BackgroundOur understanding of the eukaryotic tree of life and the tremendous diversity of microbial eukaryotes is in flux as additional genes and diverse taxa are sampled for molecular analyses. Despite instability in many analyses, there is an increasing trend to classify eukaryotic diversity into six major supergroups: the 'Amoebozoa', 'Chromalveolata', 'Excavata', 'Opisthokonta', 'Plantae', and 'Rhizaria'. Previous molecular analyses have often suffered from either a broad taxon sampling using only single-gene data or have used multigene data with a limited sample of taxa. This study has two major aims: (1) to place taxa represented by 72 sequences, 61 of which have not been characterized previously, onto a well-sampled multigene genealogy, and (2) to evaluate the support for the six putative supergroups using two taxon-rich data sets and a variety of phylogenetic approaches.ResultsThe inferred trees reveal strong support for many clades that also have defining ultrastructural or molecular characters. In contrast, we find limited to no support for most of the putative supergroups as only the 'Opisthokonta' receive strong support in our analyses. The supergroup 'Amoebozoa' has only moderate support, whereas the 'Chromalveolata', 'Excavata', 'Plantae', and 'Rhizaria' receive very limited or no support.ConclusionOur analytical approach substantiates the power of increased taxon sampling in placing diverse eukaryotic lineages within well-supported clades. At the same time, this study indicates that the six supergroup hypothesis of higher-level eukaryotic classification is likely premature. The use of a taxon-rich data set with 105 lineages, which still includes only a small fraction of the diversity of microbial eukaryotes, fails to resolve deeper phylogenetic relationships and reveals no support for four of the six proposed supergroups. Our analyses provide a point of departure for future taxon- and gene-rich analyses of the eukaryotic tree of life, which will be critical for resolving their phylogenetic interrelationships.

Recent studies have revealed the critical role of programmed death-1 (PD-1) in exhaustion of HIV- and SIV-specific CD8+ T cells. In this study, we show that high expression of PD-1 correlates with increased ex vivo spontaneous and CD95/Fas-induced apoptosis, particularly in the “effector-memory” CD8+ T cell population from HIV+ donors. High expression of PD-1 was linked to a proapoptotic phenotype characterized by low expression of Bcl-2 and IL7-Rα, high expression of CD95/Fas and high mitochondrial mass. Expression of PD-1 and CD57 was differentially associated with the maturation status of CD8+ T cells in HIV infection. CD57 was linked to higher apoptosis resistance, with cells expressing a PD-1LCD57H phenotype exhibiting lower levels of cell death. The majority of HIV-specific CD8+ T cells were found to express a PD-1HCD57L or PD-1HCD57H phenotype. No correlation was found between PD-1 expression and ex vivo polyfunctionality of either HIV- or CMV-specific CD8+ T cells. Contrary to CD57, high expression of PD-1 was characterized by translocation of PD-1 into the area of CD95/Fas-capping, an early necessary step of CD95/Fas-induced apoptosis. Thus, our data further support the role of PD-1 as a preapoptotic factor for CD8+ T cells in HIV infection.

TON may lead to profound visual disability. Because of the absence of Class I evidence relating to treatment of TON, a lack of consensus exists among clinicians regarding the appropriate treatment for TON. Our review of the recent literature finds that there is still no reliable evidence that treatment of TON with corticosteroids, surgical optic canal decompression or both confers any benefit over observation alone, and yet these interventions incur an additional risk that may not warrant their routine use.

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Background To minimize the risk of viral transmission, ophthalmology practices limited face-to-face encounters to only patients with urgent and emergent ophthalmic conditions in the weeks after the start of the COVID-19 epidemic in the United States. The impact of this is unknown. Methods We did a retrospective analysis of the change in the frequency of ICD-10 code use and patient volumes in the 6 weeks before and after the changes in clinical practice associated with COVID-19. Results The total number of encounters decreased four-fold after the implementation of clinic changes associated with COVID-19. The low vision, pediatric ophthalmology, general ophthalmology, and cornea divisions had the largest total decrease of in-person visits. Conversely, the number of telemedicine visits increased sixty-fold. The number of diagnostic codes associated with ocular malignancies, most ocular inflammatory disorders, and retinal conditions requiring intravitreal injections increased. ICD-10 codes associated with ocular screening exams for systemic disorders decreased during the weeks post COVID-19. Conclusion Ophthalmology practices need to be prepared to experience changes in practice patterns, implementation of telemedicine, and decreased patient volumes during a pandemic. Knowing the changes specific to each subspecialty clinic is vital to redistribute available resources correctly.

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Objective: To describe the ocular findings of neurosarcoidosis (NS) through a case series and review the current literature on the ocular complications of NS. Methods: Case series of 4 patients with a literature review. Results: Ophthalmic involvement in NS includes scleritis, cranial nerve palsies, uveitis, optic nerve granulomas, and occlusive retinal vasculitis. Conclusion: NS is an uncommon, but potentially lifethreatening, manifestation of sarcoidosis with ocular involvement up to 25% of patients. Patients presenting with neuro-ophthalmic manifestations of sarcoidosis are more likely to have other sites of involvement requiring ophthalmologists to maintain a high index of suspicion for systemic disease.