How do microbes evade neutrophil killing?

Many microbial pathogens evolved to circumvent the attack of neutrophils, which are essential effector cells of the innate immune system. Here we review six major strategies that pathogenic bacteria and fungi use to evade neutrophil defences: (i) turning on survival and stress responses, (ii) avoiding contact, (iii) preventing phagocytosis, (iv) surviving intracellularly, (v) inducing cell death and (vi) evading killing by neutrophil extracellular traps. For each category we give examples and further focus on one particular pathogenic microbe in more detail. Pathogens include Candida albicans, Cryptococcus neoformans, Yersinia ssp., Helicobacter pylori, Staphylococcus aureus, Streptococcus pyogenes and Streptococcus pneumoniae.     

How do flies tolerate microorganisms in the gut?

Although gut epithelia are in constant contact with a large number of microbe-derived immune elicitors such as peptidoglycan, they do not mount an intense immune response. In this issue of Cell Host & Microbe, Lhocine et al. (2008) report that the PIMS gene product induces immune tolerance by reducing the availability of the peptidoglycan receptor in the plasma membrane. These findings provide a novel insight into the molecular mechanisms by which the host gut maintains balanced host-microbe interactions.     

How do dietary flavanols improve vascular function? A position paper

Epidemiological and clinical studies revealed that high-flavanol diet or isolated (−)-epicatechin improves the function of the vascular endothelium, as assessed by flow-mediated dilation, through elevation of bioavailability and bioactivity of NO^•. We have demonstrated that exposure of human endothelial cells to (−)-epicatechin elevates the cellular levels of NO^• and cyclic GMP and protects against oxidative stress elicited by proinflammatory agonists. (−)-Epicatechin acts like a prodrug, since these effects involve O-methylation of the flavanol and are attributed to apocynin-like inhibition of endothelial NADPH oxidase. Thus, generation of superoxide and peroxynitrite is diminished and, consequently, the cellular NO^• level is preserved or augmented. We propose therefore that endothelial NO^• metabolism rather than general antioxidant activity is a major target of dietary flavanols and that NADPH oxidase activity is a crucial site of action. Moreover, flavonoid glucuronides appear to serve as plasma transport metabolites to target cells rather than solely as excretion products. Implications for the interpretation of the role of dietary polyphenols for cardiovascular health are discussed.     

How do soil microbes exert impact on soil respiration and its temperature sensitivity?

Understanding how soil microorganisms influence the direction and magnitude of soil carbon feedback to global warming is vital to predict future climate change. Although microbial activities are major contributors to soil respiration (R_S) and its temperature sensitivity (Q₁₀), the mechanisms underpinning microbial influence on R_S and Q₁₀ remain unclear. Coupling variation partitioning analysis (VPA), correlation analysis and multiple stepwise linear regression analysis, we illustrate that bacteria mainly affect R_S and its temperature sensitivity (Q₁₀) by shifting bacterial community composition (denoted by principal coordinates analysis). We also found that soil water content (SWC) and available nutrient (AN) were the factor key to changing bacterial community composition (P < 0.05). Co-occurrence network demonstrated that Mod 0 ecological cluster composed of copiotrophic taxa groups was significantly associated with R_S and Q₁₀ (P < 0.01, R > 0.5), including Proteobacteria, Actinobacteria, and Bacteroidetes. Illuminating the mechanisms underpinning the influence of soil microbes on R_S and Q₁₀ values is fundamental to understanding mechanistic soil-climate carbon cycles.     

When is dietary fiber considered a functional food?

Before answering the question of when dietary fiber can be considered a functional food we must first decide what can be called a dietary fiber. The generally accepted definition of dietary fiber is that of Trowell that dietary fiber consists of the remnants of edible plant cells polysaccharides, lignin, and associated substances resistant to (hydrolysis) digestion by the alimentary enzymes of humans. In Japan the food tables list the dietary fiber content of animal as well as plant tissues, while many countries accept saccharides of less than DP-10 as dietary fiber (inulin, oligofructose, Fibersol-2, polydextrose, fructooligosaccharides, galactooligosaccharides etc.). These shorter chain oligosaccharides do not precipitate as dietary fiber in the standard Association of Official Analytical Chemists (AOAC) method, which is accepted by the US Food & Drug Administration, the US Department of Agriculture and the Food & Agriculture Organization of the World Health Organization for nutrition labeling purposes. In the United Kingdom the term dietary fiber has been replaced in nutrition labeling by nonstarch polysaccharides. Therefore the American Association of Cereal Chemists (AACC) commissioned an ad hoc committee of scientists to evaluate continuing validity of the currently used definition, and if appropriate, to modify and update that definition. Obtaining scientific input from the community of analysts, health professionals, and dietary fiber researchers was considered a high priority. To this end three meetings were held in the space of six months to assure input from all persons knowledgeable in the field with the answer expected sometime before 2000. Dietary fiber can be considered a functional food when it imparts a special function to that food aside from the normal expected function and similarly when the dietary fiber is used as an additive to foods. For example, dietary fiber contributes to colonic health, bifidobacterial or lactobacillus stimulation in the gut, coronary artery health, cholesterol reduction, glucose metabolism, insulin response, blood lipids, cancer etc. The author discusses in detail the functional food properties of dietary fiber.     

How does DNA break during chromosomal translocations?

Chromosomal translocations are one of the most common types of genetic rearrangements and are molecular signatures for many types of cancers. They are considered as primary causes for cancers, especially lymphoma and leukemia. Although many translocations have been reported in the last four decades, the mechanism by which chromosomes break during a translocation remains largely unknown. In this review, we summarize recent advances made in understanding the molecular mechanism of chromosomal translocations.     

How do proteins fold?

This article emphasizes the importance of getting students to understand the ways in which polypeptides fold to form protein molecules with complex higher-ordered structures. Modern views on how this folding occurs in vitro and in the cell are summarized and set within an appropriate biological context.     

How do spores germinate?

Spore germination, as defined as those events that result in the loss of the spore-specific properties, is an essentially biophysical process. It occurs without any need for new macromolecular synthesis, so the apparatus required is already present in the mature dormant spore. Germination in response to specific chemical nutrients requires specific receptor proteins, located at the inner membrane of the spore. After penetrating the outer layers of spore coat and cortex, germinant interacts with its receptor: one early consequence of this binding is the movement of monovalent cations from the spore core, followed by Ca2(+) and dipicolinic acid (DPA). In some species, an ion transport protein is also required for these early stages. Early events - including loss of heat resistance, ion movements and partial rehydration of the spore core - can occur without cortex hydrolysis, although the latter is required for complete core rehydration and colony formation from a spore. In Bacillus subtilis two crucial cortex lytic enzymes have been identified: one is CwlJ, which is DPA-responsive and is located at the cortex-coat junction. The second, SleB, is present both in outer layers and at the inner spore membrane, and is more resistant to wet heat than is CwlJ. Cortex hydrolysis leads to the complete rehydration of the spore core, and then enzyme activity within the spore protoplast resumes. We do not yet know what activates SleB activity in the spore, and neither do we have any information at all on how the spore coat is degraded.     

The great escape: do parasites break Dollo's law?

A long-held assumption in evolutionary studies is that a character that changes from a complex to a simple state is unlikely to return to the same complex state. The extreme version of this assumption has been codified as Dollo's law. Unfortunately, this paradigm has supported the idea that simple and complex traits are qualitatively different, when it is more sensible to suggest that there is a quantitative difference. Dollo's law has been the predominant paradigm in parasitology, where a move from a free-living state to parasitism has been considered a unidirectional pathway or 'one-way trip' because organisms lose the structures required to return to the free-living state. Several recent studies have suggested that complex structures can be regained from simple traits, and we suggest that this is also possible for parasites.     

How to break recombinant bacteria: does it matter?

Recombinant proteins and other materials of industrial interest produced in?Escherichia coli are usually retained within the bacterial cell, in the cytoplasmic?space, where they have been produced. Different protocols for cell disruption?have been implemented as an initial downstream step, which keeps the?biological and mechanical properties of the process products. Being necessarily?mild, these approaches often result in 95-99% cell disruption, what is more than?acceptable from the yield point of view. However, when the bacterial product?are nano or microparticulate entities that tend to co-sediment with entire?bacterial cells, the remaining undisrupted bacteria appear as abounding?contaminants, making the product not suitable for a spectrum of biomedical?applications. Since bacterial inclusion bodies are now seen as bacterial?materials valuable in different fields, we have developed an alternative cell?disruption protocol that permits obtaining fully bacterial free protein particles,?keeping the conformational status of the embedded proteins and the?mechanical properties of the full aggregates.     

How do spinal segments move?

PurposeTo study and clarify the kinematics of spinal segments following cyclic torques causing axial rotation (T_z (t)), lateral-flexion (T_x (t)), flexion/extension (T_y (t)).MethodsA 6D--Measurement of location, alignment, and migration of the instantaneous helical axis (IHA) as a function of rotational angle in cervical, thoracic, and lumbar segments subjected to axially directed preloads.ResultsIHA retained an almost constant alignment, but migrated along distinct centrodes.Thoracic segmentsIHA was almost parallel to T_z (t), T_x (t), or T_y (t), stationary for T_x (t) or T_y (t), and migrating for T_z (t) along dorsally opened bows. IHA locations hardly depended on the position or size of axial preload.Lumbar segmentsIHA was also almost parallel to T_z (t), T_x (t), or T_y (t). In axial rotation IHA-migration along wide, ventrally or dorsally bent bows depending on segmental flexional/extensional status. Distances covered: 20–60 mm. In lateral-flexion: IHA-migration to the left/right joint and vice versa. In flexion/extension IHA-migration from the facets to the centre of the disc.Cervical segmentsIn flexion/flexion IHA was almost stationary for and parallel to T_y (t). In axial rotation or lateral-flexion IHA intersected T_z (t)/T_x (t) under approximately ?30°/+30°.ConclusionsGenerally joints alternate in guidance. Lumbar segments: in axial rotation and lateral-flexion parametrical control of IHA-position and IHA-migration by axial preload position. Cervical segments: kinematical coupling between axial rotation and lateral-flexion.The IHA-migration guided by the joints should be taken into account in the design of non-fusion implants. FE-calculations of spinal mechanics and kinematics should be based on detailed data of curvature morphology of the articulating surfaces of the joint facets.     

How do plants make mitochondria?

Plant mitochondria can differ in size, shape, number and protein content across different tissue types and over development. These differences are a result of signaling and regulatory processes that ensure mitochondrial function is tuned in a cell-specific manner to support proper plant growth and development. In the last decade, the processes involved in mitochondrial biogenesis are becoming clearer, including; how dormant seeds transition from empty promitochondria to fully functional mitochondria with extensive cristae structures and various biochemical activities, the regulation of nuclear genes encoding mitochondrial proteins via regulators of the diurnal cycle in plants, the mitochondrial stress response, the targeting of proteins to mitochondria and other organelles and connections between the respiratory chain and protein import complexes. All these findings indicate that mitochondrial function is a part of an integrated cellular network, and communication between mitochondria and other cellular processes extends beyond the known exchange or transport of metabolites. Our current knowledge now needs to be used to gain more insight into the molecular components at various levels of this hierarchical and complex regulatory and communication network, so that mitochondrial function can be predicted and modified in a rational manner.     

How do nutrients drive growth?

The relationship between plant nutrient concentration and relative growth rate (RGR) was studied under non-steady state conditions using data from a new N interruption experiment with young lettuce plants grown hydroponically in the glasshouse. RGRs estimated from the fit of a versatile growth model were shown to decline curvilinearly with plant N concentration as N deficiency increased. Similar curvilinear relationships were also derived when the same model was used to reanalyse data for N, P and K interruption treatments from other experiments previously published in the literature. These results clearly indicate that the rate of remobilisation of nutrient reserves varies with the nutrient status of the plant. This contrasts with the linear relationships observed where the changes in plant N concentration occurred solely as a response to increasing plant age, or when plants were grown under steady state conditions with constant relative nutrient addition rates. These differences in the pattern of response provide strong evidence to support the hypothesis that the form of the relationship between RGR and plant nutrient concentration can vary depending upon whether a plant's external supplies or internal reserves of a particular nutrient are more limiting.