Subleukaemic T-Lymphoblastic Leukaemia in a Horse.

A 20-year-old Dutch Warmblood gelding was referred with clinical signs of anorexia, weight loss, intermittent fever, cough, subcutaneous oedema and exercise intolerance. Haematological examination revealed the presence of blast cells, decreased lymphocytes, mild thrombocytopenia and anaemia but no leucocytosis. Serum analyses detected elevated aspartate aminotransferase and gamma-glutamyl transferase activities and triglyceride concentrations. Twenty-two days after the initial visit, the horse died after showing clinical signs of decreased appetite, increased body temperature, tachypnoea and tachycardia. At necropsy, there was mild splenomegaly but enlarged lymph nodes, masses or nodules were not seen in any organ. Histologically, neoplastic cells were seen in the subcapsular and medullary lymph sinus of the mediastinal, axillary, mesenteric and renal lymph nodes. The bone marrow was densely cellular with numerous large round neoplastic cells that had round nuclei with clear nucleoli and scant cytoplasm. The neoplastic cells were immunopositive for CD3 but negative for CD20, BLA36, CD204, Iba-1, CD204 and granzyme B. Based on these findings, the neoplasm was diagnosed as subleukaemic T-lymphoblastic leukaemia, which, to the best of our knowledge, is the first report of this neoplasm in horses.

Hepatic neuroendocrine carcinoma with metastases to the lymph nodes in a sika deer (Cervus nippon yakushimae).

A 26-year and 6-month-old male sika deer that was kept at the Showa Park, Tokyo, Japan, collapsed and died of severe disease wasting and severe tabefaction. Grossly, numerous masses, 0.3-1.0 cm diameter, were dispersed throughout the liver. The multiple masses were composed of tumor cells, which had hypochromatic nuclei and abundant faintly eosinophilic cytoplasm, arranged in nests of various sizes. Immunohistochemically, tumor cells were positive for cytokeratin, chromogranin A, synaptophysin and gastrin. Ultrastructurally, the cytoplasm of the tumor cells contained abundant membrane-bound electron-dense granules. A metastatic lesion was observed in the renal, hepatic and pancreatic lymph nodes. On the basis of these findings, this tumor was diagnosed as a neuroendocrine carcinoma with metastases to the lymph nodes.

Def1 mediates the degradation of excess nucleolar protein Nop1 in budding yeast.

Nucleolar proteins such as Nop1/fibrillarin are degraded by nucleophagy in nutrient-starved conditions. However, whether and how excess nucleolar proteins are removed in normal conditions is unknown. Here we show that overexpressed nucleolar protein Nop1 is toxic and degraded in nutrient-rich conditions in budding yeast. The degradation was dependent on proteasomes. The CUE domain-containing protein Def1 mediated the degradation via the CUE domain and alleviated toxicity of Nop1 overexpression. Def1 was recruited to overexpressed Nop1 in the nucleolus. Ubiquitin mutants compromised this recruitment. This study revealed that Def1 is a novel factor for ubiquitin-dependent degradation of excess nucleolar proteins.

rDNA Condensation Promotes rDNA Separation from Nucleolar Proteins Degraded for Nucleophagy after TORC1 Inactivation.

Nutrient starvation and inactivation of target of rapamycin complex 1 (TORC1) protein kinase induce nucleophagy preferentially degrading only nucleolar components in budding yeast. Nucleolar proteins are relocated to sites proximal to the nucleus-vacuole junction (NVJ), where micronucleophagy occurs, whereas rDNA, which is embedded in the nucleolus under normal conditions, moves to NVJ-distal regions, causing rDNA dissociation from nucleolar proteins after TORC1 inactivation. This repositioning is mediated via chromosome linkage INM protein (CLIP)-cohibin complexes that tether rDNA to the inner nuclear membrane. Here, we show that TORC1 inactivation-induced rDNA condensation promotes the repositioning of rDNA and nucleolar proteins. Defects in condensin, Rpd3-Sin3 histone deacetylase (HDAC), and high-mobility group protein 1 (Hmo1), which are involved in TORC1 inactivation-induced rDNA condensation, compromised the repositioning and nucleophagic degradation of nucleolar proteins, although rDNA still escaped from nucleophagic degradation in these mutants. We propose a model in which rDNA condensation after TORC1 inactivation generates a motive force for the repositioning of rDNA and nucleolar proteins.