Tyrosine-based signals within the cytoplasmic domain of integral membrane proteins mediate clathrin-dependent protein sorting in the endocytic and secretory pathways. A yeast two-hybrid system was used to identify proteins that bind to tyrosine-based signals. The medium chains (mu 1 and mu 2) of two clathrin-associated protein complexes (AP-1 and AP-2, respectively) specifically interacted with tyrosine-based signals of several integral membrane proteins. The interaction was confirmed by in vitro binding assays. Thus, it is likely that the medium chains serve as signal-binding components of the clathrin-dependent sorting machinery.

Ocular toxocariasis is an uncommon cause of uveitis that mainly affects younger patients. Inflammation is typically unilateral and presents as either a granuloma in the peripheral or posterior retina or a moderate to severe vitreous inflammation mimicking endophthalmitis.

Abstract. In Brazil, programs based on elimination of infected dogs have not curtailed the spread of visceral leishmaniasis (VL), suggesting that other reservoirs of infection exist. Persons with active VL can infect the sand fly vector, but in endemic areas, persons with asymptomatic infections, whose infectivity to sand flies is unknown, are far more numerous. In this study, a polymerase chain reaction-based assay detected kinetoplast DNA of Leishmania chagasi in the blood of eight of 108 asymptomatic persons living with patients with recently diagnosed VL. These eight persons had low or unmeasurable levels of IgG antibodies to Leishmania, demonstrating the insensitivity of serology for subclinical infection. All eight persons had positive leishmanin skin test results, as did 70% of persons living in households of persons with active VL. Even if a small proportion of such asymptomatic persons are infective to sand flies, they represent a formidable reservoir of infection in endemic areas.

Peripapillary pachychoroid syndrome is a distinct PDS variant, in which peripapillary choroidal thickening is associated with nasal macular intraretinal and/or subretinal fluid and occasional disk edema. Recognition of PPS is important to distinguish it from disorders with overlapping features such as posterior uveitis and neuro-ophthalmologic conditions.

BackgroundOcular infections remain a major cause of blindness and morbidity worldwide. While prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~50 % of presumed infectious uveitis cases. The objective of this study is to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of patients with uveitis.MethodsThis is a proof-of-concept study, in which intraocular fluid samples were obtained from five subjects with known diagnoses, and one subject with bilateral chronic uveitis without a known etiology. Samples were subjected to MDS, and results were compared with those from conventional diagnostic tests. Pathogens were identified using a rapid computational pipeline to analyze the non-host sequences obtained from MDS.ResultsUnbiased MDS of intraocular fluid produced results concordant with known diagnoses in subjects with (n = 4) and without (n = 1) uveitis. Samples positive for Cryptococcus neoformans, Toxoplasma gondii, and herpes simplex virus 1 as tested by a Clinical Laboratory Improvement Amendments-certified laboratory were correctly identified with MDS. Rubella virus was identified in one case of chronic bilateral idiopathic uveitis. The subject’s strain was most closely related to a German rubella virus strain isolated in 1992, one year before he developed a fever and rash while living in Germany. The pattern and the number of viral identified mutations present in the patient’s strain were consistent with long-term viral replication in the eye.ConclusionsMDS can identify fungi, parasites, and DNA and RNA viruses in minute volumes of intraocular fluid samples. The identification of chronic intraocular rubella virus infection highlights the eye’s role as a long-term pathogen reservoir, which has implications for virus eradication and emerging global epidemics.Electronic supplementary materialThe online version of this article (doi:10.1186/s13073-016-0344-6) contains supplementary material, which is available to authorized users.

Aged human tissue had superior mechanical stiffness despite reduced collagen content, partially because of the accumulation of nonenzymatic cross-links. Differences in collagen content and cross-link density either had no effect or offsetting effects on the ability of the tissues to absorb strain energy.

SUMMARYBackgroundOcular infections remain a major cause of blindness and morbidity worldwide. While prognosis is dependent on the timing and accuracy of diagnosis, the etiology remains elusive in ~ 50% of presumed infectious uveitis cases.1,2 We aimed to determine if unbiased metagenomic deep sequencing (MDS) can accurately detect pathogens in intraocular fluid samples of patients with uveitis.MethodsThis is a proof-of-concept study, in which intraocular fluid samples were obtained from 5 subjects with known diagnoses, and one subject with bilateral chronic uveitis without a known etiology. Samples were subjected to MDS, and results were compared with conventional diagnostic tests. Pathogens were identified using a rapid computational pipeline to analyze the non-host sequences obtained from MDS.FindingsUnbiased MDS of intraocular fluid produced results concordant with known diagnoses in subjects with (n=4) and without (n=1) uveitis. Rubella virus (RV) was identified in one case of chronic bilateral idiopathic uveitis. The subject’s strain was most closely related to a German RV strain isolated in 1992, one year before he developed a fever and rash while living in Germany.InterpretationMDS can identify fungi, parasites, and DNA and RNA viruses in minute volumes of intraocular fluid samples. The identification of chronic intraocular RV infection highlights the eye’s role as a long-term pathogen reservoir, which has implications for virus eradication and emerging global epidemics.

Surgery may be effective in some subsets of patients with lamellar macular hole, but postoperative visual loss is not uncommon and prospective controlled studies are warranted.