Vasorelaxin: A Novel Arterial Smooth Muscle-Relaxing Eicosapeptide from the Skin Secretion of the Chinese Piebald Odorous Frog (Odorrana schmackeri)

The defensive skin secretions of amphibians are a rich resource for the discovery of novel, bioactive peptides. Here we report the identification of a novel vascular smooth muscle-relaxing peptide, named vasorelaxin, from the skin secretion of the Chinese piebald odorous frog, Odorrana schmackeri. Vasorelaxin consists of 20 amino acid residues, SRVVKCSGFRPGSPDSREFC, with a disulfide-bridge between Cys-6 and Cys-20. The structure of its biosynthetic precursor was deduced from cloned skin cDNA and consists of 67 amino acid residues encoding a single copy of vasorelaxin (vasorelaxin, accession number: HE860494). Synthetic vasorelaxin caused a profound relaxation of rat arterial smooth muscle with an EC50 of 6.76 nM.

Standardization of diagnostic biomarker concentrations in urine; the hematuria caveat

Sensitive and specific urinary biomarkers can improve patient outcomes in many diseases through informing early diagnosis. Unfortunately, to date, the accuracy and translation of diagnostic urinary biomarkers into clinical practice has been disappointing. We believe this may be due to inappropriate standardization of diagnostic urinary biomarkers. Our objective was therefore to characterize the effects of standardizing urinary levels of IL-6, IL-8, and VEGF using the commonly applied standards namely urinary creatinine, osmolarity and protein. First, we report results based on the biomarker levels measured in 120 hematuric patients, 80 with pathologically confirmed bladder cancer, 27 with confounding pathologies and 13 in whom no underlying cause for their hematuria was identified, designated “no diagnosis”. Protein levels were related to final diagnostic categories (p = 0.022, ANOVA). Osmolarity (mean = 529 mOsm; median = 528 mOsm) was normally distributed, while creatinine (mean = 10163 µmol/l, median = 9350 µmol/l) and protein (0.3297, 0.1155 mg/ml) distributions were not. When we compared AUROCs for IL-6, IL-8 and VEGF levels, we found that protein standardized levels consistently resulted in the lowest AUROCs. The latter suggests that protein standardization attenuates the “true” differences in biomarker levels across controls and bladder cancer samples. Second, in 72 hematuric patients; 48 bladder cancer and 24 controls, in whom urine samples had been collected on recruitment and at follow-up (median = 11 (1 to 20 months)), we demonstrate that protein levels were approximately 24% lower at follow-up (Bland Altman plots). There was an association between differences in individual biomarkers and differences in protein levels over time, particularly in control patients.

Living is Information Processing: From Molecules to Global Systems

We extend the concept that life is an informational phenomenon, at every level of organisation, from molecules to the global ecological system. According to this thesis: (a) living is information processing, in which memory is maintained by both molecular states and ecological states as well as the more obvious nucleic acid coding; (b) this information processing has one overall function-to perpetuate itself; and (c) the processing method is filtration (cognition) of, and synthesis of, information at lower levels to appear at higher levels in complex systems (emergence). We show how information patterns, are united by the creation of mutual context, generating persistent consequences, to result in 'functional information'. This constructive process forms arbitrarily large complexes of information, the combined effects of which include the functions of life. Molecules and simple organisms have already been measured in terms of functional information content; we show how quantification may be extended to each level of organisation up to the ecological. In terms of a computer analogy, life is both the data and the program and its biochemical structure is the way the information is embodied. This idea supports the seamless integration of life at all scales with the physical universe. The innovation reported here is essentially to integrate these ideas, basing information on the 'general definition' of information, rather than simply the statistics of information, thereby explaining how functional information operates throughout life. © 2013 Springer Science+Business Media Dordrecht.

Can Certain Genotypes Predispose to Poor Asthma Control in Children? A Pharmacogenetic Study of 9 Candiate Genes in Children with Difficult Asthma

Objective: We tested the hypothesis that patients with difficult asthma have an increased frequency of certain genotypes that predispose them to asthma exacerbations and poor asthma control.

Methods: A total of 180 Caucasian children with confirmed asthma diagnosis were selected from two phenotypic groups; difficult (n = 112) versus mild/moderate asthma (n = 68) groups. All patients were screened for 19 polymorphisms in 9 candidate genes to evaluate their association with difficult asthma.

Key Results: The results indicated that LTA4H A-9188.G, TNFa G-308.A and IL-4Ra A1727.G polymorphisms were significantly associated with the development of difficult asthma in paediatric patients (p,0.001, p = 0.019 and p = 0.037, respectively). Haplotype analysis also revealed two haplotypes (ATA haplotype of IL-4Ra A1199.C, IL-4Ra T1570.C and IL- 4Ra A1727.G and CA haplotype of TNFa C-863.A and TNFa G-308.A polymorphisms) which were significantly associated with difficult asthma in children (p = 0.04 and p = 0.018, respectively).

Conclusions and Clinical Relevance: The study revealed multiple SNPs and haplotypes in LTA4H, TNFa and IL4-Ra genes which constitute risk factors for the development of difficult asthma in children. Of particular interest is the LTA4H A- 9188.G polymorphism which has been reported, for the first time, to have strong association with severe asthma in children. Our results suggest that screening for patients with this genetic marker could help characterise the heterogeneity of responses to leukotriene-modifying medications and, hence, facilitate targeting these therapies to the subset of patients who are most likely to gain benefit. ©2013 Almomani et al.

A Superfamily of Actin-Binding Proteins at the Actin-Membrane Nexus of Higher Plants

Complex animals use a wide variety of adaptor proteins to produce specialized sites of interaction between actin and membranes. Plants do not have these protein families, yet actin-membrane interactions within plant cells are critical for the positioning of subcellular compartments, for coordinating intercellular communication, and for membrane deformation [1]. Novel factors are therefore likely to provide interfaces at actin-membrane contacts in plants, but their identity has remained obscure. Here we identify the plantspecific Networked (NET) superfamily of actin-binding proteins, members of which localize to the actin cytoskeleton and specify different membrane compartments. The founding member of the NET superfamily, NET1A, is anchored at the plasma membrane and predominates at cell junctions, the plasmodesmata. NET1A binds directly to actin filaments via a novel actin-binding domain that defines a superfamily of thirteen Arabidopsis proteins divided into four distinct phylogenetic clades. Members of other clades identify interactions at the tonoplast, nuclear membrane, and pollen tube plasma membrane, emphasizing the role of this superfamily in mediating actin-membrane interactions.

Differences in Mucosal Gene Expression in the Colon of Two Inbred Mouse Strains after Colonization with Commensal Gut Bacteria

The host genotype has been proposed to contribute to individually composed bacterial communities in the gut. To provide deeper insight into interactions between gut bacteria and host, we associated germ-free C3H and C57BL/10 mice with intestinal bacteria from a C57BL/10 donor mouse. Analysis of microbiota similarity between the animals with denaturing gradient gel electrophoresis revealed the development of a mouse strain-specific microbiota. Microarray-based gene expression analysis in the colonic mucosa identified 202 genes whose expression differed significantly by a factor of more than 2. Application of bioinformatics tools demonstrated that functional terms including signaling/secretion, lipid degradation/catabolism, guanine nucleotide/guanylate binding and immune response were significantly enriched in differentially expressed genes. We had a closer look at the 56 genes with expression differences of more than 4 and observed a higher expression in C57BL/10 mice of the genes coding for Tlr1 and Ang4 which are involved in the recognition and response to gut bacteria. A higher expression of Pla2g2a was detected in C3H mice. In addition, a number of interferon-inducible genes were higher expressed in C3H than in C57BL/10 mice including Gbp1, Mal, Oasl2, Ifi202b, Rtp4, Ly6g6c, Ifi27l2a, Usp18, Ifit1, Ifi44, and Ly6g indicating that interferons may play an essential role in microbiota regulation. However, genes coding for interferons, their receptors, factors involved in interferon expression regulation or signaling pathways were not differentially expressed between the two mouse strains. Taken together, our study confirms that the host genotype is involved in the establishment of host-specific bacterial communities in the gut. Based on expression differences after colonization with the same bacterial inoculum, we propose that Pla2g2a and interferon-dependent genes may contribute to this phenomenon.

Are there species smaller than 1 mm?

The rapid advance in genetic sequencing technologies has provided an unprecedented amount of data on the biodiversity of meiofauna. It was hoped that these data would allow the identification and counting of species, distinguished as tight clusters of similar genomes. Surprisingly, this appears not to be the case. Here, we begin a theoretical discussion of this phenomenon, drawing on an individual-based ecological model to inform our arguments. The determining factor in the emergence (or not) of distinguishable genetic clusters in the model is the product of population size with mutation rate—a measure of the adaptability of the population as a whole. This result suggests that indeed one should not expect to observe clearly distinguishable species groupings in data gathered from ultrasequencing of meiofauna.

Predicting Functional Recovery after Acute Ankle Sprain

INTRODUCTION:Ankle sprains are among the most common acute musculoskeletal conditions presenting to primary care. Their clinical course is variable but there are limited recommendations on prognostic factors. Our primary aim was to identify clinical predictors of short and medium term functional recovery after ankle sprain.
METHODS:A secondary analysis of data from adult participants (N = 85) with an acute ankle sprain, enrolled in a randomized controlled trial was undertaken. The predictive value of variables (age, BMI, gender, injury mechanism, previous injury, weight-bearing status, medial joint line pain, pain during weight-bearing dorsiflexion and lateral hop test) recorded at baseline and at 4 weeks post injury were investigated for their prognostic ability. Recovery was determined from measures of subjective ankle function at short (4 weeks) and medium term (4 months) follow ups. Multivariate stepwise linear regression analyses were undertaken to evaluate the association between the aforementioned variables and functional recovery.
RESULTS:Greater age, greater injury grade and weight-bearing status at baseline were associated with lower function at 4 weeks post injury (p<0.01; adjusted R square=0.34). Greater age, weight-bearing status at baseline and non-inversion injury mechanisms were associated with lower function at 4 months (p<0.01; adjusted R square=0.20). Pain on medial palpation and pain on dorsiflexion at 4 weeks were the most valuable prognostic indicators of function at 4 months (p< 0.01; adjusted R square=0.49).
CONCLUSION:The results of the present study provide further evidence that ankle sprains have a variable clinical course. Age, injury grade, mechanism and weight-bearing status at baseline provide some prognostic information for short and medium term recovery. Clinical assessment variables at 4 weeks were the strongest predictors of recovery, explaining 50% of the variance in ankle function at 4 months. Further prospective research is required to highlight the factors that best inform the expected convalescent period, and risk of recurrence.

Water-hydrophobic compound interactions with the microbial cell

The structural interactions of biological macromolecules, their biochemical activities and, ultimately, the metabolic function of cellular systems are dependent upon weak inter- and intra-molecular forces such as hydrogen bonds, Van der Waals forces, and the hydrophobic effect. Water molecules, and those of hydrophobic substances such as hydrocarbons, can take part in and/or modify these interactions and thereby determine the operational and structural stability of the microbial cell and its macromolecular systems. We explain how the cytosol, plasma membrane and the extracellular solution form a material and energetic continuum; and discuss the behavior of hydrophobic substances of extracellular origin as they migrate into the plasma membrane and into the cell's interior. The adverse effects of substances with a log P octanol-water =2, that partition into the hydrophobic domains of biological macromolecules, are discussed in relation to microbial cell function; and we speculate whether the cellular stress that they induce is symmetrical or asymmetrical in nature. In the context of the microbial environment, we take a situational-functional approach to consider how hydrophobic stressors interact with the microbial cell, and what types of evasion tactics microbes can employ to minimize their inhibitory activities. Finally, we discuss the ecological implications of hydrocarbon-induced cellular stress for microbial systems.

Effects of oscillatory flow on fertilization in the green sea urchin Strongylocentrotus droebachiensis

Broadcast spawning invertebrates that live in shallow, high-energy coastal habitats are subjected to oscillatory water motion that creates unsteady flow fields above the surface of animals. The frequency of the oscillatory fluctuations is driven by the wave period, which will influence the stability of local flow structures and may affect fertilization processes. Using an oscillatory water tunnel, we quantified the percentage of eggs fertilized on or near spawning green sea urchins, Strongylocentrotus droebachiensis. Eggs were sampled in the water column, wake eddy, substratum and aboral surface under a range of different periods (T = 4.5 – 12.7 s) and velocities of oscillatory flow. The root-mean-square wave velocity (rms(uw)) was a good predictor of fertilization in oscillatory flow, although the root-mean-square of total velocity (rms(u)), which incorporates all the components of flow (current, wave and turbulence), also provided significant predictions. The percentage of eggs fertilized varied between 50 – 85% at low flows (rms(uw) < 0.02 m s-1), depending on the location sampled, but declined to below 10% for most locations at higher rms(uw). The water column was an important location for fertilization with a relative contribution greater than that of the aboral surface, especially at medium and high rms(uw) categories. We conclude that gametes can be successfully fertilized on or near the parent under a range of oscillatory flow conditions.

Cheetahs, Acinonyx jubatus, balance turn capacity with pace when chasing prey

Predator–prey interactions are fundamental in the evolution and structure of ecological communities. Our understanding, however, of the strategies used in pursuit and evasion remains limited. Here, we report on the hunting dynamics of the world's fastest land animal, the cheetah, Acinonyx jubatus. Using miniaturized data loggers, we recorded fine-scale movement, speed and acceleration of free-ranging cheetahs to measure how hunting dynamics relate to chasing different sized prey. Cheetahs attained hunting speeds of up to 18.94 m s-1 and accelerated up to 7.5 m s-2 with greatest angular velocities achieved during the terminal phase of the hunt. The interplay between forward and lateral acceleration during chases showed that the total forces involved in speed changes and turning were approximately constant over time but varied with prey type. Thus, rather than a simple maximum speed chase, cheetahs first accelerate to decrease the distance to their prey, before reducing speed 5–8 s from the end of the hunt, so as to facilitate rapid turns to match prey escape tactics, varying the precise strategy according to prey species. Predator and prey thus pit a fine balance of speed against manoeuvring capability in a race for survival.

Food miles or carbon emissions? Exploring labeling preference for food transport footprint with a stated choice study

The ecological footprint of food transport can be communicated using carbon dioxide emissions (CO2 label) or by providing information about both the length of time and the mileage travelled (food miles label). We use stated choice data to estimate conventional unobserved taste heterogeneity models and extend them to a specification that also addresses attribute nonattendance. The implied posterior distributions of the marginal willingness to pay values are compared graphically and are used in validation regressions. We find strong bimodality of taste distribution as the emerging feature, with different groups of subjects having low and high valuations for these labels. The best fitting model shows that CO2 and food miles valuations are much correlated. CO2 valuations can be high even for those respondents expressing low valuations for food miles. However, the reverse is not true. Taken together, the results suggest that consumers tend to value the CO2 label at least as much and sometimes more than the food miles label.

Use of the γ-H2AX Assay to Investigate DNA Repair Dynamics Following Multiple Radiation Exposures

Radiation therapy is one of the most common and effective strategies used to treat cancer. The irradiation is usually performed with a fractionated scheme, where the dose required to kill tumour cells is given in several sessions, spaced by specific time intervals, to allow healthy tissue recovery. In this work, we examined the DNA repair dynamics of cells exposed to radiation delivered in fractions, by assessing the response of histone-2AX (H2AX) phosphorylation (γ-H2AX), a marker of DNA double strand breaks. γ-H2AX foci induction and disappearance were monitored following split dose irradiation experiments in which time interval between exposure and dose were varied. Experimental data have been coupled to an analytical theoretical model, in order to quantify key parameters involved in the foci induction process. Induction of γ-H2AX foci was found to be affected by the initial radiation exposure with a smaller number of foci induced by subsequent exposures. This was compared to chromatin relaxation and cell survival. The time needed for full recovery of γ-H2AX foci induction was quantified (12 hours) and the 1:1 relationship between radiation induced DNA double strand breaks and foci numbers was critically assessed in the multiple irradiation scenarios.

Historical data reveal power-law dispersal patterns of invasive aquatic species

Understanding how invasive species spread is of particular concern in the current era of globalisation and rapid environmental change. The occurrence of super-diffusive movements within the context of Lévy flights has been discussed with respect to particle physics, human movements, microzooplankton, disease spread in global epidemiology and animal foraging behaviour. Super-diffusive movements provide a theoretical explanation for the rapid spread of organisms and disease, but their applicability to empirical data on the historic spread of organisms has rarely been tested. This study focuses on the role of long-distance dispersal in the invasion dynamics of aquatic invasive species across three contrasting areas and spatial scales: open ocean (north-east Atlantic), enclosed sea (Mediterranean) and an island environment (Ireland). Study species included five freshwater plant species, Azolla filiculoides, Elodea canadensis, Lagarosiphon major, Elodea nuttallii and Lemna minuta; and ten species of marine algae, Asparagopsis armata, Antithamnionella elegans, Antithamnionella ternifolia, Codium fragile, Colpomenia peregrina, Caulerpa taxifolia, Dasysiphonia sp., Sargassum muticum, Undaria pinnatifida and Womersleyella setacea. A simulation model is constructed to show the validity of using historical data to reconstruct dispersal kernels. Lévy movement patterns similar to those previously observed in humans and wild animals are evident in the re-constructed dispersal pattern of invasive aquatic species. Such patterns may be widespread among invasive species and could be exacerbated by further development of trade networks, human travel and environmental change. These findings have implications for our ability to predict and manage future invasions, and improve our understanding of the potential for spread of organisms including infectious diseases, plant pests and genetically modified organisms.