The influence of muscle type and dystrophin deficiency on murine expression profiles

The phenotypic differences among Duchenne muscular dystrophy patients, mdx mice, and mdx^5cv mice suggest that despite the common etiology of dystrophin deficiency, secondary mechanisms have a substantial influence on phenotypic severity. The differential response of various skeletal muscles to dystrophin deficiency supports this hypothesis. To explore these differences, gene expression profiles were generated from duplicate RNA targets extracted from six different skeletal muscles (diaphragm, soleus, gastrocnemius, quadriceps, tibialis anterior, and extensor digitorum longus) from wild-type, mdx, and mdx^5cv mice, resulting in 36 data sets for 18 muscle samples. The data sets were compared in three different ways: (1) among wild-type samples only, (2) among all 36 data sets, and (3) between strains for each muscle type. The molecular profiles of soleus and diaphragm separate significantly from the other four muscle types and from each other. Fiber-type proportions can explain some of these differences. These variations in wild-type gene expression profiles may also reflect biomechanical differences known to exist among skeletal muscles. Further exploration of the genes that most distinguish these muscles may help explain the origins of the biomechanical differences and the reasons why some muscles are more resistant than others to dystrophin deficiency. Electronic Supplementary Material Electronic Supplementary material is available for this article at and accessible for authorised users. Judith N. Haslett, Peter B. Kang These authors contributed equally to this work.     

Sensory‐based conservation of seabirds: a review of management strategies and animal behaviours that facilitate success

Sensory‐based conservation harnesses species' natural communication and signalling behaviours to mitigate threats to wild populations. To evaluate this emerging field, we assess how sensory‐based manipulations, sensory mode, and target taxa affect success. To facilitate broader, cross‐species application of successful techniques, we test which behavioural and life‐history traits correlate with positive conservation outcomes. We focus on seabirds, one of the world's most rapidly declining groups, whose philopatry, activity patterns, foraging, mate choice, and parental care behaviours all involve reliance on, and therefore strong selection for, sophisticated sensory physiology and accurate assessment of intra‐ and inter‐species signals and cues in several sensory modes. We review the use of auditory, olfactory, and visual methods, especially for attracting seabirds to newly restored habitat or deterring birds from fishing boats and equipment. We found that more sensory‐based conservation has been attempted with Procellariiformes (tube‐nosed seabirds) and Charadriiformes (e.g. terns and gulls) than other orders, and that successful outcomes are more likely for Procellariiformes. Evolutionary and behavioural traits are likely to facilitate sensory‐based techniques, such as social attraction to suitable habitat, across seabird species. More broadly, successful application of sensory‐based conservation to other at‐risk animal groups is likely to be associated with these behavioural and life‐history traits: coloniality, philopatry, nocturnal, migratory, long‐distance foraging, parental care, and pair bonds/monogamy.     

Predicting species interactions from edge responses: mongoose predation on hawksbill sea turtle nests in fragmented beach habitat

Because species respond differently to habitat boundaries and spatial overlap affects encounter rates, edge responses should be strong determinants of spatial patterns of species interactions. In the Caribbean, mongooses (Herpestes javanicus) prey on hawksbill sea turtle (Eretmochelys imbricata) eggs. Turtles nest in both open sand and vegetation patches, with a peak in nest abundance near the boundary between the two microhabitats; mongooses rarely leave vegetation. Using both artificial nests and hawksbill nesting data, we examined how the edge responses of these species predict the spatial patterns of nest mortality. Predation risk was strongly related to mongoose abundance but was not affected by nest density or habitat type. The product of predator and prey edge response functions accurately described the observed pattern of total prey mortality. Hawksbill preference for vegetation edge becomes an ecological trap in the presence of mongooses. This is the first study to predict patterns of predation directly from continuous edge response functions of interacting species, establishing a link between models of edge response and species interactions.     

Lsm Proteins are required for normal processing and stability of ribosomal RNAs

Depletion of any of the essential Lsm proteins, Lsm2-5p or Lsm8p, delayed pre-rRNA processing and led to the accumulation of many aberrant processing intermediates, indicating that an Lsm complex is required to maintain the normally strict order of processing events. In addition, high levels of degradation products derived from both precursors and mature rRNAs accumulated in Lsm-depleted strains. Depletion of the essential Lsm proteins reduced the apparent processivity of both 5' and 3' exonuclease activities involved in 5.8S rRNA processing, and the degradation intermediates that accumulated were consistent with inefficient 5' and 3' degradation. Many, but not all, pre-rRNA species could be coprecipitated with tagged Lsm3p, but not with tagged Lsm1p or non-tagged control strains, suggesting their direct interaction with an Lsm2-8p complex. We propose that Lsm proteins facilitate RNA protein interactions and structural changes required during ribosomal subunit assembly.     

Glutamate release from activated microglia requires the oxidative burst and lipid peroxidation

When activated by proinflammatory stimuli, microglia release substantial levels of glutamate, and mounting evidence suggests this contributes to neuronal damage during neuroinflammation. Prior studies indicated a role for the Xc exchange system, an amino acid transporter that antiports glutamate for cystine. Because cystine is used for synthesis of glutathione (GSH) synthesis, we hypothesized that glutamate release is an indirect consequence of GSH depletion by the respiratory burst, which produces superoxide from NADPH oxidase. Microglial glutamate release triggered by lipopolysaccharide was blocked by diphenylene iodonium chloride and apocynin, inhibitors of NADPH oxidase. This glutamate release was also blocked by vitamin E and elicited by lipid peroxidation products 4-hydroxynonenal and acrolein, suggesting that lipid peroxidation makes crucial demands on GSH. Although NADPH oxidase inhibitors also suppressed nitrite accumulation, vitamin E did not; moreover, glutamate release was largely unaffected by nitric oxide donors, inhibitors of nitric oxide synthase, or changes in gene expression. These findings indicate that a considerable degree of the neurodegenerative consequences of neuroinflammation may result from conversion of oxidative stress to excitotoxic stress. This phenomenon entails a biochemical chain of events initiated by a programmed oxidative stress and resultant mass-action amino acid transport. Indeed, some of the neuroprotective effects of antioxidants may be due to interference with these events rather than direct protection against neuronal oxidation.     

Nemaline myopathy with minicores caused by mutation of the CFL2 gene encoding the skeletal muscle actin-binding protein, cofilin-2

Nemaline myopathy (NM) is a congenital myopathy characterized by muscle weakness and nemaline bodies in affected myofibers. Five NM genes, all encoding components of the sarcomeric thin filament, are known. We report identification of a sixth gene, CFL2, encoding the actin-binding protein muscle cofilin-2, which is mutated in two siblings with congenital myopathy. The proband’s muscle contained characteristic nemaline bodies, as well as occasional fibers with minicores, concentric laminated bodies, and areas of F-actin accumulation. Her affected sister’s muscle was reported to exhibit nonspecific myopathic changes. Cofilin-2 levels were significantly lower in the proband’s muscle, and the mutant protein was less soluble when expressed in Escherichia coli, suggesting that deficiency of cofilin-2 may result in reduced depolymerization of actin filaments, causing their accumulation in nemaline bodies, minicores, and, possibly, concentric laminated bodies.     

Re‐forestation restores native dominance in an island beetle fauna

Native re‐forestation is a widely used restoration tool, typically undertaken with the expectation that planting native trees will initiate succession processes (including the re‐establishment of native fauna) that will eventually return the ecosystem to a native‐dominated state. Invertebrate groups can be used to assess restoration progress, as their life history traits enable them to respond more rapidly to environmental change than many other organisms. In this study, we assessed beetle responses to re‐forestation. Using two trapping methods (flight intercept traps and pitfall traps), we compared beetle assemblages in exotic pasture (pre‐restoration state), <10‐year‐old planted native forest (restoration intervention) and approximately 40‐year‐old unmanaged regenerating native forest (reference state). Analysis of the flight intercept‐trapped beetles suggests that re‐forestation has initiated a transition from an exotic‐dominated pasture fauna toward a native‐dominated fauna: in planted forests, 75% of all flight‐intercept‐trapped beetles were native (compared with 22% in pasture and 87% in unmanaged forest). Flight intercept‐trapped beetles also had higher native diversity and abundance in both forest types than in pasture. Pitfall‐trapped beetle species were predominantly native in both forest types, but there were few statistically significant differences between the forests and pasture in the pit‐fall trap data set. Both trapping methods detected significant compositional differences between the beetle assemblages in planted forest and unmanaged forest. Replanting native forest has increased native beetle diversity, abundance, and dominance (compared with the pre‐restoration state), but convergence with the unmanaged reference forest has not yet been achieved.