Parallel processing and image analysis in the eyes of mantis shrimps

The compound eyes of mantis shrimps, a group of tropical marine crustaceans, incorporate principles of serial and parallel processing of visual information that may be applicable to artificial imaging systems. Their eyes include numerous specializations for analysis of the spectral and polarizational properties of light, and include more photoreceptor classes for analysis of ultraviolet light, color, and polarization than occur in any other known visual system. This is possible because receptors in different regions of the eye are anatomically diverse and incorporate unusual structural features, such as spectral filters, not seen in other compound eyes. Unlike eyes of most other animals, eyes of mantis shrimps must move to acquire some types of visual information and to integrate color and polarization with spatial vision. Information leaving the retina appears to be processed into numerous parallel data streams leading into the central nervous system, greatly reducing the analytical requirements at higher levels. Many of these unusual features of mantis shrimp vision may inspire new sensor designs for machine vision.     

Synthesis and antimicrobial activity of copper(II) and manganese(II) α,ω-dicarboxylate complexes

Copper(II) ,-dicarboxylate complexes of general formulae, [Cu(O₂C(CH₂)_nCO₂)]·xH₂O, [Cu(O₂C(CH₂)_nCO₂) (phen)₂]·xH₂O and [Cu(O₂C(CH₂)_nCO₂)(bipy)_y]·xH₂O (n=1–8; y=1, 2; phen = 1,10-phenanthroline; bipy = 2,2-bipyridine) were synthesised. These copper complexes, some related manganese(II) complexes and the metal-free ligands were screened in vitro for their ability to inhibit the growth of Candida albicans. Metal-free 1,10-phenanthroline and all of the copper(II) and manganese(II) phenanthroline complexes were potent growth inhibitors, with only one bipyridine complex, [Cu(O₂C(CH₂)CO₂)(bipy)₂]·2H₂O, having moderate activity. The remaining substances were effectively inactive. Complexes which were active against C. albicans also proved effective against C. glabrata, C. tropicalis and C. kreusi with the manganese complexes retaining superior activity. For the phenanthroline complexes the active drug species is thought to be the dication [M(phen)₂(H₂O)_n]²⁺ (M = Cu, Mn). Escherichia coli and Staphylococcus aureus were resistant to all of the metal complexes and also to metal-free 1,10-phenanthroline. Only the copper phenanthroline complexes showed intermediate activity against Pseudomonas aeruginosa.     

Species–energy relationship in the deep sea: a test using the Quaternary fossil record

Little is known about the processes regulating species richness in deep‐sea communities. Here we take advantage of natural experiments involving climate change to test whether predictions of the species–energy hypothesis hold in the deep sea. In addition, we test for the relationship between temperature and species richness predicted by a recent model based on biochemical kinetics of metabolism. Using the deep‐sea fossil record of benthic foraminifera and statistical meta‐analyses of temperature‐richness and productivity‐richness relationships in 10 deep‐sea cores, we show that temperature but not productivity is a significant predictor of species richness over the past c. 130 000 years. Our results not only show that the temperature‐richness relationship in the deep‐sea is remarkably similar to that found in terrestrial and shallow marine habitats, but also that species richness tracks temperature change over geological time, at least on scales of c. 100 000 years. Thus, predicting biotic response to global climate change in the deep sea would require better understanding of how temperature regulates the occurrences and geographical ranges of species.     

Decreased lower limb muscle recruitment contributes to the inability of older adults to recover with a single step following a forward loss of balance

In response to a balance disturbance, older individuals often require multiple steps to prevent a fall. Reliance on multiple steps to recover balance is predictive of a future fall, so studies should determine the mechanisms underlying differences between older adults who can and cannot recover balance with a single step. This study compared neural activation parameters of the major leg muscles during balance recovery from a sudden forward loss of balance in older individuals capable of recovering with a single step and those who required multiple steps to regain balance. Eighty-one healthy, community dwelling adults aged 70 ± 3 participated. Loss of balance was induced by releasing participants from a static forward lean. Participants performed four trials at three initial lean magnitudes and were subsequently classified as single or multiple steppers. Although step length was shorter in multiple compared to single steppers (F = 9.64; p = 0.02), no significant differences were found between groups in EMG onset time in the step limb muscles (F = 0.033–0.769; p = 0.478–0.967). However, peak EMG normalised to values obtained during maximal voluntary contraction was significantly higher in single steppers in 6 of the 7 stepping limb muscles (F = 1.054–4.167; p = 0.045–0.024). These data suggest that compared to multiple steppers, single steppers recruit a larger proportion of the available motor unit pool during balance recovery. Thus, modulation of EMG amplitude plays a larger role in balance recovery than EMG timing in this context.     

The Association of Visceral Adiposity with Cardiovascular Events in Patients with Peripheral Artery Disease

Background

Previous studies have suggested that patients with peripheral artery disease (PAD) suffer from a high incidence of cardiovascular events (CVE). Visceral adiposity has been implicated in promoting CVEs. This study aimed to assess the association of relative visceral adipose volume with incident cardiovascular events in patients with peripheral artery disease.

Methods

This was a prospective cohort study including 260 patients with PAD who presented between 2003 and 2012. Cases were patients with diagnosed PAD including symptomatic lower limb athero-thrombosis and asymptomatic abdominal aortic aneurysm. All patients underwent computed tomography angiography (CTA). Abdominal visceral to total adipose volume ratio (relative visceral adipose volume) was estimated from CTAs using a previously validated workstation protocol. Cardiovascular risk factors were recorded at entry. The association of visceral adiposity with major CVEs (death, non-fatal myocardial infarction or stroke) was examined using Kaplan Meier and Cox proportional hazard analyses.

Results

A total of 92 major CVEs were recorded in 76 patients during a median follow-up of 2.8 (IQR 1.2 to 4.8) years, including myocardial infarction (n = 26), stroke (n = 10) and death (n = 56). At 3 years the incidence of major CVEs stratified by relative visceral adipose volume quartiles were 15% [Quartile (Q) 1], 17% (Q2), 11% (Q3) and 15% (Q4) (P = 0.517). Relative visceral adipose volume was not associated with major CVEs after adjustment for other risk factors.

Conclusion

This study suggests that visceral adiposity does not play a central role in the predisposition for major CVEs in patients with PAD.     

P2X purinergic receptor-mediated ionic current in cardiac myocytes of calsequestrin model of cardiomyopathy: implications for the treatment of heart failure

P2X purinergic receptors, activated by extracellular ATP, mediate a number of cardiac cellular effects and may be important under pathophysiological conditions. The objective of the present study was to characterize the P2X receptor-mediated ionic current and determine its role in heart failure using the calsequestrin (CSQ) model of cardiomyopathy. Membrane currents under voltage clamp were determined in myocytes from both wild-type (WT) and CSQ mice. The P2X agonist 2-methylthio-ATP (2-meSATP) induced an inward current that was greater in magnitude in CSQ than in WT ventricular cells. The novel agonist, MRS-2339, an N-methanocarba derivative of 2-chloro-AMP relatively resistant to nucleotidase, induced a current in the CSQ myocyte similar to that by 2-meSATP. When administered via a miniosmotic pump (Alzet), it significantly increased longevity compared with vehicle-injected mice (log rank test, P = 0.02). The improvement in survival was associated with decreases in the heart weight-to-body weight ratio and in cardiac myocyte cross-sectional area [MRS-2339-treated mice: 281 +/- 15.4 (SE) mum(2), n = 6 mice vs. vehicle-treated mice: 358 +/- 27.8 mum(2), n = 6 mice, P < 0.05]. MRS-2339 had no vasodilator effect in mouse aorta ring preparations, indicating that its salutary effect in heart failure is not because of any vascular unloading. The cardiac P2X current is upregulated in the CSQ heart failure myocytes. Chronic administration of a nucleotidase-resistant agonist confers a beneficial effect in the CSQ model of heart failure, apparently via an activation of the cardiac P2X receptor. Cardiac P2X receptors represent a novel and potentially important therapeutic target for the treatment of heart failure.     

Microcalorimetry of interaction of dihydro-imidazo-phenanthridinium (DIP)-based compounds with duplex DNA

Isothermal titration (ITC) and differential scanning calorimetry (DSC) have been used to screen the binding thermodynamics of a family of DNA intercalators based on the dihydro-imidazo-phenanthridinium (DIP) framework. All members of this DIP-based ligand family bind to both genomic (calf thymus and/or salmon testes) and a synthetic dodecamer d(CGCGAATTCGCG) duplex DNA with broadly similar affinities regardless of side chain size or functionality. Viscosity measurements confirm that binding satisfies standard criteria for intercalation. Binding is exothermic but with an additional favourable positive entropy contribution in most cases at 25 degrees C, although a significant negative heat capacity effect (DeltaC(p)) means that both DeltaH(0) and DeltaS(0) decrease with increasing temperature. DIP-ligand binding to DNA also shows significant entropy-enthalpy compensation effects that are now almost standard in such situations, probably reflecting the conformational flexibility of macromolecular systems involving a multiplicity of weak non-covalent interactions. This ability to vary side chain functionality without compromising DNA binding suggests that the DIP framework should be a promising basis for more adventurous chemistry at the DNA level.     

Sequencing and analysis of an Irish human genome

Background

Recent studies generating complete human sequences from Asian, African and European subgroups have revealed population-specific variation and disease susceptibility loci. Here, choosing a DNA sample from a population of interest due to its relative geographical isolation and genetic impact on further populations, we extend the above studies through the generation of 11-fold coverage of the first Irish human genome sequence.

Results

Using sequence data from a branch of the European ancestral tree as yet unsequenced, we identify variants that may be specific to this population. Through comparisons with HapMap and previous genetic association studies, we identified novel disease-associated variants, including a novel nonsense variant putatively associated with inflammatory bowel disease. We describe a novel method for improving SNP calling accuracy at low genome coverage using haplotype information. This analysis has implications for future re-sequencing studies and validates the imputation of Irish haplotypes using data from the current Human Genome Diversity Cell Line Panel (HGDP-CEPH). Finally, we identify gene duplication events as constituting significant targets of recent positive selection in the human lineage.

Conclusions

Our findings show that there remains utility in generating whole genome sequences to illustrate both general principles and reveal specific instances of human biology. With increasing access to low cost sequencing we would predict that even armed with the resources of a small research group a number of similar initiatives geared towards answering specific biological questions will emerge.     

Protein kinase C potentiates corticotropin releasing factor stimulated cyclic AMP in pituitary

The hypophysiotrophic hormone corticotropin releasing factor (CRF) stimulates the anterior pituitary corticotroph to export stress hormones such as adrenocorticotrophic hormone (ACTH). In rat anterior pituitary cells, CRF-induced elevation of cyclic AMP was profoundly potentiated (by an order of magnitude) by stimulators of protein kinase C. This effect occurred within minutes, was concentration dependent, and exhibited the appropriate pharmacological specificity to attribute the effects to protein kinase C. Phorbol myristate acetate (PMA), phorbol dibutyrate (PDB) and teleocidin were active with appropriate EC50's, while 4-alpha-PMA was inactive. PMA and PDB were also ACTH secretagogues in their own right. We suggest that protein kinase C can modulate CRF receptor coupling to the adenylate cyclase holoenzyme in anterior pituitary cells.