Does diacylglycerol serve as a signaling molecule in plants?

Diacylglycerol (DAG) is an important signaling phospholipid in animals, specifically binding to the C1 domain of proteins such as protein kinase C. In most plant species, however, DAG is present at low abundance, and no interacting proteins have yet been identified. As a result, it has been proposed that the signaling function of DAG has been discarded by plants during their evolution. In this mini-review, we summarize the accumulating experimental evidence which supports that notion that changes in DAG content in response to particular cues are a feature of plant cells. This behavior suggests that DAG does indeed act as a signaling molecule during plant development and in response to certain environmental stimuli.     

Can plants use entomopathogens as bodyguards?

For 20 years, ecologists have been gathering evidence in support of the hypothesis that plants can use insect natural enemies such as predators and parasitoids as bodyguards to protect themselves from herbivory, but entomopathogens have escaped this consideration. We extend the bodyguard hypothesis to ask whether plants can use entomopathogens as bodyguards. We first discuss the evolutionary context of such tritrophic interactions and then categorize possible mechanisms as: (1) maintaining a population of bodyguards on the plant surface, (2) increasing contact rates between insect host and pathogen and (3) increasing the susceptibility of the host. We explore these mechanisms further, examining published studies for evidence for the hypothesis. We then discuss potential costs to the plant of promoting pathogens as bodyguards which may include a reduction in the efficiency of other "bodyguard" species, the incidental promotion of plant pathogens and the risk of entomopathogens developing phytopathogenicity. Aside from our intention to stimulate the testing of the bodyguard hypothesis with entompathogens and to provide a conceptual framework for this, we hope to bring evolutionary ecology and insect pathology closer together.     

Can plants use an entomopathogenic virus as a defense against herbivores?

It is by now well established that plants use various strategies to defend themselves against herbivores. Besides conventional weapons such as spines and stinging hairs and sophisticated chemical defenses, plants can also involve the enemies of the herbivores in their defense. It has been suggested that plants could even use entomopathogens as part of their defense strategies. In this paper, we show that Brassica oleraceae plants that are attacked by Myzus persicae aphids infected with an entomopathogenic parvovirus (M. persicae densovirus) transport the virus through the phloem locally and systematically. Moreover, healthy aphids that fed on the same leaf, but separated from infected aphids were infected via the plant. Hence, this is proof of the principle that plants can be vectors of an insect virus and can possibly use this virus as a defense against herbivores.     

Can ACG serve as an initiation codon for protein synthesis in eucaryotic cells?

An ACG codon, which replaces the AUG codon used to initiate the synthesis of bacteriophage T7 gene 0.3 protein, was shown to function as a low-efficiency initiation codon in a wheat germ cell-free protein-synthesizing system.     

Can modulators of apolipoproteinB biogenesis serve as an alternate target for cholesterol-lowering drugs?

Understanding the molecular defects underlying cardiovascular disease is necessary for the development of therapeutics. The most common method to lower circulating lipids, which reduces the incidence of cardiovascular disease, is statins, but other drugs are now entering the clinic, some of which have been approved. Nevertheless, patients cannot tolerate some of these therapeutics, the drugs are costly, and/or the treatments are approved for only rare forms of disease. Efforts to find alternative treatments have focused on other factors, such as apolipoproteinB (apoB), which transports cholesterol in the blood stream. The levels of apoB are regulated by endoplasmic reticulum (ER) associated degradation as well as by a post ER degradation pathway in model systems, and we suggest that these events provide novel therapeutic targets. We discuss first how cardiovascular disease arises and how cholesterol is regulated, and then summarize the mechanisms of action of existing treatments for cardiovascular disease. We then review the apoB biosynthetic pathway, focusing on steps that might be amenable to therapeutic interventions.     

Sodium tungstate: Is it a safe option for a chronic disease setting,such as diabetes?

Diabetes is a complex metabolic disorder triggered by the deficient secretion of insulin by pancreatic β cells, the resistance of peripheral tissues to the action of the hormone, or both, and is characterized by chronic hyperglycemia leading to organ damage and failure. Tight glycemic control represents the best therapy to delay or stop progression of diabetes, with many antidiabetic drugs being commercially available nowadays. However, no ideal normoglycemic agent has been developed as yet, and those already available still induce hypoglycemia and/or weight gain as major side effects, worsening glycemic control. In this respect, the inorganic salt sodium tungstate (Na₂WO₄) has been proven to offer a good antidiabetic alternative in different animal models of diabetes, reducing body weight and normalizing glycemia without causing hypoglycemic episodes. The mechanisms of action mediating the potent antidiabetic actions but also the spectrum of undesirable effects of Na₂WO₄ are still poorly understood. In fact, along with its beneficial effects, Na₂WO₄ has been consistently reported to be toxic and even carcinogenic. Given that Na₂WO₄ is accumulated in the kidneys for elimination, here, we discuss a possible association between long-term Na₂WO₄ treatment and a higher risk of renal carcinogenesis in diabetic individuals.     

Can loss of apical dominance in potato tuber serve as a marker of physiological age?

The potato tuber constitutes a model system for the study of dormancy release and sprouting, suggested to be regulated by endogenous plant hormones and their balance inside the tuber. During dormancy, potato tubers cannot be induced to sprout without some form of stress or exogenous hormone treatment. When dormancy is released, sprouting of the apical bud may be inhibited by sprout control agents or cold temperature. Dominance of the growing apical bud over other lateral buds decreases during storage and is one of the earliest morphophysiological indicators of the tuber's physiological age. Three main types of loss of apical dominance (AD) affect sprouting shape. Hallmarks of programmed cell death (PCD) have been identified in the tuber apical bud meristem (TAB-meristem) during normal growth, and are more extensive when AD is lost following extended cold storage or chemical stress. Nevertheless, the role of hormonal regulation in TAB-meristem PCD remains unclear.     

Can iron depletion inside macrophages serve to prolong HIV disease progression?

Studies have shown that the more iron in a given population, the more that population is vulnerable to intracellular opportunistic infections (OIs) in AIDS, mainly because these microbes make use of the intracellular iron to proliferate, and could render infections deadly. In contrast, macrophages that lack iron are effective in preventing an establishment of infection. We propose that reduction in total body iron could be a valuable treatment option for some intracellular infections, including OIs. We suggest two options to deprive pathogens of using intracellular iron (i) to practice regular blood-letting, an ancient treatment option, and (ii) to down-regulate hepcidin, the key hormone involved in the regulation of iron balance and recycling. This could also deprive transformed cells of metabolizing iron for survival. Whether or these methods serve to curb the onset of OIs/cancers to prolong HIV disease progression remains to be investigated.     

Does the major histocompatibility complex serve as a specific receptor for Semliki Forest virus?

Murine F9 and PCC4 teratoma cells do not express H-2 major transplantation antigens according to virus-specific T-lymphocyte cytotoxic or serological assays. However, such cells can be infected with and readily replicate many types of viruses (coxsackie B 3, mouse hepatitis, Sindbis, Semliki Forest [SFV], lymphocytic choriomeningitis, Pichinde, vesicular stomatitis, herpes simplex type 1) to the same extent as do murine F12 teratoma cells and mouse embryo fibroblasts, all of which express the H-2 determinants. In contrast, F9 and PCC4 cells are not productively infected with murine cytomegalovirus, whereas F12 and mouse embryo fibroblast cells are. In addition to replicating in H-2-negative murine teratoma cells, SFV replicates in H-2-negative murine lymphoblastoid cells. The ability of SFV to infect cells without H-2 antigens and then to effect viral antigenic expression in the cells' cytoplasm and on their surface with similar kinetics and in equivalent amounts as cells with H-2 antigens indicates that the H-2 receptor is not needed for SFV infection. Daudi cells, which lack HLA antigens, block the replication of SFV. This occurs at some point after receptor binding, as demonstrated by diminished viral mRNA. In addition, a possible membrane defect precludes viral exit in Daudi cells transfected with SFV infectious RNA. These results indicate that a cell's possession of H-2 antigens is not a requirement for SFV infection and that major histocompatibility complex antigens are not specific receptors for this virus.     

Can a 'flawless' live vector vaccine strain be engineered?

The efficiency of any live bacterial vector vaccine hinges on its ability to present sufficient foreign antigen to the human immune system to initiate the desired protective immune response(s). However, synthesis of sufficient levels of heterologous antigen can result in an increase in metabolic burden with an accompanying decrease in the fitness of the live vector, which can ultimately lower desired immune responses to both live vector and heterologous antigen. Here, we explore the underlying mechanisms of metabolic load and propose ways of minimizing such burdens to enhance the fitness and immunogenicity of Salmonella-based live vector vaccines.     

Can hydroxyurea serve as a free radical scavenger and reduce iron overload in β-thalassemia patients?

In this study, we hypothesize that hydroxyurea could provide an additional benefit as a free radical scavenger and/or iron chelator in β-thalassemia patients with iron overload. Twenty-one β-thalassemia intermedia patients who presented between 3 and 17 years but later required regular blood transfusions were enrolled for hydroxyurea therapy for a year. Fourteen patients responded to the therapy with hemoglobin levels maintained above 7.5?g/dl without transfusions. Hydroxyurea was discontinued after 6 months in seven patients who did not respond to the therapy and had to be continued on regular blood transfusions. We observed a statistically significant decrease in serum ferritin levels from 4194?±?4850?ng/ml to 2129?±?2380?ng/ml among the responders and from 2955?±?2909?ng/ml to 2040?±?2432?ng/ml among the non-responders and statistically significant decrease in labile iron pool from 18678.7?±?10067.4 mean fluorescence intensity (MFI) to 14888.5?±?5284.0?MFI among responders and from 17986.3?±?9079.8?MFI to 15634.8?±?8976.9?MFI among the non-responders after therapy. Phosphatidylserine externalization also showed a statistically significant decrease from 44.2?±?22.2?MFI to 16.6?±?6.7?MFI among the responders and from 46.9?±?33.1?MFI to 39.8?±?7.4?MFI among the non-responders along with a statistically significant decrease in the levels of reactive oxygen species from 72.8?±?35.5?MFI to 29.0?±?8.3?MFI among the responders and from 80.9?±?41.4?MFI to 40.5?±?15.8?MFI among the non-responders after therapy. A statistically significant increase in reduced glutathione levels was also observed from 430.8?±?201.1?MFI to 715.5?±?292.4?MFI among the responders and from 359.6?±?165.6?MFI to 450.3?±?279.5?MFI among the non-responders after therapy. This suggests the possible additional role of hydroxyurea as a free radical scavenger and/or iron chelator but requires a larger study for substantiation.     

Can Babesia infections be used as a model for cerebral malaria?

Infections with certain species of Plasmodium and Babesia induce, among other symptoms, cerebral pathology. The finding of heavily parasitized cerebral capillaries upon postmortem examination has led to the assumption that blockage of capillaries with infected red blood cells caused the cerebral symptoms and subsequent death. As this type of cerebrovascular pathology is found both in humans dying from malaria and in cattle dying from babesiosis, the latter could possibly be used as an animal model for the study of human cerebral malaria. However, before such a model system is adopted, the experimental data concerning cerebral pathology of babesiosis needs critical evaluation. Here, Theo Schetters and Wijnand Eling review the pathological mechanisms in cerebral babesiosis and relate these to cerebral malaria. Finally, they discuss the use of animal model systems for specific aspects of the pathological picture.     

Can biochemical properties serve as selective pressure for gene selection during inter-species and endosymbiotic lateral gene transfer?

During the evolution of endosymbiosis, only one orthologous gene, either from the invader or the invaded genome, is preserved. Genetic and environmental factors are usually invoked to explain this gene preference. How biochemical parameters can play a role in the selection of genes that code for enzymes that constitute a metabolic pathway is explored. Simple Michaelis-Menten-like enzymes are considered whose kinetic parameters are randomly generated to construct two parallel homologous pathways to account for the contributions of the invaded and the invader. Steady-state fluxes as targets of natural selection are focused. Enzymes are eliminated one by one so that the total flux through the pathway is least disturbed. Analysis of the results, done by different criteria, indicate that the maximal velocities, both forward and backward, are more influential in selection than the respective Michaelis constants. This inclination disappears as metabolite concentrations are increased. It is shown that kinetic selection criteria can result in a mosaicism of enzymes in the same pathway in terms of their genetic origin. Analysis of the results using the control coefficient paradigm disclosed an expected robust correlation between flux control coefficients of enzymes and their selective elimination. Similar analyses, performed for the case of single gene transfer or for gene replication with subsequent mutation, yielded essentially similar results. The results conform with the phenomenon of genetic mosaicism found in phylogenetic analyses of single or double endosymbioses and lateral gene transfer.     

Serum interleukin-1β as a marker for differentiation of asthma and chronic obstructive pulmonary disease

Asthma and chronic obstructive pulmonary disease (COPD) are diseases of airway inflammation with clinical and physiological similarities, making their differentiation difficult. Airway inflammatory changes are associated with systemic changes. However, no serum marker is known for their differentiation. Therefore, serum interleukin (IL)-1β levels were determined. Out of a total of 1023 patients screened, we included in the study ten patients each with atopic asthma, non-atopic asthma and COPD and ten healthy subjects. Skin prick tests with 14 inhalant allergens were performed on each patient. Blood was collected in the symptomatic and asymptomatic phases of the diseases and serum IL-1β and IgE levels were determined. Our results showed that in the symptomatic phase in asthmatics, serum IL-1β levels were higher (P<0.05) than in patients with COPD. Serum IgE levels were higher (P<0.05) in atopic asthmatics than in non-atopic asthmatics and in COPD patients. We conclude that serum IL-1β level determination during the symptomatic phase of the diseases may help to differentiate asthmatics from patients with COPD. Serum IgE levels may differentiate atopic asthmatics from non-atopic asthmatics and COPD patients.     

Type 1 diabetes as a relapsing-remitting disease?

Chronic immunological processes that underlie persistent viral infections and autoimmune disorders such as multiple sclerosis can be relapsing-remitting in nature. The progressive loss of beta-cell mass during the development of autoimmune type 1 diabetes (T1D) can also be non-linear, but the exact nature and kinetics of the immunological processes that govern T1D are not known. Here, we propose that the immunological process that is at the root of T1D is relapsing-remitting in nature and discuss the unresolved controversies and therapeutic implications of this hypothesis.