bluuebunny/crossref_metadata_2025_split huggingface dataset:
Optimal parameters for Rapid Invisible Frequency Tagging using MEG
Authors: Minarik Tamas , Berger Barbara , Jensen Ole 
Published: December 2022

AbstractFrequency tagging has been demonstrated to be a useful tool for identifying representational-specific neuronal activity in the auditory and visual domains. However, the slow flicker (<30Hz) applied in conventional frequency tagging studies is highly visible and might entrain endogenous neuronal oscillations. Hence, stimulation at faster frequencies that is much less visible and does not interfere with endogenous brain oscillatory activity is a promising new tool. In this study, we set out to examine the optimal stimulation parameters ofrapid invisible frequency tagging (RFT/RIFT)with magnetoencephalography (MEG) by quantifying the effects of stimulation frequency, size and position of the flickering patch.Rapid frequency tagging (RFT)using flickers above 50 Hz results in almost invisible stimulation which does not interfere with slower endogenous oscillations; however, the signal is weaker as compared to tagging at slower frequencies so the optimal parameters of stimulation delivery are crucial. The here presented results examining the frequency range between 60Hz and 96Hz suggest that RFT induces brain responses with decreasing strength up to about 84Hz. In addition, even at the smallest flicker patch (2°) focally presented RFT induces a significant oscillatory brain signal at the stimulation frequency (66Hz); however, the elicited response increases with patch size. While focal RFT presentation elicits the strongest response, off-centre presentations do generally mainly elicit a measureable response if presented below the horizontal midline. The results also revealed considerable individual differences in the neuronal responses of to RFT stimulation. Finally, we discuss the comparison of oscillatory measures (coherence and power) and sensor types (planar gradiometers and magnetometers) in order to achieve optimal outcomes. Based on our extensive findings we set forward concrete recommendations for using rapid frequency tagging in human cognitive neuroscience investigations.
Electrophysiological indices of distractor processing in visual search are shaped by target expectations
Authors: van Moorselaar Dirk , Huang Changrun , Theeuwes Jan 
Published: December 2022

AbstractAlthough in many cases salient stimuli capture attention involuntarily, it has been proposed recently that under certain conditions the bottom-up signal generated by such stimuli can be proactively suppressed. In support of this signal suppression hypothesis, ERP studies have demonstrated that salient stimuli that do not capture attention elicit a distractor positivity (PD),a putative neural index of suppression. At the same time, it is becoming increasingly clear that regularities across preceding search episodes have a large influence on attentional selection. Yet to date, studies in support of the signal suppression hypothesis have largely ignored the role of selection history on the processing of distractors. The current study addressed this issue by examining how electrophysiological markers of attentional selection (N2pc) and suppression (PD) elicited by targets and distractors respectively were modulated when the search target randomly varied instead of being fixed across trials. Results showed that while target selection was unaffected by this manipulation, both in terms of manual response times, as well as in terms of the N2pc component, the PDcomponent was reliably attenuated when the target features varied randomly across trials. This result demonstrates that the distractor PD, which is typically considered the marker of selective distractor processing cannot unequivocally be attributed to suppression only, as it also, at least in part, reflects the upweighting of target features.
Variability of Phenylalanine side chain conformations facilitates promiscuity of Fatty acid binding in Cockroach milk proteins
Authors: Santhakumari Partha Radhakrishnan , Dhanabalan KanagaVijayan , Virani Saniya , Hopf-Jannasch Amber S. , Benoit Joshua B. , Chopra Gaurav , Subramanian Ramaswamy 
Published: December 2022

AbstractThe pacific beetle cockroach,Diploptera punctata, is a viviparous cockroach that produces a milk-like substance to support the growing embryo with a brood sac. The structure of thein vivogrown crystals present in the gut of the embryo showed that the milk-derived crystals are heterogenous and are made of three proteins (called Lili-Mips). Multiple fatty acids could be modeled into the active site, and we hypothesized that each of the three isoforms of the protein bound to a different fatty acid. We previously reported that the recombinantly expressed Lili-Mip2 has a structure similar to the structure of the protein determined fromin vivocrystals, and this single isoform also binds to several fatty acids. In this study, we aimed to probe the specificity and affinity of fatty acid binding and test the stability of different isoforms. We show that all the isoforms can bind to different fatty acids with very similar affinities, and the local abundance of a fatty acid determined bound fatty acid ratios. Lili-Mips’ thermostability is pH dependent, where stability is highest at acidic pH and declines as the pH increases to physiological levels near 7.0. The measurement of the pH in the gut lumen and the gut cells suggests that the pH in the gut is acidic and the pH inside the gut cells is closer to neutral pH. We propose that the protein has evolved to be highly stable in the acidic gut lumen and, when absorbed inside the gut cells, becomes less stable to enable the breakdown of the glycosylated lipo-protein complex to provide essential metabolites for survival and development of the embryo. The different orientations of Phe-98 and Phe-100 control the binding pocket volume and allow the binding of different chain-length fatty acids to bind with similar affinities.
Crosstalk between regulatory elements in the disordered TRPV4 N-terminus modulates lipid-dependent channel activity
Authors: Goretzki Benedikt , Wiedemann Christoph , McCray Brett A. , Schäfer Stefan L. , Jansen Jasmin , Tebbe Frederike , Mitrovic Sarah-Ana , Nöth Julia , Donohue Jack K. , Jeffries Cy M. , Steinchen Wieland , Stengel Florian , Sumner Charlotte J. , Hummer Gerhard , Hellmich Ute A. 
Published: December 2022

AbstractIntrinsically disordered regions (IDRs) are essential for membrane receptor regulation but often remain unresolved in structural studies. TRPV4, a member of the TRP vanilloid channel family involved in thermo- and osmosensation, has a large N-terminal IDR of approximately 150 amino acids. With an integrated structural biology approach, we analyze the structural ensemble of the TRPV4 IDR and identify a network of regulatory elements that modulate channel activity in a hierarchical lipid-dependent manner through transient long-range interactions. A highly conserved autoinhibitory patch acts as a master regulator by competing with PIP2binding to attenuate channel activity. Molecular dynamics simulations show that loss of the interaction between the PIP2-binding site and the membrane reduces the force exerted by the IDR on the structured core of TRPV4. This work demonstrates that IDR structural dynamics are coupled to TRPV4 activity and highlights the importance of IDRs for TRP channel function and regulation.
A Spatiotemporal Notch Interaction Map from Membrane to Nucleus
Authors: Martin Alexandre P. , Bradshaw Gary A. , Eisert Robyn J. , Egan Emily D. , Tveriakhina Lena , Rogers Julia M. , Dates Andrew N. , Scanavachi Gustavo , Aster Jon C. , Kirchhausen Tom , Kalocsay Marian , Blacklow Stephen C. 
Published: December 2022

ABSTRACTNotch signaling relies on ligand-induced proteolysis to liberate a nuclear effector that drives cell fate decisions. The location and timing of individual steps required for proteolysis and movement of Notch from membrane to nucleus, however, remain unclear. Here, we use proximity labeling with quantitative multiplexed mass spectrometry to monitor the microenvironment of endogenous Notch2 after ligand stimulation in the presence of a gamma secretase inhibitor and then as a function of time after inhibitor removal. Our studies show that gamma secretase cleavage of Notch2 occurs in an intracellular compartment and that formation of nuclear complexes and recruitment of chromatin-modifying enzymes occurs within 45 minutes of inhibitor washout. This work provides a spatiotemporal map of unprecedented detail tracking the itinerary of Notch from membrane to nucleus after activation and identifies molecular events in signal transmission that are potential targets for modulating Notch signaling activity.
Promoting Axon Regeneration By Inhibiting RNA N6-methyladenosine Demethylase ALKBH5
Authors: Wang Dong , Zheng Tiemei , Zhou Songlin , Liu Mingwen , Liu Yaobo , Gu Xiaosong , Mao Susu , Yu Bin 
Published: December 2022

AbstractA key limiting factor of successful axon regeneration is the intrinsic regenerative ability in both the peripheral (PNS) and central nervous system (CNS). Previous studies have identified axon regeneration regulators that act on gene expression in injured neurons. However, it is less known if RNA modifications play a role in this process. Here, we systematically screened the functions of all common m6A modification-related enzymes in axon regeneration and report ALKBH5, an evolutionarily conserved RNA m6A demethylase, as a regulator of axonal regeneration. In PNS, knockdown of ALKBH5 enhanced sensory axonal regeneration, whereas overexpressing ALKBH5 impaired axonal regeneration in an m6A-dependent manner. Mechanistically, ALKBH5 increased the stability of Lpin2 mRNA and thus limited regenerative growth associated lipid metabolism in DRG neurons. Moreover, in CNS, knockdown of ALKBH5 enhanced the survival and axonal regeneration of retinal ganglion cells after optic nerve injury. Together, our results suggest a novel mechanism regulating axon regeneration and point ALKBH5 as a potential target for promoting axon regeneration in both PNS and CNS.
Detection of horizontal sequence transfer in microorganisms in the genomic era
Authors: Tall Mamadou Lamine , Mbogning Maxime Descartes , Kuete Yimagou Edmond , Raoult Didier , Levasseur Anthony 
Published: December 2022

AbstractSequence transfer and genome remodeling are very frequent events in microorganisms, especially prokaryotes. This is due to the mosaic structure of the genomes, which calls into question the correct classification of genomes in terms of a single gene or a group of genes. We started here, as a first step, the inventory of bioinformatics tools applied to the detection of horizontal sequence transfers in microorganisms in the genomic era by applying bibliometric survey. Our bibliographic analysis allowed us to identify 17 main tools for the detection of chimeras. The first Bellerophon developed in 2004, followed by CCode and Pintail in 2005; Mallard in 2006; Mothur in 2009; Blackbox Chimera in 2010; Perseus, ChimeraSlayer, UCHIME 1 and UCHIME2, and ChimeraScan in 2011; Decipher in 2012; EBARDenovo and FunFrame in 2013; CATCh in 2015; Uchime 2 in 2016 and ChimeraMiner in April 2019. We then described each of these tools, highlighting their operating principles as well as the advantages and limitations of each (specificities, sensitivity, rapidity and frequent updates). The number of articles citing these tools has increased over the years especially for Mothur, Uchime, VSEARCH and ChimeraSlayer, thus demonstrating the interest of researchers in these tools and the need to decipher chimeras in genomic era.
Integrating pharmacogenomics and cheminformatics with diverse disease phenotypes for cell type-guided drug discovery
Authors: Halu Arda , Decano Julius L. , Matamalas Joan , Whelan Mary , Asano Takaharu , Kalicharran Namitra , Singh Sasha A. , Loscalzo Joseph , Aikawa Masanori 
Published: December 2022

AbstractLarge-scale pharmacogenomic resources, such as the Connectivity Map (CMap), have greatly assisted computational drug discovery. However, despite their widespread use, CMap-based methods have thus far been agnostic to the biological activity of drugs, as well as to the genomic effects of drugs in multiple disease contexts. Here, we present a network-based statistical approach, Pathopticon, that uses CMap to build cell type-specific gene-drug perturbation networks and integrates these networks with cheminformatic data and diverse disease phenotypes for a nested prioritization of cell lines and drugs. Pathopticon demonstrates a better prediction performance than solely cheminformatic measures and state-of-the-art methods that rely exclusively on pharmacogenomic data. Top predictions made by Pathopticon have high chemical structural diversity, suggesting their potential for building compound libraries. In a proof-of-concept application on vein graft disease, we validate the predicted drugsin vitroand demonstrate that Pathopticon helps pinpoint the shared intermediate phenotypes targeted by each prediction. Overall, our analytical framework integrating pharmacogenomics and cheminformatics provides a feasible blueprint for a cell typespecific drug discovery and repositioning platform with broad implications for the efficiency and success of drug development.
Salmonellasuccinate utilisation is inhibited by multiple regulatory systems
Authors: Wenner Nicolas , Zhu Xiaojun , Rowe Will P. M. , Händler Kristian , Hinton Jay C. D. 
Published: December 2022

AbstractSuccinate is a potent immune signalling molecule that is present in the mammalian gut and within macrophages. Both of these niches are colonised by the pathogenic bacteriumSalmonella entericaserovar Typhimurium during infection. Succinate is a C4-dicarboyxlate that can serve as a source of carbon for bacteria. When succinate is provided as the sole carbon source forin vitrocultivation,Salmonellaand other enteric bacteria exhibit a slow growth rate and a long lag phase. This growth inhibition phenomenon was known to involve the sigma factor RpoS, but the genetic basis of the repression of bacterial succinate utilisation was poorly understood. Here, we used an experimental evolution approach to isolate fast-growing mutants during growth ofS. Typhimurium on succinate containing minimal medium.Our approach reveals novel RpoS-independent systems that inhibit succinate utilisation. The CspC RNA binding protein restricts succinate utilisation, an inhibition that is antagonised by high levels of the small regulatory RNA (sRNA) OxyS. We discovered that the Fe-S cluster regulatory protein IscR inhibits succinate utilisation by repressing the C4-dicarboyxlate transporter DctA.The RNA chaperone Hfq, the exoribonuclease PNPase and their cognate sRNAs function together to repress succinate utilisationviaRpoS induction. Furthermore, the ribose operon repressor RbsR is required for the complete RpoS-driven repression of succinate utilisation, suggesting a novel mechanism of RpoS regulation.Our discoveries shed light on redundant regulatory systems that tightly regulate the utilisation of succinate. We propose that the control of central carbon metabolism by multiple regulatory systems inSalmonellagoverns the infection niche-specific utilisation of succinate.
Rapid and collective determination of the complete “hot-spring frog” mitochondrial genome containing long repeat regions using Nanopore sequencing
Authors: Asaeda Yuka , Shiraga Kento , Suzuki Makoto , Sambongi Yoshihiro , Ogino Hajime , Igawa Takeshi 
Published: December 2022

AbstractThe mitochondrial genome (mt-genome) is one of the promising molecular markers for phylogenetics and population genetics. Recently, various mt-genomes have been determined rapidly by using massively parallel sequencers. However, the control region (CR, also called D-loop) in mt-genomes remain difficult to precisely determine due to the presence of repeat regions. Here, using Nanopore sequencing, we succeeded in rapid and collective determination of complete mt-genome of the hot-spring frog,Buergeria japonica, and found that its mt-genome size was 22,274 bp including CR (6,929 bp) with two types of tandem repeat motifs forming repeat regions. Comparison of assemble strategies revealed that the long- and short-read data combined together enabled efficient determination of the CR, but the short-read data alone did not. TheB. japonicaCR was longer than that of a congenic species inhabiting cooler climate areas,Buergeria buergeri, because of the long repeat regions in the former. During the thermal adaptation ofB. japonica, the longer repeat regions in its CR may have accumulated within a short period after divergence fromB. buergeri.
CRAM compression: practical across-technologies considerations for large-scale sequencing projects
Authors: Al Ali Ayesha , Kandavel Palani Kannan , Al Mabrazi Hakeem , Carvalho George , Kusuma Vinay , Katagi Gurunath , Elavalli Santosh , Yousif Ayman , Akhter Mohammad Riyaz , Mafofo Joseph , Magalhaes Tiago , Quilez Javier 
Published: December 2022

AbstractCRAM is an efficient format to store high-throughput sequencing data and it has been widely adopted. We thus plan to use CRAM for the Emirati Genome Program, which aims to sequence the genomes of ~1 million nationals in the United Arab Emirates using short- and long-read sequencing technologies (Illumina, MGI and Oxford Nanopore Sequencing). We conducted a pilot study on the three technologies before start using CRAM at scale. We found CRAM achieved 40–70% compression depending on the sequencing platform. As expected, CRAM compression was data lossless and did not alter variant calls. In our cloud, we observed compression speeds 0.7–1.4 GB per minute, varying on the sequencing platform too. This translates into ~1–2 hours using a single CPU to compress a ~30X human whole-genome sequencing sample. Despite its wide use, we found little publicly available information about CRAM compression rate, speed, losslessness and parallelization, especially across many sequencing platforms. This work will have direct application for Emirati Genome Program and provide practical considerations for other large-scale sequencing efforts.
ATG9A regulates dissociation of recycling endosomes from microtubules leading to formation of influenza A virus liquid condensates
Authors: Vale-Costa Sílvia , Etibor Temitope Akhigbe , Brás Daniela , Sousa Ana Laura , Ferreira Mariana , Martins Gabriel G. , Mello Victor Hugo , Amorim Maria João 
Published: December 2022

ABSTRACTIt is now established that many viruses that threaten public health establish condensates via phase transitions to complete their lifecycles, and knowledge on such processes may offer new strategies for antiviral therapy. In the case of influenza A virus (IAV), liquid condensates known as viral inclusions, concentrate the 8 distinct viral ribonucleoproteins (vRNPs) that form IAV genome and are viewed as sites dedicated to the assembly of the 8-partite genomic complex. Despite not being delimited by host membranes, IAV liquid inclusions accumulate host membranes inside as a result of vRNP binding to the recycling endocytic marker Rab11a, a driver of the biogenesis of these structures. We lack molecular understanding on how Rab11a-recycling endosomes condensate specifically near the endoplasmic reticulum (ER) exit sites upon IAV infection. We show here that liquid viral inclusions interact with the ER to fuse, divide and slide. We uncover that, contrary to previous indications, the reported reduction in recycling endocytic activity is a regulated process rather than a competition for cellular resources involving a novel role for the host factor ATG9A. In infection, ATG9A mediates the removal of Rab11a-recycling endosomes carrying vRNPs from microtubules. We observe that the recycling endocytic usage of microtubules is rescued when ATG9A is depleted, which prevents condensation of Rab11a endosomes near the ER. The failure to produce viral inclusions accumulates vRNPs in the cytosol, reduces genome assembly and the release of infectious virions. We propose that the ER supports the dynamics of liquid IAV inclusions, with ATG9A facilitating their formation. This work advances our understanding on how epidemic and pandemic influenza genomes are formed. It also reveals the plasticity of recycling pathway endosomes to undergo condensation in response to infection, disclosing new roles for ATG9A beyond its classical involvement in autophagy.
Taxonomic and metabolic diversity of Actinobacteria isolated from faeces of a 28,000-year-old mammoth
Authors: van Bergeijk Doris A. , Augustijn Hannah E. , Elsayed Somayah S. , Willemse Joost , Carrión Victor J. , Urem Mia , Grigoreva Lena V. , Cheprasov Maksim Y. , Grigoriev Semyon , Wintermans Bas , Budding Andries E. , Spaink Herman P. , Medema Marnix H. , van Wezel Gilles P. 
Published: December 2022

AbstractAncient microbial communities of permafrost soils and frozen animal remains represent an archive that has barely been explored. This yet unexplored microbial world is a vast resource that can provide us with new evolutionary insights, metabolic pathways and novel chemistry. Here, we reveal that Actinobacteria isolated from a faecal sample from the intestinal tract of a 28,000-year-old Siberian mammoth are phylogenetically and metabolically distinct from currently known modern siblings. AncientMicromonospora, Oerskovia, Saccharopolyspora, SanguibacterandStreptomycesspecies were successfully revived and their genome sequences resolved. Surprisingly, the genomes of the ancestors show a large phylogenetic distance to strains isolated today and harbour many novel biosynthetic gene clusters that may well represent uncharacterised biosynthetic potential. Metabolic profiles of the strains display production of known molecules like antimycin, conglobatin and macrotetrolides, but the majority of the mass features could not be dereplicated. Our work provides a snapshot into Actinobacteria of the past, yielding unexplored genomic information that is not yet present in current databases.
Coupling of Coastal Activity with Tidal Cycles is Stronger in Tool-using Capuchins (Cebus capucinus imitator)
Authors: Goldsborough Zoë , Crofoot Margaret C. , Alavi Shauhin E. , Garza Sylvia F. , Del Rosario-Vargas Evelyn , Tiedeman Kate , Monteza-Moreno Claudio M. , Barrett Brendan J. 
Published: December 2022

AbstractTerrestrial mammals exploiting coastal resources must cope with the challenge that resource availability and accessibility fluctuate with tidal cycles. Tool use can improve foraging efficiency and provide access to structurally protected resources that are otherwise unavailable (e.g., mollusks and fruits). To understand how variable accessibility of valuable resources shapes behavioral patterns, and whether tool use aids in the efficient exploitation of intertidal resources, we compared the relationship between tidal cycles and activity patterns of tool-using vs. non-tool-using groups of white-faced capuchin monkeys on Jicarón Island in Coiba National Park, Panama. Although only a single group of capuchins on Jicarón uses tools, all coastal groups forage on intertidal resources. Using data from >3 years of camera trapping at varying distances from the coast, we found that capuchins on Jicarón showed increased coastal activity during specific parts of the tidal cycle, and that this relationship differed between tool-using and non-tool-using groups, as well as between seasons. Activity patterns of tool-using capuchins were more strongly and consistently tied to tidal cycles compared to non-tool-users, indicating that tool use might allow for more efficient exploitation of tidal resources. Our findings highlight the potential of tool use to aid niche expansion.