bluuebunny/crossref_metadata_2025_split huggingface dataset:
Single-neuron bursts encode pathological oscillations in Parkinson’s disease and essential tremor
Authors: Scherer Maximilian , Steiner Leon A , Kalia Suneil K , Hodaie Mojgan , Kühn Andrea A , Lozano Andres M , Hutchison William D , Milosevic Luka 
Published: April 2022

AbstractDeep brain stimulation procedures offer an invaluable opportunity to study disease through intracranial recordings from awake patients. Herein, we address the relationship between singleneuron and aggregate-level (local field potential; LFP) activities in the subthalamic nucleus (STN) and thalamic ventral intermediate nucleus (Vim) of patients with Parkinson’s disease (n=19) and essential tremor (n=16), respectively. Both disorders have been characterized by pathologically elevated LFP oscillations, as well as an increased tendency for neuronal bursting. Our findings suggest that periodic single-neuron bursts encode both pathophysiological beta (13-33Hz; STN) and tremor (4-10Hz; Vim) LFP oscillations, evidenced by strong time-frequency and phase-coupling relationships between the bursting and LFP signals. Spiking activity occurring outside of bursts had no relationship to the LFP. In STN, bursting activity most commonly preceded the LFP oscillation, suggesting that neuronal bursting generated within STN may give rise to an aggregate-level LFP oscillation. In Vim, LFP oscillations most commonly preceded bursting activity, suggesting that neuronal firing may be entrained by periodic afferent inputs. In both STN and Vim, the phasecoupling relationship between LFP and high-frequency oscillation (HFO) signals closely resembled the relationships between the LFP and single-neuron bursting. This suggests that periodic singleneuron bursting is likely representative of a higher spatial and temporal resolution readout of periodic increases in the amplitude of HFOs, which themselves may be a higher resolution readout of aggregate-level LFP oscillations. Overall, our results may reconcile “rate” and “oscillation” models of Parkinson’s disease and shed light onto the single-neuron basis and origin of pathophysiological oscillations in movement disorders.SignificanceIn surgical patients with Parkinson’s disease and essential tremor, we leverage intracranial recordings to establish a link between pathophysiological phenomena across various scales of observation (spatio-temporal resolutions). We provide insights and reconcile theories about aberrant neurocircuit phenomena which underly theses debilitating, medically refractory movement disorders. Furthermore, our connectivity analyses between single-neuron and local field potential activities may shed light on the origin of the deleterious neural oscillations underlying these disorders. Ultimately, our findings may aid in the development or investigation of targeted therapies to address or correct underlying neurocircuit dysfunction, which can include neuropharmaceuticals, but also novel neuromodulatory strategies like closed-loop deep brain stimulation targeting pathophysiological oscillations and phase-dependent stimulation methods seeking to stimulate “at the right time/phase.”
Revealing determinants of translation efficiency via whole-gene codon randomisation and machine learning
Authors: Nieuwkoop Thijs , Terlouw Barbara , de Ridder Dick , van der Oost John , Claassens Nico J. 
Published: April 2022

ABSTRACTCodon usage refers to the occurrence of synonymous codons in protein-coding genes. It is known for decades that codon usage contributes to translation efficiency and hence to protein production levels. However, its role in protein synthesis is still only partly understood. This lack of understanding hampers the design of synthetic genes for efficient protein production. In this study, we developed a method to generate a large, synonymous codon library of the gene encoding the red fluorescent protein (RFP). After expression in Escherichia coli, 1459 clones of this library were selected of which we measured protein production levels and determined the full coding sequences. Using different machine learning approaches, this data was used to reveal correlations between codon usage and protein production. Interestingly, protein production levels can be relatively accurately predicted (Pearson correlation of 0.762) by a Random Forest model, which only relies on the sequence information for the first 8 codons. This study clearly demonstrated the key role of codons at the start of the coding sequence. As such, it provides not only important fundamental insights on the influence of codon usage on protein production but also relevant clues on optimising the design of efficiently translated synthetic genes.
Architectural experience: clarifying its central components and their relation to core affect with a set of first-person-view videos
Authors: Gregorians Lara , Velasco Pablo Fernández , Zisch Fiona , Spiers Hugo J. 
Published: April 2022

AbstractWhen studying architectural experience in the lab, it is of paramount importance to use a proxy as close to real-world experience as possible. Whilst still images visually describe real spaces, and virtual reality allows for dynamic movement, each medium lacks the alternative attribute. To merge these benefits, we created and validated a novel dataset of valenced videos of first-person-view travel through built environments. This dataset was then used to clarify the relationship of core affect (valence and arousal) and architectural experience. Specifically, we verified the relationship between valence and fascination, coherence, and hominess - three key psychological dimensions of architectural experience which have previously been shown to explain aesthetic ratings of built environments. We also found that arousal is only significantly correlated with fascination, and that both are embedded in a relationship with spatial complexity and unusualness. These results help to clarify the nature of fascination, and to distinguish it from coherence and hominess when it comes to core affect. Moreover, these results demonstrate the utility of a video dataset of affect-laden spaces for understanding architectural experience.Highlights-Developed a video database of first-person-view journeys through built environments-We explored how core affect and architectural experience relate through the videos-Previous results are supported: valence ties to fascination, coherence and hominess-Arousal correlates only with fascination, and not coherence or hominess-Arousal and fascination are tied to spatial complexity and unusualness
Development of ultra-low-input nanoRibo-seq enables quantification of translational control, revealing broad uORF translation by subtype-specific neurons
Authors: Froberg John E. , Durak Omer , Macklis Jeffrey D. 
Published: April 2022

ABSTRACTWhile increasingly powerful approaches enable investigation of transcription using small samples of RNA, approaches to investigate translational regulation in small populations of specific cell types, and/or (sub)-cellular contexts are lacking. Comprehensive investigation of mRNAs actively translated into proteins from ultra-low input material would provide important insight into molecular machinery and mechanisms underlying many cellular, developmental, and disease processes in vivo. Such investigations are limited by the large input required for current state-of-the-art Ribo-seq. Here, we present an optimized, ultra-low input “nanoRibo-seq” approach using 102 – 103-fold less input material than standard approaches, demonstrated here in subtype-specific neurons. nanoRibo-seq requires as few as 2.5K neurons, and exhibits rigorous quality control features: 1) strong enrichment for CDS versus UTRs and non-CDS; 2) narrow, distinct length distributions over CDS; 3) ribosome P-sites predominantly in-frame to annotated CDS; and 4) sufficient ribosome-protected fragment (RPF) coverage across thousands of mRNAs. As proof-of-concept, we calculate translation efficiencies from paired Ribo-seq and alkaline fragmented control libraries from “callosal projection neurons” (CPN), revealing divergence between mRNA abundance and RPF abundance for hundreds of genes. Intriguingly, we identify substantial translation of upstream ORFs in the 5’ UTRs of genes involved in axon guidance and synapse assembly. nanoRibo-seq enables previously inaccessible investigation of translational regulation by small, specific cell populations in normal or perturbed contexts.
Evolution of Delta variant by non-Spike signature co-appearing mutations: trailblazer of COVID-19 disease outcome
Authors: Banerjee Anindita , Mazumder Anup , Roy Jayita , Majumdar Agniva , Chatterjee Ananya , Biswas Nidhan K , Sarkar Mamta Chawla , Maitra Arindam , Dutta Shanta , Das Saumitra 
Published: April 2022

AbstractThe high transmissibility and infectivity of a SARS-CoV-2 variant is usually ascribed to the Spike mutations, while emerging non-spike mutations might be a serious threat to the current Spike-recombinant vaccines. In addition to mutations in structural Spike glycoprotein, rapid accumulation of mutations across non-structural genes is leading to continuous virus evolution, altering its pathogenicity. We performed whole genome sequencing of SARS-CoV-2 positive samples collected from different clinical groups from eastern India, during the second pandemic wave (April-May, 2021). In addition to the several common spike mutations in Delta variant, two mutually explicit signature constellations of non-spike co-appearing mutations were identified, driving symptomatic and asymptomatic infections. We attempted to correlate these unique signatures of non-Spike co-appearing mutations to COVID-19 disease outcome. Results revealed that the Delta strains harboring a unique constellation of 9 non-spike co-appearing mutations could be the wheeler and dealer of symptomatic infection, even post vaccination. The strains predominantly driving asymptomatic infection possessed 7 non-spike co-appearing mutations, which were mutually exclusive in contrast to the set of mutations causing symptomatic disease. Phylodynamic analysis depicted high probability of emergence of these unique sub-clusters within India, with subsequent spread worldwide. Interestingly, some mutations of this signature were selected in Omicron and IHU variants, which suggest that gradual accumulation of such co-existing mutations may lead to emergence of more “vaccine-evading variants” in future. Hence, unfaltering genome sequencing and tracking of non-Spike mutations might be significant in formulation of any future vaccines against emerging SARS-CoV-2 variants that might evade the current vaccine-induced immunity.
Goal-directed recruitment of Pavlovian biases through selective visual attention
Authors: Algermissen Johannes , den Ouden Hanneke E.M. 
Published: April 2022

AbstractProspective outcomes bias behavior in a “Pavlovian” manner: Reward prospect invigorates action, while punishment prospect suppresses it. Theories have posited Pavlovian biases as global action “priors” in unfamiliar or uncontrollable environments. However, this account fails to explain the strength of these biases—causing frequent action slips—even in well-known environments. We propose that Pavlovian control is additionally useful if flexibly recruited by instrumental control. Specifically, instrumental action plans might shape selective attention to reward/ punishment information and thus the input to Pavlovian control. In two eye-tracking samples (N = 35/ 64), we observed that Go/ NoGo action plans influenced when and for how long participants attended to reward/ punishment information, which in turn biased their responses in a Pavlovian manner. Participants with stronger attentional effects showed higher performance. Thus, humans appear to align Pavlovian control with their instrumental action plans, extending its role beyond action defaults to a powerful tool ensuring robust action execution.
Can the Insect Path Integration Memory be a Bump Attractor?
Authors: Pisokas Ioannis , Kudryashova Nina , Hennig Matthias H. 
Published: April 2022

AbstractMany animal species are able to return to their nest after a foraging excursion without using familiar visual cues to guide them. They accomplish this by using a navigation competence known as path integration, which is vital in environments that do not have prominent visual features. To perform path integration, an animal maintains a running estimate of the distance and direction to its origin as it moves. This distance and direction estimate needs to be maintained in memory until the animal uses it to return to its nest. However, the neural substrate of this memory remains uncertain. A common hypothesis is that the information is maintained in a bump attractor’s state. We test the bump attractor hypothesis and find that its predictions are inconsistent with the path integration behaviour of ants, thus highlighting the need for alternative models of path integration memory.
Fragmented habitat compensates for the adverse effects of genetic bottleneck
Authors: Löytynoja Ari , Rastas Pasi , Valtonen Mia , Kammonen Juhana , Holm Liisa , Olsen Morten Tange , Paulin Lars , Jernvall Jukka , Auvinen Petri 
Published: April 2022

AbstractIn the face of human-caused biodiversity crisis, understanding the theoretical basis of conservation efforts of endangered species and populations has become increasingly important. According to population genetics theory, population subdivision helps organisms retain genetic diversity, crucial for adaptation in a changing environment. Habitat shape is thought to be important for generating and maintaining population subdivision, but empirical cases are needed to test this assumption. We studied Saimaa ringed seals, landlocked in a labyrinthine lake and recovering from a drastic bottleneck, by whole-genome sequencing 105 individuals and additional individuals from three other ringed seal subspecies. We analyzed the distribution of variation and genetic relatedness among the individuals in relation to the habitat shape. Despite a severe history of a genetic bottleneck with prevalent homozygosity in Saimaa ringed seals, we found evidence for population structure mirroring the subregions of the lake. Highlighting the significance of habitat connectivity in conservation biology and the power of genomic tools in understanding its impact, genome-wide analyses showed that the subpopulations had retained unique variation and largely complementary patterns of homozygosity. Integration of genetic analyses in conservation decisions gives hope to Saimaa ringed seals and other endangered species in fragmented habitats.
Microclimate is a strong predictor of the native and invasive plant-associated soil microbiota on San Cristóbal Island, Galápagos archipelago
Authors: Schoenborn Alexi A. , Yannarell Sarah M. , MacVicar Caroline T. , Barriga-Medina Noelia N. , Markillie Meng , Mitchell Hugh , Bonham Kevin S. , Leon-Reyes Antonio , Riveros-Iregui Diego , Klepac-Ceraj Vanja , Shank Elizabeth A. 
Published: April 2022

ABSTRACTUnderstanding the major drivers that influence soil bacterial and fungal communities is essential to mitigate the impacts of human activity on vulnerable ecosystems, like those found on the Galápagos Islands. Located ~1000 km off the coast of Ecuador, the volcanically formed islands are situated within distinct oceanic currents, which provide seasonal weather patterns and unique microclimates within small spatial scales across the islands. Although much is known about the impacts of human activity, such as climate change and invasive plant species, on above ground biodiversity of the Galápagos Islands, little is known about the resident soil microbial communities and the drivers that shape these communities. Here, our goal was to investigate the bacterial and fungal communities found in soil located in three distinct microclimates: Mirador (arid), Cerro Alto (transition zone), and El Junco (humid), and associated with native and invasive plant types. At each site, we collected soil at three depths (rhizosphere, 5 cm, and 15 cm) associated with the invasive plant,Psidium guajava(guava), and native plant types. We determined that the sampling location (microclimate) was the strongest driver of both bacterial and fungal communities (74 and 38%, respectively), with additional minor but significant impacts from plant type and soil depth. This study highlights the continued need to explore microbial communities across diverse environments and demonstrates the weight of different abiotic and biotic factors impacting soil microbial communities across San Cristóbal Island in the Galápagos archipelago.IMPORTANCE/SIGNIFICANCEHuman activity such as climate change, pollution, introduction of invasive species, and deforestation, poses a huge threat to biodiverse environments. Soil microbiota are an essential component to maintaining healthy ecosystems. However, a greater understanding of factors that alter these microbial communities is needed in order to find ways to mitigate and reverse the impacts imposed by human activity. The Galápagos Islands are a unique real-world laboratory, in that the islands’ biogeography and physical locations in the Pacific Ocean provide distinct microclimates within small geographic distances. Harnessing these distinct environments allowed us to investigate the influence of microclimates, soil depth, and vegetation cover on bacterial and fungal community composition.
Tracing carbon metabolism with stable isotope metabolomics reveals the legacy of diverse carbon sources in soil
Authors: Wilhelm Roland C. , Barnett Samuel E. , Swenson Tami L. , Youngblut Nicholas D. , Koechli Chantal N. , Bowen Benjamin P. , Northen Trent R. , Buckley Daniel H. 
Published: April 2022

AbstractTracking the metabolic activity of whole soil communities can improve our understanding of the transformation and fate of carbon in soils. We used stable isotope metabolomics to trace 13C from nine labeled carbon sources into the water-soluble metabolite pool of an agricultural soil over time. Soil was amended with a mixture of all nine sources, with one source isotopically labeled in each treatment. We compared changes in the 13C-enrichment of metabolites with respects to carbon source and time over a 48-day incubation and contrasted differences between soluble versus insoluble sources. Whole soil metabolite profiles varied singularly by time, while the composition of 13C-labeled metabolites differed primarily by carbon source (R2 = 0.68) rather than time (R2 = 0.07) with source-specific differences persisting throughout incubations. The 13C-labeling of metabolites from insoluble carbon sources occurred at a slower rate than soluble sources but yielded a higher average atom % 13C in metabolite markers of biomass (amino acids and nucleic acids). The 13C-enrichment of metabolite markers of biomass stabilized at between 5 – 15 atom % 13C by the end of incubations. Temporal patterns in the 13C-enrichment of TCA cycle intermediates, nucleobases (uracil and thymine), and by-products of DNA salvage (allantoin) closely tracked microbial activity. Our results demonstrate that metabolite production in soils is driven by the carbon source supplied to the community, and that the fate of carbon in metabolite profiles do not tend to converge over time as a result of ongoing microbial processing and recycling.ImportanceCarbon metabolism in soil remains poorly described due to the inherent difficulty of obtaining information on the microbial metabolites produced by complex soil communities. Our study demonstrates the use of stable isotope probing (SIP) to study carbon metabolism in soil by tracking 13C from supplied carbon sources into metabolite pools and biomass. We show that differences in the metabolism of sources influences the fate of carbon in soils. Heterogeneity in 13C-metabolite profiles corresponded with compositional differences in the metabolically active populations, providing a basis for how microbial community composition is correlated with the quality of soil carbon. Our study demonstrates the application of SIP-metabolomics in studying soils and identifies several metabolite markers of growth, activity, and other aspects of microbial function.
INTERCEPT pathogen reduction of platelet concentrates induces trans-arachidonic acids and affects eicosanoid formation
Authors: Leitner Gerda C. , Hagn Gerhard , Niederstätter Laura , Bileck Andrea , Plessl-Walder Kerstin , Horvath Michaela , Kolovratova Vera , Tanzmann Andreas , Tolios Alexander , Rabitsch Werner , Wohlfarth Philipp , Gerner Christopher 
Published: April 2022

AbstractGamma-irradiation of blood products is mandatory to avoid graft versus host disease in patients with immunosuppressed clinical conditions. Pathogen inactivation techniques were implemented to optimize safe blood component supply. The INTERCEPT treatment uses amotosalen together with UVA irradiation. The functional and molecular implications of these essential treatments have not yet been systematically assessed. The irradiation-induced inactivation of nucleic acids may actually be accompanied with modifications of chemically reactive polyunsaturated fatty acids, known to be important mediators of platelet functions. Thus, here we investigated eicosanoids and related fatty acids released upon treatment and during platelet storage for 7 days, complemented by the analysis of functional and metabolic consequences of these treatments. In contrast to gamma-irradiation, here we demonstrate that UVA treatment attenuated the formation of ALOX12-products such as 12-HETE and 12-HEPE but induced the formation of trans-arachidonic acids in addition to 11-HETE and HpODEs. Metabolic and functional issues like glucose consumption, lactate formation, platelet aggregation and clot firmness hardly differed between the two treatment groups. In vitro synthesis of trans-arachidonic acids (trans-AA) out of arachidonic acid in the presence of β-mercaptoethanol suggested that thiol radicals formed by UVA treatment are responsible for the INTERCEPT-specific effects observed in platelet concentrates. It is plausible to assume that trans-AA and other UVA-induced molecules may have specific biological effects on the recipients, which need to be addressed in future studies.Key pointsA previously unrecognized radical mechanisms for the generation of trans-fatty acids by UVA was identifiedIrradiation with UVA was found to immediately affect the generation of polyunsaturated fatty acid oxidation products