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Objective The effects of coffee consumption on serum uric acid (SUA) levels and gout risk are controversial. There have hitherto been no reports based on Mendelian randomization (MR) analysis of its effects that consider pleiotropy. Here, we evaluated the effects of coffee consumption across ancestry populations, taking pleiotropy into account. Methods We performed the first MR analyses for coffee consumption on SUA levels and gout, considering pleiotropy. We used the following summary statistics of genome‐wide association studies from a Japanese population: habitual coffee consumption (152,634 subjects), gout (3053 cases and 4554 controls), and SUA levels (121,745 subjects). In addition to fixed‐effect inverse variance weighted (IVW) meta‐analysis, we performed a robust evaluation of heterogeneity and removed several instruments for reasons of possible pleiotropy. Previous European datasets were also reevaluated while heterogeneity was considered. Results Habitual coffee consumption was significantly and inversely associated with gout (odds ratio [OR] = 0.29, 95% confidence interval [95% CI]: 0.16‐0.51, P = 1.9 × 10−5) in random‐effect IVW (Phet = 5.5 × 10−19). Excluding pleiotropic instruments, the protective effect on gout was confirmed in fixed‐effect IVW analysis (OR = 0.75, 95% CI: 0.58‐0.97, P = 0.026) without heterogeneity (Phet = 0.39). However, we observed no significance in the previous European datasets when heterogeneity was considered. Associations were not observed between coffee consumption and SUA levels in either ancestry in MR analyses that considered pleiotropy. Multivariable MR analysis showed that increased coffee consumption significantly reduced gout risk, even after adjusting for SUA levels (OR = 0.50, 95% CI: 0.31‐0.81, P = 0.0046). Conclusion With pleiotropy taken into account, our MR analyses revealed that coffee consumption can causally reduce gout risk, and that it may reduce gout risk independently of SUA levels.

The dual-use risk of infectious disease research using enhanced potential pandemic pathogens (ePPP), particularly gain-of-function (GOF) research, has been debated since 2011. As of now, research is supported on the condition that the research plan is reviewed and the actual experiment is supervised. However, the kinds of research conducted and what benefits they have brought to our society have not been adequately verified. Nevertheless, due to the COVID-19 pandemic that began at the end of 2019 and caused numerous deaths and wide economic disruption, the importance of infectious disease control from an international perspective has been recognized. Although complete control of the pandemic is still far off, positive signs include generating epidemiological trends based on genome analysis, therapeutic drug and vaccine development, clinical patient management, and public health policy interventions. In this context, the time has come to reconsider the true significance of GOF research on ePPP and the state of research governance in the post-COVID-19 era. In particular, the risks of such research are clearer than before, whereas its benefits seem less apparent. In this paper, we summarize the history of discussions on such GOF research, its significance in the light of the current COVID-19 pandemic, and the direction we shall take in the future.

Dysfunctional missense variant of organic anion transporter 10 (OAT10/SLC22A13), rs117371763 (c.1129C>T; p.R377C), is associated with a lower susceptibility to gout. OAT10 is a urate transporter; however, its physiological role in urate handling remains unclear. We hypothesized that OAT10 could be a renal urate re-absorber that will be a new molecular target of urate-lowering therapy like urate transporter 1 (URAT1, a physiologically-important well-known renal urate re-absorber) and aimed to examine the effect of OAT10 dysfunction on renal urate handling. For this purpose, we conducted quantitative trait locus analyses of serum urate and fractional excretion of uric acid (FEUA) using samples obtained from 4,521 Japanese males. Moreover, we performed immunohistochemical and functional analyses to assess the molecular properties of OAT10 as a renal urate transporter and evaluated its potential interaction with urate-lowering drugs. Clinico-genetic analyses revealed that carriers with the dysfunctional OAT10 variant exhibited significantly lower serum urate levels and higher FEUA values than the non-carriers, indicating that dysfunction of OAT10 increases renal urate excretion. Given the results of functional assays and immunohistochemical analysis demonstrating the expression of human OAT10 in the apical side of renal proximal tubular cells, our data indicate that OAT10 is involved in the renal urate reabsorption in renal proximal tubules from urine. Additionally, we found that renal OAT10 inhibition might be involved in the urate-lowering effect of losartan and lesinurad which exhibit uricosuric effects; indeed, losartan, an approved drug, inhibits OAT10 more strongly than URAT1. Accordingly, OAT10 can be a novel potential molecular target for urate-lowering therapy.

Measurement of event-related potentials (ERPs) in simulated and real environments is advantageous for understanding cognition and behavior during practice of goal-directed activities. Recently, instead of using task-irrelevant “probe stimuli” to elicit ERPs, extraction of ERPs directly from events that occur in simulated and real environments has drawn increased attention. Among the previous ERP studies using immersive virtual reality, only a few cases elicited ERPs from task-related events in dynamic task settings. Furthermore, as far as we surveyed, there were no studies that examined the source of ERPs or correlation between ERPs and behavioral performance in 360-degree immersive virtual reality using head-mounted display. In this study, EEG signals were recorded from 16 participants while they were playing the first-person shooter game with immersive virtual reality environment. Error related negativity (ERN) and correct-(response)-related negativity (CRN) elicited by shooting-related events were successfully extracted. We found the ERN amplitudes to be correlated with the individual shooting performance. Interestingly, the main source of the ERN was the rostral anterior cingulate cortex (ACC), which is different from previous studies where the signal source was often estimated to be the more caudal part of ACC. The obtained results are expected to contribute to the evaluation of cognitive functions and behavioral performance by ERPs in a simulated environment.

Genome editing technologies are increasingly coming under scrutiny, based on various social value judgments in biomedical research, clinical care, and public health. A central cause of this sociotechnical tension is that these technologies are capable of precisely and easily creating genome-modified organisms and human cells and tissues. To exemplify a general framework for a national governance system of genome editing technologies, we first look at the regulatory dynamics in Japan. Second, we expose the potential tension between national and international debates and directions for the global harmonization of genome editing technologies. Third, underpinning these two perspectives, we propose contiguous governance as a novel model of the governance of emerging biotechnologies from both synchronic and diachronic perspectives. These perspectives, derived from genome editing technologies, can contribute to a better understanding and consideration of future regulations and governance systems.

In recent years, there has been increasing evidence that gut microbiota is associated with the onset and exacerbation of various diseases, such as gastrointestinal cancer. For instance, it is well known that local inflammation of the intestinal tract in colorectal cancer that is caused by the increased number of Fusobacterium, due to changes in the intestinal bacterial flora, is involved in carcinogenesis. In contrast, gut bacteria or their products, pathogen-associated molecular patterns, not only cause intestinal inflammation but also invade the bloodstream through dysbiosis and gut barrier dysfunction, thereby leading to systemic inflammation, namely bacterial translocation. The involvement of bacterial translocation in the carcinogenesis of gastrointestinal cancers and their prognosis is increasingly being recognized. The Toll-like receptor signaling pathways plays an important role in the carcinogenesis of such cancers. In addition, bacterial translocation influences the treatment of cancers such as surgery and chemotherapy. In this review, we outline the concept of bacterial translocation, summarize the current knowledge on the relationship between gut bacteria and gastrointestinal cancer, and provide future perspectives of this field.