Miracle-dz/UniFAR-FTUs huggingface dataset:
Exploring protein sequence similarity with Protein Language UMAPs (PLUMAPs)

Visualizing relationships and similarities between proteins can reveal insightful biology. Current approaches to visualize and analyze proteins based on sequence homology, such as sequence similarity networks (SSNs), create representations of BLAST-based pairwise comparisons. These approaches could benefit from incorporating recent protein language models, which generate high-dimensional vector representations of protein sequences from self-supervised learning on hundreds of millions of proteins. Inspired by SSNs, we developed an interactive tool - Protein Language UMAPs (PLUMAPs) - to visualize protein similarity with protein language models, dimensionality reduction, and topic modeling. As a case study, we compare our tool to Sequence Similarity Network (SSN) using the proteomes of two related bacterial species, Mycobacterium tuberculosis and Mycobacterium smegmatis. Both SSNs and PLUMAPs generate protein clusters corresponding to protein families and highlight enrichment or depletion across species. However, only in PLUMAPs does the layout distance between proteins and protein clusters meaningfully reflect similarity. Thus in PLUMAPs, related protein families are displayed as nearby clusters, and larger-scale structures correlate with cellular localization. Finally, we adapt techniques from topic modeling to automatically annotate protein clusters, making them more easily interpretable and potentially insightful. We envision that as large protein language models permeate bioinformatics and interactive sequence analysis tools, PLUMAPs will become a useful visualization resource across a wide variety of biological disciplines. Anticipating this, we provide a prototype for an online, open source version of PLUMAPs.
Context-dependent requirement of G protein coupling for Latrophilin-2 in target selection of hippocampal axons

The formation of neural circuits requires extensive interactions of cell-surface proteins to guide axons to their correct target neurons. Trans-cellular interactions of the adhesion G protein-coupled receptor latrophilin-2 (Lphn2) with its partner teneurin-3 instruct the precise assembly of hippocampal networks by reciprocal repulsion. Lphn2 acts as a receptor in distal CA1 neurons to direct their axons to proximal subiculum, and as a repulsive ligand in proximal subiculum to direct proximal CA1 axons to distal subiculum. It remains unclear if Lphn2-mediated intracellular signaling is required for its role in either context. Here, we show that Lphn2 couples to Gα12/13 in heterologous cells, which is increased by constitutive exposure of the tethered agonist. Specific mutations of Lphn2’s tethered agonist region disrupt its G protein coupling and autoproteolytic cleavage, whereas mutating the autoproteolytic cleavage site prevents cleavage but preserves a functional tethered agonist. Using an in vivo misexpression assay, we demonstrate that wild-type Lphn2 misdirects proximal CA1 axons to proximal subiculum and that Lphn2 tethered agonist activity is required for its role as a repulsive receptor. By contrast, neither tethered agonist activity nor autoproteolysis was necessary for Lphn2’s role as a repulsive ligand. Thus, tethered agonist activity is required for Lphn2-mediated neural circuit assembly in a context-dependent manner.
An automated microscopy workflow to study Shigella–neutrophil interactions and antibiotic efficacy in vivo

Shigella are Gram-negative bacterial pathogens responsible for bacillary dysentery (also called shigellosis). The absence of a licensed vaccine and widespread emergence of antibiotic resistance has recently led the WHO to highlight Shigella as a priority pathogen requiring urgent attention. Several infection models have been useful to explore the Shigella infection process, yet we still lack information regarding events taking place in vivo. Here, using a Shigella-zebrafish infection model and high-content microscopy, we develop an automated microscopy workflow to non-invasively study fluorescently labelled bacteria and neutrophils in vivo. We apply our workflow to antibiotic-treated zebrafish and demonstrate that neutrophil recruitment is independent of bacterial burden. Strikingly, we discover that nalidixic acid (a bactericidal antibiotic) can restrict Shigella dissemination from the hindbrain ventricle. We envision that our automated microscopy workflow, applied here to study Shigella-neutrophil interactions and antibiotic efficacy in zebrafish, can be useful to innovate treatments for infection control in humans. SUMMARY STATEMENT We develop an automated image analysis workflow to enable fast and reliant immune cell counting in Shigella-infected zebrafish larvae, and reveal how antibiotics impact Shigella-neutrophil interactions in vivo.
Zinc-based Ultrasensitive Microscopic Barrier Assay (ZnUMBA): a live-imaging method for detecting epithelial barrier breaches with spatiotemporal precision

Epithelial barrier function is commonly analyzed using transepithelial electrical resistance (TER), which measures the ion flux across epithelia, or by adding traceable macromolecules to one side of the epithelium and monitoring their passage to the other side. While these methods effectively measure changes to global barrier function, they are not sensitive enough to detect local or transient disruptions in the barrier, and they do not reveal the location of barrier breaches within the context of cell or tissue morphology. Therefore, we developed a method that we named Zinc-based Ultrasensitive Microscopic Barrier Assay (ZnUMBA), which overcomes these limitations, allowing for detection of local tight junction (TJ) leaks with high spatial and temporal resolution (Stephenson et al., 2019; Varadarajan et al., 2021). Here, we present expanded applications for ZnUMBA. First, we show that ZnUMBA can be used in Xenopus embryos to measure the dynamics of barrier restoration and actin dynamics following laser injury of the junction. We also demonstrate that ZnUMBA can be effectively utilized in developing zebrafish embryos as well as cultured monolayers of Madin-Darby Canine Kidney II (MDCK II) epithelial cells. ZnUMBA is a powerful and flexible method that, with some optimization, can be applied to multiple systems to measure dynamic changes in barrier function with spatiotemporal precision.
Resolving inter-regional communication capacity in the human connectome

Applications of graph theory to the connectome have inspired several models of how neural signaling unfolds atop its structure. Analytic measures derived from these communication models have mainly been used to extract global characteristics of brain networks, obscuring potentially informative interregional relationships. Here we develop a simple standardization method to investigate polysynaptic communication pathways between pairs of cortical regions. This procedure allows us to determine which pairs of nodes are topologically closer and which are further than expected on the basis of their degree. We find that communication pathways delineate canonical functional systems. Relating nodal communication capacity to meta-analytic probabilistic patterns of functional specialization, we also show that areas that are most closely integrated within the network are associated with higher-order cognitive functions. We find that these regions’ proclivity towards functional integration could naturally arise from the brain’s anatomical configuration through evenly distributed connections among multiple specialized communities. Throughout, we consider two increasingly constrained null models to disentangle the effects of the network’s topology from those passively endowed by spatial embedding. Altogether, the present findings uncover relationships between polysynaptic communication pathways and the brain’s functional organization across multiple topological levels of analysis and demonstrate that network integration facilitates cognitive integration.
Theoretical treatments of the bound-free contribution and experimental best practice in X-ray Thomson scattering from warm dense matter

By comparison with high-resolution synchrotron x-ray experimental results, we assess several theoretical treatments for the bound-free (core-electron) contribution to x-ray Thomson scattering (i.e., also known as nonresonant inelastic x-ray scattering). We identify an often overlooked source of systematic error in the plane-wave form factor approximation (PWFFA) used in the inference of temperature, ionization state, and free electron density in some laser-driven compression studies of warm dense matter. This error is due to a direct violation of energy conservation in the PWFFA. We propose an improved practice for the bound-free term that will be particularly relevant for XRTS experiments performed with somewhat improved energy resolution at the National Ignition Facility or the Linac Coherent Light Source. Our results raise important questions about the accuracy of state variable determination in XRTS studies, given that the limited information content in low-resolution XRTS spectra does not strongly constrain the models of electronic structure being used to fit the spectra.
The 5.52 Year Cycle of Eta Carinae

I have discovered spectroscopic variations correlated with the photometric near-infrared (NIR) light curve in η Carinae. The fading of the high-excitation lines is coincident with the peaks in the NIR light curve, strongly resembling an S Doradus type of variability. The cycle, however, is highly stable, and the 5.52 yr period fits well all the shell episodes reported in the last 50 years. This period also recovers the three historical bursts of the last century, in phase with the present low-amplitude oscillations, which suggests a connection between the S Doradus cycle and the giant bursts. The present data reveal that η Car is continuously varying in the He I λ10830 line by thousands of solar luminosities. The last spectra in this line show that the low-excitation phase is already in progress. A test for the strict periodicity will be the confirmation of the central phase epoch of the next shell event, predicted to occur in 1997 December. A very sensitive mapping technique is also proposed for this occasion, in order to prove Homunculus geometry.
Probing charging and localization in the quantum Hall regime by graphene p-n-p junctions

Using high quality graphene pnp junctions, we observe prominent conductance fluctuations on transitions between quantum Hall (QH) plateaus as the top gate voltage Vtg is varied. In the Vtg-B plane, the fluctuations form crisscrossing lines that are parallel to those of the adjacent plateaus, with different temperature dependences for the conductance peaks and valleys. These fluctuations arise from Coulomb-induced charging of electron- or hole-doped localized states when the device bulk is delocalized, underscoring the importance of electronic interactions in graphene in the QH regime.
Probing multipartite entanglement in a coupled Jaynes-Cummings system

A single two-level atom coupled to a single cavity, orresonator, mode has been studied intensively since the intro-duction of the “Jaynes-Cummings (JC) Model” independentlyby Jaynes and Cummings [1] and by Paul [2] in 1963.Quantum-ﬁeld effects such as periodic spontaneous collapseand revival [3] are now studied and observed in many systemsand as a multitude of manifestations [4]. Coupled JC systemshave been proposed as a basis for quantum networks [5] andcould behave as a novel condensed-matter system if enoughJC systems can be coupled together [6]. In a preliminary study we developed theoretical toolsfor calculating the spectrum, stationary states, and dielectricsusceptibility [7]. Here we use and extend those tools,especially to include the nontrivial open-system effects ofspontaneous emission and cavity losses. In particular, weconsider the problem of how to probe and characterize suchsystems experimentally. Two quite different approaches areevident. One approach is to probe each component in amicroscopic paradigm, namely, drive and detect the variousatoms and cavity modes. Another approach, which we favor,is to treat the coupled JC system as a “black-box” model andprobe it as a single unit following a macroscopic paradigm.Our concept is to regard the coupled JC system as adielectric medium whose susceptibility carries a signature ofthe peculiarities of the coupled JC system. Diagonalizing theHamiltonian of the coupled JC system, we ﬁnd entangledstates and their energies. Using the Fermi’s golden rule, wecalculate the transition rates between different manifolds ofthe energy states of the system. In this paper, we restrict thecalculation to transitions from the single-excitation states tothe ground state of the system. In particular we show that thedielectric susceptibility of the coupled JC medium reveals,by probe-ﬁeld spectroscopy, quadripartite entanglement of thesystem comprising mutually coupled atoms and cavity modes.Based on our theoretical framework for JC systems mutuallycoupled by overlapping extra-cavity longitudinal ﬁelds, wecan calculate stationary states for the coupled system, energyspectrum, and dielectric susceptibility.The paper is organized as follows. In Sec. II we give aqualitative discussion and a detailed calculation of radiativeproperties of a single JC cell. Section III is devoted tothe discussion of the entangled and radiative properties oftwo coupled JC cells. We derive single-excitation statesof the system and show that they are the
Domestication of newly evolved hexaploid wheat—A journey of wild grass to cultivated wheat

Domestication of wheat started with the dawn of human civilization. Since then, improvement in various traits including resistance to diseases, insect pests, saline and drought stresses, grain yield, and quality were improved through selections by early farmers and then planned hybridization after the discovery of Mendel’s laws. In the 1950s, genetic variability was created using mutagens followed by the selection of superior mutants. Over the last 3 decades, research was focused on developing superior hybrids, initiating marker-assisted selection and targeted breeding, and developing genetically modified wheat to improve the grain yield, tolerance to drought, salinity, terminal heat and herbicide, and nutritive quality. Acceptability of genetically modified wheat by the end-user remained a major hurdle in releasing into the environment. Since the beginning of the 21st century, changing environmental conditions proved detrimental to achieving sustainability in wheat production particularly in developing countries. It is suggested that high-tech phenotyping assays and genomic procedures together with speed breeding procedures will be instrumental in achieving food security beyond 2050.
Comment on "Cosmic radio dipole from NVSS and WENSS"

We show that a recent purported correction to the effects of Doppler boosting of flux density in an erstwhile published formula for calculating the observer's motion from the cosmic radio dipole in sky brightness is erroneous. The thereby computed downward correction in the estimated magnitude for the observer's motion needs to be scrapped and the results derived therefore need to be reverted back to their erstwhile values.
A test of indirect grounding of abstract concepts using multimodal distributional semantics

How are abstract concepts grounded in perceptual experiences for shaping human conceptual knowledge? Recent studies on abstract concepts emphasizing the role of language have argued that abstract concepts are grounded indirectly in perceptual experiences and language (or words) functions as a bridge between abstract concepts and perceptual experiences. However, this “indirect grounding” view remains largely speculative and has hardly been supported directly by empirical evidence. In this paper, therefore, we test the indirect grounding view by means of multimodal distributional semantics, in which the meaning of a word (i.e., a concept) is represented as the combination of textual and visual vectors. The newly devised multimodal distributional semantic model incorporates the indirect grounding view by computing the visual vector of an abstract word through the visual vectors of concrete words semantically related to that abstract word. An evaluation experiment is conducted in which conceptual representation is predicted from multimodal vectors using a multilayer feed-forward neural network. The analysis of prediction performance demonstrates that the indirect grounding model achieves significantly better performance in predicting human conceptual representation of abstract words than other models that mimic competing views on abstract concepts, especially than the direct grounding model in which the visual vectors of abstract words are computed directly from the images of abstract concepts. This result lends some plausibility to the indirect grounding view as a cognitive mechanism of grounding abstract concepts.
Developmental assets and positive youth development in Brazilian university students

The Positive Youth Development (PYD) describes an intersection between young people and their context, emphasizing characteristics of a healthy development. The PYD’s 5Cs occur when there is an alignment between healthy individual characteristics and contextual resources. This study investigated the PYD’s 5Cs associations with the perception of social connections (family, community, academic), mental health, and stressful events. The sample was composed of 495 Brazilian College students aged between 18 and 33 years, who answered a survey with 59 questions about reflexive, constructive, and healthy behaviors. Descriptive, correlational, and regression analysis through structural equation modeling were conducted. The results focused on the role of family, community and educational institution in the PYD promotion. These results highlight the relevant contributions of social support in the construction of protective strategies of coping with stressful events and in the promotion of health behaviors and well-being, particularly in the university context.
Spatial variability of hypoxia and coupled physical-biogeochemical controls off the Changjiang (Yangtze River) Estuary in summer

Global estuarine hypoxia is among the most acute environmental issues, yet the recognition of hypoxia variability remains patchy. The Changjiang (Yangtze River) Estuary (CE) is well known as one of the largest estuarine hypoxic systems. However, the mechanisms controlling the spatial variability and heterogeneity of summer hypoxia have been rarely examined in this region. Based on observational data in the summer of 2013, the essential linkages between physical-biogeochemical processes and spatial variability of hypoxia were revealed off the CE. The hypoxia generally occurred in a transitional region off the CE, presenting to be spatially variable and heterogeneous in its distribution and intensity. The river plume, stratification, front, upwelling and localized high phytoplankton biomass combine to shape the spatial morphology and scope of hypoxia. The spatial heterogeneity of hypoxic magnitude in horizontal direction is mainly regulated by the intensity variability of stratification and phytoplankton blooms. The position of bottom front formed by the offshore Taiwan Warm Current (TWC) and coastal water under tidal mixing controls the shoreward boundary of hypoxic zone, while the river plume front-dominated outer edge of phytoplankton blooms in upper layers plays a role in determining the seaward limit of the reach of bottom hypoxia. The stratification depth controlled by the upwelling and river plume governs the upper limit of the top reach of hypoxia, and shapes the vertical morphology of hypoxic zone. We contextualize the role of physical-biogeochemical drivers to the spatially variable hypoxia in a conceptual diagram. The findings would considerably contribute to our understanding of the spatially variable hypoxia in river plume-upwelling-front coupled estuarine systems, providing a sound basis for prediction and simulation under anticipated future conditions.
Rapidly progressive Guillain–Barré syndrome following amitriptyline overdose and severe Klebsiella pneumoniae infection: A case report and literature review

Guillain–Barré syndrome (GBS) is a potentially life-threatening post-infectious autoimmune disease characterized by rapidly progressive symmetrical weakness of the extremities. Herein, we report a case of GBS associated with drug poisoning complicated by Klebsiella pneumoniae infection. A 38-year-old woman was admitted to the intensive care unit after taking an overdose of amitriptyline and was later diagnosed with coma, Klebsiella pneumoniae infection, and septic shock. Thirteen days after admission, she was diagnosed with GBS based on acute muscle pain, flaccid paralysis, hyporeflexia, reduced amplitude of compound muscle action potential, and albuminocytologic dissociation in the cerebrospinal fluid. GBS rarely occurs after a drug overdose and septic shock, and this is the first report of a rapidly progressive GBS following amitriptyline overdose and severe Klebsiella pneumoniae infection.
Dephosphorylation in nuclear reassembly after mitosis

In most animal cell types, the interphase nucleus is largely disassembled during mitotic entry. The nuclear envelope breaks down and chromosomes are compacted into separated masses. Chromatin organization is also mostly lost and kinetochores assemble on centromeres. Mitotic protein kinases play several roles in inducing these transformations by phosphorylating multiple effector proteins. In many of these events, the mechanistic consequences of phosphorylation have been characterized. In comparison, how the nucleus reassembles at the end of mitosis is less well understood in mechanistic terms. In recent years, much progress has been made in deciphering how dephosphorylation of several effector proteins promotes nuclear envelope reassembly, chromosome decondensation, kinetochore disassembly and interphase chromatin organization. The precise roles of protein phosphatases in this process, in particular of the PP1 and PP2A groups, are emerging. Moreover, how these enzymes are temporally and spatially regulated to ensure that nuclear reassembly progresses in a coordinated manner has been partly uncovered. This review provides a global view of nuclear reassembly with a focus on the roles of dephosphorylation events. It also identifies important open questions and proposes hypotheses.
Editorial: Cognitive reserve, cognitive functioning, and mental health in elderly people

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