Concerted Action of Two Formins in Gliding Motility and Host Cell Invasion by Toxoplasma gondii

The invasive forms of apicomplexan parasites share a conserved form of gliding motility that powers parasite migration across biological barriers, host cell invasion and egress from infected cells. Previous studies have established that the duration and direction of gliding motility are determined by actin polymerization; however, regulators of actin dynamics in apicomplexans remain poorly characterized. In the absence of a complete ARP2/3 complex, the formin homology 2 domain containing proteins and the accessory protein profilin are presumed to orchestrate actin polymerization during host cell invasion. Here, we have undertaken the biochemical and functional characterization of two Toxoplasma gondii formins and established that they act in concert as actin nucleators during invasion. The importance of TgFRM1 for parasite motility has been assessed by conditional gene disruption. The contribution of each formin individually and jointly was revealed by an approach based upon the expression of dominant mutants with modified FH2 domains impaired in actin binding but still able to dimerize with their respective endogenous formin. These mutated FH2 domains were fused to the ligand-controlled destabilization domain (DD-FKBP) to achieve conditional expression. This strategy proved unique in identifying the non-redundant and critical roles of both formins in invasion. These findings provide new insights into how controlled actin polymerization drives the directional movement required for productive penetration of parasites into host cells

Telomere and telomerase in stem cells

Telomeres, guanine-rich tandem DNA repeats of the chromosomal end, provide chromosomal stability, and cellular replication causes their loss. In somatic cells, the activity of telomerase, a reverse transcriptase that can elongate telomeric repeats, is usually diminished after birth so that the telomere length is gradually shortened with cell divisions, and triggers cellular senescence. In embryonic stem cells, telomerase is activated and maintains telomere length and cellular immortality; however, the level of telomerase activity is low or absent in the majority of stem cells regardless of their proliferative capacity. Thus, even in stem cells, except for embryonal stem cells and cancer stem cells, telomere shortening occurs during replicative ageing, possibly at a slower rate than that in normal somatic cells. Recently, the importance of telomere maintenance in human stem cells has been highlighted by studies on dyskeratosis congenital, which is a genetic disorder in the human telomerase component. The regulation of telomere length and telomerase activity is a complex and dynamic process that is tightly linked to cell cycle regulation in human stem cells. Here we review the role of telomeres and telomerase in the function and capacity of the human stem cells

Measurement invariance of the center for epidemiological studies depression scale (CES-D) among chinese and dutch elderly

Background: Although previous studies using non- elderly groups have assessed the factorial invariance of the Center for Epidemiological Studies Depression Scale (CES-D) across different groups with the same social-cultural backgrounds, few studies have tested the factorial invariance of the CES-D across two elderly groups from countries with different social cultures. The purposes of this study were to examine the factorial structure of the CES-D, and test its measurement invariance across two different national elderly populations. Methods. A total of 6806 elderly adults from China (n = 4903) and the Netherlands (n = 1903) were included in the final sample. The CES-D was assessed in both samples. Three strategies were used in the data analysis procedure. First, a confirmatory factor analysis (CFA) was carried out to determine the factor structures of the CES-D that best fitted the two samples. Second, the best fitting model was incorporated into a multi-group CFA model to test measurement invariance of the CES-D across the two population groups. Third, latent mean differences between the two groups were tested. Results: The results of confirmatory factor analysis (CFA) showed: 1) in both samples, Radloff's four-factor model resulted in a significantly better fit and the four dimensions (somatic complaints, depressed affect, positive affect, and interpersonal problems) of the CES-D seem to be the most informative in assessing depressive symptoms compared to the single-, three-, and the second-order factor models; and 2) the factorial structure was invariant across the populations under study. However, only partial scalar and uniqueness invariance of the CES-D items was supported. Latent means in the partial invariant model were lower for the Dutch sample, compared to the Chinese sample. Conclusions: Our findings provide evidence of a valid factorial structure of the CES-D that could be applied to elderly populations from both China and the Netherlands, producing a meaningful comparison of total scores between the two elderly groups. However, for some specific factors and items, caution is required when comparing the depressive symptoms between Chinese and Dutch elderly groups. © 2011 Zhang et al; licensee BioMed Central Ltd

Mitochondrial arginase-2 is essential for IL-10 metabolic reprogramming of inflammatory macrophages.

Mitochondria are important regulators of macrophage polarisation. Here, we show that arginase-2 (Arg2) is a microRNA-155 (miR-155) and interleukin-10 (IL-10) regulated protein localized at the mitochondria in inflammatory macrophages, and is critical for IL-10-induced modulation of mitochondrial dynamics and oxidative respiration. Mechanistically, the catalytic activity and presence of Arg2 at the mitochondria is crucial for oxidative phosphorylation. We further show that Arg2 mediates this process by increasing the activity of complex II (succinate dehydrogenase). Moreover, Arg2 is essential for IL-10-mediated downregulation of the inflammatory mediators succinate, hypoxia inducible factor 1α (HIF-1α) and IL-1β in vitro. Accordingly, HIF-1α and IL-1β are highly expressed in an LPS-induced in vivo model of acute inflammation using Arg2-/- mice. These findings shed light on a new arm of IL-10-mediated metabolic regulation, working to resolve the inflammatory status of the cell