Publish in OALib Journal
APC: Only $99
Decisive modulatory systems of compromise and systems of dynamic turnover in lymphoid cells and macrophages are activated by repeated bursts of viremia and as promotional schemes of representation of subsequent spread and replication of HIV-1. In such operative systems of micro-environmental conditioning and reconditioning, a significant mechanism towards the turnover of specific cell-types occurs within context of sequestration within macrophages and circulating monocytes. Dendritic cells in germinal follicles and within specific organs such as the Langerhans cells of the skin are allied to dysfunctionality of such cellular subtypes as exemplified by the resident microglia of the central nervous system. Decisive perturbation in cell-type number and in dysfunctional activation indicate an exquisite modulatory role for HIV-1 in promoting homeostatic-related mechanisms within organs and tissues towards utilization in terms of viral dynamics and cytokine operability. In such manner, HIV-1 replication is itself a system of promotion in spread of viruses across cell-type and host cell specificities that tend to characterize and recharacterize systems of cytokine network operability in particular.
Definition of the malignant transformation event is central to a distinction between neural stem cells and cancer stem cells. In such manner, the descriptive analysis of various tumors such as gliomas would allow for the distinction of genetic injury and probably epigenetic events that transform gene transcription pathways. Hypoxia is a major conditioning influence acting on stem cell niche microenvironments that evolve in terms particularly of micro-vascular dynamics. The incremental involvement of entire fields of cancerization allows for the establishment of permissive conditions of repetitive nature and within the contextual involvement of multiple clones of injured cells that condition, in turn, the stem cell niche. In view of the establishment of progressive malignant change, it is significant to view the cancerization as an integral involvement of both sequential and concurrent events in defining the roles of stem cells and cancer stem cells in terms of a primal process of dedifferentiation beyond simple markers of morphologic transformation.
This review article
discusses dimensional reconstruction of alternative splicing that not only
affects primarily the distributional dimensions of isoforms of various protein
species but especially influences the nature of interactivity events between
various protein species and also the structure of the given protein molecules.
In such terms, disorders of differentiation of individual tumors and of tumor
types and subtypes would correlate with distinctive dimensions of expression of
a limited number of genes in various modes of expressed selectivity programs.
In particular, the differentiation programs of normal tissues would correlate
with combinatorial systems of splicing factors and of auxiliary factors in the
development of patterns of gene expression. The significance of mis-splicing
events is consonant with the wide range of phenotypic expression of neoplastic
lesions and in the great variety of differentiation patterns and also of the
variable degrees of differentiation of various components of a given neoplasm.
The structure of given protein isoforms resulting from alternative splicing
correlate with the sequence context of exons in the enhancement or inhibition
of splicing events and would also influence pathobiologic behavior patterns of
given neoplastic lesions. The development of abnormal cell signalling pathways
and of interactivity patterns in a combinatorial way would directly influence
the stability and trafficking dynamics of given protein molecular species in inducing
an abundance of protein isoform production. Series of multi-component systems
ranging from receptivity to consequential pathways of development of differential
phenotype would allow for a high degree of modulatory effect within systems
implicating in particular the interactions of individual tumor cells with each other
and with the matrix components. It is within the context of constitutive versus
alternative splicing events that this review article proposes that proportional
recreation of differentiation pathways promotes a self-progression of the
pathobiologic processes of a given neoplastic lesion.