How venom pore placement may influence puncture performance in snake fangs.

When designing experimental studies, it is important to understand the biological context of the question being asked. For example, many biological puncture experiments embed the puncture tool to a standardized depth based on a percentage of the total tool length, to compare the performance between tools. However, this may not always be biologically relevant to the question being asked. To understand how definitions of penetration depth may influence comparative results, we performed puncture experiments on a series of venomous snake fangs using the venom pore location as a functionally relevant depth standard. After exploring variation in pore placement across snake phylogeny, we compared the work expended during puncture experiments across a set of snake fangs using various depth standards: puncture initiation, penetration to a series of depths defined by the venom pore and penetration to 15% of fang length. Contrary to our hypothesis, we found almost no pattern in pore placement between clades, dietary groups or venom toxicity. Rank correlation statistics of our experimental energetics results showed no difference in the broad comparison of fangs when different puncture depth standards were used. However, pairwise comparisons between fangs showed major shifts in significance patterns between the different depth standards used. These results imply that the interpretation of experimental puncture data will heavily depend upon which depth standard is used during the experiments. Our results illustrate the importance of understanding the biological context of the question being addressed when designing comparative experiments.

Spectrum of ocular disease in children aged between 0 and 3 years at an Australian paediatric tertiary hospital.

BACKGROUND: Childhood ocular disease can be a significant health burden to the child, family and society. Previous studies have examined the spectrum of paediatric ocular disease presenting to tertiary hospitals; however, these studies have broader age ranges, smaller sample sizes, and are largely based in developing countries. This study aims to assess the spectrum of ocular disease in the first 3 years of life presenting to the eye department of an Australian tertiary paediatric hospital. METHODS: The records of 3337 children who had their initial presentation at the eye clinic between the age of 0 and 36 months were reviewed, spanning 6.5 years from 1st July 2012 to 31st December 2018. RESULTS: The most common primary diagnoses overall were strabismic amblyopia (6.0%), retinopathy of prematurity (5.0%) and nasolacrimal duct obstruction (4.5%). Bilateral visual impairment was more common in younger children, while unilateral visual impairment was more common in older children. The proportion of all children presenting with visual impairment was 10.3%, with 5.7% of all children presenting with bilateral visual impairment and 4.6% presenting with unilateral visual impairment. In children with visual impairment, the most common sites of primary abnormality were lens (21.4%), retina (17.3%), and cerebral and visual pathways (12.1%). The most common primary diagnoses in children with visual impairment were cataract (21.4%), strabismic amblyopia (9.3%) and retinoblastoma (6.5%). CONCLUSIONS: The spectrum of eye disease and vision impairment presenting in the first 3 years of life facilitates health care planning, greater community education about vision impairment and importance of early intervention, and guidance for appropriate resource allocation. Health systems can apply these findings to aid in early identification and intervention to reduce preventable blindness and institute appropriate rehabilitation services.

Scaling and Structural Properties of Juvenile Bull Kelp (Nereocystis luetkeana).

Bull kelp (Nereocystis luetkeana), the only canopy-forming kelp in the Salish Sea, provides primary production in the nearshore subtidal environment and serves as an important habitat for economically and ecologically important species. An annual species, each year juvenile bull kelp sporophytes must grow from the hydrodynamically more benign benthos to the water column, where they experience substantial drag at the surface. Because of the differences in morphology and ecology across life stages, and the fact that previous work has focused mainly on adult bull kelp, we tested whether morphology and structural properties change with stipe length, investigating scaling of both juvenile (stipe length < 40 cm) and mature (stipe length > 40 cm) kelp, and testing how juvenile stipes fail. Juvenile bull kelp grow proportionally (isometric growth) when young, but lengthen more quickly than would be predicted by bulb size (negative allometry) at maturity. Based on our data, the predicted breakpoint between isometric and allometric growth occurred at about 33 cm, likely approximately one to two weeks of growth. Cross-sectional area of the stipe, force to failure, work to failure, and stiffness (Young's modulus) all grow more slowly than would be predicted based on length, while maximum stress and toughness increase more quickly than predicted. There is no change in extensibility over the size range we tested, suggesting that this material property does not change with stipe length. The differences in biomechanics between juvenile and adult kelp are likely a response to the varied hydrodynamic environments experienced during the annual life cycle, which highlights the importance of studying organisms across life stages.

Stabbing Spines: A review of the Biomechanics and Evolution of Defensive Spines.

Spines are ubiquitous in both plants and animals, and while most spines were likely originally used for defense, over time many have been modified in a variety of ways. Here we take an integrative approach to review the form, function, and evolution of spines as a defensive strategy in order to make new connections between physical mechanisms and functional behavior. While this review focuses on spines in mammals, we reference and draw ideas from the literature on spines in other taxa, including plants. We begin by exploring the biomechanics of defensive spines, their varied functions, and nondefensive modifications. We pay particular attention to the mechanics involved in passive puncture and the ways organisms have overcome limitations associated with the low energy input. We then focus on the ecological, physiological, and behavioral factors that promote the evolution of spiny defenses, including predator- and habitat-mediated hypotheses. While there is considerable evidence to support both, studies have generally found that (1) defensive spines are usually effective against one class of attacker (e.g., larger predators) but ineffective against or even facilitate predation by others and (2) species that are more visible or exposed to predators are under much stronger selection to evolve defensive spines or some other robust defense. What type of defensive morphology that evolves, however, is less predictable and probably strongly dependent on both the dominant source of predation and the habitat structure of the organism (e.g., arboreal, terrestrial, and fossorial). We then explore traits that often are correlated with defensive spines and armor, potentially forming armor syndromes, suites of traits that evolve together with body armor in a correlated fashion. In mammals, these include aposematic warning coloration, locomotion style, diet, metabolic rate, and relative brain size. Finally, we encourage integration of mechanistic, behavioral, and evolutionary studies of defensive spines and suggest future avenues of research in the biomechanics, evolution, and behavior of spines and spiny organisms.

The Materials of Mastication: Material Science of the Humble Tooth.

Dental functional morphology, as a field, represents a confluence of materials science and biology. Modern methods in materials testing have been influential in driving the understanding of dental tissues and tooth functionality. Here we present a review of dental enamel, the outermost tissue of teeth. Enamel is the hardest biological tissue and exhibits remarkable resilience even when faced with a variety of mechanical threats. In the light of recent work, we progress the argument that the risk of mechanical degradation across multiple scales exhibits a strong and continued selection pressure on the structural organization of enamel. The hierarchical nature of enamel structure presents a range of scale-dependent toughening mechanisms and provides a means by which natural selection can drive the specialization of this tissue from nanoscale reorganization to whole tooth morphology. There has been much learnt about the biomechanics of enamel recently, yet our understanding of the taxonomic diversity of this tissue is still lacking and may form an interesting avenue for future research.

Taking a Stab at Quantifying the Energetics of Biological Puncture.

An organism's ability to control the timing and direction of energy flow both within its body and out to the surrounding environment is vital to maintaining proper function. When physically interacting with an external target, the mechanical energy applied by the organism can be transferred to the target as several types of output energy, such as target deformation, target fracture, or as a transfer of momentum. The particular function being performed will dictate which of these results is most adaptive to the organism. Chewing food favors fracture, whereas running favors the transfer of momentum from the appendages to the ground. Here, we explore the relationship between deformation, fracture, and momentum transfer in biological puncture systems. Puncture is a widespread behavior in biology requiring energy transfer into a target to allow fracture and subsequent insertion of the tool. Existing correlations between both tool shape and tool dynamics with puncture success do not account for what energy may be lost due to deformation and momentum transfer in biological systems. Using a combination of pendulum tests and particle tracking velocimetry (PTV), we explored the contributions of fracture, deformation and momentum to puncture events using a gaboon viper fang. Results on unrestrained targets illustrate that momentum transfer between tool and target, controlled by the relative masses of the two, can influence the extent of fracture achieved during high-speed puncture. PTV allowed us to quantify deformation throughout the target during puncture and tease apart how input energy is partitioned between deformation and fracture. The relationship between input energy, target deformation and target fracture is non-linear; increasing impact speed from 2.0 to 2.5 m/s created no further fracture, but did increase deformation while increasing speed to 3.0 m/s allowed an equivalent amount of fracture to be achieved for less overall deformation. These results point to a new framework for examining puncture systems, where the relative resistances to deformation, fracture and target movement dictate where energy flows during impact. Further developing these methods will allow researchers to quantify the energetics of puncture systems in a way that is comparable across a broad range of organisms and connect energy flow within an organism to how that energy is eventually transferred to the environment.

Mechanical properties of harbor seal skin and blubber - a test of anisotropy.

The skin and blubber of marine mammals provides protection from the surrounding environment, whether that be temperature, microbes, or direct mechanical impacts. To understand the ability of harbor seals' (Phoca vitulina) skin and blubber to resist blunt force trauma, we tested the material properties of these tissues. We quantified two mechanical properties of the tissue: tensile strength and tensile stiffness, at two test speeds, three sample orientations, and two age groups. We found significant differences in material properties between test speeds, orientation, and age of the animal, but did not find a large difference with orientation. From this analysis, we conclude that harbor seal skin and blubber should be modeled as an isotropic non-linear elastic material with strain rate dependence. Moreover, we were interested in the effects of freezing on the biomechanical properties. The material was tested fresh and after being frozen for four months. Frozen data revealed an increase in stiffness and strength for the skin (epidermis and dermis), but did not show a conclusive trend in the blubber material properties. While the availability of frozen marine mammal tissue is greater than that of fresh material, frozen tissue of harbor seals, especially the skin, cannot serve as an accurate replacement for testing of fresh material.

Ocular and electrophysiological findings in a patient with Sly syndrome.

BACKGROUND: Sly syndrome (Mucopolysaccharidosis Type VII) is an autosomal recessive metabolic storage disorder due to mutations in the GUSB gene encoding the enzyme beta-glucuronidase. Deficiency of this lysosomal enzyme impairs the body's ability to break down the glycosaminoglycans - dermatan, heparan and chondroitin sulphate. Coarse facial features and macrocephaly are typically seen along with bony and skeletal abnormalities, including joint contractures and short stature. Widespread involvement occurs in many other tissues including cardiopulmonary, gastrointestinal, and neurological systems. In view of the rarity of Sly syndrome the ophthalmic features have not been well described. MATERIALS AND METHODS: Case report of a 16-year-old boy with Sly syndrome with serial OCT, ocular ultrasound, and electroretinogram (ERG). RESULTS: Corneal clouding was present but there was no evidence of glaucoma or optic neuropathy. Despite no clinical evidence of retinopathy, electrophysiology showed reduced photopic and scotopic responses, particularly involving the b-wave which appears progressive. OCT showed normal foveal architecture and normal retinal nerve fiber thickness. CONCLUSION: Corneal clouding was noted in this patient and there is no evidence of glaucoma or optic neuropathy. Although retinopathy has not been previously described in Sly syndrome, the ERG changes in this patient suggest that retinopathy may be a feature of MPS VII.

Morphology does not predict performance: jaw curvature and prey crushing in durophagous stingrays.

All stingrays in the family Myliobatidae are durophagous, consuming bivalves and gastropods, as well as decapod crustaceans. Durophagous rays have rigid jaws, flat teeth that interlock to form pavement-like tooth plates, and large muscles that generate bite forces capable of fracturing stiff biological composites (e.g. mollusk shell). The relative proportion of different prey types in the diet of durophagous rays varies between genera, with some stingray species specializing on particular mollusk taxa, while others are generalists. The tooth plate module provides a curved occlusal surface on which prey is crushed, and this curvature differs significantly among myliobatids. We measured the effect of jaw curvature on prey-crushing success in durophagous stingrays. We milled aluminum replica jaws rendered from computed tomography scans, and crushed live mollusks, three-dimensionally printed gastropod shells, and ceramic tubes with these fabricated jaws. Our analysis of prey items indicate that gastropods were consistently more difficult to crush than bivalves (i.e. were stiffer), but that mussels require the greatest work-to-fracture. We found that replica shells can provide an important proxy for investigations of failure mechanics. We also found little difference in crushing performance between jaw shapes, suggesting that disparate jaws are equally suited for processing different types of shelled prey. Thus, durophagous stingrays exhibit a many-to-one mapping of jaw morphology to mollusk crushing performance.

A negative waveform in the scotopic response in a patient with phosphoglycerate kinase deficiency: a visual electrophysiology report.

PURPOSE: Phosphoglycerate kinase (PGK) deficiency is an X-linked neurometabolic genetic disorder with variable systemic manifestations. So far, only one patient with retinal anomalies has been reported, but no visual electrophysiology findings were described. We report the first description of visual electrophysiology in a child with PGK deficiency. This provides further information for the site of involvement in the eye. METHOD: A case history of a nine-year-old boy with PGK deficiency is reported. RESULTS: This patient was diagnosed with PGK deficiency by screening soon after birth, as his mother was a known carrier of a PGK gene mutation. A bone marrow transplant was performed at the age of 9 months. He had two episodes of encephalopathy following the transplant but no acute episode of haemolysis. From the age of 6 years, his vision has been deteriorating. Visual electrophysiology results identified retinal involvement involving both rod and cone dysfunction. The visual evoked potential was normal. CONCLUSIONS: Retinal dystrophy may be one of the clinical manifestations of phosphoglycerate kinase deficiency.

Finite element modeling of occlusal variation in durophagous tooth systems.

In addition to breaking hard prey items, the teeth of durophagous predators must also resist failure under high loads. To understand the effects of morphology on tooth resistance to failure, finite element models were used to examine differences in total strain energy (J), first principal strain and the distribution of strains in a diversity of canonical durophagous tooth morphologies. By changing the way loads were applied to the models, I was also able to model the effects of large and small prey items. Tooth models with overall convex morphologies have higher in-model strains than those with a flat or concave occlusal surface. When a cusp is added to the tooth model, taller or thinner cusps increase in-model strain. While there is little difference in the relationships between tooth morphology and strain measurements for most models, there is a marked difference between effects of the large and small prey loads on the concave and flat tooth morphologies. Comparing these data with measurements of force required by these same morphologies to break prey items illustrates functional trade-offs between the need to prevent tooth failure under high loads by minimizing in-tooth strain versus the drive to reduce the total applied force.

Advantage of Whole Exome Sequencing over Allele-Specific and Targeted Segment Sequencing in Detection of Novel TULP1 Mutation in Leber Congenital Amaurosis.

BACKGROUND: Leber congenital amaurosis (LCA) is a severe form of retinal dystrophy with marked underlying genetic heterogeneity. Until recently, allele-specific assays and Sanger sequencing of targeted segments were the only available approaches for attempted genetic diagnosis in this condition. A broader next-generation sequencing (NGS) strategy, such as whole exome sequencing, provides an improved molecular genetic diagnostic capacity for patients with these conditions. MATERIALS AND METHODS: In a child with LCA, an allele-specific assay analyzing 135 known LCA-causing variations, followed by targeted segment sequencing of 61 regions in 14 causative genes was performed. Subsequently, exome sequencing was undertaken in the proband, unaffected consanguineous parents and two unaffected siblings. Bioinformatic analysis used two independent pipelines, BWA-GATK and SOAP, followed by Annovar and SnpEff to annotate the variants. RESULTS: No disease-causing variants were found using the allele-specific or targeted segment Sanger sequencing assays. Analysis of variants in the exome sequence data revealed a novel homozygous nonsense mutation (c.1081C > T, p.Arg361*) in TULP1, a gene with roles in photoreceptor function where mutations were previously shown to cause LCA and retinitis pigmentosa. The identified homozygous variant was the top candidate using both bioinformatic pipelines. CONCLUSIONS: This study highlights the value of the broad sequencing strategy of exome sequencing for disease gene identification in LCA, over other existing methods. NGS is particularly beneficial in LCA where there are a large number of causative disease genes, few distinguishing clinical features for precise candidate disease gene selection, and few mutation hotspots in any of the known disease genes.

Mega-Bites: extreme jaw forces of living and extinct piranhas (Serrasalmidae).

Here, we document in-vivo bite forces recorded from wild piranhas. Integrating this empirical data with allometry, bite simulations, and FEA, we have reconstructed the bite capabilities and potential feeding ecology of the extinct giant Miocene piranha, Megapiranha paranensis. An anterior bite force of 320 N from the black piranha, Serrasalmus rhombeus, is the strongest bite force recorded for any bony fish to date. Results indicate M. paranensis' bite force conservatively ranged from 1240-4749 N and reveal its novel dentition was capable of resisting high bite stresses and crushing vertebrate bone. Comparisons of body size-scaled bite forces to other apex predators reveal S. rhombeus and M. paranensis have among the most powerful bites estimated in carnivorous vertebrates. Our results functionally demonstrate the extraordinary bite of serrasalmid piranhas and provide a mechanistic rationale for their predatory dominance among past and present Amazonian ichthyofaunas.

Proton pumping in the bc1 complex: a new gating mechanism that prevents short circuits.

The Q-cycle mechanism of the bc1 complex explains how the electron transfer from ubihydroquinone (quinol, QH2) to cytochrome (cyt) c (or c2 in bacteria) is coupled to the pumping of protons across the membrane. The efficiency of proton pumping depends on the effectiveness of the bifurcated reaction at the Q(o)-site of the complex. This directs the two electrons from QH2 down two different pathways, one to the high potential chain for delivery to an electron acceptor, and the other across the membrane through a chain containing heme bL and bH to the Qi-site, to provide the vectorial charge transfer contributing to the proton gradient. In this review, we discuss problems associated with the turnover of the bc1 complex that center around rates calculated for the normal forward and reverse reactions, and for bypass (or short-circuit) reactions. Based on rate constants given by distances between redox centers in known structures, these appeared to preclude conventional electron transfer mechanisms involving an intermediate semiquinone (SQ) in the Q(o)-site reaction. However, previous research has strongly suggested that SQ is the reductant for O2 in generation of superoxide at the Q(o)-site, introducing an apparent paradox. A simple gating mechanism, in which an intermediate SQ mobile in the volume of the Q(o)-site is a necessary component, can readily account for the observed data through a coulombic interaction that prevents SQ anion from close approach to heme bL when the latter is reduced. This allows rapid and reversible QH2 oxidation, but prevents rapid bypass reactions. The mechanism is quite natural, and is well supported by experiments in which the role of a key residue, Glu-295, which facilitates proton transfer from the site through a rotational displacement, has been tested by mutation.