Bone tissue,lyophilized and stored at room temperature for 15 days or more,is not capable of transmitting HIV,HCV or HBV

Over the past 57 years, 17 recipients of frozen bone have been infected with: HIV (Centers for Disease Control and Prevention in Morb Mortal Wkly Rep MMWR 37(39):597–599, 1988; Li et al. in J Formos Med Assoc 100(5):350–351, 2001; Simonds et al. in NEJM 326(11):726–732, 1992; Schratt et al. in Unfallchirurg 99(9):679–684, 1996); HCV (Eggen and Nordbo in NEJM 326(6):411, 1992; Conrad et al. in J Bone Joint Surg Am 77:214–224, 1995; Trotter in J Bone Joint Surg Am 851(11):2215–2217, 2003; Tugwell et al. in Ann of Internal Med 143(9):648–654, 2005); or HBV (Shutkin in J Bone Joint Surg Am 36:160–162, 1954). However, bone, lyophilized and stored at room temperature, has never transmitted these viral diseases. A literature review was undertaken to determine whether there is any evidence that lyophilized bone is capable of transmitting HIV, HCV and HBV.     

The intertidal zoning of cockles (<Emphasis Type="Italic">Cerastoderma edule</Emphasis>) in the Wadden Sea,or why cockle fishery disturbed areas of relatively high biodiversity

Recently, Kraan et al. (ICES J Mar Sci 64:1735–1742, 2007) reported that areas in the Wadden Sea selected by mechanical cockle dredgers were of greater zoobenthic diversity than areas that remained undredged. The present paper attempts to explain this observation, focussing on the elevation-related zoning of the macrobenthic fauna on tidal flats. Dense beds of cockles Cerastoderma edule occur in a specific intermediate intertidal-height zone where more species are present (and reach their maximal abundance) than in either lower or higher zones. This coincidence of preferred intertidal zones in many species, including cockles, may cause the higher species richness (and higher total macrozoobenthic biomass) of the fisher-chosen dredging areas as compared to other nearby non-dredged tidal-flat areas.     

The infrageneric nomenclature of <Emphasis Type="Italic">Tulipa</Emphasis> (Liliaceae)

Zonneveld (Pl Syst Evol 281:217–245, 2009) proposed an infrageneric classification of Tulipa (Liliaceae) based on the nuclear content determined by flow cytometry and available morphological data. The nomenclatural consequences of this are discussed here, involving the typification of generic and infrageneric names. Additional notes on some species are given. Four subgenera are distinguished, of which two are new; ten sections are proposed, four new; three new combinations are made, and seven lectotypes are designated. Tulipa praecox Ten. is a later homonym of T. praecox Cav. (Descripcíon de las plantas. 2: 448, 625, 1803); its correct name is Tulipa agenensis DC. Tulipa lemmersii Zonn., A. Peterse, J. de Groot is validated here by giving the type citation.     

A Computational Analysis of Localized Ca<Superscript>2+</Superscript>-Dynamics Generated by Heterogeneous Release Sites

We investigate the role of heterogeneous expression of IP₃R and RyR in generating diverse elementary Ca²⁺ signals. It has been shown empirically (Wojcikiewicz and Luo in Mol. Pharmacol. 53(4):656–662, 1998; Newton et al. in J. Biol. Chem. 269(46):28613–28619, 1994; Smedt et al. in Biochem. J. 322(Pt. 2):575–583, 1997) that tissues express various proportions of IP₃ and RyR isoforms and this expression is dynamically regulated (Parrington et al. in Dev. Biol. 203(2):451–461, 1998; Fissore et al. in Biol. Reprod. 60(1):49–57, 1999; Tovey et al. in J. Cell Sci. 114(Pt. 22):3979–3989, 2001). Although many previous theoretical studies have investigated the dynamics of localized calcium release sites (Swillens et al. in Proc. Natl. Acad. Sci. U.S.A. 96(24):13750–13755, 1999; Shuai and Jung in Proc. Natl. Acad. Sci. U.S.A. 100(2):506–510, 2003a; Shuai and Jung in Phys. Rev. E, Stat. Nonlinear Soft Matter Phys. 67(3 Pt. 1):031905, 2003b; Thul and Falcke in Biophys. J. 86(5):2660–2673, 2004; DeRemigio and Smith in Cell Calcium 38(2):73–86, 2005; Nguyen et al. in Bull. Math. Biol. 67(3):393–432, 2005), so far all such studies focused on release sites consisting of identical channel types. We have extended an existing mathematical model (Nguyen et al. in Bull. Math. Biol. 67(3):393–432, 2005) to release sites with two (or more) receptor types, each with its distinct channel kinetics. Mathematically, the release site is represented by a transition probability matrix for a collection of nonidentical stochastically gating channels coupled through a shared Ca²⁺ domain. We demonstrate that under certain conditions a previously defined mean-field approximation of the coupling strength does not accurately reproduce the release site dynamics. We develop a novel approximation and establish that its performance in these instances is superior. We use this mathematical framework to study the effect of heterogeneity in the Ca²⁺-regulation of two colocalized channel types on the release site dynamics. We consider release sites consisting of channels with both Ca²⁺-activation and inactivation (“four-state channels”) and channels with Ca²⁺-activation only (“two-state channels”) and show that for the appropriate parameter values, synchronous channel openings within a release site with any proportion of two-state to four-state channels are possible, however, the larger the proportion of two-state channels, the more sensitive the dynamics are to the exact spatial positioning of the channels and the distance between channels. Specifically, the clustering of even a small number of two-state channels interferes with puff/spark termination and increases puff durations or leads to a tonic response.     

Causal isolation robustness analysis: the combinatorial strategy of circadian clock research

This paper distinguishes between causal isolation robustness analysis and independent determination robustness analysis and suggests that the triangulation of the results of different epistemic means or activities serves different functions in them. Circadian clock research is presented as a case of causal isolation robustness analysis: in this field researchers made use of the notion of robustness to isolate the assumed mechanism behind the circadian rhythm. However, in contrast to the earlier philosophical case studies on causal isolation robustness analysis (Weisberg and Reisman in Philos Sci 75:106–131, 2008; Kuorikoski et al. in Br J Philos Sci 61:541–567, 2010), robustness analysis in the circadian clock research did not remain in the level of mathematical modeling, but it combined it with experimentation on model organisms and a new type of model, a synthetic model.     

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     

Endocrine modulation of a pheromone-responsive gene in the honey bee brain

Pheromones cause dramatic changes in behavior and physiology, and are critical for honey bee colony organization. Queen mandibular pheromone (QMP) regulates multiple behaviors in worker bees (Slessor et al. in J Chem Ecol 31(11):2731–2745, 2005). We also identified genes whose brain expression levels were altered by exposure to QMP (Grozinger et al. in Proc Natl Acad Sci USA 100(Suppl 2):14519–14525, 2003). Krüppel-homolog 1 (Kr-h1) RNA levels were significantly downregulated by QMP, and were higher in foragers than in nurses (Whitfield et al. in Science 302(5643):296–299, 2003). Here we report on results of behavioral and pharmacological experiments that characterize factors regulating expression of Kr-h1. Foragers have higher brain levels of Kr-h1 than in-hive bees, regardless of age and pheromone exposure. Furthermore, forager Kr-h1 levels were not affected by QMP. Since the onset of foraging is caused, in part, by increasing juvenile hormone blood titers and brain octopamine levels, we investigated the effects of octopamine and methoprene (a juvenile hormone analog) on Kr-h1 expression. Methoprene produced a marginal (not significant) increase in Kr-h1 expression, but Kr-h1 brain levels in methoprene-treated bees were no longer downregulated by QMP. Octopamine did not modulate Kr-h1 expression. Our results demonstrate that the gene expression response to QMP is not hard-wired in the brain but is instead dependent on worker behavioral state.     

A molecular chromatographic approach to analyze the cell diffusion of arginase inhibitors

Our group demonstrated that arginase inhibition reduces endothelial dysfunction in spontaneously hypertensive rats [C. Demougeot, A. Prigent-Tessier, C. Marie, A. Berthelot, J. Hypertens. 23 (2005) 971; C. Demougeot, A. Prigent-Tessier, T. Bagnost, C. Andre, Y. Guillaume, M. Bouhaddi, C. Marie, A. Berthelot, Life Sci. 80 (2007) 1128] which opens perspectives in the development of drugs against hypertension. In previous papers [T. Bagnost, Y.C. Guillaume, M. Thomassin, J.F. Robert, A. Berthelot, A. Xicluna, C. Andre, J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci. 856 (2007) 113; T. Bagnost, Y.C. Guillaume, M. Thomassin, A. Berthelot, C. Demougeot, C. Andre, J. Chromatogr. B: Analyt. Technol. Biomed. Life Sci. 873 (2008) 37], we developed a biochromatographic column for studying the binding of an arginase inhibitor with this enzyme and the effect of magnesium on this binding. In this paper, the interaction of arginase inhibitors with an immobilized artificial membrane (IAM) has been studied using a biochromatographic approach. This IAM provided a biophysical model system to study the inhibitor passive transport across cells. It was demonstrated that more the inhibitor cross the cell membrane by passive diffusion more it is potent. As well, an analysis of the thermodynamics of the interaction of the arginase inhibitors with the IAM showed that van der Waals, hydrogen and ionic bonds were the main forces between the arginase inhibitors and the polar head groups of the IAM surface.     

Herbivory and plant competition reduce mountain beech seedling growth and establishment in New Zealand

The effect of herbivory and resource availability on the competitive ability of different plant species has been an area of intense debate amongst plant ecologists for at least two decades, but the interactive effects of herbivory and plant competition between woody and herbaceous plants are rarely studied and theory is poorly developed. This study used experimental manipulations on transplanted and naturally occurring mountain beech (Nothofagus solandri var. cliffortioides) seedlings to show the effects of deer browsing and competition from deer-induced, herbaceous turf communities on mountain beech regeneration in New Zealand. Differences in the species composition of these turfs had little effect on mountain beech seedling establishment, but turf removal increased seedling growth and survivorship, showing that competition with other plants had direct effects on mountain beech regeneration. Deer browsing reduced the establishment and growth of seedlings, but the size of this effect did not vary with light and nutrient availability. There was no immediate compositional response of turf communities following the removal of deer browsing. The addition of nutrients appeared to reduce the intensity of belowground competition (stem growth increased relative to root growth) and increase seedling mortality, but there was no effect of changing levels of light. These results showed simple and direct negative effects of deer browsing on mountain beech regeneration. Indirect negative effects on regeneration were caused by deer-induced turf communities. We found little evidence for interactive effects between herbivory, plant competition and the availability of light or nutrients on seedling regeneration, which suggests that these factors acted independently. Nomenclature: Beever et al. (1992); Parsons et al. (1995); Edgar and Connor (2000); and Brownsey and Smith-Dodsworth (2000). Raukaua simplex is described by Mitchell et al. (1997). Coprosma “taylorae” is referred to by Eagle (1986) and Halocarpus biformis, Phyllocladus alpinus, Podocarpus hallii and Podocarpus nivalis by Wilson and Galloway (1993).     

Estimation of Cell Proliferation Dynamics Using CFSE Data

Advances in fluorescent labeling of cells as measured by flow cytometry have allowed for quantitative studies of proliferating populations of cells. The investigations (Luzyanina et al. in J. Math. Biol. 54:57–89, 2007; J. Math. Biol., 2009; Theor. Biol. Med. Model. 4:1–26, 2007) contain a mathematical model with fluorescence intensity as a structure variable to describe the evolution in time of proliferating cells labeled by carboxyfluorescein succinimidyl ester (CFSE). Here, this model and several extensions/modifications are discussed. Suggestions for improvements are presented and analyzed with respect to statistical significance for better agreement between model solutions and experimental data. These investigations suggest that the new decay/label loss and time dependent effective proliferation and death rates do indeed provide improved fits of the model to data. Statistical models for the observed variability/noise in the data are discussed with implications for uncertainty quantification. The resulting new cell dynamics model should prove useful in proliferation assay tracking and modeling, with numerous applications in the biomedical sciences.     

A Closer Look at Amphetamine-Induced Reverse Transport and Trafficking of the Dopamine and Norepinephrine Transporters

Amphetamine (AMPH) and its derivatives are regularly used in the treatment of a wide array of disorders such as attention-deficit hyperactivity disorder (ADHD), obesity, traumatic brain injury, and narcolepsy (Prog Neurobiol 75:406–433, 2005; J Am Med Assoc 105:2051–2054, 1935; J Am Acad Child Adolesc Psychiatry 41:514–521, 2002; Neuron 43:261–269, 2004; Annu Rev Pharmacol Toxicol 47:681–698, 2007; Drugs Aging 21:67–79, 2004). Despite the important medicinal role for AMPH, it is more widely known for its psychostimulant and addictive properties as a drug of abuse. The primary molecular targets of AMPH are both the vesicular monoamine transporters (VMATs) and plasma membrane monoamine—dopamine (DA), norepinephrine (NE), and serotonin (5-HT)—transporters. The rewarding and addicting properties of AMPH rely on its ability to act as a substrate for these transporters and ultimately increase extracellular levels of monoamines. AMPH achieves this elevation in extracellular levels of neurotransmitter by inducing synaptic vesicle depletion, which increases intracellular monoamine levels, and also by promoting reverse transport (efflux) through plasma membrane monoamine transporters (J Biol Chem 237:2311–2317, 1962; Med Exp Int J Exp Med 6:47–53, 1962; Neuron 19:1271–1283, 1997; J Physiol 144:314–336, 1958; J Neurosci 18:1979–1986, 1998; Science 237:1219–1223, 1987; J Neurosc 15:4102–4108, 1995). This review will focus on two important aspects of AMPH-induced regulation of the plasma membrane monoamine transporters—transporter mediated monoamine efflux and transporter trafficking.     

Comparative Analysis of argK-tox Clusters and Their Flanking Regions in Phaseolotoxin-Producing Pseudomonas syringae Pathovars

DNA fragments containing argK-tox clusters and their flanking regions were cloned from the chromosomes of Pseudomonas syringae pathovar (pv.) actinidiae strain KW-11 (ACT) and P. syringae pv. phaseolicola strain MAFF 302282 (PHA), and then their sequences were determined. Comparative analysis of these sequences and the sequences of P. syringae pv. tomato DC3000 (TOM) (Buell et al., Proc Natl Acad Sci USA 100:10181–10186, 2003) and pv. syringae B728a (SYR) (Feil et al., Proc Natl Acad Sci USA 102:11064–11069, 2005) revealed that the chromosomal backbone regions of ACT and TOM shared a high similarity to each other but presented a low similarity to those of PHA and SYR. Nevertheless, almost-identical DNA regions of about 38 kb were confirmed to be present on the chromosomes of both ACT and PHA, which we named “tox islands.” The facts that the GC content of such tox islands was 6% lower than that of the chromosomal backbone regions of P. syringae, and that argK-tox clusters, which are considered to be of exogenous origin based on our previous studies (Sawada et al., J Mol Evol 54:437–457, 2002), were confirmed to be contained within the tox islands, suggested that the tox islands were an exogenous, mobile genetic element inserted into the chromosomes of P. syringae strains. It was also predicted that the tox islands integrated site-specifically into the homologous sites of the chromosomes of ACT and PHA in the same direction, respectively, wherein 34 common gene coding sequences (CDSs) existed. Furthermore, at the left end of the tox islands were three CDSs, which encoded polypeptides and had similarities to the members of the tyrosine recombinase family, suggesting that these putative site-specific recombinases were involved in the recent horizontal transfer of tox islands. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users.     

Mutational analysis of wheat (<Emphasis Type="Italic">Triticum aestivum</Emphasis> L.) nucleotide pyrophosphatase/phosphodiesterase shows the role of six amino acids in the catalytic mechanism

Nucleotide pyrophosphatases/phosphodiesterases (NPPs, PF01663) release nucleoside 5′-monophosphates from a wide range of nucleotide substrates. Only very recently, the first plant members of the NPP family were characterised (Joye et al. J Cereal Sci 51: 326–336, 2010), and little is known about their substrate-specifying residues. We elucidated the role of six amino acid residues of the recently identified and characterised Triticum aestivum L. NPP (Joye et al. J Cereal Sci 51: 326–336, 2010). Substitution of the highly conserved catalytic Thr132 into Ser or Ala completely abolished enzyme activity. Mutation of a highly conserved His255 residue into an apolar Ala suprisingly increased enzyme activity against most phosphodiester substrates. Four other residues moderately to highly conserved over NPPs of different organisms were studied as well. Mutation of the Asn153, Asn165 and Glu199 into an Arg, Ser and Asp residue, respectively, increased the relative enzyme activity against p-nitrophenyl phosphate. Furthermore, mutation of Phe194 into Ser increased the relative enzyme activity against adenosine 5′-monophosphate-containing substrates, although the overall enzyme activity of this mutant enzyme decreased. We conclude that the structural requirements and the conservation of the amino acids of the catalytic site of TaNPPr and, by extension, probably of all NPPs, are very stringent.     

1H, 13C and 15N NMR assignments of the C1A and C1B subdomains of PKC-delta

The Protein Kinase C family of enzymes is a group of serine/threonine kinases that play central roles in cell-cycle regulation, development and cancer. A key step in the activation of PKC is translocation to membranes and binding of membrane-associated activators including diacylglycerol (DAG). Interaction of novel and conventional isotypes of PKC with DAG and phorbol esters occurs through the two C1 regulatory domains (C1A and C1B), which exhibit distinct ligand binding selectivity that likely controls enzyme activation by different co-activators. PKC has also been implicated in physiological responses to alcohol consumption and it has been proposed that PKCα (Slater et al. J Biol Chem 272(10):6167–6173, 1997; Slater et al. Biochemistry 43(23):7601–7609, 2004), PKCε (Das et al. Biochem J 421(3):405–413, 2009) and PKCδ (Das et al. J Biol Chem 279(36):37964–37972, 2004; Das et al. Protein Sci 15(9):2107–2119, 2006) contain specific alcohol-binding sites in their C1 domains. We are interested in understanding how ethanol affects signal transduction processes through its affects on the structure and function of the C1 domains of PKC. Here we present the ¹H, ¹⁵N and ¹³C NMR chemical shift assignments for the Rattus norvegicus PKCδ C1A and C1B proteins.     

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.     

Evaluation of Antibody-Dependent Enhancement of SARS-CoV Infection in Rhesus Macaques Immunized with an Inactivated SARS-CoV Vaccine

正Dear Editor,In 2003,severe acute respiratory syndrome coronavirus(SARS-CoV)emerged in Guangdong Province,China,infected more than 8000 individuals,and resulted in a 10%mortality rate(Rota et al.2003).Later,in 2012,a novel CoV,Middle East respiratory syndrome coronavirus(MERS-CoV),was isolated from the sputum of a man in Saudi Arabia(Perl et al.2014).Notably,MERS-CoV     

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.