bluuebunny/crossref_metadata_2025_split huggingface dataset:
DGMP: Identifying Cancer Driver Genes by Jointing DGCN and MLP from Multi-Omics Genomic Data
Authors: Zhang Shao-Wu , Xu Jing-Yu , Zhang Tong 
Published: February 2022

AbstractIdentification of cancer driver genes plays an important role in precision oncology research, which is helpful to understand the cancer initiation and progression. However, most of existing computational methods mainly used the protein-protein interaction networks (PPIs), or treated the directed gene regulatory networks (GRNs) as the undirected gene-gene association networks to identify the cancer driver genes, which will lose the unique structure regulatory information in the directed GRNs, and then affect the outcome of the cancer driver genes identification. Here, based on the multi-omics pan-cancer data (i.e., gene expression, mutation, copy number variation and DNA methylation), we proposed a novel method (called DGMP) to identify cancer driver genes by jointing Directed Graph Convolution Network (DGCN) and Multilayer Perceptron (MLP). DGMP learns the multi-omics features of genes as well as the topological structure features in GRN with DGCN model, and uses MLP to weight more on gene features for mitigating the bias toward the graph topological features in DGCN learning process. The results on three gene regulation networks show that DGMP outperforms other existing state-of-the-art methods. It can not only identify highly mutated cancer driver genes but also the driver genes harboring other kinds of alterations (e.g., differential expression, aberrant DNA methylation) or genes involved in GRNs with other cancer genes. The source code of DGMP can be freely downloaded fromhttps://github.com/NWPU-903PR/DGMP.
Population structure and inbreeding in wild house mice (Mus musculus) at different geographic scales
Authors: Morgan Andrew P , Hughes Jonathan J , Didion John P , Jolley Wesley J , Campbell Karl J , Threadgill David W , Bonhomme Francois , Searle Jeremy B , de Villena Fernando Pardo-Manuel 
Published: February 2022

AbstractHouse mice (Mus musculus) have spread globally as a result of their commensal relationship with humans. In the form of laboratory strains, both inbred and outbred, they are also among the most widely-used model organisms in biomedical research. Although the general outlines of house mouse dispersal and population structure are well known, details have been obscured by either limited sample size or small numbers of markers. Here we examine ancestry, population structure and inbreeding using SNP microarray genotypes in a cohort of 814 wild mice spanning five continents and all major subspecies of Mus, with a focus on M. m. domesticus. We find that the major axis of genetic variation in M. m. domesticus is a south-to-north gradient within Europe and the Mediterranean. The dominant ancestry component in North America, Australia, New Zealand and various small offshore islands is of northern European origin. Next we show that inbreeding is surprisingly pervasive and highly variable, even between nearby populations. By inspecting the length distribution of homozygous segments in individual genomes, we find that inbreeding in commensal populations is mostly due to consanguinity. Our results offer new insight into the natural history of an important model organism for medicine and evolutionary biology.
Call count surveys as a tool to monitor habitats occupied by Cheer Pheasants (Catreus wallichii) in Shimla, Himachal Pradesh
Authors: Tiwari Samakshi , Ranganathan Lakshminarasimha , Kumar Sanjeev , Sharma Rajesh 
Published: February 2022

AbstractThe vulnerable Cheer Pheasant (Catreus wallichii) is found in the western Himalayas. It prefers successional grasslands which are maintained by residents near villages. Therefore, it is prone to anthropogenic pressures which have led to local extinctions and a decline in population. We conducted five call count surveys at dusk and dawn from 15 April – 15 May 2020 in grasslands of Dharbhog panchayat, Shimla, Himachal Pradesh to assess presence of Cheer Pheasants in different habitat types. We used frequency of occurrence (number of encounters / number of visits) to determine presence or absence of Cheer Pheasant in an area of 10.5 km2 with ten established call count stations. We encountered Cheer Pheasants at six call count stations and the frequency of occurrence of the species ranged from 0 – 0.60. This survey provides an index of occupancy of the species and can be used to assess the change in habitat occupied by the species with time. The local forest department can also use these results to regulate over grazing and burning of grasslands during the breeding season in areas where we recorded the species.
Transkingdom mechanism of MAMP generation by chitotriosidase (CHIT1) feeds oligomeric chitin from fungal pathogens and allergens into TLR2-mediated innate immune sensing
Authors: Chang Tzu-Hsuan , Gloria Yamel Cardona , Hellmann Margareta J. , Greve Carsten Leo , Le Roy Didier , Roger Thierry , Bork Francesca , Bugl Stefanie , Jakob Johanna , Kasper Lydia , Hube Bernhard , Pusch Stefan , Gow Neil , Sørlie Morten , Tøndervik Anne , Moerschbacher Bruno M. , Weber Alexander N.R. 
Published: February 2022

AbstractChitin is a highly abundant polysaccharide in nature and linked to immune recognition of fungal infections and asthma in humans. Ubiquitous in fungi and insects, chitin is absent in mammals and plants and, thus, represents a microbe-associated molecular pattern (MAMP). However, the highly polymeric chitin is insoluble, which potentially hampers recognition by host immune sensors. In plants, secreted chitinases degrade polymeric chitin into diffusible oligomers, which are ‘fed to’ innate immune receptors and co-receptors. In human and murine immune cells, a similar enzymatic activity was shown for human chitotriosidase (CHIT1) and oligomeric chitin is sensed via an innate immune receptor, Toll-like receptor (TLR) 2. However, a complete system of generating MAMPs from chitin and feeding them into a specific receptor/co-receptor-aided sensing mechanism has remained unknown in mammals. Here, we show that the secreted chitinolytic host enzyme, CHIT1, converts inert polymeric chitin into diffusible oligomers that can be sensed by TLR1-TLR2 co-receptor/receptor heterodimers, a process promoted by the lipopolysaccharide binding protein (LBP) and CD14. Furthermore, we observed thatChit1is induced via the β-glucan receptor Dectin-1 upon direct contact of immortalized human macrophages to the fungal pathogenCandida albicans, whereas the defined fungal secreted aspartyl proteases, Sap2 and Sap6, fromC. albicanswere able to degrade CHIT1 in vitro. Our study shows the existence of an inducible system of MAMP generation in the human host that enables contact-independent immune activation by diffusible MAMP ligands with striking similarity to the plant kingdom. Moreover, this study highlights CHIT1 as a potential therapeutic target for TLR2-mediated inflammatory processes that are fueled by oligomeric chitin.
Development of a Novel Peptide Aptamer that Interacts with the eIF4E Capped-mRNA Binding Site using Peptide Epitope Linker Evolution (PELE)
Authors: Frosi Yuri , Ng Simon , Lin Yen-Chu , Jiang Shimin , Ramlan Siti Radhiah , Lama Dilraj , Verma Chandra S , Asial Ignacio , Brown Christopher J 
Published: February 2022

AbstractIdentifying new binding sites and poses that modify biological function are an important step towards drug discovery. We have identified a novel disulphide constrained peptide that interacts with the cap-binding site of eIF4E, an attractive therapeutic target that is commonly overexpressed in many cancers and plays a significant role in initiating a cancer specific protein synthesis program though binding the 5’cap (7’methyl-guanoisine) moiety found on mammalian mRNAs. The use of disulphide constrained peptides to explore intracellular biological targets is limited by their lack of cell permeability and the instability of the disulphide bond in the reducing environment of the cell, loss of which results in abrogation of binding. To overcome these challenges, the cap-binding site interaction motif was placed in a hypervariable loop on an VH domain, and then selections performed to select a molecule that could recapitulate the interaction of the peptide with the target of interest in a process termed Peptide Epitope Linker Evolution (PELE). A novel VH domain was identified that interacted with the eIF4E cap binding site with a nanomolar affinity and that could be intracellularly expressed in mammalian cells. Additionally, it was demonstrated to specifically modulate eIF4E function by decreasing cap-dependent translation and cyclin D1 expression, common effects of eIF4F complex disruption.
Babesia divergensegress from host cells is orchestrated by essential and druggable kinases and proteases
Authors: Elsworth Brendan , Keroack Caroline D. , Rezvani Yasaman , Tennessen Jacob A. , Sack Samantha A. , Paul Aditya S. , Moreira Cristina K. , Gubbels Marc-Jan , Zarringhalam Kourosh , Duraisingh Manoj T. 
Published: February 2022

SummaryA unique aspect of apicomplexan biology is the requirement for egress from and invasion into host red blood cells (RBCs). The cellular mechanisms and molecular mediators of RBC egress and invasion remain poorly characterized inBabesiaspp., a group of parasites of veterinary importance and emerging cause of zoonotic disease. Through the use of video microscopy, transcriptomics, and chemical genetics we have implicated signaling, proteases and gliding motility in egress and/or invasion byBabesia divergens. We developed CRISPR/Cas9 and two inducible knockdown systems to perform a genetic screen of putative mediators of egress. We found that proteases ASP2 and ASP3 are required for invasion, and the latter is also required for egress. Strikingly, parasites continue to replicate intracellularly in the absence of the protein kinases, PKG or CDPK4, indicating that they are required for exit from the replication cycle and egress. These essential molecules present druggable targets forBabesia spp. All together we have established a molecular framework for the spread of infection through host RBCs, with egress ofB. divergensmore closely resemblingT. gondiithan the more evolutionarily relatedPlasmodiumspp.HighlightsEgress inBabesia divergensrequires host cell lysis and parasite motilityTranscriptomics can be used to identify egress and invasion proteinsKnockdown of the proteases, ASP2 and ASP3, inhibit egress and invasionInhibition of PKG or CDPK4 signaling results in continued intracellular replication
Photo-Electrochemical Stimulation of Neurons with Organic Donor-Acceptor Heterojunctions
Authors: Savva Achilleas , Hama Adel , Herrera-López Gabriel , Gasparini Nicola , Migliaccio Ludovico , Kawan Malak , Steiner Nadia , McCulloch Iain , Baran Derya , Fiumelli Hubert , Magistretti Pierre , Głowacki Eric D. , Inal Sahika 
Published: February 2022

AbstractRecent advancements in light-responsive materials enabled the development of devices to artificially activate tissue with light, and show great potential for use in different types of therapy. Photo-stimulation based on organic semiconductors has recently attracted interest due to their unique set of properties such as biocompatibility, better mechanical match with human tissue, and strong absorption of light in the visible spectrum. Here we show the development of solution processed organic heterojunctions that are able to control the activity of primary neurons in vitro with light. The p-type polymer semiconductor PDCBT and the n-type polymer semiconductor ITIC (also known as non-fullerene acceptor) are simply spin coated on glass substrates forming a bilayer p-n junction with high photo-sensitivity in aqueous electrolytes. Photo-electrochemical measurements reveal that high photo-voltage and photo-current is produced, as a result of a charge transfer between the polymers and oxygen in the electrolyte. The biocompatibility of the proposed materials is addressed with live/dead assays on both primary mouse cortical neurons and human cell lines that are cultured on their surface. We have found that light of low intensity (i.e. 40 mW/cm2) is absorbed, and converted into a cue that triggers action potential on primary cortical neurons directly cultured on glass/PDCBT/ITIC interfaces as proven by patch clamp measurements. The activation of neurons is most likely due to photochemical reactions at the polymer/electrolyte interface that result in hydrogen peroxide, which might lead to modulation of specific ion channels on neurons membrane. Photo-thermal effects are excluded with controlled patch clamp measurements on neurons cultured on plain glass and on photoresist thin films. The profound advantages of low intensity light stimulation, simplified fabrication, and wireless operation pave the way for the integration of these interfaces in multiplex bioelectronic devices for the development of novel light therapy concepts and powerful neuroscience research tools.
Modularity in temporal co-occurrence networks at a stopover site reveals strong co-migration fidelity in African-European migratory landbirds over time
Authors: Bellisario Bruno , Cardinale Massimiliano , Maggini Ivan , Fusani Leonida , Carere Claudio 
Published: February 2022

AbstractMigratory species are changing the timing of departures from wintering areas and arrival to breeding sites (i.e., migration phenology), as response to climate change to exploit maximum food availability at higher latitudes and improve their fitness. Despite the impact of changing migration phenology on migratory connectivity at population and community level, the extent to which such individual and species-specific response affects associations among co-migrating species has been seldom explored. By applying temporal co-occurrence network models on 15 years of standardized bird ringing data at a spring stopover site, we show that African-European migratory landbirds tend to migrate in well-defined groups of species with high temporal overlap. Such ‘co-migration fidelity’ is significantly increasing over the years and higher in trans-Saharan than North-African migrants. Our findings suggest non-random patterns of associations in co-migrating species, possibly related to the existence of regulatory mechanisms associated with changing climate conditions and different uses of stopover sites by migrants, ultimately influencing the global migration economy of landbirds in the Palearctic-African migration system.
Inhibiting Runx1 protects heart function after myocardial infarction
Authors: Martin Tamara P , MacDonald Eilidh A , Bradley Ashley , Watson Holly , Saxena Priyanka , Rog-Zielinska Eva A. , Fisher Simon , Elbassioni Ali Ali Mohamed , Almuzaini Ohood , Booth Catriona , Campbell Morna , Herzyk Pawel , Blyth Karen , Nixon Colin , Zentilin Lorena , Berry Colin , Braun Thomas , Giacca Mauro , McBride Martin W , Nicklin Stuart A , Cameron Ewan R , Loughrey Christopher M 
Published: February 2022

ABSTRACTMyocardial infarction is a major cause of death worldwide. Effective treatments are required that limit adverse cardiac remodelling and preserve cardiac contractility following myocardial infarction, with the aim of improving patient outcomes and preventing progression to heart failure. The perfused but hypocontractile myocardium bordering a newly created infarct is functionally distinct from the remote surviving myocardium; it is also a major determinant of adverse cardiac remodelling and whole heart contractility. Expression of the transcription factor RUNX1 is increased in the border zone at 1 day after myocardial infarction, suggesting potential for targeted therapeutic intervention. Here we demonstrate that RUNX1 drives reductions in cardiomyocyte contractility, sarcoplasmic reticulum-mediated calcium release, mitochondrial density, and the expression of genes important for oxidative phosphorylation.Antagonising RUNX1 expression via short-hairpin RNA interference preserved cardiac contractile function following myocardial infarction when delivered either via direct adenoviral delivery into the border zone or via an adeno-associated virus vector administered intravenously. Equivalent effects were obtained with a small molecule inhibitor (Ro5-3335) that reduces RUNX1 function by blocking its interaction with the essential co-factor CBFβ. Both tamoxifen-inducible Runx1-deficient and Cbfβ-deficient cardiomyocyte-specific mouse models demonstrated that antagonising RUNX1 function preserves the expression of genes important for oxidative phosphorylation following myocardial infarction. Our results confirm the translational potential of RUNX1 as a novel therapeutic target in myocardial infarction, with wider opportunities for use across a range of cardiac diseases where RUNX1 drives adverse cardiac remodelling.
Dense satellite data reveals landscape connectivity decline in the Andes-Amazon region
Authors: Murillo-Sandoval Paulo J. , Clerici Nicola , Correa-Ayram Camilo 
Published: February 2022

AbstractThere is a complex interplay of criminal groups’ control over land, illicit activities, and forest cover change in the Colombian Andes-Amazon region. This area is dealing with diverse forms of conflict andpeace,directly impacting landscape connectivity. While many studies have documented rapid deforestation after the peace agreement in 2016, we know little about the effect of these socio-political changes on the state of landscape connectivity. We disentanglehabitatfromconnected habitatin forest ecosystems using the Landsat archive and landscape connectivity indices. We find that in the Andes-Amazon region during 2000-2020,connected habitatloss reached 18%, whilehabitatloss was 13%. This result is worrisome, because it indicates that well-connected patches are more fragmented and isolated, affecting the natural connections between the Andes and Amazon biogeographical regions and the movement ability of species. The Colombian government should conduct a strategicpeacebuildingprocess incorporating structural changes that prevent the increase of large-scale extractive activities that are often illegal in the region. While finding a balance between extractive activities and conservation remains a big challenge, legal land tenure, census/taxation, and specific agreements with local actors can initially prevent deforestation. We discourage localized military actions and the return of aerial fumigation of coca fields, which rather than stop deforestation might exacerbate land cover change deeper into pristine forests.
Strigolactones are chemoattractants for host tropism in Orobanchaceae parasitic plants
Authors: Ogawa Satoshi , Cui Songkui , White Alexandra R.F. , Nelson David C. , Yoshida Satoko , Shirasu Ken 
Published: February 2022

AbstractParasitic plants are worldwide threats that damage major agricultural crops. To initiate infection, parasitic plants have developed the ability to locate hosts and grow towards them. This ability, called host tropism, is critical for parasite survival, but its underlying mechanism remains mostly unresolved. To characterize host tropism, we used the model facultative root parasite Phtheirospermum japonicum, a member of the Orobanchaceae. Here, we show that strigolactones (SLs) function as host-derived chemoattractants. Chemotropism to SLs is also found in Striga hermonthica, a parasitic member of the Orobanchaceae, but not in non-parasites. Intriguingly, chemotropism to SLs in P. japonicum is attenuated in ammonium ion-rich conditions, where SLs are perceived, but the resulting asymmetrical accumulation of the auxin transporter PIN2 is diminished. P. japonicum encodes putative receptors that sense exogenous SLs, whereas expression of a dominant-negative form reduces its chemotropic ability. We propose a new function for SLs as navigators for parasite roots.
Interaction mechanism between the HSV-1 glycoprotein B and the antimicrobial peptide Amyloid-β
Authors: Bourgade Karine , Frost Eric H. , Dupuis Gilles , Witkowski Jacek M. , Laurent Benoit , Calmettes Charles , Ramassamy Charles , Desroches Mathieu , Rodrigues Serafim , Fülöp Tamás 
Published: February 2022

AbstractUnravelling the mystery of Alzheimer’s Disease (AD) requires urgent resolution given the worldwide increase of the aging population. There is a growing concern that the current leading AD hypothesis, the amyloid cascade hypothesis, does not stand up to validation with respect to emerging new data. Indeed, several paradoxes are being discussed in the literature, for instance, both the deposition of the Amyloid-Beta peptide (Aβ) and the intracellular neurofibrillary tangles (NFTs) could occur within the brain without any cognitive pathology. Thus, these paradoxes suggest that something more fundamental is at play in the onset of the disease and other key and related pathomechanisms have to be investigated. The present study follows our previous investigations on the infectious hypothesis, which posits that some pathogens are linked to late onset AD. Our studies also build upon the shattering finding that Aβ is a powerful antimicrobial agent capable of inhibiting pathogens as observed in in vitro experiments. Herein, we ask what are the molecular mechanisms in play when Aβ neutralizes infectious pathogens? To answer this question, we probed at nanoscale lengths with FRET (Förster Resonance Energy Transfer), the interaction between Aβ peptides and glycoprotein B (responsible of virus-cell binding) within the HSV-1 virion. We concluded that there is indeed a close interaction, likely nonspecific or semi-specific, between the two types of molecules, which participate in virus neutralization.