The PLZF protein may be a key interaction partner of PML. The PLZF protein, originally characterized by its fusion to RARα in t(11;17)(q23;q21)-associated APL, colocalizes with PML both in myeloid and in transfected nonhematopoietic cells.216Colocalization was incomplete, and one group estimated only approximately 30% overlap of PML and PLZF in KG1 cells.228The PLZF nuclear dots and PML NBs also appeared to be in different functional compartments, because expression of the adenovirus E4 protein in KG1 cells delocalized PML from the NB (see below) but did not affect the expression pattern of PLZF. In semistable transfected cells, several days were required for the PML and PLZF proteins to sort within the cell and become colocalized, suggesting complex regulation of this association.216 Nevertheless, interaction between PML and PLZF was demonstrated by biochemical assay, and the association was found to be mediated by the coiled-coil domain of PML and the first two zinc fingers of PLZF (A. Zelent, personal communication, December 1998). PLZF could be delocalized to a microspeckled pattern in NB4 cells and reverted to the NBs upon treatment with retinoic acid. These provocative findings suggest that PML may be involved in the transcriptional modulation mediated by PLZF or, conversely, that PML regulates availability of PLZF by sequestration within the NBs.216 Thus, a common mode of leukemogenesis may exist in APL, based on disruption of a pathway that contains both PLZF and PML.
The mouse model of APL most similar to human disease was generated by use of the MRP8 promoter, which is expressed at the promyelocyte to metamyelocyte stage and continues to be active in mature neutrophils,343 as opposed to the cathepsin G gene, which is expressed during a more narrow window of promyelocyte differentiation.344 These mice also developed a preleukemic phase, and about one third developed promyelocytic leukemia with a median latency of 6 months345 (S. Kogan, personal communication, July 1998), accompanied by bleeding, anemia, thrombocytopenia, and a low leukocyte count, all characteristic of human APL. When these cells were placed into culture and treated with ATRA, differentiated neutrophils were observed. The transgenic mice also developed epidermal papillomas, which further demonstrated the neoplastic activity of the PML-RARα fusion. When the animals were treated with ATRA, mature neutrophils appeared in the peripheral blood and marrow and splenomegaly was reduced, consistent with clinical differentiation. Highly purified, residual nonleukemic progenitor cells from APL patients are PML-RARα negative,346suggesting that the PML promoter driving PML-RARα expression must function at a specific stage of myeloid differentiation. Therefore, a knock-in347 strategy for the creation of transgenic mice might yield the most physiologic model of t(15;17) translocation APL.
The PLZF gene, localized on chromosome 11q23, yields a 7-kb mRNA that codes for a zinc finger transcription factor.289,359,367,368 The PLZF gene is 1 Mb telomeric to the MLL/HRX gene, which is frequently rearranged in leukemia.369-371 The genomic structure of PLZF is incompletely known, but it is clear that the N-terminal portion is encoded on a single exon and that the C-terminal zinc finger motifs are encoded by a number of small exons (Baysal et al372 and Z. Chen, personal communication, June 1998). PLZF codes for a DNA-binding protein of 673 amino acids with nine Krüppel-like C2H2 zinc finger domains with a predicted molecular weight of 74 kD (Fig 6) that migrates through polyacrylamide gels with an apparent MW of 80 to 90 kD.
In transfected cells, PLZF is localized to the nucleus and is289,368 phosphorylated on serine and threonine residues (Shaknovich and Licht, unpublished data). MDS, a primitive leukemic cell line, expresses high levels of PLZF mRNA and PLZF protein when treated with the calcium ionophore A23187.289Confocal microscopy of MDS cells showed that PLZF localized to approximately 50 small nuclear subdomains, with a lower level of diffuse nuclear staining also noted, whereas only 10 PML-containing NBs were noted per cell. The speckled pattern of subnuclear expression of PLZF depends on the presence of the POZ/BTB domain as removal of this domain leads to expression in a diffuse nuclear pattern.383Given the potential importance of the expression of the PML protein in the NB, it became important to determine whether PLZF was expressed in the same or similar domains. In hematopoietic cells that naturally express both PML and PLZF as well as in transiently transfected nonhematopoietic cells, wild-type PML and PLZF could colocalize in nuclear body structures. However, this colocalization was not complete, indicating that PLZF may act in both the nuclear body and other subnuclear compartments.216 The PLZF-RARα fusion protein, either transfected into cells or naturally expressed in blasts from a patient with t(11;17)(q23;q21) APL, did not colocalize with PML or delocalize PML from nuclear body structures.216 This critical fact indicates that delocalization of the PML component of the nuclear body is not required for the pathogenesis of APL. In contrast, in t(15;17) APL cells, PLZF is delocalized into a microspeckled pattern identical to PML-RARα.216,299 The coiled-coil region of PML, which is also responsible for PML self-association, was required for the PML-PLZF interaction. The first two zinc fingers of PLZF and not the POZ/BTB domain mediates the interaction of PLZF with PML (A. Zelent, personal communication, December 1998). Therefore, PML and other related RING finger proteins might be cofactors for PLZF function. Delocalization of PLZF might be a common and central theme in the pathogenesis of APL, because PLZF is also found in an abnormal microspeckled pattern and in t(5;17)-APL associated with the NPM-RARα protein.384
Good communication skills are essential in your online course. There are many different ways you'll communicate with your instructor and other students in your class, so we've created this module to introduce you to common terms you'll need to know and familiarize you with some concepts that we hope will lead you to success in your class.
Think of a blog as a website journal or diary. Blogs are usually run by an individual or a small group. Entries are made periodically and typically displayed in reverse chronological order (so, the most recent post will appear first). Most blogs are set up to allow readers to post comments below each entry, and it is often just as informative to read the comments and criticisms of fellow readers as it is to read the initial blog post. Some instructors may require you to post or review blogs during your online course, and they can be a useful source of information. Keep in mind, though, that blogs are typically personal communication platforms, so be sure to double-check facts or information you might find on a blog with a verified source before using it in your research.
Online class communication often takes place asynchronously rather than in real time, giving you a chance to research, write, and edit your answers, instead of being put "on the spot" during class. Think of this as an opportunity for you to really reflect and compose your thoughts carefully before you make a response.
Yes--when you communicate asynchronously online, you create a permanent record of your words. All of your electronic communication will be dated, and because of this it can be easily organized, stored and reviewed (usually for grading purposes) at a later date. Because your words are enduring, it is a good idea to compose your electronic communications carefully before posting.
This is a valid concern, because the teacher and your classmates cannot see your body language or hear your voice, written words can sometimes be misinterpreted. Review your written communications in an online course carefully before posting and try to remove any language that could be interpreted as offensive or inappropriate.
Though during our professional life, we are maintaining formal communications through different medias, a large part of the communication takes place rather informally. That is where the term "Grapevine" comes in.
Grapevine is an informal channel of business communication. It is called so because it stretches throughout the organization in all directions irrespective of the authority levels. To hear something through the grapevine is to learn of something informally and unofficially by means of gossip or rumor.
Cluster Chain: In the cluster chain, a person tells the information to the selected persons who may in turn relay (pass) the information to other selected persons. Most of the information communication follows this chain.
The grapevine allows feelings to be expressed instead of bottled up. People need to talk about what is affecting them, and the grapevine allows this kind of expression. Employees and staff can communicate important topics using their own language, instead of the technical jargon used in formal communication channels.
Tuberculosis remains a major public health problem in India with the country accounting for 1 in 5 of all TB cases reported globally. An advocacy, communication and social mobilisation project for Tuberculosis control was implemented and evaluated in Odisha state of India. The purpose of the study was to identify the impact of project interventions including the use of 'Interface NGOs' and involvement of community groups such as women's self-help groups, local government bodies, village health sanitation committees, and general health staff in promoting TB control efforts.
The expanded use of advocacy, communication and social mobilisation activities in TB control has resulted in a number of benefits. These include bridging pre-existing gaps between the health system and the community through support and coordination of general health services stakeholders, NGOs and the community. The strategic use of 'tailored messages' to address specific TB problems in low performing areas also led to more positive behavioural outcomes and improved efficiencies in service delivery. Implications for future studies are that a comprehensive and well planned range of ACSM activities can enhance TB knowledge, attitudes and behaviours while also mobilising specific community groups to build community efficacy to combat TB. The use of rapid assessments combined with other complementary evaluation approaches can be effective when reviewing the impact of TB advocacy, communication and social mobilisation activities. 041b061a72