bluuebunny/crossref_metadata_2025_split huggingface dataset:
First evidence of virus-like particles in the bacterial symbionts of Bryozoa
Authors: Vishnyakov A.E. , Karagodina N.P. , Lim-Fong G. , Ivanov P.A. , Schwaha T.F. , Letarov A.V. , Ostrovsky A.N. 
Published: April 2020

ABSTRACTBacteriophage communities associated with humans and vertebrate animals have been extensively studied, but the data on phages living in invertebrates remain scarce. In fact, they have never been reported for most animal phyla. Our ultrastructural study showed for the first time a variety of virus-like particles (VLPs) and supposed virus-related structures inside symbiotic bacteria in two marine species from the phylum Bryozoa, the cheilostomesBugula neritinaandParalicornia sinuosa. We also documented the effect of VLPs on bacterial hosts: we explain different bacterial ‘ultrastructural types’ detected in bryozoan tissues as stages in the gradual destruction of prokaryotic cells caused by viral multiplication during the lytic cycle. We speculate that viruses destroying bacteria regulate symbiont numbers in the bryozoan hosts, a phenomenon known in some insects. We develop two hypotheses explaining exo- and endogenous circulation of the viruses during the life-cycle ofB. neritina. Finally, we compare unusual ‘sea-urchin’-like structures found in the collapsed bacteria inP. sinuosawith so-called metamorphosis associated complexes (MACs) known to trigger larval metamorphosis in a polychaete worm.ImportanceComplex symbiotic systems, including metazoan hosts, their bacterial symbionts and bacteriophages are widely studied using vertebrate models whereas much less is known about invertebrates. Our ultrastructural research revealed replication of the viruses and/or activation of virus related elements in the bacterial symbionts inhabiting tissues of the marine colonial invertebrates (phylum Bryozoa). The virus activity in the bacterial cells that are believed to be transmitted exclusively vertically is of a special importance. In addition, in the bacterial symbionts of one of the bryozoan hosts we observed the massive replication of the structures seemingly related to the Metamorphosis associated complexes (MAC). To our knowledge, MACs were never reported in the animal prokaryotic symbionts. Our findings indicate that Bryozoa may be new suitable model to study the role of bacteriophages and phage-related structures in the complex symbiotic systems hosted by marine invertebrates.
Transplantation of Muscle Stem Cell Mitochondria Rejuvenates the Bioenergetic Function of Dystrophic Muscle
Authors: Mohiuddin Mahir , Choi Jeongmoon J. , Lee Nan Hee , Jeong Hyeonsoo , Anderson Shannon E. , Han Woojin M. , Aliya Berna , Peykova Tsvetomira Z. , Verma Sumit , García Andrés J. , Aguilar Carlos A. , Jang Young C. 
Published: April 2020

SummaryMitochondrial dysfunction has been implicated in various pathologies, including muscular dystrophies. During muscle regeneration, resident stem cells, also known as muscle satellite cells (MuSCs), undergo myogenic differentiation to formde novomyofibers or fuse to existing syncytia. Leveraging this cell-cell fusion process, we postulated that mitochondria stemming from MuSCs could be transferred to myofibers during muscle regeneration to remodel the mitochondrial network and restore bioenergetic function. Here, we report that dystrophic MuSCs manifest significant mitochondrial dysfunction and fuse with existing dystrophic myofibers to propagate mitochondrial dysfunction during muscle repair. We demonstrate that by transplanting healthy donor MuSCs into dystrophic host muscle, the mitochondrial network (reticulum) and bioenergetic function can be rejuvenated. Conversely, when bioenergetically-compromised donor MuSCs are transplanted, improvements in mitochondrial organization and bioenergetic function were ablated in the dystrophic recipient. Overall, these data reveal a unique role of muscle stem cells as an essential regulator of myofiber mitochondrial homeostasis and a potential therapeutic target against mitochondrial myopathies.
Phosphoproteomics Reveals a Distinct Mode of Mec1/ATR Signaling in Response to DNA End Hyper-Resection
Authors: Sanford Ethan J. , Faça Vitor M. , Vega Stephanie C. , Comstock William J. , Smolka Marcus B. 
Published: April 2020

ABSTRACTThe Mec1/ATR kinase is crucial for genome maintenance in response to a range of genotoxic insults, although how it promotes context-dependent signaling and DNA repair remains elusive. Here we uncovered a specialized mode of Mec1/ATR signaling triggered by the extensive nucleolytic processing (resection) of DNA ends. Cells lackingRAD9, a checkpoint activator and an inhibitor of resection, exhibit a selective increase in Mec1-dependent phosphorylation of proteins associated with single strand DNA transactions, including the ssDNA binding protein Rfa2, the translocase/ubiquitin ligase Uls1 and the HR-regulatory Sgs1-Top3-Rmi1 (STR) complex. Extensive Mec1-dependent phosphorylation of the STR complex, mostly on the Sgs1 helicase subunit, promotes an interaction between STR and the DNA repair scaffolding protein Dpb11. Fusion of Sgs1 to phosphopeptide-binding domains of Dpb11 strongly impairs HR-mediated repair, supporting a model whereby Mec1 signaling regulates STR upon hyper-resection to influence recombination outcomes. Overall, the identification of a distinct mode of Mec1 signaling triggered by hyper-resection highlights the multi-faceted action of this kinase in the coordination of checkpoint signaling and HR-mediated DNA repair.
Archaeogenetic analysis of Neolithic sheep from Anatolia suggests a complex demographic history since domestication
Authors: Yurtman Erinç , Özer Onur , Yüncü Eren , Dağtaş Nihan Dilşad , Koptekin Dilek , Çakan Yasin Gökhan , Özkan Mustafa , Akbaba Ali , Kaptan Damla , Atağ Gözde , Vural Kıvılcım Başak , Gündem Can Yümni , Martin Louise , Kılınç Gülşah Merve , Ghalichi Ayshin , Açan Sinan Can , Yaka Reyhan , Sağlıcan Ekin , Lagerholm Vendela Kempe , Krzewinska Maja , Pişkin Evangelia , Şevketoğlu Müge , Bilgin C. Can , Atakuman Çiğdem , Erdal Yılmaz Selim , Sürer Elif , Lenstra Johannes , Yorulmaz Sevgi , Abazari Foad , Hoseinzadeh Javad , Baird Douglas , Bıçakçı Erhan , Çevik Özlem , Gerritsen Fokke , Özbal Rana , Götherström Anders , Somel Mehmet , Togan İnci , Özer Füsun 
Published: April 2020

AbstractSheep was among the first domesticated animals, but its demographic history is little understood. Here we present combined analyses of mitochondrial and nuclear polymorphism data from ancient central and west Anatolian sheep dating to the Late Glacial and early Holocene. We observe loss of mitochondrial haplotype diversity around 7500 BCE during the early Neolithic, consistent with a domestication-related bottleneck. Post-7000 BCE, mitochondrial haplogroup diversity increases, compatible with admixture from other domestication centres and/or from wild populations. Analysing archaeogenomic data, we further find that Anatolian Neolithic sheep (ANS) are genetically closest to present-day European breeds, and especially those from central and north Europe. Our results indicate that Asian contribution to south European breeds in the post-Neolithic era, possibly during the Bronze Age, may explain this pattern.
NPC1L1 inhibition disturbs lipid trafficking and induces large lipid droplet formation in intestinal absorptive epithelial cells
Authors: Nakano Takanari , Inoue Ikuo , Takenaka Yasuhiro , Ito Rina , Kotani Norihiro , Sato Sawako , Nakano Yuka , Hirasaki Masataka , Shimada Akira , Murakoshi Takayuki 
Published: April 2020

ABSTRACTEzetimibe inhibits Niemann-Pick C1-like 1 (NPC1L1) protein, which mediates intracellular cholesterol trafficking from the brush border membrane to the endoplasmic reticulum, where chylomicron assembly takes place in enterocytes or in the intestinal absorptive epithelial cells. Cholesterol is a minor lipid component of chylomicrons; however, whether or not a shortage of cholesterol attenuates chylomicron assembly is unknown. The aim of this study was to examine the effect of NPC1L1 inhibition on trans-epithelial lipid transport, and chylomicron assembly and secretion in enterocytes. Caco-2 cells, an absorptive epithelial model, grown onto culture inserts were given lipid micelles from the apical side, and chylomicron-like triacylglycerol-rich lipoprotein secreted basolaterally were analyzed after a 24-h incubation period in the presence of ezetimibe up to 50 μM. The secretion of lipoprotein and apolipoprotein B48 were reduced by adding ezetimibe (30%,p<0.01 and 34%,p<0.05, respectively). Additionally, ezetimibe accelerated intracellular apoB protein degradation by approximately 2.8-fold and activated sterol regulatory element binding protein 2 by approximately 1.5-fold: These are indicators whether the cells are sensing cellular cholesterol shortage. Thus, ezetimibe appeared to limit cellular cholesterol mobilization required for lipoprotein assembly. In such conditions, large lipid droplet formation in Caco-2 cells and the enterocytes in mice were induced, implying that unprocessed triglyceride was sheltered in these compartments. Although ezetimibe did not reduce the post-prandial lipid surge appreciably in triolein-infused mice, the results of the present study indicated that NPC1L1-mediated supply chylomicron with cholesterol may participate in a novel regulatory mechanism for the efficient chylomicron assembly and secretion.
Conservation and divergence of vulnerability and responses to stressors between human and mouse astrocytes
Authors: Li Jiwen , Pan Lin , Godoy Marlesa I. , Pembroke William G. , Rexach Jessica E. , Condro Michael C. , Alvarado Alvaro G. , Harteni Mineli , Chen Yen-Wei , Stiles Linsey , Chen Angela Y. , Wanner Ina B. , Yang Xia , Goldman Steven A. , Geschwind Daniel H. , Kornblum Harley I. , Zhang Ye 
Published: April 2020

SummaryHuman-mouse differences are a major barrier in translational research. Astrocytes play important roles in neurological disorders such as stroke, injury, and neurodegeneration. However, the similarities and differences between human and mouse astrocytes are largely unknown. Combining analyses of acutely purified astrocytes, experiments using serum-free cultures of primary astrocytes, and xenografted chimeric mice, we found extensive conservation in astrocytic gene expression between human and mouse. However, genes involved in defense response and metabolism showed species differences. Human astrocytes exhibited greater susceptibility to oxidative stress than mouse astrocytes, due to differences in mitochondria physiology and detoxification pathways. Mouse astrocytes, but not human astrocytes, activate a molecular program for neural repair under hypoxia. Human astrocytes, but not mouse astrocytes, activate the antigen presentation pathway under inflammatory conditions. These species-dependent properties of astrocytes may contribute to differences between mouse models and human neurological and psychiatric disorders.
gwaRs: an R shiny web application for visualizing genome-wide association studies data
Authors: Nkambule Lethukuthula L 
Published: April 2020

AbstractSummaryAlthough there is an exponential increase and extensive availability of genome-wide association studies data, the visualization of this data remains difficult for non-specialist users. Current software and packages for visualizing GWAS data are intended for specialists and have been developed to accomplish specific functions, favouring functionality over user experience. To facilitate this, we have developed an R shiny web application, gwaRs, that allows any general user to visualize GWAS data efficiently and effortlessly. The gwaRs web-browser interface allows users to visualize GWAS data using SNP-density, quantile-quantile, Manhattan, and Principal Component Analysis plots.AvailabilityThe gwaRs web application is publicly hosted athttps://gwasviz.shinyapps.io/gwaRs/and R source code is released under the GNU General Public License and freely available at GitHub:https://github.com/LindoNkambule/gwaRs.Contactlindonkambule116@gmail.com
c-Fos-MMP-9 pathway in central amygdala mediates approach motivation but not reward consumption
Authors: Lebitko T. , Nowicka K. , Dzik J. , Kanigowski D. , Jędrzejewska-Szmek J. , Chaturvedi M. , Jaworski T. , Nikolaev T. , Gorkiewicz T. , Meyza K. , Urban-Ciecko J. , Kaczmarek L. , Knapska E. 
Published: April 2020

AbstractAlthough impaired motivational and consummatory aspects of reward behavior are core symptoms of several psychiatric disorders, the underlying neural and molecular mechanisms remain poorly understood. c-Fos, as a component of AP-1 transcription factor, regulates the expression of matrix metalloproteinase 9 (MMP-9), an enzyme involved in synaptic remodeling and plasticity. Both proteins are expressed in the central amygdala (CeA) that orchestrates appetitive and aversive responses. We have examined the role of c-Fos and MMP-9 in CeA in reward and punishment processing. We have manipulated c-Fos and MMP-9 levels in vivo using: RNAi-based approach to block c-Fos expression, inhibitor-releasing nanoparticles to block MMP-9 activity, and lentiviral vector to increase MMP-9 expression. To assess motivation, consumption and learning reinforced by either a sweet or bitter-tasting solution, we employed automated behavioral tests in the IntelliCage cystem. We have used transgenic mouse lines to identify CeA cells expressing c-Fos and a specific fluorescently labelled substrate peptide to measure MMP-9 activity. Excitability of neurons was measured with patch-clamp. Blocking c-Fos expression has been found to disrupt both reward processing components, motivational and consummatory, while inhibition of MMP-9 activity has impaired only motivational aspects of the behavior. On the other hand, punishment processing has not been affected by those manipulations. Furthermore, we have observed that reward training induces c-Fos expression in both somatostatin (SST)+, and SST-neurons, while MMP-9 activity is increased in SST- subpopulation only. We have further linked SST+ population to consummatory reactions by showing that reward consumption increases excitability of the SST+ neurons. These findings reveal molecular mechanisms of motivational anhedonia, linking it to c-Fos-MMP-9 pathway and CeA SST- neurons, and consummatory anhedonia, linking it to c-Fos and CeA SST+ neurons.
Mortality of native and invasive ladybirds co-infected by ectoparasitic and entomopathogenic fungi
Authors: Haelewaters Danny , Hiller Thomas , Kemp Emily A. , van Wielink Paul S. , Shapiro-Ilan David I. , Aime M. Catherine , Nedvěd Oldřich , Pfister Donald H. , Cottrell Ted E. 
Published: April 2020

ABSTRACTHarmonia axyridisis an invasive alien ladybird in North America and Europe. Studies show that multiple natural enemies are usingHa. axyridisas a new host. However, thus far, no research has been undertaken to study the effects of simultaneous infections of multiple natural enemies onHa. axyridis. We hypothesized that high thallus densities of the ectoparasitic fungusHesperomyces virescenson a ladybird weaken the host’s defenses, thereby making it more susceptible to infection by other natural enemies. We examined mortality of the North American-nativeOlla v-nigrumandHa. axyridisco-infected withHe. virescensand an entomopathogenic fungus—eitherBeauveria bassianaorMetarhizium anisopliae. Laboratory assays revealed thatHe. virescens-infectedO. v-nigrumindividuals are more susceptible to entomopathogenic fungi, butHa. axyridisdoes not suffer the same effects. This is in line with the enemy release hypothesis, which predicts that invasive alien species in new geographic areas experience reduced regulatory effects from natural enemies compared to native species. Considering our results, we can ask howHe. virescensaffects survival when confronted by other pathogens that previously had little impact onHa. axyridis.
Membrane-bound flurophore-labelled vectors for Targeted DamID allow simultaneous profiling of expression domains and DNA binding
Authors: Delandre Caroline , McMullen John PD , Marshall Owen J 
Published: April 2020

AbstractTargeted DamID (TaDa) allows highly efficient cell-type-specific profiling of protein-DNA interactions. Cell-type-specificity, however, is governed by the GAL4/UAS system, which can exhibit differences in expression patterns depending upon the genomic insertion site and the UAS promoter strength. The TaDa system uses a bicistronic transcript to reduce the translation rates of Dam-fusion proteins, presenting the possibility of using the primary ORF within in the transcript to label expression domains and precisely identified the profiled cell populations in experimental samples. Here, we describe new TaDa vectors, pTaDaG, pTaDaG2 and pTaDaM, that use myristoylated-GFP or myristoylated-mCherry as the primary ORF. Differing lengths of the myristoylation sequence between the two GFP plasmids allows additional translational control. The mCherry plasmid allows profiled cells to be visualised when using the NanoDam system, in which an anti-GFP nanobody is fused to Dam to profile the localisation of GFP-fusion proteins. Fly lines created with this system allow easy visualisation of expression domains under both fluorescent dissecting and confocal microscopes without the use of antibody staining, whilst faithfully profiling protein-DNA interactions via Targeted DamID.
Dissociable electrophysiological measures of natural language processing reveal differences in speech comprehension strategy in healthy ageing
Authors: Broderick Michael P. , Di Liberto Giovanni M. , Anderson Andrew J. , Rofes Adrià , Lalor Edmund C. 
Published: April 2020

AbstractHealthy ageing leads to changes in the brain that impact upon sensory and cognitive processing. It is not fully clear how these changes affect the processing of everyday spoken language. Prediction is thought to play an important role in language comprehension, where information about upcoming words is pre-activated across multiple representational levels. However, evidence from electrophysiology suggests differences in how older and younger adults use context-based predictions, particularly at the level of semantic representation. We investigate these differences during natural speech comprehension by presenting older and younger subjects with continuous, narrative speech while recording their electroencephalogram. We use linear regression to test how distinct computational measures of 1) semantic dissimilarity and 2) lexical surprisal are processed in the brains of both groups. Our results reveal dissociable neural correlates of these two measures that suggest differences in how younger and older adults successfully comprehend speech. Specifically, our results suggest that, while younger and older subjects both employ context-based lexical predictions, older subjects are significantly less likely to pre-activate the semantic features relating to upcoming words. Furthermore, across our group of older adults, we show that the weaker the neural signature of this semantic pre-activation mechanism, the lower a subject’s semantic verbal fluency score. We interpret these findings as prediction playing a generally reduced role at a semantic level in the brains of older listeners during speech comprehension and that these changes may be part of an overall strategy to successfully comprehend speech with reduced cognitive resources.
Disordered Proteins Enable Histone Chaperoning on the Nucleosome
Authors: Heidarsson Pétur O. , Mercadante Davide , Sottini Andrea , Nettels Daniel , Borgia Madeleine B. , Borgia Alessandro , Kilic Sinan , Fierz Beat , Best Robert B. , Schuler Benjamin 
Published: April 2020

SUMMARYProteins with highly charged disordered regions are abundant in the nucleus, where many of them interact with nucleic acids and control key processes such as transcription. The functional advantages conferred by protein disorder, however, have largely remained unclear. Here we show that disorder can facilitate a remarkable regulatory mechanism involving molecular competition. Single-molecule experiments demonstrate that the human linker histone H1 binds to the nucleosome with ultra-high affinity. However, the large-amplitude dynamics of the positively charged disordered regions of H1 persist on the nucleosome and facilitate the interaction with the highly negatively charged and disordered histone chaperone prothymosin α. Consequently, prothymosin α can efficiently invade the H1-nucleosome complex and displace H1 via competitive substitution. By integrating experiments and simulations, we establish a molecular model that rationalizes this process structurally and kinetically. Given the abundance of charged disordered regions in the nuclear proteome, this mechanism may be widespread in cellular regulation.
Simple attributes predict the importance of plants as hosts to the richness of fungi and arthropods
Authors: Bruun Hans Henrik , Brunbjerg Ane Kirstine , Dalby Lars , Fløjgaard Camilla , Frøslev Tobias G. , Haarder Simon , Heilmann-Clausen Jacob , Høye Toke T. , Læssøe Thomas , Ejrnæs Rasmus 
Published: April 2020

AbstractConsumers constitute the vast majority of global terrestrial biodiversity. Yet, local consumer richness is poorly understood. Plant species richness offers a simple hypothesis to how the diversification of carbon substrates may promote the diversity of arthropods and fungi. We took this one step further and used databases on plant-consumer interaction links to derive the richness of associated biota per plant species (link score). Using a species inventory of 130 sites we investigated 1) how well the link score could be predicted by plant attributes and 2) if the sum of plant species’ observed or predicted link scores could predict site richness of arthropods and macrofungi better than plant species richness alone. We found plant link scores to be positively related to plant size, abundance, nativeness and ectomycorrhizal status. Link based indices generally improved prediction of richness, stressing the importance of plants as niche space for the megadiverse groups of insects and fungi.
Optimizing athlete assessment of maximal force and rate of development: A comparison of the isometric squat and mid-thigh pull
Authors: Silva Joao Renato , Sideris Vasileios , Chrismas Bryna C.R. , Read Paul J. 
Published: April 2020

ABSTRACTThis study compared force-time characteristics and muscle activity between the isometric squat (ISQ) and mid-thigh pull (IMTP) in both bilateral (ISQBI andIMTPBI) and unilateral (ISQUNI andIMTPUNI) stance. Peak force (PF), rate-of-force (RFD) (e.g. 0-300ms) and EMG of the multifidus, erector spinae (ES), gluteus maximus (GM), biceps femoris (BF), semitendinosus (ST), vastus medialis (VM), vastus lateralis (VL) and soleus were recorded in ten recreationally trained males. PF was significantly greater during the ISQBIvs. IMTPBI(p=0.016, ES=1.08) but not in the unilateral test mode although effects remained moderate (ES=0.62). A trend indicated heightened RFD300ms(p = 0.083; ES=0.81) during the IMTPBIvs. the ISQBI, but these effects were smaller in the unilateral test (ES = 0.51). Greater (p<0.0001) EMG for VL (ES=1.00-1.13) and VM were recorded during the ISQ compared to IMTP modes in both modes (ES = 0.97 – 1.18). Greater BF EMG (p = 0.030, ES = 0.31) was shown in IMTPBIvs. ISQBIand these effects were stronger in the unilateral modes (p = < 0.05; ES = 0.81 – 0.83). Significantly greater ST activation was shown in both IMTPUNI(p < 0.05; ES = 0.69-0.76) and IMTPBI(p < 0.001; ES = 1.08). These findings indicate that ISQ results in elevated PF, whereas, RFD is heightened during the IMTP and these differences are more pronounced in bilateral modes. Greater activation of the quadriceps and hamstring muscles are expected in ISQ and IMPT respectively.