Toxoplasma ceramide synthases: a curious case of gene duplication, divergence and key functionality

Toxoplasma gondii is an obligate, intracellular eukaryotic apicomplexan protozoan parasite that can cause foetal damage and abortion in both animals and humans. Sphingolipids have indispensable functions as signaling molecules and are essential and ubiquitous components of eukaryotic membranes that are both synthesized and scavenged by the Apicomplexa. Ceramide is the precursor for all sphingolipids, and here we report the identification, localisation and analyses of the Toxoplasma ceramide synthases Tg CerS1 and Tg CerS2 and, using a conditional gene regulation approach, establish their roles in pathogenicity and parasite fitness. Interestingly, we observed that whilst Tg CerS1 was a fully functional orthologue of the yeast Lag1p capable of catalysing the conversion of sphinganine to ceramide, in contrast Tg CerS2 was catalytically inactive. Furthermore, genomic deletion of Tg CerS1 using CRISPR/Cas-9 led to viable but slow growing parasites indicating its importance but not indispensability. In contrast, genomic knock out of Tg CerS2 was only accessible utilising the rapamycin-inducible Cre recombinase system. Surprisingly, the results demonstrated that this ‘pseudo’ ceramide synthase, Tg CerS2, has an even greater role in parasite fitness than its catalytically active orthologue (Tg CerS1). Phylogenetic analyses indicated that, as in humans and plants, the ceramide synthase isoforms found in Toxoplasma and other Apicomplexa arose through gene duplication. However, in the Apicomplexa the duplicated copy subsequently evolved into a non-functional ‘pseudo’ ceramide synthase. This arrangement is unique to the Apicomplexa and further illustrates the unusual biology that characterize these protozoan parasites, a feature that could potentially be exploited in the development of new antiprotozoals.

Kajian Hukum Perbandingan Kemudahan Investasi Asing di Singapura dan di Kota Batam, Indonesia Beserta Legal Standing OSS Dalam Penerapannya

Investment is one of the first steps in moving the wheels of a country's economy. In the city of Batam itself is strongly identified with the investment climate. With its strategic location, Batam City is located adjacent to its neighboring countries, namely Singapore and Malaysia. The OSS (Online Single Submission) system emerged as one of the steps aimed at increasing the competitiveness of the global region and encouraging investment growth. However, in the OSS system there are still many obstacles both in terms of regulations and implementers of regulations that are considered less than optimal in applying electronically integrated business licenses. This is also worsen by the dualism of authority in managing the region. Looking to neighboring countries, Singapore is a favorite destination for global companies wishing to expand their business in Asia. The ease of obtaining a business license has become the main focus for this Lion Country. This study uses a normative legal research method with a comparative law approach and a statutory regulation approach. The purpose of writing this article is to study the ease of foreign investment in Singapore compared to Batam City and the legal standing of OSS in its application. Based on the research conducted, the ease of investment is examined from various factors, namely in the areas of legal certainty, taxation, employment, and licensing of the Indonesian OSS system including Batam City which still does not fully support a conducive investment climate in doing business compared to Singapore.

Roles of Regulation and Lifestyle on Indonesian Coffee Consumption Behavior Across Generations

Coffee beverage consumption has become more important in the recent years and has touched the lifestyles of the old and young people. The research of coffee consumption, especially in relation to the lifestyles of the people, therefore needs to be intensified. The purpose of this study was to compare the contribution of regulation and lifestyle in determining coffee drink consumption among old and young consumers. The theory adopted was the SOR (stimulus-organism-response) theory and the AISAS (attention-interest-search-action-share) model approach. Data were collected online in April-May 2020, and obtained 413 valid respondent data, which consist of 207 old respondents and 206 young respondents. The results showed that the lifestyle variable had positive effects on attitude and search behavior of both young and old generations. The lifestyle variable also had significant effects on coffee consumption for both generations. The regulation variable had positive effects on attitude and action of young coffee consumers, but it had no effect on attitude, search and action of old consumers. The research suggests that, to increase coffee consumption, better regulation approach should consider the age of the consumer. Especially, more attention should be paid for the regulation on coffee marketing for older generation.

Meditation-Induced Psychosis: Trigger and Recurrence

Meditation is regarded as a self-regulation approach to manage emotions. Meditation has a beneficial effect on mental health. Different kinds of meditation are practiced in many religions and cultures for the general wellbeing of an individual. However, meditation-related experiences and negative effects of meditation are not uncommon. Meditation-induced psychosis has been reported in the past. Here, we present a case of a 33-year-old male patient who developed acute and transient psychosis twice after meditation and discuss the role of meditation as a precipitating factor to psychosis.