Communication Pathways Research Articles

Gut Microbiota and Autism Spectrum Disorder: A Neuroinflammatory Mediated Mechanism of Pathogenesis?

Autism spectrum disorder (ASD) is a neurodevelopmental disorder characterized by impairments in social communication and behavior, frequently accompanied by restricted and repetitive patterns of interests or activities. The gut microbiota has been implicated in the etiology of ASD due to its impact on the bidirectional communication pathway known as the gut-brain axis. However, the precise involvement of the gut microbiota in the causation of ASD is unclear. This study critically examines recent evidence to rationalize a probable mechanism in which gut microbiota symbiosis can induce neuroinflammation through intermediator cytokines and metabolites. To develop ASD, loss of the integrity of the intestinal barrier, activation of microglia, and dysregulation of neurotransmitters are caused by neural inflammatory factors. It has emphasized the potential role of neuroinflammatory intermediates linked to gut microbiota alterations in individuals with ASD. Specifically, cytokines like brain-derived neurotrophic factor, calprotectin, eotaxin, and some metabolites and microRNAs have been considered etiological biomarkers. We have also overviewed how probiotic trials may be used as a therapeutic strategy in ASD to reestablish a healthy balance in the gut microbiota. Evidence indicates neuroinflammation induced by dysregulated gut microbiota in ASD, yet there is little clarity based on analysis of the circulating immune profile. It deems the repair of microbiota load would lower inflammatory chaos in the GI tract, correct neuroinflammatory mediators, and modulate the neurotransmitters to attenuate autism. The interaction between the gut and the brain, along with alterations in microbiota and neuroinflammatory biomarkers, serves as a foundational background for understanding the etiology, diagnosis, prognosis, and treatment of autism spectrum disorder.

GPCR Signaling: A Study of the Interplay Between Structure, Energy, and Function.

G protein-coupled receptors (GPCRs) exemplify sophisticated allosteric communication, transducing extracellular signals through ligand-induced structural rearrangements that resonate through the molecular scaffold. Despite extensive study, the biophysical underpinnings of how conformational changes spread remain unclear. This work employs a novel physics-based framework to characterize the role of energy dissipation in directing intramolecular signaling pathways. By modeling each residue as a network of coupled oscillators, we generate a localization landscape depicting the vibrational energy distribution throughout the protein scaffold. Quantifying directional energy flux between residues reveals distinct pathways for energy and information transfer, illuminating sequences of allosteric communication. Our analysis of CB1 and CCR5 crystal structures unveils an anisotropic pattern of energy dissipation aligning with key functional dynamics, such as activation-related conformational changes. These anisotropic patterns of vibrational energy flow constitute pre-configured channels for allosteric signaling. Elucidating the relationship between structural topology and energy dissipation patterns provides key insights into the thermodynamic drivers of conformational signaling. This methodology significantly advances our mechanistic understanding of allostery in GPCRs and presents a broadly applicable approach for rationally dissecting allosteric communication pathways, with potential implications for structure-based drug design targeting these critical receptors.

Exosomal MicroRNAs modulate the cognitive function in fasudil treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice model of Alzheimer’s disease

Alzheimer’s disease (AD) is characterized by cognitive decline stemming from the accumulation of beta-amyloid (Aβ) plaques and the propagation of tau pathology through synapses. Exosomes, crucial mediators in neuronal development, maintenance, and intercellular communication, have gained attention in AD research. Yet, the molecular mechanisms involving exosomal miRNAs in AD remain elusive. In this study, we treated APPswe/PSEN1dE9 transgenic (APP/PS1) mice, a model for AD, with either vehicle (ADNS) or fasudil (ADF), while C57BL/6 (control) mice received vehicle (WT). Cognitive function was evaluated using the Y-maze test, and AD pathology was confirmed through immunostaining and western blot analysis of Aβ plaques and phosphorylated tau. Exosomal RNAs were extracted, sequenced, and analyzed from each mouse group. Our findings revealed that fasudil treatment improved cognitive function in AD mice, as evidenced by increased spontaneous alternation in the Y-maze test and reduced Aβ plaque load and phosphorylated tau protein expression in the hippocampus. Analysis of exosomal miRNAs identified three miRNAs (mmu-let-7i-5p, mmu-miR-19a-3p, mmu-miR-451a) common to both ADNS vs ADF and WT vs ADNS groups. Utilizing miRTarBase software, we predicted and analyzed target genes associated with these miRNAs. Gene ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis of miRNA target genes indicated that mmu-miR-19a-3p and mmu-miR-451a are implicated in signal transduction, immune response, cellular communication, and nervous system pathways. Specifically, mmu-miR-19a-3p targeted genes involved in the sphingolipid signaling pathway, such as Pten and Tnf, while mmu-miR-451a targeted Nsmaf, Gnai3, and Akt3. Moreover, mmu-miR-451a targeted Myc in signaling pathways regulating the pluripotency of stem cells. In conclusion, fasudil treatment enhanced cognitive function by modulating exosomal MicroRNAs, particularly mmu-miR-451a and mmu-miR-19a-3p. These miRNAs hold promise as potential biomarkers and therapeutic targets for novel AD treatments.Graphical

Development of a tibial intraneural ganglion cyst after surgery on a peroneal intraneural ganglion in a pediatric patient: further support for the articular origin of intraneural ganglion cysts. Illustrative case.

The articular origin of intraneural cysts has been previously described and well supported. Intraneural ganglion cysts most commonly occur in adults and in the common peroneal nerve arising from the anterior aspect of the superior tibiofibular joint (STFJ). The authors report a pediatric patient who developed a tibial intraneural cyst arising from the posterior aspect of the STFJ within months after surgical treatment of a peroneal intraneural cyst from the anterior aspect of the same joint. Surgery consisted of disconnecting the articular branch of the peroneal nerve and decompression of the cyst. Three-month postoperative magnetic resonance imaging showed resolution of the peroneal intraneural cyst and anterior compartment denervation but demonstrated a clinically occult small tibial intraneural ganglion cyst arising from the STFJ with popliteus muscle atrophy. This case underscores the importance of addressing the underlying etiology (articular synovitis) or the communication pathways (articular branches) whenever feasible to mitigate intraneural cyst recurrence. Furthermore, this report reinforces the validity of the articular theory. https://thejns.org/doi/10.3171/CASE24277.

Gamified Teaching Design and Practice for the Elderly within the Framework of Proactive Health

This paper adopts the DMC pyramid model as the theoretical foundation for gamification design. By considering the gaming capabilities of the elderly, a coherent game logic is developed. This logic serves as the basis for designing or adapting physical games tailored to the elderly, integrating health knowledge into the game content. The games are interconnected through a reward system, culminating in a comprehensive and actionable community health communication activity. This approach outlines a gamification-based pathway for elder-friendly health communication, ultimately enhancing health literacy and promoting proactive health among the elderly.

Communication between alveolar macrophages and fibroblasts via the TNFSF12-TNFRSF12A pathway promotes pulmonary fibrosis in severe COVID-19 patients

BackgroundSevere COVID-19 infection has been associated with the development of pulmonary fibrosis, a condition that significantly affects patient prognosis. Understanding the underlying cellular communication mechanisms contributing to this fibrotic process is crucial.ObjectiveIn this study, we aimed to investigate the role of the TNFSF12-TNFRSF12A pathway in mediating communication between alveolar macrophages and fibroblasts, and its implications for the development of pulmonary fibrosis in severe COVID-19 patients.MethodsWe conducted single-cell RNA sequencing (scRNA-seq) analysis using lung tissue samples from severe COVID-19 patients and healthy controls. The data was processed, analyzed, and cell types were annotated. We focused on the communication between alveolar macrophages and fibroblasts and identified key signaling pathways. In vitro experiments were performed to validate our findings, including the impact of TNFRSF12A silencing on fibrosis reversal.ResultsOur analysis revealed that in severe COVID-19 patients, alveolar macrophages communicate with fibroblasts primarily through the TNFSF12-TNFRSF12A pathway. This communication pathway promotes fibroblast proliferation and expression of fibrotic factors. Importantly, silencing TNFRSF12A effectively reversed the pro-proliferative and pro-fibrotic effects of alveolar macrophages.ConclusionThe TNFSF12-TNFRSF12A pathway plays a central role in alveolar macrophage-fibroblast communication and contributes to pulmonary fibrosis in severe COVID-19 patients. Silencing TNFRSF12A represents a potential therapeutic strategy for mitigating fibrosis in severe COVID-19 lung disease.

Alzheimer's disease genetic pathways impact cerebrospinal fluid biomarkers and imaging endophenotypes in non-demented individuals.

Unraveling how Alzheimer's disease (AD) genetic risk is related to neuropathological heterogeneity, and whether this occurs through specific biological pathways, is a key step toward precision medicine. We computed pathway-specific genetic risk scores (GRSs) in non-demented individuals and investigated how AD risk variants predict cerebrospinal fluid (CSF) and imaging biomarkers reflecting AD pathology, cardiovascular, white matter integrity, and brain connectivity. CSF amyloidbeta and phosphorylated tau were related to most GRSs. Inflammatory pathways were associated with cerebrovascular disease, whereas quantitative measures of white matter lesion and microstructure integrity were predicted by clearance and migration pathways. Functional connectivity alterations were related to genetic variants involved in signal transduction and synaptic communication. This study reveals distinct genetic risk profiles in association with specific pathophysiological aspects in predementia stages of AD, unraveling the biological substrates of the heterogeneity of AD-associated endophenotypes and promoting a step forward in disease understanding and development of personalized therapies. Polygenic risk for Alzheimer's disease encompasses six biological pathways that can be quantified with pathway-specific genetic risk scores, and differentially relate to cerebrospinal fluid and imaging biomarkers. Inflammatory pathways are mostly related to cerebrovascular burden. White matter health is associated with pathways of clearance and membrane integrity, whereas functional connectivity measures are related to signal transduction and synaptic communication pathways.

Stability of THAI in situ combustion process in reservoirs with layers of grading permeabilities and porosities: Detailed qualitative investigations

The world-wide reserves of heavy oil, tar sand, and bitumen, etc., outweigh those of conventional oil by a factor of 7/3. Given that the conventional reserves are being rapidly depleted, the need to develop and produce the unconventional resources has never been so critical. However, the proven most efficient and environmentally-friendly technology, namely the THAI process, still requires further study, and it has no documented design procedures that factor in the non-ideal geological features of heavy oil and bitumen reservoirs. Throughout the literature, there is little reported on the effects of gradations in reservoir petro-physical parameters on the performance of the THAI process. Consequently, this work reports the results of numerical simulations for four different kinds of reservoirs, each having progressive gradations in permeabilities and porosities. The major findings from this in depth study include.(i) In terms of the temperature distribution, regardless of the permeability and porosity gradations, the high temperature zone is always skewed towards the highest permeabilities and porosities zone. Furthermore, it is found that, in any model in which the shoes of the VI wells have no direct communication pathway with the highest permeabilities and porosities zones of the reservoirs, the high temperature zones occur in two chambers, otherwise, there is one high temperature zone.(ii) It is found that generally, the combustion front tends to be lopsided in favour of the most permeable and porous zone. In the case of a bottom-up progressive increase in permeabilities and porosities (model L1), the single combustion front has greatest advance horizontally at the top and axially in the middle of the reservoir, while in model L2 (the converse of model L1), the combustion fronts propagated in two chambers before the chambers overlapped in the toe region of the HP well where it advanced fastest. Therefore, the combustion zone in model L1 was far more stable than in model L2.(iii) It is found that the combustion fronts in model L3, with the lowest permeabilities and porosities at the centre in the longitudinal direction, propagated in two chambers that overlapped each other around the toe region of the HP well and advanced greatest in the HP well and on either lateral edge of the reservoir. In model L4, which has lateral gradation in permeabilities and porosities, however, the thinner edge of the wedge-shape combustion front had advanced fastest along the vertical mid-plane where the HP well was located. Thus, the combustion zone in model L3 was far more stable than that in model L4.(iv) It is found that in all the models except model L4, there exist rich oil saturation zones in the most permeable and porous regions located ahead of the mobile oil zone (MOZ) of each reservoir. These are formed due to restrictions in the pathways via which the mobilised oil can drain into the HP well. In model L4, the HP well is already in the most permeable zone and consequently, the fluids that favourably reach there are rapidly gravity-drained into the HP well.

Involvement of the gut microbiome-brain axis in alcohol use disorder.

The human intestine is colonized by a variety of microorganisms that influence the immune system, the metabolic response, and the nervous system, with consequences for brain function and behavior. Unbalance in this microbial ecosystem has been shown to be associated with psychiatric disorders, and altered gut microbiome composition related to bacteria, viruses, and fungi has been well established in patients with alcohol use disorder. This review describes the gut microbiome-brain communication pathways, including the ones related to the vagus nerve, the inflammatory cytokines, and the gut-derived metabolites. Finally, the potential benefits of microbiota-based therapies for the management of alcohol use disorder, such as probiotics, prebiotics, and fecal microbiota transplantation, are also discussed.

Empowering communication strategy for safe cyberspace: insights from trust-based quality information

Purpose The recent trends of managing how to achieve communication in a safe cyberspace have attracted the particular attention from scholars worldwide. The strategic initiative of having an active organization of communication pathways is required for further scholarly elaboration to enable a subsisting safe community in cyberspace. An example of the challenges is the issue of trust in information or questionable issues denoting lack of detail and clarity. Thus, this obviously refers to a dubious circumstance that needs to explain the situation on addressing the critical issue of trust-based quality information. To respond to such an apparent situation, this paper aims to critically explore the insightful value of trust in information as essential element of quality assurance. Such arranged strategy would enable individual capacity and accountability in achieving the efficient communication management for a safe cyberspace. Design/methodology/approach The study attempted a critical review of recent literature by analysing peer-reviewed articles from journals, books, proceedings and book chapters related to theme of communication management for safe cyberspace. Findings The finding reveals that the strategic approach of enabling effective communication management for safe cyberspace is actualized through advancing trust-based quality information. Originality/value This paper aims to contribute towards enhancing communication management for safe cyberspace by addressing issues relating to trust that would lead to the quality of information.

Respiratory diseases and gut microbiota: relevance, pathogenesis, and treatment.

Preclinical evidence has firmly established a bidirectional interaction among the lung, gut, and gut microbiome. There are many complex communication pathways between the lung and intestine, which affect each other's balance. Some metabolites produced by intestinal microorganisms, intestinal immune cells, and immune factors enter lung tissue through blood circulation and participate in lung immune function. Altered gut-lung-microbiome interactions have been identified in rodent models and humans of several lung diseases such as pulmonary fibrosis, chronic obstructive pulmonary disease, lung cancer, asthma, etc. Emerging evidence suggests that microbial therapies can prevent and treat respiratory diseases, but it is unclear whether this association is a simple correlation with the pathological mechanisms of the disease or the result of causation. In this review, we summarize the complex and critical link between the gut microbiota and the lung, as well as the influence and mechanism of the gut microbiota on respiratory diseases, and discuss the role of interventions such as prebiotics and fecal bacteria transplantation on respiratory diseases. To provide a reference for the rational design of large-scale clinical studies, the direct application of microbial therapy to respiratory-related diseases can reduce the incidence and severity of diseases and accompanying complications.

The Brain-Gut Axis, an Important Player in Alzheimer and Parkinson Disease: A Narrative Review.

Neurodegenerative diseases, such as Alzheimer's disease (AD) and Parkinson's disease (PD), are severe age-related disorders with complex and multifactorial causes. Recent research suggests a critical link between neurodegeneration and the gut microbiome, via the gut-brain communication pathway. This review examines the role of trimethylamine N-oxide (TMAO), a gut microbiota-derived metabolite, in the development of AD and PD, and investigates its interaction with microRNAs (miRNAs) along this bidirectional pathway. TMAO, which is produced from dietary metabolites like choline and carnitine, has been linked to increased neuroinflammation, protein misfolding, and cognitive decline. In AD, elevated TMAO levels are associated with amyloid-beta and tau pathologies, blood-brain barrier disruption, and neuronal death. TMAO can cross the blood-brain barrier and promote the aggregation of amyloid and tau proteins. Similarly, TMAO affects alpha-synuclein conformation and aggregation, a hallmark of PD. TMAO also activates pro-inflammatory pathways such as NF-kB signaling, exacerbating neuroinflammation further. Moreover, TMAO modulates the expression of various miRNAs that are involved in neurodegenerative processes. Thus, the gut microbiome-miRNA-brain axis represents a newly discovered mechanistic link between gut dysbiosis and neurodegeneration. MiRNAs regulate the key pathways involved in neuroinflammation, oxidative stress, and neuronal death, contributing to disease progression. As a direct consequence, specific miRNA signatures may serve as potential biomarkers for the early detection and monitoring of AD and PD progression. This review aims to elucidate the complex interrelationships between the gut microbiota, trimethylamine-N-oxide (TMAO), microRNAs (miRNAs), and the central nervous system, and the implications of these connections in neurodegenerative diseases. In this context, an overview of the current neuroradiology techniques available for studying neuroinflammation and of the animal models used to investigate these intricate pathologies will also be provided. In summary, a bulk of evidence supports the concept that modulating the gut-brain communication pathway through dietary changes, the manipulation of the microbiome, and/or miRNA-based therapies may offer novel approaches for implementing the treatment of debilitating neurological disorders.

A qualitative exploration of perceived challenges and opportunities in the implementation of injury prevention and management in amateur female sport.

Coaches, practitioners, and leadership in amateur female sport must navigate many obstacles in the pursuit of athlete availability and optimal performance. The present study aims to evaluate opportunities and challenges to both injury prevention and management in amateur female sport, as experienced by mixed-gender coaches, allied healthcare professionals, and general practitioners. Semi-structured virtual interviews of coaches, allied healthcare professionals, and general practitioners (N = 25), recruited via convenience snowball sample. Data transcribed verbatim with reflexive thematic analysis through a critical realism framework. Female-specific issues, education, and resource capital were challenges to the implementation of injury prevention and management in amateur female sport, thus negatively impacting on performance, prevention, and rehabilitation. Opportunities for improved care for female athletes were developing communication and relationships, outsourcing responsibility, and providing greater education, in response to desires for such, and lastly exposure to elite sport and national governing bodies' protocols. In amateur female sport, developing communication pathways and relationships, along with upskilling coaches, can help better support female athletes, coaches, and healthcare professionals. Leaders and stakeholders must advocate for and support greater education, resourcing, and an understanding of female-specific issues in amateur female sport. It is intended that these findings will provide evidence and opportunities for discourse between stakeholders in amateur female sport to improve standard of supports for female athletes, coaches, and healthcare professionals. These findings may also help practitioners better exploit opportunities and circumvent challenges to improve the welfare and performance of amateur female athletes.

Cross-national examination of facilitators and hindrances to the public acceptance of hydrogen refuelling facilities

Recognising the factors that shape the public acceptance of hydrogen refuelling facilities is essential for gaining social support for the widespread implementation of hydrogen infrastructure. This study applies a cross-national research perspective to investigate the public acceptance of hydrogen refuelling facilities using stated-preference survey data. Moreover, multidimensional explanatory variables encompassing hydrogen energy awareness levels, hydrogen refuelling station configurations, residential characteristics, car ownership and use, and sociodemographics are used to interpret public acceptance. The data revealed that 21.1 %, 45.5 %, and 31.5 % of the respondents in Japan, Spain, and Norway expressed support for such facilities near their residences, respectively. An important discovery was the validation of nonproportional odds in acceptance measurements across countries, which challenges the conventional assumptions of parallel regression and suggests that distinct behavioural determinants shape positive, negative, and neutral attitudes. Consequently, a generalised ordinal logistic regression approach was applied to identify the determinants of varying acceptance levels and mitigate the biases from nonproportional odds. In addition to identifying facilitators and hindrances, the results highlight several predictors with polarising effects. These findings provide public feedback for enhancing the planning of hydrogen infrastructure and offer potential pathways for hydrogen risk communication and policymaking.

Proteomics Analysis of Interactions between Drug-Resistant and Drug-Sensitive Cancer Cells: Comparative Studies of Monoculture and Coculture Cell Systems.

Cell-cell interactions, which allow cells to communicate with each other through molecules in their microenvironment, are critical for the growth, health, and functions of cells. Previous studies show that drug-resistant cells can interact with drug-sensitive cells to elevate their drug resistance level, which is partially responsible for cancer recurrence. Studying protein targets and pathways involved in cell-cell communication provides essential information for fundamental cell biology studies and therapeutics of human diseases. In the current studies, we performed direct coculture and indirect coculture of drug-resistant and drug-sensitive cell lines, aiming to investigate intracellular proteins responsible for cell communication. Comparative studies were carried out using monoculture cells. Shotgun bottom-up proteomics results indicate that the P53 signaling pathway has a strong association with drug resistance mechanisms, and multiple TP53-related proteins were upregulated in both direct and indirect coculture systems. In addition, cell-cell communication pathways, including the phagosome and the HIF-signaling pathway, contribute to both direct and indirect coculture systems. Consequently, AK3 and H3-3A proteins were identified as potential targets for cell-cell interactions that are relevant to drug resistance mechanisms. We propose that the P53 signaling pathway, in which mitochondrial proteins play an important role, is responsible for inducing drug resistance through communication between drug-resistant and drug-sensitive cancer cells.

Trigeminal ganglion neurons are directly activated by influx of CSF solutes in a migraine model.

Classical migraine patients experience aura, which is transient neurological deficits associated with cortical spreading depression (CSD), preceding headache attacks. It is not currently understood how a pathological event in cortex can affect peripheral sensory neurons. In this study, we show that cerebrospinal fluid (CSF) flows into the trigeminal ganglion, establishing nonsynaptic signaling between brain and trigeminal cells. After CSD, ~11% of the CSF proteome is altered, with up-regulation of proteins that directly activate receptors in the trigeminal ganglion. CSF collected from animals exposed to CSD activates trigeminal neurons in naïve mice in part by CSF-borne calcitonin gene-related peptide (CGRP). We identify a communication pathway between the central and peripheral nervous system that might explain the relationship between migrainous aura and headache.

Gene Expression Level and Immunohistochemical Localization of Cannabinoid and Cannabinoid-Related Receptors in The Small Intestine of Holstein Bulls (Bos Taurus Taurus)

Abstract The gastrointestinal tract plays a crucial role in nutrient absorption, secretion, and motility, ensuring proper digestion and overall homeostasis. Regulation of this complex system involves the coordination of various communication pathways, including neural and humoral mechanisms. One such mechanism is the endocannabinoid system (ECS), a signaling network comprising endogenous cannabinoids, receptors, and enzymes involved in the regulation of physiological processes in mammals and non-mammalian species. While extensive research has been conducted on the ECS in monogastric animals, limited information is available on its presence and distribution in cattle. This study aimed to investigate the distribution and localization patterns of cannabinoid receptors type 1 (CB1R) and type 2 (CB2R) and transient receptor potential vanilloid type 1 (TRPV1) in the bovine small intestine. The study included immunohistochemical analysis of intestinal tissue samples from Polish Holstein-Friesian breed bulls. Gene expression levels of CNR1, CNR2, and TRPV1 genes, encoding CB1R, CB2R, and TRPV1, respectively, were quantified using qPCR analysis. The results showed that all three receptors were expressed in the bovine small intestine, with TRPV1 exhibiting a significant upregulation in the jejunum compared to the duodenum and ileum. Immunoreactivity for CB1R and CB2R was predominantly observed in neurons of the enteric plexuses, while TRPV1 immunolabeling was detected in both enteric neurons and duodenal Brunner’s glands. These findings may establish an anatomical foundation for further investigations, lending support to the potential therapeutic efficacy of cannabinoid receptor agonists in alleviating gastrointestinal motility disorders associated with bovine enteropathies and optimizing milk production in dairy cattle.

Application of Artificial Intelligence in Higher Education: A Systematic Review

Artificial intelligence (AI) is an advanced technology that enhances communication pathways across various industries, including education. Current state-of-the-art AI technologies offer significant benefits such as improved efficiency, personalized learning, inclusive learning, adaptive learning, smarter content, and enhanced effectiveness in educational administration. This study employed a qualitative research approach and systematically reviewed the literature to explore the impact of AI on higher education. To ensure a thorough and rigorous analysis, the review adhered to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) criteria and searched databases such as Scopus, Web of Science, and IEEE Xplore. The findings indicate that AI positively influences higher education by enhancing instructional methods and administrative processes. Instructors can perform their activities more effectively, ensuring the reliability and quality of their teaching. While the integration of AI in education promotes learning effectiveness, it also addresses potential adverse effects, thereby improving the overall quality of learning. This study contributes to the academic field by providing empirical evidence of AI’s benefits in higher education and offering practical recommendations for its implementation.

Spatio-Temporal Regulation of Notch Activation in Asymmetrically Dividing Sensory Organ Precursor Cells in Drosophila melanogaster Epithelium.

The Notch communication pathway, discovered in Drosophila over 100 years ago, regulates a wide range of intra-lineage decisions in metazoans. The division of the Drosophila mechanosensory organ precursor is the archetype of asymmetric cell division in which differential Notch activation takes place at cytokinesis. Here, we review the molecular mechanisms by which epithelial cell polarity, cell cycle and intracellular trafficking participate in controlling the directionality, subcellular localization and temporality of mechanosensitive Notch receptor activation in cytokinesis.

Single Cell Analysis of Peripheral TB-Associated Granulomatous Lymphadenitis.

We successfully employed a single cell RNA sequencing (scRNA-seq) approach to describe the cells and the communication networks characterizing granulomatous lymph nodes of TB patients. When mapping cells from individual patient samples, clustered based on their transcriptome similarities, we uniformly identify several cell types that known to characterize human and non-human primate granulomas. Whether high or low Mtb burden, we find the T cell cluster to be one of the most abundant. Many cells expressing T cell markers are clearly quantifiable within this CD3 expressing cluster. Other cell clusters that are uniformly detected, but that vary dramatically in abundance amongst the individual patient samples, are the B cell, plasma cell and macrophage/dendrocyte and NK cell clusters. When we combine all our scRNA-seq data from our current 23 patients (in order to add power to cell cluster identification in patient samples with fewer cells), we distinguish T, macrophage, dendrocyte and plasma cell subclusters, each with distinct signaling activities. The sizes of these subclusters also varies dramatically amongst the individual patients. In comparing FNA composition we noted trends in which T cell populations and macrophage/dendrocyte populations were negatively correlated with NK cell populations. In addition, we also discovered that the scRNA-seq pipeline, designed for quantification of human cell mRNA, also detects Mtb RNA transcripts and associates them with their host cell's transcriptome, thus identifying individual infected cells. We hypothesize that the number of detected bacterial transcript reads provides a measure of Mtb burden, as does the number of Mtb-infected cells. The number of infected cells also varies dramatically in abundance amongst the patient samples. CellChat analysis identified predominating signaling pathways amongst the cells comprising the various granulomas, including many interactions between stromal or endothelial cells and the other component cells, such as Collagen, FN1 and Laminin,. In addition, other more selective communications pathways, including MIF, MHC-1, MHC-2, APP, CD 22, CD45, and others, are identified as originating or being received by individual immune cell components.