bluuebunny/crossref_metadata_2025_split huggingface dataset:
A magnetic pulse does not affect free-flight navigation behaviour of a medium-distance songbird migrant in spring
Authors: Karwinkel Thiemo , Winklhofer Michael , Janner Lars Erik , Brust Vera , Hüppop Ommo , Bairlein Franz , Schmaljohann Heiko 
Published: May 2022

AbstractCurrent evidence suggests that migratory animals extract map information from the geomagnetic field for true navigation. The sensory basis underlying this feat is elusive, but presumably involves magnetic particles. A common experimental manipulation procedure consists of pre-treating animals with a magnetic pulse. This aims at re-magnetising particles to alter the internal representation of the external field prior to a navigation task. While pulsing provoked deflected bearings in laboratory experiments, analogous studies with free-flying songbirds yielded inconsistent results. Here, we pulsed European robins (Erithacus rubecula), being medium-distance migrants, at an offshore stopover site during spring migration and monitored their free-flight behaviour with a regional-scale tracking system. We found no pulse effect on departure probability, nocturnal departure timing, or departure direction, in agreement with results on a long-distance migrant released at the same site in autumn. This necessitates a reassessment of the importance of geomagnetic maps for migratory decisions for free-flying birds.Summary statementMagnetic pulse pre-treatment disturbs geomagnetic map usage of birds in lab environments. However, our free-flying birds show no effect, suggesting geomagnetic map information is less important in the natural environment.
“The replication stress response suppresses mutation rates in mismatch repair deficient budding yeast and human cancers”
Authors: Shrikhande Amruta , Sørensen Simon G. , Offman Judith , Domanska Barbara , Pedersen Jakob S. , Hoffmann Eva R. 
Published: May 2022

AbstractElevated mutation rate is a hallmark of mismatch repair (MMR) deficient cells and tumours. This includes microsatellite instability (MSI), which is caused by insertions and deletions in mono-and dinucleotide repeats. MSI rates, however, are highly variable across MMR-deficient tumours. Here we show that mutation rates are genetically regulated in MMR-deficient cells. A genome-wide deletion screen in budding yeast revealed that 3% gene deletions caused mutation rates to be further elevated, whereas 11% reduced mutation rates. The genes causing an elevation are enriched for DNA repair and replication processes, whereas deletion of genes implicated in transcriptional processes reduce mutation rates. A pan-cancer analysis of MSI revealed that mutations in replication stress response (ATR, TOPBP1, CHEK1) or DNA repair genes (RAD50, TOP3A) was associated with extreme rates of MSI in MMR-defective tumours, but not when mutated on their own. Since replication stress, DNA damage and repair activities are cell-type specific, this may account for highly variable mutation rates associated with different MMR-deficient tumours.
High resolution quantitative and functional MRI indicate lower myelination of thin and thick stripes in human secondary visual cortex
Authors: Haenelt Daniel , Trampel Robert , Nasr Shahin , Polimeni Jonathan R. , Tootell Roger B. H. , Sereno Martin I. , Pine Kerrin J. , Edwards Luke J. , Helbling Saskia , Weiskopf Nikolaus 
Published: May 2022

AbstractThe characterization of cortical myelination is essential for the study of structure-function relationships in the human brain. However, knowledge about cortical myelination is largely based on post mortem histology, which generally renders direct comparison to function impossible. The repeating pattern of pale-thin-pale-thick stripes of cytochrome oxidase (CO) activity in the primate secondary visual cortex (V2) is a prominent columnar system, in which histology also indicates different myelination of thin/thick versus pale stripes. We used quantitative magnetic resonance imaging (qMRI) in conjunction with functional magnetic resonance imaging (fMRI) at ultra-high field strength (7 T) to localize and study myelination of stripes in four human participants at sub-millimeter resolutionin vivo. Thin and thick stripes were functionally localized by exploiting their sensitivity to color and binocular disparity, respectively. Resulting functional activation maps showed robust stripe patterns in V2 which enabled further comparison of quantitative relaxation parameters between stripe types. Thereby, we found lower longitudinal relaxation rates (R1) of thin and thick stripes compared to surrounding gray matter in the order of 1–2%, indicating higher myelination of pale stripes. No consistent differences were found for effective transverse relaxation rates. The study demonstrates the feasibility to investigate structure-function relationships in living humans within one cortical area at the level of columnar systems using qMRI.
Differentiated dynamic response in C. elegans chemosensory cilia
Authors: Bruggeman Christine W. , Haasnoot Guus H. , Danné Noémie , van Krugten Jaap , Peterman Erwin J.G. 
Published: May 2022

SummaryCilia are membrane-enveloped organelles that protrude from the surface of most eurokaryotic cells and play crucial roles in sensing the external environment. For maintenance and function cilia are dependent on intraflagellar transport (IFT). Here we use a combination of microfluidics and fluorescence microscopy to study the response of phasmid chemosensory neurons, in live Caenorhabditis elegans, to chemical stimuli. We found that chemical stimulation resulted in unexpected changes in IFT and ciliary structure. Notably, stimulation with hyperosmotic solutions or chemical repellents resulted in different responses, not only in IFT, ciliary structure and cargo distribution, but also in neuronal activity. The response to chemical repellents results in habituation of the neuronal activity, suggesting that IFT plays a role in regulating the chemosensory response. Our findings show that cilia are able to sense and respond to different external cues in distinct ways, highlighting the flexible nature of cilia as sensing hubs.
Modeling Transient Brain Coactivity Patterns in Latent Space with FMRI Data
Authors: Li Kaiming , Hu Xiaoping 
Published: May 2022

AbstractThe brain is a complex dynamic system that constantly evolves. Characterization of the spatiotemporal dynamics of brain activity is fundamental to understanding how brain works. Current studies with functional connectivity and linear models are limited by low temporal resolution and insufficient model capacity. With a generative variational auto encoder (VAE), the present study mapped the high-dimensional transient co-activity patterns (CAPs) of functional magnetic resonance imaging data to a low-dimensional latent representation that followed a multivariate gaussian distribution. We demonstrated with multiple datasets that the VAE model could effectively represent the transient CAPs in the latent space. Transient CAPs from high-intensity and low-intensity values reflected the same functional structure of brain and could be reconstructed from the same distribution in the latent space. With the reconstructed latent time courses, preceding CAPs successful predicted the following transient CAP with a long short-term memory recurrent neural network. Our methods provide a new avenue to characterize the brain’s transient co-activity maps and model the complex dynamics between them in a framewise manner.
Loss of heterochromatin at endogenous retroviruses creates competition for transcription factor binding
Authors: O’Hara Ryan , Banaszynski Laura A. 
Published: May 2022

AbstractThe mammalian genome is partitioned into active and inactive regions, broadly termed euchromatin and heterochromatin, respectively. The majority of heterochromatin consists of repetitive elements, including endogenous retroviruses (ERVs). ERVs are enriched in regulatory elements containing transcription factor (TF) binding sites with individual families containing hundreds to thousands of distinct copies scattered throughout the genome. We hypothesized that epigenetic derepression of ERVs (such as that observed during early development) may alter the stoichiometry between TFs and their euchromatic target sites, with ERVs effectively competing for these factors. To test this, we modeled acute heterochromatin loss using inducible deletion of the co-repressor KAP1 in mouse embryonic stem cells (ESCs). Upon KAP1 deletion, we observe clear reductions in chromatin accessibility, histone acetylation, and TF binding at euchromatic regions. To directly test the concept of global binding site competition, we designed exogenous binding site arrays (EBSAs) to introduce upwards of 1500 copies of the OCT4 TF binding motif into ESCs. OCT4 EBSAs specifically reduce chromatin accessibility at POU family motifs and result in reduced transcription of the pluripotency machinery with subsequent differentiation. Overall, these data support a model in which heterochromatin at ERVs promotes euchromatic TF binding and transcriptional homoeostasis. We propose that regulated ERV derepression during pre-implantation may serve as a developmental siphon to weaken the robustness of ongoing transcription programs in favor of the plasticity required for cell fate specification.
Rewiring of liver diurnal transcriptome rhythms by triiodothyronine (T3) supplementation
Authors: de Assis Leonardo Vinícius Monteiro , Harder Lisbeth , Lacerda José Thalles , Parsons Rex , Kaehler Meike , Cascorbi Ingolf , Nagel Inga , Rawashdeh Oliver , Mittag Jens , Oster Henrik 
Published: May 2022

ABSTRACTDiurnal (i.e., 24-hour) physiological rhythms depend on transcriptional programs controlled by a set of circadian clock genes/proteins. Systemic factors like humoral and neuronal signals, oscillations in body temperature, and food intake align physiological circadian rhythms with external time. Thyroid hormones (THs) are major regulators of circadian clock target processes such as energy metabolism, but little is known about how fluctuations in TH levels affect the circadian coordination of tissue physiology. In this study, a high triiodothyronine (T3) state was induced in mice by supplementing T3in the drinking water, which affected body temperature, and oxygen consumption in a time-of-day dependent manner. 24-hour transcriptome profiling of liver tissue identified 37 robustly and time independently T3associated transcripts as potential TH state markers in the liver. Such genes participated in xenobiotic transport, lipid and xenobiotic metabolism. We also identified 10 – 15 % of the liver transcriptome as rhythmic in control and T3groups, but only 4 % of the liver transcriptome (1,033 genes) were rhythmic across both conditions – amongst these several core clock genes. In-depth rhythm analyses showed that most changes in transcript rhythms were related to mesor (50%), followed by amplitude (10%), and phase (10%). Gene set enrichment analysis revealed TH state dependent reorganization of metabolic processes such as lipid and glucose metabolism. At high T3levels, we observed weakening or loss of rhythmicity for transcripts associated with glucose and fatty acid metabolism, suggesting increased hepatic energy turnover. In sum, we provide evidence that tonic changes in T3levels restructure the diurnal liver metabolic transcriptome independent of local molecular circadian clocks.
Sustained responses and neural synchronization to amplitude and frequency modulation in sound change with age
Authors: Herrmann Björn , Maess Burkhard , Johnsrude Ingrid S. 
Published: May 2022

AbstractPerception of speech requires sensitivity to features, such as amplitude and frequency modulations, that are often temporally regular. Previous work suggests age-related changes in neural responses to temporally regular features, but little work has focused on age differences for different types of modulations. We recorded magnetoencephalography in younger (21–33 years) and older adults (53–73 years) to investigate age differences in neural responses to slow (2-6 Hz sinusoidal and non-sinusoidal) modulations in amplitude, frequency, or combined amplitude and frequency. Audiometric pure-tone average thresholds were elevated in older compared to younger adults, indicating subclinical hearing impairment in the recruited older-adult sample. Neural responses to sound onset (independent of temporal modulations) were increased in magnitude in older compared to younger adults, suggesting hyperresponsivity and a loss of inhibition in the aged auditory system. Analyses of neural activity to modulations revealed greater neural synchronization with amplitude, frequency, and combined amplitude-frequency modulations for older compared to younger adults. This potentiated response generalized across different degrees of temporal regularity (sinusoidal and non-sinusoidal), although neural synchronization was generally lower for non-sinusoidal modulation. Despite greater synchronization, sustained neural activity was reduced in older compared to younger adults for sounds modulated both sinusoidally and non-sinusoidally in frequency. Our results suggest age differences in the sensitivity of the auditory system to features present in speech and other natural sounds.
Detergent headgroups control TolC folding in vitro
Authors: Ikujuni Ayotunde Paul , Budiardjo S. Jimmy , Slusky Joanna S.G. 
Published: May 2022

AbstractTolC is the trimeric outer membrane component of the efflux pump system in E. coli responsible for antibiotic efflux from bacterial cells. Over-expression of efflux pumps has been reported to decrease susceptibility to antibiotics in a variety of bacterial pathogens. Reliable production of membrane proteins allows for the biophysical and structural characterization needed to better understand efflux and for the development of therapeutics. Preparation of recombinant protein for biochemical/structural studies often involves the production of proteins as inclusion body aggregates from which bioactive proteins are recovered. Here we find that the in vitro folding of TolC into its functional trimeric state from inclusion bodies is dependent on the headgroup composition of detergent micelles used. Nonionic detergent favors the formation of functional trimeric TolC, whereas zwitterionic detergents induce the formation of a non-native trimeric TolC fold. We also find that nonionic detergents with shorter alkyl lengths facilitate TolC folding. It remains to be seen whether the charges in lipid headgroups have similar effects on membrane insertion and folding in biological systems.
MEIG1/PACRG associated and non-associated functions of axonemal dynein light intermediate polypeptide 1 (DNALI1) in mammalian spermatogenesis
Authors: Yap Yi Tian , Li Wei , Huang Qian , Zhou Qi , Zhang David , Mladenovic-Lucas Ljljiana , Granneman James G , Williams David C , Hess Rex A , Touré Aminata , Zhang Zhibing 
Published: May 2022

AbstractAxonemal dynein light intermediate polypeptide 1 (DNALI1) was originally cloned from Chlamydomonas reinhardtii in an effort to find motor proteins essential for flagellar motility. Here we report that DNALI1 is a binding partner of parkin co-regulated gene 1 (PACRG), which forms a complex with meiosis expressed gene 1 (MEIG1) in the manchette, a transient and unique structure only present in the elongating spermatids and required for normal spermiogenesis of the male germ cell differentiation process. DNALI1 recruits the PACRG protein in transfected CHO cells, and also stabilizes PACRG in bacteria and transfected mammalian cells. The untagged DNALI1 could also be co-purified with His-tagged PACRG in the gel filtration assay. Immunofluorescence staining on isolated male germ cells revealed that DNALI1 was present in the manchette of elongating spermatids, and colocalized with PACRG in this structure. In Pacrg mutant mice, localization of DNALI1 in the manchette was not changed, suggesting that DNALI1 and PACRG form a complex in the manchette, with DNALI1 being an upstream molecule. Mice deficiency in DNALI1 specifically in male germ cells showed dramatically reduced sperm numbers and were infertile. In addition, majority of the sperm exhibited abnormal morphology including misshapen heads, bent tails and enlarged midpiece, discontinuous accessory structure, and loss of sperm individualization, emphasizing the importance of DNALI1 in sperm development. Examination of testis histology revealed impaired spermiogenesis in the conditional Dnali1 knockout mice. Electron microscopy revealed disrupted ultrastructure in sperm of the Dnali1 mutant mice. Testicular levels of MEIG1, PACRG and SPAG16L proteins were not changed in the Dnali1 mutant mice. However, MEIG1 and SPAG16L were no longer present in the manchette in the absence of DNALI1. These findings demonstrate that DNALI1 is involved in the connection of the MEIG1/PACRG complex to carry cargo proteins along the manchette microtubules for sperm flagella formation. Given that Dnali1 mutant mice showed impaired sperm individualization that was not observed in the MEIG1 nor PACRG-deficient mice, DNALI1 might fulfill other functions beyond its role associated with the MEIG1/PACRG complex. Thus, DNALI1 plays multiple roles in sperm cell differentiation and function.Summary statementAxonemal dynein light intermediate polypeptide 1 (DNALI1) is required for sperm formation and male fertility. It associates with the MEIG1/PACRG complex in the manchette and is involved in a cargo transport system. In addition, it might be related to IFT and sperm individualization.
Inferring sources of suboptimality in perceptual decision making using a causal inference task
Authors: Shivkumar Sabyasachi , Cappelloni Madeline S. , Maddox Ross K. , Haefner Ralf M. 
Published: May 2022

AbstractPerceptual decision-making has been extensively modeled using the ideal observer framework. However, a range of deviations from optimality demand an extension of this framework to characterize the different sources of suboptimality. Prior work has mostly formalized these sources by adding biases and variability in the context of specific process models but are hard to generalize to more complex tasks. Here, we formalize suboptimalities as part of the brain’s probabilistic model of the task. Data from a traditional binary discrimination task cannot separate between different kinds of biases, or between sensory noise and approximate computations. We showed that this was possible using a recently developed causal inference task in which observers discriminated auditory cues in the presence of choice-uninformative visual cues. An extension of the task with different stimulus durations provided evidence for an increase in the precision of the computations with stimulus duration, separate from a decrease in observation noise.
An Ensemble Learning and Slice Fusion Strategy for Three-Dimensional Nuclei Instance Segmentation
Authors: Wu Liming , Chen Alain , Salama Paul , Dunn Kenneth W. , Delp Edward J. 
Published: May 2022

AbstractAutomated microscopy image analysis is a fundamental step for digital pathology and computer aided diagnosis. Most existing deep learning methods typically require post-processing to achieve instance segmentation and are computationally expensive when directly used with 3D microscopy volumes. Supervised learning methods generally need large amounts of ground truth annotations for training whereas manually annotating ground truth masks is laborious especially for a 3D volume. To address these issues, we propose an ensemble learning and slice fusion strategy for 3D nuclei instance segmentation that we call Ensemble Mask R-CNN (EMR-CNN) which uses different object detectors to generate nuclei segmentation masks for each 2D slice of a volume and propose a 2D ensemble fusion and a 2D to 3D slice fusion to merge these 2D segmentation masks into a 3D segmentation mask. Our method does not need any ground truth annotations for training and can inference on any large size volumes. Our proposed method was tested on a variety of microscopy volumes collected from multiple regions of organ tissues. The execution time and robustness analyses show that our method is practical and effective.
DeepSlice: rapid fully automatic registration of mouse brain imaging to a volumetric atlas
Authors: Carey Harry , Pegios Michael , Martin Lewis , Saleeba Christine , Turner Anita , Everett Nicholas , Puchades Maja , Bjaalie Jan , McMullan Simon 
Published: May 2022

AbstractRegistration of data to a common frame of reference is an essential step in the analysis and integration of diverse neuroscientific data modalities. To this end, volumetric brain atlases enable histological datasets to be spatially registered and analysed, yet accurate registration remains expertise-dependent and slow. We have trained a neural network, DeepSlice, to register mouse brain histology to the Allen Brain Atlas, retaining accuracy while improving speed by >1000 fold.
Genome-wide screen for enhanced noncanonical amino acid incorporation in yeast
Authors: Zackin Matthew T. , Stieglitz Jessica T. , Van Deventer James A. 
Published: May 2022

AbstractNumerous applications of noncanonical amino acids (ncAAs) in basic biology and therapeutic development require efficient protein biosynthesis using an expanded genetic code. However, achieving such incorporation at repurposed stop codons in cells is generally inefficient and limited by complex cellular processes that preserve the fidelity of protein synthesis. A more comprehensive understanding of the processes that contribute to ncAA incorporation would aid in the development of genomic engineering strategies for augmenting genetic code manipulation. In this work, we screened a pooledSaccharomyces cerevisiaemolecular barcoded yeast knockout (YKO) collection to identify single-gene knockout strains exhibiting improved ncAA incorporation efficiency in response to the amber (TAG) stop codon. We used a series of intracellular fluorescent reporters in tandem with fluorescence activated cell sorting (FACS) to identify 55 unique candidate deletion strains. Identified genes encode for proteins that participate in diverse cellular processes; many of the genes have no known connection with protein translation. We then verified that two knockouts,yil014c-aΔandalo1Δ, had improved incorporation efficiency using independently acquired strains possessing the knockouts. Characterizations of the activity ofyil014c-aΔandalo1Δwith additional orthogonal translation systems and ncAAs indicate that deletion of each of these genes enhances ncAA incorporation efficiency without loss of fidelity over a wide range of conditions. Our findings highlight opportunities for further modulating gene expression with genetic, genomic, and synthetic biology approaches to improve ncAA incorporation efficiency. In addition, these discoveries have the potential to enhance our fundamental understanding of protein translation. Ultimately, this study provides a foundation for future efforts to engineer cells to incorporate ncAA at greater efficiencies, which in turn will streamline the realization of applications utilizing expanded genetic codes ranging from basic biology to drug discovery.Abstract Figure