Naturally acquired immunity to Plasmodium falciparum malaria is thought to be non-sterile and sustained by persistence of low level parasitaemia. This study assessed the association between baseline microscopic and submicroscopic asymptomatic P. falciparum infections and anti-malarial antibody levels and whether these parasitaemia modify protective associations between antibody levels and malaria in Ghanaian children. Healthy children (N=973, aged 0.5-12 years) were recruited into a 50-week longitudinal malaria cohort study from January 2016 to January 2017. Baseline asymptomatic parasitaemia were determined by microscopy (microscopic parasitaemia) and polymerase chain reaction (submicroscopic parasitaemia) and antibody levels against crude schizont antigens measured by ELISA. Antibody levels, parasite diversity and risk of malaria in the ensuing transmission season were compared among children who had baseline asymptomatic microscopic or submicroscopic or no P. falciparum infections. Of the 99 asymptomatic baseline infections, 46 (46.5%) were microscopic and 53 (53.5%), submicroscopic. Cox regression analysis adjusting for age group, sex and community found a strong association between both baseline microscopic [Hazard ratio (HR)=0.36, 95%CI=(0.21, 0.63), p<0.001] and submicroscopic [HR=0.22, 95%CI=(0.11, 0.44), p<0.001] asymptomatic parasitaemia and a reduced risk of febrile malaria compared to those who were uninfected at baseline. Baseline asymptomatic submicroscopic parasitaemia had a significant effect on associations between anti-schizont antibodies and protection against febrile malaria (likelihood ratio test p<0.001). The study found both baseline P. falciparum asymptomatic microscopic and more strongly submicroscopic infections to be associated with protection against febrile malaria in the ensuing transmission season. This could have important implications for malaria sero-epidemiological studies and vaccine trials.

Yes-associated protein 1 (YAP1) was originally discovered as a WW domain-containing SRC kinase-binding protein. 1 YAP1 is distributed in the cytoplasm and in the nucleus. 2 YAP1 interacts with various transcription factors such as the TEAD family proteins, SMAD proteins, RUNX, and p73 to regulate gene transcription in the nucleus, while YAP1 undergoes proteasome degradation in the cytoplasm. [2][3][4][5][6][7] Therefore, cytoplasmic YAP1 is thought to be inactive, while nuclear YAP1 is considered to be active. The best characterized regulatory mechanism of the subcellular distribution of YAP1is its phosphorylation mediated by large tumor suppressor kinases (LATS1/2), the core kinases of the tumor suppressive Hippo pathway. LATS1/2 phosphorylate YAP1 at 5 serine residues. 2 The phosphorylation at

RASSF6, a member of the tumor suppressor Ras-association domain family (RASSF) proteins, regulates cell cycle arrest and apoptosis via p53 and plays a tumor suppressor role. We previously reported that RASSF6 blocks MDM2-mediated p53 degradation and enhances p53 expression. In this study, we demonstrated that RASSF6 has nuclear-localization and nuclear-export signals and that DNA damage triggers the nuclear accumulation of RASSF6. We found that RASSF6 directly binds to BAF53, the component of SWI/SNF complex. DNA damage induces CDK9-mediated phosphorylation of BAF53, which enhances the interaction with RASSF6 and increases the amount of RASSF6 in the nucleus. Subsequently, RASSF6 augments the interaction between BAF53 and BAF60a, another component of SWI/SNF complex, and further promotes the interaction of BAF53 and BAF60a with p53. BAF53 silencing or BAF60a silencing attenuates RASSF6-mediated p53-target gene transcription and apoptosis. Thus, RASSF6 is involved in the regulation of DNA damage-induced complex formation including CDK9, BAF53, BAF60a, and p53.