bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adult neural stem cells and neurogenesis are resilient to intermittent fasting
Authors: Gabarró-Solanas Rut , Davaatseren Amarbayasgalan , Kepčija Tatjana , Crespo-Enríquez Iván , Urbán Noelia 
Published: July 2022

AbstractIntermittent fasting (IF) is a promising non-pharmacological strategy to counteract ageing which has been shown to increase the number of adult-born neurons in the dentate gyrus of mice. However, it is still unclear which steps of the adult neurogenesis process are regulated by IF. The number of adult neural stem cells (NSCs) decreases with age in an activation-dependent manner. To counteract the loss of the stem cell pool, adult NSCs are mostly found in an inactive, quiescent state which ensures their long-term maintenance. We aimed to determine if and how IF impacts the activity and maintenance of adult NSCs in the hippocampus. We chose an every-other-day fasting protocol with food re-administration at night, which we found effectively induces fasting features and preserves the circadian activity pattern of mice. To determine the effects of IF on NSCs and all following steps in the neurogenic lineage, we combined fasting with lineage tracing and label retention assays. We found that IF does not affect NSC activation or maintenance. Contrary to previous reports, we also found that IF does not increase hippocampal neurogenesis. We obtained the same results regardless of strain, sex, diet length, tamoxifen administration or new-born neuron identification method. Our data suggest that NSCs maintain homeostasis upon IF and that this intervention is not a reliable strategy to increase adult neurogenesis.
Single particle profiler for measuring content and properties of nano-sized bioparticles
Authors: Sych Taras , Schlegel Jan , Barriga Hanna M.G. , Ojansivu Miina , Hanke Leo , Weber Florian , Bostancioglu R. Beklem , Ezzat Kariem , Stangl Herbert , Plochberger Birgit , Laurencikiene Jurga , El Andaloussi Samir , Fürth Daniel , Stevens Molly M. , Sezgin Erdinc 
Published: July 2022

AbstractIt is technically challenging to study the content and properties of nanoscale bioparticles in a high-throughput and single-molecule manner. We developed a high-throughput analysis method, called single particle profiler (SPP) that provides single-particle information on content and biophysical properties of thousands of particles. We applied SPP to measure the mRNA encapsulation efficiency of lipid nanoparticles, viral binding efficiency of different nanobodies and biophysical heterogeneity of liposomes, lipoproteins, exosomes and viruses.
High-resolution characterisation of short-term temporal variability in the taxonomic and resistome composition of wastewater influent
Authors: Chau KK , Goodall T , Bowes M , Easterbrook K , Brett H , Hughes J , Crook DW , Read DS , Walker AS , Stoesser N 
Published: July 2022

AbstractWastewater-based epidemiology (WBE) for population-level surveillance of antimicrobial resistance (AMR) is gaining significant traction, but the impact of wastewater sampling methods on results is unclear. In this study we characterised taxonomic and resistome differences between single-timepoint-grab and 24H-composites of wastewater influent from a large UK-based wastewater treatment work (WWTW [population equivalent:223,435]).We autosampled hourly influent grab samples (n=72) over three consecutive weekdays, and prepared additional 24H-composites (n=3) from respective grabs. For taxonomic profiling, metagenomic DNA was extracted from all samples and 16S-rRNA gene sequenced. One composite and six grabs from day one underwent metagenomic sequencing for metagenomic dissimilarity estimation and resistome profiling.Taxonomic abundances of phyla varied significantly across hourly grab samples but followed a repeating diurnal pattern for all three days. Hierarchical clustering grouped grab samples into four time periods dissimilar in both 16S rRNA gene-based profiles and metagenomic distances. 24H-composites resembled mean daily phyla abundances and showed low variability of taxonomic profiles. Of the 122 AMR gene families (AGFs) identified across all day one samples, single grab samples identified a median of 6 (IQR:5-8) AGFs not seen in the composite. However, 36/36 of these hits were at lateral coverage <0.5 (median:0.19; IQR:0.16-0.22) and potential false positives. Conversely, the 24H-composite identified three AGFs not seen in any grab with higher lateral coverage (0.82; 0.55-0.84). Additionally, several clinically significant human AGFs (blaVIM, blaIMP, blaKPC) were intermittently or completely missed by grab sampling but captured by the 24H-composite.Wastewater influent undergoes significant taxonomic and resistome changes on short timescales potentially affecting interpretation of results based on sampling strategy. Grab samples are more convenient and potentially capture low-prevalence/transient targets but are less comprehensive and temporally variable. Therefore, we recommend 24H-composite sampling where feasible. Further validation and optimisation of WBE methods is vital for its development into a robust AMR surveillance approach.HighlightsInfluent undergoes significant taxonomic/resistome changes over short timescales.Taxonomic abundances fluctuate diurnally but repeat for the 3 weekdays sampled.Detection of less prevalent AMR determinants is time-dependent for grab sampling.Single timepoint grab samples may produce temporally variable metagenomic profiles.24H-composites reflect mean daily taxa and more reliably captured AMR determinants.
Control of PHYTOCHROME KINASE SUBSTRATE subcellular localization and biological activity by protein S-acylation
Authors: Vazquez Ana Lopez , Petrolati Laure Allenbach , Dessimoz Christophe , Lampugnani Edwin R. , Glover Natasha , Fankhauser Christian 
Published: July 2022

ABSTRACTPHYTOCHROME KINASE SUBSTRATE (PKS) proteins are involved in light-regulated growth orientation responses. They act downstream of phytochromes to control hypocotyl gravitropism in the light and act early in phototropin signaling. Despite their importance for plant development, little is known about their molecular mode of action except that they belong to a protein complex comprising the phototropins at the plasma membrane. Identifying evolutionarily conservation is one approach to reveal biologically important protein motifs. Here, we show that PKS sequences are restricted to seed plants and that these proteins share 6 motifs (A to F from the N- to the C-terminus). While motif D is also found in BIG GRAIN proteins the remining domains are PKS specific. We provide evidence that motif C is S-acylated on highly conserved cysteines, which mediates PKS protein association with the plasma membrane. This motif is also required for PKS4-mediated phototropism and control of hypocotyl gravitropism in the light. Finally, our data suggests that the mode of PKS4 plasma membrane association is important for its biological activity. Our work identifies the mode of plasma membrane association of PKS proteins and strongly suggests that this is their site of action to modulate environmentally regulated organ positioning.
How Turkey vultures tune their airspeed to environmental and behavioral factors
Authors: Rader Jonathan , Hedrick Tyson L. 
Published: July 2022

AbstractAnimals must tune their physical performance to changing environmental conditions, and the breadth of environmental tolerance may contribute to delineating the species’ geographic range. A common environmental challenge that flying animals face is the reduction of air density at high elevation and a reduction in the effectiveness of lift production that accompanies it. Turkey vultures (Cathartes aura) inhabit a >3000 m elevation range, and fly considerably higher, necessitating that they compensate for air density differences through behavior, physiology, or biomechanics. We predicted that birds flying at high elevation would demonstrate higher median flight speeds while maintaining similar glide angles. We used 3-dimensional videography to track Turkey vultures flying at three elevations and found a negative relationship between median airspeed and air density that matched our prediction. Additionally, neither the ratio of horizontal speed to sinking speed nor flapping behavior varied with air density. These results were robust to varying flight behavior (climbing vs. level flight). Finally, we derived a glide polar from the free-flying vultures and showed that they are proficient at tuning their flight speed to minimize their cost of transport during straight-line flight, but transition to a minimum power strategy during gliding turns.
Deep attention based variational autoencoder for antimicrobial peptide discovery
Authors: Ghorbani Mahdi , Prasad Samarjeet , Brooks Bernard R. , Klauda Jeffery B. 
Published: July 2022

AbstractAntimicrobial peptides (AMPs) have been proposed as a potential solution against multiresistant pathogens. Designing novel AMPs requires exploration of a vast chemical space which makes it a challenging problem. Recently natural language processing and generative deep learning have shown great promise in exploring the vast chemical space and generating new chemicals with desired properties. In this study we leverage a variational attention mechanism in the generative variational autoencoder where attention vector is also modeled as a latent vector. Variational attention helps with the diversity and quality of the generated AMPs. The generated AMPs from this model are novel, have high statistical fidelity and have similar physicochemical properties such as charge, hydrophobicity and hydrophobic moment to the real to the real antimicrobial peptides.
Development of a quantitative metagenomic approach to establish quantitative limits and its application to viruses
Authors: Langenfeld Kathryn , Hegarty Bridget , Vidaurri Santiago , Crossette Emily , Duhaime Melissa , Wigginton Krista 
Published: July 2022

ABSTRACTQuantitative metagenomic methods are maturing but continue to lack clearly-defined analytical limits. Here, we developed a computational tool, QuantMeta, to determine the absolute abundance of targets in metagenomes spiked with synthetic DNA standards. The tool establishes (1) entropy-based detection thresholds to confidently determine the presence of targets, and (2) an approach to identify and correct read mapping or assembly errors and thus improve the quantification accuracy. Together this allows for an approach to confidently quantify absolute abundance of targets, be they microbial populations, genes, contigs, or metagenome assembled genomes (MAGs). We applied the approach to quantify single- and double-stranded DNA viruses in wastewater viral metagenomes, including pathogens and bacteriophages. Concentrations of total DNA viruses in wastewater influent and effluent were greater than 108copies/mL using QuantMeta. Human-associated DNA viruses were detected and quantifiable with QuantMeta thresholds, including polyomavirus, papillomavirus, and crAss-like phages, at concentrations similar to previous reports that utilized quantitative PCR-based assays. Our results highlight the higher detection thresholds of quantitative metagenomics (∼500 copies/μL) as compared to PCR-based quantification (∼10 copies/μL) despite a sequencing depth of 200 million reads per sample. The QuantMeta approach, applicable to both viral and cellular metagenomes, advances quantitative metagenomics by improving the accuracy of measured target absolute abundances.
A manually curated annotation characterises genomic features of P. falciparum lncRNAs
Authors: Hoshizaki Johanna , Adjalley Sophie H. , Thathy Vandana , Judge Kim , Berriman Matthew , Reid Adam James , Lee Marcus C. S. 
Published: July 2022

AbstractBackgroundImportant regulation occurs at the level of transcription in Plasmodium falciparum and growing evidence suggests that these apicomplexan parasites have complex regulatory networks. Recent studies implicate long noncoding RNAs (lncRNAs) as transcriptional regulators in P. falciparum. However, due to limited research and the lack of necessary experimental tools, our understanding of their role in the malaria-causing parasite remains largely unelucidated. In this work, we address one of these limitations, the lack of an updated and improved lncRNA annotation in P. falciparum.ResultsWe generated long-read RNA sequencing data and integrated information extracted and curated from multiple sources to manually annotate lncRNAs. We identified 1522 novel lncRNAs and validated and refined 847 existing annotations. Utilising the collated datasets, we generated evidence-based ranking scores for each annotation and characterised the distinct genomic contexts and features of P. falciparum lncRNAs. Certain features indicated subsets with potential biological significance such as 25 lncRNAs containing multiple introns, 335 lncRNAs lacking mutations in piggyBac mutagenic studies and lncRNAs associated with specific biologic processes including two new types of lncRNAs found proximal to var genes.ConclusionsThe insights and the annotation presented in this study will serve as valuable tools for researchers seeking to understand the role of lncRNAs in parasite biology through both bioinformatics and experimental approaches.
‘Sniff Olfactometer (SO) Protocols
Authors: Ni Jiayue , Tang Qi , Huang Jianbo Dave , Solla Leto , Kelson Hannah , Weeks Marcus , Alcott Zoe , Ong Justin , Gomez Andrea , Ding Kaifeng , Acree A. Terry E. 
Published: July 2022

AbstractMost olfactometers used to study human olfaction have stimulus durations of more than 1 second and often lasting minutes(Dravnieks 1975; Leland et al. 2001; Schmidt and Cain 2010). During long stimulations, olfactory receptor responses and their resulting behaviors are modulated by adaptation and habituation to the stimulus(Pellegrino et al. 2017; Rankin 2009; Wilson and Linster 2008). For example, EOG results from the first deorphanized olfactory receptor tissue reached a maximum in ∼1 s, dropping to 1/2 maximum in the next second, and showing little signal reduction until the stimulation stopped after 6 seconds(Zhao et al. 1998). Longer stimulations can result in complete habituation; receptors still respond even though the behavior shows complete habituation (Barwich 2014). To minimize the effects of adaption and habituation on stimulus responses, the sniff olfactometer (SO) combined the precision of a blast olfactometer with the gentleness of a stream olfactometer by blasting a brief odorant puff (70ms duration) into a subject’s self-imposed inhalation air stream(Rochelle 2017; Rochelle et al. 2017b; Wyckoff and Acree 2017). Here we describe SO protocols for threshold determinations of odorants in aqueous headspaces using odorant recognition probabilities associated with Log(odorant-concentrations(Rochelle et al. 2017a)). During a single trial a subject, preconditioned to associate a veridical name with a given odor (e.g., a pyrazine with “nuts” when the odor was detected and “not nuts” if it wasn’t) was cued to “inhale” and 750ms later, a 15ml-70ms puff of odorant headspace was delivered into their inhalation airstream. A session consisted of 12 randomized double-blind trials of 3 different odorant concentrations. Additional sessions with different concentrations were conducted until the response probability to the samples ranged from below 0.2 to above 0.8. The robustness of the fitted function and the size of their confidence intervals depended on the difference between the concentrations of the odorants during a single session: small differences in sample concentration resulted in the data failing to fit a logistic function; larger concentration differences resulted in a better fit to the model. However, if one of the stimuli had no odorant at all i.e., a blank, the response to the blank was random.
Reducing Merkel cell activity in the whisker follicle disrupts cortical encoding of whisker movement amplitude and velocity
Authors: Lemercier Clément E. , Krieger Patrik 
Published: July 2022

AbstractMerkel cells (MCs) and associated primary sensory afferents of the whisker follicle-sinus complex robustly code whisker self-movement, angle, and whisk phase during whisking. However, direct evidence of their roles in encoding whisker movement at cortical level is currently missing. To this end, spiking activity of primary somatosensory barrel cortex (wS1) neurons was measured in response to varying whisker deflection amplitude and velocity in transgenic mice with previously established reduced mechanoelectrical coupling at MC-associated afferents. Under reduced MC activity, wS1 neurons exhibited increased sensitivity to whisker deflection. This appeared to arise from a lack of variation in response magnitude to varying whisker deflection amplitude and velocity. This latter effect was further indicated by weaker variation in the temporal profile of the evoked spiking activity when whisker deflection amplitude and velocity varied. Nevertheless, under reduced MC activity, wS1 neurons retained the ability to discriminate stimulus features based on the timing of the first post-stimulus spike. Collectively, results from this study suggest that MCs contribute to both cortical encoding of whisker amplitude and velocity predominantly by tuning cortical response magnitude and by patterning evoked spiking activity, rather than in tuning cortical response latency.
A translational swine model for Crohn’s disease
Authors: Winogrodzki T , Metwaly A , Grodziecki A , Liang W , Klinger B , Flisikowski K , Flisikowska T , Fischer K , Steiger K , Haller D , Schnieke A 
Published: July 2022

AbstractCrohn’s Disease (CD) is incurable, and represents a lifelong burden for patients and its incidence is increasing worldwide. A key contributing factor is a dysregulated immune response. Here we report the generation of genome edited pigs with a deletion of the transcript-destabilizing AU-rich element (ARE) and a constitutive decay element (CDE) in the TNF gene which recapitulate major characteristics of human CD, including ulcerative transmural ileocolitis, increased abundance of proinflammatory cytokines, evidence for impaired integrity of the intestinal epithelial cell barrier, immune cell infiltration, and dysbiotic microbial communities. This physiologically relevant CD model enables human-scale and long-term studies to assess diagnostic, nutritional or microbial interventions, filling the gap for translating findings into the clinic.
The SSU Processome Component Utp25p is a Pseudohelicase
Authors: Helwer Rafe , Charette J. Michael 
Published: July 2022

AbstractRNA helicases are involved in nearly all aspects of RNA metabolism and factor prominently in ribosome assembly. The SSU processome includes 10 helicases and many helicase-cofactors. Together, they mediate the structural rearrangements that occur during ribosomal SSU assembly. During the identification of the SSU processome component Utp25, it was noticed that the protein displays some sequence similarity to DEAD-box RNA helicases and is essential for growth. Interestingly, mutational ablation showed that Utp25’s DEAD-box motifs are dispensable. Here, we use AlphaFold to show that Utp25 retains considerable structural similarity to DEAD-box helicases and is the first fully validated pseudohelicase.
Brain Network Architecture Constrains Age-related Cortical Thinning
Authors: Petersen Marvin , Nägele Felix L. , Mayer Carola , Schell Maximilian , Rimmele D. Leander , Petersen Elina , Kühn Simone , Gallinat Jürgen , Hanning Uta , Fiehler Jens , Twerenbold Raphael , Gerloff Christian , Thomalla Götz , Cheng Bastian 
Published: July 2022

AbstractAge-related cortical atrophy, approximated by cortical thickness measurements from magnetic resonance imaging, follows a characteristic pattern over the lifespan. Although its determinants remain unknown, mounting evidence demonstrates correspondence between the connectivity profiles of structural and functional brain networks and cortical atrophy in health and neurological disease. Here, we performed a cross-sectional multimodal neuroimaging analysis of 2633 individuals from a large population-based cohort to characterize the association between age-related differences in cortical thickness and functional as well as structural brain network topology. We identified a widespread pattern of age-related cortical thickness differences including “hotspots” of strong age effects located in brain areas with high centrality (structural network hubs). Regional age-related differences were furthermore strongly correlated within the structurally defined node neighborhood. The overall pattern of thickness differences as well as its change throughout the later lifespan was found to be anchored in the functional network hierarchy as encoded by macroscale functional connectivity gradients. Lastly, the identified difference pattern covaried significantly with cognitive and motor performance. Our findings indicate that connectivity profiles of functional and structural brain networks might act as organizing principles behind age-related cortical thinning as an imaging surrogate of cortical atrophy.
Swapped genetic code blocks viral infections and gene transfer
Authors: Nyerges Akos , Vinke Svenja , Flynn Regan , Owen Siân V. , Rand Eleanor A. , Budnik Bogdan , Keen Eric , Narasimhan Kamesh , Marchand Jorge A. , Baas-Thomas Maximilien , Liu Min , Chen Kangming , Chiappino-Pepe Anush , Hu Fangxiang , Baym Michael , Church George M. 
Published: July 2022

AbstractRemoving cellular transfer RNAs (tRNAs), making their cognate codons unreadable, creates a genetic firewall that prevents viral replication and horizontal gene transfer. However, numerous viruses and mobile genetic elements encode parts of the translational apparatus, including tRNAs, potentially rendering a genetic-code-based firewall ineffective. In this paper, we show that such horizontally transferred tRNA genes can enable viral replication in Escherichia coli cells despite the genome-wide lack of three codons and the previously essential cognate tRNAs and release factor 1. By repurposing viral tRNAs, we then develop recoded cells bearing an amino-acid-swapped genetic code that reassigns two of the six serine codons to leucine during translation. This amino-acid-swapped genetic code renders cells completely resistant to viral infections by mistranslating viral proteomes and prevents the escape of synthetic genetic information by engineered reliance on serine codons to produce leucine-requiring proteins. Finally, we also repurpose the third free codon to biocontain this virus-resistant host via dependence on an amino acid not found in nature.