Methylation of the suppressor gene p16INK4a: Mechanism and consequences

Tumor suppressor genes in the CDKN2A/B locus (p15INK4b, p16INK4a, and p14ARF) function as biological barriers to transformation and are the most frequently silenced or deleted genes in human cancers. This gene silencing frequently occurs due to DNA methylation of the promoter regions, although the underlying mechanism is currently unknown. We present evidence that methylation of p16INK4a promoter is associated with DNA damage caused by interference between transcription and replication processes. Inhibition of replication or transcription significantly reduces the DNA damage and CpGs methylation of the p16INK4a promoter. We conclude that de novo methylation of the promoter regions is dependent on local DNA damage. DNA methylation reduces the expression of p16INK4a and ultimately removes this barrier to oncogene-induced senescence

Losing sight of Luck: Automatic approach tendencies toward gambling cues in Canadian moderate- to high-risk gamblers – A replication study

Evidence for approach bias tendencies to underly automatic behavioural impulses towards seeking out gambling activities in the presence of appetitive salient cues was first shown by Boffo et al. (2018) in a Dutch sample. Relative to non-problem gamblers, moderate-to-high-risk gamblers demonstrated stronger approach tendencies towards gambling-related stimuli compared with neutral ones. Moreover, gambling approach bias was associated with past-month gambling behaviour and predictive of gambling activity persistence over time. The current study aimed to replicate these findings within a Canadian sample evaluating the concurrent and longitudinal correlates of gambling approach bias. The study was conducted online, available throughout Canada. Twenty-seven non-treatment-seeking moderate-to-high-risk gamblers and 26 non-problem gamblers community-recruited via multiple channels (i.e., internet and newspaper advertisements, land-based flyers, and university recruitment portals). Participants completed two online assessment sessions 6-months apart. Each session included (1) self-report measures of gambling behaviour (frequency, duration, and expenditure), (2) self-report assessment of problem gambling severity (PGSI), and (3) a gambling approach-avoidance task, utilising culturally relevant stimuli tailored to individual gambling habits. However, our study failed to replicate Boffo et al. (2018) findings in a Canadian sample. Relative to non-problem gamblers, moderate-to-high-risk gamblers did not exhibit greater approach bias tendencies towards gambling-related stimuli compared to neutral stimuli. Moreover, gambling approach bias was not predictive of prospective gambling behaviour (frequency, duration, or expenditure) or severity of gambling problems. Reported results do not provide evidence for approach tendencies contributing to problematic gambling behaviour in a Canadian sample of moderate-to-high-risk gamblers compared to non-problematic gambler controls. Further replications on the topic are needed. Future research should evaluate approach tendencies within the gambling context, considering the potential impact of task reliability to assess approach bias in light of individual gambling modality preferences.</p

Production of 5-hydroxy-7-methoxy-4-methylphthalide in a culture of Penicillium crustosum.

The chemical reactions carried out by microorganisms have been used as a tool in modern chemistry. This paper reports the production of mycophenolic acid and a new phthalide by the endophytic fungus Penicillium crustosum obtained from coffee seeds. The fungus was cultivated in a liquid medium for a period of seven days and after that the culture medium was divided into four treatments: A, B, C and D, to which different organic substances were added. Treatment A was maintained as the control to evaluate the occurrence of biotransformation. Organic acids were added to the culture media of treatments B (ferulic and quinic acids) and C [cinnamic and 3,4-(methylenedioxy) cinnamic acids], and caffeine was added in the treatment D. All these organic compounds were dissolved in DMSO, and the fermentation was maintained for more 13 days, totalizing 20 days. Mycophenolic acid was isolated from the culture with no added acids (treatment A). Mycophenolic acid and a new phthalide, 5-hydroxy-7-methoxy-4-methylphthalide were isolated from treatments B and C, and mycophenolic acid and caffeine (added to the culture medium) were isolated from treatment D. The structures were determined by NMR techniques and confi rmed by MS and MS/MS technique

The crosstalk between prostate cancer and microbiota inflammation: Nutraceutical products are useful to balance this interplay?

The human microbiota shows pivotal roles in urologic health and disease. Emerging studies indicate that gut and urinary microbiomes can impact several urological diseases, both benignant and malignant, acting particularly on prostate inflammation and prostate cancer. Indeed, the microbiota exerts its influence on prostate cancer initiation and/or progression mechanisms through the regulation of chronic inflammation, apoptotic processes, cytokines, and hormonal production in response to different pathogenic noxae. Additionally, therapies’ and drugs’ responses are influenced in their efficacy and tolerability by microbiota composition. Due to this complex potential interconnection between prostate cancer and microbiota, exploration and understanding of the involved relationships is pivotal to evaluate a potential therapeutic application in clinical practice. Several natural compounds, moreover, seem to have relevant effects, directly or mediated by microbiota, on urologic health, posing the human microbiota at the crossroad between prostatic inflammation and prostate cancer development. Here, we aim to analyze the most recent evidence regarding the possible crosstalk between prostate, microbiome, and inflammation

Losing sight of Luck: Automatic approach tendencies toward gambling cues in Canadian moderate- to high-risk gamblers – A replication study

Evidence for approach bias tendencies to underly automatic behavioural impulses towards seeking out gambling activities in the presence of appetitive salient cues was first shown by Boffo et al. (2018) in a Dutch sample. Relative to non-problem gamblers, moderate-to-high-risk gamblers demonstrated stronger approach tendencies towards gambling-related stimuli compared with neutral ones. Moreover, gambling approach bias was associated with past-month gambling behaviour and predictive of gambling activity persistence over time. The current study aimed to replicate these findings within a Canadian sample evaluating the concurrent and longitudinal correlates of gambling approach bias. The study was conducted online, available throughout Canada. Twenty-seven non-treatment-seeking moderate-to-high-risk gamblers and 26 non-problem gamblers community-recruited via multiple channels (i.e., internet and newspaper advertisements, land-based flyers, and university recruitment portals). Participants completed two online assessment sessions 6-months apart. Each session included (1) self-report measures of gambling behaviour (frequency, duration, and expenditure), (2) self-report assessment of problem gambling severity (PGSI), and (3) a gambling approach-avoidance task, utilising culturally relevant stimuli tailored to individual gambling habits. However, our study failed to replicate Boffo et al. (2018) findings in a Canadian sample. Relative to non-problem gamblers, moderate-to-high-risk gamblers did not exhibit greater approach bias tendencies towards gambling-related stimuli compared to neutral stimuli. Moreover, gambling approach bias was not predictive of prospective gambling behaviour (frequency, duration, or expenditure) or severity of gambling problems. Reported results do not provide evidence for approach tendencies contributing to problematic gambling behaviour in a Canadian sample of moderate-to-high-risk gamblers compared to non-problematic gambler controls. Further replications on the topic are needed. Future research should evaluate approach tendencies within the gambling context, considering the potential impact of task reliability to assess approach bias in light of individual gambling modality preferences

Recent developments in electropolishing and tumbling R&D at Fermilab

Fermi National Accelerator Lab (Fermilab) is continuing to improve its infrastructure for research and development on the processing of superconducting radio frequency cavities. A single cell 3.9 GHz electropolishing tool built at Fermilab and operated at an industrial partner was recently commissioned. The EP tool was used to produce a single cell 3.9 GHz cavity that reached an accelerating gradient of 30 MV/m with a quality factor of 5 x 10{sup 9}. A single cell 1.3 GHz cavity was also electropolished at the same industrial vendor using the vendor's vertical full-immersion technique. On their first and only attempt the vendor produced a single cell 1.3 GHz cavity that reached 30 MV/m with a quality factor of 1 x 10{sup 10}. These results will be detailed along with preliminary tumbling results

Long-lasting effects of chronic exposure to chemical pollution on the hologenome of the Manila clam

Chronic exposure to pollutants affects natural populations, creating specific molecular and biochemical signatures. In the present study, we tested the hypothesis that chronic exposure to pollutants might have substantial effects on the Manila clam hologenome long after removal from contaminated sites. To reach this goal, a highly integrative approach was implemented, combining transcriptome, genetic and microbiota analyses with the evaluation of biochemical and histological profiles of the edible Manila clam Ruditapes philippinarum, as it was transplanted for 6 months from the polluted area of Porto Marghera (PM) to the clean area of Chioggia (Venice lagoon, Italy). One month post‐transplantation, PM clams showed several modifications to its resident microbiota, including an overrepresentation of the opportunistic pathogen Arcobacter spp. This may be related to the upregulation of several immune genes in the PM clams, potentially representing a host response to the increased abundance of deleterious bacteria. Six months after transplantation, PM clams demonstrated a lower ability to respond to environmental/physiological stressors related to the summer season, and the hepatopancreas‐associated microbiota still showed different compositions among PM and CH clams. This study confirms that different stressors have predictable effects in clams at different biological levels and demonstrates that chronic exposure to pollutants leads to long‐lasting effects on the animal hologenome. In addition, no genetic differentiation between samples from the two areas was detected, confirming that PM and CH clams belong to a single population. Overall, the obtained responses were largely reversible and potentially related to phenotypic plasticity rather than genetic adaptation. The results here presented will be functional for the assessment of the environmental risk imposed by chemicals on an economically important bivalve species