Force field measurements within the exclusion zone of water

Water molecules play critical roles in many biological functions, such as protein dynamics, enzymatic activities, and cellular responses. Previous nuclear magnetic resonance and neutron scattering studies have shown that water molecules bind to specific sites on surfaces and form localized clusters. However, most current experimental techniques cannot measure dynamic behaviors of ordered water molecules on cell-size (10 μm) scale. Recently, the long-distance effect of structured water has been demonstrated by Pollack and his colleagues. Namely, there is a structured water layer near the hydrophilic surface that can exclude solutes (Zheng et al, Adv Colloid Interface Sci 127:19–27, 2006; Pollack 2006, Adv Colloid Interface Sci 103:173–196, 2003). The repelling forces of water clusters inside this exclusion region are investigated in this study. With a laser tweezers system, we found the existence of an unexpected force fields inside the solute-free exclusion zone near a Nafion surface. Our results suggest that the water clusters could transduce mechanical signals on the micrometer range within the exclusion zone. This unexpected inhomogeneous force field near the hydrophilic surface would provide a new insight into cellular activities, leading to a potential new physical chemistry mechanism for cell biology.     

Photoreceptor spectral sensitivity in island and mainland populations of the bumblebee, <Emphasis Type="Italic">Bombus terrestris</Emphasis>

Most species of flower-visiting Hymenoptera are trichromatic, with photoreceptor spectral sensitivity peaks in the UV, blue and green regions of the spectrum. Red flowers, therefore, should be relatively difficult to detect for such insects. Nevertheless, in population biological studies in the bumblebee, Bombus terrestris, the Sardinian island population (B. t. sassaricus) displayed significantly higher responses to red artificial flowers (in tests of innate colour choice and detectability) than several mainland populations of the same species (Chittka et al. in Cognitive ecology of pollination, pp 106–126, 2001; Popul Ecol 46:243–251, 2004). Since there is relatively little physiological data on population differences in sensory systems, we used intracellular recording to compare photoreceptor spectral sensitivity in B. t. sassaricus and the southern European and Mediterranean population, B. t. dalmatinus. The results show both populations to be UV–blue–green trichromats, but with a small but significant increase in long-wave sensitivity in island bees. Spectral peaks were estimated at 348, 435 and 533 nm (B. t. dalmatinus) and 347, 436 and 538 nm (B. t. sassaricus) for UV, blue and green receptors, respectively. There were no significant differences in UV and blue receptor sensitivities. We found no photoreceptors maximally sensitive to red spectral light in the Sardinian population and model calculations indicate that the behavioural population differences in colour responses cannot be directly explained by receptor population differences. Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Comment arising from a paper by Wittmer et al.: hypothesis testing for top-down and bottom-up effects in woodland caribou population dynamics

Conservation strategies for populations of woodland caribou Rangifer tarandus caribou frequently emphasize the importance of predator–prey relationships and the availability of lichen-rich late seral forests, yet the importance of summer diet and forage availability to woodland caribou survival is poorly understood. In a recent article, Wittmer et al. (Can J Zool 83:407–418, 2005b) concluded that woodland caribou in British Columbia were declining as a consequence of increased predation that was facilitated by habitat alteration. Their conclusion is consistent with the findings of other authors who have suggested that predation is the most important proximal factor limiting woodland caribou populations (Bergerud and Elliot in Can J Zool 64:1515–1529, 1986; Edmonds in Can J Zool 66:817–826, 1988; Rettie and Messier in Can J Zool 76:251–259, 1998; Hayes et al. in Wildl Monogr 152:1–35, 2003). Wittmer et al. (Can J Zool 83:407–418, 2005b) presented three alternative, contrasting hypotheses for caribou decline that differed in terms of predicted differences in instantaneous rates of increase, pregnancy rates, causes of mortality, and seasonal vulnerability to mortality (Table 1, p 258). These authors rejected the hypotheses that food or an interaction between food and predation was responsible for observed declines in caribou populations; however, the use of pregnancy rate, mortality season and cause of mortality to contrast the alternative hypotheses is problematic. We argue here that the data employed in their study were insufficient to properly evaluate a predation-sensitive foraging hypothesis for caribou decline. Empirical data on seasonal forage availability and quality and plane of nutrition of caribou would be required to test the competing hypotheses. We suggest that methodological limitations in studies of woodland caribou population dynamics prohibit proper evaluation of the mechanism of caribou population declines and fail to elucidate potential interactions between top-down and bottom-up effects on populations. An erratum to this article can be found at     

A role for anions in ATP synthesis and its molecular mechanistic interpretation

ATP, the ‘universal biological energy currency’, is synthesized by utilizing energy either from oxidation of fuels or from light, via the process of oxidative and photo-phosphorylation respectively. The process is mediated by the enzyme F₁F₀-ATP synthase, using the free energy of ion gradients in the final energy catalyzing step, i.e., the synthesis of ATP from ADP and inorganic phosphate (P_i). The details of the molecular mechanism of ATP synthesis are among the most important fundamental issues in biology and hence need to be properly understood. In this work, a role for anions in making ATP has been found. New experimental data has been reported on the inhibition of ATP synthesis at nanomolar concentrations by the potent, specific anion channel blockers 4,4′-diisothiocyanostilbene-2, 2′-disulphonic acid (DIDS) and tributyltin chloride (TBTCl). Based on these inhibition studies, attention has been drawn to anion translocation (in addition to proton translocation) as a requirement for ATP synthesis. The type of inhibition has been quantified and an overall kinetic scheme for mixed inhibition that explains the data has been evolved. The experimental data and the type of inhibition found have been interpreted in the light of the torsional mechanism of energy transduction and ATP synthesis (Nath J Bioenerg Biomembr 42:293–300, 2010a; J Bioenerg Biomembr 42:301–309, 2010b). This detailed and unified mechanism resolves long-standing problems and inconsistencies in the first theories (Slater Nature 172:975–978, 1953; Williams J Theor Biol 1:1–17, 1961; Mitchell Nature 191:144–148, 1961; Mitchell Biol Rev 41:445–502, 1966), makes several novel predictions that are experimentally verifiable (Nath Biophys J 90:8–21, 2006a; Process Biochem 41:2218–2235, 2006b), and provides us with a new and fruitful paradigm in bioenergetics. The interpretation presented here provides intelligent answers to the unexplained existing results in the literature. It is shown that mechanistic interpretation of the experimental data requires substantial addition to available conceptual foundations such that present concepts, theories, and mechanisms must be revised.     

The Potential Impact of Disease on the Migratory Structure of a Partially Migratory Passerine Population

Since its introduction into eastern North America in the 1940s, the eastern population of house finches (Carpodacus mexicanus) has become partially migratory, unlike its nonmigratory source population in southern California (Able and Belthoff in Proc. R. Soc. Lond. 265 (1410), 2063–2071, 1998; Belthoff and Gauthreaux in Condor 93, 374–382, 1991). The infectious disease mycoplasmal conjunctivitis (pathogen Mycoplasma gallisepticum or “MG”), which has been monitored in the house finch population since its appearance around 1993 (Dhondt et al. in J. Wild. Dis. 34 (2), 265–280, 1998), may induce higher mortality rates among populations in more northerly latitudes relative to more southerly populations. Here, we investigate the potential impact of this differential disease mortality on the migratory structure of the eastern house finch population using an epidemic modeling approach. Analytical and computational results suggest the ongoing MG epidemic in the eastern house finch could lead to increases in the percentage of and the total number of migrating individuals in a population despite overall population declines, assuming relatively high winter mortality rates in the north eastern part of their range. These results also suggest that empirical evidence of such a change in migratory structure would be most noticeable in northerly inland populations that showed significant declines following the initial outbreak of MG in the east.     

Synchronized changes to relative neuron populations in postnatal human neocortical development

Mammalian prenatal neocortical development is dominated by the synchronized formation of the laminae and migration of neurons. Postnatal development likewise contains “sensitive periods” during which functions such as ocular dominance emerge. Here we introduce a novel neuroinformatics approach to identify and study these periods of active development. Although many aspects of the approach can be used in other studies, some specific techniques were chosen because of a legacy dataset of human histological data (Conel in The postnatal development of the human cerebral cortex, vol 1–8. Harvard University Press, Cambridge, 1939–1967). Our method calculates normalized change vectors from the raw histological data, and then employs k-means cluster analysis of the change vectors to explore the population dynamics of neurons from 37 neocortical areas across eight postnatal developmental stages from birth to 72 months in 54 subjects. We show that the cortical “address” (Brodmann area/sub-area and layer) provides the necessary resolution to segregate neuron population changes into seven correlated “k-clusters” in k-means cluster analysis. The members in each k-cluster share a single change interval where the relative share of the cortex by the members undergoes its maximum change. The maximum change occurs in a different change interval for each k-cluster. Each k-cluster has at least one totally connected maximal “clique” which appears to correspond to cortical function.     

Hypericum sp.: essential oil composition and biological activities

Phytochemical composition of Hypericum genus has been investigated for many years. In the recent past, studies on the essential oils (EO) of this genus have been progressing and many of them have reported interesting biological activities. Variations in the EO composition of Hypericum species influenced by seasonal variation, geographic distribution, phenological cycle and type of the organ in which EO are produced and/or accumulated have also been reported. Although many reviews attributed to the characterization as well as biological activities of H. perforatum crude extracts have been published, no review has been published on the EO composition and biological activities of Hypericum species until recently (Crockett in Nat Prod Commun 5(9):1493–1506, 2010; Bertoli et al. in Global Sci Books 5:29–47, 2011). In this article, we summarize and update information regarding the composition and biological activities of Hypericum species EO. Based on experimental work carried out in our laboratory we also mention possible biotechnology approaches envisaging EO improvement of some species of the genus.     

Use of weighted reference panels based on empirical estimates of ancestry for capturing untyped variation

Many association methods use a subset of genotyped single nucleotide polymorphisms (SNPs) to capture or infer genotypes at other untyped SNPs. We and others previously showed that tag SNPs selected to capture common variation using data from The International HapMap Consortium (Nature 437:1299–1320, 2005), The International HapMap Consortium (Nature 449:851–861, 2007) could also capture variation in populations of similar ancestry to HapMap reference populations (de Bakker et al. in Nat Genet 38:1298–1303, 2006; González-Neira et al. in Genome Res 16:323–330, 2006; Montpetit et al. in PLoS Genet 2:282–290, 2006; Mueller et al. in Am J Hum Genet 76:387–398, 2005). To capture variation in admixed populations or populations less similar to HapMap panels, a “cosmopolitan approach,” in which all samples from HapMap are used as a single reference panel, was proposed. Here we refine this suggestion and show that use of a “weighted reference panel,” constructed based on empirical estimates of ancestry in the target population (relative to available reference panels), is more efficient than the cosmopolitan approach. Weighted reference panels capture, on average, only slightly fewer common variants (minor allele frequency > 5%) than the cosmopolitan approach (mean r ² = 0.977 vs. 0.989, 94.5% variation captured vs. 96.8% at r ² > 0.8), across the five populations of the Multiethnic Cohort, but entail approximately 25% fewer tag SNPs per panel (average 538 vs. 718). These results extend a recent study in two Indian populations (Pemberton et al. in Ann Hum Genet 72:535–546, 2008). Weighted reference panels are potentially useful for both the selection of tag SNPs in diverse populations and perhaps in the design of reference panels for imputation of untyped genotypes in genome-wide association studies in admixed populations. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users.     

Identification of <Emphasis Type="Italic">Porphyra yezoensis</Emphasis> (Rhodophyta) meiosis by DNA quantification using confocal laser scanning microscopy

Conchospore germlings of Porphyra yezoensis were stained with a fluorescent dye for DNA and observed with confocal laser scanning microscopy (CLSM). Relative DNA values of the germling nuclei were obtained by measuring fluorescence intensities of nuclear regions of the optically sliced specimens, using the mean value of the smallest blade cells as a reference of the genomic n value. Such quantification revealed that the nuclear DNA amounts of the one-cell, two-cell, and four-cell-stage germlings are approximately 4 × n, 2 × n, and n ∼2 × n values respectively; these values agreed well with the expected ones from the hypothesis that meiosis corresponds to the first successive cell divisions after the conchospore germination. These results are consistent with a previous study on cytogenetic analysis of the chimaera blade formation (Ohme and Miura 1988, Plant Sci 57:135–140) and not consistent with a recent microscopic study (Wang et al. 2006, Phycol Res 54:201–207) which proposed that the first meiotic division occurs at the conchospore formation and the second division at the germination.     

Hadamard Phylogenetic Methods and the <Emphasis Type="Italic">n</Emphasis>-taxon Process

The Hadamard transform (Hendy and Penny, Syst. Zool. 38(4):297–309, 1989; Hendy, Syst. Zool. 38(4):310–321, 1989) provides a way to work with stochastic models for sequence evolution without having to deal with the complications of tree space and the graphical structure of trees. Here we demonstrate that the transform can be expressed in terms of the familiar P[τ]=e ^Q[τ] formula for Markov chains. The key idea is to study the evolution of vectors of states, one vector entry for each taxa; we call this the n-taxon process. We derive transition probabilities for the process. Significantly, the findings show that tree-based models are indeed in the family of (multi-variate) exponential distributions.     

Genome-wide meta-analysis for rheumatoid arthritis

Meta-analysis is being increasingly used as a tool for integrating data from different studies of complex phenotypes, because the power of any one study to identify causal loci is limited. We applied a novel meta-analytical approach (Loesgen et al. in Genet Epidemiol 21(Suppl 1):S142–S147, 2001) in compiling results from four studies of rheumatoid arthritis in Caucasians including two studies from NARAC (Jawaheer et al. in Am J Hum Genet 68:927–936, 2001; Jawaheer et al. in Arthritis Rheum 48:906–916, 2003), one study from the UK (MacKay et al. in Arthritis Rheum 46:632–639, 2001) and one from France (Cornelis et al. in Proc Natl Acad Sci USA 95:10746–10750, 1998). For each study, we obtained NPL scores by performing interval mapping (2 cM intervals) using GeneHunter2 (Kruglyak et al. in Am J Hum Genet 58:1347–1363, 1996; Markianos et al. in Am J Hum Genet 68:963–977, 2001). The marker maps differed among the three consortium groups, therefore, the marker maps were aligned after the interval mapping was completed and the NPL scores that were within 1 cM of each other were combined using the method of Loesgen et al. (Genet Epidemiol 21(Suppl 1):S142–S147, 2001) by calculating the weighted average of the NPL score. This approach avoids some problems in analysis encountered by using GeneHunter2 when some markers in the sample are not genotyped. This procedure provided marginal evidence (P<0.05) of linkage on chromosome 1, 2, 5 and 18, strong evidence (P<0.01) on chromosomes 8 and 16, and overwhelming evidence in the HLA region of chromosome 6.     

The low phytic acid1-241 (lpa1-241) maize mutation alters the accumulation of anthocyanin pigment in the kernel

The lpa1 mutations in maize are caused by lesions in the ZmMRP4 (multidrug resistance-associated proteins 4) gene. In previous studies (Raboy et al. in Plant Physiol 124:355–368, 2000; Pilu et al. in Theor Appl Genet 107:980–987, 2003a; Shi et al. Nat Biotechnol 25:930–937, 2007), several mutations have been isolated in this locus causing a reduction of phytic acid (myo-inositol-1,2,3,4,5,6-hexakisphosphate, or InsP₆) content and an equivalent increasing of free phosphate. In particular, the lpa1-241 mutation causes a reduction of up to 90% of phytic acid, associated with strong pleiotropic effects on the whole plant. In this work, we show, for the first time to our knowledge, an interaction between the accumulation of anthocyanin pigments in the kernel and the lpa mutations. In fact the lpa1-241 mutant accumulates a higher level of anthocyanins as compared to wild type either in the embryo (about 3.8-fold) or in the aleurone layer (about 0.3-fold) in a genotype able to accumulate anthocyanin. Furthermore, we demonstrate that these pigments are mislocalised in the cytoplasm, conferring a blue pigmentation of the scutellum, because of the neutral/basic pH of this cellular compartment. As a matter of fact, the propionate treatment, causing a specific acidification of the cytoplasm, restored the red pigmentation of the scutellum in the mutant and expression analysis showed a reduction of ZmMRP3 anthocyanins’ transporter gene expression. On the whole, these data strongly suggest a possible interaction between the lpa mutation and anthocyanin accumulation and compartmentalisation in the kernel.     

Electrophysiological recording from parasitic nematode muscle

Infection of man and animals with parasitic nematodes is recognized as a significant global problem (McLeod in Int J Parasitol 25(11):1363–1367, 1994; Hotez et al. in N Engl J Med 357(10):1018–1027, 2007). At present control of these infections relies primarily on chemotherapy. There are a limited number of classes of anthelmintic compounds and the majority of these act on ion-channels of the parasite (Martin et al. in Parasitology 113:S137–S156, 1996). In this report, we describe electrophysiological recording techniques as applied to parasitic nematodes. The aim of this report is: (1) to promote the study of ion channels in nematodes to help further the understanding of antinematodal drug action; (2) to describe our recording equipment and experimental protocols; and (3) provide some examples of the information to be gleaned from this approach and how it can increase our understanding of these important pathogens.     

Kinetic models of photosystem II should accommodate the effect of donor side quenching on variable chlorophyll <Emphasis Type="Italic">a</Emphasis> fluorescence in the microseconds time range

Quantitative data on laser flash-induced variable fluorescence in the 100 ns to 1 ms time range (Belyaeva et al. in Photosynth Res 98:105–119, 2008) confirming those of others (Steffen et al. in Biochemistry 40:173–180, 2001, Biochemistry 44:3123–3132, 2005; Belyaeva et al. in Biophysics 51(6):976–990, 2006), need a substantial correction with respect to magnitude of the normalized variable fluorescence associated with single turnover-induced charge separation in RCs of PS II. Their data are conclusive with the involvement of donor side quenching, the release of which occurs with a rate constant in the range of tens of ms⁻¹, and presumed to be associated with reduction of Y_\textz ⁺ Y_{\text{z}}^{ + } by the OEC.     

The heme environment of mouse neuroglobin: histidine imidazole plane orientations obtained from solution NMR and EPR spectroscopy as compared with X-ray crystallography

The ¹H NMR chemical shifts of the heme methyl groups of the ferriheme complex of metneuroglobin (Du et al. in J. Am. Chem. Soc. 125:8080–8081, 2003) predict orientations of the axial histidine ligands (Shokhirev and Walker in J. Biol. Inorg. Chem. 3:581–594, 1998) that are not consistent with the X-ray data (Vallone et al. in Proteins Struct. Funct. Bioinf. 56:85–94, 2004), and the EPR spectrum (Vinck et al. in J. Am. Chem. Soc. 126:4516–4517, 2004) is only marginally consistent with these data. The reasons for these inconsistencies appear to be rooted in the high degree of aqueous solution exposure of the heme group and the fact that there are no strong hydrogen-bond acceptors for the histidine imidazole N–H protons provided by the protein. Similar inconsistencies may exist for other water-soluble heme proteins, and ¹H NMR spectroscopy provides a simple means to verify whether the solution structure of the heme center is the same as or different from that in the crystalline state.     

Leader neurons in leaky integrate and fire neural network simulations

In this paper, we highlight the topological properties of leader neurons whose existence is an experimental fact. Several experimental studies show the existence of leader neurons in population bursts of activity in 2D living neural networks (Eytan and Marom, J Neurosci 26(33):8465–8476, 2006; Eckmann et al., New J Phys 10(015011), 2008). A leader neuron is defined as a neuron which fires at the beginning of a burst (respectively network spike) more often than we expect by chance considering its mean firing rate. This means that leader neurons have some burst triggering power beyond a chance-level statistical effect. In this study, we characterize these leader neuron properties. This naturally leads us to simulate neural 2D networks. To build our simulations, we choose the leaky integrate and fire (lIF) neuron model (Gerstner and Kistler 2002; Cessac, J Math Biol 56(3):311–345, 2008), which allows fast simulations (Izhikevich, IEEE Trans Neural Netw 15(5):1063–1070, 2004; Gerstner and Naud, Science 326:379–380, 2009). The dynamics of our lIF model has got stable leader neurons in the burst population that we simulate. These leader neurons are excitatory neurons and have a low membrane potential firing threshold. Except for these two first properties, the conditions required for a neuron to be a leader neuron are difficult to identify and seem to depend on several parameters involved in the simulations themselves. However, a detailed linear analysis shows a trend of the properties required for a neuron to be a leader neuron. Our main finding is: A leader neuron sends signals to many excitatory neurons as well as to few inhibitory neurons and a leader neuron receives only signals from few other excitatory neurons. Our linear analysis exhibits five essential properties of leader neurons each with different relative importance. This means that considering a given neural network with a fixed mean number of connections per neuron, our analysis gives us a way of predicting which neuron is a good leader neuron and which is not. Our prediction formula correctly assesses leadership for at least ninety percent of neurons.     

Acidithiobacillus thiooxidans secretome containing a newly described lipoprotein Licanantase enhances chalcopyrite bioleaching rate

The nature of the mineral–bacteria interphase where electron and mass transfer processes occur is a key element of the bioleaching processes of sulfide minerals. This interphase is composed of proteins, metabolites, and other compounds embedded in extracellular polymeric substances mainly consisting of sugars and lipids (Gehrke et al., Appl Environ Microbiol 64(7):2743–2747, 1998). On this respect, despite Acidithiobacilli—a ubiquitous bacterial genera in bioleaching processes (Rawlings, Microb Cell Fact 4(1):13, 2005)—has long been recognized as secreting bacteria (Jones and Starkey, J Bacteriol 82:788–789, 1961; Schaeffer and Umbreit, J Bacteriol 85:492–493, 1963), few studies have been carried out in order to clarify the nature and the role of the secreted protein component: the secretome. This work characterizes for the first time the sulfur (meta)secretome of Acidithiobacillus thiooxidans strain DSM 17318 in pure and mixed cultures with Acidithiobacillus ferrooxidans DSM 16786, identifying the major component of these secreted fractions as a single lipoprotein named here as Licanantase. Bioleaching assays with the addition of Licanantase-enriched concentrated secretome fractions show that this newly found lipoprotein as an active protein additive exerts an increasing effect on chalcopyrite bioleaching rate.     

The NMR restraints grid at BMRB for 5,266 protein and nucleic acid PDB entries

Several pilot experiments have indicated that improvements in older NMR structures can be expected by applying modern software and new protocols (Nabuurs et al. in Proteins 55:483–186, 2004; Nederveen et al. in Proteins 59:662–672, 2005; Saccenti and Rosato in J Biomol NMR 40:251–261, 2008). A recent large scale X-ray study also has shown that modern software can significantly improve the quality of X-ray structures that were deposited more than a few years ago (Joosten et al. in J. Appl Crystallogr 42:376–384, 2009; Sanderson in Nature 459:1038–1039, 2009). Recalculation of three-dimensional coordinates requires that the original experimental data are available and complete, and are semantically and syntactically correct, or are at least correct enough to be reconstructed. For multiple reasons, including a lack of standards, the heterogeneity of the experimental data and the many NMR experiment types, it has not been practical to parse a large proportion of the originally deposited NMR experimental data files related to protein NMR structures. This has made impractical the automatic recalculation, and thus improvement, of the three dimensional coordinates of these structures. We here describe a large-scale international collaborative effort to make all deposited experimental NMR data semantically and syntactically homogeneous, and thus useful for further research. A total of 4,014 out of 5,266 entries were ‘cleaned’ in this process. For 1,387 entries, human intervention was needed. Continuous efforts in automating the parsing of both old, and newly deposited files is steadily decreasing this fraction. The cleaned data files are available from the NMR restraints grid at .