No abstract

The death effector domain (DED) occurs in proteins that regulate programmed cell death. Both pro- and anti-apoptotic proteins containing DEDs have been identified. For Fas and possibly other death receptors, homotypic DED interactions connect the Fas-associated death domain (FADD) protein to caspase-8 and caspase-10 to mediate formation of the death-inducing signal complex. This complex can be inhibited by other DED-containing proteins. Accumulating evidence now suggests that DED-containing proteins have additional roles in controlling pathways of cellular activation and proliferation. Thus, the DED defines a family of proteins that may be pivotal to cellular homeostasis by establishing a 'cell renewal set point' that coregulates proliferation and apoptosis in parallel.

Competence data will aid understanding of the spread of human babesiosis.

Humans in the northeastern and midwestern United States are at increasing risk of acquiring tickborne diseases – not only Lyme disease, but also two emerging diseases, human granulocytic anaplasmosis and human babesiosis. Co-infection with two or more of these pathogens can increase the severity of health impacts. The risk of co-infection is intensified by the ecology of these three diseases because all three pathogens (Borrelia burgdorferi, Anaplasma phagocytophilum, and Babesia microti) are transmitted by the same vector, blacklegged ticks (Ixodes scapularis), and are carried by many of the same reservoir hosts. The risk of exposure to multiple pathogens from a single tick bite and the sources of co-infected ticks are not well understood. In this study, we quantify the risk of co-infection by measuring infection prevalence in 4,368 questing nymphs throughout an endemic region for all three diseases (Dutchess County, NY) to determine if co-infections occur at frequencies other than predicted by independent assortment of pathogens. Further, we identify sources of co-infection by quantifying rates of co-infection on 3,275 larval ticks fed on known hosts. We find significant deviations of levels of co-infection in questing nymphs, most notably 83% more co-infection with Babesia microti and Borrelia burgdorferi than predicted by chance alone. Further, this pattern of increased co-infection was observed in larval ticks that fed on small mammal hosts, but not on meso-mammal, sciurid, or avian hosts. Co-infections involving A. phagocytophilum were less common, and fewer co-infections of A. phagocytophilum and B. microti than predicted by chance were observed in both questing nymphs and larvae fed on small mammals. Medical practitioners should be aware of the elevated risk of B. microti/B. burgdorferi co-infection.

Fourteen vertebrate species (10 mammals and 4 birds) were assessed for their ability to transmit Anaplasma phagocytophilum, the bacterium that causes human granulocytic anaplasmosis, to uninfected feeding ixodid ticks. Small mammals were most likely to infect ticks but all species assessed were capable of transmitting the bacterium, in contrast to previous findings.

Purpose To test the hypothesis that uncultured organisms may be present in cases of culture-negative endophthalmitis, by use of deep DNA sequencing of vitreous biopsies. Design Single center consecutive prospective observational study. Participants and Controls Aqueous or vitreous biopsies from 21 consecutive patients presenting with presumed infectious endophthalmitis, and seven vitreous samples from patients undergoing surgery for non-infectious retinal disorders. Methods Traditional bacterial and fungal culture, 16S quantitative polymerase chain reaction (qPCR) and a representational deep-sequencing method (Biome Representational in Silico Karyotyping [BRiSK]) were applied in parallel to samples to identify DNA sequences corresponding to potential pathogens. Main Outcome Measures Presence of potential pathogen DNA in ocular samples. Results None of 7 control eyes undergoing routine vitreous surgery yielded positive results for bacteria or virus by culture or 16S PCR. Fourteen of the 21 samples (66.7%) from eyes harboring suspected infectious endophthalmitis were culture-positive, the most common being Staphylococcal and Streptococcal species. There was good agreement among culture, 16S bacterial PCR, and BRiSK methodologies for culture-positive cases (Fleiss’ kappa of 0.621). 16S PCR did not yield a recognizable pathogen sequence in any culture-negative sample, while BRiSK suggested presence of Steptococcus in one culture-negative sample. Surprisingly, using BRiSK, 57.1% of culture-positive and 100% of culture-negative samples demonstrated presence of Torque Teno Virus (TTV) sequences, compared to none in the controls (Fisher exact, p = 0.0005). Presence of TTV viral DNA was confirmed in seven cases by qPCR. No other known viruses or potential pathogens were identified in these samples. Conclusion Culture, 16S qPCR, and BRiSK provide complementary information in presumed infectious endophthalmitis. The majority of culture-negative endophthalmitis samples did not contain significant levels of bacterial DNA. ‘culture-negativity’ does not appear to be due to failure of growth of fastidious bacteria. The small DNA virus TTV was unexpectedly found in all culture-negative samples and some culture-positive samples. The current study cannot distinguish whether TTV is a direct intraocular pathogen, an adjuvant for inflammation, a general marker of inflammation, or a commensal virus, but provides a testable hypothesis for a pathogenic mechanism in culture-negative endophthalmitis.

Stem cell therapy is a promising treatment under active investigation in multiple retinal diseases. Ongoing clinical trials should yield further insights into the potential for stem cell-based retinal therapies.

Abstract. Anaplasmosis is an emerging infectious disease caused by infection with the bacterium Anaplasma phagocytophilum. In the eastern United States, A. phagocytophilum is transmitted to hosts through the bite of the blacklegged tick, Ixodes scapularis. We determined the realized reservoir competence of 14 species of common vertebrate hosts for ticks by establishing the probability that each species transmits two important strains of A. phagocytophilum (A. phagocytophilum human-active, which causes human cases, and A. phagocytophilum variant 1, which does not) to feeding larval ticks. We also sampled questing nymphal ticks from~150 sites in a single county over 2 years and sampled over 6 years at one location. White-footed mice (Peromyscus leucopus) and Eastern chipmunks (Tamias striatus) were the most competent reservoirs for infection with the A. phagocytophilum human-active strain. Across the county, prevalence in ticks for both strains together was 8.3%; ticks were more than two times as likely to be infected with A. phagocytophilum human-active as A. phagocytophilum variant 1.