Dynamics of Neurogenic Signals as Biological Switchers of Brain Plasticity.

The discovery of adult neurogenesis in the middle of the past century is considered one of the most important breakthroughs in neuroscience. Despite its controversial nature, this discovery shaped our concept of neural plasticity, revolutionizing the way we look at our brains. In fact, after the discovery of adult neurogenesis, we started to consider the brain as something even more dynamic and highly adaptable. In neurogenic niches, adult neurogenesis is supported by neural stem cells (NSCs). These cells possess a unique set of characteristics such as being quiescent for long periods while actively sensing and reacting to their surroundings to influence a multitude of processes, including the generation of new neurons and glial cells. Therefore, NSCs can be viewed as sentinels to our brain's homeostasis, being able to replace damaged cells and simultaneously secrete numerous factors that restore regular brain function. In addition, it is becoming increasingly evident that NSCs play a central role in memory formation and consolidation. In this review, we will dissect how NSCs influence their surroundings through paracrine and autocrine types of action. We will also depict the mechanism of action of each factor. Finally, we will describe how NSCs integrate different and often opposing signals to guide their fate.

Bone niches in the regulation of tumour cell dormancy.

Secondary metastases, accounting for 90 % of cancer-related deaths, pose a formidable challenge in cancer treatment, with bone being a prevalent site. Importantly, tumours may relapse, often in the skeleton even after successful eradication of the primary tumour, indicating that tumour cells may lay dormant within bone for extended periods of time. This review summarises recent findings in the mechanisms underlying tumour cell dormancy and the role of bone cells in this process. Hematopoietic stem cell (HSC) niches in bone provide a model for understanding regulatory microenvironments. Dormant tumour cells have been shown to exploit similar niches, with evidence suggesting interactions with osteoblast-lineage cells and other stromal cells via CXCL12-CXCR4, integrins, and TAM receptor signalling, especially through GAS6-AXL, led to dormancy, with exit of dormancy potentially regulated by osteoclastic bone resorption and neuronal signalling. A comprehensive understanding of dormant tumour cell niches and their regulatory mechanisms is essential for developing targeted therapies, a critical step towards eradicating metastatic tumours and stopping disease relapse.

Hepatic macrophage niche: a bridge between HBV-mediated metabolic changes with intrahepatic inflammation.

Hepatitis B Virus (HBV) is a stealthy and insidious pathogen capable of inducing chronic necro-inflammatory liver disease and hepatocellular carcinoma (HCC), resulting in over one million deaths worldwide per year. The traditional understanding of Chronic Hepatitis B (CHB) progression has focused on the complex interplay among ongoing virus replication, aberrant immune responses, and liver pathogenesis. However, the dynamic progression and crucial factors involved in the transition from HBV infection to immune activation and intrahepatic inflammation remain elusive. Recent insights have illuminated HBV's exploitation of the sodium taurocholate co-transporting polypeptide (NTCP) and manipulation of the cholesterol transport system shared between macrophages and hepatocytes for viral entry. These discoveries deepen our understanding of HBV as a virus that hijacks hepatocyte metabolism. Moreover, hepatic niche macrophages exhibit significant phenotypic and functional diversity, zonal characteristics, and play essential roles, either in maintaining liver homeostasis or contributing to the pathogenesis of chronic liver diseases. Therefore, we underscore recent revelations concerning the importance of hepatic niche macrophages in the context of viral hepatitis. This review particularly emphasizes the significant role of HBV-induced metabolic changes in hepatic macrophages as a key factor in the transition from viral infection to immune activation, ultimately culminating in liver inflammation. These metabolic alterations in hepatic macrophages offer promising targets for therapeutic interventions and serve as valuable early warning indicators, shedding light on the disease progression.

Navigating the biophysical landscape: how physical cues steer the journey of bone metastatic tumor cells.

Many tumors prefer to metastasize to bone, but the underlying mechanisms remain elusive. The human skeletal system has unique physical properties, that are distinct from other organs, which play a key role in directing the behavior of tumor cells within bone. Understanding the physical journey of tumor cells within bone is crucial. In this review we discuss bone metastasis in the context of how physical cues in the bone vasculature and bone marrow niche regulate the fate of tumor cells. Our objective is to inspire innovative diagnostic and therapeutic approaches for bone metastasis from a mechanobiological perspective.

The Potential of Immunotherapy for SMARCA4-Deficient Undifferentiated Uterine Sarcoma (SDUS).

(1) Background: SMARCA4-deficient undifferentiated uterine sarcoma (SDUS) is a rare and aggressive cancer that urgently requires novel therapeutic strategies. Despite the proven efficacy of immunotherapy in various cancer types, its application in SDUS remains largely unexplored. This study aims to investigate the immune microenvironment of SDUS to evaluate the feasibility of utilizing immunotherapy. (2) Methods: Multiplex immunofluorescence (mIF) was employed to examine the immune microenvironment in two cases of SDUS in comparison to other subtypes of endometrial stromal sarcomas (ESSs). This research involved a comprehensive evaluation of immune cell infiltration, cellular interactions, and spatial organization within the tumor immune microenvironment (TiME). Statistical analysis was performed to assess differences in immune cell densities and interactions between SDUS and other ESSs. (3) Results: SDUS exhibited a significantly higher density of cytotoxic T lymphocytes (CTLs), T helper (Th) cells, B cells, and macrophages compared to other ESSs. Notable cellular interactions included Th-CTL and Th-B cell interactions, which were more prominent in SDUS. The spatial analysis revealed distinct immune niches characterized by lymphocyte aggregation and a vascular-rich environment, suggesting an active and engaged immune microenvironment in SDUS. (4) Conclusions: The results suggest that SDUS exhibits a highly immunogenic TiME, characterized by substantial lymphocyte infiltration and dynamic cellular interactions. These findings highlight the potential of immunotherapy as an effective treatment approach for SDUS. However, given the small number of samples evaluated, these conclusions should be drawn with caution. This study underscores the importance of additional investigation into immune-targeted therapies for this challenging cancer subtype, with a larger sample size to validate and expand upon these preliminary findings.

Niche separation in bacterial communities and activities in porewater, loosely attached, and firmly attached fractions in permeable surface sediments.

Heterotrophic microbes are central to organic matter degradation and transformation in marine sediments. Currently, most investigations of benthic microbiomes do not differentiate between processes in the porewater and on the grains and, hence, only show a generalized picture of the community. This limits our understanding of the structure and functions of sediment microbiomes. To address this problem, we fractionated sandy surface sediment microbial communities from a coastal site in Isfjorden, Svalbard, into cells associated with the porewater, loosely attached to grains, and firmly attached to grains; we found dissimilar bacterial communities and metabolic activities in these fractions. Most (84%-89%) of the cells were firmly attached, and this fraction comprised more anaerobes, such as sulfate reducers, than the other fractions. The porewater and loosely attached fractions (3% and 8%-13% of cells, respectively) had more aerobic heterotrophs. These two fractions generally showed a higher frequency of dividing cells, polysaccharide (laminarin) hydrolysis rates, and per-cell O2 consumption than the firmly attached cells. Thus, the different fractions occupy distinct niches within surface sediments: the firmly attached fraction is potentially made of cells colonizing areas on the grain that are protected from abrasion, but might be more diffusion-limited for organic matter and electron acceptors. In contrast, the porewater and loosely attached fractions are less resource-limited and have faster growth. Their cell numbers are kept low possibly through abrasion and exposure to grazers. Differences in community composition and activity of these cell fractions point to their distinct roles and contributions to carbon cycling within surface sediments.

Heterotypic interaction promotes asymmetric division of human hematopoietic progenitors.

Hematopoietic stem and progenitor cells (HSPCs) give rise to all cell types of the hematopoietic system through various processes, including asymmetric divisions. However, the contribution of stromal cells of the hematopoietic niches in the control of HSPC asymmetric divisions remains unknown. Using polyacrylamide microwells as minimalist niches, we show that specific heterotypic interactions with osteoblast and endothelial cells promote asymmetric divisions of human HSPCs. Upon interaction, HSPCs polarize in interphase with the centrosome, the Golgi apparatus, and lysosomes positioned close to the site of contact. Subsequently, during mitosis, HSPCs orient their spindle perpendicular to the plane of contact. This division mode gives rise to siblings with unequal amounts of lysosomes and of the differentiation marker CD34. Such asymmetric inheritance generates heterogeneity in the progeny, which is likely to contribute to the plasticity of the early steps of hematopoiesis.

Repeated migration, interbreeding and bottlenecking shaped the phylogeography of the selfing grass Brachypodium stacei.

Brachypodium stacei is the most ancestral lineage in the genus Brachypodium, a model system for grass functional genomics. B. stacei shows striking and sometimes contradictory biological and evolutionary features, including a high selfing rate yet extensive admixture, an ancient Miocene origin yet with recent evolutionary radiation, and adaptation to different dry climate conditions in its narrow distribution range. Therefore, it constitutes an ideal system to study these life history traits. We studied the phylogeography of 17 native circum-Mediterranean B. stacei populations (39 individuals) using genome-wide RADseq SNP data and complete plastome sequences. Nuclear SNP data revealed the existence of six distinct genetic clusters, low levels of intra-population genetic diversity and high selfing rates, albeit with signatures of admixture. Coalescence-based dating analysis detected a recent split between crown lineages in the Late Quaternary. Plastome sequences showed incongruent evolutionary relationships with those recovered by the nuclear data, suggesting interbreeding and chloroplast capture events between genetically distant populations. Demographic and population dispersal coalescent models identified an ancestral origin of B. stacei in the western-central Mediterranean islands, followed by an early colonization of the Canary Islands and two independent colonization events of the eastern Mediterranean region through long-distance dispersal and bottleneck events as the most likely evolutionary history. Climate niche data identified three arid niches of B. stacei in the southern Mediterranean region. Our findings indicate that the phylogeography of B. stacei populations was shaped by recent radiations, frequent extinctions, long-distance dispersal events, occasional interbreeding, and adaptation to local climates.

Oral microbiota and gastric cancer: recent highlights and knowledge gaps.

Gastric cancer is one of the most common malignant tumors worldwide and has a high mortality rate. However, tests for the early screening and diagnosis of gastric cancer are limited and invasive. Certain oral microorganisms are over-expressed in gastric cancer, but there is heterogeneity among different studies. Notably, each oral ecological niche harbors specific microorganisms. Among them, tongue coating, saliva, and dental plaque are important and unique ecological niches in the oral cavity. The colonization environment in different oral niches may be a source of heterogeneity. In this paper, we systematically discuss the latest developments in the field of the oral microbiota and gastric cancer and elucidate the enrichment of microorganisms in the oral ecological niches of the tongue coatings, saliva, and dental plaque in gastric cancer patients. The various potential mechanisms by which the oral microbiota induces gastric cancer (activation of an excessive inflammatory response; promotion of proliferation, migration, invasion, and metastasis; and secretion of carcinogens, leading to imbalance in gastric microbial communities) are explored. In this paper, we also highlight the applications of the rapeutics targeting the oral microbiota in gastric cancer and suggests future research directions related to the relationship between the oral microbiota and gastric cancer.

Multi-modal fusion and feature enhancement U-Net coupling with stem cell niches proximity estimation for voxel-wise GBM recurrence prediction.

Objective.We aim to develop a Multi-modal Fusion and Feature Enhancement U-Net (MFFE U-Net) coupling with stem cell niche proximity estimation to improve voxel-wise Glioblastoma (GBM) recurrence prediction.Approach.57 patients with pre- and post-surgery magnetic resonance (MR) scans were retrospectively solicited from 4 databases. Post-surgery MR scans included two months before the clinical diagnosis of recurrence and the day of the radiologicaly confirmed recurrence. The recurrences were manually annotated on the T1ce. The high-risk recurrence region was first determined. Then, a sparse multi-modal feature fusion U-Net was developed. The 50 patients from 3 databases were divided into 70% training, 10% validation, and 20% testing. 7 patients from the 4th institution were used as external testing with transfer learning. Model performance was evaluated by recall, precision, F1-score, and Hausdorff Distance at the 95% percentile (HD95). The proposed MFFE U-Net was compared to the support vector machine (SVM) model and two state-of-the-art neural networks. An ablation study was performed.Main results.The MFFE U-Net achieved a precision of 0.79 ± 0.08, a recall of 0.85 ± 0.11, and an F1-score of 0.82 ± 0.09. Statistically significant improvement was observed when comparing MFFE U-Net with proximity estimation couple SVM (SVMPE), mU-Net, and Deeplabv3. The HD95 was 2.75 ± 0.44 mm and 3.91 ± 0.83 mm for the 10 patients used in the model construction and 7 patients used for external testing, respectively. The ablation test showed that all five MR sequences contributed to the performance of the final model, with T1ce contributing the most. Convergence analysis, time efficiency analysis, and visualization of the intermediate results further discovered the characteristics of the proposed method.Significance. We present an advanced MFFE learning framework, MFFE U-Net, for effective voxel-wise GBM recurrence prediction. MFFE U-Net performs significantly better than the state-of-the-art networks and can potentially guide early RT intervention of the disease recurrence.

Review of pre-metastatic niches induced by osteosarcoma-derived extracellular vesicles in lung metastasis: A potential opportunity for diagnosis and intervention.

Osteosarcoma (OS) has a high propensity for lung metastasis, which is the leading cause of OS-related death and treatment failure. Intercellular communication between OS cells and distant lung host cells is required for the successful lung metastasis of OS cells to the lung. Before OS cells infiltrate the lung, in situ OS cells secrete extracellular vesicles (EVs) that act as mediators of cell-to-cell communication. In recent years, EVs have been confirmed to act as bridges and key drivers between in situ tumors and metastatic lesions by regulating the formation of a pre-metastatic niche (PMN), defined as a microenvironment suitable for disseminated tumor cell engraftment and colonization, in distant target organs. This review summarizes the current knowledge about the underlying mechanisms of PMN formation induced by OS-derived EVs and the potential roles of EVs as targets or drug carriers in regulating PMN formation in the lung. We also provide an overview of their potential EV-based therapeutic strategies for hindering PMN formation in the context of OS lung metastasis.

Network ecology: Tie fitness in social context(s).

Social relations are embedded in material, cultural, and institutional settings that affect network dynamics and the resulting topologies. For example, romantic entanglements are subject to social and cultural norms, interfirm alliances are constrained by country-specific legislation, and adolescent friendships are conditioned by classroom settings and neighborhood effects. In short, social contexts shape social relations and the networks they give rise to. However, how and when they do so remain to be established. This paper presents network ecology as a general framework for identifying how the proximal environment shapes social networks by focusing interactions and social relations, and how these interactions and relations in turn shape the environment in which social networks form. Tie fitness is introduced as a metric that quantifies how well particular dyadic social relations would align with the setting. Using longitudinal networks collected on two cohorts each in 18 North American schools, i.e., 36 settings, we develop five generalizable observations about the time-varying fitness of adolescent friendship. Across all 252 analyzed networks, tie fitness predicted new tie formation, tie longevity, and tie survival. Dormant fit ties cluster in relational niches, thereby establishing a resource base for social identities competing for increased representation in the relational system.

Fluffy hybrid nanoadjuvants for reversing the imbalance of osteoclastic and osteogenic niches in osteoporosis.

Osteoporosis is majorly caused by an imbalance between osteoclastic and osteogenic niches. Despite the development of nationally recognized first-line anti-osteoporosis drugs, including alendronate (AL), their low bioavailability, poor uptake rate, and dose-related side effects present significant challenges in treatment. This calls for an urgent need for more effective bone-affinity drug delivery systems. In this study, we produced hybrid structures with bioactive components and stable fluffy topological morphology by cross-linking calcium and phosphorus precursors based on mesoporous silica to fabricate nanoadjuvants for AL delivery. The subsequent grafting of -PEG-DAsp8 ensured superior biocompatibility and bone targeting capacity. RNA sequencing revealed that these fluffy nanoadjuvants effectively activated adhesion pathways through CARD11 and CD34 molecular mechanisms, hence promoting cellular uptake and intracellular delivery of AL. Experiments showed that small-dose AL nanoadjuvants effectively suppress osteoclast formation and potentially promote osteogenesis. In vivo results restored the balance between osteogenic and osteoclastic niches against osteoporosis as well as the consequent significant recovery of bone mass. Therefore, this study constructed a drug nanoadjuvant with peculiar topological structures and high bone targeting capacities, efficient intracellular drug delivery as well as bone bioactivity. This provides a novel perspective on drug delivery for osteoporosis and treatment strategies for other bone diseases.

Who inhabits the built environment? A microbiological point of view on the principal bacteria colonizing our urban areas.

Modern lifestyle greatly influences human well-being. Indeed, nowadays people are centered in the cities and this trend is growing with the ever-increasing population. The main habitat for modern humans is defined as the built environment (BE). The modulation of life quality in the BE is primarily mediated by a biodiversity of microbes. They derive from different sources, such as soil, water, air, pets, and humans. Humans are the main source and vector of bacterial diversity in the BE leaving a characteristic microbial fingerprint on the surfaces and spaces. This review, focusing on articles published from the early 2000s, delves into bacterial populations present in indoor and outdoor urban environments, exploring the characteristics of primary bacterial niches in the BE and their native habitats. It elucidates bacterial interconnections within this context and among themselves, shedding light on pathways for adaptation and survival across diverse environmental conditions. Given the limitations of culture-based methods, emphasis is placed on culture-independent approaches, particularly high-throughput techniques to elucidate the genetic and -omic features of BE bacteria. By elucidating these microbiota profiles, the review aims to contribute to understanding the implications for human health and the assessment of urban environmental quality in modern cities.

Morpho-histology of co-occurrence of somatic embryos, shoots, and inflorescences within a callus of Limonium 'Misty Blue'.

This is the first attempt to report the co-occurrence of somatic embryos, shoots, and inflorescences and their sequential development from stem cell niches of an individual callus mass through morpho-histological study of any angiosperm. In the presence of a proper auxin/cytokinin combination, precambial stem cells from the middle layer of a compact callus, which was derived from the thin cell layer of the inflorescence rachis of Limonium, expressed the highest level of totipotency and pluripotency and simultaneously developed somatic embryos, shoots, and inflorescences. This study also proposed the concept of programmed cell death during bipolar somatic embryo and unipolar shoot bud pattern formation. The unique feature of this research was the stepwise histological description of in vitro racemose inflorescence development. Remarkably, during the initiation of inflorescence development, either a unipolar structure with open vascular elements or an independent bipolar structure with closed vascular elements were observed. The protocol predicted the production of 6.6 ± 0.24 and 7.4 ± 0.24 somatic embryos and shoots, respectively, from 400 mg of callus, which again multiplied, rooted, and acclimatised. The plants' ploidy level and genetic fidelity were assessed randomly before acclimatisation by flow cytometry and inter simple sequence repeats (ISSR) marker analysis. Finally, the survivability and flower quality of the regenerated plants were evaluated in the field.

Crosstalk between CD8+ T cells and mesenchymal stromal cells in intestine homeostasis and immunity.

The intestine represents the most complex cellular network in the whole body. It is constantly faced with multiple types of immunostimulatory agents encompassing from food antigen, gut microbiome, metabolic waste products, and dead cell debris. Within the intestine, most T cells are found in three primary compartments: the organized gut-associated lymphoid tissue, the lamina propria, and the epithelium. The well-orchestrated epithelial-immune-microbial interaction is critically important for the precise immune response. The main role of intestinal mesenchymal stromal cells is to support a structural framework within the gut wall. However, recent evidence from stromal cell studies indicates that they also possess significant immunomodulatory functions, such as maintaining intestinal tolerance via the expression of PDL1/2 and MHC-II molecules, and promoting the development of CD103+ dendritic cells, and IgA+ plasma cells, thereby enhancing intestinal homeostasis. In this review, we will summarize the current understanding of CD8+ T cells and stromal cells alongside the intestinal tract and discuss the reciprocal interactions between T subsets and mesenchymal stromal cell populations. We will focus on how the tissue residency, migration, and function of CD8+ T cells could be potentially regulated by mesenchymal stromal cell populations and explore the molecular mediators, such as TGF-ß, IL-33, and MHC-II molecules that might influence these processes. Finally, we discuss the potential pathophysiological impact of such interaction in intestine hemostasis as well as diseases of inflammation, infection, and malignancies.

Maternal Effects and Trophodynamics Drive Interannual Larval Growth Variability of Atlantic Bluefin Tuna (Thunnus thynnus) from the Gulf of Mexico.

Two cohorts of Atlantic bluefin tuna (Thunnus thynnus) larvae were sampled in 2017 and 2018 during the peak of spawning in the Gulf of Mexico (GOM). We examined environmental variables, daily growth, otolith biometry and stable isotopes and found that the GOM18 cohort grew at faster rates, with larger and wider otoliths. Inter and intra-population analyses (deficient vs. optimal growth groups) were carried out for pre- and post-flexion developmental stages to determine maternal and trophodynamic influences on larval growth variability based on larval isotopic signatures, trophic niche sizes and their overlaps. For the pre-flexion stages in both years, the optimal growth groups had significantly lower δ15N, implying a direct relationship between growth potential and maternal inheritance. Optimal growth groups and stages for both years showed lower C:N ratios, reflecting a greater energy investment in growth. The results of this study illustrate the interannual transgenerational trophic plasticity of a spawning stock and its linkages to growth potential of their offsprings in the GOM.

The Contributions of Sub-Communities to the Assembly Process and Ecological Mechanisms of Bacterial Communities along the Cotton Soil-Root Continuum Niche Gradient.

Soil microbes are crucial in shaping the root-associated microbial communities. In this study, we analyzed the effect of the soil-root niche gradient on the diversity, composition, and assembly of the bacterial community and co-occurrence network of two cotton varieties. The results revealed that the bacterial communities in cotton soil-root compartment niches exhibited a skewed species abundance distribution, dominated by abundant taxa showing a strong spatial specificity. The assembly processes of the rhizosphere bacterial communities were mainly driven by stochastic processes, dominated by the enrichment pattern and supplemented by the depletion pattern to recruit bacteria from the bulk soil, resulting in a more stable bacterial community. The assembly processes of the endosphere bacterial communities were determined by processes dominated by the depletion pattern and supplemented by the enrichment pattern to recruit species from the rhizosphere, resulting in a decrease in the stability and complexity of the community co-occurrence network. The compartment niche shaped the diversity of the bacterial communities, and the cotton variety genotype was an important source of diversity in bacterial communities within the compartment niche. We suggest that the moderate taxa contribute to significantly more changes in the diversity of the bacterial community than the rare and abundant taxa during the succession of bacterial communities in the cotton root-soil continuum.

Revealing microbial community assembly patterns and succession process in the blackening process of black-odor water.

Human-imported pollutants could induce water black, changing microbial community structure and function. Employed 16S rRNA high-throughput sequencing, field-scale investigations and laboratory-scale experiments were successively conducted to reveal mechanistic insights into microbial community assembly and succession of black-odor waters (BOWs). In the field-scale investigation, livestock breeding wastewater (56.7 ± 3.2%) was the most critical microbial source. Moreover, fermentation (27.1 ± 4.4%) was found to be the dominant function. Combined with laboratory experiments, the critical environmental factors, such as total organic carbon (30-100 mg/L), ammonia nitrogen (2.5-9 mg/L), initial dissolved oxygen (2-8 mg/L) and chlorophyll a (0-90 mg/L), impacted the intensity of blackening. The differentiation of ecological niches within the microbial community played a significant role in driving the blackening speed. In laboratory-scale experiments, the microbial ecological niche determined the blackening timing and dominations of the stochastic processes in the microbial assembly process (88 - 51%). The three stages, including the anaerobic degradation stage, blackening stage and slow recovery stage, were proposed to understand the assembly of the microbial communities. These findings enhance our understanding of microorganisms in BOWs and provide valuable insights for detecting and managing heavily organic polluted waters.