N6-methyladenosine (m
A) modification is known to impact many aspects of RNA metabolism, including mRNA stability and translation, and is highly prevalent in the brain.
We show that m
A modification ...displays temporal and spatial dynamics during neurodevelopment and aging. Genes that are temporally differentially methylated are more prone to have mRNA expression changes and affect many pathways associated with nervous system development. Furthermore, m
A shows a distinct tissue-specific methylation profile, which is most pronounced in the hypothalamus. Tissue-specific methylation is associated with an increase in mRNA expression and is associated with tissue-specific developmental processes. During the aging process, we observe significantly more m
A sites as age increases, in both mouse and human. We show a high level of overlap between mouse and human; however, humans at both young and old ages consistently show more m
A sites compared to mice. Differential m
A sites are found to be enriched in alternative untranslated regions of genes that affect aging-related pathways. These m
A sites are associated with a strong negative effect on mRNA expression. We also show that many Alzheimer-related transcripts exhibit decreased m
A methylation in a mouse model of Alzheimer's disease, which is correlated with reduced protein levels.
Our results suggest that m
A exerts a critical function in both early and late brain development in a spatio-temporal fashion. Furthermore, m
A controls protein levels of key genes involved in Alzheimer's disease-associated pathways, suggesting that m
A plays an important role in aging and neurodegenerative disease.
Fat mass and obesity-associated gene (FTO) is a member of the Fe (II)- and oxoglutarate-dependent AlkB dioxygenase family and is linked to both obesity and intellectual disability. The role of FTO in ...neurodevelopment and neurogenesis, however, remains largely unknown. Here we show that FTO is expressed in adult neural stem cells and neurons and displays dynamic expression during postnatal neurodevelopment. The loss of FTO leads to decreased brain size and body weight. We find that FTO deficiency could reduce the proliferation and neuronal differentiation of adult neural stem cells in vivo, which leads to impaired learning and memory. Given the role of FTO as a demethylase of N6-methyladenosine (m6A), we went on to perform genome-wide m6A profiling and observed dynamic m6A modification during postnatal neurodevelopment. The loss of FTO led to the altered expression of several key components of the brain derived neurotrophic factor pathway that were marked by m6A. These results together suggest FTO plays important roles in neurogenesis, as well as in learning and memory.
Algicidal bacteria have received broad acceptance as an ecofriendly tool for controlling harmful algal blooms. However, their practical application is still limited to the lab-scale tests due to the ...complex alga-bacterium interactions in different nutrient statuses. In this study, the Aeromonas sp. L23 that exhibit relatively wide-spectrum in algicidal activity was isolated from a eutrophic agricultural lake. The physiological response of cyanobacteria and green to the algicidal activity under varied nutritional status were studied in an alga-bacterial co-culture. The algicidal activities of L23 against Microcystis aeruginosa UTEX LB 2385, Microcystis aeruginosa NHSB, Anabaena variabilis AG10064, Scenedesmus quadricauda AG10003, and Chlorella vulgaris AG10034 were 88 ± 1.2%, 94 ± 2.6%, 93 ± 0.5%, 82 ± 1.1%, and 47 ± 0.9%, respectively. The L23 cells had low algicidal activity in cell pellet (3%-9%) compared with the cell-free supernatant (78%-93%), indicating that the activity is induced by extracellular substances. Adding glucose, NaNO3, NH4Cl, and KH2PO4 to the co-culture raised the algicidal activity of the L23 against green algae by 5%-50%. Conversely, a 10%-20% decrease in activity occurred against the target cyanobacteria except M. aeruginosa UTEX LB 2385. These results indicated that the interspecific algicidal activity changes according to the nutritional status, which means that the alga-bacterium interaction will be more complex in the field where the nutritional status changes from time to time.
To investigate SARS-CoV-2 transmission from humans to animals in Seoul, South Korea, we submitted samples from companion animals owned by persons with confirmed COVID-19. Real-time PCR indicated ...higher SARS-CoV-2 viral infection rates for dogs and cats than previously reported from the United States and Europe. Host-specific adaptations could introduce mutant SARS-CoV-2 to humans.
...it is of paramount importance to initiate a special issue that specifically highlights the advancements made in the generation and utilization of organoids derived from stem cells. Interestingly, ...exosomes derived from MSCs that were pretreated with KGN (wingless-related integration site 7a (Wnt7a)) exhibited an even more remarkable stimulation of proliferation. ...the combined treatments demonstrated significant potential in facilitating the repair of articular cartilage damage, thus illuminating a promising strategy for future therapeutic applications. ...two independent review articles by Ma et al. and Xu et al. focus on the recent progress made in the generation methodology and applications of human brain organoids.
Public healthcare has transformed from treatment to preventive care and disease management. The Common Data Model (CDM) provides a standard data structure defined to utilize hospitals’ data. Digital ...identity takes a significant role as the body of information about an individual used by computer systems to identify and establish trust among organizations. The CDM research network, composed of users handling medical information, has several digital identities associated with their activity. A high central authority cost can be reduced by Distributed Ledger Technology (DLT). It enables users to control their identities independently of a third party. To preserve the privacy of researchers in clinical studies, secure identification is the main concern of identifying the researcher and its agents. To do so, they should pose a legally verifiable credential in the cloud CDM. By presenting the proof represented by the capability that the user has, each identity has access control that is linked to an authentication credential that the cloud CDM can verify. Assurance in one’s identity is confirmed by asserting claims with the identity and its capability, providing its verifiable credential to the authentication entity in the cloud CDM. This paper describes the user-centric claim-based identity operation model based on use cases to handle researcher identity in the cloud CDM. In this model, credentials are designed as a capability and presented to them to access SPs in the cloud CDM. To provide well-controlled access control in the cloud CDM, we build and prototype a capability based CDM management system.
In contrast with numerous studies of glutamate receptor-associated proteins and their involvement in the modulation of excitatory synapses, much less is known about mechanisms controlling ...postsynaptic GABAA receptor (GABAAR) numbers. Using tandem affinity purification from tagged GABAAR γ2 subunit transgenic mice and proteomic analysis, we isolated several GABAAR-associated proteins, including Cleft lip and palate transmembrane protein 1 (Clptm1). Clptm1 interacted with all GABAAR subunits tested and promoted GABAAR trapping in the endoplasmic reticulum. Overexpression of Clptm1 reduced GABAAR-mediated currents in a recombinant system, in cultured hippocampal neurons, and in brain, with no effect on glycine or AMPA receptor-mediated currents. Conversely, knockdown of Clptm1 increased phasic and tonic inhibitory transmission with no effect on excitatory synaptic transmission. Furthermore, altering the expression level of Clptm1 mimicked activity-induced inhibitory synaptic scaling. Thus, in complement to other GABAAR-associated proteins that promote receptor surface expression, Clptm1 limits GABAAR forward trafficking and regulates inhibitory homeostatic plasticity.
•Transgenic proteomic analysis reveals Clptm1 association with many GABAAR subunits•Clptm1 limits GABAAR forward trafficking by trapping receptors in the ER and Golgi•Altering the expression of Clptm1 scales phasic and tonic inhibitory transmission•Clptm1 modulates activity-dependent inhibitory synaptic homeostasis
Ge et al. identify Clptm1 as a GABAAR-associated protein that interacts with multiple subunits. They show that Clptm1 traps GABAARs in the ER and Golgi to scale phasic and tonic inhibitory transmission and modulate activity-induced inhibitory homeostasis.
Emerging evidence suggests that active DNA demethylation machinery plays important epigenetic roles in mammalian adult neurogenesis; however, the precise molecular mechanisms and critical functional ...players of DNA demethylation in this process remain largely unexplored. Ten-eleven translocation (Tet) proteins convert 5-methylcytosine (5mC) to 5-hydroxymethylcytosine (5hmC) and its downstream derivatives. Here we show that 5hmC is elevated during the differentiation of adult neural stem cells (aNSCs), and Tet2 is primarily responsible for modulating 5hmC dynamics. Depletion of Tet2 leads to increased aNSC proliferation and reduced differentiation in vitro and in vivo. Genome-wide transcriptional analyses reveal important epigenetic roles of Tet2 in maintaining the transcriptome landscape related to neurogenesis. Mechanistically, transcription factor forkhead box O3 (Foxo3a) physically interacts with Tet2 and regulates the expression of genes related to aNSC proliferation. These data together establish an important role for the Tet2-Foxo3a axis in epigenetically regulating critical genes in aNSCs during adult neurogenesis.
Genetic analyses have linked microRNA-137 (MIR137) to neuropsychiatric disorders, including schizophrenia and autism spectrum disorder. miR-137 plays important roles in neurogenesis and neuronal ...maturation, but the impact of miR-137 loss-of-function in vivo remains unclear. Here we show the complete loss of miR-137 in the mouse germline knockout or nervous system knockout (cKO) leads to postnatal lethality, while heterozygous germline knockout and cKO mice remain viable. Partial loss of miR-137 in heterozygous cKO mice results in dysregulated synaptic plasticity, repetitive behavior, and impaired learning and social behavior. Transcriptomic and proteomic analyses revealed that the miR-137 mRNA target, phosphodiesterase 10a (Pde10a), is elevated in heterozygous knockout mice. Treatment with the Pde10a inhibitor papaverine or knockdown of Pde10a ameliorates the deficits observed in the heterozygous cKO mice. Collectively, our results suggest that MIR137 plays essential roles in postnatal neurodevelopment and that dysregulation of miR-137 potentially contributes to neuropsychiatric disorders in humans.
School closures and family economic instability caused by the COVID-19 lockdown measures have threatened the mental health and academic progress of adolescents. Through secondary data analysis of ...World Vision Asia Pacific Region's COVID-19 response-assessments in May-June 2020, this study examined whether adolescents' study, physical, and leisure activities, psychosocial status, and sources of COVID-19 information differed by gender.
The assessments used cross-sectional surveys of adolescents in poor communities served by World Vision (n = 5552 males and n = 6680 females) aged 10-18 years old in six countries. The study households of adolescents were selected either by random sampling or non-probability convenience sampling and assessed using telephone or in-person interviews. Multivariate logistic regression analyses examined the relationship between gender and psychosocial status; daily activities (e.g., play, study); and sources of information about COVID-19.
Participation in remote education was low (range: 0.5-20.7% across countries), with gender difference found only in Vietnam. Compared to males, female adolescents were less likely to play physically with a range of AOR: 0.36-0.55 (n = 5 countries) or play video games with a range of AOR: 0.55-0.72 (n = 2 countries). Female adolescents were more likely to feel isolated or stressed (India, AOR = 1.13, 95%CI:1.00, 1.26); feel unsafe (the Philippines, AOR = 2.22, 95%CI:1.14, 4.33; Vietnam, AOR = 1.31, 95%CI:1.03, 1.47); be concerned about education (India, AOR = 1.24, 95%CI:1.09, 1.41; Myanmar, AOR = 1.59, 95%CI:1.05, 2.40); or be concerned about household income (India, AOR = 1.13, 95%CI:1.00, 1.28; Vietnam, AOR = 1.31, 95%CI:1.09, 1.58). Female adolescents were also less likely to obtain COVID-19 related information through internet/social media (Bangladesh, AOR = 0.51, 95%CI:0.41, 0.64; India, AOR = 0.84, 95%CI:0.73, 0.96; and Myanmar, AOR = 0.65, 95%CI:0.43, 0.97) and mobile call or short message (India, AOR = 0.88, 95%CI:0.80, 0.98) but more likely to get the information from friends (Vietnam, AOR = 1.18, 95%CI:1.02, 1.36) and family (Bangladesh, AOR = 1.44, 95% CI:1.21, 1.70; India, AOR = 1.29, 95% CI:1.15, 1.45).
An understanding of gender differences in the impacts of COVID-19 on adolescents' schooling, physical, and mental health can inform adolescent protection interventions. Psychosocial support during response and recovery phases needs to pay special attention to gender differences, since female adolescents' psychosocial status is at higher risk when facing the challenges of this pandemic.
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