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The Brothers (San Francisco Bay)

The Brothers are a pair of small islands, East Brother and West Brother, located in the San Rafael Bay embayment of San Pablo Bay 1,000 feet west of Point San Pablo in Contra Costa County, California. The 19th century Mexican Diseño del Rancho de San Pablo, names East Brother Island as Isla de Pajaros or "Bird Island." The Brothers, along with The Sisters on the opposite side of San Pablo Strait, were reserved for military purposes by order of President Andrew Johnson in 1867. After many a court battle, the plans were scrapped. East Brother Island is home to the East Brother Island Light, a light house and a Victorian house that are a present-day bed and breakfast inn. Islands of San Francisco Bay List of islands of California East Brother Light Station

NT5C3

Cytosolic 5'-nucleotidase 3 known as cytosolic 5'-nucleotidase 3A, pyrimidine 5’-nucleotidase, p56, is an enzyme that in humans is encoded by the NT5C3, or NT5C3A, gene on chromosome 7. This gene encodes a member of the 5'-nucleotidase family of enzymes that catalyze the dephosphorylation of nucleoside 5'-monophosphates; the encoded protein is the type 1 isozyme of pyrimidine 5' nucleotidase and catalyzes the dephosphorylation of pyrimidine 5' monophosphates. Mutations in this gene are a cause of hemolytic anemia due to uridine 5-prime monophosphate hydrolase deficiency. Alternatively spliced transcript variants encoding multiple isoforms have been observed for this gene, pseudogenes of this gene are located on the long arm of chromosomes 3 and 4; the NT5C3 gene consists of 10 exons and can be alternatively spliced at exon 2. Four possible isoforms have been identified, encoding proteins with lengths of 336 residues, 297 residues, 286 residues, 285 residues; the 286-residue long isozyme is a monomeric protein containing 5 cysteine residues and no disulfide bridges or phosphate content.

It has a predicted mass of 32.7 kDa and a predicted globular tertiary structure consisting of 30% α-helices and 26% extended strands. This enzyme structurally resembles members of the haloacid dehalogenase superfamily in regards to the shared α/β-Rossmann-like domain and a smaller 4-helix bundle domain. Three motifs in the α/β-Rossmann-like domain form the catalytic phosphate-binding site. Motif I is responsible for the 5′-nucleotidase activity: the first Asp makes a nucleophilic attack on the phosphate of the nucleoside monophosphate substrate, while the second Asp donates a proton to the leaving nucleoside; the active site is located in a cleft between the α/β-Rossmann-like domain and 4-helix bundle domain. NT5C3 is a member of the 5'-nucleotidase family and one of the five cytosolic members identified in humans. NTC53 catalyzes the dephosphorylation of the pyrimidine 5′ monophosphates UMP and CMP to the corresponding nucleosides; this function contributes to RNA degradation during the erythrocyte maturation process.

As a result, NT5C3 regulates both the endogenous nucleoside and nucleotide pool balance, as well as that of pyrimidine analogs such as gemcitabine and AraC. NT5C3 was first discovered in red blood cells, but its expression has been observed in multiple tumors, fetal tissues, adult testis, the brain. In particular, the 297-residue isoform of this enzyme is expressed in lymphoblastoid cells; the loss of NT5C3 in pyrimidine 5' nucleotidase deficiency, an autosomal recessive condition, leads to the accumulation of high concentrations of pyrimidine nucleotides within erythrocytes. This deficiency is characterized by moderate hemolytic anemia, jaundice and marked basophilic stippling, has been associated with learning difficulties. Two homozygous mutations identified in this gene produced large deletions that could cripple the enzyme’s structure and function, are thus causally linked to pyrimidine 5' nucleotidase deficiency and hemolytic anemia. Heterozygous mutations in pyrimidine 5' nucleotidase deficiency may contribute to the large variability in thalassemia phenotypes.

Pyrimidine 5' nucleotidase deficiency is linked to the conversion of hemoglobin E disease into an unstable hemoglobinopathy-like disease. NT5C3 is identical to p36, a identified alpha-interferon-induced protein involved in forming lupus inclusions. Since NT5C3 can metabolize AraC, a nucleoside analog used in chemotherapy for acute myeloid leukemia patients, genotyping one of its polymorphisms may aid detection of patients who will respond favorably to this therapy. NTC53 is known to interact with pyrimidine nucleoside monophosphates UMP and CMP, as well as the anineoplastic agents 5’-AZTMP and 5’-Ara-CMP

Francis Bernard (judge)

Francis Bernard SL was an Irish lawyer and judge. He was the son of Francis Bernard of Castle Mahon and Mary Freke, daughter of Arthur Freke and Dorothy Smyth and sister of Percy Freke. Bernard sat as Member of Parliament in the Irish House of Commons, he represented Clonakilty between 1692 and 1695 and subsequently Bandonbridge between 1695 and 1727. He was appointed Solicitor-General for Ireland in 1711, a post he held until 1714, Prime Serjeant in 1724. Two years he became a Judge on the Irish Court of Common Pleas. In 1693, Bernard married Alice Ludlow, daughter of Stephen Ludlow M. P, they had a daughter, who married firstly James Caulfeild, 3rd Viscount Charlemont, secondly Thomas Adderley, six sons. His grandson James, son of Major North Ludlow Bernard and his first wife Rose Echlin, was the ancestor of the Earls of Bandon; the leading statesman James Caulfeild, 1st Earl of Charlemont was another of Bernard's grandsons