bluuebunny/crossref_metadata_2025_split huggingface dataset:
TGF-β1 induced S100 family protein expression is associated with epithelial to mesenchymal transition states and poor survival in pancreatic cancer
Authors: Jie Low Ronnie Ren , Fung Ka Yee , Gao Hugh , Preaudet Adele , Dagley Laura F. , Yousef Jumana , Lee Belinda , Larsen Rune H. , Kershaw Nadia J. , Burgess Antony W. , Gibbs Peter , Hollande Frédéric , Griffin Michael D.W. , Grimmond Sean M. , Putoczki Tracy L. 
Published: February 2022

SUMMARYEpithelial-mesenchymal transition (EMT) is a continuum that includes epithelial, partial EMT (P-EMT) and mesenchymal states, each of which are associated with cancer progression, invasive capabilities and ultimately metastasis. We have employed a lineage traced sporadic model of pancreatic cancer to generate a murine organoid biobank from primary and secondary tumors, including sublines that have undergone P-EMT and complete EMT (C-EMT). Using an unbiased proteomics approach, we found that the morphology of the organoids predicts the EMT state, with solid organoids associated with a P-EMT signature. We also observed that exogenous TGFβ1 induces a solid organoid morphology that is associated with changes in the S100 family, C-EMT and the formation of high-grade tumors. S100A4 may represent a useful biomarker to predict EMT state, disease progression and outcome for pancreatic cancer patients.
Infection by a eukaryotic gut parasite in wild Daphnia sp. associates with a distinct bacterial community
Authors: Rajarajan Amruta , Wolinska Justyna , Walser Jean-Claude , Mäder Minea , Spaak Piet 
Published: February 2022

AbstractHost-associated bacterial communities can play an important role in host fitness and resistance to diseases. Yet, few studies have investigated tripartite interaction between a host, parasite and host-associated bacterial communities in natural settings. Here, we use 16S amplicon sequencing to compare gut- and body-bacterial communities of wild water fleas belonging to the Daphnia longispina complex, between uninfected hosts and those infected with the common and virulent eukaryotic gut parasite Caullerya mesnili (Family: Ichthyosporea). We report community-level changes in host-associated bacteria with the presence of the parasite infection; namely decreased alpha diversity and increased beta diversity at the site of infection, i.e. host gut (but not host body). We also report decreased abundance of bacterial taxa proposed elsewhere to be beneficial for the host, and an appearance of taxa specifically associated with infected hosts. Our study highlights the host-microbiota-infection link in a natural system and raises questions about the role of host-associated microbiota in natural disease epidemics as well as the functional roles of bacteria specifically associated with infected hosts.
Proteomic analysis of human milk reveals nutritional and immune benefits in the colostrum from mothers with COVID-19
Authors: Guo Juanjuan , Tan Minjie , Zhu Jing , Tian Ye , Liu Huanyu , Luo Fan , Wang Jianbin , Huang Yanyi , Zhang Yuanzhen , Yang Yuexin , Wang Guanbo 
Published: February 2022

ABSTRACTThe range of benefits breastfeeding provides neonates and infants include nutrition, improved neonatal survival, and reduced morbidity from certain diseases. It also aids maternal health by speeding postpartum recovery. However, due to concern about the risk of SARS-CoV-2 transmission and the lack of evidence of breastmilk’s protective effects against the virus, whether mothers with COVID-19 should be encouraged to breastfeed is under debate. Here, we present the results of proteomic and glycoproteomic studies of breast milk (colostrum and mature milk) from mothers with confirmed COVID-19. All colostrum samples exhibited significantly upregulated immune-related proteins, especially whey proteins with antiviral properties against SARS-CoV-2, and increased glycosylation levels and heterogeneity at those proteins. Such adaptive differences in milk from COVID-19 mothers tend to fade in mature milk from the same mothers one month postpartum. These results suggest the immune benefits of colostrum from mothers with COVID-19 and provide molecular-level insights that aid breastmilk feeding decisions in cases of active infection.
Data based slurry treatment decision tree to minimise antibiotic resistance and pathogen transfer while maximising nutrient recycling
Authors: Do Thi Thuy , Nolan Stephen , Hayes Nicky , O’Flaherty Vincent , Burgess Catherine , Brennan Fiona , Walsh Fiona 
Published: March 2022

AbstractDirect application of pig slurry to agricultural land, as a means of nutrient recycling, introduces pathogens, antibiotic resistant bacteria, or genes, to the environment. With global environmental sustainability policies mandating a reduction in synthetic fertilisation and a commitment to a circular economy it is imperative to find effective on-farm treatments of slurry that maximises its fertilisation value and minimises risk to health and the environment. We assessed and compared the effect of storage, composting, and anaerobic digestion on pig slurry microbiome, resistome and nutrient content. Shotgun metagenomic sequencing and HT-qPCR arrays were implemented to understand the dynamics across the treatments. Our results identified that each of the treatment methods had advantages and disadvantages, depending on the parameter measured. The data suggests that storage and composting are optimal for the removal of human pathogens and anaerobic digestion for the reduction in AMR genes and mobile genetic elements. The nitrogen content is increased in storage and AD and reduced in composting. Thus, depending on the requirement for increased or reduced nitrogen the optimum treatment varies. Combining the results indicates that composting provides the greatest gain by reducing risk to human health and the environment. Network analysis revealed reducing Proteobacteria and Bacteroidetes while increasing Firmicutes will reduce the AMR content. KEGG analysis identified no significant change in the pathways across all treatments. This novel study provides a data driven decision tree to determine the optimal treatment for best practice to minimise pathogen, AMR and excess or increasing nutrient transfer from slurry to environment.Graphical abstract
Transcriptomic analysis of sorted lung cells revealed a proviral activity of the NF-κB pathway towards SARS-CoV-2
Authors: Bhargava Anvita , Szachnowski Ugo , Chazal Maxime , Foretek Dominika , Aicher Sophie-Marie , Pipoli da Fonseca Juliana , Jeannin Patricia , Beauclair Guillaume , Monot Marc , Morillon Antonin , Jouvenet Nolwenn 
Published: February 2022

AbstractInvestigations of cellular responses to viral infection are commonly performed on mixed populations of infected and uninfected cells or using single-cell RNA sequencing, leading to inaccurate and low-resolution gene expression interpretations. Here, we performed deep polyA+transcriptome analyses and novel RNA profiling of SARS-CoV-2 infected lung epithelial cells, sorted based on the expression of the viral spike (S) protein. Infection caused a massive reduction in mRNAs and lncRNAs, including transcripts coding for antiviral factors, such as interferons (IFN). This absence of IFN signaling probably explained the poor transcriptomic response of bystander cells co-cultured with S+ones. NF-κB pathway and the inflammatory response escaped the global shutoff in S+cells. Functional investigations revealed the proviral function of the NF-κB pathway and the antiviral activity of CYLD, a negative regulator of the pathway. Thus, our transcriptomic analysis on sorted cells revealed additional genes that modulate SARS-CoV-2 replication in lung cells.
A loss-of-function cysteine mutant in fibulin-3 (EFEMP1) forms aberrant extracellular disulfide-linked homodimers and alters extracellular matrix composition
Authors: Woodard DaNae R. , Daniel Steffi , Nakahara Emi , Abbas Ali , DiCesare Sophia M. , Hulleman John D. 
Published: February 2022

ABSTRACTFibulin-3 (F3 or EFEMP1) is a disulfide-rich, secreted glycoprotein necessary for maintaining extracellular matrix (ECM) and connective tissue integrity. Two studies have identified distinct autosomal recessive F3 mutations in individuals with Marfan Syndrome-like phenotypes. Herein we characterized how one of these mutations, c.163T>C; p.Cys55Arg (C55R), disrupts F3 secretion, quaternary structure, and function by forming unique extracellular disulfide-linked homodimers. Dual cysteine mutants suggest that the C55R-induced disulfide species forms because of new availability of Cys70 on adjacent F3 monomers. Surprisingly, mutation of single cysteines located near C55 (i.e., C29, C42, C48, C61, C70, C159, and C171) also produced similar extracellular disulfide-linked dimers, suggesting that this is not a phenomenon isolated to the C55R mutant. To assess C55R functionality, F3 knockout (KO) retinal pigmented epithelial (RPE) were generated, followed by reintroduction of wild-type (WT) or C55R F3. F3 KO cells produced lower levels of the ECM remodeling enzyme, matrix metalloproteinase 2 and reduced formation of collagen VI ECM filaments, both of which were partially rescued by WT F3 overexpression. However, C55R F3 was unable to compensate for these same ECM-related defects. Our results highlight the unique behavior of particular cysteine mutations in F3 and uncover potential routes to restore C55R F3 loss-of-function.
Hand Gesture Prediction via Transient-phase sEMG using Transfer Learning of Dilated Efficient CapsNet: Towards Generalization for Neurorobotics
Authors: Tyacke Eion , Reddy Shreyas P. J. , Feng Natalie , Edlabadkar Rama , Zhou Shucong , Patel Jay , Hu Qin , Atashzar S. Farokh 
Published: March 2022

AbstractThere has been an accelerated surge to utilize the deep neural network for decoding central and peripheral activations of the human’s nervous system to boost up the spatiotemporal resolution of neural interfaces used in neurorobotics. Such algorithmic solutions are motivated for use in human-centered robotic systems, such as neurorehabilitation, prosthetics, and exoskeletons. These methods are proved to achieve higher accuracy on individual data when compared with the conventional machine learning methods but are also challenged by their assumption of having access to massive training samples.ObjectiveIn this letter, we propose Dilated Efficient CapsNet to improve the predictive performance when the available individual data is very minimum and not enough to train an individualized network for controlling a personalized robotic system.MethodWe proposed the concept of transfer learning using a new design of the dilated efficient capsular neural network to relax the need of having access to massive individual data and utilize the field knowledge which can be learned from a group of participants. In addition, instead of using complete sEMG signals, we only use the transient phase, reducing the volume of training samples to 20% of the original and maximizing the agility.ResultsIn experiments, we validate our model performance with various amounts of injected personalized training data (25%-100% of transient phase) that is segmented once by time and once by repetition. The results of this paper support the use of transfer learning using a dilated capsular neural network and show that with the use of such a model, the knowledge domain learned on a small number of subjects can be utilized to minimize the need for new data of new subjects while focusing only on the transient phase of contraction (which is a challenging neural interfacing problem).
PSMA-bearing extracellular vesicles secreted from prostate cancer convert the microenvironment to a tumor-supporting, pro-angiogenic state
Authors: Machado Camila Maria Longo , Skubal Magdalena , Haedicke Katja , Silva Fabio Pittella , Stater Evan Paul , de Oliveira Silva Thais Larissa Araujo , Costa Erico Tosoni , Masotti Cibele , Otake Andreia Hanada , Andrade Luciana Nogueira Sousa , de Souza Junqueira Mara , Hsu Hsiao-Ting , Das Sudeep , Larney Benedict Mc , Pratt Edwin Charles , Romin Yevgeniy , Fan Ning , Manova-Todorova Katia , Pomper Martin , Grimm Jan 
Published: February 2022

AbstractExtracellular vesicles (EV) are comprised of vesicles budding from cell membranes and smaller intracellular vesicles shed by cells. EV play a role in remodeling the tumor microenvironment (TME) and support tumor progression. Prostate-specific membrane antigen (PSMA) is a transmembrane glycoprotein with a carboxypeptidase function, frequently associated with poor clinical prognosis in prostate cancer (PCa). We previously identified an oncogenic PSMA signaling function in prostate cancer. Others demonstrated that EV isolated from the plasma of patients with high-grade PCa carry PSMA, but so far no pathophysiological effect has been associated with PSMA-bearing EV. Here we demonstrate that EV from PCa cells are able to transfer PSMA and its functionality to cells in the TME. The consequence of that EV-mediated PSMA transfer is an acute to long-term increased secretion of vascular endothelial growth factor-A (VEGF-A), angiogenin, pro-angiogenic and pro-lymphangiogenic mediators and increased 4E binding protein 1 (4EBP-1) phosphorylation in tumors. We compare EV from PCa cells with or without PSMA expression to address the role of PSMA-bearing EV in promoting pro-tumoral changes in the TME using classical molecular biology and novel molecular imaging approaches.
Estimating the overall fraction of phenotypic variance attributed to high-dimensional predictors measured with error
Authors: Mandal Soutrik , Kim Do Hyun , Hua Xing , Li Shilan , Shi Jianxin 
Published: March 2022

AbstractIn prospective genomic studies (e.g., DNA methylation, metagenomics, and transcriptomics), it is crucial to estimate the overall fraction of phenotypic variance (OFPV) attributed to the high-dimensional genomic variables, a concept similar to heritability analyses in genome-wide association studies (GWAS). Unlike genetic variants in GWAS, these genomic variables are typically measured with error due to technical limitation and temporal instability. While the existing methods developed for GWAS can be used, ignoring measurement error may severely underestimate OFPV and mislead the design of future studies. Assuming that measurement error variances are distributed similarly between causal and noncausal variables, we show that the asymptotic attenuation factor equals to the average intraclass correlation coefficients of all genomic variables, which can be estimated based on a pilot study with repeated measurements. We illustrate the method by estimating the contribution of microbiome taxa to body mass index and multiple allergy traits in the American Gut Project. Finally, we show that measurement error does not cause meaningful bias when estimating the correlation of effect sizes for two traits.
Fine-scale survey of intertidal macroalgae reveals recent changes in a cold-water biogeographic stronghold
Authors: Monteiro Cátia , Pereira Joana , Seabra Rui , Lima Fernando P. 
Published: March 2022

AbstractGlobal warming has been causing severe impacts on marine ecosystems, a notorious one being shifts in the geographical ranges of species. The north-western coast of the Iberian Peninsula is an especially interesting zone to study distributional shifts as it has a strong latitudinal thermal gradient, is influenced by the Canary upwelling system (which partially cancels coastal warming) and holds some of the most diverse macroalgae communities in Europe. Notably, it is within this region that many cold-water species, common in northern Europe, have their southernmost distribution refuge. Recent studies hypothesize that the environmental conditions may be nonetheless changing and already threatening this biodiversity hotspot.The main goal of this study was to carry out a fine-scale assessment of the distributional limits of several macroalgae in North-western Iberia, as well as identify possible population and range shifts using historical data (2001-2005) as reference. In addition, invasive species were also surveyed. We also assessed if the regions of (i) Galicia, (ii) Northern Portugal, and (iii) Central Portugal displayed distinctive characters regarding macroalgae composition and abundance.We identified an increase in abundance of some invasive macroalgae as well as a decrease in the abundance of some cold-water species. In the most severe cases, cold-water species were extirpated along hundreds of km. The compounded effect of the decrease in the abundance of cold-water species and the increase in the abundance of invasive species is leading to the homogenization of macroalgae communities in north-western Iberia.
Zebrafish her3 knockout impacts developmental and cancer-related gene signatures
Authors: Kent Matthew R. , Calderon Delia , Silvius Katherine M. , LaVigne Collette A. , Cannon Matthew V. , Kendall Genevieve C. 
Published: February 2022

AbstractHES3 is a basic helix-loop-helix transcription factor that regulates neural stem cell renewal during development. HES3 overexpression is predictive of reduced overall survival in patients with fusion-positive rhabdomyosarcoma, a pediatric cancer that resembles immature and undifferentiated skeletal muscle. However, the mechanisms of HES3 cooperation in fusion-positive rhabdomyosarcoma are unclear and are likely related to her3/HES3’s role in neurogenesis. To investigate HES3’s function during development, we generated a zebrafish CRISPR/Cas9 knockout of her3, the zebrafish ortholog of HES3. Loss of her3 is not embryonic lethal and adults exhibit expected Mendelian ratios. Embryonic her3 zebrafish mutants are significantly smaller than wildtype and a subset present with lens defects as adults. Transcriptomic analysis of her3 mutant embryos indicates that genes involved in organ development, such as pctp and grinab, are significantly downregulated. Further, differentially expressed genes in her3 knockout embryos are enriched for HOX and SOX10 motifs. Several cancer-related gene pathways are impacted, including the inhibition of matrix metalloproteinases. Altogether, this new model is a powerful system to study her3/HES3-mediated neural development and its misappropriation in cancer contexts.Summary StatementHere, we generate and characterize a zebrafish her3/HES3 knockout to elucidate the functional role of her3/HES3, a transcriptional repressor, in neural development and tumorigenic processes.
A Tensor Decomposition Uncovers the Effect of Ageing on Muscle and Grip-Load Force Couplings During Grasping
Authors: Ye Chang , Saboksayr Seyed Saman , Shaw William , Coats Rachel O. , Astill Sarah L. , Mateos Gonzalo , Delis Ioannis 
Published: March 2022

ABSTRACTDo motor patterns of grasp-to-lift movements change as a result of ageing? Previous studies often relied on simple temporal and kinetic variables to unveil differences caused by ageing, yet their neuromuscular origins remain largely unknown. Here we employed a bimanual grasping protocol with younger and older adults and combined measurements of muscle activity with grip and load forces to provide a window into the neuromuscular strategies underlying effective grasping. We introduced a tensor decomposition to identify patterns of muscle activity and grip-load force ratios while also characterising their temporal profiles and relative activation across object weights and participants of different age groups. This approach extracted the motor components underpinning object grasping across participants. We then probed age-induced changes in these components. A classification analysis revealed two motor components that are differentially recruited between the two age groups. Linear regression analyses further showed that advanced age and poorer manual dexterity can be predicted by the coupled activation of forearm and hand muscles which is associated with high levels of grip force. Our findings suggest that ageing may induce stronger muscle couplings in distal aspects of the upper limbs, and a less economic grasping strategy to overcome age-related decline in manual dexterity.
Structural basis for the simultaneous recognition of NEMO and acceptor ubiquitin by the HOIP NZF1 domain
Authors: Rahighi Simin , Iyer Mamta , Oveisi Hamid , Nasser Sammy , Duong Vincent 
Published: February 2022

SummaryUbiquitination of NEMO by the linear ubiquitin chain assembly complex (LUBAC) is essential for activating the canonical NF-κB signaling pathway. While the NZF1 domain of the HOIP subunit of LUBAC recognizes the NEMO substrate, it is unclear how it cooperates with the catalytic domains in the ubiquitination process. Here, we report a crystal structure of NEMO in complex with HOIP NZF1 and linear diubiquitin chains, in which the two proteins bind to distinct sites on NEMO. Moreover, the NZF1 domain simultaneously interacts with NEMO and Ile44 surface of a proximal ubiquitin from a linear diubiquitin chain, where the C-term tail of the ubiquitin is in the proximity of the NEMO ubiquitination site (Lys285). We further propose a model for the linear ubiquitination of NEMO by HOIP. In the model, NZF1 binds the monoubiquitinated NEMO and recruits the catalytic domains to the ubiquitination site, thereby ensuring site-specific ubiquitination of NEMO.
Rapid weed adaptation and range expansion in response to agriculture over the last two centuries
Authors: Kreiner Julia M. , Latorre Sergio M. , Burbano Hernán A. , Stinchcombe John R. , Otto Sarah P. , Weigel Detlef , Wright Stephen I. 
Published: March 2022

AbstractNorth America has seen a massive increase in cropland use since 1800, accompanied more recently by the intensification of agricultural practices. Through genome analysis of present-day and historical samples spanning environments over the last two centuries, we studied the impact of these changes in farming on the extent and tempo of evolution across the native range of common waterhemp (Amaranthus tuberculatus), a now pervasive agricultural weed. Modern agriculture has imposed strengths of selection rarely observed in the wild, with striking shifts in allele frequency trajectories since agricultural intensification in the 1960s. An evolutionary response to this extreme selection was facilitated by a concurrent human-mediated range shift. By reshaping genome-wide diversity across the landscape, agriculture has driven the success of this weed in the 21st-century.One Sentence SummaryModern agriculture has shaped the evolution of a native plant into a weed by driving range shifts and strengths of selection rarely observed in the wild.