Targeting Bim via a lncRNA Morrbid Regulates the Survival of Preleukemic and Leukemic Cells

Inhibition of anti-apoptotic proteins BCL-2 and MCL-1 to release pro-apoptotic protein BIM and reactivate cell death could potentially be an efficient strategy for the treatment of leukemia. Here, we show that a lncRNA, MORRBID, a selective transcriptional repressor of BIM, is overexpressed in human acute myeloid leukemia (AML), which is associated with poor overall survival. In both human and animal models, MORRBID hyperactivation correlates with two recurrent AML drivers, TET2 and FLT3ITD. Mice with individual mutations of Tet2 or Flt3ITD develop features of chronic myelomonocytic leukemia (CMML) and myeloproliferative neoplasm (MPN), respectively, and combined presence results in AML. We observe increased levels of Morrbid in murine models of CMML, MPN, and AML. Functionally, loss of Morrbid in these models induces increased expression of Bim and cell death in immature and mature myeloid cells, which results in reduced infiltration of leukemic cells in tissues and prolongs the survival of AML mice

Studies of the roles of the Hunk serine-threonine kinase and the c -Myc oncogene in mammary gland development and carcinogenesis

Breast cancer is the most commonly diagnosed malignancy in women in the United States. Unfortunately, the current breast cancer related mortality rate remains comparable to the mortality rate of more than a decade ago. These facts highlight the need for a better understanding of the biological pathways that lead to breast cancer. This dissertation addresses the role of specific genes implicated in the regulation of mammary development and breast cancer. The novel, SNF1-related serine/threonine kinase, Hunk (Hormonally Upregulated Neu-Tumor Associated Kinase), has recently been identified and has been demonstrated to inhibit murine mammary epithelial proliferation and differentiation when overexpressed. To address further the role of Hunk in development, we generated mice that possess homozygous null mutations at the Hunk locus. These mice do not demonstrate overt developmental defects, and mammary gland development proceeds normally in Hunk-deficient mice. These results suggest that Hunk is dispensable for normal embryonic development as well as post-natal mammary development. We also investigated the role of Hunk in tumorigenesis in vivo . Loss of Hunk significantly affects mammary tumorigenesis in an oncogene-specific manner. Primary mammary tumorigenesis initiated by the neu oncogene is delayed in Hunk-deficient animals relative to their wild type counterparts, whereas secondary tumorigenesis is inhibited by loss of Hunk in c-myc initiated tumors. The decreased metastatic potential in c-myc-induced Hunk-deficient tumors correlates with reduced TGF-β activity. TGF-β signaling and c-myc activity have been shown to play opposing roles in mammary epithelial proliferation and differentiation. We present evidence that, in vivo, c-myc expression can inhibit mammary gland Tgfb1 expression directly. This effect is likely to be mediated at the level of transcription and may involve the zinc-finger protein Miz-1. c-Myc-mediated inhibition of Tgfb1 expression, as well as the expression of other TGF-β target genes, occurs in a developmental stage-specific manner

New Species of Andrya and Paranoplocephala (Cestoidea: Anoplocephalidae) from Voles and Mole-Rats in Israel and Syria

Andrya rauschi n. sp. from Microtus guentheri differs from all other species in testes number (22-40) and distribution. Andryar auschi is superficially similar to Paranoplocephala omphalodes but differs in the development of the uterus. Paranoplocephala nevoi n. sp. from Spalax ehrenbergi, is most similar to Paranoplocephala gundii,/i\u3e and Paranoplocephalaja nickii but differs in the number of testes (26-44). Paranoplocephala nevoi differs from the remaining species in the distribution of testes and in having unilateral genital pores

Raillietina (Raillietina) alectori sp. n. and other avian cestodes from Israel and Sinai

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Clinical Impact of Genomic Information in Pediatric Leukemia

Pediatric leukemia remains a significant contributor to childhood lethality rates. However, recent development of new technologies including next-generation sequencing (NGS) has increased our understanding of the biological and genetic underpinnings of leukemia, resulting in novel diagnostic and treatment paradigms. The most prevalent pediatric leukemias include B-cell acute lymphoblastic leukemia (B-ALL) and acute myeloid leukemia (AML). These leukemias are highly heterogeneous, both clinically and genetically. There are multiple genetic subgroups defined by the World Health Organization, each with distinct clinical management. Clinical laboratories have started adopting genomic testing strategies to include high-throughput sequencing assays which, together with conventional cytogenetic techniques, enable optimal patient care. This review summarizes genetic and genomic techniques used in clinical laboratories to support management of pediatric leukemia, highlighting technical, biological, and clinical advances. We illustrate clinical utilities of comprehensive genomic evaluation of leukemia genomes through clinical case examples, which includes the interrogations of hundreds of genes and multiple mutation mechanisms using NGS technologies. Finally, we provide a future perspective on clinical genomics and precision medicine

Biologicalisation: Biological transformation in manufacturing

A new emerging frontier in the evolution of the digitalisation and the 4th industrial revolution (Industry 4.0) is considered to be that of “Biologicalisation in Manufacturing”. This has been defined by the authors to be “The use and integration of biological and bio-inspired principles, materials, functions, structures and resources for intelligent and sustainable manufacturing technologies and systems with the aim of achieving their full potential.” In this White Paper, detailed consideration is given to the meaning and implications of “Biologicalisation” from the perspective of the design, function and operation of products, manufacturing processes, manufacturing systems, supply chains and organisations. The drivers and influencing factors are also reviewed in detail and in the context of significant developments in materials science and engineering. The paper attempts to test the hypothesis of this topic as a breaking new frontier and to provide a vision for the development of manufacturing science and technology from the perspective of incorporating inspiration from biological systems. Seven recommendations are delivered aimed at policy makers, at funding agencies, at the manufacturing research community and at those industries involved in the development of next generation manufacturing technology and systems. It is concluded that it is valid to argue that Biologicalisation in Manufacturing truly represents a new and breaking frontier of digitalisation and Industry 4.0 and that the market potential is very strong. It is evident that extensive research and development is required in order to maximise on the benefits of a biological transformation