bluuebunny/crossref_metadata_2025 huggingface dataset:
A complete morphological characterization of all life stages of the phorid flyM. scalaris
Authors: Pallavi Jayakumar , Snehal Harshita , Salazar Daniela , Hanbar Mrunal , Chiramel Larina Bejoy , Jha Khushi Alok , Kolipakala Rakshita Sukruth , Lakshmi Venkatesh Sai Bhumica , Shetty Tanishka Dayanand , Madhusudan Navya , Mohan Amrutha , John Amulia , D’souza Naomi Deep , Sheet Priyanka , Nagarajan Deepesh
Published: May 2023

Megaselia scalaris, commonly known as the scuttle fly, is a cosmopolitan species in the family Phoridae. It is an easily cultured fly species that is an emerging model organism in the fields of genetics and developmental biology. Its affinity for carrion and its predictable life cycle makes it useful in the field of forensic science for estimating the post-mortem interval (PMI) of human remains. Cases of human myasis caused byM. scalarishave also been reported in the medical literature. Despite its ubiquitous prevalence and its relevance across multiple fields, its morphology has not been adequately characterized. Here, we report the complete morphological characterization of all lifestages ofM. scalaris, ranging from egg to adult. Scanning electron microscopy has enabled us to uncover morphological features and developmental processes that have previously not been reported in the literature. Our data lays the groundwork for future genetic studies: a morphological characterization of the wild type must be performed before mutants displaying different phenotypes can be identified. In this vein, we also report the observation of a acephalic, or ‘headless’, adult phenotype whose study could yield insights into the process of cephalogenesis.
GPX4-VIM equates a proliferating DTP state in TNBC subtypes with converged vulnerabilities to autophagy and glutathione inhibition
Authors: Chaudhary Nazia , Choudhary Bhagya Shree , Patra Sushmita , Malvankar Shivani , Shivashankar Anusha , Jog Eeshrita , Kailje Vaishali V. , Khanna Sonal , Manna Subhakankha , Sahoo Sarthak , R Soundharya , Jolly Mohit Kumar , Dalal Sorab N. , Verma Nandini
Published: May 2023

Frequent metastatic relapses in Triple-Negative Breast Cancer (TNBC) patients with residual disease is a clinical challenge, largely due to tumor heterogeneity and absence of strategies that target proliferating chemo-tolerant cells. Here, we longitudinally modeled cellular state transitions from dormant drug-tolerant persister (DTP) into proliferating drug-tolerant persister (PDTP) in cells representing all TNBC subtypes. Combining subcellular imaging with phenotypic and biochemical assays, we identified distinct and converged spectrums of alterations in TNBC-PDTPs. We show that PDTPs retain acquired resistance with increased invasion potential. Moreover, Basal-Like DTPs enter into a non-reversible mesenchymal state while luminal androgen receptor-positive gain partial-Epithelial-to-Mesenchymal Transition (EMT) with vimentin upregulation. PDTP state dwells on high autophagy with reduced glutathione and GPX4 levels, rendering it vulnerable to autophagy suppression and ferroptosis. Interestingly, we find that GPX4 negatively regulates EMT and autophagy in TNBC, and an inverse correlation of GPX4-VIM expression along with autophagy genes predicts survival in TNBC patients undergoing chemotherapy.
Multiple p38/JNK Mitogen-activated protein kinase (MAPK) signaling pathways mediate salt chemotaxis learning inC. elegans
Authors: Huang Taoruo , Suzuki Kota , Kunitomo Hirofumi , Tomioka Masahiro , Iino Yuichi
Published: May 2023

Animals are able to adapt their behaviors to their environment. In order to achieve this, the nervous system plays integrative roles, such as perception of external signals, sensory processing, and behavioral regulations via various signal transduction pathways. Here genetic analyses ofC. elegansfound that mutants of components of JNK and p38 Mitogen-activated protein kinase (MAPK) signaling pathways, also known as stress-activated protein kinase (SAPK) signaling pathways, exhibit various types of defects in the learning of salt chemotaxis.C. eleganshomologues of JNK MAPKKK and MAPKK, MLK-1 and MEK-1, respectively, are required to avoid salt concentrations experienced during starvation. In contrast, homologues of p38 MAPKKK and MAPKK, NSY-1 and SEK-1, respectively, are required for high-salt chemotaxis after conditioning. Genetic interaction analyses suggest that a JNK family MAPK, KGB-1, functions downstream of both signaling pathways to regulate salt chemotaxis learning. Furthermore, we found that the NSY-1/SEK-1 pathway functions in sensory neurons, ASH, ADF, and ASER, to regulate the learned high-salt chemotaxis. A neuropeptide, NLP-3, expressed in ASH, ADF, and ASER neurons, and a neuropeptide receptor, NPR-15, expressed in AIA interneurons that receive synaptic input from these sensory neurons, function in the same genetic pathway as NSY-1 / SEK-1 signaling. These findings suggest that this MAPK pathway may affect neuropeptide signaling between sensory neurons and interneurons, thus promoting high-salt chemotaxis after conditioning.
Multiscale imaging of corneal endothelium damage and effects of Rho Kinase inhibitor application in mouse models of acute ocular hypertension
Authors: Cai Zhen , Zhang Yang , Fang Raymond S. , Brenner Benjamin , Kweon Junghun , Sun Cheng , Goldberg Jeffery , Zhang Hao F.
Published: May 2023

We developed a multiscale optical imaging workflow, integrating and correlating visible-light optical coherence tomography, confocal laser scanning microscopy, and single-molecule localization microscopy to investigate the mouse cornea damages from thein-vivotissue level to the nanoscopic single-molecule level. We used electron microscopy to validate the imaged nanoscopic structures. We imaged wild-type mice and mice with acute ocular hypertension and examined the effects of Rho Kinase inhibitor application. We defined four types of intercellular tight junction structures as healthy, compact, partially-distorted, and fully-distorted types by labeling the Zonula occludens-1 protein in the corneal endothelial cell layer. We correlated the statistics of the four types of tight junction structures with cornea thickness and intraocular pressure. We found that the population of fully-distorted tight junctions correlated well with the level of cornea edema, and applying Rho Kinase inhibitor reduced the population of fully-distorted tight junctions under acute ocular hypertension.
Foveated metamers of the early visual system
Authors: Broderick William F. , Rufo Gizem , Winawer Jonathan , Simoncelli Eero P.
Published: May 2023

Human ability to discriminate and identify visual attributes varies across the visual field, and is generally worse in the periphery than in the fovea. This decline in performance is revealed in many kinds of tasks, from detection to recognition. A parsimonious hypothesis is that the representation of any visual feature is blurred (spatially averaged) by an amount that differs for each feature, but that in all cases increases with eccentricity. Here, we examine models for two such features: local luminance and spectral energy. Each model averages the corresponding feature in pooling windows whose diameters scale linearly with eccentricity. We performed psychophysical experiments with synthetic stimuli to determine the window scaling for which human and model discrimination abilities match, called the critical scaling. We used much larger stimuli than those of previous studies, subtending 53.6 by 42.2 degrees of visual angle. We found the critical scaling for the luminance model was approximately one-fourth that of the energy model, and consistent with earlier studies, that a smaller critical scaling value was required when discriminating a synthesized image from a natural image than when discriminating two synthesized images. We offer a coherent explanation for these results in terms of alignments and misalignments of the models with human perceptual representations.
Adaptive therapy in cancer: the role of restrictions in the accumulation of mutations
Authors: Fontaneda David , Diaz-Uriarte Ramon
Published: May 2023

BACKGROUND

Cancer is currently one of the leading causes of premature death in the world, and is predicted to continue rising even despite the continuous discovery of novel treatments. New approaches, like adaptive therapy, try to minimize the problem of drug resistance, but there are still many open questions and unstudied phenomena that need to be tackled in order to make this approaches viable in real patients; among these, the possible effects that restrictions in the order of accumulation of mutations could have.

RESULTS

We have developed a spatially explicit agent-based model capable of simulating tumor growth and adaptive therapy in a highly flexible way. We show that when we consider restrictions in the order of accumulation of mutations and their effect in tumor architecture, the predicted genotypes of the cells that are inhibiting the growth of resistant cells can be very different to the ones predicted by perfectly mixed models.

CONCLUSION

We identify a divergence between the expected and real genotypes of the cells inhibiting the growth of the resistant population that has not been previously documented. This effect, if not taken into account, could negatively affect our predictions of adaptive therapy success and could hinder our advances in the development of new approaches to improve adaptive therapy. This discovery suggests the need for more studies that take into account the spatial component of cancer, specially when dealing with tumors with high heterogeneity. Furthermore, our model is able to simulate scenarios of tumor development and adaptive therapy, making it useful both for research and for education.
Single cell transcriptomics reveals cell type specific features of developmentally regulated responses to lipopolysaccharide between birth and 5 years
Authors: Read James F. , Serralha Michael , Armitage Jesse , Iqbal Muhammad Munir , Cruickshank Mark N. , Saxena Alka , Strickland Deborah H. , Waithman Jason , Holt Patrick G. , Bosco Anthony
Published: May 2023

Human perinatal life is characterized by a period of extraordinary change during which newborns encounter abundant environmental stimuli and exposure to potential pathogens. To meet such challenges, the neonatal immune system is equipped with unique functional characteristics that adapt to changing conditions as development progresses across the early years of life, but the molecular characteristics of such adaptations remain poorly understood. The application of single cell genomics to birth cohorts provides an opportunity to investigate changes in gene expression programs elicited downstream of innate immune activation across early life at unprecedented resolution. In this study, we performed single cell RNA-sequencing of mononuclear cells collected from matched birth cord blood and 5-year peripheral blood samples following stimulation (18hrs) with two well-characterized innate stimuli; lipopolysaccharide (LPS) and Polyinosinic:polycytidylic acid (Poly(I:C)). We found that the transcriptional response to LPS was constrained at birth and predominantly partitioned into classical proinflammatory gene upregulation primarily by monocytes and IFN-signaling gene upregulation by lymphocytes. Moreover, these responses featured substantial cell-to-cell communication which appeared markedly strengthened between birth and 5 years. In contrast, stimulation with Poly(I:C) induced a robust IFN-signalling response across all cell types identified at birth and 5 years. Analysis of gene regulatory networks revealed IRF1 and STAT1 were key drivers of the LPS-induced IFN-signaling response in lymphocytes with a potential developmental role for IRF7 regulation. Additionally, we observed distinct activation trajectory endpoints for monocytes derived from LPS-treated cord and 5-year blood, which was not apparent among Poly(I:C)-induced monocytes. Taken together, our findings provide new insight into the gene regulatory landscape of immune cell function between birth and 5 years and point to regulatory mechanisms relevant to future investigation of infection susceptibility in early life.
Physically informed Monte Carlo simulation of dual-wedge prism-based spectroscopic single-molecule localization microscopy
Authors: Yeo Wei-Hong , Sun Cheng , Zhang Hao F.
Published: May 2023

Significance

The dual-wedge prism (DWP)-based spectroscopic single-molecule localization microscopy (sSMLM) system offers improved localization precision and adjustable spectral or localization performance, but its nonlinear spectral dispersion presents a challenge. A systematic method can help understand the challenges and thereafter optimize the DWP system’s performance by customizing system parameters to maximize spectral or localization performance for various molecular labels.

Aim

We developed an MC-based model which predicts the imaging output of the DWP-based sSMLM system given different system parameters.

Approach

We assessed our MC model’s localization and spectral precisions by comparing our simulation against theoretical equations and fluorescent microspheres. Furthermore, we simulated the DWP-based system using beamsplitters of Reflectance (R):Transmittance (T) of R50:T50 and R30:T70 and their tradeoffs.

Results

Our MC simulation showed average deviations of 2.5 nm and 2.1 nm for localization and spectral precisions against theoretical equations; and 2.3 nm and 1.0 nm against fluorescent microspheres. An R30:T70 beamsplitter improved spectral precision by 8% but worsened localization precision by 35% on average compared to an R50:T50 beamsplitter.

Conclusions

The MC model accurately predicted localization precision, spectral precision, spectral peaks, and spectral widths of fluorescent microspheres, as validated by experimental data. Our work enhances the theoretical understanding of DWP-based sSMLM for multiplexed imaging, enabling performance optimization.
Preliminary Development of a Robotic Hip-Knee Exoskeleton with 3D-Printed Backdrivable Actuators
Authors: Sanchez Alyssia , Rossos Trent , Mihailidis Alex , Laschowski Brokoslaw
Published: May 2023

Robotic exoskeletons can provide powered locomotor assistance and rehabilitation to persons with mobility impairments due to aging and/or physical disabilities. Here we present the preliminary development and systems integration of T-BLUE - a modular, bilateral robotic hip-knee exoskeleton with 3D-printed backdriveable actuators. We retrofitted commercially available passive postoperative orthoses with open-source 3D-printed actuators to minimize cost and improve accessibility. The actuators are of quasi-direct drive design with high-torque density brushless DC motors and low gearing (15:1 transmission ratio) for low output impedance and high backdrivability, therein allowing for energy-efficient and dynamic human-robot physical interaction and legged locomotion. The modular design allows the exoskeleton to be customized and adapted to different users (e.g., persons with lateral vs. bilateral mobility impairments) and different hip-knee joint configurations. The goals of this preliminary study were to describe our experience with regards to the repeatability of the open-source 3D-printed actuators in engineering practice and the feasibility of integrating the actuators into wearable robotics hardware. This qualitative research serves as a first step towards using the robotic exoskeleton to support the development and testing of novel controller designs and rehabilitation protocols for different locomotor activities of daily living. We are especially interested in populations that could benefit from partial locomotor assistance such as older adults and/or persons with osteoarthritis. Future research will involve benchtop testing to quantitatively evaluate the actuator performance in terms of dynamics and energy-efficiency.
Discovering Biomarker Proteins and Peptides for Parkinson’s Disease Prognosis Prediction with Machine Learning and Interpretability Methods
Authors: Park Ho-min , Kabanga Espoir , Moon Dongin , Chung Minjae , Im Jiwon , Kim Yujin , Van Messem Arnout , De Neve Wesley
Published: May 2023

Parkinson’s disease is a neurodegenerative disorder that affects millions of people worldwide, posing significant challenges for diagnosis and treatment. This study presents a machine learning pipeline for identifying candidate biomarker proteins and peptides from cerebrospinal fluid mass spectrometry (CSF-MS) tests in Parkinson’s disease patients. Our pipeline comprises two main stages: (1) model training using mutual information-based feature selection and five different machine learning regressors and (2) identification of candidate biomarkers by combining three types of interpretability methods. Our regression models demonstrated promising effectiveness in predicting the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) scores, with UPDRS-1 receiving the best predictions, followed by UPDRS-3 and UPDRS-2. Furthermore, our pipeline identified 11 proteins and peptides as potential biomarkers for Parkinson’s disease, excluding Levodopa usage which trivially has the most significant impact on the prognosis prediction. Comparisons with four additional pipelines confirmed the effectiveness of our approach in terms of both model performance and biomarker identification. In conclusion, our study presents a comprehensive machine learning pipeline that demonstrates effectiveness in predicting the severity of Parkinson’s disease using CSF-MS tests. Our approach also identifies potential biomarkers, which could aid in the development of new diagnostic tools and treatments for patients with Parkinson’s disease.
scTIE: data integration and inference of gene regulation using single-cell temporal multimodal data
Authors: Lin Yingxin , Wu Tung-Yu , Chen Xi , Wan Sheng , Chao Brian , Xin Jingxue , Yang Jean Y.H. , Wong Wing H. , Wang Y. X. Rachel
Published: May 2023

Single-cell technologies offer unprecedented opportunities to dissect gene regulatory mecha-nisms in context-specific ways. Although there are computational methods for extracting gene regulatory relationships from scRNA-seq and scATAC-seq data, the data integration problem, essential for accurate cell type identification, has been mostly treated as a standalone challenge. Here we present scTIE, a unified method that integrates temporal multimodal data and infers regulatory relationships predictive of cellular state changes. scTIE uses an autoencoder to embed cells from all time points into a common space using iterative optimal transport, followed by extracting interpretable information to predict cell trajectories. Using a variety of synthetic and real temporal multimodal datasets, we demonstrate scTIE achieves effective data integration while preserving more biological signals than existing methods, particularly in the presence of batch effects and noise. Furthermore, on the exemplar multiome dataset we generated from differentiating mouse embryonic stem cells over time, we demonstrate scTIE captures regulatory elements highly predictive of cell transition probabilities, providing new potentials to understand the regulatory landscape driving developmental processes.
Integrative proteomics and network biology approach to identify potential urine based biomarkers for tuberculosis
Authors: Subramaniam Sangeetha , Varshney Ankur , Singla Rupak , Behera Digamber , Nanda Ranjan Kumar
Published: May 2023

Urine based biomarker discovery employing proteomics platform has been successfully attempted for multiple diseases. Urine is an excellent source of biomarker discovery but its potential is not fully tapped in tuberculosis (TB) diagnostics. In the present study, proteomic profiling of urine samples from thirty five subjects (Mean age=41 years (15-76), M/F=28/7) belonging to active TB, latent TB, lung cancer, chronic obstructive pulmonary disorders (COPD) and healthy subjects were carried out employing a robust multiplex technique. We identified 131 proteins out of which 16 molecules showed at least two-fold change in TB. The study identified a signature of three putative markers, leucine-rich alpha-2-glycoprotein (up-regulated), roundabout homolog 4 and isoform 2 of prostatic acid phosphatase (down-regulated) that could differentiate active TB from other pulmonary diseases. Besides, we investigated whether a network based approach can be efficiently used to expand dynamic coverage, gain a comprehensive view of underlying perturbed functions during the infection and to discover potential biomarkers. While comparing the functionally associated sub-networks of active TB with healthy urine proteome, we identified 54 proteins from the discriminative TB sub-network, some of which are known to be involved in the infection process. Few examples in this study like serpin peptidase inhibitor and catenin that has not been identified in the experiment but detected in the difference network demonstrate that proteomic profiling when integrated with network biology method could be a holistic approach to expand the dynamic range and identify potential candidate biomarkers and also provide a broad overview of perturbed functions during the infection.
Systematic Review of Monogenic Diabetes Prognostics
Authors: Naylor Rochelle N. , Amouyal Chloé , Philipson Louis H. , Vatier Camille , Dickens Laura T. ,   ADA/EASD PMDI, Greeley Siri Atma W
Published: May 2023

Background

Individuals with monogenic diabetes are at risk for diabetes-related complications; however, overall prognosis and whether prognosis is similar to other diabetes forms is poorly understood.

Aim

To assess diabetes-related microvascular and macrovascular complications in the common forms of monogenic diabetes.

Methods

Systematic review with data sources from Pubmed, Medline and Embase was performed to assess diabetes-related complications in KCNJ11-neonatal diabetes, ABBC8-neontal diabetes, HNF1A-diabetes, HNF4-diabetes and GCK-related hyperglycemia.

Results

Data was extracted from 67 studies. Most studies had moderate to high risk of bias. In neonatal diabetes, 16 of 20 studies reported at least one microvascular complication, with complications occurring as early as the second decade of life. Macrovascular complications were reported in only 1 individual who was 40 years old at the time of study. Diabetes complications were frequent in HNF1A-diabetes and HNF4A-diabetes, but did show a temporal trend of improved prognosis (e.g., 47% versus 13.6% retinopathy) and better prognosis compared to type 1 diabetes. Death due to cardiovascular disease was higher in HNF1A-diabetes compared to unaffected relatives (66% versus 43%). GCK-related hyperglycemia showed overall low rates of complications.

Conclusion

While KCNJ11-neonatal diabetes, ABBC8-neontal diabetes, HNF1A-diabetes and HNF4-diabetes are clearly at risk for diabetes-related complications, microvascular complications were infrequently reported before the third decade of life. GCK-related hyperglycemia showed a low prevalence of complications with rates not significantly different from control groups except for mild retinopathy. Future prospective studies to determine age at onset of complications and the impact of precision therapy are warranted to best guide surveillance practices for each subtype.
The Protective Effect of Virus Capsids on RNA and DNA Virus Genomes in Wastewater
Authors: Harrison Katherine R. , Snead Delaney , Kilts Anna , Ammerman Michelle L. , Wigginton Krista R.
Published: May 2023

Virus concentrations measured in municipal wastewater help inform both the water treatment necessary to protect human health and wastewater-based epidemiology. Wastewater measurements are typically PCR-based, and interpreting gene copy concentrations requires an understanding of the form and stability of the nucleic acids. Here, we study the persistence of model virus genomes in wastewater, the protective effects provided by the virus capsids, and the relative decay rates of genome and infectious viruses. In benchtop batch experiments at 25 °C, extraviral (+)ssRNA and dsDNA amplicons degraded by 90% within 15-19 minutes and 1.6-1.9 hours, respectively. When encapsidated, the T90for MS2 (+)ssRNA increased by 424× and the T90for T4 dsDNA increased by 52×. The (+)ssRNA decay rates were similar for a range of amplicon sizes. For our model phages MS2 and T4, the nucleic acid signal in untreated wastewater disappeared shortly after the viruses lost infectivity. Combined, these results suggest that most viral genome copies measured in wastewater are part of intact virus particles, that measured concentrations are independent of assay amplicon sizes, and that the virus genome decay rates of naked viruses are similar to inactivation rates. These findings will be valuable for the interpretation of wastewater virus measurements.
Utility of Multimodal Longitudinal Imaging Data for Dynamic Prediction of Cardiovascular and Renal Disease: The CARDIA Study
Authors: Nguyen Hieu , Vasconcellos Henrique D. , Keck Kimberley , Carr John , Launer Lenore J , Guallar Eliseo , Lima João A.C. , Ambale-Venkatesh Bharath
Published: May 2023

Background

Medical examinations contain repeatedly measured data from multiple visits, including imaging variables collected from different modalities. However, the utility of such data for the prediction of time-to-event is unknown, and only a fraction of the data is typically used for risk prediction. We hypothesized that multimodal longitudinal imaging data could improve dynamic disease prognosis of cardiovascular and renal disease (CVRD).

Methods

In a multi-centered cohort of 5114 CARDIA participants, we included 166 longitudinal imaging variables from five imaging modalities: Echocardiography (Echo), Cardiac and Abdominal Computed Tomography (CT), Dual-Energy X-ray Absorptiometry (DEXA), Brain Magnetic Resonance Imaging (MRI) collected from young adulthood to mid-life over 30 years (1985-2016) to perform dynamic survival analysis of CVRD events using machine learning dynamic survival analysis (Dynamic-DeepHit, LTRCforest, and Extended Cox for Time-varying Covariates). Risk probabilities were continuously updated as new data were collected. Model performance was assessed using integrated AUC and C-index and compared to traditional risk factors.

Results

Longitudinal imaging data, even when being irregularly collected with high missing rates, improved CVRD dynamic prediction (0.03 in integrated AUC, up to 0.05 in C-index compared to traditional risk factors) from young adulthood followed up to midlife. Among imaging variables, Echo and CT variables contributed significantly to improved risk estimation. Echo measured in early adulthood predicted midlife CVRD risks almost as well as Echo measured 10-15 years later (0.01 C-index difference). The most recent CT exam provided the most accurate prediction for short-term risk estimation. Brain MRI markers provided additional information from cardiac Echo and CT variables that led to a slightly improved prediction.

Conclusions

Longitudinal multimodal imaging data readily collected from follow-up exams can improve CVRD dynamic prediction. Echocardiography measured early can provide a good long-term risk estimation, while CT/calcium scoring variables carry atherosclerotic signatures that benefit more immediate risk assessment starting in middle-age.
Genetic excision of the regulatory cardiac troponin I extension in high heart rate mammal clades
Authors: Joyce William , He Kai , Zhang Mengdie , Ogunsola Samuel , Wu Xini , Joseph Kelvin T. , Bogomolny David , Yu Wenhua , Springer Mark S. , Xie Jiuyong , Signore Anthony V. , Campbell Kevin L.
Published: May 2023

Mammalian cardiac troponin I (cTnI) contains a highly conserved N-terminal extension harboring protein kinase A targets (Ser23/24) which are phosphorylated during ß-adrenergic stimulation to increase cardiomyocyte relaxation rate. Here, we show that the Ser23/24encoding exon 3 ofTNNI3was pseudoexonized multiple times in shrews and moles to mimic Ser23/24phosphorylation without adrenergic stimulation, facilitating the evolution of exceptionally high resting heart rates (∼1000 beats min-1). We further reveal alternative exon 3 splicing in distantly related bat families and that both exon 3-and exon 3+cTnI isoforms are incorporated into cardiac myofibrils. Finally, exon 3 of humanTNNI3is shown to exhibit a relatively low splice strength score, offering an evolutionarily informed strategy to excise this exon to improve diastolic function during heart failure.
Listening to tropical forest soils
Authors: Metcalf Oliver , Baccaro Fabricio , Barlow Jos , Berenguer Erika , Bradfer-Lawrence Tom , Rossi Liana Chesini , do Vale Érica Marinho , Lees Alexander
Published: May 2023

PAM has proven to be an effective tool for monitoring biotic soundscapes in the marine, terrestrial, and aquatic realms. Recently it has been suggested that it could also be an effective method for monitoring soil fauna, but has so far been used in only four studies in temperate and polar regions. We present the first study of soil soundscapes in tropical forests, using a novel analytical pipeline allowing for the use of in-situ recording of soundscapes with minimal soil disturbance. We found significant differences in soil soundscapes between burnt and unburnt forests and the first indications of a diel cycle in soil soundscapes. These promising results and methodological advances highlight the potential of PAM for large-scale and long-term monitoring of soil biodiversity. We use the results to discuss research priorities, including relating soil biophony to biodiversity, community structure and ecosystem functioning, and the use of appropriate hardware and analytical techniques.
Distinct axo-protective and axo-destructive roles for Schwann cells after injury in a novel compartmentalised mouse myelinating coculture system
Authors: Mutschler Clara , Fazal Shaline V. , Schumacher Nathalie , Loreto Andrea , Coleman Michael P. , Arthur-Farraj Peter
Published: May 2023

Myelinating Schwann cell (SC)– dorsal root ganglion (DRG) neuron cocultures have been an important technique over the last four decades in understanding cell-cell signalling and interactions during peripheral nervous system (PNS) myelination, injury, and regeneration. While methods using rat SCs and rat DRG neurons are commonplace, there are no established protocols in the field describing the use of mouse SCs with mouse DRG neurons in dissociated myelinating cocultures. There is a great need for such a protocol as this would allow the use of cells from many different transgenic mouse lines. Here we describe a protocol to coculture dissociated mouse SCs and DRG neurons and induce robust myelination. Use of microfluidic chambers permits fluidic isolation for drug treatments, allows cultures to be axotomised to study injury responses, and cells can readily be transfected with lentiviruses to permit live imaging. We used this model to quantify the rate of degeneration after traumatic axotomy in the presence and absence of myelinating SCs and axon aligned SCs that were not induced to myelinate. We find that SCs, irrespective of myelination status, are axo-protective and delay axon degeneration early on. At later time points after injury, we use live imaging of cocultures to show that once axonal degeneration has commenced SCs break up, ingest, and clear axonal debris.

Summary statement

A novel compartmentalised dissociated mouse myelinating SC-DRG coculture system reveals distinct axo-protective and axo-destructive phases of Schwann cells on axon integrity after trauma.
AMLdb: A comprehensive multi-omics platform to understand the pathogenesis and discover biomarkers for acute myeloid leukemia
Authors: Kumar Keerthana Vinod , Kumar Ambuj , Kundal Kavita , Sengupta Avik , R Kunjulakshmi , Nishana Mayilaadumveettil , Kumar Rahul
Published: May 2023

Acute myeloid leukemia (AML) is one of the leading leukemic malignancies in adults. The heterogeneity of the disease makes the diagnosis and treatment extremely difficult. Despite the significant developments and the rapid advancements in finding new medication targets, the treatment for AML remains a challenge. With the advent of next-generation sequencing (NGS) technologies, exploration at the molecular level for the identification of biomarkers and drug targets has been the main focus for the researchers to come up with novel therapies for better prognosis and survival outcomes of AML patients. However, the massive amounts of data generated from the NGS platforms demands the necessity to create a comprehensive platform on AML to save the time invested in mining literature. To facilitate this, we developed AMLdb, an interactive multi-omics platform that allows users to query, visualize, retrieve and analyze AML-related multi-omics data. It provides a diverse collection of data resourced from various repositories allowing for a more comprehensive analysis. AMLdb contains 86 datasets for gene expression profiles, 15 datasets for methylation profiles, CRISPR-Cas9 knockout screens of 26 AML cell lines, sensitivity of 26 AML cell lines to 288 drugs, mutations in 41 unique genes in 23 AML cell lines and information on 27 experimentally validated biomarkers. The data provided can be used for deriving conclusions on potential targets for therapies, sensitivity of these targets towards the drugs, patient classification, prediction of treatment strategies and outcomes, chances of relapse etc. In this study, we have reported five genes i.e.,CBFB, ENO1, IMPDH2, SEPHS2 and MYH9identified via our analysis using AMLdb as potential targets. Amongst this,CBFB, IMPDH2, SEPHS2 and MYH9have been previously validated as targets by experimental studies which is in par with our results. However,ENO1is a novel target identified using AMLdb which needs further investigation. We anticipates that, AMLdb can be a valuable resource to aid the research community accelerate the development of effective therapies for AML. AMLdb is freely accessible athttps://project.iith.ac.in/cgntlab/amldb/without any restrictions.
Flavodiiron proteins associate pH-dependently with the thylakoid membrane for ferredoxin-1 powered O2photoreduction
Authors: Nikkanen Lauri , Vakal Serhii , Santana-Sánchez Anita , Hubáček Michal , Konert Grzegorz , Wang Yingying , Boehm Marko , Gutekunst Kirstin , Salminen Tiina A. , Allahverdiyeva Yagut
Published: May 2023

Flavodiiron proteins (FDPs) catalyse light-dependent reduction of oxygen to water in photosynthetic organisms, creating an electron sink on the acceptor side of Photosystem I that protects the photosynthetic apparatus. However, the identity of the electron donor(s) and the molecular mechanisms regulating FDP activity have remained elusive. To elucidate these issues, we employed spectroscopic and gas flux analysis of photosynthetic electron transport, bimolecular fluorescence complementation assays forin vivoprotein–protein interactions in the model cyanobacteriumSynechocystissp. PCC 6803, as well asin silicosurface charge modelling. We demonstrated that Ferredoxin-1 interacts with Flv1, Flv2, and Flv3, and is the main electron donor to FDP heterooligomers, which are responsible for the photoreduction of oxygen. Moreover, we revealed that association of FDP heterooligomers with thylakoid membranes is promoted by dissipation of the trans-thylakoid proton motive force, providing the firstin vivoevidence of a self-regulatory feedback mechanism allowing dynamic control of FDP activity and maintenance of photosynthetic redox balance in fluctuating environments. Our findings have direct implications for rationally directing electron flux toward desired reactions in biotechnological applications.
HEMU: an integrated Andropogoneae comparative genomics database and analysis platform
Authors: Zhu Yuzhi , Wang Zijie , Zhou Zanchen , Liu Yuting , Shi Junpeng
Published: May 2023

The Andropogoneae tribe encompasses various crops with substantial agronomic value such as maize (Zea mays) and sorghum (Sorghum bicolor). Despite the prevalence in released multi-omics data resources, there is a dearth of comprehensive, tribe-level integration and multi-layer omics dataset platform within the tribe, assisting inter- and intra-species comparative analysis from a multi-omics aspect. Here, we first collected a comprehensive atlas of multi-omics datasets within the tribe, including 75 genomes from 20 unique species, transcriptomes from 4,747 samples comprising more than 50 tissues, epigenome data from 90 ChIP-seq samples and 39 ATAC-seq samples, as well as transposable element (TE) annotation for all the genomes. Then, an integrated database and analysis platform, HEMU (http://shijunpenglab.com/HEMUdb/), was constructed. HEMU comprises six sophisticated toolkits, namely genome analysis toolkit, transcriptome-derived analysis toolkit, gene family analysis toolkit, transposable element (TE) analysis toolkit, epigenome analysis toolkit and miscellaneous analysis toolkit, facilitating convenient inter- and intra-species comparative analysis taking advantage of the multi-omics data. Three case studies substantiated the capability of HEMU in conducting gene-centered analysis, transcriptome derived analysis and gene family analysis from a both multi-omics and comparative perspective. In a nutshell, HEMU lowers the barrier of traditional code-based analysis workflow, providing novel insights into modern genetic breeding in the tribe Andropogoneae.
Incidental learning of predictive temporal context within cortical representations of visual shape
Authors: Kakaei Ehsan , Braun Jochen
Published: May 2023

Incidental learning of spatio-temporal regularities and consistencies – also termed ‘statistical learning’ – may be important for discovering the causal principles gov-erning the world. We studied statistical learning of temporal structure at two temporal scales: the presentation of rotating visual objects (3 s) and predictive temporal context (30 s) in a sequence of such objects.

Observers viewed fifteen initially unfamiliar synthetic objects recurring many times each, intermixed with other similar objects that appeared only once, while whole-brain BOLD activity was recorded. Analyzing multivariate BOLD activity, we located view-independent responses to synthetic objects throughout the ventral occipitotemporal cortex, revealing a view-invariant representation of object shape.

Predictive temporal context modified representations of object shape at early and middle levels of the visual processing hierarchy. Approximately 20% of the sites representing shape also exhibited a significant representation of temporal context. A few higher-level sites represented temporal context, without also representing object shape. Additionally, objects marking transitions between communities were distinctly represented at many sites.

We conclude that, at the sensitivity afforded by fMRI, the cortical represen-tations of invariant visual shape and of predictive temporal context are largely coextensive. Our results suggest that incidental learning of causal principles and structures operating at different timescales (“structural learning”) may involve vi-sually responsive areas in the ventral occipitotemporal cortex.
Computational models for state-dependent traveling waves in hippocampal formation
Authors: Wu Yuxuan , Chen Zhe Sage
Published: May 2023

Hippocampal theta (4-10 Hz) oscillations have been identified as traveling waves in both rodents and humans. In freely foraging rodents, the theta traveling wave is a planar wave propagating from the dorsal to ventral hippocampus along the septotemporal axis. Motivated from experimental findings, we develop a spiking neural network of excitatory and inhibitory neurons to generate state-dependent hippocampal traveling waves to improve current mechanistic understanding of propagating waves. Model simulations demonstrate the necessary conditions for generating wave propagation and characterize the traveling wave properties with respect to model parameters, running speed and brain state of the animal. Networks with long-range inhibitory connections are more suitable than networks with long-range excitatory connections. We further generalize the spiking neural network to model traveling waves in the medial entorhinal cortex (MEC) and predict that traveling theta waves in the hippocampus and entorhinal cortex are in sink.
Extracellular vesicle-mediated Transfer of miR-1 from Primary tumor Repress Distant Metastasis Growth
Authors: Kim Hui-Su , Lee Kang-Hoon , Son Keun Hong , Shin Tae-Jin , Cho Je-Yoel
Published: May 2023

Metastases originate from primary tumors that conquer distant organs. Growing evidence suggests that metastases are still under primary tumor dominance, even out of the primary territory. However, the mechanism by which primary tumors prime the fate of metastasis is unclear. Here, we investigated the influence of primary tumor-derived extracellular vesicles (pTDEs) on distant metastasis. Metastatic growth was remarkably suppressed when cells were treated with pTDEsin vitroand intravenously in a spontaneous metastatic mouse model. pTDEs from primary tumors with cancer stem cell (CSC) characteristics inhibit metastatic growth by inducing intracellular ROS/DNA double-stranded damage, thus inhibiting G2/M phase accumulation. We found that miR-1 was the most abundant in pTDEs and showed a stronger inhibitory effect when miR-1 was overloaded in pTDEs. Collectively, we demonstrated that the primary tumor could control distant metastatic cancer via primary tumor-derived EV-miR-1. Additionally, our approach suggests the development of anticancer drugs for metastasis based on pTDE-miR-1.
The Secondary Somatosensory Cortex Gates Mechanical and Thermal Sensitivity
Authors: Taub Daniel G. , Jiang Qiufen , Pietrafesa Francesca , Su Junfeng , Greene Caitlin , Blanchard Michael R. , Jain Aakanksha , El-Rifai Mahmoud , Callen Alexis , Yager Katherine , Chung Clara , He Zhigang , Chen Chinfei , Woolf Clifford J.
Published: May 2023

The cerebral cortex is vital for the perception and processing of sensory stimuli. In the somatosensory axis, information is received by two distinct regions, the primary (S1) and secondary (S2) somatosensory cortices. Top-down circuits stemming from S1 can modulate mechanical and cooling but not heat stimuli such that circuit inhibition causes blunted mechanical and cooling perception. Using optogenetics and chemogenetics, we find that in contrast to S1, an inhibition of S2 output increases mechanical and heat, but not cooling sensitivity. Combining 2-photon anatomical reconstruction with chemogenetic inhibition of specific S2 circuits, we discover that S2 projections to the secondary motor cortex (M2) govern mechanical and thermal sensitivity without affecting motor or cognitive function. This suggests that while S2, like S1, encodes specific sensory information, that S2 operates through quite distinct neural substrates to modulate responsiveness to particular somatosensory stimuli and that somatosensory cortical encoding occurs in a largely parallel fashion.
Common and distinct BOLD correlates of Simon and flanker conflicts which can(not) be reduced to time-on-task effects
Authors: Wojciechowski Jakub , Jurewicz Katarzyna , Dzianok Patrycja , Antonova Ingrida , Paluch Katarzyna , Wolak Tomasz , Kublik Ewa
Published: May 2023

The ability to identify and resolve conflicts between standard, well trained behaviors, and behaviors required by the current context is an essential feature of cognitive control. To date, no consensus has been reached on the brain mechanisms involved in exerting such control: while some studies identified diverse patterns of activity across different conflicts, other studies reported common resources across conflict tasks or even across simple tasks devoid of conflict component. The latter reports attributed the entire activity observed in the presence of conflict to longer time spent on the task (i.e. to the so-called time-on-task effects). Here we used an extended Multi-Source Interference Task (MSIT) which combines Simon and flanker types of interference to determine shared and conflict-specific mechanisms of conflict resolution in fMRI, and their separability from the time-on-task effects. Large portions of the activity in the dorsal attention network and decreases of activity in the default mode network were shared across the tasks and scaled in parallel with increasing reaction times. Importantly, activity in the sensory and sensorimotor cortices, as well as in the posterior medial frontal cortex (pMFC)–a key region implicated in conflict processing–could not be exhaustively explained by the time-on-task effects.
Exercise modulates human hippocampal-cortical ripple dynamics
Authors: Cardenas Araceli R. , Ramirez-Villegas Juan F. , Kovach Christopher K. , Gander Phillip E. , Cole Rachel C. , Grossbach Andrew J. , Kawasaki Hiroto , Greenlee Jeremy D.W. , Howard Mathew A. , Nourski Kirill V. , Banks Matthew I. , Voss Michelle W.
Published: May 2023

Physical exercise acutely improves hippocampal-based learning and memory in rodents and humans. While animal studies have mainly offered cellular- and synaptic-level accounts of these effects, human neuroimaging studies show that exercise improves hippocampal-cortical connectivity at the macroscale level. However, the neurophysiological basis for exercise-induced effects on human hippocampal-cortical circuits remains unknown. A growing body of evidence supports the critical role of hippocampal sharp wave-ripples (SWRs) in learning and memory. Moreover, recent studies suggest that the coupling between ripples in the hippocampus and neocortex reflect acute modulations in inter-regional connectivity required by mnemonic processes. Here, we examine the hypothesis that exercise modulates hippocampal SWR events and their coupling with ripples in other cortical areas. We performed intracranial recordings in neurosurgery patients during awake resting state, before and after one session of aerobic exercise. Exercise elicited an increase in ripple rate and duration in mesio-temporal areas (hippocampus, amygdala and parahippocampal gyrus). These changes in ripple features were also observed in the limbic and the default mode (DMN) networks. Furthermore, after exercise, we observed an increase in coupling and phase synchrony between ripples in these two networks and hippocampal SWRs. Our results elucidate the potential mechanisms by which aerobic exercise elicits its reported short-term effects in cognition. Further investigations are needed to explore how these exercise-induced acute modulations contribute to long-term changes in neural plasticity.

Significance Statement

Physical activity is a modifiable lifestyle factor that improves cognitive function and prevents age-related cognitive decline. Even one session of exercise can enhance hippocampal-based memory and learning. However, the neurophysiological mechanisms by which exercise acutely affects human cognition remain unknown. Using intracranial recordings in neurosurgical patients we show that the hippocampus and neocortex often synchronize their activities via high-frequency neural synchrony events known as ripples. After exercise, hippocampal and neocortical ripples were prolonged and emerged more frequently. Moreover, hippocampal and neocortical ripples exhibited increased coupling and phase synchrony. These effects were neocortical region-specific, favoring structures of the limbic and default mode networks. Ultimately, our results shed light on the mechanisms behind the preventive and therapeutic potential of exercise interventions.