Miracle-dz/UniFAR-FTUs huggingface dataset:
Experimental evolution of environmental tolerance, acclimation, and physiological plasticity in a randomly fluctuating environment

Environmental tolerance curves, representing absolute fitness against the environment, are an empirical assessment of the fundamental niche, and emerge from the phenotypic plasticity of underlying phenotypic traits. Dynamic plastic responses of these traits can lead to acclimation effects, whereby recent past environments impact current fitness. Theory predicts that higher levels of phenotypic plasticity should evolve in environments that fluctuate more predictably, but there have been few experimental tests of these predictions. Specifically, we still lack experimental evidence for the evolution of acclimation effects in response to environmental predictability. Here, we exposed 25 genetically diverse populations of the halotolerant microalgae Dunaliella salina to different constant salinities, or to randomly fluctuating salinities, for over 200 generations. The fluctuating treatments differed in their autocorrelation, which determines the similarity of subsequent values, and thus environmental predictability. We then measured acclimated tolerance surfaces, mapping population growth rate against past (acclimation) and current (assay) environments. We found that experimental mean and variance in salinity caused the evolution of niche position (optimal salinity) and breadth, with respect to not only current but also past (acclimation) salinity. We also detected weak but significant evidence for evolutionary changes in response to environmental predictability, with higher predictability leading notably to lower optimal salinities and stronger acclimation effect of past environment on current fitness. We further showed that these responses are related to the evolution of plasticity for intracellular glycerol, the major osmoregulatory mechanism in this species. However, the direction of plasticity evolution did not match simple theoretical predictions. Our results underline the need for a more explicit consideration of the dynamics of environmental tolerance and its underlying plastic traits to reach a better understanding of ecology and evolution in fluctuating environments.
AI ‘Everywhere and Nowhere’: Addressing the AI Intelligibility Problem in Public Service Journalism

Abstract Growing prevalence of algorithmic systems and artificial intelligence in news production has prompted concerns over journalists’ ability to understand and engage with them in ways that do not compromise journalistic norms and values. This ‘intelligibility’ issue is particularly acute for public service media due to the risks such complex and opaque systems pose for disrupting accountability, decision-making, and professional judgment. This article draws from document analysis and interviews with fourteen journalists to outline where AI is deployed in BBC news production and analyse how journalists make sense of AI and algorithms. We find a disconnect between increasingly pervasive AI and the level of understanding amongst BBC journalists, who are using guesswork and imagination in place of accurate conceptions of these technologies. This could limit journalists’ ability to effectively and responsibly use AI systems, to question their outputs and role in news production, or to adapt and shape them – and could also hinder responsible reporting on how AI impacts society. We recommend PSM develop strategies for fostering AI intelligibility and literacy on three levels: individual, organisational, and community, and we reframe the AI intelligibility problem in sociocultural rather than solely technical terms in order to better address normative considerations.
Gβγ activates PIP2 hydrolysis by recruiting and orienting PLCβ on the membrane surface

PLCβs catalyze the hydrolysis of PIP2 into IP3 and DAG. PIP2 regulates the activity of many membrane proteins, while IP3 and DAG lead to increased intracellular Ca2+ levels and activate PKC, respectively. PLCβs are regulated by GPCRs through direct interaction with Gαq and Gβγ. This study addresses the mechanism by which Gβγ activates PLCβ3. We show that PLCβ3 functions as a slow Michaelis-Menten enzyme (kcat~2 sec−1, KM~0.43 mol%) on membrane surfaces. Its partition coefficient (Kx~2.9 * 104) is such that only a small quantity of PLCβ3 exists in the membrane in the absence of Gβγ. When Gβγ is present, equilibrium binding (Keq~0.009 mol%) increases PLCβ3 in the membrane, increasing Vmax in proportion. Atomic structures on membrane vesicle surfaces show that two Gβγ anchor PLCβ3 with its catalytic site oriented toward the membrane surface. This principle of activation explains rapid stimulated catalysis with low background catalysis.
Choice of Parcellation Atlas Might Not be Too Critical for Connectomic Analysis

Connectomics has been a rapidly growing discipline in neuroimaging and neuroscience that evolved our understanding of the brain. Connectomics involves representing the brain as a network of regions, where the parcellation of the brain into regions using a template atlas is an integral part of the analysis. Over developmental and young adult cohorts of healthy individuals, we investigated how choosing parcellation atlases at certain resolutions affect sex classification and age prediction tasks performed using deep learning on structural connectomes. Datasets were processed on a total of 35 parcellations, where the only significant difference was observed for age prediction on the developmental cohort with a slight improvement on higher resolutions. This indicates that choice of parcellation scheme is generally not critical for deep learningbased age prediction and sex classification. Therefore, results between studies using different parcellation schemes could be comparable and repeating analyses on multiple atlases might be unnecessary.
Coronary vessel assembly involves patterned endocardial sprouting and tip-cell-to artery specification

The coronary vasculature comprises superficial coronary veins and deeper coronary arteries and capillaries that critically support the high metabolic activity of the beating heart. Understanding how different endothelial progenitor sources jointly shape and remodel the coronary vasculature into its adult pattern has recently attracted great research interest, and spurred much debate. Here, using lineage tracing tools in combination with three-dimensional imaging, live-imaging in explants and single-cell transcriptional profiling, we demonstrate that sprouting angiogenesis drives both sinus venosus and endocardial contribution to coronary plexus. Whereas previous studies limit endocardial contribution to coronary vessels to the interventricular septum and ventral aspect of the heart, our study demonstrates extensive endocardial sprouting angiogenesis in the free ventricular walls. In particular, we identify a distinct subpopulation of endocardial cells that express future coronary markers and reside in both the embryonic and adult ventricular wall endocardium. Most importantly, we provide evidence for sprouting angiogenesis from both endocardium and subepicardial plexus towards the inner myocardial wall to determine pre-arterial specification. Additionally, sprouting from the endocardium leads to the establishment of perfused connections to the advancing coronary plexus, also followed by transitioning to the pre-arterial cell state. Distinct molecular profiles characterize sprouting populations in the intramyocardial and subepicardial layers that shape the prospective coronary arteries and veins, respectively. Harnessing the endocardial progenitors and targeting the distinct sprouting populations may in the future serve to tailor cardiac vascular adaptations for therapeutic purposes.
Nature and biological irrelevance of mixed-type enzyme inhibition

Mixed-type enzyme inhibitors were originally envisaged to decrease the enzyme affinity for the substrates and the maximum turnover rate by simultaneously targeting two distinct protein sites, i.e., the active site and an allosteric site. After a century from the first formulation of this hypothesis, the consensus on its validity is still unanimous, although several of its implications are in open conflict with the current knowledge on molecular recognition mechanisms. In particular, there is no plausible explanation for the experimental evidence that mixed-type inhibitors bind the enzyme active sites always more effectively than the allotopic sites. In an attempt to solve this controversy, it was found that the preference of mixed inhibitors for active sites emerges as an inevitable numerical artifact that is implicit in the equations used to model the apparent mixed inhibition caused under certain circumstances by active site-bound competitive inhibitors. Hence, proving that the consolidated model of mixed inhibition is incorrect and, more generally, strongly pointing to the biological irrelevance of mixed-type inhibition.
Neural distinctiveness and discriminability in regions of the core network representations support associative unitization

Previous work has suggested unitized pairs behave as a single unit and more critically, are processed neurally different than those of associative memories. The current works examines the neural differences between unitization and non-unitized memory using fMRI and multivoxel analyses. Specifically, we examined the differences across face-occupation pairings as a function of whether the pairing was viewed as a person performing the given job (unitized binding) or a person saying they knew someone who had a particular job (non-unitized binding). The results show that at encoding, the angular gyrus can discriminate between unitized and non-unitized target trials. Additionally, during encoding, the medial temporal lobe (hippocampus and perirhinal cortex), frontal parietal regions (angular gyrus and medial frontal gyrus) and visual regions (middle occipital cortex) exhibit distinct neural patterns to recollected unitized and non-unitized targets. Furthermore, the medial frontal gyrus and middle occipital cortex show greater neural similarity for recollected unitized trials than those of recollected non-unitized trials. We conclude that visually unitized pairs may enhance unitization in older adults due to greater similarity of trials within the same condition during the encoding process.
A Transfer entropy-based methodology to analyze information flow under eyes-open and eyes-closed conditions with a clinical perspective

Studying brain dynamics under normal or pathological conditions has proven to be a challenging task, as there is no unified consensus on the best approach. In this article, we present a methodology based on Transfer Entropy to study the information flow between different brain hemispheres in healthy subjects during eyes-open (EO) and eyes-closed (EC) resting states. We used an experimental setup that mimics the technical conditions found in clinical settings and collected data sets from short records of 24 channels electroencephalogram (EEG) at a sampling rate of 65 Hz. Our methodology accounts for interhemispheric and intrahemispheric information flow analysis in both conditions and relies on 4 indexes calculated from the transfer entropy estimations between EEG channels. These indexes provide information on the number, strength, and directionality of active connections. Our results suggest an increase in information transfer in the EC condition for the alpha, beta1, and beta2 frequency bands, but no preferred direction of interhemispheric information movement under either condition. These results are consistent with previously reported studies conducted with denser EEG recordings sampled at a higher rate. In conclusion, our methodology shows a significant difference in the brain’s dynamics of information transfer between EO and EC resting states, which can also be applied to regular clinical sessions.
Metabolism is correlative not causative for age-related auditory decline in an insect model

Aging is due to a complex decline of multiple biological processes. Some of the causes include oxidative damage, mitochondrial and proteostatic dysfunction, and DNA damage. The result is that as biological systems age their performance deteriorates. This age-related decline is well quantified, and experienced, for human hearing and is presumed to be due to a decrease in the ear’s metabolism – specifically a decrease in ability to maintain an electrochemical gradient, the endocochlear potential. However, direct measurements of metabolism across a lifespan in an auditory system are lacking. Even if metabolism does decrease with age, the question remains is it a cause of age-related auditory decline or simply correlative? All auditory systems across the animal kingdom share functional principles including ion pumping cells, auditory receptors, spiking auditory nerves and multiple supporting cells. Therefore, we used an insect, the desert locust, Schistocerca gregaria, as a physiologically versatile model to understand how cellular metabolism correlates with age and impacts on age-related auditory decline. We found that although metabolism correlates with age-related auditory decline it is not causative.
Transposable element and host silencing activity in gigantic genomes

Transposable elements (TEs) and the silencing machinery of their hosts are engaged in a germline arms-race dynamic that shapes TE accumulation and, therefore, genome size. In animal species with extremely large genomes (>10 Gb), TE accumulation has been pushed to the extreme, prompting the question of whether TE silencing also deviates from typical conditions. To address this question, we characterize TE silencing via two pathways — the piRNA pathway and KRAB-ZFP transcriptional repression — in the male and female gonads of Ranodon sibiricus, a salamander species with a ∼21 Gb genome. We quantify 1) genomic TE diversity, 2) TE expression, and 3) small RNA expression and find a significant relationship between the expression of piRNAs and TEs they target for silencing in both sexes. We also quantified TE silencing pathway gene expression in R. sibiricus and 14 other vertebrates with genome sizes ranging from 1 – 130 Gb and find no association between pathway expression and genome size. Taken together, our results reveal that the gigantic R. sibiricus genome includes at least 19 putatively active TE superfamilies, all of which are targeted by the piRNA pathway in proportion to their expression levels, suggesting comprehensive piRNA-mediated silencing. Males have higher TE expression than females, suggesting that they may contribute more to the species’ high genomic TE load. We posit that apparently conflicting interpretations of TE silencing and genomic gigantism in the literature, as well as the absence of a correlation between TE silencing pathway gene expression and genome size, can be reconciled by considering whether the TE community or the host is currently “on the attack” in the arms race dynamic.
Couette - Poiseuille Two-Layer Flow of a Third Grade Fluid

The two-layer Couette-Poiseuille flow of a third grade fluid is examined. The problem is reduced to solving nonlinear differential equations governing the motion of the two immiscible fluids in case of different thickness of layers. The solutions are used to study the effect of the third grade material parameter on the velocity profiles. The investigation focuses especially on the location of the velocity maximum as function of the viscosity and third grade material constant.
Dynamic Evolution of Retroviral Envelope Genes in Egg-Laying Mammalian Genomes

Independently acquired envelope (env) genes from endogenous retroviruses have contributed to the placental trophoblast cell-cell fusion in therian mammals. Egg-laying mammals (monotremes) are an important sister clade for understanding mammalian placental evolution, but the env genes in their genomes have yet to be investigated. Here, env-derived open reading frames (env-ORFs) encoding more than 400 amino-acid lengths were searched in the genomes of two monotremes: platypus and echidna. Only two env-ORFs were present in the platypus genome, whereas 121 env-ORFs were found in the echidna genome. The echidna env-ORFs were phylogenetically classified into seven groups named env-Tac1 to -Tac7. Among them, the env-Tac1 group contained only a single gene, and its amino acid sequence showed high similarity to those of the RD114/simian type D retroviruses. Using the pseudotyped virus assay, we demonstrated that the Env-Tac1 protein utilizes echidna sodium-dependent neutral amino acid transporter type 1 and 2 (ASCT1 and ASCT2) as entry receptors. Moreover, the Env-Tac1 protein caused cell-cell fusion in human 293T cells depending on the expression of ASCT1 and ASCT2. These results illustrate that fusogenic env genes are not restricted to placental mammals, providing insights into the evolution of retroviral genes and the placenta.
A refined pH-dependent coarse-grained model for peptide structure prediction in aqueous solution

Peptides carry out diverse biological functions and the knowledge of the conformational ensemble of polypeptides in various experimental conditions is important for biological applications. All fast dedicated softwares perform well in aqueous solution at neutral pH. In this study, we go one step beyond by combining the Debye-Hückel formalism for charged-charged amino acid interactions and a coarse-grained potential of the amino acids to treat pH and salt variations. Using the PEP-FOLD framework, we show that our approach performs as well as the machine-leaning AlphaFold2 and TrRosetta methods for 15 well-structured sequences, but shows significant improvement in structure prediction of six poly-charged amino acids and two sequences that have no homologous in the Protein Data Bank, expanding the range of possibilities for the understanding of peptide biological roles and the design of candidate therapeutic peptides.
Spatially distinct phytohormone responses of individual Arabidopsis thaliana root cells to infection and colonization by Fusarium oxysporum

Jasmonic acid (JA), ethylene (ET) and salicylic acid (SA) are the three major phytohormones coordinating a plant’s defense response to pathogenic attack. While JA and ET are assumed to primarily control the defense against necrotrophic pathogens, SA-induced defense responses target mainly biotrophic microbes, and can include drastic measures such as programmed cell death as part of the plant’s hypersensitive response (HR). Fusarium oxysporum is a hemibiotrophic fungal pathogen of several plant species, including many important food crops, and the model plant species Arabidopsis thaliana. Colonization of the plant’s root vascular tissue by the fungus eventually results in wilting and plant death. A general role for JA, ET and SA in combating infection and colonization of the plant by F. oxysporum has been demonstrated, but their distinct roles and modes of action have so far not been described. Here, using high resolution microscopy with fluorescent marker lines of A. thaliana roots infected with F. oxysporum we show that SA acts spatially separate from JA, in a distinct set of root cells immediately neighboring the fungal colonization site. There, SA induces HR to stop the spread of colonization. JA acts in a different, but also clearly defined set of cells, slightly removed from the colonization site, where it initiates a defense response to actively resist the invader. ET is activated in a stretch of cells that covers both, the cells with activated SA and JA signaling, and may be involved in creating these two distinct zones. These results show how the three phytohormones act together, but spatially and functionally separate from each other, to fight this hemibiotrophic pathogen. Such a high-resolution analysis to resolve the plant’s immune response to pathogenic infection on an individual cell level and in intact tissue has so far been lacking. Graphical Abstract Colonization of the A. thaliana root tip by F. oxysporum strain Fo5176 leads to immediate cell death of the colonized and surrounding tissue. As the colonization front progresses through the vasculature, the cell death front moves along with it through not only the vasculature, but also the surrounding tissues. WRKY70 positively regulates salicylic acid (SA) biosynthesis in cells immediately adjacent to the colonized tissue, inducing a hypersensitive response (HR), thereby killing off the cells deemed lost to the intruder, establishing the cell death front. Slightly further removed from the HR zone, WRKY11 induces jasmonate (JA) biosynthesis in cells of the vasculature to launch a defense response aimed at actively repelling the fungus.
Assessing intra‐individual changes in health related quality of life data in psychiatric clinical trials

Assessment of intra‐individual changes in health related quality of life (HRQOL) measures is important to develop individual change standards and to provide help in clinical practice. Methodological issues related to the analysis of HRQOL data depend on the nature of medical illnesses and the target population. However, one issue—the need to assess HRQOL changes across individuals over time—spans most conditions. Modest improvement in HRQOL may be harder to assess in elderly depressed persons who also have high rates of co‐existing medical and neurobiological illnesses. Powerful statistical techniques are necessary to assess these improvements. Focusing on methods related to the issue of measuring change, we describe the potential of a mixed‐modeling approach for the assessment of intra‐individual changes using HRQOL data measured in a large group of elderly patients with recurrent major depression. These patients were treated with combined pharmacotherapy and interpersonal psychotherapy. We used a mixed‐modeling approach and two pre‐post difference score methods. The percentage of intra‐individual statistically significant improvement rates was found to be largest for the mixed‐modeling approach. We conducted simulation studies to compare these three approaches for assessing these changes. The simulated data reflected the observed data. Results from the two simulation studies are in agreement with the observed results and provide positive evidence for an earlier hypothesis (Speer and Greenbaum, 1995) that the mixed‐modeling approach is more sensitive for assessing changes across individuals over time compared to the pre‐post difference score methods. Thus, we recommend the use of the mixed‐modeling approach to measure intra‐individual changes, based on a larger array of supporting evidence than has been available previously. Copyright © 2004 John Wiley & Sons, Ltd.
Computer-aided drug design combined network pharmacology to explore anti-SARS-CoV-2 or anti-inflammatory targets and mechanisms of Qingfei Paidu Decoction for COVID-19

Introduction Coronavirus Disease-2019 (COVID-19) is an infectious disease caused by SARS-CoV-2. Severe cases of COVID-19 are characterized by an intense inflammatory process that may ultimately lead to organ failure and patient death. Qingfei Paidu Decoction (QFPD), a traditional Chines e medicine (TCM) formula, is widely used in China as anti-SARS-CoV-2 and anti-inflammatory. However, the potential targets and mechanisms for QFPD to exert anti-SARS-CoV-2 or anti-inflammatory effects remain unclear. Methods In this study, Computer-Aided Drug Design was performed to identify the antiviral or anti-inflammatory components in QFPD and their targets using Discovery Studio 2020 software. We then investigated the mechanisms associated with QFPD for treating COVID-19 with the help of multiple network pharmacology approaches. Results and discussion By overlapping the targets of QFPD and COVID-19, we discovered 8 common targets (RBP4, IL1RN, TTR, FYN, SFTPD, TP53, SRPK1, and AKT1) of 62 active components in QFPD. These may represent potential targets for QFPD to exert anti-SARS-CoV-2 or anti-inflammatory effects. The result showed that QFPD might have therapeutic effects on COVID-19 by regulating viral infection, immune and inflammation-related pathways. Our work will promote the development of new drugs for COVID-19.