bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of oral baits and distribution methods for Tasmanian devils (Sarcophilus harrisii)
Authors: Dempsey Sean , Pye Ruth J. , Gilbert Amy T. , Fountain-Jones Nicholas M. , Moffat Jennifer M. , Benson-Amram Sarah , Smyser Timothy J. , Flies Andrew S. 
Published: April 2022

AbstractContextDiseases are increasingly contributing to wildlife population declines. Tasmanian devil (Sarcophilus harrisii) populations have locally declined by 82% largely due to the morbidity and mortality associated with two independent transmissible devil facial tumours (DFT1 and DFT2). Toxic baits are often used as a management tool for controlling vertebrate pest populations in Australia, but in other areas of the world oral baits are also used to deliver vaccines or pharmaceuticals to wildlife. Oral vaccine bait products have been distributed for more than 50 years at a landscape scale to protect wildlife from rabies virus and contributed to the elimination of fox rabies from more than ten European nations. An oral bait vaccine to protect against devil facial tumours has been proposed as a management tool to improve the population health, resiliency and fitness of wild Tasmanian devils.AimOur goal was to evaluate the potential use of edible baits as vehicles for vaccine delivery to Tasmanian devils.MethodWe tested placebo versions of baits that are already used in Australia.Key resultsCaptive devils consumed all types of placebo baits but exhibited a preference for ruminant- and fish-based baits. Captive devils also consumed inert capsules inserted into placebo baits. Bait fate trials in the field revealed that baits were generally removed within 24 hours. Tasmanian pademelons (Thylogale billardierii), brushtail possums (Trichosurus vulpecula), and Eastern quolls (Dasyurus viverrinus) were the most common nontarget bait competitors at six private properties in southern Tasmania; wild devils removed approximately 5% of ground baits at these sites. We also evaluated an automated bait dispenser, which reduced nontarget uptake and resulted in over 50% of the baits being removed by devils.ConclusionsThis study demonstrates that captive and wild devils will accept and consume placebo versions of commercial baits. Bait dispensers or modified baits or baiting strategies are needed to increase bait uptake by devils.ImplicationsBait dispensers can be used at a regional scale to deliver baits to Tasmanian devils. These could act as vehicles for preventive or therapeutic vaccines to mitigate the impacts of disease on devil populations.Short summaryThis study aimed to test oral baits as potential vaccine delivery vehicles for Tasmanian devils. Captive and wild devils consumed placebo versions of commercial baits used on mainland Australia. Abundant non-target species, such as brushtail possums, Tasmanian pademelons, and eastern quolls consumed most baits in the wild. Implementation of automated bait dispensers increased bait uptake by devils to over 50% at the same regional field sites.
The tissue-specific chromatin accessibility landscape of Papaver somniferum
Authors: Xu Yu , Jia Yanyan , Wang Bo , Guo Li , Guo Mengyao , Che Xiaofei , Ye Kai 
Published: April 2022

AbstractAccessible chromatin regions (ACRs) at promoters, enhancers, and other gene regulatory regions allow transcription factors (TFs) to bind, which regulate gene transcription involved in plant development and metabolism. Papaver somniferum has been widely applied in clinical medicine as one of the most important and oldest medicinal plants due to its unique and effective active ingredients. However, the transcriptional regulatory mechanism of tissue-specific distribution of active ingredients remains unknown. In this study, transcriptome and chromatin accessibility analysis by RNA sequencing (RNA-seq) and assay for transposase-accessible chromatin sequencing (ATAC-seq) was performed to investigate these underlying molecular mechanisms. We identified tissue-specific chromatin Tn5 hypersensitive site (THS) and gene expression by examining the variation of THS and transcripts across six tissues (capsule, stem, fine root, tap root, leaf, and petal). Our results provide insight into the epigenetic mechanism of transcriptional plasticity for P. somniferum organ development. Sequence motif analysis within accessible chromatin regions for co-expressed gene modules revealed enriched binding sites of hub transcription factors that regulate tissue-specific functions. Furthermore, we identified regulatory elements for tissue-specific accumulation of morphine and noscapine in P. somniferum. This is the first tissue-specific chromatin accessibility landscape of P. somniferum providing an important resource for functional epigenetic analysis and future molecular breeding in P. somniferum for variety improvement.
Gene Expression Changes in Therapeutic Ultrasound-Treated Human Chronic Wound Tissue
Authors: Boerman Olivia , Abedin Zahidur , DiMaria-Ghalili Rose Ann , Weingarten Michael S. , Neidrauer Michael , Lewin Peter A. , Spiller Kara L. 
Published: April 2022

AbstractLow-frequency, low-intensity ultrasound has been previously shown to promote healing of chronic wounds in humans, but mechanisms behind these effects are poorly understood. The purpose of this study was to evaluate gene expression differences in debrided human venous ulcer tissue from patients treated with low-frequency (20 kHz), low-intensity (100 mW/cm2) ultrasound compared to a sham treatment in an effort to better understand the potential biological mechanisms. Debrided venous ulcer tissue was collected from 32 subjects one week after sham treatment or low-frequency, low-intensity ultrasound treatment. Of these samples, 7 samples (3 ultrasound treated and 4 sham treated) yielded sufficient quality total RNA for analysis by ultra-high multiplexed PCR (Ampliseq) and expression of more than 24,000 genes was analyzed. 477 genes were found to be significantly different between the ultrasound and sham groups using cut-off values of p<0.05 and fold change of 2. Gene set enrichment analysis identified 20 significantly enriched gene sets from upregulated genes and 4 significantly enriched gene sets from downregulated genes. Most of the enriched gene sets from upregulated genes were related to cellcell signaling pathways. The most significantly enriched gene set from downregulated genes was the inflammatory response gene set. These findings show that therapeutic ultrasound influences cellular behavior in chronic wounds as early as one week after application. Considering the well-known role of chronic inflammation in impairing wound healing in chronic wounds, these results suggest that a downregulation of inflammatory genes is a possible biological mechanism of ultrasound-mediated venous chronic wound healing. Such increased understanding may ultimately lead to the enhancement of ultrasound devices to accelerate chronic wound healing and increase patient quality of life.
The meiotic LINC complex component KASH5 is an activating adaptor for cytoplasmic dynein
Authors: Garner Kirsten E. L. , Salter Anna , Lau Clinton K. , Gurusaran Manickam , Villemant Cécile , Granger Elizabeth P. , McNee Gavin , Woodman Philip G. , Davies Owen R. , Burke Brian E. , Allan Victoria J. 
Published: April 2022

AbstractCytoplasmic dynein-driven movement of chromosomes during prophase I of mammalian meiosis is essential for synapsis and genetic exchange. Dynein connects to chromosome telomeres via KASH5 and SUN1 or SUN2, which together span the nuclear envelope. Here, we show that KASH5 promotes dynein motility in vitro, and cytosolic KASH5 inhibits dynein’s interphase functions. KASH5 interacts with either dynein light intermediate chain (DYNC1LI1 or DYNC1LI2) via a conserved helix in the LIC C-terminal, and this region is also needed for dynein’s recruitment to other cellular membranes. KASH5’s N-terminal EF-hands are essential, as the interaction with dynein is disrupted by mutation of key calcium-binding residues, although it is not regulated by cellular calcium levels. Dynein can be recruited to KASH5 at the nuclear envelope independently of dynactin, while LIS1 is essential for dynactin incorporation into the KASH5-dynein complex. Altogether, we show that the trans-membrane protein KASH5 is an activating adaptor for dynein, and shed light on the hierarchy of assembly of KASH5-dynein-dynactin complexes.
A pulse-chasable reporter processing assay for mammalian autophagic flux with HaloTag
Authors: Yim Willa Wen-You , Yamamoto Hayashi , Mizushima Noboru 
Published: April 2022

AbstractMonitoring autophagic flux is necessary for most autophagy studies. The autophagic flux assays currently available for mammalian cells are generally complicated and do not yield highly quantitative results. Yeast autophagic flux is routinely monitored with the GFP-based processing assay, whereby the amount of GFP proteolytically released from GFP-containing reporters (e.g., GFP-Atg8), detected by immunoblotting, reflects autophagic flux. However, this simple and effective assay is typically inapplicable to mammalian cells because GFP is efficiently degraded in lysosomes while the more proteolytically resistant RFP accumulates in lysosomes under basal conditions. Here, we report a HaloTag (Halo)-based reporter processing assay to monitor mammalian autophagic flux. We found that Halo is sensitive to lysosomal proteolysis but becomes resistant upon ligand binding. When delivered into lysosomes by autophagy, pulse-labeled Halo-based reporters (e.g., Halo-LC3 and Halo-GFP) are proteolytically processed to generate Haloligand when delivered into lysosomes by autophagy. Hence, the amount of free Haloligand detected by immunoblotting or in-gel fluorescence imaging reflects autophagic flux. We demonstrate the applications of this assay by monitoring the autophagy pathways, macroautophagy, selective autophagy, and even bulk nonselective autophagy. With the Halo-based processing assay, mammalian autophagic flux and lysosome-mediated degradation can be monitored easily and precisely.
Rescue of Escherichia coli auxotrophy by de novo small proteins
Authors: Babina Arianne M. , Surkov Serhiy , Ye Weihua , Jerlström-Hultqvist Jon , Larsson Mårten , Holmqvist Erik , Jemth Per , Andersson Dan I. , Knopp Michael 
Published: April 2022

ABSTRACTIncreasing numbers of small proteins with diverse physiological roles are being identified and characterized in both prokaryotic and eukaryotic systems, but the origins and evolution of these proteins remain unclear. Recent genomic sequence analyses in several organisms suggest that new functions encoded by small open reading frames (sORFs) may emerge de novo from noncoding sequences. However, experimental data demonstrating if and how randomly generated sORFs can confer beneficial effects to cells are limited. Here we show that by up-regulating hisB expression, de novo small proteins (≤ 50 amino acids in length) selected from random sequence libraries can rescue Escherichia coli cells that lack the conditionally essential SerB enzyme. The recovered small proteins are hydrophobic and confer their rescue effect by binding to the 5’ end regulatory region of the his operon mRNA, suggesting that protein binding promotes structural rearrangements of the RNA that allow increased hisB expression. This study adds RNA regulatory elements as another interacting partner for de novo proteins isolated from random sequence libraries, and provides further experimental evidence that small proteins with selective benefits can originate from the expression of nonfunctional sequences.
A nanobody toolbox to investigate localisation and dynamics ofDrosophilatitins
Authors: Loreau Vincent , Rees Renate , Chan Eunice HoYee , Taxer Waltraud , Gregor Kathrin , Mußil Bianka , Pitaval Christophe , Luis Nuno Miguel , Mangeol Pierre , Schnorrer Frank , Görlich Dirk 
Published: April 2022

AbstractMeasuring the positions and dynamics of proteins in intact tissues or whole animals is key to understand protein function. However, to date this is still a challenging task, as accessibility of large antibodies to dense tissues is often limited and fluorescent proteins inserted close to a domain of interest may affect function of the tagged protein. These complications are particularly present in the muscle sarcomere, arguably one of the most protein dense structures in nature, which makes studying morphogenesis at molecular resolution challenging. Here, we have employed an efficient pipeline to generate a nanobody toolbox specifically recognising various domains of two largeDrosophilatitin homologs, Sallimus and Projectin. We demonstrate the superior labelling qualities of our nanobodies compared to conventional antibodies in intact muscle tissue. Applying our nanobody toolbox to larval muscles revealed a gigantic Sallimus isoform stretched more than 2 µm to bridge the sarcomeric I-band. Furthermore, N- and C-terminal nanobodies against Projectin identified an unexpected polar orientation of Projectin covering the myosin filaments in larval muscles. Finally, expression of a Sallimus nanobody in living larval muscles confirmed the high affinity binding of nanobodies to target epitopes in living tissue and hence demonstrated their power to reveal thein vivodynamics of sarcomeric protein domains. Together, our toolbox substantiates the multiple advantages of nanobodies to study sarcomere biology. It may inspire the generation of similar toolboxes for other large protein complexes inDrosophilaor mammals.
Evolutionary Origin of Vertebrate OCT4/POU5 Functions in Supporting Pluripotency
Authors: Sukparangsi Woranop , Morganti Elena , Lowndes Molly , Mayeur Hélène , Weisser Melanie , Hammachi Fella , Peradziryi Hanna , Roske Fabian , Hölzenspies Jurriaan , Livigni Alessandra , Godard Benoit Gilbert , Sugahara Fumiaki , Kuratani Shigeru , Montoya Guillermo , Frankenberg Stephen R. , Mazan Sylvie , Brickman Joshua M 
Published: April 2022

AbstractThe support of pluripotent cells over time is an essential feature of development. In eutherian embryos, pluripotency is maintained from naïve states in peri-implantation to primed pluripotency at gastrulation. To understand how these states emerged, we reconstruct the evolutionary trajectory of the Pou5 gene family, which contains the central pluripotency factor OCT4. By coupling evolutionary sequence analysis with functional studies in mouse Embryonic Stem Cells (ESCs), we found that the ability of POU5 proteins to support pluripotency originated in the gnathostome lineage, prior to the generation of two paralogues, Pou5f1 and Pou5f3 via gene duplication. In osteichthyans, retaining both genes, the paralogues differ in their support of naïve and primed pluripotency. This specialization of these duplicates enables the diversification of function in self-renewal and differentiation. By integrating sequence evolution, ESC phenotypes, developmental contexts and structural modelling, we pinpoint OCT4 regions sufficient for naïve pluripotency and describe their adaptation over evolutionary time.
RadGenNets: Deep Learning-Based Radiogenomics Model For Gene Mutation Prediction In Lung Cancer
Authors: Tripathi Satvik , Moyer Ethan Jacob , Augustin Alisha Isabelle , Zavalny Alex , Dheer Suhani , Sukumaran Rithvik , Schwartz Daniel , Gorski Brandon , Dako Farouk , Kim Edward 
Published: April 2022

AbstractIn this paper, we present our methodology that can be used for predicting gene mutation in patients with non-small cell lung cancer (NSCLC). There are three major types of gene mutations that a NSCLC patient’s gene structure can change to: epidermal growth factor receptor (EGFR), Kirsten rat sarcoma virus (KRAS), and Anaplastic lymphoma kinase (ALK). We worked with the clinical and genomics data for each patient as well CT scans. We preprocessed all of the data and then built a novel pipeline to integrate both the image and tabular data. We built a novel pipeline that used a fusion of Convolutional Neural Networks and Dense Neural Networks. Also, using a search approach, we pick an ensemble of deep learning models to classify the separate gene mutations. These models include EfficientNets, SENet, and ResNeXt WSL, among others. Our model achieved a high area under curve (AUC) score of 94% in detecting gene mutation.
A joint learning approach for genomic prediction in polyploid grasses
Authors: Aono Alexandre Hild , Ulbricht Ferreira Rebecca Caroline , Moraes Aline da Costa Lima , de Castro Lara Letícia Aparecida , Pimenta Ricardo José Gonzaga , Costa Estela Araujo , Pinto Luciana Rossini , de Andrade Landell Marcos Guimarães , Santos Mateus Figueiredo , Jank Liana , Lima Barrios Sanzio Carvalho , do Valle Cacilda Borges , Chiari Lucimara , Franco Garcia Antonio Augusto , Kuroshu Reginaldo Massanobu , Lorena Ana Carolina , Gorjanc Gregor , de Souza Anete Pereira 
Published: April 2022

ABSTRACTPoaceae, among the most abundant plant families, includes many economically important polyploid species, such as forage grasses and sugarcane (Saccharumspp.). These species have elevated genomic complexities and limited genetic resources, hindering the application of marker-assisted selection strategies. Currently, the most promising approach for increasing genetic gains in plant breeding is genomic selection. However, due to the polyploidy nature of these polyploid species, more accurate models for incorporating genomic selection into breeding schemes are needed. This study aims to develop a machine learning method by using a joint learning approach to predict complex traits from genotypic data. Biparental populations of sugarcane and two species of forage grasses (Urochloa decumbens, Megathyrsus maximus) were genotyped, and several quantitative traits were measured. High-quality markers were used to predict several traits in different cross-validation scenarios. By combining classification and regression strategies, we developed a predictive system with promising results. Compared with traditional genomic prediction methods, the proposed strategy achieved accuracy improvements exceeding 50%. Our results suggest that the developed methodology could be implemented in breeding programs, helping reduce breeding cycles and increase genetic gains.
A genetic model for in vivo proximity labeling of the mammalian secretome
Authors: Yang Rui , Meyer Amanda S. , Droujinine Ilia A. , Udeshi Namrata D. , Hu Yanhui , Guo Jinjin , McMahon Jill A. , Carey Dominique K. , Xu Charles , Fang Qiao , Sha Jihui , Qin Shishang , Rocco David , Wohlschlegel James , Ting Alice Y. , Carr Steven A. , Perrimon Norbert , McMahon Andrew P. 
Published: April 2022

AbstractOrgan functions are highly specialized and interdependent. Secreted factors regulate organ development and mediate homeostasis through serum trafficking and inter-organ communication. Enzyme-catalyzed proximity labeling enables the identification of proteins within a specific cellular compartment. Here, we report a BirA*G3 mouse strain that enables CRE-dependent promiscuous biotinylation of proteins trafficking through the endoplasmic reticulum. When broadly activated throughout the mouse, widespread labeling of proteins was observed within the secretory pathway. Streptavidin affinity purification and peptide mapping by quantitative mass spectrometry (MS) proteomics revealed organ-specific secretory profiles and serum trafficking. As expected, secretory proteomes were highly enriched for signal peptide-containing proteins, highlighting both conventional and non-conventional secretory processes, and ectodomain shedding. Lower-abundance proteins with hormone-like properties were recovered and validated using orthogonal approaches. Hepatocyte-specific activation of BirA*G3 highlighted liver-specific biotinylated secretome profiles. The BirA*G3 mouse model demonstrates enhanced labeling efficiency and tissue specificity over viral transduction approaches and will facilitate a deeper understanding of secretory protein interplay in development, and healthy and diseased adult states.
Whole-body metabolic modelling predicts isoleucine dependency of SARS-CoV-2 replication
Authors: Thiele Ines , Fleming Ronan M.T. 
Published: April 2022

AbstractWe aimed at investigating host-virus co-metabolism during SARS-CoV-2 infection. Therefore, we extended comprehensive sex-specific, whole-body organ resolved models of human metabolism with the necessary reactions to replicate SARS-CoV-2 in the lung as well as selected peripheral organs. Using this comprehensive host-virus model, we obtained the following key results: 1. The predicted maximal possible virus shedding rate was limited by isoleucine availability. 2. The supported initial viral load depended on the increase in CD4+ T-cells, consistent with the literature. 3. During viral infection, the whole-body metabolism changed including the blood metabolome, which agreed well with metabolomic studies from COVID-19 patients and healthy controls. 4. The virus shedding rate could be reduced by either inhibition of the guanylate kinase 1 or availability of amino acids, e.g., in the diet. 5. The virus variants achieved differed in their maximal possible virus shedding rates, which could be inversely linked to isoleucine occurrences in the sequences. Taken together, this study presents the metabolic crosstalk between host and virus and emphasis the role of amino acid metabolism during SARS-CoV-2 infection, in particular of isoleucine. As such, it provides an example of how computational modelling can complement more canonical approaches to gain insight into host-virus crosstalk and to identify potential therapeutic strategies.
Multisite Test-Retest Reliability and Compatibility of Brain Metrics derived from FreeSurfer Versions 7.1, 6.0, and 5.3
Authors: Haddad Elizabeth , Pizzagalli Fabrizio , Zhu Alyssa H. , Bhatt Ravi R. , Islam Tasfiya , Gari Iyad Ba , Dixon Daniel , Thomopoulos Sophia I. , Thompson Paul M. , Jahanshad Neda 
Published: April 2022

AbstractAutomatic neuroimaging segmentation and parcellation tools provide convenient and systematic methods for extracting numerous features from brain MRI scans, and are becoming standard practice for large-scale coordinated studies. One such tool, FreeSurfer, provides an easy-to-use pipeline to extract metrics describing cortical and subcortical morphometry. Over the past two decades, there have been over 25 stable releases of FreeSurfer, and different versions are used across published works. Despite this, the reliability and compatibility of metrics derived from the most recent major version releases have yet to be assessed empirically. Here, we use test-retest data from three public brain MRI datasets to assess within-version reliability and between-version compatibility across 42 regional outputs from three versions of FreeSurfer: the latest, v7.1, and two previous stable releases - v5.3, and v6.0. We find v7.1 was less compatible with older versions for measuring cortical thickness. In particular, the thickness of the cingulate gyrus had low compatibility (intraclass correlation coefficient (ICC) between 0.37 and 0.61) between versions. Temporal and frontal poles, and the medial orbitofrontal surface area metrics, also showed low to moderate compatibility with v7.1. While our work compares all three versions, our sub-comparisons between the older versions (v5.3 and v6.0) replicates earlier findings of low compatibility of pallidum and putamen volumes. Low between-version compatibility was not always indicative of low within-version reliability – all versions showed good to excellent reliability across most regional measures (ICC>0.8). Age associations, quality control metrics, and Dice coefficients in an independent sample of 106 individual scans, processed with all three versions of FreeSurfer, revealed differences in results of downstream statistical analysis. As neuroimaging studies adopt more recently released software, we provide researchers with a reference to highlight the regions and metrics that may yield findings inconsistent with published works using older FreeSurfer software. An interactive viewer for the results is provided at http://data.brainescience.org/Freesurfer_Reliability/