bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractBrain 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

AbstractBrain 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 StatementAperiodic 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

AbstractThe 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

AbstractPurposeTo 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).MethodsA 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.ResultsEddy 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.ConclusionStrong 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

AbstractCalling 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.AvailabilityTRcaller 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

AbstractMotivationConcept 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.ResultsWe 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.AvailabilityBORD is publicly available fromhttps://github.com/bio-ontology-research-group/BORDContactrobert.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

AbstractDNA 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

AbstractThe 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

ABSTRACTFusariumhead 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 IDEASThe 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

AbstractRationaleRare 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.ObjectivesTo investigate the role of SOX17 deficiency in pulmonary hypertension (PH) development.MethodsHuman 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 ResultsSOX17 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.ConclusionsOur 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

ABSTRACTWhile 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

AbstractThe 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

AbstractAutomated 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.