bluuebunny/crossref_metadata_2025 huggingface dataset:
Impact of cryopreservation on immune cell metabolism as measured by SCENITH
Authors: Luscombe Curtis , Jones Eben , Gregorova Michaela , Jones Nicholas , Rivino Laura
Published: June 2024

The dynamic functioning of immune cells is regulated by cellular metabolic processes, and there is growing interest in the study of immunometabolic correlates of dysfunctional immune responses. SCENITH is a novel flow cytometry-based technique that allows forex vivometabolic profiling of immune cells within heterogeneous samples. Cryopreservation of clinical samples is frequently undertaken to facilitate high throughput processing, but is thought to lead to cellular metabolic dysfunction. We aimed to investigate the impact of cryopreservation on immune cell metabolism, harnessing SCENITH’s unique ability to describe the divergent bioenergetic characteristics of distinct immune cell subsets.

We demonstrate that T cells undergoing activation with a CD3/CD28 stimulus are less readily metabolically reprogrammed following cryopreservation. Additionally, we find that cryopreservation introduces a time-dependent metabolic artefact that favours glycolysis and impairs oxidative phosphorylation, suggesting that cryopreservation results in mitochondrial dysfunction. Despite this artefact, SCENITH was still able to reveal the distinct bioenergetic profiles of contrasting immune cells populations following cryopreservation – for example, non-classical monocytes have a higher mitochondrial dependence than classical monocytes, and T cell CD69 expression is associated with an upregulation of glycolytic capacity.

Whilst we believe that SCENITH can provide valuable information about immune cell metabolism even in cryopreserved samples, our findings have important implications for the design of future studies. Investigators should carefully consider how to process and store clinical samples to ensure that cryopreservation does not confound analyses, particularly where longitudinal sampling is required.
Inferring metabolite states from spatial transcriptomes using multiple graph neural network
Authors: Luo Jiaxu , Ai Daosheng , Sun Wenzhi
Published: June 2024

Metabolism serves as the pivotal interface connecting genotype and phenotype. While various methods are available for predicting metabolite levels from transcriptomic data, their efficacy remains poor. We developed an efficient and adaptable algorithm known as Multiple Graph-based Flux Estimation Analysis (MGFEA). By leveraging single-cell and spatial transcriptomic data, MGFEA enables the inference of metabolite levels. Furthermore, MGFEA can further improve the accuracy of these inferences through exploiting additional metabolome data.
Immunological correlates of protection mediated by a whole organismCryptococcus neoformansvaccine deficient in chitosan
Authors: Specht Charles A. , Wang Ruiying , Oliveira Lorena V. N. , Hester Maureen M. , Gomez Christina , Mou Zhongming , Carlson Diana , Lee Chrono K. , Hole Camaron R. , Lam Woei C. , Upadhya Rajendra , Lodge Jennifer K. , Levitz Stuart M.
Published: June 2024

The global burden of infections due to the pathogenic fungusCryptococcusis substantial in persons with low CD4+T cell counts. Previously, we deleted three chitin deacetylase genes fromC. neoformansto create a chitosan-deficient, avirulent strain, designatedcda1Δ2Δ3Δwhich, when used as a vaccine, protected mice from challenge with virulentC. neoformansstrain KN99. Here, we explored the immunological basis for protection. Vaccine-mediated protection was maintained in mice lacking B cells or CD8+T cells. In contrast, protection was lost in mice lacking α/β T cells or CD4+T cells. Moreover, CD4+T cells from vaccinated mice conferred protection upon adoptive transfer to naive mice. Importantly, while monoclonal antibody-mediated depletion of CD4+T cells just prior to vaccination resulted in complete loss of protection, significant protection was retained in mice depleted of CD4+T cells after vaccination, but prior to challenge. Vaccine-mediated protection was lost in mice genetically deficient in IFNγ, TNFα, or IL-23p19. A robust influx of leukocytes and IFNγ- and TNFα-expressing CD4+T cells was seen in the lungs of vaccinated and challenged mice. Finally, a higher level of IFNγ production by lung cells stimulated ex vivo correlated with lower fungal burden in the lungs. Thus, while B cells and CD8+T cells are dispensable, IFNγ and CD4+T cells have overlapping roles in generating protective immunity prior tocda1Δ2Δ3Δvaccination. However, once vaccinated, protection becomes less dependent on CD4+T cells, suggesting a strategy for vaccinating HIV+persons prior to loss of CD4+T cells.

Importance

The fungusCryptococcus neoformansis responsible for >100,000 deaths annually, mostly in persons with impaired CD4+T cell function such as AIDS. There are no approved human vaccines. We previously created a genetically engineered avirulent strain ofC. neoformans, designatedcda1Δ2Δ3Δ. When used as a vaccine,cda1Δ2Δ3Δprotects mice against a subsequent challenge with a virulentC. neoformansstrain. Here, we defined components of the immune system responsible for vaccine-mediated protection. We found that while B cells and CD8+T cells were dispensible, protection was lost in mice genetically deficient in CD4+T cells, and the cytokines IFNγ, TNFα, or IL-23. A robust influx of cytokine-producing CD4+T cells was seen in the lungs of vaccinated mice following infection. Importantly, protection was retained in mice depleted of CD4+T cells following vaccination, suggesting a strategy to protect persons who are at risk for future CD4+T cell dysfunction.
Automated and high throughput measurement of leaf stomatal traits in canola
Authors: Yao Lingtian , von Caemmerer Susanne , Danila Florence R
Published: June 2024

Background

Automating stomatal trait measurement has gained popularity because of their inherent importance for field phenotyping application as stomata are critical for both carbon capture and water use efficiency in plants. Such tool has been reported for rice, wheat, tomato, barley and oil palm. However, none exist yet for canola, which is an important economic and agronomic crop globally.

Results

We developed a new toolkit called Stomatal Comprehensive Automated Neural Network or SCAN by combining the use of high-resolution portable digital microscopy with machine learning based on You Only Look Once algorithm (YOLOv8). Digital micrographs of leaf surfaces enter the SCAN pipeline, which includes stomata detection, stomata segmentation and stomatal pore segmentation models, to measure stomatal density, stomatal size and stomatal pore area, respectively. In addition to SCAN’s ability to measure leaf stomatal traits in canola at 89 to 94% accuracy, we also showed that SCAN can be used to predict stomatal density even in species not included in the training set such as Arabidopsis, tobacco, rice, wheat, maize and proso millet. SCAN was designed for the biological science community with the premise that users are not required to possess advanced programming capabilities to manage dependency prerequisites, execute the models, and integrate the analysis. This was achieved by packaging the models into a desktop application system that can be accessed offline.

Conclusion

Overall, SCAN provides a non-destructive, real-time, portable, and high-throughput measurement of leaf stomatal traits in canola. The minimised hardware requirement and user-friendly desktop application system make SCAN suitable for field phenotyping application.
Benchmarking and quality control for nanopore sequencing and feasibility of rapid genomics in New Zealand: validation phase at a single quaternary hospital
Authors: Nyaga Denis M. , Tsai Peter , Gebbie Clare , Phua Hui Hui , Yap Patrick , Stabej Polona Le Quesne , Farrow Sophie , Rong Jing , Toldi Gergely , Thorstensen Eric , Stark Zornitza , Lunke Sebastian , Gamet Kimberley , Dyk Jodi Van , Greenslade Mark , O’Sullivan Justin M.
Published: June 2024

Approximately 200 critically ill infants and children in New Zealand are in high-dependency neonatal/paediatric acute care at any given time, many with suspected genetic conditions, necessitating a scalable distributed solution for rapid genomic testing. We adopt the existing acute care genomics protocol of an accredited laboratory and established an expandable acute care clinical pipeline based around the Oxford Nanopore Technologies PromethION 2 solo system connected to a Bayesian AI-based clinical decision support tool (Fabric GEM™ software). In the establishment phase, we performed benchmarking using Global Alliance for Genomics and Health (GA4GH) benchmarking tools and Genome in a Bottle samples HG002-HG007. We evaluated single nucleotide variants (SNVs) and small insertions-deletions (indels) calls and achieved SNV precision and recall of 0.997 ± 0.0006 and 0.992 ± 0.001, respectively. Small indel identification approached a precision of 0.922 ± 0.019 and recall of 0.838 ± 0.043. Rarefaction analyses demonstrated that SNV identification plateaus at ∼20X coverage, while small indels plateaus at ∼40X coverage. Large genomic variations from Coriell Copy Number Variation Reference Panel 1 (CNVPANEL01) were reliably detected with ∼2M long reads. Finally, we present results obtained from ten trio samples that were processed through the pipeline validation phase, averaging a 5-day turnaround time, conducted in parallel with a clinically accredited short-read rapid genomic testing pipeline.
Preterm birth and paternal mental health during the perinatal period: A systematic review protocol
Authors: Philpott Lloyd Frank , Torsy Tim , D’haenens Florence , Van denhaute Ellen , Tency Inge
Published: June 2024

Introduction

Despite the evidence that fatherhood has a long-term positive and protective effect on men’s health, there is also evidence that fatherhood in the perinatal period can be complex and demanding. The challenging nature of fatherhood during the perinatal period can be further compounded by the experience of preterm birth. Preterm birth, defined as a birth occurring before 37 weeks of gestation, has been identified as a risk factor for maternal stress, anxiety, depression and post-traumatic stress. It can be hypothesised that preterm birth is also a risk factor for fathers mental health; however, as no attempt has been made to systematically review studies that have examined preterm births and father’s mental health during the perinatal period it is currently not known how common or signficant the impact of a preterm birth is on father’s mental health during this life stage.

Aim

The aim of the systematic review will be to critically appraise the empirical evidence that examined preterm birth and father’s mental health during the perinatal period.

Design

Systematic review

Methods

The review will be guided by the PRISMA reporting process. Electronic databases Medline, CINAHL, the Cochrane Library, PsycARTICLES, PsycINFO, Psychology and Behavioural Sciences Collections will be searched to identify studies that meet the inclusion criteria. Studies that researched preterm birth during the perinatal period will be included if fathers mental health was the principal focus of the research, if fathers mental health was in the title and/or aim of the study or if fathers mental health was an outcome or dependent variable. Data will be extracted and presented in narrative form including tables and figures.

Trial registration

Trial registration: the protocol for this systematic review has been registered in PROSPERO [CRD42024536317].

https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=536317
HIV-1 infection promotes neuroinflammation and neuron pathogenesis in novel microglia-containing cerebral organoids
Authors: Narasipura Srinivas D. , Zayas Janet P. , Ash Michelle K. , Reyes Anjelica , Shull Tanner , Gambut Stephanie , Schneider Jeffrey R. , Lorenzo-Redondo Ramon , Al-Harthi Lena , Mamede João I.
Published: June 2024

Cerebral organoids (COs) are a valuable tool to study the intricate interplay between glial cells and neurons in brain development and disease, including HIV-associated neuroinflammation. We developed a novel approach to generate microglia containing COs (CO-iMs) by co-culturing hematopoietic progenitors and induced pluripotent stem cells. This approach allowed for the differentiation of microglia within the organoids concomitantly to the neuronal progenitors. CO- iMs exhibited higher efficiency in generation of CD45+/CD11b+/Iba-1+microglia cells compared to conventional COs with physiologically relevant proportion of microglia (∼7%). CO-iMs exhibited substantially higher expression of microglial homeostatic and sensome markers as well as markers for the complement cascade. CO-iMs showed susceptibility to HIV infection resulting in a significant increase in several pro-inflammatory cytokines/chemokines and compromised neuronal function, which were abrogated by addition of antiretrovirals. Thus, CO-iM is a robust model to decipher neuropathogenesis, neurological disorders, and viral infections of brain cells in a 3D culture system.
Wide-scale Geographical Analysis of Genetic Ancestry in the South African Coloured Population
Authors: Lankheet Imke , Hammarén Rickard , Caballero Lucía Ximena Alva , Larena Maximilian , Malmström Helena , Jolly Cecile , Soodyall Himla , de Jongh Michael , Schlebusch Carina
Published: June 2024

The South African Coloured (SAC) population, a prominent admixed population in South Africa, reflects centuries of migration, admixture, and historical segregation. Descendants of local Khoe-San and Bantu-speaking populations, European settlers, and enslaved individuals from Africa and Asia, SAC individuals embody diverse ancestries. This study investigates the genetic makeup of SAC individuals, utilizing autosomal genotypes, mitochondrial DNA and Y-chromosome data. We analyze new genotype data for 125 SAC individuals from seven locations. Our analysis, based on a dataset comprising 356 SAC individuals from 22 geographic locations, revealed significant regional variations in ancestry. Khoe-San ancestry predominates in 14 locations, highlighting its lasting influence. Inland regions exhibit higher proportions of Khoe-San ancestry, eastern regions show more Bantu-speaker/West African ancestry, and western/coastal areas, particularly around Cape Town, display increased Asian ancestry. These patterns reflect historical migrations and settlement patterns. Additionally, sex-biased admixture ratios show male-biased admixture from East Africans and Europeans, and female-biased admixture from Khoe-San populations, which is supported by mitochondrial and Y-chromosome data. This research underscores the importance of studying the SAC population to understand South Africa’s historical migrations, providing insights into the complex genetic heritage of South Africans.
A sensorimotor-association axis of thalamocortical connection development
Authors: Sydnor Valerie J. , Bagautdinova Joëlle , Larsen Bart , Arcaro Michael J. , Barch Deanna M. , Bassett Dani S. , Alexander-Bloch Aaron F. , Cook Philip A. , Covitz Sydney , Franco Alexandre R. , Gur Raquel E. , Gur Ruben C. , Mackey Allyson P. , Mehta Kahini , Meisler Steven L. , Milham Michael P. , Moore Tyler M. , Müller Eli J. , Roalf David R. , Salo Taylor , Schubiner Gabriel , Seidlitz Jakob , Shinohara Russell T. , Shine James M. , Yeh Fang-Cheng , Cieslak Matthew , Satterthwaite Theodore D.
Published: June 2024

Human cortical development follows a sensorimotor-to-association sequence during childhood and adolescence1–6. The brain’s capacity to enact this sequence over decades indicates that it relies on intrinsic mechanisms to regulate inter-regional differences in the timing of cortical maturation, yet regulators of human developmental chronology are not well understood. Given evidence from animal models that thalamic axons modulate windows of cortical plasticity7–12, here we evaluate the overarching hypothesis that structural connections between the thalamus and cortex help to coordinate cortical maturational heterochronicity during youth. We first introduce, cortically annotate, and anatomically validate a new atlas of human thalamocortical connections using diffusion tractography. By applying this atlas to three independent youth datasets (ages 8-23 years; totalN= 2,676), we reproducibly demonstrate that thalamocortical connections develop along a maturational gradient that aligns with the cortex’s sensorimotor-association axis. Associative cortical regions with thalamic connections that take longest to mature exhibit protracted expression of neurochemical, structural, and functional markers indicative of higher circuit plasticity as well as heightened environmental sensitivity. This work highlights a central role for the thalamus in the orchestration of hierarchically organized and environmentally sensitive windows of cortical developmental malleability.
Has AlphaFold 3 reached its success for RNAs?
Authors: Bernard Clément , Postic Guillaume , Ghannay Sahar , Tahi Fariza
Published: June 2024

Predicting the 3D structure of RNA is a significant challenge despite ongoing advancements in the field. Although AlphaFold has successfully addressed this problem for proteins, RNA structure prediction raises difficulties due to fundamental differences between proteins and RNAs, which hinder direct adaptation. The latest release of AlphaFold, AlphaFold 3, has broadened its scope to include multiple different molecules like DNA, ligands and RNA. While the article discusses the results of the last CASP-RNA dataset, the scope of performances and the limitations for RNAs are unclear. In this article, we provide a comprehensive analysis of the performances of AlphaFold 3 in the prediction of RNA 3D structures. Through an extensive benchmark over five different test sets, we discuss the performances and limitations of AlphaFold 3. We also compare its performances with ten existing state-of-the-artab initio, template-based and deep-learning approaches. Our results are freely available on the EvryRNA platform:https://evryrna.ibisc.univ-evry.fr/evryrna/alphafold3/.
Electrophysiology and Morphology of Human Cortical Supragranular Pyramidal Cells in a Wide Age Range
Authors: Barzó Pál , Szöts Ildikó , Tóth Martin , Csajbók Éva Adrienn , Molnár Gábor , Tamás Gábor
Published: June 2024

The basic excitatory neurons of the cerebral cortex, the pyramidal cells, are the most important signal integrators for the local circuit. They have quite characteristic morphological and electrophysiological properties that are known to be largely constant with age in the young and adult cortex. However, the brain undergoes several dynamic changes throughout life, such as in the phases of early development and cognitive decline in the aging brain. We set out to search for intrinsic cellular changes in supragranular pyramidal cells across a broad age range: from birth to 85 years of age and we found differences in several biophysical properties between defined age groups. During the first year of life, subthreshold and suprathreshold electrophysiological properties changed in a way that shows that pyramidal cells become less excitable with maturation, but also become temporarily more precise. According to our findings, the morphological features of the three-dimensional reconstructions from different life stages showed consistent morphological properties and systematic dendritic spine analysis of an infantile and an old pyramidal cell showed clear significant differences in the distribution of spine shapes. Overall, the changes that occur during development and aging may have lasting effects on the properties of pyramidal cells in the cerebral cortex. Understanding these changes is important to unravel the complex mechanisms underlying brain development, cognition and age-related neurodegenerative diseases.
A neural alternative splicing program controls cellular function and growth in Pancreatic Neuroendocrine tumours
Authors: Potiri M. , Moschou C. , Erpapazoglou Z , Rouni G. , Kotsoni A. , Andreadou M. , Dragolia M. , Ntafis V. , Schrader J. , Juan-Mateu J. , Kostourou V. , Dedos S.G. , Rogalska M.E. , Kafasla P.
Published: June 2024

Pancreatic neuroendocrine tumours (PanNETs) are a rare heterogeneous group of neoplasms that arise from pancreatic islet cells. The hormone secreting function of pancreatic neuroendocrine cells is altered in PanNETs, rendering these tumours functional or non— functional (secreting excessive or lower levels of hormones, respectively). Genome wide approaches have revealed the genomic landscape of PanNETs but have not shed light on this problematic hormone secretion. In the present work, we show that alternative splicing (AS) deregulation is responsible for changes in the secretory ability of PanNET cells. We reveal a group of alternative microexons that are regulated by the RNA binding protein SRRM3 and are preferentially included in mRNAs in PanNET cells, where SRRM3 is also upregulated. These microexons are part of a larger neural program regulated by SRRM3. We show that their inclusion gives rise to protein isoforms that change stimulus-induced secretory vesicles and their trafficking in PanNET cells. Moreover, the increased inclusion of these microexons results in an enhanced neuronal component in PanNET tumours. Using knock-down and splicing switching oligonucleotides in cellular and animal PanNET models, we show that decrease of the SRRM3 levels or even of the inclusion levels of the three most deregulated microexons can significantly alter the PanNET cell characteristics. Collectively, our study links secretory impairment and nerve dependency to alternative splicing deregulation in PanNETs, providing promising therapeutic targets for PanNET treatment.
Evolution of Omicron lineage towards increased fitness in the upper respiratory tract in the absence of severe lung pathology
Authors: Wickenhagen Arthur , Flagg Meaghan , Port Julia , Yinda Claude Kwe , Goldin Kerry , Gallogly Shane , Schulz Jonathan E , Lutterman Tessa , Williamson Brandi , Kaiser Franziska , Mukesh Reshma , Van Tol Sarah , Smith Brian , van Doremalen Neeltje , Russell Colin , de Wit Emmie , Munster Vincent
Published: June 2024

The emergence of the Omicron lineage represented a major genetic drift in SARS-CoV-2 evolution. This was associated with phenotypic changes including evasion of pre-existing immunity and decreased disease severity. Continuous evolution within the Omicron lineage raised concerns of potential increased transmissibility and/or disease severity. To address this, we evaluated the fitness and pathogenesis of contemporary Omicron variants XBB.1.5, XBB.1.16, EG.5.1, and JN.1 in the upper (URT) and lower respiratory tract (LRT). We compared in vivo infection in Syrian hamsters with infection in primary human nasal and lung epithelium cells and assessed differences in transmissibility, antigenicity, and innate immune activation. Omicron variants replicated efficiently in the URT but displayed limited pathology in the lungs compared to previous variants and failed to replicate in human lung organoids. JN.1 was attenuated in both URT and LRT compared to other Omicron variants and failed to transmit in the hamster model. Our data demonstrate that Omicron lineage evolution has favored increased fitness in the URT.
Centrosomes act as organizing centers to promote Polo kinase-mediated adaptation to persistent DNA damage
Authors: Langlois-Lemay Laurence , D’Amours Damien
Published: June 2024

The ability of cells to overcome cell cycle arrest and adapt to the presence of unrepairable DNA damage is under the control of polo-like kinases (PLKs) in eukaryotes. How DNA damage checkpoints are silenced or bypassed during the adaptation response is unknown, but the process requires enrichment of the Cdc5 PLK to microtubule organizing centers (MTOCs), such as the yeast centrosomes or spindle pole bodies (SPBs). Here we found that SPBs play an active role as supramolecular organizing centers that coordinate Cdc5 recruitment and signaling to downstream effectors during the adaptation response to DNA damage. We show that SPB components Nud1, Spc110, and Spc72 are key effectors of Cdc5 recruitment to SPB in the presence of sustained DNA damage. Following recruitment, Cdc5 transduces a phospho-signal to key structural subunits of the SPB, including Cnm67 and Mps3. We demonstrate these phosphorylation events are required to bypass cell cycle checkpoint arrest and enable effective adaptation to DNA damage. This response is specific because it cannot be recapitulated by a generic inactivation of MTOC activity. Collectively, our results indicate that centrosomes can act as supramolecular platforms to coordinate dynamic recruitment and substrate selection of PLKs during the DNA damage response.
A New Approach for Discovering Functional Links Connecting Non-Coding Regulatory Variants to Gene Targets
Authors: Farooq Hammad , Du Lin , Delafrouz Pourya , Jiang Wei , Chronis Constantinos , Liang Jie
Published: June 2024

Genome-wide association studies (GWAS) have linked thousands of genetic variants to various complex traits or diseases. However, most identified variants have weak individual effects, are correlated with nearby polymorphisms due to linkage disequilibrium (LD), and are located in non-coding cis-regulatory elements (CREs). These characteristics complicate the assessment of the direct impact of each variant on tissue specific gene expression and phenotype. To address this challenge, we have developed a novel algorithm that leverages polymer folding and 3D chromatin interactions to prioritize and identify putative causal variants and their target genes. From the millions of eQTL-Gene pairs identified by GTEx in human somatic tissues, we classify only ∼10-20% as putative functional eQTL-Gene pairs supported by phenotypic associations confirmed through CRISPR deletion experiments. Our findings show that unlike most variants, functional eQTL-Gene pairs predominantly reside within the same topologically associating domain (TAD) and have strong associations with cell-type specific cis-regulatory elements (CREs), enriched for binding sites of tissue-specific transcription factors. Unlike most approaches that rely on linear distance or other chromatin features (histone code, accessibility), our algorithm emphasizes the importance of physical interactions and 3D chromatin folding in gene regulation, as the identified eQTL-Gene pairs are all among the small fraction of physical chromatin interactions sufficient for chromatin locus folding. Overall, our algorithm reduces false positive associations between DNA variants and genes identified by eQTL analysis and uncovers novel variant-gene pair associations. These findings suggest a mechanism where a small number of regulatory variants control tissue specific gene expression via their physical association with target genes confined within the same TAD. Our approach provides new insights into the molecular mechanisms driving GWAS phenotypes.
Microglia target synaptic sites early during excitatory circuit disassembly in neurodegeneration
Authors: Yu Alfred , Tan Li Xuan , Lakkaraju Aparna , Santina Luca Della , Ou Yvonne
Published: June 2024

During development, microglia prune excess synapses to refine neuronal circuits. In neurodegeneration, the role of microglia-mediated synaptic pruning in circuit remodeling and dysfunction is important for developing therapies aimed at modulating microglial function. Here we analyzed the role of microglia in the synapse disassembly of degenerating postsynaptic neurons in the inner retina. After inducing transient intraocular pressure elevation to injure retinal ganglion cells, microglia increase in number, shift to ameboid morphology, and exhibit greater process movement. Furthermore, due to the greater number of microglia, there is increased colocalization of microglia with synaptic components throughout the inner plexiform layer and with excitatory synaptic sites along individual ganglion cell dendrites. Microglia depletion partially restores ganglion cell function, suggesting that microglia activation may be neurotoxic in early neurodegeneration. Our results demonstrate the important role of microglia in synapse disassembly in degenerating circuits, highlighting their recruitment to synaptic sites early after neuronal injury.

Highlights

Early after transient intraocular pressure elevation:

Microglia increase in number, complexity, and process movement

Microglia-synaptic contacts increase in the inner plexiform layer

Microglia-synaptic contacts increase on retinal ganglion cell dendrites

Microglia depletion partially restores ganglion cell function
Unveiling stem cell induction mechanisms from spatiotemporal cell-type-specific gene regulatory networks in postembryonic root organogensis
Authors: Cabrera Javier , Sanchez-Corrionero Álvaro , de Luis Balaguer Angels , Serrano-Ron Laura , del Barrio Cristina , Cubas Pilar , Perez-Garcia Pablo , Sozzani Rosangela , Moreno-Risueno Miguel
Published: June 2024

Plants grow continuously by developing new organs, a complex process that requires the formation of specific and functional tissue patterns. Tap root systems, as observed inArabidopsis thaliana, undergo lateral root formation, a developmental mechanism that necessitates the establishment of stem cell lineages. However, the underlying mechanisms remain poorly understood. We have reconstructed a spatiotemporal cell-type-specific transcriptional map of early lateral root organogenesis in Arabidopsis, profiling single and double fluorescent markers across 8 different cell types in the root stem cell lineage. Employing dynamic Bayesian network inference, based on time-course experiments and developmental time, alongside tree-based methods, we investigated lineage developmental progression and precursor stem-cell specification. Our results reveal a morphogenic cascade of hierarchical interdependent transcription factors driving stem cell initiation, and identify the QC/Endodermis transitioning cells as root stem cell progenitors. The associated formative program involves a profound transcriptomic re-arrangement, which, remarkably, precedes the activation of known stem-cell transcriptional signatures. Our data support a model in which root-stem-cell networks do not initiate stem formation, although various stem cell regulators are involved. Collectively, our study identifies core transcriptional signatures associated with stem cell induction and elucidates the dynamic regulatory mechanism driving early stem cell lineage establishment.
Statistical description of mobile oscillators in embryonic pattern formation
Authors: Uriu Koichiro , Morelli Luis G.
Published: June 2024

Synchronization of mobile oscillators occurs in numerous contexts, including physical, chemical, biological and engineered systems. In vertebrate embryonic development, a segmental body structure is generated by a population of mobile oscillators. Cells in this population produce autonomous gene expression rhythms, and interact with their neighbors through local signaling. These cells form an extended tissue where frequency and cell mobility gradients coexist. Gene expression kinematic waves travel through this tissue and pattern the segment boundaries. It has been shown that oscillator mobility promotes global synchronization. However, in vertebrate segment formation, mobility may also introduce local fluctuations in kinematic waves and impair segment boundaries. Here we derive a general framework for mobile oscillators that relates local mobility fluctuations to synchronization dynamics and pattern robustness. We formulate a statistical description of mobile phase oscillators in terms of a probability density. We obtain and solve diffusion equations for the average phase and variance, revealing the relationship between local fluctuations and global synchronization in a homogeneous population of oscillators. Analysis of the probability density for large mobility identifies a mean-field transition, where locally coupled oscillators start behaving as if each oscillator was coupled with all the others. We extend the statistical description to inhomogeneous systems to address the gradients present in the vertebrate segmenting tissue. The theory relates pattern stability to mobility, coupling and pattern wavelength. The general approach of the statistical description may be applied to mobile oscillators in other contexts, as well as to other patterning systems where mobility is present.
Flow-Mediated Modulation of the Endothelial Cell Lipidome
Authors: Hong Soon-Gook , Kennelly John P. , Williams Kevin J. , Bensinger Steve J. , Mack Julia J.
Published: June 2024

The luminal surface of the endothelium is exposed to dynamic blood flow patterns that are known to affect endothelial cell phenotype. While many studies have documented the phenotypic changes by gene or protein expression, less is known about the role of blood flow pattern on the endothelial cell (EC) lipidome. In this study, shotgun lipidomics was conducted on human aortic ECs (HAECs) exposed to unidirectional laminar flow (UF), disturbed flow (DF), or static conditions for 48 hrs. A total of 520 individual lipid species from 17 lipid subclasses were detected. Total lipid abundance was significantly increased for HAECs exposed to DF compared to UF conditions. Despite the increase in the total lipid abundance, HAECs maintained equivalent composition of each lipid subclass (% of total lipid) under both DF and UF. However, by lipid composition (% of total subclass), 28 lipid species were significantly altered between DF and UF. Complimentary RNA sequencing of HAECs exposed to UF or DF revealed changes in transcripts involved in lipid metabolism. Shotgun lipidomics was also performed on HAECs exposed to pro-inflammatory agonists lipopolysaccharide (LPS) or Pam3CSK4 (Pam3) for 48 hrs. Exposure to LPS or Pam3 reshaped the EC lipidome in both unique and overlapping ways. In conclusion, exposure to flow alters the EC lipidome and ECs undergo stimulus-specific lipid reprogramming in response to pro-inflammatory agonist exposure. Ultimately, this work provides a resource to profile the transcriptional and lipidomic changes that occur in response to applied flow that can be accessed by the vascular biology community to further dissect and extend our understanding of endothelial lipid biology.
ANTIMICROBIAL ACTIVITY OF CLOVE EXTRACTS AGAINST MICROORGANISMS ISOLATED FROM VAGINAL DISCHARGE
Authors: Omoniyi Aishat Taiye , Yaqub Muneer
Published: June 2024

Infections of the genitourinary and reproductive tracts pose significant health concerns for women, particularly those of reproductive age. These infections often manifest as vaginal discharge and can be caused by a variety of microorganisms, including pathogenic bacteria and fungi. Traditional antibiotic treatments are increasingly challenged by the rise of antibiotic-resistant strains, underscoring the need for alternative therapies. This study aimed to isolate and identify microorganisms from vaginal swab samples and evaluate the antimicrobial efficacy of clove (Eugenia caryophyllata) extracts against these isolates. Using CLED agar, nutrient agar, and Sabouraud dextrose agar, a diverse range of bacterial and fungal flora were isolated from eight vaginal swab samples. The primary bacterial isolates included Proteus mirabilis, Escherichia coli, Staphylococcus aureus, and Lactobacillus spp., while Candida albicans was the main fungal isolate. Biochemical tests confirmed the identity of these microorganisms. The study found that ethanol clove extract exhibited significant antimicrobial activity, particularly against Staphylococcus aureus and Candida albicans, with the minimum inhibitory concentration (MIC) values being 20 mg/ml and 10 mg/ml, respectively. Additionally, ciprofloxacin, used as a control antibiotic, showed maximum inhibition against Lactobacillus spp., highlighting a potential risk for disrupting beneficial vaginal flora when using conventional antibiotics. The findings suggest that ethanol clove extract could serve as an effective alternative antimicrobial agent, reducing the risk of antibiotic resistance and preserving the balance of the vaginal microbiome. This research emphasizes the importance of exploring plant-based antimicrobial agents as viable alternatives to traditional antibiotics. The significant antimicrobial properties of clove extract against common vaginal pathogens offer promising implications for future therapeutic applications in managing vaginal infections.
Expanding salivary biomarker detection by creating a synthetic neuraminic acid sensor via chimeragenesis
Authors: Verzino Samuel J. , Priyev Sharona A. , Estrada Valeria A. Sánchez , Crowley Gemma X. , Rutkowski Alexandra , Lam Amelia C. , Nazginov Elizabeth S. , Kotemelo Paola , Bacelo Agustina , Sukhram Desiree T. , Vázquez Frank X. , Juárez Javier F.
Published: June 2024

Accurate and timely diagnosis of oral squamous cell carcinoma (OSCC) is crucial in preventing its progression to advanced stages with a poor prognosis. As such, the construction of sensors capable of detecting previously established disease biomarkers for the early and non-invasive diagnosis of this and many other conditions has enormous therapeutic potential. In this work, we apply synthetic biology techniques for the development of a whole-cell biosensor (WCB) that leverages the physiology of engineered bacteriain vivoto promote the expression of an observable effector upon detection of a soluble molecule. To this end, we have constructed a bacterial strain expressing a novel chimeric transcription factor (Sphnx) for the detection of N-acetylneuraminic acid (Neu5Ac), a salivary biomolecule correlated with the onset of OSCC. This WCB serves as the proof-of-concept of a platform that can eventually be applied to clinical screening panels for a multitude of oral and systemic medical conditions whose biomarkers are present in saliva.
Network connectivity differences in music listening among older adults following a music-based intervention
Authors: Faber Sarah , Belden Alexander , McIntosh Randy , Loui Psyche
Published: June 2024

Music-based interventions are a common feature in long-term care with clinical reports highlighting music’s ability to engage individuals with complex diagnoses. While these findings are promising, normative findings from healthy controls are needed to disambiguate treatment effects unique to pathology and those seen in healthy aging. The present study examines brain network dynamics during music listening in a sample of healthy older adults before and after a music-based intervention. We found intervention effects from hidden Markov model-estimated fMRI network data. Following the intervention, participants demonstrated greater occupancy (the amount of time a network was occupied) in a temporal-mesolimbic network. We conclude that network dynamics in healthy older adults are sensitive to music-based interventions. We discuss these findings’ implications for future studies with individuals with neurodegeneration.
Inverse Reinforcement Learning to Study Motivation in Mouse Behavioral Paradigms
Authors: Telfer Andre , Shamsabadi Afsoon Alidadi , Savin George , Wen Junfeng , Abizaid Alfonso
Published: June 2024

Motivation describes the underlying goals that drive animal and agent behavior. In Neuroscience, behavioral paradigms are used to quantify the motivations of mice and used to gain insights into traits and diseases which can be translated to humans. In recent years, Computer Vision models are becoming widely adopted by Neuroscientists to score mouse behavior associated with motivations such as hunger and anxiety. However, a single motivation can be expressed by multiple different behaviors, and a single behavior can be linked to multiple motivations. Therefore the ideal analysis of motivational paradigms would attempt to directly recover the underlying motivations guiding behavior, rather than indirectly score their associated behaviors. In this paper, we move towards this goal by applying Inverse Reinforcement Learning to study the underlying motivations that drive mouse behavior.
Physiological Evaluation of Far Infrared-Emitting Garments on Sleep and Thermoregulation
Authors: Nishida Masaki , Nishii Taku , Suyama Shutaro , Youn Sumi , Funayama Kenta
Published: June 2024

Garments engineered to emit far-infrared (FIR) spectral frequencies have potential conditioning benefits. This study aimed to explore the physiological effects of FIR-emitting clothes on sleep propensities involving thermoregulation and autonomic nervous function. In this double-blind, randomized, placebo-controlled, crossover study, fifteen healthy male participants (age 21.6 ± 1.5 years, body mass index 23.1 ± 1.9, Pittsburgh Sleep Quality Index 5.0 ± 2.0) wore a whole-body FIR garment (wavelength: 5–20 μm at 40°C), while a total body garment with the 100% polyester fiber without ceramic components was used as control for the intervention. To compare the physiological variables between the two electroencephalograms, the tympanic membrane temperature, sweating rate, skin temperature, and humidity were measured during sleep. Heart rate variability during sleep was also calculated. The percentage of rapid eye movement (REM) sleep was significantly higher in the FIR compared than in control (p= 0.027). We found a significant main effect of tympanic membrane temperature in time, equivalent to core body temperature. (2-way ANOVA; (F(26, 234)=4.046,p<0.001). Furthermore, the sweating rate was significantly lower when sleeping with FIR predominantly in the final phase of sleep (garment × time interaction (F(26,572)=55.05,p<0.001). Although there were no significant differences in skin surface temperature between the two garments, FIR provided significantly lower skin humidity during the middle of night sleep compared with the control. Regarding LF, a significant garment type x time interaction (F(1.87, 48.57)=3.36,p=0.046). Post-hoc analysis revealed that the LF value of FIR was higher in the final phase of sleep than that of control (p=0.027). Then present results suggest that sleeping with FIR in comparison to with control, has a beneficial effect to facilitate restorative sleep, presumably involving proper thermoregulation.
Maternal total sleep deprivation causes oxidative stress and mitochondrial dysfunction in oocytes associated with fertility decline in mice
Authors: Yi Zi-Yun , Liang Qiu-Xia , Zhou Qian , Yang Lin , Meng Qing-Ren , Li Jian , Lin Yi-hua , Cao Yan-pei , Zhang Chun-Hui , Schatten Heide , Qiao Jie , Sun Qing-Yuan
Published: June 2024

Previous studies have shown sleep deprivation has an impact on several aspects of health and disease. Sleep deprivation suppresses melatonin production and excessive HPA activation in women, which may reduce the chances of fertility. However, little is known about how and by what relevant mechanisms it affects female fertility. In this study, female mice underwent 72 hours of total sleep deprivation (TSD) caused by rotating wheel or 2 different controls: a stationary wheel, or forced movement at night. Even though, there was no evident anomaly of natural ovulation, the TSD female mice showed impaired early embryo development . Overall levels of estrogen and FSH were lower throughout the estrus cycle (especially in proestrus). RNA Sequencing (RNA-Seq) was used to discover differentially expressed genes (DEGs) that might be involved in oocyte quality after TSD. A total of 42 genes showed significant differential expression in GV oocytes after TSD. These included genes such asUsmg5, Atp5k, Ccnd2andTpm3, which were enriched in gene ontology terms of mitochondrial protein complex, oxidoreductase activity, cell division, cell cycle G1/S phase transition, as well as others. The increased concentrations of reactive oxygen species (ROS) in germinal vesicle (GV) and metaphase II (MII) oocytes from TSD mice were observed, which might be induced by impaired mitochondrial function caused by TSD. The GV oocytes displayed increased mitochondrial DNA (mtDNA) copy number and a significant transient increase in inner mitochondrial membrane potential (△ψm) from the TSD mice probably due to compensatory effect. In contrast, MII oocytes in the TSD group showed a decrease in the mtDNA copy number and a lower △ ψm compared with the controls. Furthermore, abnormal distribution of mitochondria in the GV and MII oocytes was also observed in TSD mice, suggesting mitochondrial dysfunction. In addition, abnormal spindle and abnormal arrangement of chromosomes in MII oocytes were markedly increased in the TSD mice compared with the control mice. In conclusion, our results suggest that TSD significantly alters the oocyte transcriptome, contributing to oxidative stress and disrupted mitochondrial function, which then resulted in oocyte defects and impaired early embryo development in female mice.
Occurrence, risk assessment of antibiotics and antimicrobial resistance inEscherichia coliin typical rivers of Sichuan
Authors: Sha Jingzhou , Wu Minghao , Zhou Yaliang , Chen Tao , Liu Haisha , Zhang Jingjing , Luo Wan , Huang Yi , Liu Yinshan , Wang Baoming , Song Tao , Lin Jiafu
Published: June 2024

Worldwide interest has been generated by the presence and distribution of antibiotics and antibiotic resistance genes (ARGs) in rivers. However, there was a dearth of research on the contamination of Sichuan province’s typical rivers with antibiotics. In this study, the residual level of antibiotics in 42 national/provincial sites of 9 rivers was analyzed by UPLC-MS/MS, the ecological risk level was evaluated using risk assessment method, and the drug resistance ofE. coliin water was evaluated by Kirby-Bauer method. Redundancy analysis demonstrated how residual antibiotics affect the structure of the microbial community in the Minjiang River basin (RDA). Nine rivers all contained antibiotics. Among them, the MinJiang, TuoJiang, and JiaLingJiang rivers were severely contaminated with antibiotic concentrations ranging from 0.29 to 2233.71 ng/L. The Sichuan Basin’s antibiotic pollution level was significantly higher when compared to other Sichuan zones, which was consistent with the region’s high population density. Additionally, it was discovered that 9.77% of theE. coliisolated from 9 rivers had antibiotic resistance, and more than 5.8% of them had multidrug resistance. Moreover, Norfloxacin, amoxicillin, ampicillin, and tetracycline were the main risk factors for high ecological risk in 26 of the 42 monitoring sites. Additionally, there is a strong correlation between the microbial community change and residual antibiotic. These results offered some reference information regarding the distribution of antibiotics and ARGs in typical rivers in the Chinese province of Sichuan, and this study showed that more attention needs to be paid to antibiotic pollution in Sichuan’s typical rivers.