Are fusion peptides a good model to study viral cell fusion?

Fusion peptides are hydrophobic and conserved sequences located within glycoprotein ectodomains that protrude from the virion surface. Direct participation of fusion peptides in the viral membrane fusion phenomenon has been inferred from genetic analyses showing that even a single residue substitution or a deletion within these sequences may completely block the process. However, the specific fusion peptide activities associated to the multi-step fusion mechanism are not well defined. Based on the assumption that fusion peptides are transferred into target membranes, biophysical methodologies have been applied to study integration into model membranes of synthetic fragments representing functional and non-functional sequences. From these studies, it is inferred that, following insertion, functional sequences generate target membrane perturbations and adopt specific structural arrangements within. Further characterization of these artificial systems may help in understanding the molecular processes that bring initial bilayer destabilizations to the eventual opening of a fusion pore.     

Yeast as a model to study apoptosis?

Programmed cell death (PCD) serves as a major mechanism for the precise regulation of cell numbers, and as a defense mechanism to remove unwanted and potentially dangerous cells. Despite the striking heterogeneity of cell death induction pathways, the execution of the death program is often associated with characteristic morphological and biochemical changes termed apoptosis. Although for a long time the absence of mitochondrial changes was considered as a hallmark of apoptosis, mitochondria appear today as the central executioner of programmed cell death. This crucial position of mitochondria in programmed cell death control is not due to a simple loss of function (deficit in energy supplying), but rather to an active process in the regulation of effector mechanisms.The large diversity of regulators of apoptosis in mammals and their numerous interactions complicate the analysis of their individual functions. Yeast, eukaryotic but unicellular organism, lack the main regulators of apoptosis (caspases, Bcl-2 family members, . . .) found in mammals. This absence render them a powerful tool for heterologous expression, functional studies, and even cloning of new regulators of apoptosis.Great advances have thus been made in our understanding of the molecular mechanisms of Bcl-2 family members interactions with themselves and other cellular proteins, specially thanks to the two hybrid system and the easy manipulation of yeast (molecular biology and genetics).This review will focus on the use of yeast as a tool to identify new regulators and study function of mammalian apoptosis regulators.     

Arabidopsis, a model to study biological functions of isoprene emission?

The volatile hemiterpene isoprene is emitted from plants and can affect atmospheric chemistry. Although recent studies indicate that isoprene can enhance thermotolerance or quench oxidative stress, the underlying physiological mechanisms are largely unknown. In this work, Arabidopsis (Arabidopsis thaliana), a natural nonemitter of isoprene and the model plant for functional plant analyses, has been constitutively transformed with the isoprene synthase gene (PcISPS) from Grey poplar (Populus x canescens). Overexpression of poplar ISPS in Arabidopsis resulted in isoprene-emitting rosettes that showed transiently enhanced growth rates compared to the wild type under moderate thermal stress. The findings that highest growth rates, higher dimethylallyl diphosphate levels, and enzyme activity were detected in young plants during their vegetative growth phase indicate that enhanced growth of transgenic plants under moderate thermal stress is due to introduced PcISPS. Dynamic gas-exchange studies applying transient cycles of heat stress to the wild type demonstrate clearly that the prime physiological role of isoprene formation in Arabidopsis is not to protect net assimilation from damage against thermal stress, but may instead be to retain the growth potential or coordinated vegetative development of the plant. Hence, this study demonstrates the enormous potential but also the pitfalls of transgenic Arabidopsis (or other nonnatural isoprenoid emitters) in studying isoprene biosynthesis and its biological function(s).     

Are predicted structures good enough to preserve functional sites?

BACKGROUND: A principal goal of structure prediction is the elucidation of function. We have studied the ability of computed models to preserve the microenvironments of functional sites. In particular, 653 model structures of a calcium-binding protein (generated using an ab initio folding protocol) were analyzed, and the degree to which calcium-binding sites were recognizable was assessed. RESULTS: While some model structures preserve the calcium-binding microenvironments, many others, including some with low root mean square deviations (rmsds) from the crystal structure of the native protein, do not. There is a very weak correlation between the overall rmsd of a structure and the preservation of calcium-binding sites. Only when the quality of the model structure is high (rmsd less than 2 A for atoms in the 7 A local neighborhood around calcium) does the modeling of the binding sites become reliable. CONCLUSIONS: Protein structure prediction methods need to be assessed in terms of their preservation of functional sites. High-resolution structures are necessary for identifying binding sites such as calcium-binding sites.     

Can antimicrobial peptides scavenge around a cell in less than a second?

Antimicrobial peptides, which play multiple host-defense roles, have garnered increased experimental focus because of their potential applications in the pharmaceutical and food production industries. While their mechanisms of action are richly debated, models that have been advanced share modes of peptide-lipid interactions that require peptide dynamics. Before the highly cooperative and specific events suggested in these models take place, peptides must undergo an important process of migration along the membrane surface and delivery from their site of binding on the membrane to the actual site of functional performance. This phenomenon, which contributes significantly to antimicrobial function, is poorly understood, largely due to a lack of experimental and computational tools needed to assess it. Here, we use ¹⁵N solid-state nuclear magnetic resonance to obtain molecular level data on the motions of piscidin's amphipathic helices on the surface of phospholipid bilayers. The studies presented here may help contribute to a better understanding of the speed at which the events that lead to antimicrobial response take place. Specifically, from the perspective of the kinetics of cellular processes, we discuss the possibility that piscidins and perhaps many other amphipathic antimicrobial peptides active on the membrane surface may represent a class of fast scavengers rather than static polypeptides attached to the water-lipid interface.     

Are the fusion processes involved in birth, life and death of the cell depending on tilted insertion of peptides into membranes?

Various peptide segments have been modeled as asymmetric amphipathic alpha-helices. Theoretical calculations have shown that they insert obliquely into model membranes. They have been named "tilted peptides". Molecular modeling results reported here also evidence the presence of tilted peptides in ADM-1 protein of Caenorhabditis elegans that may be involved in fusion events, in meltrin alpha, a protein implicated in myoblast fusion, in hemagglutinin of influenza virus, in the E2 glycoprotein of rubella virus, in the S protein of hepatitis B virus, in a subdomain of Ebola virus and in the malaria CS protein. Experimental results have indicated that tilted peptide fragments may be involved in cellular life events like sperm-egg fecondation, muscle development, protein translocation through signal sequences and cellular death caused by viral infection or parasite infestation. We speculate that membrane destabilization by these tilted peptides may be an important common step in life processes involving fusion phenomena.     

Salinity tolerance of Arabidopsis: a good model for cereals?

Arabidopsis is a glycophyte species that is sensitive to moderate levels of NaCl. Arabidopsis offers unique benefits to genetic and molecular research and has provided much information about both Na(+) transport processes and Na(+) tolerance. A compilation of data available on Na(+) accumulation and Na(+) tolerance in Arabidopsis is presented, and comparisons are made with several crop plant species. The relationship between Na(+) tolerance and Na(+) accumulation is different in Arabidopsis and cereals, with an inverse relationship often found within cereal species that is not as evident in Arabidopsis ecotypes. Results on salinity tolerance obtained in Arabidopsis should therefore be extrapolated to cereals with caution. Arabidopsis remains a useful model to study and discover plant Na(+) transport processes.     

Are Chironomidae (Diptera) good indicators of water scarcity? Dryland streams as a case study

Water scarcity is becoming one of the greatest challenges that human societies will face during this century. Monitoring water availability is expensive and technically challenging. In this regard, biological communities (e.g. aquatic insects) offer a cost-effective alternative, since they integrate temporal and spatial hydrological variability.Here we explore the potential of Chironomidae (Diptera), which have been usually neglected due to their complex taxonomy, as indicators of both local habitat condition and water scarcity. The study took place in 28 sites across seven dryland streams distributed within a 400 km² section of the Upper San Pedro River basin, southeastern Arizona. The selected streams covered a wide range of hydrological variability, which was continuously measured through the deployment of 15 electrical resistance (ER) sensors. Chironomidae taxa with no drought-resistance strategies were rarely found in streams that experienced frequent drying events (i.e. intermittent and ephemeral streams), suggesting that droughts have the potential to reduce species richness due to local extinctions of drought-intolerant taxa. Intermittent and ephemeral streams registered low canopy cover and a significantly higher abundance of scrapers (which mainly feed on algae) and shredders (feeding on poorly decomposed coarse organic material). This suggests that structural changes associated to drought (e.g. reduced canopy cover and decomposition rates) might lead to changes in the functional composition of the Chironomidae assemblages. We conclude that Chironomidae species can be used as indicators of hydrological variability and the impacts of drought on streams in the absence of flow gauges.     

Influenza A virus—a model for viral antigen presentation to cytotoxic T lymphocytes

Human influenza A virus is characterized by its high degree of variability and by its ability to cause frequent epidemics of disease. Most of the variation occurs in the two surface glycoproteins of the virus, against which protective antibodies are directed. In contrast, the strong MHC class I-restricted CTL response to infection with virus is predominantly specific for internal viral proteins which are relatively well conserved, and is cross-reactive between different strains of influenza A virus. However, the natural evolution of influenza viruses is largely driven by selection with antibody, with no firm evidence of selection by CTL. In normal individuals influenza virus produces an acute, localized infection, and this in part may reflect an inability to escape the CTL response.     

Umbilical cord clamping in term piglets: a useful model to study perinatal asphyxia?

Perinatal asphyxia results in tissue and cellular changes during the reperfusion period and clinical signs like perinatal mortality and decreased vitality at birth in newborn piglets. This study aimed to develop and validate a model of birth asphyxia, mimicking the evolvement of birth asphyxia in natural farrowings by conducting umbilical cord clamping (UCC) in term piglets during caesarean sections under general anaesthesia. In total 23 piglets were subjected to 5-8min of UCC and 24 piglets served as controls. Acid-base balance values and heart rates measured before UCC remained fairly constant throughout the surgical procedure, indicating nearly identical starting conditions of piglets within and between litters. UCC resulted in a significant, mild, mixed respiratory-metabolic acidosis (pH 7.22, pCO(2) 9.8kPa, BE(ecf) 2mmol/L, lactate 6.5mmol/L; controls: pH 7.31, pCO(2) 8.5kPa, BE(ecf) 5mmol/L, lactate 4mmol/L) at 10min after birth (defined as simultaneous cutting of the umbilical cord and removal of a plastic bag that had been placed over the head to avoid air intake). Heart rates were significantly decreased during UCC (range: 83-107beats/min versus 128-134beats/min in controls). Rectal temperatures and changes in body weight until 72h of life were not affected by UCC. Interestingly, four control and seven clamped piglets did not survive as no independent respiration could be attained. Birth weights and duration of UCC of these piglets did not differ significantly from those in surviving control and clamped piglets. In conclusion the mixed respiratory-metabolic acidosis arising in the surviving clamped piglets is not as severe as can be expected in highly asphyxiated, vaginally delivered newborn piglets. Repeatability of the model is compromised by considerable variation in the individual response to UCC.     

Can zebrafish be used as a model to study the neurodevelopmental causes of autism?

The zebrafish has proven to be an excellent model for analyzing issues of vertebrate development. In this review we ask whether the zebrafish is a viable model for analyzing the neurodevelopmental causes of autism. In developing an answer to this question three topics are considered. First, the general attributes of zebrafish as a model are discussed, including low cost maintenance, rapid life cycle and the multitude of techniques available. These techniques include large-scale genetic screens, targeted loss and gain of function methods, and embryological assays. Second, we consider the conservation of zebrafish and mammalian brain development, structure and function. Third, we discuss the impressive use of zebrafish as a model for human disease, and suggest several strategies by which zebrafish could be used to dissect the genetic basis for autism. We conclude that the zebrafish system could be used to make important contributions to understanding autistic disorders.