Miracle-dz/UniFAR-FTUs huggingface dataset:
Evaluation of data-driven MEG analysis approaches for the extraction of fMRI resting state networks

The electrophysiological basis of resting state networks (RSN) is still under debate. In particular, no principled mechanism has been determined that is capable of explaining all RSN equally well. While magnetoencephalography (MEG) and electroencephalography (EEG) are the methods of choice to determine the electrophysiological basis of RSN, no standard analysis pipeline of RSN yet exists. In this paper, we compare the two main existing data-driven analysis strategies for extracting resting state networks from MEG data. The first approach extracts RSN through an independent component analysis (ICA) of the Hilbert envelope in different frequency bands. The second approach uses phase –amplitude coupling to determine the RSN. To evaluate the performance of these approaches, we compare the MEG-RSN to the functional magnetic resonance imaging (fMRI)-RSN from the same subjects. Overall, it was possible to extract the canonical fMRI RSN with MEG. The approach based on phase-amplitude coupling yielded the best correspondence to the fMRI-RSN. The Hilbert envelope-ICA produced different dominant frequency-bands underlying RSN for different ICA runs, suggesting the absence of a single dominant frequency underlying the RSN. Our results also suggest that individual RSN are not characterized by one single dominant frequency. Instead, the resting state networks seem to be based on a combination of the delta/theta phase and gamma amplitude.
Enhanced lipogenesis through Pparγ helps cavefish adapt to food scarcity

Nutrient availability varies seasonally and spatially in the wild. The resulting nutrient limitation or restricted access to nutrients pose a major challenge for every organism. While many animals, such as hibernating animals, evolved strategies to overcome periods of nutrient scarcity, the cellular mechanisms of these strategies are poorly understood. Cave environments represent an extreme example of nutrient deprived environments since the lack of sunlight and therefore primary energy production drastically diminishes the nutrient availability. Here, we used Astyanax mexicanus, which includes river-dwelling surface fish and cave adapted cavefish populations to study the genetic adaptation to nutrient limitations. We show that cavefish populations store large amounts of fat in different body regions when fed ad libitum in the lab. We found higher expression of lipogenesis genes in cavefish livers when fed the same amount of food as surface fish, suggesting an improved ability of cavefish to use lipogenesis to convert available energy into triglycerides for storage into adipose tissue. Moreover, the lipid metabolism regulator, Peroxisome proliferator-activated receptor γ (Pparγ), is upregulated at both transcript and protein levels in cavefish livers. Chromatin Immunoprecipitation sequencing (ChIP seq) showed that Pparγ binds cavefish promoter regions of genes to a higher extent than surface fish. Finally, we identified two possible regulatory mechanisms of Pparγ in cavefish: higher amounts of ligands of the nuclear receptor, and nonsense mutations in per2, a known repressor of Pparγ. Taken together, our study reveals that upregulated Pparγ promotes higher levels of lipogenesis in the liver and contributes to higher body fat accumulation in cavefish populations, an important adaptation to nutrient limited environments.
Selective neural coding of object, feature, and geometry spatial cues in humans

Orienting in space requires the processing and encoding of visual spatial cues. The dominant hypothesis about the brain structures mediating the coding of spatial cues stipulates the existence of a hippocampal-dependent system for the representation of geometry and a striatal-dependent system for the representation of landmarks. However, this dual-system hypothesis is based on paradigms that presented spatial cues conveying either conflicting or ambiguous spatial information and that amalgamated the concept of landmark into both discrete 3D objects and wall features. These confounded designs introduce difficulties in interpreting the spatial learning process. Here, we test the hypothesis of a complex interaction between the hippocampus and the striatum during landmark and geometry visual coding in humans. We also postulate that object-based and feature-based navigation are not equivalent instances of landmark-based navigation as currently considered in human spatial cognition. We examined the neural networks associated with geometry-, object-, and feature-based spatial navigation in an unbiased, two-choice behavioral paradigm using fMRI. We showed evidence of a synergistic interaction between hippocampal and striatal coding underlying flexible navigation behavior. The hippocampus was involved in all three types of cue-based navigation, whereas the striatum was more strongly recruited in the presence of geometric cues than object or feature cues. We also found that unique, specific neural signatures were associated with each spatial cue. Critically, object-based navigation elicited a widespread pattern of activity in temporal and occipital regions relative to feature-based navigation. These findings challenge and extend the current view of a dual, juxtaposed hippocampal-striatal system for visual spatial coding in humans. They also provide novel insights into the neural networks mediating object vs. feature spatial coding, suggesting a need to distinguish these two types of landmarks in the context of human navigation. Highlights Complex hippocampal-striatal interaction during visual spatial coding for flexible human navigation behavior. Distinct neural signatures associated with object-, feature-, and geometry-based navigation. Object- and feature-based navigation are not equivalent instances of landmark-based navigation.
Social steerability modulates perceptual biases

Verbal hints can bias perceptual decision-making, even when the information they provide is false. Whether individuals may be more or less susceptible to such perceptual influences, however, remains unclear. We asked naive participants to indicate the dominant color in a series of stimuli, after giving them a false statement about which color would likely dominate. As anticipated, this statement biased participants’ perception of the dominant color, as shown by a correlated shift of their perceptual decisions, confidence judgments and response times. Crucially, this perceptual bias was more pronounced in participants with higher levels of susceptibility to social influence, as measured by a standard suggestibility scale. Together, these results indicate that even without much apparatus, simple verbal hints can affect our perceptual reality, and that social steerability can determine how much they do so. Susceptibility to suggestion might thus be considered an integral part of perceptual processing. Statement of relevance At a time when fake news soar, understanding the role that simple verbal descriptions play in how we perceive the world around us is paramount. Extensive research has shown that perception is permeable to well-orchestrated manipulation. Comparatively less attention has been paid to the perceptual impact of false information when the latter is imparted simply and straightforwardly, through short verbal hints and instructions. Here we show that even a single sentence suffices to bias perceptual decision-making, and that critically, this bias varies across individuals as a function of susceptibility to social influence. Considering how here perception was biased by a single, plain sentence, we argue that researchers, communicators and policy-makers should pay careful attention to the role that social suggestibility plays in how we build our perceptual reality.
Water Stress and Disruption of Mycorrhizae Induce Parallel Shifts in Phyllosphere Microbiome Composition

Water and nutrient limitation are key stressors that affect plant health and ecosystem function. These environmental factors impact both soil- and root-associated microbial communities, and systemically alter plant physiology, but it is less clear how they affect aboveground plant-microbe interactions. Through experimental manipulations in the field and growth chamber, we examined the interacting effects of irrigation, soil fertility, and root mycorrhizal associations on bacterial and fungal communities of the tomato phyllosphere (Solanum lycopersicum). Both water stress and mycorrhizal disruption reduced bacterial richness within plants, homogenized bacterial community diversity among plants, and reduced the relative abundance of dominant fungal taxa. We observed striking parallelism in the individual microbial taxa affected by irrigation and mycorrhizal associations. Given the increasingly understood role of the phyllosphere in shaping plant health and pathogen susceptibility, these results offer an additional mechanism by which belowground conditions shape plant fitness.
Regulation of Lysosomal Associated Membrane Protein 3 (LAMP3) in Lung Epithelial Cells by Coronaviruses (SARS-CoV-1/2) and Type I Interferon Signaling

Abstract Severe Acute Respiratory Syndrome CoronaVirus-2 (SARS-CoV-2) infection is a major risk factor for mortality and morbidity in critical care hospitals around the world. Lung epithelial type II cells play a major role in the recognition and clearance of respiratory viruses as well as repair of lung injury in response to environmental toxicants. Gene expression profiling studies revealed that mouse lung epithelial type II cells express several cell-specific markers including surfactant proteins and Lysosomal associated membrane protein 3 (LAMP3) located in lysosomes, endosomes and lamellar bodies. These intracellular organelles are involved in vesicular transport and facilitate viral entry and release of the viral genome into the host cell cytoplasm. In this study, regulation of LAMP3 expression in human lung epithelial cells by several respiratory viruses and type I interferon signaling was investigated. Respiratory viruses including SARS-CoV-1 and SARS-CoV-2 significantly induced LAMP3 expression in lung epithelial cells within 24 hours after infection that required the presence of ACE2 viral entry receptors. Time course experiments revealed that the induced expression of LAMP3 was correlated with the induced expression of Interferon–beta (IFNB1) and STAT1 at mRNA levels. LAMP3 was also induced by direct IFN-beta treatment in multiple lung epithelial cell lines or by infection with influenza virus lacking the non-structural protein1(NS1) in NHBE bronchial epithelial cells. LAMP3 expression was also induced by several respiratory viruses in human lung epithelial cells including RSV and HPIV3. Location in lysosomes and endosomes aswell as induction by respiratory viruses and type I Interferon suggests that LAMP3 may have an important role in inter-organellar regulation of innate immunity and a potential target for therapeutic modulation in health and disease. Furthermore, bioinformatics revealed that a subset of lung type II genes were differentially regulated in the lungs of COVID-19 patients.
Testing the adaptive walk model of gene evolution

Understanding the dynamics of species adaptation to their environments has long been a central focus of the study of evolution. Theories of adaptation propose that populations evolve by “walking” in a fitness landscape. This “adaptive walk” is characterised by a pattern of diminishing returns, where populations further away from their fitness optimum take larger steps than those closer to their optimal conditions. Hence, we expect young genes to evolve faster and experience mutations with stronger fitness effects than older genes because they are further away from their fitness optimum. Testing this hypothesis, however, constitutes an arduous task. Young genes are small, encode proteins with a higher degree of intrinsic disorder, are expressed at lower levels, and are involved in species-specific adaptations. Since all these factors lead to increased protein evolutionary rates, they could be masking the effect of gene age. While controlling for these factors, we used population genomic datasets of Arabidopsis and Drosophila and estimated the rate of adaptive substitutions across genes from different phylostrata. We found that a gene’s evolutionary age significantly impacts the molecular rate of adaptation. Moreover, we observed that substitutions in young genes tend to have larger physicochemical effects. Our study, therefore, provides strong evidence that molecular evolution follows an adaptive walk model across a large evolutionary timescale.
From musk to body odor: Decoding olfaction through genetic variation

The olfactory system combines input from multiple receptor types to represent odor information, but there are few explicit examples relating olfactory receptor (OR) activity patterns to odor perception. To uncover these relationships, we performed genome-wide scans on odor-perception phenotypes for ten odors in 1003 Han Chinese and validated results for six of these odors in an ethnically diverse population (n=364). In both populations, we replicated three previously reported associations (β-ionone/OR5A, androstenone/OR7D4, cis-3-hexen-1-ol/OR2J3 LD-band), suggesting that olfactory phenotype/genotype studies are robust across populations. Two novel associations between an OR and odor perception contribute to our understanding of olfactory coding. First, we found a SNP in OR51B2 that associated with trans-3-methyl-2-hexenoic acid, a key component of human underarm odor. Second, we found two linked SNPs associated with the musk Galaxolide in a novel musk receptor, OR4D6, which is also the first OR shown to drive specific anosmia to a musk compound. We also found that the derived alleles of the SNPs reportedly associated with odor perception tend to reduce odor intensity, supporting the hypothesis that the primate olfactory gene repertoire has degenerated over time. This study provides information about coding for human body odor, and gives us insight into broader mechanisms of olfactory coding, such as how differential OR activation can converge on a similar percept.
Sewage Promotes Vibrio vulnificus Growth and Alters Gene Expression

Vibrio vulnificus is a naturally-occurring, potentially lethal pathogen found in coastal waters, fish, and shellfish. Sewage spills in coastal waters occur when infrastructure fails due to severe storms or age, and may affect bacterial populations by altering nutrient levels. This study investigated effects of sewage on clonal and natural V. vulnificus populations in microcosms. Addition of 1% sewage to estuarine water caused the density of a pure culture of V. vulnificus CMCP6 and a natural V. vulnificus population to increase significantly, whether measured by qPCR or culture. Changes in the transcription of six virulence- and survival-associated genes in response to sewage were assessed using continuous culture. Exposure to sewage affected transcription of genes that may be associated with virulence. Specifically, sewage modulated the oxidative stress response by altering superoxide dismutase transcription, significantly increasing sodB transcription while repressing sodA. Sewage also repressed transcription of nptA, which encodes a sodium-phosphate cotransporter. Sewage had no effect on sodC transcription or the putative virulence-associated genes hupA or wza. The effects of environmentally relevant levels of sewage on V. vulnificus populations and gene transcription suggest that sewage spills that impact warm coastal waters could lead to an increased risk of V. vulnificus infections. Importance Vibrio vulnificus infections have profound impacts such as limb amputation and death for individuals with predisposing conditions. The warming climate is contributing to rising V. vulnificus prevalence in waters that were previously too cold to support high levels of the pathogen. Climate change is also expected to increase precipitation in many regions, which puts more pressure on wastewater infrastructure and will result in more frequent sewage spills. The finding that 1% wastewater in estuarine water leads to tenfold to 1000-fold greater V. vulnificus concentrations suggests that human exposure to oysters and estuarine water could have greater health impacts in the future. Further, wastewater had a significant effect on gene transcription and has the potential to affect virulence during the initial environment-to-host transition.
An Aerobic Anoxygenic Phototrophic Bacterium Fixes CO2 via the Calvin-Benson-Bassham Cycle

Aerobic anoxygenic phototrophic bacteria (AAnPB) are photoheterotrophs, which use light as auxiliary energy and require organic carbon (OC) for growth. Herein, we report the unusual strain B3, which is a true AAnPB because it requires oxygen for growth, harbours genes for cbb3- and bd-type cytochromes and acsF, and produces bacteriochlorophyll. The B3 genome encodes the complete metabolic pathways for AAnPB light utilization, CO2 fixation via Calvin-Benson-Bassham (CBB) cycle and oxidation of sulfite and H2, and the transcriptome indicated that all components of these pathways were fully transcribed. Expression of the marker genes related to photosynthesis, including pufM for light harnessing and rbcL for CO2 fixation, and the activity of RubisCO, the key enzyme in the Calvin-Benson-Bassham (CBB) cycle, increased in response to decreased OC supply. Large amounts of cell biomass were obtained in liquid BG11 medium under illumination. The strain thus likely photoautotrophically grows using sulfite or H2 as an electron donor. Similar GC contents between photosynthesis, the CBB cycle and 16S rRNA genes and the consistency of their phylogenetic topologies implied that light harnessing and carbon fixation genes evolved vertically from an anaerobic phototrophic ancestor of Rhodospirillaceae in Alphaproteobacteria. In conclusion, strain B3 represents a novel AAnPB characterized by photoautotrophy using the CBB cycle. This kind of AAnPB may be ecologically significant in the global carbon cycle.
Handedness and midsagittal corpus callosum morphology: A systematic meta-analytic evaluation

Following a series of seminal studies in the 1980s, left or mixed hand preference is widely considered to be associated with a larger corpus callosum, influencing the interpretation of findings and various theories related to inter-hemispheric processing, brain lateralisation, and hand preference. Recent reviews of the literature, however, report inconsistencies in the literature and cast doubt on the existence of such an association. The aim of the present study was to systematically evaluate and meta-analytically integrate the available data on the effect of hand preference on corpus-callosum morphology. For this purpose, articles were identified via a search in PubMed and Web of Science databases. Studies reporting findings relating handedness (assessed as hand preference) and corpus-callosum morphology in healthy participants were considered eligible. On the basis of a total of k = 25 identified studies, random-effects meta-analyses were conducted considering four different group comparisons found in the literature. That is, studies comparing participants of (a) predominantly right- (dRH) and left-hand preference (dLH), (b) consistent right (cRH) and non-cRH preference, (c) cRH with mixed-hand preference (MH), and (d) cRH with consistent left-hand hand preference (cLH). For none of these meta-analyses did we find a significant effect of hand preference, and narrow confidence intervals suggest that the existence of substantial population effect sizes can be excluded. For example, considering the comparison of dRH and dLH, (summarizing k = 14 studies incorporating 1910 dRH and 646 dLH participants) the estimated mean effect size was g = 0.016 (95% confidence interval: −0.12 to 0.15). Thus, the common practice of assuming an increase in callosal connectivity based on hand preference is likely invalid.
Sleep-dependent upscaled excitability and saturated neuroplasticity in the human brain: From brain physiology to cognition

Sleep and cognition are strongly linked via their impact on synaptic strength. Whether and how sleep deprivation modulates human brain physiology and cognition is, however, not well understood. Here we examined how cortical excitability, inducibility of LTP- and-LTD-like plasticity, learning and memory formation and higher-order cognition are affected by overnight sleep deprivation. We show that sleep deprivation upscales cortical excitability due to enhanced glutamate-related cortical facilitation and decreased and/or reversed GABAergic cortical inhibition. We furthermore demonstrate that non-invasive brain stimulation-induced LTP-like plasticity is abolished while LTD-like plasticity converts to excitatory LTP-like under sleep deprivation, likely caused by synaptic saturation and upscaled brain excitability. This was associated with increased synaptic strength measured by EEG theta activity. Finally, we show that learning and memory formation, behavioral counterparts of plasticity, and working memory and attention, which rely on cortical excitability, are impaired during sleep deprivation. Our data show converging effects of sleep deprivation on human brain physiology and cognition.
Benchmarking a highly selective USP30 inhibitor for enhancement of mitophagy and pexophagy

A detailed look at the properties of a novel USP30 inhibitor applied to studies of mitophagy and pexophagy. The deubiquitylase USP30 is an actionable target considered for treatment of conditions associated with defects in the PINK1-PRKN pathway leading to mitophagy. We provide a detailed cell biological characterization of a benzosulphonamide molecule, compound 39, that has previously been reported to inhibit USP30 in an in vitro enzymatic assay. The current compound offers increased selectivity over previously described inhibitors. It enhances mitophagy and generates a signature response for USP30 inhibition after mitochondrial depolarization. This includes enhancement of TOMM20 and SYNJ2BP ubiquitylation and phosphoubiquitin accumulation, alongside increased mitophagy. In dopaminergic neurons, generated from Parkinson disease patients carrying loss of function PRKN mutations, compound 39 could significantly restore mitophagy to a level approaching control values. USP30 is located on both mitochondria and peroxisomes and has also been linked to the PINK1-independent pexophagy pathway. Using a fluorescence reporter of pexophagy expressed in U2OS cells, we observe increased pexophagy upon application of compound 39 that recapitulates the previously described effect for USP30 depletion. This provides the first pharmacological intervention with a synthetic molecule to enhance peroxisome turnover.