bluuebunny/crossref_metadata_2025_split huggingface dataset:
Rapid, dose-dependent and efficient inactivation of surface dried SARS-CoV-2 by 254 nm UV-C irradiation
Authors: Ruetalo Natalia , Businger Ramona , Schindler Michael 
Published: September 2020

AbstractBackgroundThe SARS-CoV-2 pandemic urges for cheap, reliable, and rapid technologies for disinfection and decontamination. One frequently proposed method is UV-C irradiation. However, UV-C doses necessary to achieve inactivation of high-titer SARS-CoV-2 are poorly defined.MethodsUsing a box and two handheld systems designed to decontaminate objects and surfaces we evaluated the efficacy of 254 nm UV-C treatment to inactivate surface dried SARS-CoV-2.ResultsDrying for two hours did not have a major impact on the infectivity of SARS-CoV-2, indicating that exhaled virus in droplets or aerosols stays infectious on surfaces at least for a certain amount of time. Short exposure of high titer surface dried virus (3-5*10^6 IU/ml) with UV-C light (16 mJ/cm2) resulted in a total inactivation of SARS-CoV-2. Dose-dependency experiments revealed that 3.5 mJ/cm2were still effective to achieve a > 6-log reduction in viral titers whereas 1.75 mJ/cm2lowered infectivity only by one order of magnitude.ConclusionsOur results demonstrate that SARS-CoV-2 is rapidly inactivated by relatively low doses of UV-C irradiation. Furthermore, the data reveal that the relationship between UV-C dose and log-viral titer reduction of surface residing SARS-CoV-2 is non-linear. In the context of UV-C-based technologies used to disinfect surfaces, our findings emphasize the necessity to assure sufficient and complete exposure of all relevant areas by integrated UV-C doses of at least 3.5 mJ/cm2at 254 nm. Altogether, UV-C treatment is an effective non-chemical possibility to decontaminate surfaces from high-titer infectious SARS-CoV-2.
Supplementation of a lacto-fermented rapeseed-seaweed blend promotes gut microbial- and gut immune-modulation in weaner piglets
Authors: Hui Yan , Tamez-Hidalgo Paulina , Cieplak Tomasz , Satessa Gizaw Dabessa , Kot Witold , Søren Søren Kjærulff , Nielsen Mette Olaf , Nielsen Dennis Sandris , Krych Lukasz 
Published: September 2020

AbstractThe direct use of medical zinc oxide (ZnO) in feed will be abandoned after 2022 in Europe, leaving an urgent need for substitutes to prevent post-weaning disorders. This study assessed whether rapeseed meal added two brown macroalagae species (Saccharina latissimaandAscophylum nodosum) and fermented using lactic acid bacteria (FRS) could improve piglet performance and gut health. The weaned piglets were fed one of three different feeding regimens (n = 230 each): basal diet, 2.5% and 5% FRS from day 28 of life to day 85. The piglets fed with 2.5% FRS presented superior phenotype with alleviated intraepithelial and stromal lymphocytes infiltration in the gut, enhanced colon mucosa barrier as well as numerically improvements of final body weight. Colon microbiota composition was determined using amplicon sequencing of the V3 and V1 – V8 region of the 16S rRNA gene using Illumina Nextseq and Oxford Nanopore MinION sequencing, respectively. The two amplicon sequencing strategies showed high consistence between the detected bacteria. Both sequencing technologies showed that the FRS fed piglets had a distinctly different microbial composition relative to the basal diet. Compared with piglets fed the basal diet,Prevotella stercoreawas verified by both technologies to be more abundant in the FRS piglets, and positively correlated with colon mucosa thickness and negatively correlated with blood levels of leucocytes and IgG. In conclusion, FRS supplementation improved gut health of weaner piglets, and altered their gut microbiota composition. Increasing the dietary inclusion of FRS from 2.5% to 5% did not cause further improvements.
The protected physiological status of intracellularSalmonella entericapersisters reduces host cell-imposed stress
Authors: Schulte Marc , Olschewski Katharina , Hensel Michael 
Published: September 2020

AbstractToday, we are faced with increasingly occurring bacterial infections that are hard to treat and often tend to relapse. These recurrent infections can occur possibly due to antibiotic-tolerant persister cells. Antibiotic persistent bacteria represent a small part of a bacterial population that enters a non-replicating (NR) state arising from phenotypic switching. Intracellularly, after uptake by phagocytic cells,Salmonella entericaserovar Typhimurium (STM) forms persister cells that are able to subvert immune defenses of the host. However, the clear physiological state and perceptual properties are still poorly understood and many questions remain unanswered. Here we describe further development of fluorescent protein-based reporter plasmids that were used to detect intracellular NR persister cells and monitor the expression of stress response genes via extensive flow cytometric analyses. Moreover, we performed extensive measurements of the metabolic properties of NR STM at the early course of infection. Our studies demonstrate that NR STM persister cells perceive their environment and are capable respond to stress factors. Since persisters showed a lower stress response compared to replicating (R) STM, which was not a consequence of a lower metabolic capacity, the persistent status of STM serves as protective niche. Furthermore, up to 95% of NR STM were metabolically active at the beginning of infection additionally showing no difference in the metabolic capacity compared to R STM. The accessory capability of NR STM persisters to sense and to react to stress with constant metabolic activity may supports the pathogen to create a more permissive environment for recurrent infections.
Humans Discriminate Individual Large-Billed Crows by their Calls
Authors: Schalz Sabrina , Dickins Thomas E. 
Published: September 2020

AbstractPrevious research has shown that humans can discriminate two individual rhesus monkeys (Macaca mulatta), as well as two individual zebra finches (Taeniopygia guttata) by their vocalizations. The discrimination of individual zebra finches largely relies on differences in pitch contour, although this is not the only relevant cue. The purpose of the present experiment was to examine whether humans can also discriminate two individual large-billed crows (Corvus macrorhynchos) by their calls. Discrimination was tested with a forced-choice Same-Different Paradigm. Results show a high discrimination accuracy without prior training, although the scores obtained here were lower than those in the zebra finch discrimination task. There was no significant learning trend across trials. Future studies should investigate which acoustic cues participants use for the discrimination of individual crows and expand these findings with more non-human animal vocalizations.
Mis-splicing ofMdm2leads to Increased P53-Activity and Craniofacial Defects in a MFDMEftud2Mutant Mouse Model
Authors: Beauchamp Marie-Claude , Djedid Anissa , Bareke Eric , Merkuri Fjodor , Aber Rachel , Tam Annie S. , Lines Matthew A. , Boycott Kym M. , Stirling Peter C. , Fish Jennifer L. , Majewski Jacek , Jerome-Majewska Loydie A. 
Published: September 2020

SummaryEFTUD2, a GTPase and core component of the splicesome, is mutated in patients with mandibulofacial dysostosis with microcephaly (MFDM). We generated a mutant mouse line with conditional mutation inEftud2and usedWnt1-Cre2to delete it in neural crest cells. Homozygous deletion ofEftud2leads to neural crest cell death and malformations in the brain and craniofacial region of embryos. RNAseq analysis of embryonic mutant heads revealed a significant increase in exon skipping, in retained introns and enriched levels ofMdm2transcripts lacking exon 3. Mutants also had increased nuclear P53, higher expression of P53-target genes, and increased cell death. Their craniofacial development was significantly improved when treated with Pifithrin-α, an inihibitor of P53. We propose that craniofacial defects caused by mutations ofEFTUD2are a result of mis-splicing ofMdm2and P53-associated cell death. Hence, drugs that reduce P53 activity may help prevent craniofacial defects associated with spliceosomopathies.
The fitness landscapes of translation
Authors: Josupeit Mario , Krug Joachim 
Published: September 2020

AbstractMotivated by recent experiments on an antibiotic resistance gene, we investigate genetic interactions between synonymous mutations in the framework of exclusion models of translation. We show that the range of possible interactions is markedly different depending on whether translation efficiency is assumed to be proportional to ribosome current or ribosome speed. In the first case every mutational effect has a definite sign that is independent of genetic background, whereas in the second case the effect-sign can vary depending on the presence of other mutations. The latter result is demonstrated using configurations of multiple translational bottlenecks induced by slow codons.
Actuation Enhances Patterning in Human Neural Tube Organoids
Authors: Fattah Abdel Rahman Abdel , Daza Brian , Rustandi Gregorius , Berrocal-Rubio Miguel Angel , Gorissen Benjamin , Poovathingal Suresh , Davie Kristofer , Cao Xuanye , Rosenzweig Derek Hadar , Lei Yunping , Finnell Richard , Verfaillie Catherine , Sampaolesi Maurilio , Dedecker Peter , Van Oosterwyck Hans , Aerts Stein , Ranga Adrian 
Published: September 2020

AbstractTissues achieve their complex spatial organization through an interplay between gene regulatory networks, cell-cell communication, and physical interactions mediated by mechanical forces. Current strategies to generate in-vitro tissues have largely failed to implement such active, dynamically coordinated mechanical manipulations, relying instead on extracellular matrices which respond to, rather than impose mechanical forces. Here we develop devices that enable the actuation of organoids. We show that active mechanical forces increase growth and lead to enhanced patterning in an organoid model of the neural tube derived from single human pluripotent stem cells (hPSC). Using a combination of single-cell transcriptomics and immunohistochemistry, we demonstrate that organoid mechanoregulation due to actuation operates in a temporally restricted competence window, and that organoid response to stretch is mediated extracellularly by matrix stiffness and intracellularly by cytoskeleton contractility and planar cell polarity. Exerting active mechanical forces on organoids using the approaches developed here is widely applicable and should enable the generation of more reproducible, programmable organoid shape, identity and patterns, opening avenues for the use of these tools in regenerative medicine and disease modelling applications.
Aptamer based spatiotemporally controlled growth factor patterning for tunable local microvascular network formation in engineered tissues
Authors: Rana Deepti , Kandar Ajoy , Salehi-Nik Nasim , Inci Ilyas , Koopman Bart , Rouwkema Jeroen 
Published: September 2020

AbstractSpatiotemporally controlled growth factor availability is of crucial importance for achieving hierarchically organized vascular network formation within engineering tissues. Even though current growth factor delivery systems can provide sustained release and growth factor delivery on demand, they generally do not facilitate temporal control over the release rates and thus adaptation in accordance with the needs of growing engineered tissue. Additionally, with conventional growth factor loading methods, growth factors are often subjected to organic solvents or harsh conditions, leading to lower bioactivity and denaturation of the proteins. To overcome these limitations, this manuscript reports on the development of VEGF specific 5’ acrydite modified aptamer functionalized GelMA hydrogels. The covalently incorporated aptamers can selectively bind to proteins with high affinity and specificity, and can thus sequester the target protein from the surrounding environment. The manuscript shows that this not only provides temporal control over the growth factor release via complementary sequence hybridization, but also enables local control of microvascular network formation in 3D.
Protonation states in SARS-CoV-2 main protease mapped by neutron crystallography
Authors: Kneller Daniel W. , Phillips Gwyndalyn , Weiss Kevin L. , Pant Swati , Zhang Qiu , O’Neill Hugh M. , Coates Leighton , Kovalevsky Andrey 
Published: September 2020

AbstractThe main protease (3CL Mpro) from SARS-CoV-2, the etiological agent of COVID-19, is an essential enzyme for viral replication, possessing an unusual catalytic dyad composed of His41 and Cys145. A long-standing question in the field has been what the protonation states of the ionizable residues in the substrate-binding active site cavity are. Here, we present the room-temperature neutron structure of 3CL Mprofrom SARS-CoV-2, which allows direct determination of hydrogen atom positions and, hence, protonation states. The catalytic site natively adopts a zwitterionic reactive state where His41 is doubly protonated and positively charged, and Cys145 is in the negatively charged thiolate state. The neutron structure also identified the protonation states of other amino acid residues, mapping electrical charges and intricate hydrogen bonding networks in the SARS-CoV-2 3CL Mproactive site cavity and dimer interface. This structure highlights the ability of neutron protein crystallography for experimentally determining protonation states at near-physiological temperature – the critical information for structure-assisted and computational drug design.
The extracellular contractile injection system is enriched in environmental microbes and associates with numerous toxins
Authors: Geller Alexander Martin , Pollin Inbal , Zlotkin David , Danov Aleks , Nachmias Nimrod , Andreopoulos William B , Shemesh Keren , Levy Asaf 
Published: September 2020

AbstractBacteria employ toxin delivery systems to exclude bacterial competitors and to infect host cells. Characterization of these systems and the toxins they secrete is important for understanding microbial interactions and virulence in different ecosystems. The extracellular Contractile Injection System (eCIS) is a toxin delivery particle that evolved from a bacteriophage tail. Four known eCIS systems have been shown to mediate interactions between bacteria and their invertebrate hosts, but the broad ecological function of these systems remains unknown. Here, we identify eCIS loci in 1,249 prokaryotic genomes and reveal a striking enrichment of these loci in environmental microbes and absence from mammalian pathogens. We uncovered 13 toxin genes that associate with eCIS from diverse microbes and show that they can inhibit growth of bacteria, yeast or both. We also found immunity genes that protect bacteria from self-intoxication, supporting an antibacterial role for eCIS. Furthermore, we identified multiple new eCIS core genes including a conserved eCIS transcriptional regulator. Finally, we present our data through eCIStem; an extensive eCIS repository. Our findings define eCIS as a widespread environmental prokaryotic toxin delivery system that likely mediates antagonistic interactions with eukaryotes and prokaryotes. Future understanding of eCIS functions can be leveraged for the development of new biological control systems, antimicrobials, and cell-free protein delivery tools.
De novoDNA methylation controls neuronal maturation during adult hippocampal neurogenesis
Authors: Zocher Sara , Overall Rupert W , Berdugo-Vega Gabriel , Rund Nicole , Karasinsky Anne , Adusumilli Vijay S , Steinhauer Christina , Scheibenstock Sina , Händler Kristian , Schultze Joachim L , Calegari Federico , Kempermann Gerd 
Published: September 2020

SummaryDynamic DNA methylation controls gene-regulatory networks underlying cell fate specification. How DNA methylation patterns change during adult hippocampal neurogenesis and their relevance for adult neural stem cell differentiation and related brain function has, however, remained unknown. Here, we show that neurogenesis-associatedde novoDNA methylation is critical for maturation and functional integration of adult-born hippocampal neurons. Cell stage-specific bisulfite sequencing revealed a pronounced gain of DNA methylation at neuronal enhancers, gene bodies and binding sites of pro-neuronal transcription factors during adult neurogenesis, which mostly correlated with transcriptional up-regulation of the associated loci. Inducible deletion of bothde novoDNA methyltransferasesDnmt3aandDnmt3bin adult neural stem cells specifically impaired dendritic outgrowth and synaptogenesis of new-born neurons, resulting in reduced hippocampal excitability and specific deficits in hippocampus-dependent learning and memory. Our results highlight that, during adult neurogenesis, remodeling of neuronal methylomes is fundamental for proper hippocampal function.
Coherent theta activity in the medial and orbital frontal cortices encodes reward value
Authors: Amarante Linda M. , Laubach Mark 
Published: September 2020

ABSTRACTThis study examined how the medial frontal (MFC) and orbital frontal (OFC) cortices process reward information. We simultaneously recorded local field potentials in the two areas as rats consumed liquid sucrose rewards. Both areas exhibited a 4-8 Hz “theta” rhythm that was phase locked to the lick cycle. The rhythm tracked shifts in sucrose concentrations and fluid volumes, demonstrating that it is sensitive to differences in reward magnitude. The coupling between the rhythm and licking was stronger in MFC than OFC and varied with response vigor and absolute reward value in the MFC. Spectral analysis revealed zero-lag coherence between the cortical areas, and found evidence for a directionality of the rhythm, with MFC leading OFC. Our findings suggest that consummatory behavior generates simultaneous theta range activity in the MFC and OFC that encodes the value of consumed fluids, with the MFC having a top-down role in the control of consumption.
Dengue activates mTORC2 signaling to counteract apoptosis and maximize viral replication
Authors: Carter Christoph C. , Olivier Jean Paul , Kaushansky Alexis , Mast Fred D. , Aitchison John D. 
Published: September 2020

ABSTRACTThe mechanistic target of rapamycin (mTOR) functions in at least two distinct complexes: mTORC1, which regulates cellular anabolic-catabolic homeostasis, and mTORC2, which is an important regulator of cell survival and cytoskeletal maintenance. mTORC1 has been implicated in the pathogenesis of flaviviruses including dengue, where it contributes to the establishment of a pro-viral autophagic state. In contrast, the role of mTORC2 in viral pathogenesis is unknown. In this study, we explore the consequences of a physical protein-protein interaction between dengue non-structural protein 5 (NS5) and host cell mTOR proteins during infection. Using shRNA to differentially target mTORC1 and mTORC2 complexes, we show that mTORC2 is required for optimal dengue replication. Furthermore, we show that mTORC2 is activated during viral replication, and that mTORC2 counteracts virus-induced apoptosis, promoting the survival of infected cells. This work reveals a novel mechanism by which the dengue flavivirus can promote cell survival to maximize viral replication.
The His-tag as a decoy modulating preferred orientation in cryoEM
Authors: Bromberg Raquel , Guo Yirui , Plymire Daniel , Emde Tabitha , Puzio Maciej , Borek Dominika , Otwinowski Zbyszek 
Published: September 2020

AbstractThe His-tag is a widely used affinity tag that facilitates purification by means of affinity chromatography of recombinant proteins for functional and structural studies. We show here that His-tag presence affects how coproheme decarboxylase interacts with the water-air interface during grid preparation for cryoEM. Depending on His-tag presence or absence, we observe significant changes in patterns of preferred orientation. The analysis of particle orientations suggests that His-tag presence can mask the hydrophobic patches on a protein’s surface that mediate the interactions with the water-air interface, while the hydrophobic linker between a His-tag and the coding sequence of the protein may enhance other interactions with water-air interface. Our observations suggest that tagging, including rational design of the linkers between an affinity tag and a protein of interest, offer a promising approach to modulating interactions with the water-air interface.SynopsisA His-tag affects the interactions of particles with the water-air interface in cryo-electron microscopy (cryoEM) single particle reconstruction (SPR), and thus may be used to modulate these interactions, including inducing changes in patterns of preferred orientation.
Cone Opponent Functional Domains in Primary Visual Cortex Combine Signals for Color Appearance Mechanisms
Authors: Li Peichao , Garg Anupam K. , Zhang Li A. , Rashid Mohammad S. , Callaway Edward M. 
Published: September 2020

AbstractStudies of color perception have led to mechanistic models of how cone-opponent signals from retinal ganglion cells are integrated to generate color appearance. But it is unknown how this hypothesized integration occurs in the brain. Here we show that cone-opponent signals transmitted from retina to primary visual cortex (V1) are integrated through highly organized circuits within V1 to implement the color opponent interactions required for color appearance. Combining intrinsic signal optical imaging (ISI) and 2-photon calcium imaging (2PCI) at single cell resolution, we demonstrate cone-opponent functional domains (COFDs) that combine L/M cone-opponent and S/L+M cone-opponent signals following the rules predicted from psychophysical studies of color perception. These give rise to an orderly organization of hue preferences of the neurons within the COFDs and the generation of hue “pinwheels”. Thus, spatially organized neural circuits mediate an orderly transition from cone-opponency to color appearance that begins in V1.
The interplay between asymmetric and symmetric DNA loop extrusion
Authors: Banigan Edward J. , Mirny Leonid A. 
Published: September 2020

AbstractCompaction of chromosomes is essential for reliable transmission of genetic information. Experiments suggest that this ∼ 1000-fold compaction is driven by condensin complexes that extrude chromatin loops,i.e., progressively collect chromatin fiber from one or both sides of the complex to form a growing loop. Theory indicates thatsymmetrictwo-sided loop extrusion can achieve such compaction, but recent single-molecule studies observed diverse dynamics of condensins that perform one-sided, symmetric two-sided, andasymmetrictwo-sided extrusion.We use simulations and theory to determine how these molecular properties lead to chromosome compaction. High compaction can be achieved if even a small fraction of condensins have two essential properties: a long residence time and the ability to perform two-sided (not necessarily symmetric) extrusion. In mixtures of condensins I and II, coupling of two-sided extrusion and stable chromatin binding by condensin II promotes compaction. These results provide missing connections between single-molecule observations and chromosome-scale organization.