Microsatellite Instability in Mouse Models of Colorectal Cancer

Microsatellite instability (MSI) is caused by DNA mismatch repair deficiency and is an important prognostic and predictive biomarker in colorectal cancer but relatively few studies have exploited mouse models in the study of its clinical utility. Furthermore, most previous studies have looked at MSI in the small intestine rather than the colon of mismatch repair deficient Msh2-knockout (KO) mice. Here we compared Msh2-KO, p53-KO, and wild type (WT) mice that were treated with the carcinogen azoxymethane (AOM) and the nonsteroidal anti-inflammatory drug sulindac or received no treatment. The induced tumors and normal tissue specimens from the colon were analysed with a panel of five mononucleotide repeat markers. MSI was detected throughout the normal colon in untreated Msh2-KO mice and this involved contraction of the repeat sequences compared to WT. The markers with longer mononucleotide repeats (37–59) were the most sensitive for MSI while the markers with shorter repeats (24) showed only minor change. AOM exposure caused further contraction of the Bat37 and Bat59 repeats in the distal colon of Msh2-KO mice which was reversed by sulindac. Thus AOM-induced carcinogenesis is associated with increased instability of mononucleotide repeats in the colon of Msh2-KO mice but not in WT or p53-KO mice. Chemoprevention of these tumors by sulindac treatment reversed or prevented the increased MSI

Earth Observations and Integrative Models in Support of Food and Water Security

Global food production depends upon many factors that Earth observing satellites routinely measure about water, energy, weather, and ecosystems. Increasingly sophisticated, publicly-available satellite data products can improve efficiencies in resource management and provide earlier indication of environmental disruption. Satellite remote sensing provides a consistent, long-term record that can be used effectively to detect large-scale features over time, such as a developing drought. Accuracy and capabilities have increased along with the range of Earth observations and derived products that can support food security decisions with actionable information. This paper highlights major capabilities facilitated by satellite observations and physical models that have been developed and validated using remotely-sensed observations. Although we primarily focus on variables relevant to agriculture, we also include a brief description of the growing use of Earth observations in support of aquaculture and fisheries

Microsatellite Instability in Mouse Models of Colorectal Cancer

Microsatellite instability (MSI) is caused by DNA mismatch repair deficiency and is an important prognostic and predictive biomarker in colorectal cancer but relatively few studies have exploited mouse models in the study of its clinical utility. Furthermore, most previous studies have looked at MSI in the small intestine rather than the colon of mismatch repair deficient Msh2-knockout (KO) mice. Here we compared Msh2-KO, p53-KO, and wild type (WT) mice that were treated with the carcinogen azoxymethane (AOM) and the nonsteroidal anti-inflammatory drug sulindac or received no treatment. The induced tumors and normal tissue specimens from the colon were analysed with a panel of five mononucleotide repeat markers. MSI was detected throughout the normal colon in untreated Msh2-KO mice and this involved contraction of the repeat sequences compared to WT. The markers with longer mononucleotide repeats (37–59) were the most sensitive for MSI while the markers with shorter repeats (24) showed only minor change. AOM exposure caused further contraction of the Bat37 and Bat59 repeats in the distal colon of Msh2-KO mice which was reversed by sulindac. Thus AOM-induced carcinogenesis is associated with increased instability of mononucleotide repeats in the colon of Msh2-KO mice but not in WT or p53-KO mice. Chemoprevention of these tumors by sulindac treatment reversed or prevented the increased MSI

Synthesis and Pharmacological Evaluation of Novel Schiff Base Analogues of 3-(4-amino) Phenylimino) 5-fluoroindolin-2-one

In our study, a series of novel 3-(4-(benzylideneamino) phenylimino) 4-fluoroindolin-2-one derivatives were synthesized and characterized by spectral (I.R, 1H NMR, mass) and elemental analysis. The title compounds (N1-N10) were evaluated for analgesic, anti-inflammatory, and ulcerogenic index activities. Results displayed that compound N3 exhibited significant analgesic activity. Among the title compounds studied, N2, N3, and N8 exhibited significant anti- inflammatory activity comparable to reference standard diclofenac sodium. Interestingly, the test compounds showed only mild ulcerogenic side effect when compared to aspirin

Adar3 is involved in learning and memory in mice

© 2018 Mladenova, Barry, Konen, Pineda, Guennewig, Avesson, Zinn, Schonrock, Bitar, Jonkhout, Crumlish, Kaczorowski, Gong, Pinese, Franco, Walkley, Vissel and Mattick. The amount of regulatory RNA encoded in the genome and the extent of RNA editing by the post-transcriptional deamination of adenosine to inosine (A-I) have increased with developmental complexity and may be an important factor in the cognitive evolution of animals. The newest member of the A-I editing family of ADAR proteins, the vertebrate-specific ADAR3, is highly expressed in the brain, but its functional significance is unknown. In vitro studies have suggested that ADAR3 acts as a negative regulator of A-I RNA editing but the scope and underlying mechanisms are also unknown. Meta-analysis of published data indicates that mouse Adar3 expression is highest in the hippocampus, thalamus, amygdala, and olfactory region. Consistent with this, we show that mice lacking exon 3 of Adar3 (which encodes two double stranded RNA binding domains) have increased levels of anxiety and deficits in hippocampus-dependent short- and long-term memory formation. RNA sequencing revealed a dysregulation of genes involved in synaptic function in the hippocampi of Adar3-deficient mice. We also show that ADAR3 transiently translocates from the cytoplasm to the nucleus upon KCl-mediated activation in SH-SY5Y cells. These results indicate that ADAR3 contributes to cognitive processes in mammals

Mental Health among Adults during the COVID-19 Pandemic Lockdown: A Cross-Sectional Multi-Country Comparison

Despite the global impact of COVID-19, studies comparing the effects of COVID-19 on population mental health across countries are sparse. This study aimed to compare anxiety and depression symptoms during the COVID-19 lockdown among adults from 11 countries and to examine their associations with country-level COVID-19 factors and personal COVID-19 exposure. A cross-sectional survey was conducted among adults (≥18 years) in 11 countries (Brazil, Bulgaria, China, India, Ireland, North Macedonia, Malaysia, Singapore, Spain, Turkey, United States). Mental health (anxiety, depression, resilient coping, hope) and other study data were collected between June-August 2020. Of the 13,263 participants, 62.8% were female and 51.7% were 18-34 years old. Participants living in Brazil had the highest anxiety and depression symptoms while participants living in Singapore had the lowest. Greater personal COVID-19 exposure was associated with increased anxiety and depression symptoms, but country-level COVID-19 factors were not. Higher levels of hope were associated with reduced anxiety and depression; higher levels of resilient coping were associated with reduced anxiety but not depression. Substantial variations exist in anxiety and depression symptoms across countries during the COVID-19 lockdown, with personal COVID-19 exposure being a significant risk factor. Strategies that mitigate COVID-19 exposure and enhance hope and resilience may reduce anxiety and depression during global emergencies