Natural malaria infection reduces starvation resistance of nutritionally stressed mosquitoes.

In disease ecology, there is growing evidence that environmental quality interacts with parasite and host to determine host susceptibility to an infection. Most studies of malaria parasites have focused on the infection costs incurred by the hosts, and few have investigated the costs on mosquito vectors. The interplay between the environment, the vector and the parasite has therefore mostly been ignored and often relied on unnatural or allopatric Plasmodium/vector associations. Here, we investigated the effects of natural avian malaria infection on both fecundity and survival of field-caught female Culex pipiens mosquitoes, individually maintained in laboratory conditions. We manipulated environmental quality by providing mosquitoes with different concentrations of glucose-feeding solution prior to submitting them to a starvation challenge. We used molecular-based methods to assess mosquitoes' infection status. We found that mosquitoes infected with Plasmodium had lower starvation resistance than uninfected ones only under low nutritional conditions. The effect of nutritional stress varied with time, with the difference of starvation resistance between optimally and suboptimally fed mosquitoes increasing from spring to summer, as shown by a significant interaction between diet treatment and months of capture. Infected and uninfected mosquitoes had similar clutch size, indicating no effect of infection on fecundity. Overall, this study suggests that avian malaria vectors may suffer Plasmodium infection costs in their natural habitat, under certain environmental conditions. This may have major implications for disease transmission in the wild.

PRDM1 is a tumor suppressor gene in natural killer cell malignancies.

Natural killer cell lymphoma (NKCL) constitutes a rare and aggressive form of non-Hodgkin lymphoma, and there is little insight into its pathogenesis. Here we show that PRDM1 is a tumor suppressor gene in NKCLs that is inactivated by a combination of monoallelic deletion and promoter CpG island hypermethylation. We observed monoallelic deletion of PRDM1 loci in 8 of 18 (44%) NKCL cases. The other allele showed significant promoter methylation in 12 of 17 (71%) cases. In support of its role as a tumor suppressor gene, the reconstitution of PRDM1 in PRDM1-null NK cell lines led to G2/M cell cycle arrest, increased apoptosis, and a strong negative selection pressure with progressive elimination of PRDM1-expressing cells, which was enhanced when IL-2 concentration is limiting. We observed a progressive increase in PRDM1 expression-in particular, PRDM1α-in normal NK cells in response to IL-2 and in normal NK cells activated with an engineered NK cell target, K562-Cl9-mb21, suggesting its role in NK cell homeostasis. In support of this role, knockdown of PRDM1 by shRNA in normal NK cells resulted in the positive selection of these cells. We identified MYC and 4-1BBL as targets of PRDM1 in NK cells. Disruption of homeostatic control by PRDM1 may be an important pathogenetic mechanism for NKCL.

Psychotherapy for Personality Disorders in a Natural Setting: A Pilot Study over Two Years of Treatment.

Long-term assessment of the effects of psychotherapy for personality disorders (PDs) in a natural environment is an important task. Such research contributes to enlarge the practice-based evidence, embedded in broad collaborations between clinicians and researchers in psychotherapy for PDs. The present pilot study used rigorous assessment procedures and incorporated feedback loops of outcome information to the therapists in demonstrating the effects of psychotherapy for PD in a natural setting. The number of Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV), criteria for any PD was the primary outcome (along with psychological distress, depression, impulsiveness, and quality of life as secondary measures), assessed at intake, 6, 12, 18, and 24 months of psychotherapy for N = 13 patients with PD. Data were analyzed using hierarchical linear modeling. Results demonstrated a large pre-post effect (d = 2.22) for the observer-rated measure (primary outcome), and small to medium effects for the secondary outcomes; these results were corroborated by a steady decrease of symptoms over all five time points, which was significant for several outcomes. These results add a piece to the literature by demonstrating the effects of long-term psychotherapy for PDs in increasingly diverse contexts and suggest that practice-oriented research can be carried out in a collaborative and systematic manner.