Differential gene expression in anatomical compartments of the human eye

BACKGROUND: The human eye is composed of multiple compartments, diverse in form, function, and embryologic origin, that work in concert to provide us with our sense of sight. We set out to systematically characterize the global gene expression patterns that specify the distinctive characteristics of the various eye compartments. RESULTS: We used DNA microarrays representing approximately 30,000 human genes to analyze gene expression in the cornea, lens, iris, ciliary body, retina, and optic nerve. The distinctive patterns of expression in each compartment could be interpreted in relation to the physiology and cellular composition of each tissue. Notably, the sets of genes selectively expressed in the retina and in the lens were particularly large and diverse. Genes with roles in immune defense, particularly complement components, were expressed at especially high levels in the anterior segment tissues. We also found consistent differences between the gene expression patterns of the macula and peripheral retina, paralleling the differences in cell layer densities between these regions. Based on the hypothesis that genes responsible for diseases that affect a particular eye compartment are likely to be selectively expressed in that compartment, we compared our gene expression signatures with genetic mapping studies to identify candidate genes for diseases affecting the cornea, lens, and retina. CONCLUSION: Through genome-scale gene expression profiling, we were able to discover distinct gene expression 'signatures' for each eye compartment and identified candidate disease genes that can serve as a reference database for investigating the physiology and pathophysiology of the eye

Transitive and Gallai colorings

A Gallai coloring of the complete graph is an edge-coloring with no rainbow triangle. This concept first appeared in the study of comparability graphs and anti-Ramsey theory. We introduce a transitive analogue for acyclic directed graphs, and generalize both notions to Coxeter systems, matroids and commutative algebras. It is shown that for any finite matroid (or oriented matroid), the maximal number of colors is equal to the matroid rank. This generalizes a result of Erd\H{o}s-Simonovits-S\'os for complete graphs. The number of Gallai (or transitive) colorings of the matroid that use at most $k$ colors is a polynomial in $k$. Also, for any acyclic oriented matroid, represented over the real numbers, the number of transitive colorings using at most 2 colors is equal to the number of chambers in the dual hyperplane arrangement. We count Gallai and transitive colorings of the root system of type A using the maximal number of colors, and show that, when equipped with a natural descent set map, the resulting quasisymmetric function is symmetric and Schur-positive.Comment: 31 pages, 5 figure

Brain abscess and stroke in children and adults with hereditary hemorrhagic telangiectasia: Analysis of a large national claims database

BACKGROUND AND OBJECTIVES: Hereditary hemorrhagic telangiectasia (HHT) is an inherited disease associated with pathogenic variants in transforming growth factor-β signaling pathway-related genes, resulting in abnormal vascular development in various organs. Brain arteriovenous malformations (AVMs) may lead to intracranial hemorrhage, and brain abscess or ischemic stroke may result from right to left shunting via pulmonary AVMs. We aimed to investigate the risk for these severe complications in both adults and children with HHT. METHODS: We conducted a case-control study among participants aged 1-64 years in the MarketScan Commercial (2006-2019) and Multistate Medicaid Databases (2011-2019). We identified cases with HHT using RESULTS: A total of 5,796 patients with HHT, of whom 588 were children (age younger than 16 years), were matched with 57,960 controls. There was an increased incidence of brain abscesses in HHT cases compared with controls, with an RR of 35.6 (95% CI 15.4-82.5). No brain abscesses were recorded in children aged 15 years or younger. Hemorrhagic strokes/subarachnoid hemorrhages were more common in HHT cases, with an RR of 4.01 (95% CI 2.8-5.7) in adults and 60.2 (95% CI 7.2-500.4) in children. Ischemic strokes were also more common in cases, with an RR of 3.7 (95% CI, 3.0-4.5) in adults and 70.4 (95% CI 8.7-572.3) in children. DISCUSSION: We observed a much higher incidence of severe CNS vascular complications in patients with HHT, particularly in children. Although a higher incidence of brain abscesses was noted in adult patients with HHT, no brain abscesses were recorded in children, a result that may be considered when surveillance recommendations for this population are revisited

Clinical disorders affecting mesopic vision

Vision in the mesopic range is affected by a number of inherited and acquired clinical disorders. We review these conditions and summarize the historical background, describing the clinical characteristics alongside the genetic basis and molecular biological mechanisms giving rise to rod and cone dysfunction relevant to twilight vision. The current diagnostic gold standards for each disease are discussed and curative and symptomatic treatment strategies are summarized

To whom does the law speak? Canvassing a neglected picture of law’s interpretive field

Among the most common strategies underlying the so-called indeterminacy thesis is the following two-step argument: (1) that law is an interpretive practice, and that evidently legal actors more generally hold different (and competing) theories of meaning, which lead to disagreements as to what the law says (that is, as to what the law is); (2) and that, as there is no way to establish the prevalence of one particular theory of meaning over the other, indeterminacy is pervasive in law. In this paper I offer some reflections to resist this trend. In particular I claim that a proper understanding of law as an authoritative communicative enterprise sheds new light on the relation between the functioning of the law and our theories of interpretation, leading to what can be considered a neglected conclusion: the centrality of the linguistic criterion of meaning in our juridical interpretive practices. In the first part of the chapter I discuss speech-act theory in the study of law, assessing its relevance between alternative options. Then I tackle the ‘to whom does the law speak?’ question, highlighting the centrality of lay-people for our juridical practices. Lastly, I examine the consequences of this neglected fact for our interpretive theories

Idiopathic osteonecrosis of the medial tibial plateau

Osteonecrosis of the medial tibial plateau is characterized by acute pain on the medial aspect of the knee. Progression can lead to articular collapse and requires early diagnosis and treatment. We studied seven patients affected of idiopathic osteonecrosis of the tibial plateau. The mean age was 62 years and the mean follow-up 42 months. We performed roentgenograms in all patients, bone scans in three patients and magnetic resonance image (MRI) in five. MRI shows T1-weighted low-intensity signal and T2-weighted high-intensity signal with a surrounding area of intermediate low-intensity signal. An increased focal uptake was seen at bone scan. Histological findings showed necrotic bone with empty lacunae. Surgical treatment consisted of tibial subchondral drilling in four patients-two of them by failure of conservative treatment, and a total knee arthroplasty in other two. One patient had a satisfactory evolution with conservative treatment. Idiopathic osteonecrosis of the tibial plateau must be considered in elderly patients with knee pain over the medial tibial plateau. At early stages, decompression with tibial drilling must be considered. This procedure allows a prompt and effective relief of symptom

Cone-rod dystrophy can be a manifestation of Danon disease

Background Danon disease is a neuromuscular disorder with variable expression in the eye. We describe a family with Danon disease and cone-rod dystrophy (CRD). Methods Affected males of one family with Danon were invited for an extensive ophthalmologic examination, including color vision testing, fundus photography, Goldmann perimetry, full-field electroretinogram (ERG), and SD-OCT. Previous ophthalmologic data were retrieved from medical charts. The LAMP2 and RPGR gene were analyzed by direct sequencing. Results Two siblings had no ocular phenotype. The third sibling and a cousin developed CRD leading to legal blindness. Visual acuity deteriorated progressively over time, color vision was severely disturbed, and ERG showed reduced photopic and scotopic responses. SD-OCT revealed thinning of the photoreceptor and RPE layer. Visual fieldsdemonstrated central scotoma. The causal mutation was p. Gly384Arg in LAMP2; no mutations were found in RPGR. Conclusions This is the first description of CRD in Danon disease. The retinal phenotype was a late onset but severe dystrophy characterized by loss of photoreceptors and RPE cells. With this report, we highlight the importance of a comprehensive ophthalmologic examination in the clinical work-up of Danon disease