Search

BACKGROUND:Resistant starch is a prebiotic metabolized by the gut bacteria. It has been shown to attenuate chronic kidney disease (CKD) progression in rats. Previous studies employed taxonomic analysis using 16S rRNA sequencing and untargeted metabolomics profiling. Here we expand these studies by metaproteomics, gaining new insight into the host-microbiome interaction. METHODS:Differences between cecum contents in CKD rats fed a diet containing resistant starch with those fed a diet containing digestible starch were examined by comparative metaproteomics analysis. Taxonomic information was obtained using unique protein sequences. Our methodology results in quantitative data covering both host and bacterial proteins. RESULTS:5,834 proteins were quantified, with 947 proteins originating from the host organism. Taxonomic information derived from metaproteomics data surpassed previous 16S RNA analysis, and reached species resolutions for moderately abundant taxonomic groups. In particular, the Ruminococcaceae family becomes well resolved-with butyrate producers and amylolytic species such as R. bromii clearly visible and significantly higher while fibrolytic species such as R. flavefaciens are significantly lower with resistant starch feeding. The observed changes in protein patterns are consistent with fiber-associated improvement in CKD phenotype. Several known host CKD-associated proteins and biomarkers of impaired kidney function were significantly reduced with resistant starch supplementation. Data are available via ProteomeXchange with identifier PXD008845. CONCLUSIONS:Metaproteomics analysis of cecum contents of CKD rats with and without resistant starch supplementation reveals changes within gut microbiota at unprecedented resolution, providing both functional and taxonomic information. Proteins and organisms differentially abundant with RS supplementation point toward a shift from mucin degraders to butyrate producers.

Background Chat Generative Pre-trained Transformer (ChatGPT) and other ChatBots have emerged as tools for interacting with information in manners resembling natural human speech. Consequently, the technology is used across various disciplines, including business, education, and even in biomedical sciences. There is a need to better understand how ChatGPT can be used to advance gerontology research. Therefore, we evaluated ChatGPT responses to questions on specific topics in gerontology research, and brainstormed recommendations for its use in the field. Methods We conducted semistructured brainstorming sessions to identify uses of ChatGPT in gerontology research. We divided a team of multidisciplinary researchers into 4 topical groups: (a) gero-clinical science, (b) basic geroscience, (c) informatics as it relates to electronic health records, and (d) gero-technology. Each group prompted ChatGPT on a theory-, methods-, and interpretation-based question and rated responses for accuracy and completeness based on standardized scales. Results ChatGPT responses were rated by all groups as generally accurate. However, the completeness of responses was rated lower, except by members of the informatics group, who rated responses as highly comprehensive. Conclusions ChatGPT accurately depicts some major concepts in gerontological research. However, researchers have an important role in critically appraising the completeness of its responses. Having a single generalized resource like ChatGPT may help summarize the preponderance of evidence in the field to identify gaps in knowledge and promote cross-disciplinary collaboration. [ABSTRACT FROM AUTHOR]

The space extending beyond Earth's magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body 1H (0.5 Gy; 150 MeV/n; 18–19 cGy/minute) and an hour later to 16O (0.1Gy; 600 MeV/n; 18–33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci. [ABSTRACT FROM AUTHOR]

Breast cancer (BC) is the most common cancer among women. Fortunately, BC survival rates have increased because the implementation of adjuvant chemotherapy leading to a growing population of survivors. However, chemotherapy-induced cognitive impairments (CICIs) affect up to 75% of BC survivors and may be driven by inflammation and oxidative stress. Chemotherapy-induced cognitive impairments can persist 20 years and hinder survivors' quality of life. To identify early effects of CMF administration in mice, we chose to evaluate adult female mice at 2-week postchemotherapy. Mice received weekly IP administration of CMF (or saline) for 4 weeks, completed behavioral testing, and were sacrificed 2 weeks following their final CMF injection. Behavioral results indicated long-term memory (LTM) impairments postchemotherapy, but did not reveal short-term memory deficits. Dendritic morphology and spine data found increases in overall spine density within CA1 basal and CA3 basal dendrites, but no changes in DG, CA1 apical, or CA3 apical dendrites. Further analysis revealed decreases in arborization across the hippocampus (DG, CA1 apical and basal, CA3 apical and basal). These physiological changes within the hippocampus correlate with our behavioral data indicating LTM impairments following CMF administration in female mice 2-week postchemotherapy. Hippocampal cytokine analysis identified decreases in IL-1α, IL-1β, IL-3, IL-10, and TNF-α levels. [ABSTRACT FROM AUTHOR]

• TAC significantly compromised the dendritic architecture. • TAC downregulation of proteins within key metabolic and signaling pathways associated with cognitive dysfunction. • TAC impaired hippocampal dependent behavior. Breast cancer is the most commonly diagnosed cancer among women and it is estimated that about 30% of newly diagnosed cancers in women will be breast cancers. While advancements in treating breast cancer have led to an average 5-year survival rate of 90%, many survivors experience cognitive impairments as a result of chemotherapy treatment. Doxorubicin, cyclophosphamide, and docetaxel (TAC) are commonly administered as breast cancer treatments; however, there are few studies that have tested the cognitive effects of TAC. In the current study, 12-week-old female C57BL/6 mice received 4 weekly intraperitoneal injections of either saline or a combination therapy of doxorubicin and cyclophosphamide followed by 4 weekly docetaxel injections. Four weeks after the last injection, mice were tested for hippocampus-dependent cognitive performance in the Y-maze and the Morris water maze. During Y-maze testing, mice exposed to TAC exhibited impairment. During the water maze assessment, all animals were able to locate the visible and hidden platform locations. However, mice that received the TAC presented with a significant impairment in spatial memory retention on the probe trial days. TAC treatment significantly decreases the dendritic complexity of arborization in the dentate gyrus region of the hippocampus. In addition, comparative proteomic analysis revealed downregulation of proteins within key metabolic and signaling pathways associated with cognitive dysfunction, such as oxidative phosphorylation, ephrin signaling, and calcium signaling. [ABSTRACT FROM AUTHOR]

Competing Interests: None

The effects of radiation in space on human cognition are a growing concern for NASA scientists and astronauts as the possibility for long-duration missions to Mars becomes more tangible. Oxygen ( 16 O) radiation is of utmost interest considering that astronauts will interact with this radiation frequently. 16 O radiation is a class of galactic cosmic ray (GCR) radiation and also present within spacecrafts. Whole-body exposure to high linear energy transfer (LET) radiation has been shown to affect hippocampal-dependent cognition. To assess the effects of high-LET radiation, we gave 6-month-old female C57BL/6 mice whole-body exposure to 16 O at 0.25 or 0.1 Gy at NASA's Space Radiation Laboratory. Three months following irradiation, animals were tested for cognitive performance using the Y-maze and Novel Object Recognition paradigms. Our behavioral data shows that 16 O radiation significantly impairs object memory but not spatial memory. Also, dendritic morphology characterized by the Sholl analysis showed that 16 O radiation significantly decreased dendritic branch points, ends, length, and complexity in 0.1 Gy and 0.25 Gy dosages. Finally, we found no significant effect of radiation on single nucleotide polymorphisms in hippocampal genes related to oxidative stress, inflammation, and immediate early genes. Our data suggest exposure to heavy ion 16 O radiation modulates hippocampal neurons and induces behavioral deficits at a time point of three months after exposure in female mice., (Copyright © 2021 Elsevier B.V. All rights reserved.)

The space extending beyond Earth's magnetosphere is subject to a complex field of high-energy charged nuclei, which are capable of traversing spacecraft shielding and human tissues, inducing dense ionization events. The central nervous system is a major area of concern for astronauts who will be exposed to the deep-space radiation environment on a mission to Mars, as charged-particle radiation has been shown to elicit changes to the dendritic arbor within the hippocampus of rodents, and related cognitive-behavioral deficits. We exposed 6-month-old male mice to whole-body 1 H (0.5 Gy; 150 MeV/n; 18-19 cGy/minute) and an hour later to 16 O (0.1Gy; 600 MeV/n; 18-33 Gy/min) at NASA's Space Radiation Laboratory as a galactic cosmic ray-relevant model. Animals were housed with bedding which provides cognitive enrichment. Mice were tested for cognitive behavior 9 months after exposure to elucidate late radiation effects. Radiation induced significant deficits in novel object recognition and short-term spatial memory (Y-maze). Additionally, we observed opposing morphological differences between the mature granular and pyramidal neurons throughout the hippocampus, with increased dendritic length in the dorsal dentate gyrus and reduced length and complexity in the CA1 subregion of the hippocampus. Dendritic spine analyses revealed a severe reduction in mushroom spine density throughout the hippocampus of irradiated animals. Finally, we detected no general effect of radiation on single-nucleotide polymorphisms in immediate early genes, and genes involved in inflammation but found a higher variant allele frequency in the antioxidants thioredoxin reductase 2 and 3 loci., (Copyright © 2020 Kiffer, Alexander, Anderson, Groves, McElroy, Wang, Sridharan, Bauer, Boerma and Allen.)