How does hepatitis C virus enter cells?

Hepatitis C virus (HCV) exists in different forms in the circulation of infected people: lipoprotein bound and lipoprotein free, enveloped and nonenveloped. Viral particles with the highest infectivity are associated with lipoproteins, whereas lipoprotein-free virions are poorly infectious. The detection of HCV's envelope proteins E1 and E2 in lipoprotein-associated virions has been challenging. Because lipoproteins are readily endocytosed, some forms of HCV might utilize their association with lipoproteins rather than E1 and E2 for cell attachment and internalization. However, vaccination of chimpanzees with recombinant envelope proteins protected the animals from hepatitis C infection, suggesting an important role for E1 and E2 in cell entry. It seems possible that different forms of HCV use different receptors to attach to and enter cells. The putative receptors and the assays used for their validation are discussed in this review.     

How does your virus grow? Understanding and interfering with virus assembly

Viruses have a coat to protect their genome. For about half of the known virus families, the coat is a ‘spherical’ or icosahedral capsid. The capsid can also play a role in binding to a host cell and in movement of the virus within it. Capsids are composed of hundreds of copies of individual components that must assemble rapidly and reproducibly on a biological timescale. Assembly implies stability, but many viruses also require a ‘switch’ that renders the capsid unstable so that the viral genome can be released. Although interfering with capsid assembly and stability could be an important target for antiviral therapeutics, no such therapeutics are currently available. We are just beginning to understand how to analyze the stability and the assembly kinetics of capsids.     

How does a legume nodule work?

Nitrogen fixation in legume root nodules requires biochemical cooperation between the plant and Rhizobium cells. Bacteroids contribute the N₂-fixing system and haem for leghaemoglobin, but apart from the production of the globin moiety of leghaemoglobin and the assimilation and export of the NH₃ produced, little is known about the contributions of the plant. It now appears that the plant cell may regulate the type and/or quantity of carbon compounds supplied to the Rhizobium bacteroids.     

How does a hopping kangaroo breathe?

We developed a model to demonstrate how a hopping kangaroo breathes. Interestingly, a kangaroo uses less energy to breathe while hopping than while standing still. This occurs, in part, because rather than using muscle power to move air into and out of the lungs, air is pulled into (inspiration) and pushed out of (expiration) the lungs as the abdominal organs "flop" within the kangaroo's body. Specifically, as the kangaroo hops upward, the abdominal organs lag behind, and the insertion of the diaphragm is pulled toward its origin, flattening the dome and increasing the vertical dimension of the thoracic cavity (the thoracic cavity and lungs enlarge). Increasing the volume of the thoracic cavity reduces alveolar pressure below atmospheric pressure (barometric pressure), and air moves into the alveoli by bulk flow. In contrast, the impact of the organs against the diaphragm at each landing causes expiration. Specifically, upon landing, the abdominal organs flop into the diaphragm, causing it to return to its dome shape and decreasing the vertical dimension of the thoracic cavity. This compresses the alveolar gas volume and elevates alveolar pressure above barometric pressure, so air is expelled. To demonstrate this phenomenon, the plunger of a syringe model of the respiratory system was inserted through a compression spring. Holding the syringe and pressing the plunger firmly against a hard surface expels air from the lungs (the balloon within the syringe deflates) and compresses the spring. This models the kangaroo landing after a hop forward. Subsequently, the compression spring provides the energy for the "kangaroo" to "hop" forward upon the release of the syringe, and air enters the lungs (the balloon within the syringe inflates). The model accurately reflects how a hopping kangaroo breathes. A model was chosen to demonstrate this phenomenon because models engage and inspire students as well as significantly enhance student understanding.     

How does a cell repair damaged DNA?

DNA in living cells is constantly subjected to different chemical and physical factors of the environment and to cell metabolites. Some changes altering DNA structure occur spontaneously. This raises the potential danger of harmful mutations that could be transmitted to offspring. To avoid the danger of mutations and changing genetic information, a cell is capable to switch on multiple mechanisms of DNA repair that remove damage and restore native structure. In many cases, removal of the same damage may involve several alternative pathways; this is very important for DNA repair under the most unfavorable conditions. This review summarizes data about all known mechanisms of eukaryotic DNA repair including excision repair (base excision repair and nucleotide excision repair), mismatch repair, repair of double-strand breaks, and cross-link repair. Special attention is given to the regulation of excision repair by different proteins—proliferating cell nuclear antigen (PCNA), p53, and proteasome. The review also highlights problem of bypassing irremovable lesions in DNA.Translated from Biokhimiya, Vol. 70, No. 3, 2005, pp. 341–359.Original Russian Text Copyright © 2005 by Sharova.     

How much water does a river need?

1. This paper introduces a new approach for setting streamflow-based river ecosystem management targets and this method is called the 'Range of Variability Approach' (RVA). The proposed approach derives from aquatic ecology theory concerning the critical role of hydrological variability, and associated characteristics of timing, frequency, duration, and rates of change, in sustaining aquatic ecosystems. The method is intended for application on rivers wherein the conservation of native aquatic biodiversity and protection of natural ecosystem functions are primary river management objectives.
2. The RVA uses as its starting point either measured or synthesized daily streamflow values from a period during which human perturbations to the hydrological regime were negligible. This streamflow record is then characterized using thirty-two different hydrological parameters, using methods defined in Richter et al . (1996). Using the RVA, a range of variation in each of the thirty-two parameters, e.g. the values at ± 1 standard deviation from the mean or the twenty-fifth to seventy-fifth percentile range, are selected as initial flow management targets.
3. The RVA targets are intended to guide the design of river management strategies (e.g. reservoir operations rules, catchment restoration) that will lead to attainment of these targets on an annual basis. The RVA will enable river managers to define and adopt readily interim management targets before conclusive, long-term ecosystem research results are available. The RVA targets and management strategies should be adaptively refined as suggested by research results and as needed to sustain native aquatic ecosystem biodiversity and integrity.     

How does spittlebug oviposition affect shoot growth and bud production in two willow species?

We measured the effects of oviposition by the spittlebug Aphrophora pectoralis on shoot growth and bud production in two willow species, Salix miyabeana and Salix sachalinensis. In autumn, adult females of A.pectoralis insert their ovipositor into the apical region of 1-year-old shoots, resulting in the death of most shoot tips within 1week. Consequently, an increase in the number of dead buds and a decrease in the number of vegetative buds on 1-year-old shoots was recorded. In the following spring, the growth of current-year shoots was greatly increased on 1-year-old shoots damaged by spittlebug oviposition. Furthermore, spittlebug oviposition increased the production rate of vegetative buds in both S.miyabeana and S.sachalinensis. However, no impact on the production rate of reproductive buds was detected in either willow. We conclude that the compensatory growth of current-year shoots and an increase in vegetative buds in the two willow species was caused by oviposition of A.pectoralis.     

How many patents does a biopharmaceutical company need?

Young biotech companies may not need extensive patent portfolios to survive or grow.     

How does the brain sustain a visual percept?

Perception involves the processing of sensory stimuli and their translation into conscious experience. A novel percept can, once synthesized, be maintained or discarded from awareness. We used event-related functional magnetic resonance imaging to separate the neural responses associated with the maintenance of a percept, produced by single-image, random-dot stereograms, from the response evoked at the onset of the percept. The latter was associated with distributed bilateral activation in the posterior thalamus and regions in the occipito-temporal, parietal and frontal cortices. In contrast, sustained perception was associated with activation of the pre-frontal cortex and hippocampus. This observation suggests that sustaining a visual percept involves neuroanatomical systems which are implicated in memory function and which are distinct from those engaged during perceptual synthesis.     

How does a millimeter-sized cell find its center?

Microtubules play a central role in centering the nucleus or mitotic in eukaryotic cells. However, despite common use of microtubules for centering, physical mechanisms can vary greatly, and depend on cell size and cell type. In the small fission yeast cells, the nucleus can be centered by pushing forces that are generated when growing microtubules hit the cell boundary. This mechanism may not be possible in larger cells, because the compressive force that microtubules can sustain are limited by buckling, so maximal force decreases with microtubule length. In a well-studied intermediate sized cell, the C. elegans fertilized egg, centrosomes are centered by cortex-attached motors that pull on microtubules. This mechanism is widely assumed to be general for larger cells. However, re-evaluation of classic experiments in a very large cell, the fertilized amphibian egg, argues against such generality. In these large eggs, movement of asters away from a part of the cell boundary that they are touching cannot be mediated by cortical pulling, because the astral microtubules are too short to reach the opposite cell boundary. A century ago, Herlant and Brachet discovered that multiple asters within a single egg center relative to the cell boundary, but also relative to each other. Here, we summarize current understanding of microtubule organization during the first cell cycle in a fertilized Xenopus egg, discuss how microtubule asters move towards the center of this very large cell, and how multiple asters shape and position themselves relative to each other.     

How does a cell anchor and invade an organ?

In multicellular organisms, most cells are confined to a particular tissue. However, some cells invade organs during normal development and in diseases (e.g., angiogenesis and cancer). Recent studies reveal a fascinating step-by-step process in which specific vulval cells induce and attract a single gonadal cell to invade an epithelial tubular organ in order to connect the uterus to the vulva in C. elegans.     

How does a small molecule bind at a cryptic binding site?

Protein-protein interactions (PPIs) are ubiquitous biomolecular processes that are central to virtually all aspects of cellular function. Identifying small molecules that modulate specific disease-related PPIs is a strategy with enormous promise for drug discovery. The design of drugs to disrupt PPIs is challenging, however, because many potential drug-binding sites at PPI interfaces are “cryptic”: When unoccupied by a ligand, cryptic sites are often flat and featureless, and thus not readily recognizable in crystal structures, with the geometric and chemical characteristics of typical small-molecule binding sites only emerging upon ligand binding. The rational design of small molecules to inhibit specific PPIs would benefit from a better understanding of how such molecules bind at PPI interfaces. To this end, we have conducted unbiased, all-atom MD simulations of the binding of four small-molecule inhibitors (SP4206 and three SP4206 analogs) to interleukin 2 (IL2)—which performs its function by forming a PPI with its receptor—without incorporating any prior structural information about the ligands’ binding. In multiple binding events, a small molecule settled into a stable binding pose at the PPI interface of IL2, resulting in a protein–small-molecule binding site and pose virtually identical to that observed in an existing crystal structure of the IL2-SP4206 complex. Binding of the small molecule stabilized the IL2 binding groove, which when the small molecule was not bound emerged only transiently and incompletely. Moreover, free energy perturbation (FEP) calculations successfully distinguished between the native and non-native IL2–small-molecule binding poses found in the simulations, suggesting that binding simulations in combination with FEP may provide an effective tool for identifying cryptic binding sites and determining the binding poses of small molecules designed to disrupt PPI interfaces by binding to such sites.     

How does a bacterium grow during its cell cycle?

Rod-shaped bacteria such as Escherichia coli and Bacillus subtilis appear to extend continuously in length between divisions. However, the kinetics of growth of the individual cell in the steady state is still unknown. A brief, critical account of the main approaches used to determine the pattern of surface extension is given. In general, these approaches are of three types. Firstly, attempts have been made to relate average cell size to growth rate of the culture and to determine possible stages in the cell cycle at which the rate of length extension might change. Secondly, comparisons have been made between the measured length distribution of cells and theoretical distributions, based on three primary hypotheses (linear, bilinear and exponential growth). Thirdly, the principle of Collins and Richmond, involving the calculation of growth rate from the length distributions of extant, separating and new-born cells, is described. It is emphasized that there is a strong element of variation in size at different stages of the cell cycle. This variation imposes severe limitations on models which utilize only average cellular dimensions. We conclude that the Collins-Richmond principle affords the most powerful approach to the analysis of bacterial growth kinetics. However, we propose that the method be modified to permit calculation of separate rates of growth of cells between discernible events in the cell cycle, as well as simply between birth and division.