bluuebunny/crossref_metadata_2025 huggingface dataset:
MoveApps - a serverless no-code analysis platform for animal tracking data
Authors: Kölzsch Andrea , Davidson Sarah C. , Gauggel Dominik , Hahn Clemens , Hirt Julian , Kays Roland , Lang Ilona , Lohr Ashley , Russell Benedict , Scharf Anne K. , Schneider Gabriel , Vinciguerra Candace M. , Wikelski Martin , Safi Kamran
Published: February 2022

Background

Bio-logging and animal tracking datasets continuously grow in volume and complexity, documenting animal behaviour and ecology in unprecedented extent and detail, but greatly increasing the challenge of extracting knowledge from the data obtained. A large variety of analysis methods are being developed, many of which in effect are inaccessible to potential users, because they remain unpublished, depend on proprietary software or require significant coding skills.

Results

We developed MoveApps, an open analysis platform for animal tracking data, to make sophisticated analytical tools accessible to a global community of movement ecologists and wildlife managers. As part of the Movebank ecosystem, MoveApps allows users to design and share workflows composed of analysis modules (Apps) that access and analyse tracking data. Users browse Apps, build workflows, customise parameters, execute analyses and access results through an intuitive web-based interface.

Apps, coded in R or other programming languages, have been developed by the MoveApps team and can be contributed by anyone developing analysis code. They become available to all user of the platform. To allow long-term and cross-system reproducibility, Apps have public source code and are compiled and run in Docker containers that form the basis of a serverless cloud computing system. To support reproducible science and help contributors document and benefit from their efforts, workflows of Apps can be shared, published and archived with DOIs in the Movebank Data Repository.

The platform was beta launched in spring 2021 and currently contains 44 Apps that are used by 156 registered users. We illustrate its use through two workflows that (1) provide a daily report on active tag deployments and (2) segment and map migratory movements.

Conclusions

The MoveApps platform is meant to empower the community to supply, exchange and use analysis code in an intuitive environment that allows fast and traceable results and feedback. By bringing together analytical experts developing movement analysis methods and code with those in need of tools to explore, answer questions and inform decisions based on data they collect, we intend to increase the pace of knowledge generation and integration to match the huge growth rate in bio-logging data acquisition.
TCRen: predicting TCR recognition of unseen epitopes based on residue-level pairwise statistical potential
Authors: Karnaukhov Vadim K. , Shcherbinin Dmitrii S. , Chugunov Anton O. , Chudakov Dmitriy M. , Efremov Roman G. , Zvyagin Ivan V. , Shugay Mikhail
Published: February 2022

Prediction of TCR-peptide interactions has great importance for therapy of cancer, infectious and autoimmune diseases, but remains a major challenge, particularly for unseen epitopes. We present a structure-based method that enables scoring of TCR-peptide interactions using an energy potential (TCRen) derived from statistics of TCR-peptide contacts in existing crystal structures. We show that TCRen has high performance in discriminating cognate/unrelated peptides and can facilitate the identification of cancer neoepitopes recognized by tumor-infiltrating lymphocytes.
Cold-inducible promoter-driven knockdown of Brachypodium antifreeze proteins confers freeze sensitivity
Authors: Juurakko Collin L. , Bredow Melissa , diCenzo George C. , Walker Virginia K.
Published: February 2022

The model forage crop, Brachypodium distachyon, has a family of ice recrystallization inhibition (BdIRI) genes, which encode antifreeze proteins that function by adsorbing to ice crystals and inhibiting their growth. The genes were previously targeted for knockdown using a constitutive CaMV 35S promoter and the resulting transgenic Brachypodium showed reduced antifreeze activity and a greater susceptibility to freezing. However, the transgenic plants also showed developmental defects with shortened stem lengths and were almost completely sterile, raising the possibility that their reduced freeze tolerance could be attributed to developmental deficits. A cold-induced promoter from rice (prOsMYB1R35) has now been substituted for the constitutive promoter to generate temporal miRNA-mediated Brachypodium antifreeze protein knockdowns. Although transgenic lines showed no apparent pleiotropic developmental defects, they demonstrated reduced antifreeze activity as assessed by assays for ice-recrystallization inhibition, thermal hysteresis, electrolyte leakage, leaf infrared thermography, and leaf damage after infection with an ice nucleating phytopathogen. Strikingly, the number of cold-acclimated transgenic plants that survived freezing at -8 °C was reduced by half or killed entirely, depending on the line, compared to cold-acclimated wild type plants. Although these proteins have been studied for almost 60 years, this is the first unequivocal demonstration in any organism of the utility of antifreeze protein function and their contribution to freeze protection, independent of obvious developmental defects. These proteins are thus of potential interest in a wide range of biotechnological applications from accessible cryopreservation, to frozen product additives, to the engineering of transgenic crops with enhanced freezing tolerance.
Squamation and scale morphology at the root of jawed vertebrates
Authors: Wang Yajing , Zhu Min
Published: February 2022

Placoderms, the most basal jawed vertebrates, are crucial to understanding how the characters of crown gnathostomes comprising Chondrichthyes and Osteichthyes evolved from their stem relatives. Despite the growing knowledge on the anatomy and diversity of placoderms over the past decade, the dermal scales of placoderms are predominantly known from isolated material, either morphologically or histologically, resulting in their squamation being poorly understood. Here we provide a comprehensive description of the squamation and scale morphology of a primitive taxon of Antiarcha (a clade at the root of jawed vertebrates),Parayunnanolepis xitunensis, based on the virtual restoration of an articulated specimen by using X-ray computed tomography. Thirteen morphotypes of scales are classified to exhibit how the morphology changes with their position on the body in primitive antiarchs, based on which nine areas of the post-thoracic body are distinguished to show their scale variations in the dorsal, flank, ventral, and caudal lobe regions. In this study, the histological structure of yunnanolepidoid scales was described for the first time based on disarticulated scales from the type locality and horizon ofP. xitunensis, demonstrating that yunnanolepidoid scales are remarkably different from the dermal plates of antiarchs including yunnanolepidoids in the absence of developed middle layer. Together, our study reveals that the high regionalization of squamation and the bipartite histological structure of scale might be plesiomorphic for antiarchs, and jawed vertebrates in general.
Managing beach access and vehicle impacts following reconfiguration of the landscape by a natural hazard event
Authors: Orchard Shane , Fischman Hallie S. , Schiel David R.
Published: February 2022

After New Zealand’s 7.8 Mw Kaikōura earthquake in late 2016 an unexpected anthropogenic effect involved increased motorised vehicle access to beaches. We show how these effects were generated by landscape reconfiguration associated with coastal uplift and widening of high-tide beaches, and present analyses of the distribution of natural environment values in relation to vehicle movements and impacts. Access changes led to extensive vehicle tracking in remote areas that had previously been protected by natural barriers. New dunes formed seaward of old dunes and have statutory protection as threatened ecosystems, yet are affected by vehicle traffic. Nesting grounds of nationally vulnerable banded dotterel (Charadrius bicinctus bicinctus) co-occur with vehicle tracking. An artificial nest experiment showed that vehicle strikes pose risks to nesting success, with 91% and 83% of nests destroyed in high and moderate-traffic areas, respectively, despite an increase in suitable habitat. Despite gains for recreational vehicle users there are serious trade-offs with environmental values subject to legal protection and associated responsibilities for management authorities. In theory, a combination of low-impact vehicle access and environmental protection could generate win-win outcomes from the landscape changes, but is difficult to achieve in practice. Detailed information on sensitive areas would be required to inform designated vehicle routes as a potential solution, and such sensitivities are widespread. Alternatively, vehicle access areas that accommodate longstanding activities such as boat launching could be formally established using identified boundaries to control impacts further afield. Difficulties for the enforcement of regulatory measures in remote areas also suggest a need for motivational strategies that incentivise low-impact behaviours. We discuss options for user groups to voluntarily reduce their impacts, the importance of interactions at the recreation-conservation nexus, and need for timely impact assessments across the social-ecological spectrum after physical environment changes -- all highly transferable principles for other natural hazard and disaster recovery settings worldwide.
Reclassifying Cancer: Defining tumour cell cycle activity in terms of its tissue of origin in over 13,000 samples
Authors: Lundberg Arian , Yi Joan Jong Jing , Lindström Linda S. , Tobin Nicholas P.
Published: February 2022

Genomic alterations resulting in loss of control over the cell cycle is a fundamental hallmark of human malignancies. Whilst pan-cancer studies have broadly assessed tumour genomics and their impact on oncogenic pathways, analyses taking the baseline signalling levels in normal tissue into account are lacking. To this end, we aimed to reclassify the cell cycle activity of tumours in terms of their tissue of origin and determine the DNA mutations, chromosome arm-level changes and signalling pathways driving cell cycle activity. Combining normal tissue and pan-cancer data from over 13,000 samples we demonstrate that tumours of gynaecological origin show the highest levels of baseline corrected cell cycle activity, partially owing to hormonal signalling and gene expression changes. We also show that normal and tumour tissues can be separated into groups (quadrants) of low/high cell cycle activity and propose the novel hypothesis of an upper limit on these activity levels in tumours.
Mechanistic model for human brain metabolism and its connection to the neurovascular coupling
Authors: Sundqvist Nicolas , Sten Sebastian , Engström Maria , Cedersund Gunnar
Published: February 2022

The neurovascular and neurometabolic couplings (NVC and NMC) connects cerebral activity, blood flow, and metabolism. This interconnection is used in for instance functional imaging, which analyses the blood-oxygen-dependent (BOLD) signal. The mechanisms underlying the NVC are complex, which warrants a model-based analysis of data. We have previously developed a mechanistically detailed model for the NVC, and others have proposed detailed models for cerebral metabolism. However, existing metabolic models are still not fully utilizing available magnetic resonance spectroscopy (MRS) data and are not connected to detailed models for NVC. Therefore, we herein present a new model that integrates mechanistic modelling of both MRS and BOLD data. The metabolic model covers central metabolism, using a minimal set of interactions, and can describe time-series data for glucose, lactate, aspartate, and glutamate, measured after visual stimuli. Statistical tests confirm that the model can describe both estimation data and predict independent validation data, not used for model training. The interconnected NVC model can simultaneously describe BOLD data and can be used to predict expected metabolic responses in experiments where metabolism has not been measured. This model is a step towards a useful and mechanistically detailed model for cerebral blood flow and metabolism, with potential applications in both basic research and clinical applications.

Author summary

The neurovascular and neurometabolic couplings are highly central for several clinical imaging techniques since these frequently use blood oxygenation (the BOLD signal) as a proxy for neuronal activity. This relationship is described by the highly complex neurovascular and neurometabolic couplings, which describes the balancing between increased metabolic demand and blood flow, and which involves several cell-types and regulatory systems, which all change dynamically over time. While there are previous works that describe the neurovascular coupling in detail, neither we nor others have developed connections to corresponding mechanistic models for the third aspect, the metabolic aspect. Furthermore, magnetic resonance spectroscopy (MRS) data for such modelling readily is available. In this paper we present a minimal mechanistic model that can describe the metabolic response to visual stimuli. The model is trained to describe experimental data for the relative change in metabolic concentrations of several metabolites in the visual cortex during stimulation. The model is also validated against independent validation data, that was not used for model training. Finally, we also connect this metabolic model to a detailed mechanistic model of the neurovascular coupling. Showing that the model can describe both the metabolic response and a neurovascular response simultaneously.
Mismatches in gene deletions and kidney-related proteins are novel histocompatibility factors in kidney transplantation
Authors: Markkinen Salla , Helanterä Ilkka , Lauronen Jouni , Lempinen Marko , Partanen Jukka , Hyvärinen Kati
Published: February 2022

Background

The genomic mismatch level between donor and recipient is associated with the risk of acute rejection and long-term graft survival. In the present study, we determined the association of genome-level matching with acute rejection in a single-center kidney transplantation cohort.

Methods

Altogether, 1025 pairs of deceased donors and kidney transplant recipients transplanted in 2007–2017 were genotyped. The associations between the sums of whole genome missense variant mismatches and missense mismatches in transmembrane, secretory, and kidney-related proteins, with acute rejection were estimated using Cox proportional hazards model. Additionally, we analyzed 40 common deletion-tagging variants using Cox model.

Results

The increasing mismatch sum in kidney-related proteins associated with acute rejection with an unadjusted HR of 1.15 (95% CI, 1.01–1.30; P=0.029) when dividing the sum into quartiles. The sums of other mismatches were not associated with acute rejection. In deletion analysis, a mismatch in rs7542235 (NC_000001.11:g.196854483A>G), genotype GG tagging a homozygous deletion at the complement Factor H-related (CFHR) proteins locus, predisposed to acute rejection with adjusted HR of 2.97 (95% CI, 1.46–6.05; P=0.003).

Conclusions

The present study supports that mismatches in gene deletions and kidney-related proteins are novel histocompatibility factors in kidney transplantation. The relative importance of different gene deletions varies between populations, as we found evidence for CFH-related gene deletion but not for the previously reported LIMS1 deletion.

SIGNIFICANCE STATEMENT

The first genome-wide association studies have not identified strong candidate genes for complication risks of kidney transplantation whereas matching of non-HLA genes may be promising. The current study determined the association of genome-level matching with acute rejection among 1025 kidney transplant pairs. The increasing mismatch sum in kidney-related proteins was associated with acute allograft rejection. Also, an association between acute allograft rejection and rs7542235 genotype GG, tagging a homozygous deletion at the complement factor H-related (CFHR) loci on chr 1 was found. The present study suggests that mismatches in gene deletions and kidney-related proteins are important novel histocompatibility factors in kidney transplantation.
Genetic and immune landscape evolution defines subtypes of MMR deficient colorectal cancer
Authors: Challoner Benjamin R. , Woolston Andrew , Lau David , Buzzetti Marta , Fong Caroline , Barber Louise J. , Anandappa Gayathri , Crux Richard , Assiotis Ioannis , Fenwick Kerry , Begum Ruwaida , Begum Dipa , Lund Tom , Sivamanoharan Nanna , Sansano Harold B. , Domingo-Arada Melissa , Tran Amina , Eccles Bryony , Ellis Richard , Falk Stephen , Hill Mark , Krell Daniel , Murugaesu Nirupa , Nolan Luke , Potter Vanessa , Saunders Mark , Shiu Kai-Keen , Guettler Sebastian , Alexander James L. , Lázare-Iglesias Héctor , Kinross James , Murphy Jamie , Loga Katharina von , Cunningham David , Chau Ian , Starling Naureen , Ruiz-Bañobre Juan , Dhillon Tony , Gerlinger Marco
Published: February 2022

Mismatch repair deficient colorectal cancers have high mutation loads and many respond to immune checkpoint-inhibitors. We investigated how genetic and immune landscapes co-evolve in these tumors. All cases had high truncal mutation loads. Driver aberrations showed a clear hierarchy despite pervasive intratumor heterogeneity: Those in WNT/βCatenin, mitogen-activated protein kinase and TGFβ receptor family genes were almost always truncal. Immune evasion drivers were predominantly subclonal and showed parallel evolution. Pan-tumor evolution, subclonal evolution, and evolutionary stasis of genetic immune evasion drivers defined three MMRd CRC subtypes with distinct T-cell infiltrates. These immune evasion drivers have been implicated in checkpoint-inhibitor resistance. Clonality and subtype assessments are hence critical for predictive immunotherapy biomarker development. Cancer cell PD-L1 expression was conditional on loss of the intestinal homeobox transcription factor CDX2. This explains infrequent PD-L1 expression by cancer cells and likely contributes to the high recurrence risk of MMRd CRCs with impaired CDX2 expression.
Polyfunctional pathogen-specific CD4+ T cells reside in the lungs and tumors of NSCLC patients
Authors: Oja Anna E. , Morgana Florencia , Hagen Ruth , Ghandour Cherien A. , Nolte Martijn A. , Rooijakkers Suzan H.M. , van Lier René A.W. , Bardoel Bart W. , Hombrink Pleun
Published: February 2022

Local T cell responses are required for optimal protection of the lungs against airborne pathogens. This localized protection is mediated by various immune cells, including resident memory T cells (TRM). While human lung CD8+ TRM line the epithelium and are enriched for recognition of respiratory viruses, we found CD4+ TRM to exhibit more heterogeneous localization patterns, surrounding airways, forming clusters in the lung parenchyma, and lining the epithelium. This heterogeneity was also reflected functionally, as lung CD4+ TRM were enriched for recognition of diverse classes of respiratory pathogens. Upon stimulation, lung CD4+ TRM expressed different polyfunctional cytokine profiles depending on the pathogen recognized. CD4+ TRM responding to respiratory viruses and bacteria were biased for production of IFN-γ and IL-17, respectively. Strikingly, pathogen-specific CD4+ TRM also represent a significant fraction in NSCLC tumors that remained polyfunctional despite high PD-1 expression. These findings are not only important for vaccine design, but also provide a rationale for reinvigorating anti-tumor immunity through triggering of polyfunctional pathogen-specific CD4+ tumor infiltrating lymphocytes.
A balanced measure shows superior performance of pseudobulk methods over mixed models and pseudoreplication approaches in single-cell RNA-sequencing analysis
Authors: Murphy Alan E , Skene Nathan G
Published: February 2022

Recently, Zimmermanet al.,1highlighted the importance of accounting for the dependence between cells from the same individual when conducting differential expression analysis on single-cell RNA-sequencing data. Their work proved the inadequacy of pseudoreplication approaches for such analysis – This was an important step forward that was conclusively proven by them. A hierarchical single-cell expression simulation approach (hierarchicell) was developed by Zimmermanet al.,1to generate non-differentially expressed genes upon which performance was evaluated using the type 1 error rate; the proportion of non-differentially expressed genes indicated as differentially expressed by a model. However, evaluating such models on their type 1 or type 2 error rate in isolation is insufficient to determine their true performance – for example, a method with low type 1 error may have a high type 2 error rate. Moreover, because no seed was set for the pseudo-random number generator used in hierarchicell, the different methods evaluated by Zimmermanet al. were done so on different simulated datasets. Here, we corrected these issues, reran the author’s analysis and found pseudobulk methods outperformed mixed models.

Contact

Alan Murphy:a.murphy@imperial.ac.uk, Nathan Skene:n.skene@imperial.ac.uk

Code availability

The modified version of hierarchicell which returns all error metrics, uses the same simulated data across approaches and has checkpointing capabilities (if runs are aborted or crashed) is available at:https://github.com/neurogenomics/hierarchicell.

The benchmarking script along with the results are available at:https://github.com/Al-Murphy/reanalysis_scRNA_seq_benchmark.
modelRxiv: A platform for the dissemination and interactive display of models
Authors: Harris Keith D. , Hadari Guy , Greenbaum Gili
Published: February 2022

Modeling the dynamics of biological processes is ubiquitous across the ecological and evolutionary disciplines. However, the increasing complexity of these models poses a significant challenge to the dissemination of model-derived results. With the existing requirements of scientific publishing, most often only a small subset of model results are generated, presented in static figures or tables, and made available to the scientific community. Further exploration of the parameter space of a model, investigation of possible variations of a model, and validation of the results in relation to model assumptions commonly rely on local deployment of code supplied by the authors. This can pose a technical challenge due to the diversity of frameworks and environments in which models are developed, and preclude model validation and exploration by readers and reviewers. To address this issue, we developed a platform that serves as an interactive repository of biological models, calledmodelRxiv. The platform provides a unified interface for the analysis of models that does not require any technical understanding of the model implementation. To facilitate adding models tomodelRxiv, we utilize OpenAI large-language models (LLMs) to make code written in different programming languages compatible withmodelRxiv, making the platform language-agnostic.modelRxivis designed to serve as an interactive extension of published models, allowing users to regenerate model results under user-defined parameterizations of the model. By making published models accessible, this platform promises to significantly improve the accessibility, reproducibility, and validation of ecological and evolutionary models.
Phenotypic Characterization of indigenous goat population in Southern, Ethiopia
Authors: Muluneh Teshager , Tadesse Wondimagegn
Published: February 2022

A study was conducted at Abaya and Yirgachafe districts to characterize indigenous goat types phenotypically. Data were collected through field measurements and visual observation of qualitative traits. Totally 540 goats were used for metric and morphometric measurement. Results of the study revealed that the goat populations found in Abaya and Yirgachafe district were different characteristics which are physically Abaya goats were closest with Arsi-Bale whereas yirgachafee with Woyto-Guji which are mostly distributed goat breeds in southern Ethiopia. The dominant coat color pattern in study area was plain, patchy, and spotted with proportions of 55.19, 37.04, and 7.78% and 46.67, 38.89, and 14.44% in Abaya and Yirgachafee district respectively. A strong and positive correlation(r = 0.83, 0.76) was observed between heart girth and body weight for male and female goat populations respectively. Generally, the indigenous goat population has its own difference in its morphological and morphometric traits. Traits have their own economic contribution. Therefore, identifying these important traits for further genetic improvements, conservation and sustainable utilization of the genetic resources of the diversified goat population is important.
Endocytosis-mediated vitellogenin absorption and lipid metabolism in the hindgut-derived pseudoplacenta of the viviparous teleost Xenotoca eiseni
Authors: Iida Atsuo , Nomura Jumpei , Yoshida Junki , Suzuki Takayuki , Yokoi Hayato , Hondo Eiichi
Published: February 2022

Certain viviparous animals possess mechanisms for mother-to-embryo nutrient transport during gestation. Xenotoca eiseni is one such viviparous teleost species in which the mother supplies proteins and other components to the offspring developing in the ovary. The embryo possesses trophotenia, a hindgut-derived pseudoplacenta to receive the maternal supplement. However, the molecular mechanisms underlying viviparous non-mammalian animals remain elusive. We conducted this study to investigate the mechanism for nutrient absorption and degradation in trophoenia of X. eiseni. The tracer assay indicated that a lipid transfer protein, vitellogenin (Vtg), was absorbed into the epithelial layer cells of trophotaenia. Vtg uptake was significantly suppressed by Pitstop-2, an inhibitor of clathrin-mediated endocytosis. Gene expression analysis indicated that the genes involved in endocytosis-mediated lipolysis and lysosomal cholesterol transport were expressed in trophotaenia. In contrast, plasma membrane transporters expressed in the intestinal tract were not functional in trophotaenia. Our results suggested that endocytosis-mediated lysosomal lipolysis is one of the mechanisms underlying maternal component metabolism. Thus, our study demonstrated how viviparous teleost species have acquired a unique developmental system that is based on the hindgut-derived pseudoplacenta.
The Effect of Lipid Composition on the Dynamics of Tau Fibrils
Authors: Chowdhury Unmesh D. , Paul Arnav , Bhargava B. L.
Published: February 2022

Knowledge of the interaction of the tau fibrils with the cell membrane is critical for the understanding of the underlying tauopathy pathogenesis. Lipid composition is found to effect the conformational ensemble of the tau fibrils. Using coarse grained and all-atom molecular dynamics simulations we have shown the effect of the lipid composition in modulating the tau structure and dynamics. Molecular dynamics simulations show that tau proteins interact differentially with the zwitterionic compared to the charged lipid membranes. The negatively charged POPG lipid membranes increase the binding affinity of the tau fibrils. The addition of cholesterol is also found to modify the tau binding to the membrane.
The Development and Evaluation of a Fully Automated Markerless Motion Capture Workflow
Authors: Needham Laurie , Evans Murray , Wade Logan , Cosker Darren P. , McGuigan Polly M. , Bilzon James L. , Colyer Steffi L.
Published: February 2022

This study presented a fully automated deep learning based markerless motion capture workflow and evaluated its performance against marker-based motion capture during overground running, walking and counter movement jumping. Multi-view high speed (200 Hz) image data were collected concurrently with marker-based motion capture (criterion data), permitting a direct comparison between methods. Lower limb kinematic data for 15 participants were computed using 2D pose estimation, our 3D fusion process and OpenSim based inverse kinematics modelling. Results demonstrated high levels of agreement for lower limb joint angles, with mean differences ranging between 0.1° - 10.5° for 6 DoF hip joint rotations, and 0.7° - 3.9° for knee and ankle rotations. These differences generally fall within the documented uncertainties of marker-based motion capture, suggesting that our markerless approach could be used for appropriate biomechanics applications. We used an open-source, modular and customisable workflow, allowing for integration with other popular biomechanics tools such as OpenSim. By developing open-source tools, we hope to facilitate the democratisation of markerless motion capture technology and encourage the transparent development of markerless methods. This presents exciting opportunities for biomechanics researchers and practitioners to capture large amounts of high quality, ecologically valid data both in the laboratory and in the wild.
Multi-omics approach reveals dysregulation of protein phosphorylation correlated with lipid metabolism in mouse fatty liver
Authors: Kim Sora Q. , Mohallem Rodrigo , Franco Jackeline , Buhman Kimberly K. , Kim Kee-Hong , Aryal Uma K.
Published: February 2022

Obesity caused by overnutrition is a major risk factor for non-alcoholic fatty liver disease (NAFLD). Several lipid intermediates such as fatty acids, glycerophospholipids and sphingolipids are implicated in NAFLD, but detailed characterization of lipids and their functional links to proteome and phosphoproteome remain to be elucidated. To characterize this complex molecular relationship, we used multi-omics approach by conducting comparative proteomic, phoshoproteomic and lipidomic analyses of high fat (HFD) and low fat (LFD) diet fed mice livers. We quantified 2447 proteins and 1339 phosphoproteins containing 1650 class I phosphosites (with localization probability > 0.75), of which 669 phosphosites were significantly different between HFD and LFD mice livers. We detected alterations of proteins associated with cellular metabolic processes such as small molecule catabolic process, monocarboxylic acid, long- and medium-chain fatty acid, and ketone body metabolic processes, and peroxisome organization. We observed significant downregulation of protein phosphorylation in HFD fed mice liver in general. Untargeted lipidomics identified upregulation of triacylglycerols, glycerolipids and ether glycerophosphocholines and downregulation of glycerophospholipids such as lysoglycerophospholipids, as well as ceramides and acylcarnitines. Analysis of differentially regulated phosphosites revealed phosphorylation dependent deregulation of insulin signaling as well as lipogenic and lipolytic pathways during HFD induced obesity. Thus, this study reveals a molecular connection between decreased protein phosphorylation and lipolysis, as well as lipid-mediated signaling in diet-induced obesity.
CellNeighborEX: Deciphering Neighbor-Dependent Gene Expression from Spatial Transcriptomics Data
Authors: Kim Hyobin , Lövkvist Cecilia , Palma António M. , Martin Patrick , Kim Junil , Kumar Amit , Peixoto Maria Leonor , Madan Esha , Gogna Rajan , Won Kyoung Jae
Published: February 2022

Cells have evolved communication methods to sense their microenvironments and send biological signals. In addition to the communication using ligands and receptors, cells use diverse channels including gap junctions to communicate with their immediate neighbors. Current approaches, however, cannot effectively capture the influence of various microenvironments. Here, we propose a novel approach that identifiescell neighbor-dependent geneexpression (CellNeighborEX). After categorizing cells based on their microenvironment from spatial transcriptomics (ST) data, CellNeighborEX identifies diverse gene sets associated with partnering cell types, providing further insight. To categorize cells along with their environment, CellNeighborEX uses direct cell location or the mixture of transcriptome from multiple cells depending on the ST technology. We show that cells express different gene sets depending on the neighboring cell types in various tissues including mouse embryos, brain, and liver cancer. These genes were associated with development (in embryos) or metastases (liver cancer). We further validate that gene expression can be induced by neighboring partners. The neighbor-dependent gene expression suggests new potential genes involved in cell-cell interactions beyond what ligand-receptor co-expression can discover.
A Bayesian Hierarchical Model for Signal Extraction from Protein Microarrays
Authors: Bérubé Sophie , Kobayashi Tamaki , Wesolowski Amy , Norris Douglas E. , Ruczinski Ingo , Moss William J. , Louis Thomas A.
Published: February 2022

Summary

Protein microarrays are a promising technology that measure protein levels in serum or plasma samples. Due to the high technical variability of these assays and high variation in protein levels across serum samples in any population, directly answering biological questions of interest using protein microarray measurements is challenging. Using within-array ranks of protein levels for analysis can mitigate the impact of between-sample variation on downstream analysis. Although ranks are sensitive to pre-processing steps, ranking methods that accommodate uncertainty provide robust and loss-function optimal ranks. Such ranking methods require Bayesian modeling that produces full posterior distributions for parameters of interest. Bayesian models that produce such outputs have been developed for other assays, for example DNA microarrays, but those modeling assumptions are not appropriate for protein microarrays. We develop and evaluate a Bayesian model to extract a full posterior distribution of normalized fluorescent signals and associated ranks for protein microarrays, and show that it fits well to data from two studies that use protein microrarrays from different manufacturing processes. We validate the model via simulation and demonstrate the downstream impact of using estimates from this model to obtain optimal ranks.
Regulatory dynamics distinguishing desiccation tolerance strategies within resurrection grasses
Authors: Aubin Brian St. , Wai Ching Man , Kenchanmane Raju Sunil K. , Niederhuth Chad E. , VanBuren Robert
Published: February 2022

Desiccation tolerance has evolved recurrently in grasses using two unique strategies to mitigate photooxidative damage under anhydrobiosis. The grassOropetium thomaeumprotects and retains chlorophyll, thylakoids, and the photosynthetic apparatus during desiccation (Homoiochlorophyly), whileEragrostis nindensisdegrades and resynthesizes these components under desiccation and rehydration (Poikilochlorophyly). Here, we surveyed chromatin architecture and gene expression during desiccation in these two closely related species to identify regulatory dynamics underlying the distinct desiccation tolerance strategies in grasses. In both grasses, we observed a strong association between nearby chromatin accessibility and gene expression in desiccated tissues compared to well-watered, reflecting an unusual chromatin stability under anhydrobiosis. Integration of chromatin accessibility (ATACseq) and expression data (RNAseq) revealed a core desiccation response across these two grasses including many genes with binding sites for the core seed development transcription factor ABI5.O. thomaeumhad a unique set of desiccation induced genes and regulatory elements associated with photoprotection, pigment biosynthesis, and response to high light, reflecting its adaptation of homoiochlorophyly. A tandem array of early light induced proteins (ELIPs) had massive shifts in gene expression and chromatin openness under desiccation in onlyO. thomaeum, and ELIPs acquired a novel desiccation related cis-regulatory motif, reflecting regulatory neofunctionalization during the evolution of desiccation tolerance. Together, our results highlight the complex regulatory and expression dynamics underlying desiccation tolerance in grasses.
ApiaceaeFNS Ioriginated fromF3Hthrough tandem gene duplication
Authors: Pucker Boas , Iorizzo Massimo
Published: February 2022

Background

Flavonoids are specialized metabolites with numerous biological functions in stress response and reproduction of plants. Flavones are one subgroup that is produced by the flavone synthase (FNS). Two distinct enzyme families evolved that can catalyze the biosynthesis of flavones. While the membrane-bound FNS II is widely distributed in seed plants, one lineage of soluble FNS I appeared to be unique to Apiaceae species.

Results

We show through phylogenetic and comparative genomic analyses that ApiaceaeFNS Ievolved through tandem gene duplication of flavanone 3-hydroxylase (F3H)followed by neofunctionalization. Currently available datasets suggest that this event happened within the Apiaceae in a common ancestor ofDaucus carotaandApium graveolens. The results also support previous findings thatFNS Iin the Apiaceae evolved independent ofFNS Iin other plant species.

Conclusion

We validated a long standing hypothesis about the evolution of Apiaceae FNS I and predicted the phylogenetic position of this event. Our results explain how an Apiaceae-specificFNS Ilineage evolved and confirm independence from otherFNS Ilineages reported in non-Apiaceae species.
High variation in handling times confers 35-year stability to predator feeding rates despite altered prey abundances and apparent diet proportions
Authors: Novak Mark
Published: February 2022

Historical resurveys of ecological communities are important for placing the structure of modern ecosystems in context. Rarely, however, are snapshot surveys alone sufficient for providing direct insight into the rates of ecological processes that underlie how communities function, either now or in the past. In this study, I used a statistically-reasoned observational approach to estimate the feeding rates of a New Zealand intertidal predator,Haustrum haustorium, using diet surveys performed at several sites by Robert Paine in 1968–9 and by me in 2004. Comparisons between time periods reveal a remarkable consistency inH. haustorium’s prey-specific feeding rates, which contrasts with the changes I observed in prey abundances,H. haustorium’s body size distribution, and the proportional contributions ofH. haustorium’s prey to its apparent diet. Although these results imply accompanying and perhaps adaptive changes inH. haustorium’s prey preferences, they are nonetheless anticipated byH. haustorium’s high range of variation in prey-specific handling times that dictate not only its maximum possible feeding rates but also the probabilities with which feeding events may be detected during diet surveys. Similarly high variation in detection times (i.e. handling and digestion times) is evident in predator species throughout the animal kingdom. The potential disconnect between a predator’s apparent diet and its actual feeding rates suggests that much of the temporal and biogeographic variation that is perceived in predator diets and food-web structures may be of less functional consequence than currently assumed.
Enhanced photosynthetic efficiency for increased carbon assimilation and woody biomass production in hybrid poplar INRA 717-1B4
Authors:   Living Carbon Team, Tao Yumin , Chiu Li-Wei , Hoyle Jacob W. , Du Jessica , Rasmussen Karli , Mellor Patrick , Richey Christian , Kuiper Julie , Fried Madeline , Dewhirst Rebecca A. , Tucker Dominick , Crites Alex , Orr Gary A. , Heckert Matthew J. , Vidal Damaris G. , Orosco-Cardenas Martha L. , Hall Madeline E.
Published: February 2022

Increasing CO2 levels in the atmosphere and the resulting negative impacts on climate change have compelled global efforts to achieve carbon neutrality or negativity. Most such efforts focus on carbon sequestration through chemical or physical approaches. We aim to harness the power of synthetic biology to enhance plants’ natural ability to draw down and sequester carbon, thereby positively affecting climate change. Past decades of scientific progress have shed light on strategies to overcome the intrinsic limitations of carbon drawdown and fixation through photosynthesis, particularly in row crops in hopes of improving agricultural productivity for food security. Incorporating a photorespiration bypass in C3 plants has shown promising results of increased biomass and grain yield. Despite their globally dominant role in atmospheric carbon flux, the drawdown rates of most trees are currently limited by their C3 photosynthetic metabolism, and efforts to improve the photosynthetic capacity of trees, such as by reducing energy loss in photorespiration, are currently lacking. Here, we selected a photorespiration bypass pathway and tested its effectiveness on photosynthetic enhancement in hybrid poplar INRA717-IB4. The design includes a RNAi strategy to reduce the transportation of the photorespiration byproduct, glycolate, out of chloroplast and a shunt pathway to metabolize the retained glycolate back to CO2 for fixation through the Calvin-Benson cycle. Molecular and physiological data collected from two repeated growth experiments indicates that transgenic plants expressing genes in the photorespiration bypass pathway have increased photosynthetic efficiency, leading to faster plant growth and elevated biomass production. One lead transgenic event accumulated 53% more above-ground dry biomass over a five month growth period in a controlled environment. Pilot projects with photosynthesis-enhanced trees in the field are in progress. Our results provide a proof-of-concept for engineering trees to help combat climate change.
Spatiotemporally Mapping Thermodynamics of Lysosomes and Mitochondria using Cascade Organelle-Targeting Upconversion Nanoparticles
Authors: Di Xiangjun , Su Qian Peter , Wang Dejiang , Liu Yongtao , Maddahfar Mahnaz , Zhou Jiajia , Jin Dayong
Published: February 2022

The intracellular metabolism of organelles, like lysosomes and mitochondria, are highly coordinated spatiotemporally and functionally. The activities of lysosomal enzymes significantly rely on the cytoplasmic temperature, and heat is constantly released by mitochondria as the byproduct of ATP generation during active metabolism. Here, we develop temperature-sensitive LysoDots and MitoDots to monitor the in situ thermodynamics of lysosomes and mitochondria. The design is based on upconversion nanoparticles (UCNPs) with high-density surface modifications to achieve the exceptionally high sensitivity of 2.7% K-1 and accuracy of 0.8 K for nanothermometry to be used in living cells. We show the measurement is independent of the intracellular ion concentrations- and pH values. With Ca2+ ion shock, the temperatures of both lysosomes and mitochondria increased by 2∼4 °C. Intriguingly, with Chloroquine treatment, the lysosomal temperature was observed to decrease by up to ∼3 °C, while mitochondria remained relatively stable. Lastly, with oxidative phosphorylation inhibitor treatment, we observed a 3∼7 °C thermal increase and transition from mitochondria to lysosomes. These observations indicate different metabolic pathways and thermal transitions between lysosomes and mitochondria inside HeLa cells. The nanothermometry probes provide a powerful tool for multi-modality functional imaging of subcellular organelles and interactions with high spatial, temporal and thermal dynamics resolutions.

Graphical Abstract

Cascade organelle-targeted nano-thermometers based on upconversion LysoDots and MitoDots.
A comparison of four epidemic waves of COVID-19 in Malawi; an observational cohort study
Authors: Anscombe Catherine , Lissauer Samantha , Thole Herbert , Rylance Jamie , Dula Dingase , Menyere Mavis , Kutambe Belson , van der Veer Charlotte , Phiri Tamara , Banda Ndaziona P. , Mndolo Kwazizira S. , Mponda Kelvin , Phiri Chimota , Mallewa Jane , Nyirenda Mulinda , Katha Grace , Mwandumba Henry , Gordon Stephen B. , Jambo Kondwani C. , Cornick Jennifer , Feasey Nicholas , Barnes Kayla G. , Morton Ben , Ashton Philip M. ,   Blantyre COVID-19 Consortium
Published: February 2022

Background

Compared to the abundance of clinical and genomic information available on patients hospitalised with COVID-19 disease from high-income countries, there is a paucity of data from low-income countries. Our aim was to explore the relationship between viral lineage and patient outcome.

Methods

We enrolled a prospective observational cohort of adult patients hospitalised with PCR-confirmed COVID-19 disease between July 2020 and March 2022 from Blantyre, Malawi, covering four waves of SARS-CoV-2 infections. Clinical and diagnostic data were collected using an adapted ISARIC clinical characterization protocol for COVID-19. SARS-CoV-2 isolates were sequenced using the MinION™ in Blantyre.

Results

We enrolled 314 patients, good quality sequencing data was available for 55 patients. The sequencing data showed that 8 of 11 participants recruited in wave one had B.1 infections, 6/6 in wave two had Beta, 25/26 in wave three had Delta and 11/12 in wave four had Omicron. Patients infected during the Delta and Omicron waves reported fewer underlying chronic conditions and a shorter time to presentation. Significantly fewer patients required oxygen (22.7% [17/75] vs. 58.6% [140/239], p<0.001) and steroids (38.7% [29/75] vs. 70.3% [167/239], p<0.001) in the Omicron wave compared with the other waves. Multivariable logistic-regression demonstrated a trend toward increased mortality in the Delta wave (OR 4.99 [95% CI 1.0-25.0 p=0.05) compared to the first wave of infection.

Conclusions

Our data show that each wave of patients hospitalised with SARS-CoV-2 was infected with a distinct viral variant. The clinical data suggests that patients with severe COVID-19 disease were more likely to die during the Delta wave.

We used genome sequencing to identify the variants of SARS-CoV-2 causing disease in Malawi, and found that each of the four waves was caused by a distinct variant. Clinical investigation suggested that the Delta wave had the highest mortality.
Enhancing imagery rehearsal therapy for nightmares with targeted memory reactivation
Authors: Schwartz Sophie , Clerget Alice , Perogamvros Lampros
Published: February 2022

Nightmare disorder (ND) is characterized by dreams with strong negative emotions occurring during rapid-eye movement (REM) sleep. ND is mainly treated by imagery rehearsal therapy (IRT), where the patients are asked to change the negative story line of their nightmare to a more positive one. We here used targeted memory reactivation (TMR) during REM sleep to strengthen IRT-related memories and accelerate remission of ND. Thirty-six patients with ND were asked to perform an initial IRT session and, while they generated a positive outcome of their nightmare, half of the patients were exposed to a sound (TMR group), while no such pairing took place for the other half (control group). During the next two weeks, all patients performed IRT every evening at home, and were exposed to the sound during REM sleep with a wireless headband, which automatically detected sleep stages. The frequency of nightmares per week at two weeks was used as the primary outcome measure. We found that the TMR group had less frequent nightmares and more positive dream emotions than the control group after two weeks of IRT, and a sustained decrease of nightmares after three months. By demonstrating the effectiveness of TMR during sleep to potentiate therapy, these results have clinical implications for the management of ND, with relevance to other psychiatric disorders too. Additionally, these findings show that TMR applied during REM sleep can modulate emotions in dreams.