Fine Pathogen Discrimination within the APL1 Gene Family Protects Anopheles gambiae against Human and Rodent Malaria Species

Genetically controlled resistance of Anopheles gambiae mosquitoes to Plasmodium falciparum is a common trait in the natural population, and a cluster of natural resistance loci were mapped to the Plasmodium-Resistance Island (PRI) of the A. gambiae genome. The APL1 family of leucine-rich repeat (LRR) proteins was highlighted by candidate gene studies in the PRI, and is comprised of paralogs APL1A, APL1B and APL1C that share ≥50% amino acid identity. Here, we present a functional analysis of the joint response of APL1 family members during mosquito infection with human and rodent Plasmodium species. Only paralog APL1A protected A. gambiae against infection with the human malaria parasite P. falciparum from both the field population and in vitro culture. In contrast, only paralog APL1C protected against the rodent malaria parasites P. berghei and P. yoelii. We show that anti-P. falciparum protection is mediated by the Imd/Rel2 pathway, while protection against P. berghei infection was shown to require Toll/Rel1 signaling. Further, only the short Rel2-S isoform and not the long Rel2-F isoform of Rel2 confers protection against P. falciparum. Protection correlates with the transcriptional regulation of APL1A by Rel2-S but not Rel2-F, suggesting that the Rel2-S anti-parasite phenotype results at least in part from its transcriptional control over APL1A. These results indicate that distinct members of the APL1 gene family display a mutually exclusive protective effect against different classes of Plasmodium parasites. It appears that a gene-for-pathogen-class system orients the appropriate host defenses against distinct categories of similar pathogens. It is known that insect innate immune pathways can distinguish between grossly different microbes such as Gram-positive bacteria, Gram-negative bacteria, or fungi, but the function of the APL1 paralogs reveals that mosquito innate immunity possesses a more fine-grained capacity to distinguish between classes of closely related eukaryotic pathogens than has been previously recognized

Esophageal motor abnormalities in scleroderma and related diseases

Esophageal motor activity was measured by intra-esophageal pressure recordings in 53 patients with scleroderma and 29 patients with other collagen diseases. The purpose of the study was to determine the relationship of motor abnormalities to esophageal symptoms, to compare the abnormalities in scleroderma with those in other collagen diseases, and to try to increase understanding of the responsible mechanism. Methacholine was given to 36 of the 53 patients with scleroderma to confirm that the Mecholyl test is negative in scleroderma and to see whether intraluminal pressure changes accompany the resulting improvement in esophageal emptying.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/44360/1/10620_2005_Article_BF02233564.pd

Prospective evaluation of luteal phase length and natural fertility

OBJECTIVE: To evaluate the impact of a short luteal phase on fecundability. DESIGN: Prospective, time to pregnancy cohort study SETTING: Community-based cohort PATIENT(S): Women trying to conceive, ages 30–44 years, without known infertility INTERVENTION(S): Daily diaries, ovulation prediction testing, standardized pregnancy testing MAIN OUTCOME MEASURE(S): Subsequent cycle fecundability RESULT(S): 1,635 cycles from 284 women were included in the analysis. A short luteal phase (length of 11 days or less including the day of ovulation) occurred in 18% of observed cycles. Mean luteal phase length was 14 days. Significantly more women with a short luteal phase were smokers. After adjustment for age, women with a short luteal phase had 0.82 times the odds of pregnancy (95% CI: 0.46–1.47) in the subsequent cycle immediately following the short luteal phase when compared to women without a short luteal phase. Women with a short luteal length in the first observed cycle had significantly lower fertility after the first 6 months of pregnancy attempt, but at 12 months, there was no significant difference in cumulative probability of pregnancy. CONCLUSION(S): Although an isolated cycle with a short luteal phase may negatively impact short-term fertility, incidence of infertility at 12 months was not significantly higher among these women