Protein C-mannosylation: facts and questions

Among the posttranslational modifications of proteins, glycosylation is probably the most abundant one. Two main types of protein glycosylation have been known for several years, namely N-glycosylation and O-glycosylation. Their biochemical properties, structure and biosynthesis, have been described extensively. Their biological functions are also known for a number of proteins, although in many cases the function remains speculative despite continuous efforts. A few years ago, a new type of protein glycosylation was found, which is different from the above-mentioned ones. It was called C-glycosylation, since the sugar is linked to the protein through a carbon-carbon bond. This article reviews the biochemistry of C-glycosylation, the biosynthetic pathway and structural requirements. Possible biological functions of this modification are also discussed.     

Morphogenesis of insect-induced plant galls: facts and questions

Insect-induced galls (‘galls’ hereafter) represent highly regulated growth manifestations on plants. They present unique geometrical forms, which are, usually, unknown in the normal plant system. Galls are the best examples for modified natural structures that arise solely because of messages from an alien organism - the insect. Galls develop as an extension of the host-plant phenotype. But how the physiological networks and signal-activated subsystems work in coordination in expressing galls that serve the nutritional and shelter needs of the inducing insect are unclear. In galls and bacteria-induced tumors, the basic developmental events are essentially similar. However, tightly regulated specific differentiation processes occur in galls, making them different from tumors. Moreover variations in differentiation patterns occur in galls induced by insects of different taxonomic groups. While providing an overview of the control of shape and structure in galls, this article identifies the unanswered questions in gall morphogenesis.By analyzing the recognizable steps in gall morphogenesis, viz., gall initiation, stimulus recognition in host plants, signal transduction in host plants, growth of galls, and qualitative differentiation in galls, I have indicated that the insect saliva flushed on the wounded plant site alters the subcellular environment of cells and thus places it in a state of chemical shock. This shock induces osmotic changes, which establishes the first recognizable stage in gall induction. To repair the wound and neutralize the osmotic-change induced stress, the plant responds by establishing from one to a few metaplasied cell(s). Localized metabolic changes spread, from these cells, not throughout the involved plant organ, but in a limited manner around the immediate site of insect occurrence. When the shock is of low intensity, the plant responds with the development of one or more metaplasied cell(s) and gall development starts; when the shock factor is of high intensity, the cells under the insect action die, rejecting the inducing insect, defending plant tissue. These changes dictate the new morphogenetic events. Insects feed on gall tissue continuously for a specific period (synchronizing with their life history) and therefore, the osmotic-change related stress prevails for that span of time, which in turn triggers a sequence of plant-mediated changes including synthesis of growth promotors. Osmotic stress affects electrical properties of the plasma membrane and impacts on IAA activity, which in turn, alters H⁺-transport systems. During the physical action of insect feeding, the host-cell wall breaks down, and the degenerated wall materials act as elicitors.Using galls (e.g., ‘cecidial shoots’ on leaves, modified vegetative buds) induced on species of south and south-east Asian Dipterocarpaceae by different Beesoniidae (Coccoidea) as model complexity in gall morphogenesis is discussed. Manipulatory experimental studies done on the regeneration of epiphyllous buds on Pteridium, Begonia, and a Helianthus hybrid indicate that insect-induced neoplasmic shoots that arise on the leaves of tropical Dipterocarpaceae fall into the morphogenetic regulation of leaf, yet maintaining their freedom of differentiation. Even though a gall is a part of the plant - a multicellular organism made of the same genetic material - organismal development generates a range of cell types with dictated functions fitting into of Waddington's epigenetic-landscape model. As of today, our knowledge stops here.Plants as living systems display different strategies to mitigate and neutralize stress. Although these strategies exist in their genetic constitution, they are mediated by complex molecular interactions. Plants have a flexible short-term strategy to respond to stress; organisms that can modify gene expression reversibly have an advantage in evolutionary terms, since they can avoid rearrangements and species diversification. Mechanisms of DNA methylation and histone modifications possibly regulate inheritance of stress ‘memories’. Inherited genetic traits also play a role in gall morphogenesis, followed by roles played by correlating morphogenetic factors. An articulated reconstruction of the developmental process commencing from either one or a group of metaplasied cells that gets transmitted through subsequent growth promoter-mediated cell expansion, until the commitment of the metaplastic cell and those in its neighbourhood enabling the start of ‘novel’ cell-cycle patterns, cell multiplication, programmed differentiation, and control is needed to explain symmetry - a morphogenetic phenomenon that makes the insect-induced galls distinct from the bacteria-induced tumors.     

Immunologic reconstitution by interleukin-2: facts and open questions

Interleukin-2 (IL-2), one of the most potent immunoregulatory and inflammatory cytokines, is being tested in phase III clinical trials in order to demonstrate its efficacy in combination with current antiviral agents in preventing the occurrence of opportunistic infections and death in individuals infected by the human immunodeficiency virus (HIV). In the meantime, its capacity to boost the number of CD4+ T cells in peripheral blood has been confirmed by a number of individual phase I/II trials conducted in different countries by independent investigators. In the face of this remarkable result, little is known of the effects exerted by this cytokine once administered to infected individuals in terms of its impact on different immunologic functions. The recent acquisitions on the important role played by latently infected cells in in vivo infection in reinitiating HIV replication and cytopathicity once antiviral therapy is suspended or becomes suboptimal, has shed new light on the possibility of utilizing immunologic strategies, including IL-2, for eradicating the virus from latent reservoirs. Results from a clinical trial conducted at our Institute indicate a decrease in lymphocyte-associated HIV DNA after IL-2 administration, supporting this hypothesis.     

HP1: facts,open questions,and speculation

The demonstration, over a decade ago, that HP1 is a highly conserved constituent of heterochromatin was accompanied by the explicit view that this protein plays a pivotal role in epigenetic regulation (P.B. Singh, J.R. Miller, J. Pearce, R. Kothary, R.D. Burton, R. Paro, T.C. James, and S.J. Gaunt, 1991, Nucleic Acids Res. 19, 789-794). Recent studies have confirmed this view, unveiling specific interactions of HP1 with a variety of histone and nonhistone proteins. We discuss here some of these observations, concentrating on structure-function relationships and intracellular dynamics. Integrating the available information, we also present a hypothetical model describing how HP1, acting as a bifunctional cross-linker, could organize peripheral heterochromatin and contribute in the compartmentalization of the cell nucleus.     

Mammalian diurnality: some facts and gaps

A major factor contributing to the evolution of mammals was their ability to be active during the night, a niche previously underused by terrestrial vertebrates. Diurnality subsequently reemerged multiple times in a variety of independent lineages. This paper reviews some recent data on circadian mechanisms in diurnal mammals and considers general themes that appear to be emerging from this work. Careful examination of behavioral studies suggests that although subtle differences may exist, the fundamental functions of the circadian system are the same, as seems to be the case with respect to the molecular mechanisms of the clock. This suggests that responses to signals originating in the clock must be different, either within the SCN or at its targets or downstream from them. Some features of the SCN vary from species to species, but none of these has been clearly associated with diurnality. The region immediately dorsal to the SCN, which receives substantial input from it, exhibits dramatically different rhythms in nocturnal lab rats and diurnal grass rats. This raises the possibility that it functions as a relay that transforms the signal emitted by the SCN and transmits different patterns to downstream targets in nocturnal and diurnal animals. Other direct targets of the SCN include neurons containing orexin and those containing gonadotropin-releasing hormone, and both of these populations of cells exhibit patterns of rhythmicity that are inverted in at least one diurnal compared to one nocturnal species. The patterns that emerge from the data on diurnality are discussed in terms of the implications they have for the evolution and neural substrates of a day-active way of life.     

Adaptive response--the general biological tendency: facts, hipothesis, questions

It is leading up to the proofs testifying about the general-biological nature of adaptive response (AR), which is similar unspecific defense effect: for example, small doses induce cytokines synthesis, providing the resistance to different infectious agents. The connection between AR, DNA-repair, anti-oxidative status, expression of TP53 gene is discussed. The absence of AR at some patients can be explained either individual sensitivity to challenging treatment or criteria of the estimation (chromosome aberration, apoptosis et. al.). These facts are showing that the absence of AR cannot be the indicator of the risk for health. So the idea about general biological existence of AR is postulated because it is a characteristic for different species.