Nanobody generation and structural characterization of Plasmodium falciparum 6-cysteine protein Pf12p.

Surface-associated proteins play critical roles in the Plasmodium parasite life cycle and are major targets for vaccine development. The 6-cysteine (6-cys) protein family is expressed in a stage-specific manner throughout Plasmodium falciparum life cycle and characterized by the presence of 6-cys domains, which are ß-sandwich domains with conserved sets of disulfide bonds. Although several 6-cys family members have been implicated to play a role in sexual stages, mosquito transmission, evasion of the host immune response and host cell invasion, the precise function of many family members is still unknown and structural information is only available for four 6-cys proteins. Here, we present to the best of our knowledge, the first crystal structure of the 6-cys protein Pf12p determined at 2.8 Šresolution. The monomeric molecule folds into two domains, D1 and D2, both of which adopt the canonical 6-cys domain fold. Although the structural fold is similar to that of Pf12, its paralog in P. falciparum, we show that Pf12p does not complex with Pf41, which is a known interaction partner of Pf12. We generated 10 distinct Pf12p-specific nanobodies which map into two separate epitope groups; one group which binds within the D2 domain, while several members of the second group bind at the interface of the D1 and D2 domain of Pf12p. Characterization of the structural features of the 6-cys family and their associated nanobodies provide a framework for generating new tools to study the diverse functions of the 6-cys protein family in the Plasmodium life cycle.

The prevalence rates of major chronic diseases in retired and in-service Chinese military officers (2000-2016): a meta-analysis.

BACKGROUND: Chronic diseases cause a tremendous burden to the military medical system. However, the prevalence rates of major chronic diseases among military officers remain unclear in China. METHODS: China National Knowledge Infrastructure (CNKI), Wanfang Database, VIP Database for Chinese Technical Periodicals (VIP), PubMed and Web of Science were searched for studies (from 2000 to 2016) concerning 6 major chronic diseases: hypertension, hyperlipidemia, diabetes mellitus, heart diseases, cerebrovascular diseases, and chronic obstructive pulmonary diseases (COPD) in Chinese military officers following strict inclusion and exclusion criteria. Three researchers independently extracted data from the included studies, and a fourth researcher reviewed and solved every disagreement. Statistical analysis was performed with STATA 14.0 and R 3.3.2. Heterogeneity was evaluated by the I 2 value. A random effect model was performed to combine the heterogeneous data. The Egger test was performed to test the publication bias. RESULTS: A total of 90,758 military officers derived from 75 articles were pooled together. Publication bias was only observed in 37 studies reporting heart disease (P Egger test = 0.01). The overall prevalence rates of hypertension, hyperlipidemia, diabetes mellitus, heart diseases, cerebrovascular diseases, and COPD were 46.6% (95% CI 41.8-51.5%), 30.9% (26.4-35.7%), 20.7% (16.5-25.7%), 48.2% (41.7-54.9%), 20.2% (14.8-26.9%) and 16.6% (12.9-21.0%), respectively. The prevalence rates of hypertension, diabetes, heart disease, cerebrovascular disease, and COPD, rather than hyperlipidemia, increased with age in Chinese military officers. Heart diseases (P Q-test  < 0.001) and hypertension (P Q-test  < 0.001) increased sharply in retired officers compared with officers in service. Cerebrovascular disease was more frequent in Northern Theater Command than in any other theater command (P Q-test  < 0.001). CONCLUSIONS: Major chronic diseases heavily affect Chinese military officers, especially retirees. Medical intervention should be enforced on the prevention of cerebrovascular diseases in those working in cold areas in the north, as well as hypertension and heart diseases in retirees.