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Communications Biology Jun 2024Distinct Natural Killer (NK)-like CD57 and PD-1 CD8 exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type...
Distinct Natural Killer (NK)-like CD57 and PD-1 CD8 exhausted-like T cell populations (Tex) have both been linked to beneficial immunotherapy response in autoimmune type 1 diabetes (T1D) patients. The origins and relationships between these cell types are poorly understood. Here we show that while PD-1 and CD57 Tex populations are epigenetically similar, CD57 Tex cells display unique increased chromatin accessibility of inhibitory Killer Cell Immunoglobulin-like Receptor (iKIR) and other NK cell genes. PD-1 and CD57 Tex also show reciprocal expression of Inhibitory Receptors (IRs) and iKIRs accompanied by chromatin accessibility of Tcf1 and Tbet transcription factor target sites, respectively. CD57 Tex show unappreciated gene expression heterogeneity and share clonal relationships with PD-1 Tex, with these cells differentiating along four interconnected lineage trajectories: Tex-PD-1, Tex-CD57, Tex-Branching, and Tex-Fluid. Our findings demonstrate new relationships between Tex-like populations in human autoimmune disease and suggest that modulating common precursor populations may enhance response to autoimmune disease treatment.
Topics: Diabetes Mellitus, Type 1; Humans; CD8-Positive T-Lymphocytes; Killer Cells, Natural; Programmed Cell Death 1 Receptor; CD57 Antigens; Cell Lineage; Hepatocyte Nuclear Factor 1-alpha; Female; Male; Adult
PubMed: 38937521
DOI: 10.1038/s42003-024-06456-3 -
Nature Communications Jun 2024Stramenopile algae contribute significantly to global primary productivity, and one class, Eustigmatophyceae, is increasingly studied for applications in high-value...
Stramenopile algae contribute significantly to global primary productivity, and one class, Eustigmatophyceae, is increasingly studied for applications in high-value lipid production. Yet much about their basic biology remains unknown, including the nature of an enigmatic, pigmented globule found in vegetative cells. Here, we present an in-depth examination of this "red body," focusing on Nannochloropsis oceanica. During the cell cycle, the red body forms adjacent to the plastid, but unexpectedly it is secreted and released with the autosporangial wall following cell division. Shed red bodies contain antioxidant ketocarotenoids, and overexpression of a beta-carotene ketolase results in enlarged red bodies. Infrared spectroscopy indicates long-chain, aliphatic lipids in shed red bodies and cell walls, and UHPLC-HRMS detects a C32 alkyl diol, a potential precursor of algaenan, a recalcitrant cell wall polymer. We propose that the red body transports algaenan precursors from plastid to apoplast to be incorporated into daughter cell walls.
Topics: Cell Wall; Stramenopiles; Plastids
PubMed: 38937455
DOI: 10.1038/s41467-024-49277-y -
Cell Reports. Medicine Jun 2024In rodents with unilateral ablation of neurons supplying dopamine to the striatum, chronic treatment with the dopamine precursor L-DOPA induces a progressive increase of...
In rodents with unilateral ablation of neurons supplying dopamine to the striatum, chronic treatment with the dopamine precursor L-DOPA induces a progressive increase of behavioral responses, a process known as behavioral sensitization. This sensitization is blunted in arrestin-3 knockout mice. Using virus-mediated gene delivery to the dopamine-depleted striatum of these mice, we find that the restoration of arrestin-3 fully rescues behavioral sensitization, whereas its mutant defective in c-Jun N-terminal kinase (JNK) activation does not. A 25-residue arrestin-3-derived peptide that facilitates JNK3 activation in cells, expressed ubiquitously or selectively in direct pathway striatal neurons, also fully rescues sensitization, whereas an inactive homologous arrestin-2-derived peptide does not. Behavioral rescue is accompanied by the restoration of JNK3 activity, as reflected by JNK-dependent phosphorylation of the transcription factor c-Jun in the dopamine-depleted striatum. Thus, arrestin-3-assisted JNK3 activation in direct pathway neurons is a critical element of the molecular mechanism underlying sensitization upon dopamine depletion and chronic L-DOPA treatment.
PubMed: 38936368
DOI: 10.1016/j.xcrm.2024.101623 -
Neural Regeneration Research Jun 2024The N-terminal EF-hand calcium-binding proteins 1-3 (NECAB1-3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one...
The N-terminal EF-hand calcium-binding proteins 1-3 (NECAB1-3) constitute a family of predominantly neuronal proteins characterized by the presence of at least one EF-hand calcium-binding domain and a functionally less well characterized C-terminal antibiotic biosynthesis monooxygenase domain. All three family members were initially discovered due to their interactions with other proteins. NECAB1 associates with synaptotagmin-1, a critical neuronal protein involved in membrane trafficking and synaptic vesicle exocytosis. NECAB2 interacts with predominantly striatal G-protein-coupled receptors, while NECAB3 partners with amyloid-beta A4 precursor protein-binding family A members 2 and 3, key regulators of β-amyloid production. This demonstrates the capacity of the family for interactions with various classes of proteins. NECAB proteins exhibit distinct subcellular localizations: NECAB1 is found in the nucleus and cytosol, NECAB2 resides in endosomes and the plasma membrane, and NECAB3 is present in the endoplasmic reticulum and Golgi apparatus. The antibiotic biosynthesis monooxygenase domain, an evolutionarily ancient component, is akin to atypical heme oxygenases in prokaryotes but is not well-characterized in vertebrates. Prokaryotic antibiotic biosynthesis monooxygenase domains typically form dimers, suggesting that calcium-mediated conformational changes in NECAB proteins may induce antibiotic biosynthesis monooxygenase domain dimerization, potentially activating some enzymatic properties. However, the substrate for this enzymatic activity remains uncertain. Alternatively, calcium-mediated conformational changes might influence protein interactions or the subcellular localization of NECAB proteins by controlling the availability of protein-protein interaction domains situated between the EF hands and the antibiotic biosynthesis monooxygenase domain. This review summarizes what is known about genomic organization, tissue expression, intracellular localization, interaction partners, and the physiological and pathophysiological role of the NECAB family.
PubMed: 38934399
DOI: 10.4103/NRR.NRR-D-24-00094 -
Heliyon Jun 2024The remediation of dye pollutants remains a concern in contemporary water management practices. Hence, the need for efficient and cost-effective techniques for dye...
The remediation of dye pollutants remains a concern in contemporary water management practices. Hence, the need for efficient and cost-effective techniques for dye removal from wastewater. In this study, the epicarp of fruits was treated with orthophosphoric acid for enhanced porosity and efficiency in the uptake of Indigo carmine dye (ICD). Treated fruit waste (RHPW) presented morphologically distributed pores as well as high porosity with Branneur-Emmet-Teller (BET) surface area of 945.43 m/g. RHPW displayed functional groups suitable for adsorption. The maximum ICD uptake was observed at pH 5 while the maximum uptake (q) was 20.41 mg/g in the concentration range of 2-10 mg/L. Freundlich isotherm and Pseudo-second order kinetics well-described equilibrium and kinetics data respectively. This indicated a multilayered adsorption. The Dubinin-Radushkecich model energy value was 40.82 kJ/mol, indicating chemical adsorption. The ridge regression, the Lasso and the Elastic net statistical models were used to establish a positive relationship between the various adsorption operational parameters studied. Lasso provided the best result based on the estimated mean squared error. The RHPW-ICD adsorption system was more favorable at room temperature, as the removal efficiency decreased with temperature rise. The findings established fruit epicarp as an economical and sustainable precursor for the preparation of potent adsorbent for Indigo carmine dye removal. This can find possible application in wastewater treatment.
PubMed: 38933985
DOI: 10.1016/j.heliyon.2024.e32121 -
Nanoscale Advances Jun 2024Mesoporous silica nanoparticles hosting guest molecules are a versatile tool with applications in various fields such as life and environmental sciences. Current...
Mesoporous silica nanoparticles hosting guest molecules are a versatile tool with applications in various fields such as life and environmental sciences. Current commonly applied pore blocking strategies are not universally applicable and are often not robust enough to withstand harsh ambient conditions ( geothermal). In this work, a titania layer is utilized as a robust pore blocker, with a test-case where it is used for the encapsulation of fluorescent dyes. The layer is formed by a hydrolysis process of a titania precursor in an adapted microemulsion system and demonstrates effective protection of both the dye payload and the silica core from disintegration under otherwise damaging external conditions. The produced dye-MSN@TiO particles are characterized by means of electron microscopy, elemental mapping, ζ-potential, X-ray diffraction (XRD), nitrogen adsorption, Thermogravimetric analysis (TGA), fluorescence and absorbance spectroscopy and Fourier Transform Infrared Spectroscopy - Total Attenuated Reflectance (FT-IR ATR). Finally, the performance of the titania-encapsulated MSNs is demonstrated in long-term aqueous stability and in flow-through experiments, where owing to improved dispersion encapsulated dye results in improved flow properties compared to free dye properties. This behavior exemplifies the potential advantage of carrier-borne marker molecules over free dye molecules in applications where accessibility or targeting are a factor, thus this encapsulation method increases the variety of fields of application.
PubMed: 38933859
DOI: 10.1039/d4na00242c -
Nanoscale Advances Jun 2024The key parameters of semiconductor quantum dots (QDs) that determine the suitability and efficiency for the design of most optoelectronic devices are the spectral...
The key parameters of semiconductor quantum dots (QDs) that determine the suitability and efficiency for the design of most optoelectronic devices are the spectral positions of absorbance (ABS) and photoluminescence (PL) maxima, Stokes shift, photoluminescence quantum yield (PL QY) and photoluminescence lifetime (PL LT). All these parameters have been considered in the design of new ternary core CdTeS and core/shell CdTeS/Cd Zn S QDs. One-pot synthesis conducted in an organic medium at 160 °C using substituted thioureas as new, highly reactive sulfur sources allowed for the formation of a series of size- and emission-tunable CdTeS QDs. Gram-scale synthesis of yellow-red emitting CdTeS and CdTeS cores was performed through the manipulation of their precursor ratio for the controllable formation of CdTeS/Cd Zn S ( = 0.1, 0.2, and 0.3) core/shell QDs. The development of the designed nanomaterials was carried out with a special emphasis on their optical properties, in particular a high PL QY up to 87% and extremely large Stokes shift, reaching ≈280 nm for core/shell QDs. Promisingly, for biolabeling and diagnostics, the synthesized core/shell QDs were transferred into water surface ligand modification with the expected loss of photoluminescence efficiency. The results indicated that the availability of initial components, high yield of the desired product, stability in the organic phase, and high optical characteristics can scale up the synthesis of the developed nanomaterials from the laboratory level to industrial production.
PubMed: 38933857
DOI: 10.1039/d4na00287c -
Frontiers in Bioengineering and... 2024In the brains of most adult mammals, neural precursor cells (NPCs) from the subventricular zone (SVZ) migrate through the rostral migratory stream (RMS) to replace...
In the brains of most adult mammals, neural precursor cells (NPCs) from the subventricular zone (SVZ) migrate through the rostral migratory stream (RMS) to replace olfactory bulb interneurons. Following brain injury, published studies have shown that NPCs can divert from the SVZ-RMS-OB route and migrate toward injured brain regions, but the quantity of arriving cells, the lack of survival and terminal differentiation of neuroblasts into neurons, and their limited capacity to re-connect into circuitry are insufficient to promote functional recovery in the absence of therapeutic intervention. Our lab has fabricated a biomimetic tissue-engineered rostral migratory stream (TE-RMS) that replicates some notable structural and functional components of the endogenous rat RMS. Based on the design attributes for the TE-RMS platform, it may serve as a regenerative medicine strategy to facilitate sustained neuronal replacement into an injured brain region or an tool to investigate cell-cell communication and neuroblast migration. Previous work has demonstrated that the TE-RMS replicates the basic structure, unique nuclear shape, cytoskeletal arrangement, and surface protein expression of the endogenous rat RMS. Here, we developed an enhanced TE-RMS fabrication method in hydrogel microchannels that allowed more robust and high-throughput TE-RMS assembly. We report unique astrocyte behavior, including astrocyte bundling into the TE-RMS, the presence of multiple TE-RMS bundles, and observations of discontinuities in TE-RMS bundles, when microtissues are fabricated in agarose microchannels containing different critical curved or straight geometric features. We also demonstrate that we can harvest NPCs from the SVZ of adult rat brains and that EGFP+ cells migrate in chain formation from SVZ neurospheres through the TE-RMS . Overall, the TE-RMS can be utilized as an platform to investigate the pivotal cell-cell signaling mechanisms underlying the synergy of molecular cues involved in immature neuronal migration and differentiation.
PubMed: 38933539
DOI: 10.3389/fbioe.2024.1410717 -
Frontiers in Cellular Neuroscience 2024Human cerebral organoids (hCOs) derived from pluripotent stem cells are very promising for the study of neurodevelopment and the investigation of the healthy or diseased...
INTRODUCTION
Human cerebral organoids (hCOs) derived from pluripotent stem cells are very promising for the study of neurodevelopment and the investigation of the healthy or diseased brain. To help establish hCOs as a powerful research model, it is essential to perform the morphological characterization of their cellular components in depth.
METHODS
In this study, we analyzed the cell types consisting of hCOs after culturing for 45 days using immunofluorescence and reverse transcriptase qualitative polymerase chain reaction (RT-qPCR) assays. We also analyzed their subcellular morphological characteristics by transmission electron microscopy (TEM).
RESULTS
Our results show the development of proliferative zones to be remarkably similar to those found in human brain development with cells having a polarized structure surrounding a central cavity with tight junctions and cilia. In addition, we describe the presence of immature and mature migrating neurons, astrocytes, oligodendrocyte precursor cells, and microglia-like cells.
DISCUSSION
The ultrastructural characterization presented in this study provides valuable information on the structural development and morphology of the hCO, and this information is of general interest for future research on the mechanisms that alter the cell structure or function of hCOs.
PubMed: 38933177
DOI: 10.3389/fncel.2024.1406839 -
Vaccines Jun 2024The reported study compared the impact of four influence strategies (agency assignment, enhanced active choice, deviance regulation marking, and temporal framing) on...
The reported study compared the impact of four influence strategies (agency assignment, enhanced active choice, deviance regulation marking, and temporal framing) on English- and Spanish-speaking parents' reported intention to vaccinate their children for HPV. An online experiment was conducted to examine the impact of the strategies. In a fractional factorial design, participating parents (N = 1663) were exposed to combinations of influence strategies in text messages presented as reminders they might receive from a healthcare provider about their child's eligibility for the vaccine series. The results indicated small but significant impacts of agency assignment, enhanced active choice, and deviance regulation marking on parents' reported vaccination intentions. The study adds to the research literature on HPV vaccination communication in two important respects. First, it demonstrated how incorporating evidence-based influence strategies into reminder messages can increase parents' vaccination intentions, an important precursor and predictor of actual vaccine uptake. Second, it sets an important precedent by examining the effects of influence strategies on vaccination intentions across different languages.
PubMed: 38932379
DOI: 10.3390/vaccines12060650