Chromatin methylation: who's on first?

Two recent studies have exploited Arabidopsis mutants and chromatin immunoprecipitation to reveal the complexity of the interaction between histone H3 methyl K9 and cytosine methylation, two epigenetic marks that characterize silent chromatin.     

Integrin adhesions: Who’s on first? What's on second?

Cell migration requires the coordination of adhesion site assembly and turnover. Canonical models for nascent adhesion formation postulate that integrin binding to extracellular matrix (ECM) proteins results in the rapid recruitment of cytoskeletal proteins such as talin and paxillin to integrin cytoplasmic domains. It is thought that integrin-talin clusters recruit and activate tyrosine kinases such as focal adhesion kinase (FAK). However, the molecular connections of this linkage remain unresolved. Our recent findings support an alternative model whereby FAK recruits talin to new sites of β1 integrin-mediated adhesion in mouse embryonic fibroblasts and human ovarian carcinoma cells. This is dependent on a direct binding interaction between FAK and talin and occurs independently of direct talin binding to β1 integrin. Herein, we discuss differences between nascent and mature adhesions, interactions between FAK, talin and paxillin, possible mechanisms of FAK activation and how this FAK-talin complex may function to promote cell motility through increased adhesion turnover.     

Cartoons on bacterial balloons: scientists’ opinion on the popularization of synthetic biology

How do scientists perceive the media coverage of synthetic biology (SB)? In this paper, we approach this question by studying a set of cartoons devoted to SB. Based on a categorization of the cartoons into five large thematic groups an international survey was carried out to assess the opinion of SB research groups on science communication with regard to the public image of their discipline. The 101 responses obtained indicate that in general, their perception of the communication is not negative, although many respondents raised concerns on the media’s inclination to sensationalism and over-simplification. However, the results also suggest that (in the light of the unfortunate experiences with GMO communication) scientists should think twice before proposing metaphorical interpretations of their research.     

Centriole duplication: centrin in on answers?

Many aspects of centriole biology remain mysterious. A new study has shed light on the role of the centriolar protein centrin-2: reducing levels of centrin-2 in HeLa cells has been found to block centriole duplication, eventually leading to cell death.     

Salt effects on β-glucosidase: pH-profile narrowing

Salts inhibit the activity of sweet almond β-glucosidase. For cations (Cl⁻ salts) the effectiveness follows the series: Cu⁺², Fe⁺² > Zn⁺² > Li⁺ > Ca⁺² > Mg⁺² > Cs⁺ > NH₄⁺ > Rb⁺ > K⁺ > Na⁺ and for anions (Na⁺ salts) the series is: I⁻ > ClO₄⁻ > ⁻SCN > Br⁻ ≈ NO₃⁻ > Cl⁻ ≈ ⁻OAc > F⁻ ≈ SO₄^− 2. The activity of the enzyme, like that of most glycohydrolases, depends on a deprotonated carboxylate (nucleophile) and a protonated carboxylic acid for optimal activity. The resulting pH-profile of k_cat/K_m for the β-glucosidase-catalyzed hydrolysis of p-nitrophenyl glucoside is characterized by a width at half height that is strongly sensitive to the nature and concentration of the salt. Most of the inhibition is due to a shift in the enzymic pK_as and not to an effect on the pH-independent second-order rate constant, (k_cat/K_m)^lim. For example, as the NaCl concentration is increased from 0.01 M to 1.0 M the apparent pK_a1 increases (from 3.7 to 4.9) and the apparent pK_a2 decreases (from 7.2 to 5.9). With p-nitrophenyl glucoside, the value of the pH-independent (k_cat/K_m)^lim (= 9 × 10⁴ M^− 1 s^− 1) is reduced by less than 4% as the NaCl concentration is increased. There is a similar shift in the pK_as when the LiCl concentration is increased to 1.0 M. The results of these salt-induced pK_a shifts rule out a significant contribution of reverse protonation to the catalytic efficiency of the enzyme. At low salt concentration, the fraction of the catalytically active monoprotonated enzyme in the reverse protonated form (i.e., proton on the group with a pK_a of 3.7 and dissociated from the group with a pK_a of 7.2) is very small (≈ 0.03%). At higher salt concentrations, where the two pK_as become closer, the fraction of the monoprotonated enzyme in the reverse protonated form increases over 300-fold. However, there is no increase in the intrinsic reactivity, (k_cat/K_m)^lim, of the monoprotonated species. For other enzymes which may show such salt-induced pK_a shifts, this provides a convenient test for the role of reverse protonation.     

The bacterial replisome: back on track?

It has been postulated that bacterial DNA replication occurs via a factory mechanism in which unreplicated DNA is spooled into a centrally located replisome and newly synthesized DNA is discharged towards opposite cell poles. Although there is considerable support for this view, it does not fit with many key observations. I review new findings, and provide alternative interpretations for old findings, which challenge this model. As a whole, current data suggest that the replisome, at least in slowly growing Escherichia coli cells, tracks along a stationary chromosome. These replisomes are not stationary, tethered or restricted in their movement, but rather travel throughout the nucleoid. One possibility is that the replisome navigates along a chromosome made up of looped domains as has been previously envisioned.     

Amphipods on seaweeds: partners or pests?

Summary Herbivorous marine amphipods have been implicated as important grazers on filamentous and ephemeral algae, and thus as beneficial to macrophytes in reducing overgrowth by epiphytic competitors. In North Carolina, USA, amphipods comprise 97% of all macroscopic animals inhabiting the abundant brown seaweed Sargassum filipendula, and peak in abundance between late winter and early summer. I used outdoor tank experiments to test the species-specific impact of common phytal amphipods on the growth of Sargassum and its epiphytes. The results show that seaweed-associated amphipods are a trophically diverse group that could either increase or decrease host fitness depending on their feeding preferences. The amphipods Ampithoe marcuzii, Caprella penantis, and Jassa falcata each significantly reduced growth of epiphytes on Sargassum plants relative to amphipod-free controls, while Ericthonius brasiliensis had no significant effect on Sargassum or its epiphytes. However, amphipod grazing was not necessarily beneficial to Sargassum. A. marcuzii consumed Sargassum in one outdoor tank experiment, reducing its mass by 11%, while Sargassum plants without amphipods grew by 81%. Epiphytes (mostly diatoms and the filamentous brown alga Ectocarpus siliculosus) and detritus remained abundant on these plants suggesting that A. marcuzii preferred the host to its epiphytes. Similarly, when given simultaneous access to Sargassum and to several common foliose and filamentous epiphytes in the lab, A. marcuzii ate Sargassum almost exclusively. The other three amphipods ate no macroalgae. In contrast to A. marcuzii, C. penantis consistently reduced epiphytes with no negative effect on Sargassum. Thus the species composition of the amphipod fauna can determine whether these animals increase or decrease seaweed fitness.     

Spectrum of CFTR mutations on Réunion Island: impact on neonatal screening

The large heterogeneity in the cystic fibrosis (CF) gene is the main difficulty for genotype characterization. Numerous studies have reported considerable variations in frequencies of CF transmembrane conductance regulator (CFTR) mutations in different populations, such as African, Asian, or European populations. To completely characterize the spectrum of mutations in the CFTR gene in the Réunion Island population, we screened 228 CF chromosomes using denaturing high-pressure liquid chromatography and denaturing gradient gel electrophoresis following by direct sequencing. We identified 27 mutations, accounting for 93% of CF chromosomes. They included three novel mutations (M1T, 3121-3C-->G, and L1324P), which are described in this paper. The detection of such a high proportion of Réunion Island CFTR mutations is important for improving neonatal screening of CF on Réunion Island.     

Studies on trimethoprim:hydroxypropyl-β-cyclodextrin: aggregate and complex formation

The present study is focused on the characterization of the interaction between trimethoprim, a dihydropteroate synthesase inhibitor, and hydroxypropyl-β-cyclodextrin (HP-β-CD) in aqueous solution and solid state. The freeze-drying method was used to prepare solid complexes, while simple blending was employed to obtain physical mixtures. The phase solubility was AN type, and demonstrated that trimethoprim solubility was significantly increased upon complexation with HP-β-CD. Conductivity experiments showed the presence of aggregates that explains the type profile for the solubility isotherm. The critical concentration for the aggregate formation was determined to be 69.3 mg/ml for pure HP-β-CD and 117.7 mg/ml in the presence of trimethoprim. Nuclear magnetic resonance spectroscopy provided evidence of trimethoprim:HP-β-CD molecular interaction in solution. Moreover, the complex was characterized in solid stated using Fourier-transform infrared spectroscopy (FT-IR) and scanning electron microscopy (SEM). The use of differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA) showed that the thermal stability of the drug is enhanced in the presence of HP-β-CD.     

Threshold foraging behaviour of basking sharks on zooplankton: life on an energetic knife-edge?

The minimum threshold foraging response of basking sharks has not been determined despite the widely held view that has been perpetuated in the literature for the past 45 years that this species cannot use low prey densities for net energy gain and so lives on an energetic ''knife-edge''. An early theoretical estimate suggested basking sharks would expend more energy collecting zooplankton at concentrations less than 1.36 g m^-3 than could be obtained from it. This led to the claim that basking sharks will feed at an energetic loss for much of the annual cycle as zooplankton abundance outside summer months is too low for net energy gain to occur. Here I show from theoretical calculations and behavioural studies on individual and group-feeding sharks in the English Channel that basking sharks have a theoretical threshold prey density of between 0.55 and 0.74 g m^-3 and an observed foraging threshold of between 0.48 and 0.70 g m^-3 (mean = 0.62 g m^-3). The close agreement between theoretical and empirical threshold values suggests basking sharks can achieve net energy gain in much lower zooplankton densities than previously thought. The findings imply that this species may not be reliant upon the ''migration–hibernation'' energy conservation strategy it is purported to exhibit when seasonal zooplankton abundance decreases below 1.36 g m^-3.     

Effects of Polyphenols on Brain Ageing and Alzheimer’s Disease: Focus on Mitochondria

The global trend of the phenomenon of population ageing has dramatic consequences on public health and the incidence of neurodegenerative diseases. Physiological changes that occur during normal ageing of the brain may exacerbate and initiate pathological processes that may lead to neurodegenerative disorders, especially Alzheimer's disease (AD). Hence, the risk of AD rises exponentially with age. While there is no cure currently available, sufficient intake of certain micronutrients and secondary plant metabolites may prevent disease onset. Polyphenols are highly abundant in the human diet, and several experimental and epidemiological evidences indicate that these secondary plant products have beneficial effects on AD risks. This study reviews current knowledge on the potential of polyphenols and selected polyphenol-rich diets on memory and cognition in human subjects, focusing on recent data showing in vivo efficacy of polyphenols in preventing neurodegenerative events during brain ageing and in dementia. Concentrations of polyphenols in animal brains following oral administration have been consistently reported to be very low, thus eliciting controversial discussion on their neuroprotective effects and potential mechanisms. Whether polyphenols exert any direct antioxidant effects in the brain or rather act by evoking alterations in regulatory systems of the brain or even the body periphery is still unclear. To understand the mechanisms behind the protective abilities of polyphenol-rich foods, an overall understanding of the biotransformation of polyphenols and identification of the various metabolites arising in the human body is also urgently needed.     

Mineralization and non-ideality: on nature’s foundry

Understanding how ions, ion-clusters and particles behave in non-ideal environments is a fundamental question concerning planetary to atomic scales. For biomineralization phenomena wherein diverse inorganic and organic ingredients are present in biological media, attributing biomaterial composition and structure to the chemistry of singular additives may not provide a holistic view of the underlying mechanisms. Therefore, in this review, we specifically address the consequences of physico-chemical non-ideality on mineral formation. Influences of different forms of non-ideality such as macromolecular crowding, confinement and liquid-like organic phases on mineral nucleation and crystallization in biological environments are presented. Novel prospects for the additive-controlled nucleation and crystallization are accessible from this biophysical view. In this manner, we show that non-ideal conditions significantly affect the form, structure and composition of biogenic and biomimetic minerals.