Miracle-dz/UniFAR-FTUs huggingface dataset:
The dynamics of accretion flows near to the innermost stable circular orbit

Accretion flows are fundamentally turbulent systems, yet are classically modelled with viscous theories only valid on length scales significantly greater than the typical size of turbulent eddies in the flow. We demonstrate that, while this will be a reasonable bulk description of the flow at large radii, this must break down as the flow approaches absorbing boundaries, such as the innermost stable circular orbit (ISCO) of a black hole disc. This is because in a turbulent flow large velocity fluctuations can carry a fluid element over the ISCO from a finite distance away, from which it will not return, a process without analogy in conventional models. This introduces a non-zero directional bias into the velocity fluctuations in the near-ISCO disc. By studying reduced random walk problems, we derive a number of implications of the presence of an absorbing boundary in an accretion context. In particular, we show that the average velocity with which a typical fluid element crosses the ISCO is much larger than is assumed in traditional theories. This enhanced velocity modifies the thermodynamic properties of black hole accretion flows on both sides of the ISCO. In particular, thermodynamic quantities for larger ISCO stresses no longer display pronounced cusps at the ISCO in this new formalism, a result with relevance for a number of observational probes of the intra-ISCO region. Finally, we demonstrate that these extended models reproduce the trans-ISCO behaviour observed in GRMHD simulations of thin discs.
Duality for condensed cohomology of the Weil group of a p-adic field

We use the theory of Condensed Mathematics to build a condensed cohomology theory for the Weil group of a $p$-adic field. The cohomology groups are proved to be locally compact abelian groups of finite ranks in some special cases. This allows us to enlarge the local Tate Duality to a more general category of non-necessarily discrete coefficients, where it takes the form of a Pontryagin duality between locally compact abelian groups.
Quantum Melting of a Disordered Wigner Solid

The behavior of two-dimensional electron gas (2DEG) in extreme coupling limits are reasonably well-understood, but our understanding of intermediate region remains limited. Strongly interacting electrons crystalize into a solid phase known as the Wigner crystal at very low densities, and these evolve to a Fermi liquid at high densities. At intermediate densities, however, where the Wigner crystal melts into a strongly correlated electron fluid that is poorly understood partly due to a lack of microscopic probes for delicate quantum phases. Here we report the first imaging of a disordered Wigner solid and its quantum densification and quantum melting behavior in a bilayer MoSe2 using a non-invasive scanning tunneling microscopy (STM) technique. We observe a Wigner solid with nanocrystalline domains pinned by local disorder at low hole densities. With slightly increasing electrostatic gate voltages, the holes are added quantum mechanically during the densification of the disordered Wigner solid. As the hole density is increased above a threshold (p ~ 5.7 * 10e12 (cm-2)), the Wigner solid is observed to melt locally and create a mixed phase where solid and liquid regions coexist. With increasing density, the liquid regions gradually expand and form an apparent percolation network. Local solid domains appear to be pinned and stabilized by local disorder over a range of densities. Our observations are consistent with a microemulsion picture of Wigner solid quantum melting where solid and liquid domains emerge spontaneously and solid domains are pinned by local disorder.
Variability in drought gene expression datasets highlight the need for community standardization

Physiologically relevant drought stress is difficult to apply consistently, and the heterogeneity in experimental design, growth conditions, and sampling schemes make it challenging to compare water deficit studies in plants. Here, we re-analyzed hundreds of drought gene expression experiments across diverse model and crop species and quantified the variability across studies. We found that drought studies are surprisingly uncomparable, even when accounting for differences in genotype, environment, drought severity, and method of drying. Many studies, including most Arabidopsis work, lack high-quality phenotypic and physiological datasets to accompany gene expression, making it impossible to assess the severity or in some cases the occurrence of water deficit stress events. From these datasets, we developed supervised learning classifiers that can accurately predict if RNA-seq samples have experienced a physiologically relevant drought stress, and suggest this can be used as a quality control for future studies. Together, our analyses highlight the need for more community standardization, and the importance of paired physiology data to quantify stress severity for reproducibility and future data analyses.
A 20-year time-series of a freshwater lake reveals seasonal dynamics and environmental drivers of viral diversity, ecology, and evolution

Long-term ecological studies are powerful tools to investigate microbiomes and ecosystem change but have mostly ignored viruses. Here, we leveraged a 20-year time-series of a freshwater lake to characterize 1.3 million viral genomes over time, seasonality, and environmental factors. We identified 578 auxiliary metabolic gene (AMG) clusters representing over 150,000 AMGs, the most abundant of which, including psbA for photosynthesis, pmoC for methane oxidation, and katG for hydrogen peroxide decomposition, were consistently represented in viruses across decades and seasons. We observed positive associations and niche differentiation between virus-host pairs during seasonal change including in keystone taxa, Cyanobacteria, methanotrophs, and Nanopelagicales. Environmental constraints, specifically inorganic carbon and ammonium influenced viral abundances over time, and highlighted roles of viruses in both “top-down” and “bottom-up” interactions. Key evolutionary processes shaping gene and genome-wide selection included favored fitness genes, reduced genomic heterogeneity, and dominant sub-populations carrying specific genes. Overall, our study advances understanding of diversity, ecological dynamics, and evolutionary trajectories of viruses in Earth’s microbiomes and ecosystems.
Protein interaction map of APOBEC3 enzyme family reveals deamination-independent role in cellular function

Human APOBEC3 enzymes are a family of single-stranded (ss)DNA and RNA cytidine deaminases that act as part of the intrinsic immunity against viruses and retroelements. These enzymes deaminate cytosine to form uracil which can functionally inactivate or cause degradation of viral or retroelement genomes. In addition, APOBEC3s have deamination independent antiviral activity through protein and nucleic acid interactions. If expression levels are misregulated, some APOBEC3 enzymes can access the human genome leading to deamination and mutagenesis, contributing to cancer initiation and evolution. While APOBEC3 enzymes are known to interact with large ribonucleoprotein complexes, the function and RNA dependence is not entirely understood. To further understand their cellular roles, we determined by affinity purification mass spectrometry (AP-MS) the protein interaction network for the human APOBEC3 enzymes and map a diverse set of protein-protein and protein-RNA mediated interactions. Our analysis identified novel RNA-mediated interactions between APOBEC3C, APOBEC3H Haplotype I and II, and APOBEC3G with spliceosome proteins, and APOBEC3G and APOBEC3H Haplotype I with proteins involved in tRNA methylation and ncRNA export from the nucleus. In addition, we identified RNA-independent protein-protein interactions with APOBEC3B, APOBEC3D, and APOBEC3F and the prefoldin family of protein folding chaperones. Interaction between prefoldin 5 (PFD5) and APOBEC3B disrupted the ability of PFD5 to induce degradation of the oncogene cMyc, implicating the APOBEC3B protein interaction network in cancer. Altogether, the results uncover novel functions and interactions of the APOBEC3 family and suggest they may have fundamental roles in cellular RNA biology, their protein-protein interactions are not redundant, and there are protein-protein interactions with tumor suppressors, suggesting a role in cancer biology.
Plastid phylogenomics reveals evolutionary relationships in the mycoheterotrophic orchid genus Dipodium and provides insights into plastid gene degeneration

The orchid genus Dipodium R.Br. (Epidendroideae) comprises leafy autotrophic and leafless mycoheterotrophic species, the latter confined to sect. Dipodium. This study examined plastome degeneration in Dipodium in a phylogenomic and temporal context. Whole plastomes were reconstructed and annotated for 24 Dipodium samples representing 14 species and two putatively new species, encompassing over 80% of species diversity in sect. Dipodium. Phylogenomic analysis based on 68 plastid loci including a broad outgroup sampling across Orchidaceae found sect. Leopardanthus as sister lineage to sect. Dipodium. Dipodium ensifolium, the only leafy autotrophic species in sect. Dipodium was found sister to all leafless, mycoheterotrophic species, supporting a single evolutionary origin of mycoheterotrophy in the genus. Divergence time estimations found that Dipodium arose ca. 33.3 Ma near the lower boundary of the Oligocene and crown diversification commenced in the late Miocene, ca. 11.3 Ma. Mycoheterotrophy in the genus was estimated to have evolved in the late Miocene, ca. 7.3 Ma, in sect. Dipodium. The comparative assessment of plastome structure and gene degradation in Dipodium revealed that plastid ndh genes were pseudogenised or physically lost in all Dipodium species, including in leafy autotrophic species of both Dipodium sections. Levels of plastid ndh gene degradation were found to vary among species as well as within species, providing evidence of relaxed selection for retention of the NADH dehydrogenase complex within the genus. Dipodium exhibits an early stage of plastid genome degradation as all species were found to have retained a full set of functional photosynthesis-related genes and housekeeping genes. This study provides important insights into plastid genome degradation along the transition from autotrophy to mycoheterotrophy in a phylogenomic and temporal context.
Kappa Opioid Receptors Negatively Regulate Real Time Spontaneous Dopamine Signals by Reducing Release and Increasing Uptake

The role of the dynorphin/kappa opioid receptor (KOR) system in dopamine (DA) regulation has been extensively investigated. KOR activation reduces extracellular DA concentrations and increases DA transporter (DAT) activity and trafficking to the membrane. To explore KOR influences on real-time DA fluctuations, we used the photosensor dLight1.2 with fiber photometry in the nucleus accumbens (NAc) core of freely moving male and female C57BL/6 mice. First, we established that the rise and fall of spontaneous DA signals were due to DA release and reuptake, respectively. Then mice were systemically administered the KOR agonist U50,488H (U50), with or without pretreatment with the KOR antagonist aticaprant (ATIC). U50 reduced both the amplitude and width of spontaneous signals in males, but only reduced width in females. Further, the slope of the correlation between amplitude and width was increased in both sexes, suggesting that DA uptake rates were increased. U50 also reduced the frequency of signals in both males and females. All effects of KOR activation were stronger in males. Overall, KORs exerted significant inhibitory control over spontaneous DA signaling, acting through at least three mechanisms - inhibiting DA release, promoting DAT-mediated uptake, and reducing the frequency of signals.
Brain and grammar: revealing electrophysiological basic structures with competing statistical models

Acoustic, lexical and syntactic information is simultaneously processed in the brain. Therefore, distinguishing the electrophysiological activity pertaining to these components requires complex and indirect strategies. Capitalizing on previous works which factor out acoustic information, we could concentrate on the lexical and syntactic contribution to language processing by testing competing statistical models. We exploited EEG recordings and compared different surprisal models selectively involving lexical information, part of speech or syntactic structures in various combinations. EEG responses were recorded in 32 participants during listening to affirmative active declarative sentences and compared the activation corresponding to basic syntactic structures, such as noun phrases vs verb phrases. Lexical and syntactic processing activates different frequency bands, different time windows and different networks. Moreover, surprisal models based on part of speech inventory only do not explain well the electrophysiological data, while those including syntactic information do. Finally, we confirm previous measures obtained with intracortical recordings independently supporting the original hypothesis addressed here in a robust way.
mTORC1 activity oscillates throughout the cell cycle promoting mitotic entry and differentially influencing autophagy induction

Mechanistic Target of Rapamycin Complex 1 (mTORC1) is a master metabolic regulator that stimulates anabolic cell growth while suppressing catabolic processes such as autophagy. mTORC1 is active in most, if not all, proliferating eukaryotic cells. However, it remains unclear whether and how mTORC1 activity changes from one cell cycle phase to another. Here we tracked mTORC1 activity through the complete cell cycle and uncover oscillations in its activity. We find that mTORC1 activity peaks in S and G2, and is lowest in mitosis and G1. We further demonstrate that multiple mechanisms are involved in controlling this oscillation. The interphase oscillation is mediated through the TSC complex, an upstream negative regulator of mTORC1, but is independent of major known regulatory inputs to the TSC complex, including Akt, Mek/Erk, and CDK4/6 signaling. By contrast, suppression of mTORC1 activity in mitosis does not require the TSC complex, and instead involves CDK1-dependent control of the subcellular localization of mTORC1 itself. Functionally, we find that in addition to its well-established role in promoting progression through G1, mTORC1 also promotes progression through S and G2, and is important for satisfying the Wee1- and Chk1-dependent G2/M checkpoint to allow entry into mitosis. We also find that low mTORC1 activity in G1 sensitizes cells to autophagy induction in response to partial mTORC1 inhibition or reduced nutrient levels. Together these findings demonstrate that mTORC1 is differentially regulated throughout the cell cycle, with important phase-specific functional consequences in proliferating cells.
The Brain Tells a Story: Unveiling Distinct Representations of Semantic Content in Speech, Objects, and Stories in the Human Brain with Large Language Models

In recent studies, researchers have utilized Large Language Models (LLMs) to investigate semantic representation within the brain. However, in many of these studies, the researchers often examined various semantic information contents separately, such as speech content, objects in scenes, and background stories. To quantitatively evaluate the contribution of various semantic contents in the brain, we recorded brain activity using functional magnetic resonance imaging (fMRI) while participants watched a total of 8.3 hours of videos of dramas or movies. Importantly, we densely annotated these videos at multiple semantic levels related to video contents, which allowed us to extract latent representations of LLMs for a range of semantic contents. We show that LLMs explain human brain activity more accurately than traditional language models, particularly for the high-level background story. Additionally, we show that distinct brain regions correspond to different semantic contents, thereby underscoring the importance of simultaneously modeling various levels of semantic contents. We will make our fMRI dataset publicly available for future research as a biological metric of the alignment between LLMs and humans.
Maximum Likelihood Estimation for Unrooted 3-Leaf Trees: An Analytic Solution for the CFN Model

Maximum likelihood estimation is among the most widely-used methods for inferring phylogenetic trees from sequence data. This paper solves the problem of computing solutions to the maximum likelihood problem for 3-leaf trees under the 2-state symmetric mutation model (CFN model). Our main result is a closed-form solution to the maximum likelihood problem for unrooted 3-leaf trees, given generic data; this result characterizes all of the ways that a maximum likelihood estimate can fail to exist for generic data and provides theoretical validation for predictions made in [27]. Our proof makes use of both classical tools for studying group-based phylogenetic models such as Hadamard conjugation and reparameterization in terms of Fourier coordinates, as well as more recent results concerning the semi-algebraic constraints of the CFN model. To be able to put these into practice, we also give a complete characterization to test genericity.
Internal Transcribed Spacers as Phylogenetic Markers Enable Species-level Metataxonomic Analysis of Ciliated Protozoa

Background The conventional morphology-based classification of ciliates is often inaccurate and time-consuming. To address this issue, sequencing, and analysis of the 18S rRNA gene of ciliates have been used as an alternative. However, this method has limitations because the highly conserved nature of this gene makes it challenging to achieve species-level resolution. This study assesses the capability of two internal transcribed spacers, ITS1 and ITS2, along with the 28S rRNA gene, to enhance the taxonomic resolution beyond that offered by the 18S rRNA gene in free-living and host-associated ciliates. Results We compared sequences of ITSI, ITS2, and the 18S and the 28S rRNA genes downloaded from public databases and found that ITS1 and ITS2 are more divergent at both inter- and intra-specific levels than the 18S rRNA gene. We designed universal primers specific to the two ITS regions and the 28S rRNA gene for free-living and rumen ciliates. We then systematically evaluated these primers using in-silico analysis, PCR assays, and metataxonomic or metabarcoding analysis and compared them to universal 18S rRNA gene primers. We found that the new primers are specific and inclusive, with an inclusiveness rate of over 80% based on in-silico analysis and confirmed their specificity using PCR evaluation. We validated the new primers with metagenomic DNA from freshwater samples and from rumen samples. Our metataxonomic analysis demonstrated that the ITS regions and the 28S rRNA gene could reveal greater ciliate diversity than the 18S rRNA gene in both environments. In particular, ITS1 detected the highest number of ciliate species, including species and genera that were not detected by the 18S rRNA gene. Conclusions The ITS regions, particularly ITS1, offer superior taxonomic resolution, and the NCBI ITS RefSeq database allows more species to be classified. Therefore, ITS1, and to a lesser extent ITS2, is recommended for enhancing metataxonomic analysis of ciliate communities in both freshwater and rumen environments.
Restraining Wnt activation and intestinal tumorigenesis by a Rab35 dependent GTPase relay

Maintenance of homeostatic processes ensure curtailment of intestinal tumorigenesis. Inactivating mutations to Adenomatous Polyposis Coli (Apc) result in aberrantly activated Wnt signalling and initiates colorectal cancer (CRC) in approx. 80% of cases, yet our understanding of the subcellular mechanisms that modulate dysregulated pathway activity is limited. Here, using a conditional in vivo genetic screen, we identify Rab35 GTPase as a novel tumour suppressor that modulates regional Wnt activity after loss of Apc in progenitor cells. Single cell analysis revealed that progenitor cells respond to Apc depletion by increasing the expression of a GTPase activating protein, which we named blackbelt, and triggering Rab35 disassociation from the plasma membrane. Mechanistically, we demonstrate that Rab35 controls the localisation and activation of the Rho GTPase, Cdc42, which functions as a relay to regulate JNK signalling. This in turn tunes the Wnt pathway upstream of β-catenin to direct proliferation and differentiation of progenitor cells. Importantly, we show that maintaining active JNK signalling is important for the propagation of Apc mutant mouse colon organoids. Our findings highlight a novel GTPase cascade that sustains aberrant Wnt activity in specific segments of the intestine and provides impetus to therapeutically exploit this pathway to target CRC.
A covariant model of molecular and diversification patterns through time and the history of large clades

Rate shifts in speciation and extinction have been recognised as important contributors to the creation of evolutionary patterns. In particular, the distribution of modern clade sizes is difficult to reconcile with models that do not include them. Although recent advances have allowed rate shifts to be integrated into evolutionary models, these have largely been for the purpose of inferring historical rate shifts across phylogenetic trees. In addition, these models have typically assumed an independence between patterns of diversification and rates of molecular and morphological evolution, despite there being mounting evidence of a connection between them. Here, we develop a new model with two principal goals: first, to explore the general patterns of diversification implied by constantly changing rates, and secondly to integrate diversification, molecular and morphological evolution into a single coherent framework. We thus develop and analyse a covariant birth-death process in which rates of all evolutionary processes (i.e. speciation, extinction and molecular and morphological change) covary continuously, both for each species and through time. We use this model to show that modern diversity is likely to be dominated by a small number of extremely large clades at any historical epoch; that these large clades are expected to be characterised by explosive early radiations accompanied by elevated rates of molecular evolution; and that extant organisms are likely to have evolved from species with unusually fast evolutionary rates. In addition, we show that under such a model, the amount of molecular change along a particular lineage is essentially independent of its height, which further weakens the molecular clock hypothesis. Finally, our model predicts the existence of “living fossil” sister groups to large clades that are both species poor and have exhibited slow rates of morphological and molecular change. Although our model is highly stochastic, it includes no special evolutionary moments or epochs. Our results thus demonstrate that the observed historical patterns of evolution can be modelled without invoking special evolutionary mechanisms or innovations that are unique to specific times or taxa, even when they are highly non-uniform: instead they could emerge from a process that is fundamentally homogeneous throughout time.