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1.
Article in English | MEDLINE | ID: mdl-39093820

ABSTRACT

TIAM Rac1 associated GEF 2 short-form protein (TIAM2S) is abundant in specific brain tissues, especially in the hippocampus, a brain region critical for processing and consolidation of spatial memory. However, how TIAM2S plasticizes the microstructure and circuits of the hippocampus to shape spatial memory as a neuroplastic regulator during aging, remains to be determined. In this study, transgenic mice overexpressing human TIAM2S protein (TIAM2S-TG mice) were included, and interdisciplinary approaches, such as spatial memory tests and multiparametric magnetic resonance imaging sequences, were conducted to determine the role and the mechanism of TIAM2S in age-related spatial memory deficits. Despite no changes in their neural and glial markers and neuropathological hallmarks expression of the hippocampus, behavioral tests showed that the TIAM2S-TG mice, and not wild-type (WT) mice, developed spatial memory impairment at 18 months old. The T2-weighted and diffusion tensor images analysis were performed to further study the possible role of TIAM2S overexpression in altering the hippocampal structure or neuronal circlets of the mice, increasing their vulnerability to developing spatial memory deficits during aging. The results revealed that the 12-month-old TIAM2S-TG mice had hippocampal dysplasticity, with larger volume, increased fiber numbers, and changed mean fractional anisotropy compared to those in the age-matched WT mice. The fiber tractography analysis exhibited significantly attenuated structural connectivity between the hippocampus and medial prefrontal cortex in the TIAM2S-TG mice. In conclusion, overexpression of TIAM2S, a detrimental factor affecting hippocampus plasticity, causes attenuation of the connectivity within hippocampus-mPFC circuits, leading to age-related spatial memory impairment.

2.
FASEB J ; 37(11): e23242, 2023 11.
Article in English | MEDLINE | ID: mdl-37801065

ABSTRACT

TIAM Rac1-associated GEF 2 short form (TIAM2S) as an oncoprotein alters the immunity of peripheral immune cells to construct an inflammatory tumor microenvironment. However, its role in the activation of microglia, the primary innate immune cells of the brain, and neuroinflammation remains unknown. This study investigated the mechanism underlying TIAM2S shapes immune properties of microglia to facilitate neuron damage. Human microglial clone 3 cell line (HMC3) and human brain samples were applied to determine the presence of TIAM2S in microglia by western blots and double immunostaining. Furthermore, TIAM2S transgenic mice combined with multiple reconstituted primary neuron-glial culture systems and a cytokine array were performed to explore how TIAM2S shaped immune priming of microglia and participated in lipopolysaccharide (LPS)-induced neuron damage. TIAM2S protein was detectable in HMC3 cells and presented in a small portion (~11.1%) of microglia in human brains referred to as TIAM2S-positive microglia. With the property of secreted soluble factor-mediated immune priming, TIAM2S-positive microglia enhanced LPS-induced neuroinflammation and neural damage in vivo and in vitro. The gain- and loss-of-function experiments showed soluble intercellular adhesion molecule-1 (sICAM-1) participated in neurotoxic immune priming of TIAM2S+ microglia. Together, this study demonstrated a novel TIAM2S-positive microglia subpopulation enhances inflammation and neurotoxicity through sICAM-1-mediated immune priming.


Subject(s)
Inflammation , Intercellular Adhesion Molecule-1 , Microglia , Tumor Microenvironment , Animals , Humans , Mice , Inflammation/metabolism , Intercellular Adhesion Molecule-1/genetics , Intercellular Adhesion Molecule-1/metabolism , Lipopolysaccharides/pharmacology , Mice, Transgenic , Microglia/metabolism , Neuroinflammatory Diseases/immunology , Tumor Microenvironment/immunology
3.
J Hazard Mater ; 443(Pt B): 130349, 2023 Feb 05.
Article in English | MEDLINE | ID: mdl-36370479

ABSTRACT

Cu-based functional materials are excellent candidates for the elimination of iodine anions. However, the low utilization rate of Cu and its unsatisfactory adsorption performance limit its large-scale practical applications. This paper proposes a co-gelation method to obtain Cu/Al2O3 aerogels with a high specific area (537 m2/g). Cu/Al2O3 aerogels have a hierarchical porous structure and contain a high proportion of Cu (20.5 wt%). The high dispersibility of Cu, which is based on an in-situ gel process, provides conditions for the high-efficiency elimination of iodide anions. We conducted adsorption experiments that demonstrated that the fabricated Cu/Al2O3 aerogel had an ultrahigh adsorption capacity (407.6 mg/g) and a fast adsorption equilibrium time (0.5 h) for iodide anions. Additionally, the Cu/Al2O3 aerogel could selectively capture iodine anions even in the presence of high concentrations of competing ions (NO3-, SO42-, and Cl- at 60 mmol/L). Importantly, the aerogel can operate in a wide pH range of 3-11 without causing secondary pollution. This work demonstrates that low-cost Cu/Al2O3 aerogels exhibit great potential for eliminating radioactive iodine anions.

4.
Autism ; 27(3): 723-736, 2023 04.
Article in English | MEDLINE | ID: mdl-35999699

ABSTRACT

LAY ABSTRACT: Research has found differences in responding to various sensory stimuli among autistic individuals, which are associated with social and adaptive skills. However, our understanding of sensory profiles in autism has been complicated due to the variable presentation of sensory symptoms. One way to better understand variability in sensory symptoms is to use advanced statistical approaches, such as latent profile analysis, that allow for the identification of more similar sensory classes in otherwise variable groups. We used the Short Sensory Profile to identify homogeneous classes of sensory reactivity in autistic children based on both severity and modality and examined whether sensory classes differed in terms of autism characteristics, adaptive skills, and attention-deficit/hyperactivity disorder symptoms. Based on the pattern of both severity and modality, four sensory classes emerged and were named Moderate/Mixed (35.5%; probable-to-definite differences in all modalities except in movement sensitivity and low energy/weakness), Severe/Mixed (8.5%; definite sensory differences in all modalities except in low energy/weakness), Moderate/Broad (14.6%; probable-to-definite differences in all modalities), and Low/Mixed (41.1%; typical scores in most modalities with probable differences in taste/smell sensitivity, under-responsive/seeks sensation, and auditory filtering). The Severe/Mixed class exhibited greater problems in a variety of areas such as social, adaptive, and attention-deficit/hyperactivity disorder symptoms, whereas the Low/Mixed class showed overall fewer problems. This may provide insight for clinicians and researchers aiming to understand whether autistic children who exhibit distinct sensory patterns are more or less likely to also experience social, adaptive, and/or attention/behavior-related difficulties.


Subject(s)
Autism Spectrum Disorder , Autistic Disorder , Humans , Child , Child, Preschool , Autistic Disorder/complications , Autism Spectrum Disorder/diagnosis , Sensation , Surveys and Questionnaires , Perception
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