MASH1 activates expression of the paired homeodomain transcription factor Phox2a, and couples pan-neuronal and subtype-specific components of autonomic neuronal identity

We have investigated the genetic circuitry underlying the determination of neuronal identity, using mammalian peripheral autonomic neurons as a model system. Previously, we showed that treatment of neural crest stem cells (NCSCs) with bone morphogenetic protein-2 (BMP-2) leads to an induction of MASH1 expression and consequent autonomic neuronal differentiation. We now show that BMP2 also induces expression of the paired homeodomain transcription factor Phox2a, and the GDNF/NTN signalling receptor tyrosine kinase c-RET. Constitutive expression of MASH1 in NCSCs from a retroviral vector, in the absence of exogenous BMP2, induces expression of both Phox2a and c-RET in a large fraction of infected colonies, and also promotes morphological neuronal differentiation and expression of pan-neuronal markers. In vivo, expression of Phox2a in autonomic ganglia is strongly reduced in Mash1 -/- embryos. These loss- and gain-of-function data suggest that MASH1 positively regulates expression of Phox2a, either directly or indirectly. Constitutive expression of Phox2a, by contrast to MASH1, fails to induce expression of neuronal markers or a neuronal morphology, but does induce expression of c-RET. These data suggest that MASH1 couples expression of pan-neuronal and subtype-specific components of autonomic neuronal identity, and support the general idea that identity is established by combining subprograms involving cascades of transcription factors, which specify distinct components of neuronal phenotype

Cell-Based Biosensor to Report DNA Damage in Micro- and Nanosystems

Understanding how newly engineered micro- and nanoscale materials and systems that interact with cells impact cell physiology is crucial for the development and ultimate adoption of such technologies. Reports regarding the genotoxic impact of forces applied to cells in such systems that can both directly or indirectly damage DNA emphasize the need for developing facile methods to assess how materials and technologies affect cell physiology. To address this need we have developed a TurboRFP-based DNA damage reporter cell line in NIH-3T3 cells that fluoresce to report genotoxic stress caused by a wide variety of agents, from chemical genotoxic agents to UV-C radiation. Our biosensor was successfully implemented in reporting the genotoxic impact of nanomaterials, demonstrating the ability to assess size dependent geno- and cyto-toxicity. The biosensor cells can be assayed in a high throughput, noninvasive manner, with no need for overly sophisticated equipment or additional reagents. We believe that this open-source biosensor is an important resource for the community of micro- and nanomaterials and systems designers and users who wish to evaluate the impact of systems and materials on cell physiology.National Institutes of Health (U.S.) (Grant GM090194

Fulfilling the ‘Chinese Dream’:The Hong Kong Theater and the New Cold War

This article attempts to approach Sino-US relations from a Chinese foreign policy perspective. I will first discuss one of the main sources of Chinese assertiveness in its current foreign policy strategy and the implications for its behavior. Next, I will elaborate on the latest diplomatic tensions between China and US, the role of Hong Kong as the main theater of the new Cold War, and how COV- ID-19 could be a game-changer for Chinese ascendance and US declinism. I will conclude by suggesting strategies China could adopt in times of a global COVID-19 outbreak and the possible “decoupling” of Sino-US relations

Carbon and nitrogen isotopic ratios of urine and faeces as novel nutritional biomarkers of meat and fish intake

Purpose Meat and fish consumption are associated with changes in the risk of chronic diseases. Intake is mainly assessed using self-reporting, as no true quantitative nutritional biomarker is available. The measurement of plasma fatty acids, often used as an alternative, is expensive and time-consuming. As meat and fish differ in their stable isotope ratios, δ13C and δ15N have been proposed as biomarkers. However, they have never been investigated in controlled human dietary intervention studies. Objective In a short-term feeding study, we investigated the suitability of δ13C and δ15N in blood, urine and faeces as biomarkers of meat and fish intake. Methods The dietary intervention study (n = 14) followed a randomised cross-over design with three eight-day dietary periods (meat, fish and half-meat–half-fish). In addition, 4 participants completed a vegetarian control period. At the end of each period, 24-h urine, fasting venous blood and faeces were collected and their δ13C and δ15N analysed. Results There was a significant difference between diets in isotope ratios in faeces and urine samples, but not in blood samples (Kruskal–Wallis test, p < 0.0001). In pairwise comparisons, δ13C and δ15N were significantly higher in urine and faecal samples following a fish diet when compared with all other diets, and significantly lower following a vegetarian diet. There was no significant difference in isotope ratio between meat and half-meat–half-fish diets for blood, urine or faecal samples. Conclusions The results of this study show that urinary and faecal δ13C and δ15N are suitable candidate biomarkers for short-term meat and fish intake

The effect of Chinese vaccine diplomacy during COVID-19 in the Philippines and Vietnam: A multiple case study from a soft power perspective

BackgroundVaccine diplomacy is a subset of global health diplomacy and refers to the use anddelivery of vaccines to achieve a country's global health goals and foreign policyobjectives. Countries have used vaccine diplomacy to increase their soft power duringthe COVID-19 pandemic. China, an emerging world power, was no exception in thistrend. By December 2022, China has dispatched 1,65 billion vaccines worldwide;approximately one-third of the Chinese vaccines have been sent to the Association ofSoutheast Asian Nations (ASEAN) countries. China attempted to increase its softpower via vaccine diplomacy to appeal to its neighbours with which it has longstanding territorial disputes in the South China Sea (SCS). Using the soft powerperspective, our study examines the effectiveness of Chinese COVID-19 vaccinediplomacy in the Philippines and Vietnam, two primary claimants in the SCS.MethodsThrough a qualitative multiple case study research design, we determine theeffectiveness of Chinese vaccine diplomacy in the Philippines and Vietnam by usingfour indicators of soft power: public opinion, foreign policy, attractiveness, and businessand trade. Data collection consisted of a semi-systematic literature search of academicliterature and newspaper articles that were published before 13 June 2022. A thematicanalysis was conducted to analyse the data.ResultsAnalysing the effectiveness of Chinese vaccine diplomacy based on the four indicatorsof soft power, our results show that only the indicators of attractiveness in Vietnam andbusiness and trade in the Philippines have somewhat improved. In contrast, theindicators of public opinion and foreign policy showed neutral or negative results forChina.ConclusionsThis study concludes that Chinese vaccine diplomacy in the Philippines and Vietnamduring the COVID-19 pandemic was unsuccessful from a soft power perspective. Onereason is that China has undermined its soft power approach by simultaneously usinghard power tactics in Southeast Asia. Using vaccine diplomacy to increase soft poweris not always desirable from a global health perspective. Instead, countries sh

The effect of Chinese vaccine diplomacy during COVID-19 in the Philippines and Vietnam: A multiple case study from a soft power perspective

BackgroundVaccine diplomacy is a subset of global health diplomacy and refers to the use anddelivery of vaccines to achieve a country's global health goals and foreign policyobjectives. Countries have used vaccine diplomacy to increase their soft power duringthe COVID-19 pandemic. China, an emerging world power, was no exception in thistrend. By December 2022, China has dispatched 1,65 billion vaccines worldwide;approximately one-third of the Chinese vaccines have been sent to the Association ofSoutheast Asian Nations (ASEAN) countries. China attempted to increase its softpower via vaccine diplomacy to appeal to its neighbours with which it has longstanding territorial disputes in the South China Sea (SCS). Using the soft powerperspective, our study examines the effectiveness of Chinese COVID-19 vaccinediplomacy in the Philippines and Vietnam, two primary claimants in the SCS.MethodsThrough a qualitative multiple case study research design, we determine theeffectiveness of Chinese vaccine diplomacy in the Philippines and Vietnam by usingfour indicators of soft power: public opinion, foreign policy, attractiveness, and businessand trade. Data collection consisted of a semi-systematic literature search of academicliterature and newspaper articles that were published before 13 June 2022. A thematicanalysis was conducted to analyse the data.ResultsAnalysing the effectiveness of Chinese vaccine diplomacy based on the four indicatorsof soft power, our results show that only the indicators of attractiveness in Vietnam andbusiness and trade in the Philippines have somewhat improved. In contrast, theindicators of public opinion and foreign policy showed neutral or negative results forChina.ConclusionsThis study concludes that Chinese vaccine diplomacy in the Philippines and Vietnamduring the COVID-19 pandemic was unsuccessful from a soft power perspective. Onereason is that China has undermined its soft power approach by simultaneously usinghard power tactics in Southeast Asia. Using vaccine diplomacy to increase soft poweris not always desirable from a global health perspective. Instead, countries sh

Targeted genome editing across species using ZFNs and TALENs

Evolutionary studies necessary to dissect diverse biological processes have been limited by the lack of reverse genetic approaches in most organisms with sequenced genomes. We established a broadly applicable strategy using zinc finger nucleases (ZFNs) and transcription activator-like effector nucleases (TALENs) for targeted disruption of endogenous genes and cis-acting regulatory elements in diverged nematode species