Dynamic reconfiguration of brain coactivation states that underlying working memory correlates with cognitive decline in clinically unimpaired older adults.

Impairments in working memory (WM) are evident in both clinically diagnosed patients with mild cognitive decline and older adults at risk, as indicated by lower scores on neuropsychological tests. Examining the WM-related neural signatures in at-risk older adults becomes essential for timely intervention. WM functioning relies on dynamic brain activities, particularly within the frontoparietal system. However, it remains unclear whether the cognitive decline would be reflected in the decreased dynamic reconfiguration of brain coactivation states during WM tasks. We enrolled 47 older adults and assessed their cognitive function using the Montreal Cognitive Assessment. The temporal dynamics of brain coactivations during a WM task were investigated through graph-based time-frame modularity analysis. Four primary recurring states emerged: two task-positive states with positive activity in the frontoparietal system (dorsal attention and central executive); two task-negative states with positive activity in the default mode network accompanied by negative activity in the frontoparietal networks. Heightened WM load was associated with increased flexibility of the frontoparietal networks, but the cognitive decline was correlated with reduced capacity for neuroplastic changes in response to increased task demands. These findings advance our understanding of aberrant brain reconfiguration linked to cognitive decline, potentially aiding early identification of at-risk individuals.

Fusion analysis of gray matter and white matter in subjective cognitive decline and mild cognitive impairment by multimodal CCA-joint ICA.

BACKGROUND: Previous multimodal neuroimaging studies analyzed each dataset independently in subjective cognitive decline (SCD) and mild cognitive impairment (MCI), missing the cross-information. Multi-modal fusion analysis can provide more integral and comprehensive information regarding the brain. There has been a paucity of research on fusion analysis of sMRI and DTI in SCD and MCI. MATERIALS AND METHODS: In the present study, we conducted fusion analysis of structural MRI and DTI by applying multimodal canonical correlation analysis with joint independent component analysis (mCCA-jICA) to capture the cross-information of gray matter (GM) and white matter (WM) in 62 SCD patients, 99 MCI patients, and 70 healthy controls (HCs). We further analyzed correlations between the mixing coefficients of mCCA-jICA and neuropsychological scores among the three groups. RESULTS: A set of joint-discriminative independent components of GM and fractional anisotropy (FA) exhibited significant links between SCD and HCs, as well as between MCI and HCs. The covariant abnormalities primarily involved the frontal lobe/middle temporal gyrus/calcarine sulcus-anterior thalamic radiation/superior longitudinal fasciculus in SCD, and middle temporal gyrus/ fusiform gyrus/caudate necleus-forceps minor/anterior thalamic radiation in MCI. There was no significant difference between SCD and MCI groups. CONCLUSIONS: The covariant GM-WM abnormalities in SCD and MCI were found in specific brain regions involved in cognitive processing, which confirms the simultaneous GM and WM changes underlying cognitive decline. These findings suggest that multimodal fusion analysis allows for a more comprehensive understanding of the association among different types of brain tissues and its crucial role in the neuropathological mechanism of SCD and MCI.

Exposure to Deepwater Horizon Crude Oil Burnoff Particulate Matter Induces Pulmonary Inflammation and Alters Adaptive Immune Response.

The ″in situ burning" of trapped crude oil on the surface of Gulf waters during the 2010 Deepwater Horizon (DWH) oil spill released numerous pollutants, including combustion-generated particulate matter (PM). Limited information is available on the respiratory impact of inhaled in situ burned oil sail particulate matter (OSPM). Here we utilized PM collected from in situ burn plumes of the DWH oil spill to study the acute effects of exposure to OSPM on pulmonary health. OSPM caused dose-and time-dependent cytotoxicity and generated reactive oxygen species and superoxide radicals in vitro. Additionally, mice exposed to OSPM exhibited significant decreases in body weight gain, systemic oxidative stress in the form of increased serum 8-isoprostane (8-IP) levels, and airway inflammation in the form of increased macrophages and eosinophils in bronchoalveolar lavage fluid. Further, in a mouse model of allergic asthma, OSPM caused increased T helper 2 cells (Th2), peribronchiolar inflammation, and increased airway mucus production. These findings demonstrate that acute exposure to OSPM results in pulmonary inflammation and alteration of innate/adaptive immune responses in mice and highlight potential respiratory effects associated with cleaning up an oil spill.

Specific assembly pathway of sarcoglycans is dependent on beta- and delta-sarcoglycan.

Mutations in sarcoglycans (SG) have been reported to cause autosomal-recessive limb-girdle muscular dystrophy (LGMD) and dilated cardiomyopathy. In skeletal and cardiac muscle, sarcoglycans exist as a complex of four transmembrane proteins (alpha-, beta-, gamma-, and delta-SG). In this study, the assembly of the sarcoglycan complex was examined in a heterologous expression system. Our results demonstrated that the assembly process occurs as a discrete stepwise process. We found that beta-SG appears to play an initiating role and its association with delta-SG is essential for the proper localization of the sarcoglycan complex to the cell membrane. The incorporation of alpha-SG into the sarcoglycan complex occurs at the final stage by interaction with gamma-SG. These findings were supported by chemical cross-linking of endogenous sarcoglycans in cultured myotubes. We have also provided evidence that glycosylation-defective mutations in beta-SG and a common mutation in gamma-SG (C283Y) disrupt sarcoglycan-complex formation. Our proposed model for the assembly and structure of sarcoglycans should generate important insight into their function in muscle as well as their role in muscular dystrophies and cardiomyopathies.