and inflammatory characteristics.

Conclusions

These findings revealed that glycerophospholipid metabolism plays a crucial role in the development and progression of RA, providing new ideas for early clinical diagnosis and optimizing treatment strategies.
Genome-wide identification and characterization of major RNAi genes highlighting their regulatory factors in Cowpea (Vigna unguiculata(L.) Walp.)
Authors: Hasan Mohammad Nazmol , Mosharaf Md Parvez , Uddin Khandoker Saif , Das Keya Rani , Sultana Nasrin , Noorunnahar Mst. , Naim Darun , Mollah Md. Nurul Haque
Published: February 2023

In different regions of the world, cowpea (Vigna unguiculata (L.) Walp.) is an important vegetable and an excellent source of protein. It lessens the malnutrition of the underprivileged in developing nations and has some positive effects on health, such as a reduction in the prevalence of cancer and cardiovascular disease. However, occasionally, certain biotic and abiotic stresses caused a sharp fall in cowpea yield. Currently, short RNAs (sRNAs) are thought to play a crucial role in controlling how stress-related genes are expressed in plants as they go through various developmental phases. Major RNA interference (RNAi) genes like Dicer-like (DCL), Argonaute (AGO), and RNA-dependent RNA polymerase (RDR) are essential for sRNA synthesis processes and shield plants from biotic and abiotic stresses. In this study, applying BLASTP search and phylogenetic tree analysis with reference to theArabidopsisRNAi (AtRNAi) genes, we discovered 28 VuRNAi genes, including 7VuDCL, 14VuAGO, and 7VuRDRgenes in cowpea. We looked at the domains, motifs, gene structures, chromosomal locations, sub-cellular locations, gene ontology (GO) terms and regulatory factors (transcription factors, micro-RNAs, andcis-acting factors) to characterize the VuRNAi genes and proteins in cowpea. PredictedVuDCL1,VuDCL2(a, b),VuAGO7,VuAGO10andVuRDR6genes might have an impact on cowpea growth, development of the vegetative and flowering stages and antiviral defense. The VuRNAi gene regulatory features miR395 and miR396 might contribute to grain quality improvement, immunity boosting, and pathogen infection resistance under salinity and drought conditions. Predictedcis-acting elements (CAEs) from the VuRNAi gene associated with light responsiveness (LR), stress responsiveness (SR) and hormone responsiveness (HR) might play a role in plant growth and development, improving grain quality and production and protecting plants from biotic and abiotic stresses. Therefore, our study provides crucial information about the functional roles of VuRNAi genes and their regulatory components, which would aid in the development of future cowpeas that are more resilient to biotic and abiotic stress.
Linking structural and functional changes during aging using multilayer brain network analysis
Authors: Jauny Gwendolyn , Mijalkov Mite , Canal-Garcia Anna , Volpe Giovanni , Pereira Joana , Eustache Francis , Hinault Thomas
Published: February 2023

Brain structure and function are intimately linked, however this association remains poorly understood of the complexity of this relationship has remained understudied. Healthy aging is characterized by heterogenous levels of structural integrity changes that influence functional network dynamics. Here, we used the multilayer brain network analysis on structural (diffusion tensor imaging) and functional (magnetoencephalography) data from the Cam-CAN database. We found that the level of similarity of connectivity patterns between brain structure and function in the parietal and temporal regions (alpha frequency band) was associated with cognitive performance in healthy older individuals. These results highlight the impact of structural connectivity changes on the reorganisation of functional connectivity associated with the preservation of cognitive function, and provide a mechanistic understanding of the concepts of brain maintenance and compensation with aging. Investigation of the link between structure and function could thus represent a new marker of individual variability, and of pathological changes.
Slope of the power spectral density flattens at low frequencies (<150 Hz) with healthy aging but also steepens at higher frequency (>200 Hz) in human electroencephalogram
Authors: Aggarwal Srishty , Ray Supratim
Published: February 2023

Brain signals such as electroencephalogram (EEG) often show oscillations at various frequencies, which are represented as distinct “bumps” in the power spectral density (PSD) of these signals. In addition, the PSD also shows a distinct reduction in power with increasing frequency, which pertains to aperiodic activity and is often termed as the “1/f” component. While a change in periodic activity in brain signals with healthy aging and mental disorders has been reported, recent studies have shown a reduction in the slope of the aperiodic activity with these factors as well. However, these studies only analysed PSD slopes over a limited frequency range (<100 Hz). To test whether the PSD slope is affected over a wider frequency range with aging and mental disorder, we collected EEG data with high sampling rate (2500 Hz) from a large population of elderly subjects (>49 years) who were healthy (N=217) or had mild cognitive impairment (MCI; N=11) or Alzheimer’s Disease (AD; N=5), and analysed the PSD slope till 800 Hz. Consistent with previous studies, the 1/f slope up to ~150 Hz reduced with healthy aging. Surprisingly, we found the opposite at higher frequencies (>200 Hz): the slope increased with age. This result was observed in all electrodes, for both eyes open and eyes closed conditions, and for different reference schemes. Slopes were not significantly different in MCI/AD subjects compared to age and gender matched healthy controls. Overall, our results constrain the biophysical mechanisms that are reflected in the PSD slopes in healthy and pathological aging.

Significance Statement

Aperiodic activity in the brain is characterized by measuring the slope of the power spectrum of brain signals. This slope has been shown to flatten with healthy aging, suggesting an increase in some sort of “neural noise”. However, this flattening has been observed only over a limited frequency range (<150 Hz). We found that at higher frequencies (>200 Hz), the opposite happens: the slope steepens with age. This occurs at all electrodes, irrespective of state and referencing techniques. However, the slope is unchanged in subjects with early Alzheimer’s Disease (AD) and their controls. Our results shed new light on the properties of neural noise and the neurophysiological processes affecting AD and the aperiodic activity.
Antibiotic-mediated interactions underlying microbial diversity
Authors: Athreya Gaurav S. , Gokhale Chaitanya S. , Verma Prateek
Published: February 2023

The immense diversity observed in natural microbial communities is surprising in light of the numerous weapons microbes have evolved to inhibit each other’s growth. It is thus imperative to understand which interaction patterns can sustain a biodiverse community when individual species antagonistically affect one another. In this study, we leverage potent methods from theoretical ecology to show how antibiotic-mediated interactions between microbes drive biological diversity. Building on previous experimental and theoretical results, we analyse the dynamics induced by various interaction graphs involving antibiotic production, resistance, and degradation. Previous work has recognised the importance of a particular producer-sensitive-degrader (PSD) motif in the interaction graph. We study this motif in detail and elucidate the mechanistic reason for this importance. Concretely, we give exact rules for coexistence in some simple cases where exhaustive enumeration of the interaction graphs is feasible. More generally, our results suggest that the PSD motif, in combination with a cyclic interaction structure, is sufficient for stable coexistence in well-mixed populations. Using individual-based simulations, we then study the importance of the PSD motif in spatially structured populations. We show that community coexistence is robust for an extensive range of antibiotic and degrader diffusivities. Together, these findings illuminate the interaction patterns that give rise to diversity in complex microbial communities, stressing that antagonism does not imply a lack of diversity and suggesting clear approaches for culturing synthetic microbial consortia.
Eddy current-induced artifacts correction in high gradient strength diffusion MRI with dynamic field monitoring: demonstration in ex vivo human brain imaging
Authors: Ramos-Llordén Gabriel , Park Daniel , Kirsch John E. , Scholz Alina , Keil Boris , Maffei Chiara , Lee Hong-Hsi , Bilgiç Berkin , Edlow Brian L. , Mekkaoui Choukri , Yendiki Anastasia , Witzel Thomas , Huang Susie Y.
Published: February 2023

Purpose

To demonstrate the advantages of spatiotemporal magnetic field monitoring to correct eddy current-induced artifacts (ghosting and geometric distortions) in high gradient strength diffusion MRI (dMRI).

Methods

A dynamic field camera with 16 NMR field probes was used to characterize eddy current fields induced from diffusion gradients for different gradients strengths (up to 300 mT/m), diffusion directions, and shots in a 3D multi-shot EPI sequence on a 3T Connectom scanner. The efficacy of dynamic field monitoring-based image reconstruction was demonstrated on high-resolution whole brain ex vivo dMRI. A 3D multi-shot image reconstruction framework was informed with the actual nonlinear phase evolution measured with the dynamic field camera, thereby accounting for high-order eddy currents fields on top of the image encoding gradients in the image formation model.

Results

Eddy current fields from diffusion gradients at high gradient strength in a 3T Connectom scanner are highly nonlinear in space and time, inducing high-order spatial phase modulations between odd/even echoes and shots that are not static during the readout. Superior reduction of ghosting and geometric distortion was achieved with dynamic field monitoring compared to ghosting approaches such as navigator- and structured low-rank-based methods or MUSE, followed by image-based distortion correction with eddy. Improved dMRI analysis is demonstrated with diffusion tensor imaging and high-angular resolution diffusion imaging.

Conclusion

Strong eddy current artifacts characteristic of high gradient strength dMRI can be well corrected with dynamic field monitoring-based image reconstruction, unlike the two-step approach consisting of ghosting correction followed by geometric distortion reduction with eddy.
Precise and ultrafast tandem repeat variant detection in massively parallel sequencing reads
Authors: Wang Xuewen , Huang Meng , Budowle Bruce , Ge Jianye
Published: February 2023

Calling tandem repeat (TR) variants from DNA sequences is of both theoretical and practical significance. A large number of software tools have been developed for detecting TRs. However, little study has been done to detect TR alleles from long-read sequences, and the effectiveness of detecting TR alleles from whole genome sequence (WGS) data still needs to be improved. Herein, a novel algorithm is described to retrieve TR regions from sequence alignment, and a software program, TRcaller, has been developed to call TR alleles from both short- and long-read sequences, both whole genome and targeted sequences generated from multiple sequencing platforms. The results showed that TRcaller could provide substantially higher accuracy in detecting TR alleles with magnitudes faster than the mainstream software tools. TRcaller is able to facilitate scalable, accurate, and ultrafast TR allele calling from large-scale sequence datasets in various applications, such as DNA forensics, medical research, disease diagnosis, evolution, and breeding programs.

Availability

TRcaller is available atwww.trcaller.com.
BORD: A Biomedical Ontology based method for concept Recognition using Distant supervision: Application to Phenotypes and Diseases
Authors: Toonsi Sumyyah , Kafkas Şenay , Hoehndorf Robert
Published: February 2023

Motivation

Concept recognition in biomedical text is an important yet challenging task. The two main approaches to recognize concepts in text are dictionary-based approaches and supervised machine learning approaches. While dictionary-based approaches fail in recognising new concepts and variations of existing concepts, supervised methods require sufficiently large annotated datasets which are expensive to obtain. Methods based on distant supervision have been developed to use machine learning without large annotated corpora. However, for biomedical concept recognition, these approaches do not yet exploit the context in which a concept occurs in literature, and they do not make use of prior knowledge about dependencies between concepts.

Results

We developed BORD, a Biomedical Ontology-based method for concept Recognition using Distant supervision. BORD utilises context from corpora which are lexically annotated using labels and synonyms from the classes of a biomedical ontology for model training. Furthermore, BORD utilises the ontology hierarchy for normalising the recognised mentions to their concept identifiers. We show how our method improves the performance of state of the art methods for recognising disease and phenotype concepts in biomedical literature. Our method is generic, does not require manually annotated corpora, and is robust to identify mentions of ontology classes in text. Moreover, to the best of our knowledge, this is the first approach utilising the ontology hierarchy for concept recognition.

Availability

BORD is publicly available fromhttps://github.com/bio-ontology-research-group/BORD

Contact

robert.hoehndorf@kaust.edu.sa
Gene body DNA hydroxymethylation restricts the magnitude of transcriptional changes during aging
Authors: Occean James R. , Yang Na , Sun Yan , Dawkins Marshall S. , Munk Rachel , Belair Cedric , Dar Showkat , Anerillas Carlos , Wang Lin , Shi Changyou , Dunn Christopher , Bernier Michel , Price Nathan L. , Kim Julie S. , Cui Chang-Yi , Fan Jinshui , Bhattacharyya Moitrayee , De Supriyo , Maragkakis Manolis , deCabo Rafael , Sidoli Simone , Sen Payel
Published: February 2023

DNA hydroxymethylation (5hmC), the most abundant oxidative derivative of DNA methylation, is typically enriched at enhancers and gene bodies of transcriptionally active and tissue-specific genes. Although aberrant genomic 5hmC has been implicated in age-related diseases, its functional role in aging remains unknown. Here, using mouse liver and cerebellum as model organs, we show that 5hmC accumulates in gene bodies associated with tissue-specific function and restricts the magnitude of gene expression changes with age. Mechanistically, 5hmC decreases the binding of splicing associated factors and correlates with age-related alternative splicing events. We found that various age-related contexts, such as prolonged quiescence and senescence, drive the accumulation of 5hmC with age. We provide evidence that this age-related transcriptionally restrictive function is conserved in mouse and human tissues. Our findings reveal that 5hmC regulates tissue-specific function and may play a role in longevity.
No evidence for angiosperm mass extinction at the Cretaceous–Paleogene (K-Pg) boundary
Authors: Thompson Jamie , Ramírez-Barahona Santiago
Published: February 2023

The Cretaceous-Paleogene mass extinction event (K-Pg) witnessed up to 75% of animal species going extinct, most notably among these are the non-avian dinosaurs. A major question in macroevolution is whether this extinction event influenced the rise of flowering plants (angiosperms). The fossil record suggests that the K-Pg event had a minor impact on the extinction rates of angiosperm lineages, yet the diversification of extant angiosperms was delayed and started after the K-Pg boundary. However, phylogenetic evidence for angiosperm extinction dynamics remains unexplored. Through the analyses of two angiosperm mega-phylogenies containing ~32,000–74,000 extant species, here we show relatively constant extinction rates throughout geological time and no evidence for a mass extinction at the K-Pg boundary. Despite uncertainty of earliest angiosperm branching times, their staggering diversity, and complex evolutionary dynamics, our preliminary analyses provide congruent results with the fossil record and support the macroevolutionary resilience of angiosperms to the K-Pg mass extinction.
UTILIZATION OF A PUBLICLY AVAILABLE DIVERSITY PANEL IN GENOMIC PREDICTION OFFUSARIUMHEAD BLIGHT RESISTANCE TRAITS IN WHEAT
Authors: Winn Z. J. , Lyerly J. H. , Brown-Guedira G. , Murphy J. P. , Mason R. E.
Published: February 2023

Fusariumhead blight (FHB) is an economically and environmentally concerning disease of wheat (Triticum aestivumL). A two-pronged approach of marker assisted selection (MAS) coupled with genomic selection (GS) has been suggested when breeding for FHB resistance. An historical dataset comprised of entries in the Southern Uniform Winter Wheat Scab Nursery (SUWWSN) from 2011-2021 was partitioned and used in genomic prediction. Two traits were curated from 2011-2021 in the SUWWSN: percentFusariumdamaged kernels (FDK) and Deoxynivalenol (DON) content. Heritability was estimated for each trait-by-environment combination. A consistent set of check lines was drawn from each year in the SUWWSN, and K-means clustering was performed across environments to assign environments into clusters. Two clusters were identified for FDK and three for DON. Cross-validation on SUWWSN data from 2011-2019 indicated no outperforming training population in comparison to the combined dataset. Forward validation for FDK on the SUWWSN 2020 and 2021 data indicated a predictive accuracyr≈ 0.58 andr≈ 0.53, respectively. Forward validation for DON indicated a predictive accuracy ofr≈ 0.57 andr≈ 0.45, respectively. Forward validation using environments in cluster one for FDK indicated a predictive accuracy ofr≈ 0.65 andr≈ 0.60, respectively. Forward validation using environments in cluster one for DON indicated a predictive accuracy ofr≈ 0.67 andr≈ 0.60, respectively. These results indicated that selecting environments based on check performance may produce higher forward prediction accuracies. This work may be used as a model to create a public resource for genomic prediction of FHB resistance traits across public wheat breeding programs.

CORE IDEAS

The data from the Southern Uniform Winter Wheat Nursery may be used for genomic prediction.

Creating training populations based on like-check performance improves forward genomic predictive accuracies.

Filtering out locations with low genomic, per-plot, narrow-sense heritability may improve predictive accuracies.
E2F1 Mediates SOX17 Deficiency-Induced Pulmonary Hypertension
Authors: Yi Dan , Liu Bin , Ding Hongxu , Li Shuai , Li Rebecca , Pan Jiakai , Ramirez Karina , Xia Xiaomei , Kala Mrinalini , Singh Indrapal , Ye Qinmao , Lee Won Hee , Frye Richard E. , Wang Ting , Zhao Yutong , Knox Kenneth S. , Glembotski Christopher C. , Fallon Michael B. , Dai Zhiyu
Published: February 2023

Rationale

Rare genetic variants and genetic variation at loci in an enhancer in SRY-Box Transcription Factor 17 (SOX17) are identified in patients with idiopathic pulmonary arterial hypertension (PAH) and PAH with congenital heart disease. However, the exact role of genetic variants or mutation in SOX17 in PAH pathogenesis has not been reported.

Objectives

To investigate the role of SOX17 deficiency in pulmonary hypertension (PH) development.

Methods

Human lung tissue and endothelial cells (ECs) from IPAH patients were used to determine the expression of SOX17. Tie2Cre-mediated and EC-specific deletion of Sox17 mice were assessed for PH development. Single-cell RNA sequencing analysis, human lung ECs, and smooth muscle cell culture were performed to determine the role and mechanisms of SOX17 deficiency. A pharmacological approach was used in Sox17 deficiency mice for therapeutic implication.

Measurement and Main Results

SOX17 expression was downregulated in the lungs and pulmonary ECs of IPAH patients. Mice with Tie2Cre mediated Sox17 knockdown and EC-specific Sox17 deletion developed spontaneously mild PH. Loss of endothelial Sox17 in EC exacerbated hypoxia-induced PH in mice. Loss of SOX17 in lung ECs induced endothelial dysfunctions including upregulation of cell cycle programming, proliferative and anti-apoptotic phenotypes, augmentation of paracrine effect on pulmonary arterial smooth muscle cells, impaired cellular junction, and BMP signaling. E2F Transcription Factor 1 (E2F1) signaling was shown to mediate the SOX17 deficiency-induced EC dysfunction and PH development.

Conclusions

Our study demonstrated that endothelial SOX17 deficiency induces PH through E2F1 and targeting E2F1 signaling represents a promising approach in PAH patients.
Endocytosis is regulated through the pH-dependent phosphorylation of Rab GTPases by Parkinson’s kinase LRRK2
Authors: Maxson Michelle E. , Huynh Kassidy K. , Grinstein Sergio
Published: February 2023

While it has been known for decades that luminal acidification is required for normal traffic along the endocytic pathway, the precise underlying mechanism(s) remain unknown. We found that dissipation of the endomembrane pH gradient resulted in acute formation of large Rab5- or Rab7-positive vacuoles. Vacuole formation was associated with and required hyperactivation of the Rabs, which was attributable to impaired GTPase activity, despite normal recruitment of cognate GAPs. Surprisingly, LRRK2 –a kinase linked to Parkinson’s disease–was recruited to endomembranes and markedly activated upon dissipation of luminal acidification. LRRK2 phosphorylated Rab GTPases, rendering them insensitive to deactivation. Importantly, genetic deletion of LRRK2 prevented the ΔpH-induced vacuolation, implying that the kinase is required to modulate vesicular traffic. We propose that by dictating the state of activation of LRRK2 and in turn that of Rab GTPases, the development of a progressive luminal acidification serves as a timing device to control endocytic maturation.
Assessment of contaminants, health and survival of migratory shorebirds in natural versus artificial wetlands – the potential of wastewater treatment plants as alternative habitats
Authors: Ross Tobias A. , Zhang Junjie , Wille Michelle , Ciesielski Tomasz Maciej , Asimakopoulos Alexandros G. , Lemesle Prescillia , Skaalvik Tonje G. , Atkinson Robyn , Jessop Roz ,   Victorian Wader Study Group, Jaspers Veerle L. B. , Klaassen Marcel
Published: February 2023

The rapid destruction of natural wetland habitats over past decades has been partially offset by an increase in artificial wetlands. However, these also include wastewater treatment plants, which may pose a pollution risk to the wildlife using them. We studied two long-distance Arctic-breeding migratory shorebird species, curlew sandpiper (Calidris ferruginea, n=70) and red-necked stint (Calidris ruficollis, n=100), while on their Australian non-breeding grounds using a natural wetland versus an artificial wetland at a wastewater treatment plant (WTP). We compared pollutant exposure (elements and per- and poly-fluoroalkyl substances/PFASs), disease (avian influenza), physiological status (oxidative stress) of the birds at the two locations from 2011-2020, and population survival from 1978-2019. Our results indicated no significant differences in blood pellet pollutant concentrations between the habitats except mercury (WTP median: 224 ng/g, range: 19-873 ng/g; natural wetland: 160 ng/g, 22-998 ng/g) and perfluorooctanesulfonic acid (WTP median: 52 ng/g, range: <0.01-1280 ng/g; natural wetland: 14 ng/g, <0.01-379 ng/g) which were higher at the WTP, and selenium which was lower at the WTP (WTP median: 5000 ng/g, range: 1950-34400 ng/g; natural wetland: 19200 ng/g, 4130-65200 ng/g). We also measured higher blood o,o’-dityrosine (an indicator of protein damage) at the WTP. No significant differences were found for adult survival, but survival of immature birds at the WTP appeared to be lower which could be due to higher dispersal to other wetlands. Interestingly, we found active avian influenza infections were higher in the natural habitat, while seropositivity was higher in the WTP, seemingly not directly related to pollutant exposure. Overall, we found negligible differences in pollutant exposure, health and survival of the shorebirds in the two habitats. Our findings suggest that appropriately managed wastewater treatment wetlands may provide a suitable alternative habitat to these migratory species, curbing the decline of shorebird populations from widespread habitat loss.
Automatic Abdominal Multi Organ Segmentation using Residual UNet
Authors: Murugesan Gowtham Krishnan , McCrumb Diana , Brunner Eric , Kumar Jithendra , Soni Rahul , Grigorash Vasily , Chang Anthony , Peck Anderson , VanOss Jeff , Moore Stephen
Published: February 2023

Automated segmentation of abdominal organs plays an important role in supporting computer-assisted diagnosis, radiotherapy, biomarker extraction, surgery navigation, and treatment planning. Segmenting multiple abdominal organs using a single algorithm would improve model development efficiency and accelerate model deployment into clinical workflows. To achieve broadly generalized performance, we trained a residual UNet using 500 CT/MRI scans collected from multi-center, multi-vendor, multi-phase, multi-disease patients, each with voxel-level annotation of 15 abdominal organs. Using the model trained on multimodality (CT/MRI), we achieved an average dice of 0.8990 in the held-out test dataset with only CT scans (N=100). An average dice of 0.8948 was achieved in the held-out test dataset with both CT and MRI scans (N=120. Our results demonstrate broad generalization of the model.
BinderSpace: A Package for Sequence Space Analyses for Datasets of Affinity-Selected Oligonucleotides and Peptide-Based Molecules
Authors: Kelich Payam , Zhao Huanhuan , Vuković Lela
Published: February 2023

Discovery of target-binding molecules, such as aptamers and peptides, is usually performed with the use of high-throughput experimental screening methods. These methods typically generate large datasets of sequences of target-binding molecules, which can be enriched with high affinity binders. However, the identification of the highest affinity binders from these large datasets often requires additional low-throughput experiments or other approaches. Bioinformatics-based analyses could be helpful to better understand these large datasets and identify the parts of the sequence space enriched with high affinity binders. BinderSpace is an open-source Python package that performs motif analysis, sequence space visualization, clustering analyses, and sequence extraction from clusters of interest. The motif analysis, resulting in text-based and visual output of motifs, can also provide heat maps of previously measured user-defined functional properties for all the motif-containing molecules. Users can also run principal component analysis (PCA) and t-distributed stochastic neighbor embedding (t-SNE) analyses on whole datasets and on motif-related subsets of the data. Functionally important sequences can also be highlighted in the resulting PCA and t-SNE maps. If points (sequences) in two-dimensional maps in PCA or t-SNE space form clusters, users can perform clustering analyses on their data, and extract sequences from clusters of interest. We demonstrate the use of BinderSpace on a dataset of oligonucleotides binding to single-wall carbon nanotubes in the presence and absence of a bioanalyte, and on a dataset of cyclic peptidomimetics binding to bovine carbonic anhydrase protein.

Abstract Figure
Visualizing H2O2and NO in endothelial cells: strategies and pitfalls
Authors: Altun Hamza Yusuf , Secilmis Melike , Caglar Tuba Akgul , Vatandaslar Emre , Öztürk Gürkan , Vilain Sven , Eroglu Emrah
Published: February 2023

The relationship between hydrogen peroxide (H2O2) and nitric oxide (NO) in the vasculature is multifaceted and remains controversial because the dynamic detection of these reactive molecules is challenging. Genetically encoded biosensors (GEBs) allow visualizing real-time dynamics in living cells and permit multiparametric detection of several analytes. Although robust, GEBs’ utility depends on several parameters that need fine-tuning for proper imaging and correct data analysis: i.e., camera binning, temperature, and the resolution power of the imaging instruments are some critical parameters that require optimization. We have generated a new double-stable transgenic endothelial cell line stably expressing the biosensors HyPer7 and O-geNOp and systematically tested different imaging modes and their impact on the performance of each biosensor. Ambient temperature and the type of imaging mode did not influence the results, while camera resolution settings significantly affected readouts of HyPer probes but not O-geNOp. Changing a single parameter in a co-imaging mode significantly altered the biosensor’s dynamic measurements, potentially causing misinterpretation. This study provides a general guide and the pitfalls of employing GEBs in a multispectral imaging mode.
Transcriptional read through interrupts boundary function in Drosophila
Authors: Kyrchanova Olga , Sokolov Vladimir , Tikhonov Maxim , Schedl Paul , Georgiev Pavel
Published: February 2023

In higher eukaryotes enhancer-promoter interactions are known to be restricted by the chromatin insulators/boundaries that delimit topologically associated domains (TADs); however, there are instances in which enhancer-promoter interactions span one or more boundary elements/TADs. At present, the mechanisms that enable cross-TAD regulatory interaction are not known. In the studies reported here we have taken advantage of the well characterizedDrosophilaBithorax complex (BX-C) to study one potential mechanism for controlling boundary function and TAD organization. The regulatory domains of BX-C are flanked by boundaries which function to block crosstalk with their neighboring domains and also to support long distance interactions between the regulatory domains and their target gene. As many lncRNAs have been found in BX-C, we asked whether transcriptional readthrough can impact boundary function. For this purpose, we took advantage of two BX-C boundary replacement platforms,Fab-7attP50andF2attP, in which theFab-7andFubboundaries, respectively, are deleted and replaced with anattPsite. We introduced boundary elements, promoters and polyadenylation signals arranged in different combinations and then assayed for boundary function. Our results show that transcriptional readthrough can interfere with boundary activity. Since lncRNAs represent a significant fraction of Pol II transcripts in multicellular eukaryotes, it is possible that many of them may function in the regulation of TAD organization.

Author Summary

Recent studies have shown that much genome in higher eukaryotes is transcribed into non-protein coding lncRNAs. It is though that lncRNAs may preform important regulatory functions, including the formation of protein complexes, organization of functional interactions between enhancers and promoters and the maintenance of open chromatin. Here we examined how transcription from promoters inserted into theDrosophilaBithorax complex can impact the boundaries that are responsible for establishing independent regulatory domains. Surprisingly, we found that even a relatively low level of transcriptional readthrough can impair boundary function. Transcription also affects the activity of enhancers located in BX-C regulatory domains. Taken together, our results raise the possibility that transcriptional readthrough may be a widely used mechanism to alter chromosome structure and regulate gene expression.
Attention network for predicting T cell receptor-peptide binding can associate attention with interpretable protein structural properties
Authors: Koyama Kyohei , Hashimoto Kosuke , Nagao Chioko , Mizuguchi Kenji
Published: February 2023

Understanding how a T cell receptor (TCR) recognizes its specific ligand peptide is crucial for gaining insight into biological functions and disease mechanisms. Despite its importance, experimentally determining TCR-peptide interactions is expensive and time-consuming. To address this challenge, computational methods have been proposed, but they are typically evaluated by internal retrospective validation only, and few have incorporated and tested an attention layer from language models into structural information.

Therefore, in this study, we developed a machine learning model based on a modified version of the Transformer, a source-target-attention neural network, to predict TCR-peptide binding solely from the amino acid sequences of the TCR’s complementarity-determining region (CDR) 3 and the peptide. This model achieved competitive performance on a benchmark dataset of TCR-peptide binding, as well as on a truly new external dataset. Additionally, by analyzing the results of binding predictions, we associated the neural network weights with protein structural properties. By classifying the residues into large and small attention groups, we identified statistically significant properties associated with the largely attended residues, such as hydrogen bonds within the CDR3. The dataset that we have created and our model’s ability to provide an interpretable prediction of TCR-peptide binding should increase our knowledge of molecular recognition and pave the way to designing new therapeutics.
Identification of a new substrate for the ribosome associated endoribonuclease Rae1 reveals a link to theB. subtilisresponse and sensitivity to chloramphenicol
Authors: Deves Valentin , Trinquier Aude , Gilet Laetitia , Alharake Jawad , Leroy Magali , Condon Ciarán , Braun Frédérique
Published: February 2023

Rae1 is a well-conserved endoribonuclease among Gram-positive bacteria, cyanobacteria and the chloroplasts of higher plants. We have previously shown that Rae1 cleaves theBacillus subtilis yrzIoperon mRNA in a translation-dependent manner, within a short open reading frame (ORF) called S1025, encoding a 17-amino acid (aa) peptide of unknown function. Here, we map a new Rae1 cleavage site in thebmrBCDoperon mRNA encoding a multidrug transporter, within a previously unannotated 26-aa short ORF that we have namedbmrX. Similar to S1025, Rae1 cleavage withinbmrXis both translation- and reading frame-dependent. Both mRNAs were previously shown to be induced by the presence of the protein synthesis inhibitor chloramphenicol (Cm). Strikingly, arae1deletion strain shows greater resistance to Cm than the wild-type strain, while its over-expression leads to increased Cm sensitivity, suggesting a link to translation quality control. Consistent with this, we show that cleavage by Rae1 promotes ribosome rescue by the tmRNA. Globally, our data point to a role of Rae1 in mRNA surveillance by eliminating mRNAs that encounter problems with translation.
Toxoplasma gondiiaspartic protease 5 (TgASP5): Understanding structural details and inhibition mechanism
Authors: Chakraborty Satadru , Deshmukh Anuradha , Kesari Pooja , Bhaumik Prasenjit
Published: February 2023

Toxoplasma gondii, a worldwide prevalent parasite, is responsible for causing toxoplasmosis by infecting almost all warm-blooded animals, including humans. To establish a successful infection, the parasite exports a series of effector proteins which modulates the host immune system; Golgi-residentT. gondiiaspartyl protease 5 (TgASP5) plays an essential role in the maturation and export of these effector proteins. This is the first report of the detailed structural investigation of theTgASP5 mature enzyme. Molecular modeling and all-atom simulation provided in-depth knowledge of the active site architecture ofTgASP5. The analysis of the binding mode of TEXEL substrate highlighted the importance of the active site residues forming the pocket; the Ser505, Ala776 and Tyr689 in the S2 binding pocket provide the specificity towards Arg at the P2 position. Our study also provides insights into the binding mode of the known inhibitor RRLStatine.Screening the known aspartic protease inhibitors againstTgASP5 active site and performing 100 ns all-atom molecular dynamic simulations, MM-PBSA binding energy calculations provided the best nine inhibitor protein complexes. Besides that, Principal Component Analysis (PCA) was employed to identify the change in protein dynamics with respect to the substrate and ligand binding.TgASP5 is essential for the fitness and virulence of the parasite; inhibiting this enzyme can be a possible therapeutic strategy against toxoplasmosis. Our study put forth the inhibitors which can act as initial scaffolds for developing potent mechanistic inhibitors againstTgASP5.
The effects of dihedral angle on hover rigidity and planar maneuvers in rotary-wing UAVs
Authors: Kayatas Erol , Celik Murat
Published: February 2023

Purpose

Any consensus about the effects of dihedral angle on hover rigidity of rotary-wing unmanned aerial vehicles (RW-UAVs) does not exist in the literature. There are researchers who state that the dihedral angle has an effect on flight stability and researchers who claim the opposite. The discord stems from the different approaches of these groups to the concept of “stability,” the fact that they conduct experiments whose measurements are largely influenced by environmental conditions, and the physical assumptions are not similar. On the other hand, there is no study examining the effect of dihedral angle on the maneuverability of drones either. This study aims to analytically reveal the consequences of dihedral angles in RW-UAVs in terms of flight agility and maneuverability.

Design/methodology/approach

Dihedral angle examinations on both hover rigidity and maneuverability are carried out analytically. Equations of motions for a multicopter’s rigid body with a dihedral angle under two different conditions (zero and nonzero dihedral angles) are derived. Numerical simulations are conducted by defining the simulation parameters, and then displacement graphics for the center of mass are interpreted.

Findings

The presence of a dihedral angle makes the multicopter platforms behave like a pendulum, and this pendulum motion affects the disturbance rejection and the planar maneuver capabilities of multicopters. Since deflections can be spread to the orthonormal axes thanks to rotation about a pivot, net deflections of the geometric center may be diminished. Besides, pendulum motion eases the maneuvers with yaw rotations since the required rotation might occur without rotors’ revolution per minute changes.

Practical implications

Proposed dihedral angle implementation may enhance the hover stiffness and maneuverability capabilities of multicopters which, in turn, raise the performance of the drones.

Originality/value

This paper presents the analytical basis for the dihedral angle's effects on flight stability and agility.
Impact of COVID-19 on education in India: stakeholders' voice
Authors: Kalia Prateek , Behal Bhavana , Kaur Kulvinder , Mehta Deepa
Published: February 2023

Purpose

This exploratory study aims to discover the different forms of challenges encountered by school stakeholders, including students, teachers, parents and management due to the coronavirus disease 2019 (COVID-19) pandemic.

Design/methodology/approach

Qualitative methodology was deployed for the study. A purposive sampling technique was used to select the respondents for a semi-structured interview. Data were examined using interpretative phenomenological analysis (IPA).

Findings

It was found that each stakeholder faced four different challenges: mental distress, physical immobility, financial crunches and technological concerns. Findings suggest that teachers are experiencing higher financial, technological and physical challenges as compared to other stakeholders followed by parents.

Originality/value

This paper discusses the major challenges faced by each stakeholder along with the opportunities. These findings will be useful for educationists, regulatory authorities, policymakers and management of educational institutions in developing countries to revisit their policy frameworks to develop new strategies and processes for the smooth implementation of remote learning during a period of uncertainty.
The effects of power imbalance on supply chain sustainability adoption: evidence from the artisanal fishing industry
Authors: Rivera-Valle Sylvia , Silva Minelle E.
Published: February 2023

Purpose

Grounded on resource dependence theory, the authors explored how power and dependence affect sustainability adoption in an artisanal fishing supply chain (AFSC) in Mexico.

Design/methodology/approach

An in-depth longitudinal case study was conducted to identify relationships among fishers, a cooperative and intermediaries using a content analysis of data gathered from a combination of interviews, focus groups, observations, participatory workshops and secondary data.

Findings

As a result of the existing power imbalance among AFSC members, mediated forces (e.g. rewards for intermediary–fishers relationship) were the most prominent observed. In addition, a close and high dependence on resources affecting supply chain sustainability (SCS) adoption was identified. For example, within intermediary–cooperative relationships, a power imbalance caused mostly by financial resource dependence generated a negative impact on economic sustainability related to unfair prices and unfair trade. The results, thus, showed the detrimental influence of intermediaries among AFSC members on SCS adoption.

Practical implications

A greater understanding of power imbalance and dependence can help AFSC members to identify their weaknesses and develop actions to adopt sustainability.

Originality/value

Unlike previous research, the authors go beyond the often positive research focus of SCS studies and provide, through the resource dependence theory, a longitudinal view on how power imbalance negatively affects SCS adoption.