pwc-archive/papers-with-abstracts huggingface dataset:
MetaEnzyme: Meta Pan-Enzyme Learning for Task-Adaptive Redesign
Authors: Jiangbin Zheng, Han Zhang, Qianqing Xu, An-Ping Zeng, Stan Z. Li
Date: 2024-08-05 00:00:00

Enzyme design plays a crucial role in both industrial production and biology. However, this field faces challenges due to the lack of comprehensive benchmarks and the complexity of enzyme design tasks, leading to a dearth of systematic research. Consequently, computational enzyme design is relatively overlooked within the broader protein domain and remains in its early stages. In this work, we address these challenges by introducing MetaEnzyme, a staged and unified enzyme design framework. We begin by employing a cross-modal structure-to-sequence transformation architecture, as the feature-driven starting point to obtain initial robust protein representation. Subsequently, we leverage domain adaptive techniques to generalize specific enzyme design tasks under low-resource conditions. MetaEnzyme focuses on three fundamental low-resource enzyme redesign tasks: functional design (FuncDesign), mutation design (MutDesign), and sequence generation design (SeqDesign). Through novel unified paradigm and enhanced representation capabilities, MetaEnzyme demonstrates adaptability to diverse enzyme design tasks, yielding outstanding results. Wet lab experiments further validate these findings, reinforcing the efficacy of the redesign process.
Comparison of algorithms used in single-cell transcriptomic data analysis
Authors: Jafar Isbarov, Elmir Mahammadov
Date: 2024-08-21 00:00:00

Single-cell analysis is an increasingly relevant approach in "omics'' studies. In the last decade, it has been applied to various fields, including cancer biology, neuroscience, and, especially, developmental biology. This rise in popularity has been accompanied with creation of modern software, development of new pipelines and design of new algorithms. Many established algorithms have also been applied with varying levels of effectiveness. Currently, there is an abundance of algorithms for all steps of the general workflow. While some scientists use ready-made pipelines (such as Seurat), manual analysis is popular, too, as it allows more flexibility. Scientists who perform their own analysis face multiple options when it comes to the choice of algorithms. We have used two different datasets to test some of the most widely-used algorithms. In this paper, we are going to report the main differences between them, suggest a minimal number of algorithms for each step, and explain our suggestions. In certain stages, it is impossible to make a clear choice without further context. In these cases, we are going to explore the major possibilities, and make suggestions for each one of them.
Extrinsic Fluctuations in the p53 Cycle
Authors: Manuel Eduardo Hernández-García, Mariana Gómez-Schiavon, Jorge Velázquez-Castro
Date: 2024-08-22 00:00:00
Tasks: Computational Efficiency

Fluctuations are inherent to biological systems, arising from the stochastic nature of molecular interactions, and influence various aspects of system behavior, stability, and robustness. These fluctuations can be categorized as intrinsic, stemming from the system's inherent structure and dynamics, and extrinsic, arising from external factors, such as temperature variations. Understanding the interplay between these fluctuations is crucial for obtaining a comprehensive understanding of biological phenomena. However, studying these effects poses significant computational challenges. In this study, we used an underexplored methodology to analyze the effect of extrinsic fluctuations in stochastic systems using ordinary differential equations instead of solving the Master Equation with stochastic parameters. By incorporating temperature fluctuations into reaction rates, we explored the impact of extrinsic factors on system dynamics. We constructed a master equation and calculated the equations for the dynamics of the first two moments, offering computational efficiency compared with directly solving the chemical master equation. We applied this approach to analyze a biological oscillator, focusing on the p53 model and its response to temperature-induced extrinsic fluctuations. Our findings underscore the impact of extrinsic fluctuations on the nature of oscillations in biological systems, with alterations in oscillatory behavior depending on the characteristics of extrinsic fluctuations. We observed an increased oscillation amplitude and frequency of the p53 concentration cycle. This study provides valuable insights into the effects of extrinsic fluctuations on biological oscillations and highlights the importance of considering them in more complex systems to prevent unwanted scenarios related to health issues.
Imaging mitochondrial calcium dynamics in the central nervous system
Authors: Roman Serrat, Alexandre Oliveira-Pinto, Giovanni Marsicano, Sandrine Pouvreau
Date: 2024-08-22 00:00:00

Mitochondrial calcium handling is a particularly active research area in the neuroscience field, as it plays key roles in the regulation of several functions of the central nervous system, such as synaptic transmission and plasticity, astrocyte calcium signaling, neuronal activity{\ldots} In the last few decades, a panel of techniques have been developed to measure mitochondrial calcium dynamics, relying mostly on photonic microscopy, and including synthetic sensors, hybrid sensors and genetically encoded calcium sensors. The goal of this review is to endow the reader with a deep knowledge of the historical and latest tools to monitor mitochondrial calcium events in the brain, as well as a comprehensive overview of the current state of the art in brain mitochondrial calcium signaling. We will discuss the main calcium probes used in the field, their mitochondrial targeting strategies, their key properties and major drawbacks. In addition, we will detail the main roles of mitochondrial calcium handling in neuronal tissues through an extended report of the recent studies using mitochondrial targeted calcium sensors in neuronal and astroglial cells, in vitro and in vivo.
ST-USleepNet: A Spatial-Temporal Coupling Prominence Network for Multi-Channel Sleep Staging
Authors: Jingying Ma, Qika Lin, Ziyu Jia, Mengling Feng
Date: 2024-08-21 00:00:00
Tasks: graph construction, Image Segmentation, Semantic Segmentation, Sleep Quality, Sleep Staging

Sleep staging is critical to assess sleep quality and diagnose disorders. Despite advancements in artificial intelligence enabling automated sleep staging, significant challenges remain: (1) Simultaneously extracting prominent temporal and spatial sleep features from multi-channel raw signals, including characteristic sleep waveforms and salient spatial brain networks. (2) Capturing the spatial-temporal coupling patterns essential for accurate sleep staging. To address these challenges, we propose a novel framework named ST-USleepNet, comprising a spatial-temporal graph construction module (ST) and a U-shaped sleep network (USleepNet). The ST module converts raw signals into a spatial-temporal graph based on signal similarity, temporal, and spatial relationships to model spatial-temporal coupling patterns. The USleepNet employs a U-shaped structure for both the temporal and spatial streams, mirroring its original use in image segmentation to isolate significant targets. Applied to raw sleep signals and graph data from the ST module, USleepNet effectively segments these inputs, simultaneously extracting prominent temporal and spatial sleep features. Testing on three datasets demonstrates that ST-USleepNet outperforms existing baselines, and model visualizations confirm its efficacy in extracting prominent sleep features and temporal-spatial coupling patterns across various sleep stages. The code is available at https://github.com/Majy-Yuji/ST-USleepNet.
Manifold Transform by Recurrent Cortical Circuit Enhances Robust Encoding of Familiar Stimuli
Authors: Weifan Wang, Xueyan Niu, Tai-Sing Lee
Date: 2024-08-20 00:00:00

A ubiquitous phenomenon observed throughout the primate hierarchical visual system is the sparsification of the neural representation of visual stimuli as a result of familiarization by repeated exposure, manifested as the sharpening of the population tuning curves and suppression of neural responses at the population level. In this work, we investigated the computational implications and circuit mechanisms underlying these neurophysiological observations in an early visual cortical circuit model. We found that such a recurrent neural circuit, shaped by BCM Hebbian learning, can also reproduce these phenomena. The resulting circuit became more robust against noises in encoding the familiar stimuli. Analysis of the geometry of the neural response manifold revealed that recurrent computation and familiar learning transform the response manifold and the neural dynamics, resulting in enhanced robustness against noise and better stimulus discrimination. This prediction is supported by preliminary physiological evidence. Familiarity training increases the alignment of the slow modes of network dynamics with the invariant features of the learned images. These findings revealed how these rapid plasticity mechanisms can improve contextual visual processing in even the early visual areas in the hierarchical visual system.
On the alternatives to the ideal mathematical points-like separatedness
Authors: Bartosz Jura
Date: 2024-08-10 00:00:00

In a recent paper as an alternative to models based on the notion of ideal mathematical point, characterized by a property of separatedness, we considered a viewpoint based on the notion of continuous change, making use of elements of a non-classical logic, in particular the fuzzy sets theory, with events represented as spatiotemporally blurred blobs. Here we point out and discuss a number of aspects of this imperfect symbolic description that might potentially be misleading. Besides that, we analyze its relation to various concepts used commonly to model physical systems, denoted by terms like: point, set, continuous, discrete, infinite, or local, clarifying further how our viewpoint is different and asking whether, in light of our main postulate, any of these notions, or their opposites, if exist, are in their usual meanings suitable to accurately describe the natural phenomena.
The Unbearable Slowness of Being: Why do we live at 10 bits/s?
Authors: Jieyu Zheng, Markus Meister
Date: 2024-08-03 00:00:00

This article is about the neural conundrum behind the slowness of human behavior. The information throughput of a human being is about 10 bits/s. In comparison, our sensory systems gather data at ~10^9 bits/s. The stark contrast between these numbers remains unexplained and touches on fundamental aspects of brain function: What neural substrate sets this speed limit on the pace of our existence? Why does the brain need billions of neurons to process 10 bits/s? Why can we only think about one thing at a time? The brain seems to operate in two distinct modes: the "outer" brain handles fast high-dimensional sensory and motor signals, whereas the "inner" brain processes the reduced few bits needed to control behavior. Plausible explanations exist for the large neuron numbers in the outer brain, but not for the inner brain, and we propose new research directions to remedy this.
Comment on Miscalibration of the Honeybee Odometer
Authors: Mandyam Srinivasan, Juergen Tautz, Geoffrey W Stuart
Date: 2024-08-21 00:00:00

This is a point-by-point response to a non-peer-reviewed document titled The Miscalibration of the Honeybee Odometer [arXiv:2405.12998], authored by L. Luebbert and L. Pachter, that was published on arXiv on 8 May 2024 and subsequently publicised via social and mainstream media. The authors never contacted Srinivasan or Tautz personally with their queries, nor did they seek clarification. They do not work in this research area, and they have drawn several unjustified conclusions that reflect a limited understanding of the data they have examined.
Effect of IBA concentration and water soaking on rooting hardwood cuttings of black mulberry (Morus nigra L.)
Authors: Rasul Rafiq Aziz, Aram Akram Mohammed, Faraydwn Karim Ahmad, Ari Jamil Ali
Date: 2024-08-20 00:00:00

The research was conducted at the College of Agricultural Sciences Engineering/University of Sulaimani/ Kurdistan Region-Iraqi to investigate effects of different concentrations of IBA (0, 3000, 4000 and 5000 ppm) and soaking in water for 24 hours on propagation black mulberry (Morus nigra L.) by hardwood cuttings. In this research the parameters of rooting percentage, root number, root length, sprout bud number, shoot length and shoot diameter were measured. Effect of individual factors showed that the highest rooting percentage (15%) was achieved in cuttings soaked in water for 24 hours, as well as improving other traits. Also, the best (23.33%) rooting was found in cuttings dipped in 4000 ppm IBA. Interaction effects of the two factors showed that cuttings treated with 4000 ppm IBA and soaked in water for 24 hours gave the highest (40%) rooting, and the highest other root and shoot traits were achieved in the same interaction as well.
Patterns of Transposable Element Distribution Around Chromatin Ligation Points Revealed by Micro-C Data Analysis
Authors: Alexandr V. Vikhorev, Michael M. Rempel, Oksana O. Polesskaya, Ivan V. Savelev, Max V. Myakishev-Rempel
Date: 2024-08-20 00:00:00

Transposable elements (TEs) constitute a significant portion of eukaryotic genomes, yet their role in chromatin organization remains poorly understood. This study investigates the distribution patterns of TEs around chromatin ligation points (LPs) identified through Micro-C experiments in human cells. We analyzed the density of various TE families within a 100kb window centered on LPs, focusing on major families such as Alu and LINE-1 (L1) elements. Our findings reveal distinct, non-random distribution patterns that differ between TE families and exhibit consistent strand-specific biases. These patterns were reproducible across two independent datasets and showed marked differences from random genomic distributions. Notably, we observed family-specific variations in TE density near LPs, with some families showing depletion at LPs followed by periodic fluctuations in density. The consistency of these patterns across TE families and their orientation relative to chromosome arms suggest a fundamental relationship between TEs and higher-order chromatin structure. Our results provide new insights into the potential role of TEs in genome organization and challenge the notion of TEs as passive genomic components. This study lays the groundwork for future investigations into the functional implications of TE distribution in chromatin architecture and gene regulation.
Sex chromosome evolution: The classical paradigm and so much beyond
Authors: Paris Veltsos, Sagar Shinde, Wen-Juan Ma
Date: 2024-08-21 00:00:00

Sex chromosomes have independently evolved in species with separate sexes in most lineages across the tree of life. However, the well-accepted canonical model of sex chromosome evolution is not universally supported. There is no single trajectory for sex chromosome formation and evolution across the tree of life, suggesting the underlying mechanisms and evolutionary forces are diverse and lineage specific. We review the diversity of sex chromosome systems, describe the canonical model of sex chromosome evolution, and summarize studies challenging various aspects of this model. They include evidence that many lineages experience frequent sex chromosome turnovers or maintain homomorphic sex chromosomes over long periods of time, suggesting sex chromosome degeneration is not inevitable. Sometimes the sex-limited Y/W chromosomes expand before they contract in size. Both transposable elements and gene gains could contribute to this size expansion, which further challenges gene loss being the hallmark of sex chromosome degeneration. Finally, empirical support for the role of sexually antagonistic selection as a driver of recombination suppression on sex chromosomes remains elusive. We summarize models that result in loss of recombination without invoking sexually antagonistic selection, which have not been empirically verified yet, and suggest future avenues for sex chromosome research.
What you saw is what you got? -- Correcting reported incidence data for testing intensity
Authors: Rasmus Kristoffer Pedersen, Christian Berrig, Tamás Tekeli, Gergely Röst, Viggo Andreasen
Date: 2024-08-21 00:00:00

During the COVID-19 pandemic, different types of non-pharmaceutical interventions played an important role in the efforts to control outbreaks and to limit the spread of the SARS-CoV-2 virus. In certain countries, large-scale voluntary testing of non-symptomatic individuals was done, with the aim of identifying asymptomatic and pre-symptomatic infections as well as gauging the prevalence in the general population. In this work, we present a mathematical model, used to investigate the dynamics of both observed and unobserved infections as a function of the rate of voluntary testing. The model indicate that increasing the rate of testing causes the observed prevalence to increase, despite a decrease in the true prevalence. For large testing rates, the observed prevalence also decrease. The non-monotonicity of observed prevalence explains some of the discrepancies seen when comparing uncorrected case-counts between countries. An example of such discrepancy is the COVID-19 epidemics observed in Denmark and Hungary during winter 2020/2021, for which the reported case-counts were comparable but the true prevalence were very different. The model provides a quantitative measure for the ascertainment rate between observed and true incidence, allowing for test-intensity correction of incidence data. By comparing the model to the country-wide epidemic of the Omicron variant (BA.1 and BA.2) in Denmark during the winter 2021/2022, we find a good agreement between the cumulative incidence as estimated by the model and as suggested by serology-studies. While the model does not capture the full complexity of epidemic outbreaks and the effect of different interventions, it provides a simple way to correct raw case-counts for differences in voluntary testing, making comparison across international borders and testing behaviour possible.
A Review of Lagrangian Formalism in Biology: Recent Advances and Perspectives
Authors: Diana T. Pham, Zdzislaw E. Musielak
Date: 2024-08-20 00:00:00

The Lagrangian formalism has attracted the attention of mathematicians and physicists for more than 250 years and has played significant roles in establishing modern theoretical physics. The history of the Lagrangian formalism in biology is much shorter, spanning only the last 50 years. In this paper, a broad review of the Lagrangian formalism in biology is presented in the context of both its historical and modern developments. Detailed descriptions of different methods to derive Lagrangians for five selected population dynamics models are given and the resulting Lagrangians are presented and discussed. The procedure to use the obtained Lagrangians to gain new biological insights into the evolution of the populations without solving the equations of motion is described and applied to the models. Finally, perspectives of the Lagrangian formalism in biology are discussed.
Spatio-Temporal Variability of the Pepper Mild Mottle Virus Biomarker in Wastewater
Authors: AnnaElaine L. Rosengart, Amanda L. Bidwell, Marlene K. Wolfe, Alexandria B. Boehm, F. William Townes
Date: 2024-08-21 00:00:00
Tasks: Epidemiology

Since the start of the coronavirus-19 pandemic, the use of wastewater-based epidemiology (WBE) for disease surveillance has increased throughout the world. Because wastewater measurements are affected by external factors, processing WBE data typically includes a normalization step in order to adjust wastewater measurements (e.g. viral RNA concentrations) to account for variation due to dynamic population changes, sewer travel effects, or laboratory methods. Pepper mild mottle virus (PMMoV), a plant RNA virus abundant in human feces and wastewater, has been used as a fecal contamination indicator and has been used to normalize wastewater measurements extensively. However, there has been little work to characterize the spatio-temporal variability of PMMoV in wastewater, which may influence the effectiveness of PMMoV for adjusting or normalizing WBE measurements. Here, we investigate its variability across space and time using data collected over a two-year period from sewage treatment plants across the United States. We find that most variation in PMMoV measurements can be attributed to longitude and latitude followed by site-specific variables. Further research into cross-geographical and -temporal comparability of PMMoV-normalized pathogen concentrations would strengthen the utility of PMMoV in WBE.
Towards an Accessible, Noninvasive Micronutrient Status Assessment Method: A Comprehensive Review of Existing Techniques
Authors: Andrew Balch, Maria A. Cardei, Sibylle Kranz, Afsaneh Doryab
Date: 2024-08-20 00:00:00

Nutrients are critical to the functioning of the human body and their imbalance can result in detrimental health concerns. The majority of nutritional literature focuses on macronutrients, often ignoring the more critical nuances of micronutrient balance, which require more precise regulation. Currently, micronutrient status is routinely assessed via complex methods that are arduous for both the patient and the clinician. To address the global burden of micronutrient malnutrition, innovations in assessment must be accessible and noninvasive. In support of this task, this article synthesizes useful background information on micronutrients themselves, reviews the state of biofluid and physiological analyses for their assessment, and presents actionable opportunities to push the field forward. By taking a unique, clinical perspective that is absent from technological research on the topic, we find that the state of the art suffers from limited clinical relevance, a lack of overlap between biofluid and physiological approaches, and highly invasive and inaccessible solutions. Future work has the opportunity to maximize the impact of a novel assessment method by incorporating clinical relevance, the holistic nature of micronutrition, and prioritizing accessible and noninvasive systems.
Portable-CELLxGENE: standalone executables of CELLxGENE for easy installation
Authors: George T. Hall
Date: 2024-08-07 00:00:00

Biologists who want to analyse their single-cell transcriptomics dataset must install and use specialist software via the command line. This is often impractical for non-bioinformaticians. Whilst the popular CELLxGENE software provides an intuitive graphical interface to facilitate analysis outside the command line, its server-side installation and execution remain complex. A version that is easier to install and run would allow non-bioinformaticians to take advantage of this valuable tool without needing to use the command line. Portable-CELLxGENE is a standalone distribution of CELLxGENE that can be installed via a graphical interface. It contains an easy-to-use extension of the CELLxGENE-Gateway Python package to allow the analysis of multiple datasets. Availability and implementation: Versions of Portable-CELLxGENE for Windows and MacOS, along with its source code, are available at github.com/george-hall-ucl/portable-cellxgene. It is licensed under the GNU General Public License v3.