bluuebunny/crossref_metadata_2025 huggingface dataset:
Stochastic microbial dispersal drives local extinction and global diversity
Authors: Garrido Zornoza Miguel , Mitarai Namiko , Haerter Jan O.
Published: May 2024

Airborne dispersal of microorganisms is a ubiquitous migration mechanism, allowing otherwise independent microbial habitats to interact via biomass exchange. Here, we study the ecological implications of such advective transport using a simple spatial model for bacteria–phage interactions: the population dynamics at each habitat are described by classical Lotka–Volterra equations; however, species populations are taken as integer, that is, a discrete, positive extinction threshold exists. Spatially, species can spread from habitat to habitat by stochastic airborne dispersal. In any given habitat, the spatial biomass exchange causes incessant population density oscillations, which, as a consequence, occasionally drive species to extinction. The balance between local extinction events and dispersal-induced migration allows species to persist globally, even though diversity would be depleted by competitive exclusion, locally. The disruptive effect of biomass dispersal thus acts to increase microbial diversity, allowing system-scale coexistence of multiple species that would not coexist locally.
Advancements in application of modified biochar as a green and low-cost adsorbent for wastewater remediation from organic dyes
Authors: Hama Aziz Kosar Hikmat , Fatah Nazhad Majeed , Muhammad Khalid Taib
Published: May 2024

Synthetic organic dyes, which are resistant to biodegradation, pose a notable health risk, potentially leading to cancer and respiratory infections. Researchers have addressed this concern by exploring physicochemical methods to remove organic dyes from wastewater. A particularly promising solution involves modified biochar adsorbents, which demonstrate high efficiency in organic dye removal. Biochar, a charcoal-like material derived from biomass pyrolysis, offers advantages such as low cost, eco-friendliness, high efficiency and reusability. Beyond its role in sustainable soil remediation, biochar proves effective in removing organic dyes from wastewater after undergoing physical or chemical modification. Acid–base activation or metal–heteroatom impregnation enhances biochar's adsorption capacity. This comprehensive review examines the attributes of biochar, common methods for production and modification, and the impacts of raw materials, pyrolysis temperature, heating rate and residence time. It further elucidates the biochar adsorption mechanism in the removal of organic dyes, assessing factors influencing efficiency, including biochar feedstock, solution pH, adsorption temperature, particle size, initial dye concentration, biochar dosage and reaction time. It explores challenges, opportunities, reusability and regeneration methods of biochar in treating organic dye wastewater. It also discusses recent advances in organic dye removal using adsorption-based biochar. The review ultimately advocates for enhancing biochar's adsorption performance through post-modification.
A complex network approach to analyse pre-trained language models for ancient Chinese
Authors: Zheng Jianyu , Xiao Xin'ge
Published: May 2024

Ancient Chinese is a splendid treasure within Chinese culture. To facilitate its compilation, pre-trained language models for ancient Chinese are developed. After that, researchers are actively exploring the factors contributing to their success. However, previous work did not study how language models organized the elements of ancient Chinese from a holistic perspective. Hence, we adopt complex networks to explore how language models organize the elements in ancient Chinese system. Specifically, we first analyse the characters’ and words’ co-occurrence networks in ancient Chinese. Then, we study characters’ and words’ attention networks, generated by attention heads within SikuBERT from two aspects: static and dynamic network analysis. In the static network analysis, we find that (i) most of attention networks exhibit small-world properties and scale-free behaviour, (ii) over 80% of attention networks exhibit high similarity with the corresponding co-occurrence networks, (iii) there exists a noticeable gap between characters’ and words’ attention networks across layers, while their fluctuations remain relatively consistent, and (iv) the attention networks generated by SikuBERT tend to be sparser compared with those from Chinese BERT. In dynamic network analysis, we find that the sentence segmentation task does not significantly affect network metrics, while the part-of-speech tagging task makes attention networks sparser.
Discrete and continuous mathematical models of sharp-fronted collective cell migration and invasion
Authors: Simpson Matthew J. , Murphy Keeley M. , McCue Scott W. , Buenzli Pascal R.
Published: May 2024

Mathematical models describing the spatial spreading and invasion of populations of biological cells are often developed in a continuum modelling framework using reaction–diffusion equations. While continuum models based on linear diffusion are routinely employed and known to capture key experimental observations, linear diffusion fails to predict well-defined sharp fronts that are often observed experimentally. This observation has motivated the use of nonlinear degenerate diffusion; however, these nonlinear models and the associated parameters lack a clear biological motivation and interpretation. Here, we take a different approach by developing a stochastic discrete lattice-based model incorporating biologically inspired mechanisms and then deriving the reaction–diffusion continuum limit. Inspired by experimental observations, agents in the simulation deposit extracellular material, which we call a
substrate
, locally onto the lattice, and the motility of agents is taken to be proportional to the substrate density. Discrete simulations that mimic a two-dimensional circular barrier assay illustrate how the discrete model supports both smooth and sharp-fronted density profiles depending on the rate of substrate deposition. Coarse-graining the discrete model leads to a novel partial differential equation (PDE) model whose solution accurately approximates averaged data from the discrete model. The new discrete model and PDE approximation provide a simple, biologically motivated framework for modelling the spreading, growth and invasion of cell populations with well-defined sharp fronts. Open-source Julia code to replicate all results in this work is available on
GitHub
.
Theory of elastic wave propagation in a fluid-saturated multi-porous medium with multi-permeability
Authors: Pramanik Dipendu , Manna Santanu , Nobili Andrea
Published: May 2024

This paper establishes the concept of elastic wave propagation in a multi-porous medium with different permeabilities by assuming there are

n

distinct pore fluid phases. The dynamic equation of motion of elastic wave propagation through this multi-porous medium is derived based on Lagrangian mechanics. In this regard, the generalized form of mass coefficients and then the energy loss due to the fluid phases in terms of dissipation coefficients are presented for low-frequency limits with the help of Darcy’s Law of multi-phases system. The elastic coefficients of the constitutive equation in terms of compliance matrix are identified using a series of Gedanken experiments. Some significant results regarding the compressional and rotational waves in a multi-porosity medium are derived. The validation of the theory has been shown by comparing it with the existing theory of single and double porosity. It is observed that there are

(
n
+
1
)

compressional waves corresponding to solid and fluid phases, whereas only one rotational wave is associated with the solid phase. The concept of multi-porosity theory can contribute to a deeper understanding of wave behaviour in a porous medium.
Naturally occurring viruses of
Drosophila
reduce offspring number and lifespan
Authors: Wallace Megan A. , Obbard Darren J.
Published: May 2024

Drosophila
remains a pre-eminent insect model system for host–virus interaction, but the host range and fitness consequences of the drosophilid virome are poorly understood. Metagenomic studies have reported approximately 200 viruses associated with Drosophilidae, but few isolates are available to characterize the
Drosophila
immune response, and most characterization has relied on injection and systemic infection. Here, we use a more natural infection route to characterize the fitness effects of infection and to study a wider range of viruses. We exposed laboratory
Drosophila melanogaster
to 23 naturally occurring viruses from wild-collected drosophilids. We recorded transmission rates along with two components of female fitness: survival and the lifetime number of adult offspring produced. Nine different viruses transmitted during contact with laboratory
D. melanogaster
, although for the majority, rates of transmission were less than 20%. Five virus infections led to a significant decrease in lifespan (D. melanogaster Nora virus, D. immigrans Nora virus, Muthill virus, galbut virus and Prestney Burn virus), and three led to a reduction in the total number of offspring. Our findings demonstrate the utility of the
Drosophila
model for community-level studies of host–virus interactions, and suggest that viral infection could be a substantial fitness burden on wild flies.
Downregulation of KLF5 by EBER1 via the ERK signaling pathway in EBV-positive nasopharyngeal carcinoma cells: implications for latent EBV infection
Authors: Hu Jieke , Xin Fangjie , Liu Wen , Gong Zhiyuan , Zhang Yan , Liu Shuzhen
Published: May 2024

Nasopharyngeal carcinoma (NPC) carcinogenesis and malignant transformation are intimately associated with Epstein-Barr virus (EBV) infection. A zinc-fingered transcription factor known as Krüppel-like factor 5 (KLF5) has been shown to be aberrantly expressed in a number of cancer types. However, little is known about the regulatory pathways and roles of KLF5 in EBV-positive NPC. Our study found that KLF5 expression was significantly lower in EBV-positive NPC than in EBV-negative NPC. Further investigation revealed that EBER1, which is encoded by EBV, down-regulates KLF5 via the extracellular signal-regulated kinase (ERK) signalling pathway. This down-regulation of KLF5 by EBER1 contributes to maintaining latent EBV infection in NPC. Furthermore, we uncovered the biological roles of KLF5 in NPC cells. Specifically, KLF5 may influence the cell cycle, prevent apoptosis, and encourage cell migration and proliferation – all of which have a generally pro-cancer impact. In conclusion, these findings offer novel strategies for EBV-positive NPC patients’ antitumour treatment.
How to Use Gravity to Accelerate Bone Adaptation: A Computational/Experimental Investigation of Exercises for Bone
Authors: Wilzman Andrew R. , Wong Devin Tomoko , Troy Karen L.
Published: May 2024

Impact exercises are known to increase bone mineral density (BMD) and in turn, bone strength and resistance to fracture. The biochemical pathways driving changes in BMD take months to complete, complicating our ability to understand how specific exercises influence the remodeling stimulus received by the bone. The purpose of this study was to compare several measures that have been theoretically linked to bone remodeling stimulus, including accelerations measured by Inertial Measurement Units (IMUs) at the middle of the tibia, ground reaction forces measured by force plate, joint contact forces estimated by musculoskeletal modeling, and tibia strains estimated by finite element modeling informed by high-resolution CT imaging. Twenty healthy adults (10 male: 22.1 +/- 2.2 years; 10 female: 21.3 +/- 1.3 years) participated in a biomechanical investigation of how drop height and landing style (bilateral vs. unilateral) affect the various bone remodeling stimuli. The results showed that while drop height consistently had significant direct relationships with stimulus magnitude, there was little benefit to drop heights greater than 0.4 m. In contrast, switching from a bilateral to a unilateral landing had a large positive effect. The stimuli calculated based on IMU data showed opposite trends compared to force plate and musculoskeletal modeling-based calculations, highlighting the need for caution in how IMUs are placed, and the resulting data interpreted, in the context of bone loading. A post-hoc analysis showed that a linear regression with predictor variables of kinematics, jump height, landing type (unilateral vs. bilateral) and the Ground Reaction Force FFT Integral could explain 79% of the variance in the bone remodeling stimulus that was predicted using much more sophisticated (and labor intensive) modeling. We conclude that higher level biomechanical modeling may not be necessary to understand the magnitude of a bone remodeling stimulus of an exercise.
Reconstructing parent genomes using siblings and other relatives
Authors: Qiao Ying , Jewett Ethan M. , McManus Kimberly F. , Freyman William A. , Curran Joanne E. , Williams-Blangero Sarah , Blangero John ,   The 23andMe Research Team, Williams Amy L.
Published: May 2024

Reconstructing the DNA of ancestors from their descendants has the potential to empower phenotypic analyses (including association and genetic nurture studies), improve pedigree reconstruction, and shed light on the ancestral population and phenotypes of ancestors. We developed HAPI-RECAP, a method that reconstructs the DNA of parents from full siblings and their relatives. This tool leverages HAPI2’s output, a new phasing approach that applies to siblings (and optionally one or both parents) and reliably infers parent haplotypes but does not link the ungenotyped parents’ DNA across chromosomes or between segments flanking ambiguities. By combining IBD between the reconstructed parents and the relatives, HAPI-RECAP resolves the source parent of these segments. Moreover, the method exploits crossovers the children inherited and sex-specific genetic maps to infer the reconstructed parents’ sexes. We validated these methods on research participants from both 23andMe, Inc. and the San Antonio Mexican American Family Studies. Given data for one parent, HAPI2 reconstructs large fractions of the missing parent’s DNA, between 77.6% and 99.97% among all families, and 90.3% on average in three- and four-child families. When reconstructing both parents, HAPI-RECAP inferred between 33.2% and 96.6% of the parents’ genotypes, averaging 70.6% in four-child families. Reconstructed genotypes have average error rates < 10−3, or comparable to those from direct genotyping. HAPI-RECAP inferred the parent sexes 100% correctly given IBD-linked segments and can also reconstruct parents without any IBD. As datasets grow in size, more families will be implicitly collected; HAPI-RECAP holds promise to enable high quality parent genotype reconstruction.
Convolutional architectures are cortex-aligned de novo
Authors: Kazemian Atlas , Elmoznino Eric , Bonner Michael F.
Published: May 2024

What underlies the emergence of cortex-aligned representations in deep neural network models of vision? The success of widely varied architectures has motivated the prevailing hypothesis that large-scale pre-training is the primary factor underlying the similarities between brains and neural networks. Here, we challenge this view by revealing the role of architectural inductive biases in models with minimal training. We examined networks with varied architectures but no pre-training and quantified their ability to predict image representations in the visual cortices of both monkeys and humans. We found that cortex-aligned representations emerge in convolutional architectures that combine two key manipulations of dimensionality: compression in the spatial domain and expansion in the feature domain. We further show that the inductive biases of convolutional architectures are critical for obtaining performance gains from feature expansion—dimensionality manipulations were relatively ineffective in other architectures and in convolutional models with targeted lesions. Our findings suggest that the architectural constraints of convolutional networks are sufficiently close to the constraints of biological vision to allow many aspects of cortical visual representation to emerge even before synaptic connections have been tuned through experience.
Efficacy of BianShi Moxibustion for bowel preparation: study protocol for a randomized controlled trial
Authors: Zhang Qiang , Zhang Xiao-Ping , Wang Li-Jie
Published: May 2024

Background

Adequate bowel preparation is one of the most important prerequisite during the colonoscopy. It is conductive to detect the polypus, adenoma and early colorectal carcinoma and decrease the rate of overuse of medical resource. BianShi Moxibustion(BSM) is one of the most important Traditional Chinese Medicine(TCM) treatment options, which is called TCM proper technology. BSM is applied to prevent and cure digestive system disorder widely, including functional constipation(FC), irritable bowel syndrome(IBS), functional dyspepsia(FD) etc. we speculate that BSM can improve the bowel preparation quality through ameliorating the function of digestive tract, especially in high risk of inadequate bowel preparation patients, including elderly individual, diabetes mellitus, neurodegenerative changes etc. Hence, the objective of this research is to evaluate the efficacy of BSM on the quality of bowel preparation before colonoscopy.

Method

This is a randomized triple-blinded, single-center, prospective study. We will recruit 72 inpatients who are scheduled to undergo colonoscopy for screening and diagnostic or therapeutical purposes for the first time will be randomized to assign into treatment group or control group at a ratio of 1:1. The intervention plan in the treatment group consists of 3L polyethylene glycol(PEG) solution plus BSM(Treatment period is 3 days, Qd). In the control group, the plan is 3L PEG plus sham BSM. Boston Bowel Preparation Scale(BBPS) will be used to evaluate the efficacy of the bowel preparation and regarded as the primary outcome measure. The secondary outcomes including caecal intubation rate, the willingness to repeat colonoscopy, the tolerance of bowel preparation regimens, the rate of adverse events.

Discussion

The aim of this clinical trial is to confirm the influence of BSM on the quality of bowel preparation. The hypothesis of this study is that the BSM has a positive role on the quality of bowel preparation. The routine bowel preparation regime combines with TCM proper technology will enhance bowel preparation quality and ameliorate the subjective feeling of participants. In addition, it will provide the reliable evidence of bowel preparation prior to colonoscopy from the point of view of integrative medicine.

Trial registration

This protocol and trial was registered in the Chinese Clinical Trial Registry(ChiCTR2300077168).
Calcitonin gene-related peptide and intermedin induce phosphorylation of p44/42 MAPK in primary human lymphatic endothelial cells in vitro
Authors: Hasan Shirin R , Manolis Dimitrios , Stephenson Ewan , Ryskiewicz-Sokalska Oktawia A , Maraveyas Anthony , Nikitenko Leonid L
Published: May 2024

Background: Calcitonin gene-related peptide (CGRP) is a 37-amino acid peptide that belongs to the calcitonin family of peptides together with adrenomedullin (AM), adrenomedullin 2 (AM2), also known as intermedin (IMD), amylin (AMY) and calcitonin. Recent reports demonstrated the efficacy of drugs targeting the CGRP signalling axis for the treatment of migraine, but also revealed significant side effects such as inflammation and microvascular complications, including aberrant neovascularisation in the skin. These findings highlight the importance of studying cellular targets of CGRP in human tissues. Recent studies using animal models implicate the role of CGRP in lymphangiogenesis and lymphatic vessel function. However, whether CGRP has direct effects on lymphatic endothelial cells (LEC) remains unknown. In this study, we analysed phosphorylation of p44/42 mitogen-activated protein kinases (MAPK) in proliferating primary human dermal LEC (HDLEC) stimulated with CGRP and compared with responses to AM2/IMD and AM. Materials and Methods: Primary breast HDLEC from two female donors (39 and 46 years old) were cultured in vitro. Cell viability and proliferation of sub-confluent HDLEC were confirmed by MTS assay and Ki67 immunostaining. Phosphorylation of p44/42 MAPK in HDLEC treated with CGRP, AM2/IMD or AM at different time points (1-30 min) and concentrations (10-12-10-6M) was assessed by immunoblotting. All experiments have been performed at least 4 times. Statistical analysis was done using Shapiro-Wilk and Kruskal Wallis tests followed by uncorrected Dunn's test, with p<0.05 interpreted as significant. Results: CGRP induced p44/42 MAPK phosphorylation in a time- and dose-dependent manner in proliferating primary HDLEC from both donors. p44/42 MAPK phosphorylation was induced by all three peptides (10-6M) at 5-15 min (p<0.05), but only CGRP-induced effect was sustained at 30 min. CGRP consistently induced p44/42 MAPK phosphorylation at 10-7-10-6M (p<0.05) in HDLEC from both donors, whilst responses to AM2/IMD and AM varied. Conclusions: Our study shows that CGRP and AM2/IMD have direct effects on proliferating primary HDLEC. These new findings reveal CGRP and AM2/IMD as novel regulators of lymphatic endothelial cell biology and warrant further investigation of their roles in pathologies associated with lymphatic function in the skin and other organs.
COCOA: A Framework for Fine-scale Mapping Cell-type-specific Chromatin Compartmentalization Using Epigenomic Information
Authors: Li Kai , Zhang Ping , Xu Jinsheng , Wen Zi , Zhang Junying , Zi Zhike , Li Li
Published: May 2024

Chromatin compartmentalization and epigenomic modification are crucial factors in cell differentiation and diseases development. However, mapping precise chromatin compartmental patterns across multiple cell types requires Hi-C or Micro-C data at high sequencing depth. Exploring the systematic relationship between epigenomic modifications and compartmental patterns remains a challenge. To address these issues, we present COCOA, a deep neural network framework that uses convolution and attention mechanisms to infer reliable fine-scale chromatin compartment patterns from six representative histone modification signals. COCOA achieves this by extracting 1-D track features through bi-directional feature reconstruction after resolution-specific binning epigenomic signals. These track features are then cross-fused with contact features using an attention mechanism. Subsequently, the contact features are transformed into chromatin compartment patterns through residual feature reduction. COCOA demonstrates accurate inference of chromatin compartmentalization at a fine-scale resolution and exhibits stable performance on test sets. In addition, we explored the impact of histone modifications on the chromatin compartmentalization throughin silicoepigenomic perturbation experiments. When using 1kb resolution high-depth experimental data, obscure compartments are observed, whereas COCOA can generate clear and detailed compartmental patterns. Finally, we demonstrated that COCOA enables cell-type-specific prediction of unrevealed chromatin compartment patterns in various biological processes. Thus, COCOA is an effective tool for gaining chromatin compartmentalization insights from epigenomics in a wide range of biological scenarios.
IFDlong: an isoform and fusion detector for accurate annotation and quantification of long-read RNA-seq data
Authors: Wang Wenjia , Li Yuzhen , Ko Sungjin , Feng Ning , Zhang Manling , Liu Jia-Jun , Zheng Songyang , Ren Baoguo , Yu Yan P. , Luo Jian-Hua , Tseng George C. , Liu Silvia
Published: May 2024

Advancements in long-read transcriptome sequencing (long-RNA-seq) technology have revolutionized the study of isoform diversity. These full-length transcripts enhance the detection of various transcriptome structural variations, including novel isoforms, alternative splicing events, and fusion transcripts. By shifting the open reading frame or altering gene expressions, studies have proved that these transcript alterations can serve as crucial biomarkers for disease diagnosis and therapeutic targets. In this project, we proposed IFDlong, a bioinformatics and biostatistics tool to detect isoform and fusion transcripts using bulk or single-cell long-RNA-seq data. Specifically, the software performed gene and isoform annotation for each long-read, defined novel isoforms, quantified isoform expression by a novel expectation-maximization algorithm, and profiled the fusion transcripts. For evaluation, IFDlong pipeline achieved overall the best performance when compared with several existing tools in large-scale simulation studies. In both isoform and fusion transcript quantification, IFDlong is able to reach more than 0.8 Spearman’s correlation with the truth, and more than 0.9 cosine similarity when distinguishing multiple alternative splicing events. In novel isoform simulation, IFDlong can successfully balance the sensitivity (higher than 90%) and specificity (higher than 90%). Furthermore, IFDlong has proved its accuracy and robustness in diverse in-house and public datasets on healthy tissues, cell lines and multiple types of diseases. Besides bulk long-RNA-seq, IFDlong pipeline has proved its compatibility to single-cell long-RNA-seq data. This new software may hold promise for significant impact on long-read transcriptome analysis. The IFDlong software is available athttps://github.com/wenjiaking/IFDlong.
Metabolic adaptations of micrometastases alter EV production to generate invasive microenvironments
Authors: Gounis Michalis , Campos America V. , Shokry Engy , Mitchell Louise , Dornier Emmanuel , Rooney Nicholas , Dhayade Sandeep , Pardo Luis , Moore Madeleine , Novo David , Mowat Jenna , Jamieson Craig , Kay Emily , Zanivan Sara , Nixon Colin , Macpherson Iain , Tardito Saverio , Sumpton David , Blyth Karen , Norman Jim C. , Clarke Cassie J.
Published: May 2024

Altered cellular metabolism has been associated with acquisition of invasive phenotypes during metastasis. To study this, we combined a genetically engineered mouse model of mammary carcinoma with syngeneic transplantation and primary tumour resection to generate isogenic cells from primary tumours and their corresponding lung micrometastases. Metabolic analyses indicated that micrometastatic cells increase proline production at the expense of glutathione synthesis leading to a reduction in total glutathione levels. Micrometastatic cells also have altered sphingomyelin metabolism leading to increased intracellular levels of specific ceramides. The combination of these two metabolic adaptations alters small extracellular vesicle (sEV) production to drive generation of an invasive microenvironment. Indeed, micrometastatic cells shut-down Rab27-dependent production of sEVs and, instead, switch-on neutral sphingomyelinase-2 (nSM2)-dependent sEV release. sEVs released in a nSM2-dependent manner from micrometastatic cells, in turn, influence the ability of fibroblasts to deposit extracellular matrix which promotes cancer cell invasiveness. These data provide evidence that metabolic rewiring drives invasive processes in metastasis by influencing sEV release.

Breast cancer cells isolated from lung micrometastases have altered metabolism which influences extracellular vesicle production to generate invasive microenvironments.
Ketamine reverses stress-induced hypersensitivity to sunk costs
Authors: Cuttoli Romain Durand-de , Sweis Brian M.
Published: May 2024

How mood interacts with information processing in the brain is thought to mediate the maladaptive behaviors observed in depressed individuals. However, the neural mechanisms underlying impairments in emotion-cognition interactions are poorly understood. This includes influencing the balance between how past-sensitive vs. future-looking one is during decision-making. Recent insights from the field of neuroeconomics offer novel approaches to study changes in such valuation processes in a manner that is biologically tractable and readily translatable across species. We recently discovered that rodents are sensitive to “sunk costs” – a feature of higher cognition previously thought to be unique to humans. The sunk costs bias describes the phenomenon in which an individual overvalues and escalates commitment to continuing an ongoing endeavor, even if suboptimal, as a function of irrecoverable past (sunk) losses – information that, according to classic economic theory, should be ignored. In the present study, mice were exposed to chronic social defeat stress paradigm, a well-established animal model used for the study of depression. Mice were then tested on our longitudinal neuroeconomic foraging task, Restaurant Row. We found mice exposed to this severe stressor displayed an increased sensitivity to sunk costs, without altering overall willingness to wait. Mice were then randomly assigned to receive a single intraperitoneal injection of either saline or ketamine (20 mg/kg). We discovered that stress-induced hypersensitivity to sunk costs was renormalized following a single dose of ketamine. Interestingly, in non-defeated mice, ketamine treatment completely abolished sunk cost sensitivity, causing mice to no longer value irrecoverable losses during re-evaluation decisions who instead based choices solely on the future investment required to obtain a goal. These findings suggest that the antidepressant effects of ketamine may be mediated in part through changes in the processing of past-sensitive information during on-going decision-making, reducing its weight as a potential source of cognitive dissonance that could modulate behavior and instead promoting more future-thinking behavior.
MSLASpheroidStamp: 3d cell spheroids for everyone
Authors: Minin A. , Semerikova T. , Belousova A.V. , Karavashkova O. , Pozdina V. , Tomilina M. , Zubarev I.
Published: May 2024

3D cell cultures, such as cell spheroids, are actively used in biology for modeling biological processes, studying intercellular interactions and pharmacological compounds screening and are becoming indispensable objects in cell culture laboratories. There are many methods for producing spheroids, varying in cost and convenience. One of the most handy and affordable is the use of agarose microwells. We have developed approaches to fabricate agarose microwells in standard culture plastic with the assistance of a hobby-grade MSLA 3D printer. The use of 3D printing allows you to customize microwells in a wide range of shapes and sizes and scale the production process from a few spheroids to tens of thousands. We have shown that it is possible to create gel microwells in a dish with a glass bottom, which allows us to easily realize time-lapse confocal microscopy of spheroids, and we have also performed in situ optical clearing in the same dishes to study the spheroid structure. We demonstrated the ability to study the cytotoxicity of various substances and nanoparticles in commonly used 96-well plates.

And finally, in this article we describe the difficulties and limitations of our approach and suggest ways for solving them, allowing the reader not only to reproduce it, but also to adapt it to the specific needs of a certain laboratory, using provided 3D models and instructions.
Spatial Coherence in DNA Barcode Networks
Authors: Bonet David Fernandez , Blumenthal Johanna I. , Lang Shuai , Dahlberg Simon K , Hoffecker Ian T.
Published: May 2024

Sequencing-based microscopy is a novel, optics-free method for imaging molecules in biological samples using molecular DNA barcodes, spatial networks, and sequencing technologies. Despite its promise, the principles determining how these networks preserve spatial information are not fully understood. Current validation methods, which rely on comparing reconstructed positions to expected results, would benefit from a deeper understanding of these principles. Here, we introduce the concept of spatial coherence— a set of fundamental properties of spatial networks that quantifies the alignment between topological relationships and Euclidean geometry. Our findings show that spatial coherence is an effective method for evaluating a network’s capacity to maintain spatial fidelity and identify distortions, independent of prior information. This framework provides a cost-effective validation tool for sequencing-based microscopy by taking advantage of the fundamental properties of spatial networks in nanoscale systems.
Total testosterone is not associated with muscle mass, function or exercise adaptations in pre-menopausal females
Authors: Alexander Sarah E , Gatto Briana , Knowles Olivia E , Williams Ross M , Fiebig Kinga N , Jansons Paul , Della Gatta Paul A , Garnham Andrew , Eynon Nir , Wadley Glenn D , Aisbett Brad , Hiam Danielle , Lamon Severine
Published: May 2024

Testosterone, the major androgen hormone, influences the reproductive and non-reproductive systems in males and females via binding to the androgen receptor (AR). Both circulating endogenous testosterone and muscle AR protein content are positively associated with muscle mass and strength in males, but there is no such evidence in females. Here, we tested whether circulating testosterone levels were associated with muscle mass, function, or the muscle anabolic response to resistance training in pre-menopausal females. Twenty-seven pre-menopausal, untrained females (aged 23.5 +/- 4.8) underwent a 12-week resistance training program. Muscle strength, size, power and plasma and urine androgen hormone levels were measured. Skeletal muscle biopsies were collected before and after the training program to quantify the effect of resistance training on AR protein and mRNA content, and nuclear localisation. Primary muscle cell lines were cultured from a subset (n=6) of the participants biopsies and treated with testosterone to investigate its effect on myotube diameter, markers of muscle protein synthesis and AR cellular localisation. Total testosterone was not associated with muscle mass or strength at baseline or with the changes in muscle mass and strength that occurred in response to resistance training. In vitro, supra-physiological doses of testosterone increased myocyte diameter, but this did not occur via the Akt/mTOR pathway as previously suggested. Instead, we show a marked increase in AR nuclear localisation with testosterone administration. In conclusion, we found that, bioavailable testosterone and the proportion of nuclear-localised AR, but not total testosterone, with skeletal muscle mass and strength in pre-menopausal females.
Sleep Apnea and Hypertension Control among Hispanic/Latino Adults in the United States: Results from the Hispanic Community Health Study / Study of Latinos (HCHS/SOL)
Authors: Castro-Diehl Cecilia , Pirzada Amber , de las Fuentes Lisa , Sotres-Alvarez Daniela , Isasi Carmen R. , Durazo-Arvizu Ramon A , Makarem Nour , Perreira Krista M. , Ramos Alberto R. , Wassertheil-Smoller Sylvia , Stamatakis Katie , Stickel Ariana M. , Redline Susan , Daviglus Martha L.
Published: May 2024

Objectives

Hispanic/Latino adults have a high prevalence of uncontrolled hypertension predisposing them to CVD. We hypothesize that sleep apnea severity is associated with uncontrolled blood pressure (BP) and resistant hypertension in Hispanic/Latino adults.

Methods

This was a cross-sectional study of 2,849 Hispanic Community Health Study/Study of Latinos participants with hypertension (i.e., systolic BP ≥130 mm Hg, or diastolic BP ≥80 mm Hg or self-reported antihypertensive medication use) who were taking at least one class of antihypertensive medication. Participants were categorized as havingcontrolled (BP < 130/80 mmHgamong those on hypertension treatment), uncontrolled (BP≥ 130/80 mmHg using one or two classes of antihypertensive medications), orresistant hypertension (BP≥ 130/80 mmHg while on ≥ 3 classes of antihypertensive medications or the use of ≥ 4 classes of antihypertensive medications regardless of BP control). Sleep apnea was classified based on the respiratory event index (REI; events/h) asmild(REI ≥ 5 and < 15), moderate-to-severe (REI ≥ 15), orno sleepapnea (REI < 5).

Results

In multinomial logistic regression, moderate-to-severe sleep apnea (vs. no sleep apnea) was associated with higher odds of resistant hypertension (Odds Ratio [OR], 2.15; 95% CI, 1.36-3.39 at 4% desaturation and OR 1.68; 95% CI, 1.05-2.67 at 3% desaturation). Neither mild nor moderate-to-severe sleep apnea was associated with uncontrolled hypertension.

Conclusion

Among diverse Hispanic/Latino persons, moderate-to-severe but not mild sleep apnea was associated with resistant hypertension. Identification and management of sleep apnea in this population may improve BP control and subsequently prevent adverse cardiovascular outcomes.
Visual context affects the perceived timing of tactile sensations elicited through intra-cortical microstimulation
Authors: Rosenthal Isabelle A. , Bashford Luke , Bjånes David , Pejsa Kelsie , Lee Brian , Liu Charles , Andersen Richard A.
Published: May 2024

Intra-cortical microstimulation (ICMS) is a technique to provide tactile sensations for a somatosensory brain-machine interface (BMI). A viable BMI must function within the rich, multisensory environment of the real world, but how ICMS is integrated with other sensory modalities is poorly understood. To investigate how ICMS percepts are integrated with visual information, ICMS and visual stimuli were delivered at varying times relative to one another. Both visual context and ICMS current amplitude were found to bias the qualitative experience of ICMS. In two tetraplegic participants, ICMS and visual stimuli were more likely to be experienced as occurring simultaneously when visual stimuli were more realistic, demonstrating an effect of visual context on the temporal binding window. The peak of the temporal binding window varied but was consistently offset from zero, suggesting that multisensory integration with ICMS can suffer from temporal misalignment. Recordings from primary somatosensory cortex (S1) during catch trials where visual stimuli were delivered without ICMS demonstrated that S1 represents visual information related to ICMS across visual contexts.
RNAseq analysis reveals transcriptome changes associated with the progression of non-alcoholic liver disease in livers fromEfcab4bknockout mice
Authors: Cheng Chew W. , Pedicini Lucia , Morales Alcala Cintli , Deligianni Fenia , Forde Niamh , Smith Jessica , McKeown Lynn
Published: May 2024

EFCAB4Bis an evolutionarily conserved protein that encodes for the Rab GTPase Rab46, and the CRAC channel modulator, CRACR2A. Previous genome wide association studies have demonstrated the association ofEFCAB4Bvariants in the progression of non-alcoholic liver disease (NAFLD). In this study we show that mice with global depletion ofEfcab4b-/-have significantly larger livers than their wild-type (WT) counterparts. We performed RNA-sequencing (RNA-seq) analysis of liver tissues to investigate differential global gene expression amongEfcab4b-/-and WT mice. Of the 69 differentially expressed genes (DEGs), analyses of biological processes found significant enrichment in liver and bile development, with 6 genes (Pck1, Aacs, Onecut1, E2f8, Xbp1,andHes1) involved in both processes. Specific consideration of possible roles of DEGs or their products in NAFLD progression to (NASH) and hepatocarcinoma (HCC), demonstrated DEGs in the livers ofEfcab4b-/-mice had roles in molecular pathways including lipid metabolism, inflammation, ER stress and fibrosis. The results in this study provide additional insights into molecular mechanisms responsible for increasing susceptibility of liver injuries associated withEFCAB4B.
Fluorescent substances in cotton fibers treated with a labeling probe
Authors: Tamogami Shigeru , Watanabe Akio , Agrawal Ganesh K. , Rakwal Randeep
Published: May 2024

Usability of the labeling probe, previously developed to uncover the targets of cellulose synthase (CESA) inhibition herbicides, was examined with fibers and cultured ovules of the cotton plant (Gossypium hirsutum). Using this probe, various fluorescent substances were found with attributes, such as bands, particles and other unique structures. Elucidation of these fluorescent substances might provide hints to understand the mechanism of cellulose biosynthesis in the cotton fibers and ovules, as well as to distinguish features of the cotton fibers.
Phased ERK-responsiveness and developmental robustness regulate teleost skin morphogenesis
Authors: Ramkumar Nitya , Richardson Christian , O’Brien Makinnon , Butt Faraz Ahmed , Park Jieun , Chao Anna T , Bagnat Michel , Poss Kenneth , Di Talia Stefano
Published: May 2024

Elongation of the vertebrate embryonic axis necessitates rapid expansion of the epidermis to accommodate the growth of underlying tissues. Here, we generated a toolkit to visualize and quantify signaling in entire cell populations of periderm, the outermost layer of the epidermis, in live developing zebrafish. We find that oriented cell divisions facilitate growth of the early periderm during axial elongation rather than cell addition from the basal layer. Activity levels of ERK, a downstream effector of MAPK pathway, gauged by a live biosensor, predicts cell cycle entry, and optogenetic ERK activation controls proliferation dynamics. As development proceeds, rates of peridermal cell proliferation decrease, ERK activity becomes more pulsatile and functionally transitions to promote hypertrophic cell growth. Targeted genetic blockade of cell division generates animals with oversized periderm cells, yet, unexpectedly, development to adulthood is not impaired. Our findings reveal stage-dependent differential responsiveness to ERK signaling and marked developmental robustness in growing teleost skin.
Kynurenine monooxygenase blockade reduces endometriosis-like lesions, improves visceral hyperalgesia, and rescues mice from a negative behavioural phenotype in experimental endometriosis
Authors: Higgins Ben , Simitsidellis Ioannis , Zheng Xiaozhong , Collins Frances , Homer Natalie Z.M. , Denham Scott G. , Simpson Joanna P. , Millar Mike , Boswell Lyndsey , Lee Hee Y. , Kim Yeon G. , Park Kyung H. , Park Larry C. , Sweeney Patrick J. , Feraille Gerard , Taddei Alessandro , Chagras David , Alvarez Thierry , Webster Scott P. , Horne Andrew , Saunders Philippa T.K. , Mole Damian J.
Published: May 2024

Endometriosis is a common and debilitating neuro-inflammatory disorder that is associated with chronic pain. Definitive diagnosis is based on the presence of endometrial-like tissue (lesions) in sites outside the uterus. Kynurenine monooxygenase (KMO) is a mitochondrial enzyme of tryptophan metabolism that regulates inflammation and immunity. Here, we show that KMO is expressed in epithelial cells in human endometriosis tissue lesions and in corresponding lesions in a mouse model of endometriosis. In mice, oral treatment with the potent KMO inhibitor KNS898 induced a biochemical state of KMO blockade with accumulation of kynurenine, diversion to kynurenic acid and ablation of 3-hydroxykynurenine production. In the mouse model of endometriosis, KMO inhibition improved histological outcomes and endometriosis pain-like behaviours, even when KNS898 treatment commenced one week after initiation of lesions. Taken together, these results suggest that KMO blockade is a promising new non-hormonal therapeutic modality for endometriosis.
Diversity and evolution of the human anellome
Authors: Modha Sejal , Hughes Joseph , Orton Richard J. , Lytras Spyros
Published: May 2024

Anelloviruses are a group of small, circular, single-stranded DNA viruses that are found ubiquitously across mammalian hosts. Here, we explored a large number of publicly available human microbiome datasets and retrieved a total of 829 anellovirus genomes, substantially expanding the known diversity of these viruses. The majority of new genomes fall within the three major human anellovirus genera:Alphatorquevirus,BetatorquevirusandGammatorquevirus, while we also present one new genome of the under-sampledHetorquevirusgenus. The phylogeny reconstructed from the conserved ORF1 gene reveals three additional, previously undescribed, human anellovirus clades. We performed recombination analysis and show evidence of extensive recombination across all human anelloviruses. Interestingly, more than 95% of the detected events are between members of the same clade and only 15 inter-clade recombination events were detected. The breakpoints of recombination cluster in hotspots at the ends and outside of the ORF1 gene, while a recombination coldspot was detected within the gene. Our analysis suggests that anellovirus evolution is governed by homologous recombination, however events between distant viruses or ones producing chimaeric ORF1s likely lead to non-viable recombinants. The large number of genomes further allowed us to examine how essential genomic features vary across anelloviruses. These include functional domains in the ORF1 protein and the nucleotide motif of the replication loop region, required for the viruses’ rolling-circle replication. A subset of the genomes assembled in both this and previous studies are completely lacking these essential elements, opening up the possibility that anellovirus intracellular populations contain defective virus genomes (DVGs). Overall, our study highlights key features of anellovirus genomics and evolution, a largely understudied group of viruses whose potential in virus-based therapeutics is recently being explored.
Partitioning biota along the Elbe River estuary: where are the community transitions?
Authors: Branoff Benjamin B. , Grüterich Luise , Wilson Monica , Tobias-Hunefeldt Sven Patrik , Saadaoui Youssef , Mittmann-Goetsch Julian , Neiske Friederike , Lexmond Fay , Becker Joscha N. , Grossart Hans-Peter , Porada Philipp , Streit Wolfgang R. , Eschenbach Annette , Kutzbach Lars , Jensen Kai
Published: May 2024

Estuarine zonation and community assemblages are frequently correlated with salinity, although the extent or nature of this correlation varies considerably among the published studies. While a smooth transition in biological communities is often conceptualized in association with estuarine fresh, brackish, and marine conditions, many studies have shown more distinct communities and the altogether absence of a brackish community. We explore these viewpoints in light of plant observations and soil and aquatic microbial analyses from permanent plots established on the Elbe River Estuary of northern Germany. Generally, two distinct communities were observed, a polyhaline assemblage towards the mouth of the system, and another that was associated with both the fresh and brackish mesohaline regimes further upriver. This was most pronounced among plant and soil bacteria communities, while aquatic 16S assemblages reflected little distinction at all. The proportion of marine classified taxa declined from the mouth to upriver and suggests that while the transition from marine to brackish or fresh vegetation falls within the sampled area, the same transition for microbial taxa could not be observed and may be further upriver. Thus, although we were able to identify two distinct communities, the “limit” of marine taxa was only evident for vegetation. While tidal and weather-related hydrology, as well as soil properties were also influential in distinguishing the communities, much of the variance remains unexplained. Further sampling, classification, and partitioning is necessary to determine the origin and/or autochthonous habitat, if any, for the Elbe River estuarine taxa.

Geographic bounds

bottom left: 53.556216°N, 8.824398°E

top right: 53.917760 °N, 10.155669 °E