Cotranslational protein folding--fact or fiction?

MOTIVATION: Experimentalists have amassed extensive evidence over the past four decades that proteins appear to fold during production by the ribosome. Protein structure prediction methods, however, do not incorporate this property of folding. A thorough study to find the fingerprint of such sequential folding is the first step towards using it in folding algorithms, so assisting structure prediction. RESULTS: We explore computationally the existence of evidence for cotranslational folding, based on large sets of experimentally determined structures in the PDB. Our perspective is that cotranslational folding is the norm, but that the effect is masked in most classes. We show that it is most evident in alpha/beta proteins, confirming recent findings. We also find mild evidence that older proteins may fold cotranslationally. A tool is provided for determining, within a protein, where cotranslation is most evident.     

Slow axoplasmic transport: a fiction?

Ribosomes have not been observed in axoplasm. This had led to the notions that the perikaryon is the only source of neuronal proteins and that the axoplasm is supplied by a (slow) transport mechanism. However, we question these two notions because they are unable to give an account of real neurones in accordance with the body of biological knowledge. We point out, for example, that the synthetic rate of perikarya or the life span of axoplasmic proteins should be beyond known ranges for animal cells and that a uniform axon is unlikely to result if it is fed from one end. We propose an alternative view for the maintenance of the axon which accepts the controversial idea of axoplasmic synthesis of proteins; as a result, the slow transport becomes unnecessary. Our view gives a qualitative account of the observations dealing with the maintenance of the axoplasm. To account for the phenomenology in a more quantitative fashion, a computer simulation was carried out where the equations of the program provided only for axoplasmic synthesis of proteins; the set of curves retrieved were in good agreement with experimental findings believed so far to support the notion of slow transport. In conclusion, we think that the notion of "slow axoplasmic transport" has been a misinterpretation of good observations because the frame of reference was incomplete in not providing for axoplasmic synthesis of proteins.     

Intraguild predation: fiction or reality?

Intraguild predation has become a major research topic in biological control. Quantification of multipredator interactions and an understanding of the consequences on target prey populations are needed, which only highlights the importance of population dynamics models in this field. However, intraguild predation models are usually based on Lotka–Volterra equations, which have been shown not to be adequate for modeling population dynamics of aphidophagous insects and their prey. Here we use a simple model developed for simulation of population dynamics of aphidophagous insects, which is based on the type of egg distribution made by predatory females, to estimate the real strength of intraguild predation in the aphidophagous insects. The model consists of two components: random egg distribution among aphid colonies, and between-season population dynamics of the predatory species. The model is used to estimate the proportion of predatory individuals that face a conflict with a heterospecific competitor at least once during their life. Based on this, predictions are made on the population dynamics of both predatory species. The predictions are confronted with our data on intraguild predation in ladybirds.     

Superoxide reductase: fact or fiction?

It was recently proposed that anaerobic microorganisms contain a new pathway for detoxification of reactive oxygen species. This is centered around a novel mononuclear iron-containing enzyme, superoxide reductase (SOR), which catalyzes the reduction, rather than the dismutation, of superoxide to hydrogen peroxide. A surprisingly large amount of relevant data has accumulated in the two years or so since the proposal was made. Herein we address the questions: to what extent has the pathway been validated, and what fundamental issues have yet to be answered in considering the response of anaerobes to reactive oxygen species? The evidence for superoxide reduction by SOR is now overwhelming and comes from a variety of anaerobic and microaerophilic species. Moreover, the available spectroscopic and structural information provide a convincing case that the catalytic Fe site of SOR is structurally and electronically tuned to mediate superoxide reduction rather than oxidation. Kinetic analyses also support the original proposal of NAD(P)H, via rubredoxin and NAD(P)H:rubredoxin oxidoreductase, as the source of reductant. What is still to be determined is the fate of the peroxide generated by the SOR reaction. In particular, the role of otherwise well-characterized proteins like rubrerythrin, NADH peroxidase, and rubredoxin:oxygen oxidoreductase in "anaerobic" oxygen metabolism has yet to be established.     

Tumor counterattack: fact or fiction?

Cancer development relies on a variety of mechanisms that facilitate tumor growth despite the presence of a functioning immune system. Understanding these mechanisms may foster novel therapeutic approaches for oncology and organ transplantation. By expression of the apoptosis-inducing protein CD95L (FasL, APO-1L, CD178), tumors may eliminate tumor-infiltrating lymphocytes and suppress anti-tumor immune responses, a phenomenon called tumor counterattack. On the one hand, preliminary evidence of tumor counterattack in human tumors exists, and CD95L expression can prevent T-cell responses in vitro. On the other hand, CD95L-expressing tumors are rapidly rejected and induce inflammation in mice. Here, we summarize and discuss the consequences of CD95L expression of tumor cells and its contribution to immune escape.This article is a symposium paper from the conference Tumor Escape and Its Determinants, held in Salzburg, Austria, on 10–13 October 2004.     

Human age reversal: Fact or fiction?

Although chronological age correlates with various age‐related diseases and conditions, it does not adequately reflect an individual''s functional capacity, well‐being, or mortality risk. In contrast, biological age provides information about overall health and indicates how rapidly or slowly a person is aging. Estimates of biological age are thought to be provided by aging clocks, which are computational models (e.g., elastic net) that use a set of inputs (e.g., DNA methylation sites) to make a prediction. In the past decade, aging clock studies have shown that several age‐related diseases, social variables, and mental health conditions associate with an increase in predicted biological age relative to chronological age. This phenomenon of age acceleration is linked to a higher risk of premature mortality. More recent research has demonstrated that predicted biological age is sensitive to specific interventions. Human trials have reported that caloric restriction, a plant‐based diet, lifestyle changes involving exercise, a drug regime including metformin, and vitamin D3 supplementation are all capable of slowing down or reversing an aging clock. Non‐interventional studies have connected high‐quality sleep, physical activity, a healthy diet, and other factors to age deceleration. Specific molecules have been associated with the reduction or reversal of predicted biological age, such as the antihypertensive drug doxazosin or the metabolite alpha‐ketoglutarate. Although rigorous clinical trials are needed to validate these initial findings, existing data suggest that aging clocks are malleable in humans. Additional research is warranted to better understand these computational models and the clinical significance of lowering or reversing their outputs.     

Signaling across myoendothelial gap junctions--fact or fiction?

Gap junctions interconnect vascular cells homocellularly, thereby allowing the spread of signals along the vessel wall, which serve to coordinate vessel behavior. In addition, gap junctions provide heterocellular coupling between endothelial and vascular smooth muscle cells, creating so-called myoendothelial gap junctions (MEGJs). Endothelial cells control vascular tone by the release of factors that relax vascular smooth muscle. Endothelial factors include nitric oxide, prostaglandins, and an additional dilator principle, which acts by smooth muscle hyperpolarization and is therefore named endothelium-derived hyperpolarizing factor (EDHF). Whether this principle indeed relies on a factor or on intact MEGJs, which allow direct current transfer from endothelial to smooth muscle cells, has recently been questioned. Careful studies revealed the presence of vascular cell projections that make contact through the internal elastic lamina, exhibit the typical GJ morphology, and express connexins in many vessels. The functional study of the physiological role of MEGJs is confined by the difficulty of selectively blocking these channels. However, in different vessels studied in vitro, the dilation related to EDHF was sensitive to experimental interventions that block MEGJs more or less specifically. Additionally, bidirectional electrical coupling between endothelial and smooth muscle cells was demonstrated in isolated small vessels. In marked contrast, similar approaches used in conjunction with intravital microscopy, which allows examination of vascular behavior in the intact animal, did not verify electrical or dye-coupling in different models investigated. The discrepancy between in vitro and in vivo investigations may be due to size and origin of the vessels studied using these distinct experimental approaches. Additionally, MEGJ coupling is possibly tightly controlled in vivo by yet unknown mechanisms that prevent unrestricted direct signaling between endothelial and smooth muscle cells.     

Mangrove growth rings: fact or fiction?

The analysis of tree rings in the tropics is less straightforward than in temperate areas with a demarcated unfavourable winter season. But especially in mangroves, the highly dynamic intertidal environment and the overriding ecological drivers therein have been a reason for questioning the existence of growth rings. This study aimed at casting light on growth rings in mangroves. In six mangrove species growing in Gazi Bay, Kenya (Sonneratia alba, Heritiera littoralis, Ceriops tagal, Bruguiera gymnorrhiza, Xylocarpus granatum and Lumnitzera racemosa), the occurrence of growth rings was examined. Growth rate of each species was determined based on a 1-year period using the cambial marking technique. The effect of climate was furthermore considered by comparing the results with a number of wood samples originating from contrasting climatic regions. We can conclude that for growth rings to appear in mangroves more than one condition has to be fulfilled, making general statements impossible and explaining the prevalent uncertainty. Climatic conditions that result in a range of soil water salinity experienced over the year are a prerequisite for the formation of growth rings. For species with an anatomy characterized by indistinct ring boundaries, this should be combined with a growth rate of at least 0.3 mm/year. The use of growth rings for age or growth rate determinations should thus be evaluated on a case by case basis.     

Radiation induced isostaining: fact or fiction?

Two different experiments were set up to induce differential staining in M-1¹ cells or to induce isostaining in M-2 cells after -irradiation of human lymphocytes. Neither of these two unusual staining patterns previously described by Luchnik and Porjadkova (1977) were observed. Possible explanations for this disagreement are discussed.Abbreviations SCE Sister chromatid exchange - IS Isostained regions - S-1, S-2, S-3 and S-4 First, second, third and fourth DNA synthetic periods after addition of 5-bromodeoxyuridine - M-1, M-2, M-3, M-4 and M-5 First, second, third, fourth and fifth mitosis after addition of 5-bromodeoxyuridine - BrdU 5-bromodeoxyuridine - EMEM Eagle's Minimum Essential Medium     

Diabetic pulmonary microangiopathy - fact or fiction?

Elevated levels of serum glucose have deleterious effects on the walls of blood vessels, leading to microangiopathy. Such a destructive process involves also pulmonary circulation, where it is referred to as diabetic pulmonary microangiopathy. This hypothesis has been confirmed in histopathologic examinations of pulmonary parenchyma, as well as in pulmonary function tests. However, so far there have been no clinical implications of these findings. Another phenomenon requiring further discussion involves diabetics with clinically silent respiratory dysfunction. That may result from significant vascular and ventilation reserves that compensate for partial loss of pulmonary parenchyma in the course of diabetes. In this review, we present an overview of the available publications on pulmonary microangiopathy and its influence on the functioning of the respiratory system.     

Sexual cannibalism in scorpions: fact or fiction?

Females of several scorpion species are currently deemed to be sexual cannibals, but this reputation is, however, largely built on anecdotal evidence from the older literature. Theoretical models predict that given the low rates of female-male encounter, males should allow themselves to be cannibalized after sperm transfer. The present paper examines the information available for a number of species to determine (a) whether sexual cannibalism is as widespread as previously suggested, and (b) whether it is likely to involve male self-sacrifice. Information on three scorpions currently regarded as sexual cannibals is presented: the bothriurids Bothriurus bonariensis (C.L. Koch) and Urophonius jheringii Pocock, and the buthid Leiurus quinquestriatus (Hemprich & Ehrenberg). No post-mating cannibalism was ever observed in these species, nor in another 19 representatives of four families. In L. quinquestriatus only two cases of cannibalism of the male by the female occurred, both in the beginning of courtship and after long periods of food deprivation. We suggest that if sexual cannibalism occurs in scorpions, it is most likely to be of an 'economic' type, where females perceive males as prey rather than mates, and not a 'self-sacrificial', post-mating cannibalism enhancing the fitness of the offspring of the male.     

Renal stem cells: fact or science fiction?

The kidney is widely regarded as an organ without regenerative abilities. However, in recent years this dogma has been challenged on the basis of observations of kidney recovery following acute injury, and the identification of renal populations that demonstrate stem cell characteristics in various species. It is currently speculated that the human kidney can regenerate in some contexts, but the mechanisms of renal regeneration remain poorly understood. Numerous controversies surround the potency, behaviour and origins of the cell types that are proposed to perform kidney regeneration. The present review explores the current understanding of renal stem cells and kidney regeneration events, and examines the future challenges in using these insights to create new clinical treatments for kidney disease.