Uniparental isodisomy of chromosome 2 causing MRPL44-related multisystem mitochondrial disease

Mutations in nuclear-encoded protein subunits of the mitochondrial ribosome are an increasingly recognised cause of oxidative phosphorylation system (OXPHOS) disorders. Among them, mutations in the MRPL44 gene, encoding a structural protein of the large subunit of the mitochondrial ribosome, have been identified in four patients with OXPHOS defects and early-onset hypertrophic cardiomyopathy with or without additional clinical features. A 23-year-old individual with cardiac and skeletal myopathy, neurological involvement, and combined deficiency of OXPHOS complexes in skeletal muscle was clinically and genetically investigated. Analysis of whole-exome sequencing data revealed a homozygous mutation in MRPL44 (c.467 T?>?G), which was not present in the biological father, and a region of homozygosity involving most of chromosome 2, raising the possibility of uniparental disomy. Short-tandem repeat and genome-wide SNP microarray analyses of the family trio confirmed complete maternal uniparental isodisomy of chromosome 2. Mitochondrial ribosome assembly and mitochondrial translation were assessed in patient derived-fibroblasts. These studies confirmed that c.467 T?>?G affects the stability or assembly of the large subunit of the mitochondrial ribosome, leading to impaired mitochondrial protein synthesis and decreased levels of multiple OXPHOS components. This study provides evidence of complete maternal uniparental isodisomy of chromosome 2 in a patient with MRPL44-related disease, and confirms that MRLP44 mutations cause a mitochondrial translation defect that may present as a multisystem disorder with neurological involvement.

     

Focus: Sex and Gender Health: Associations of Gender,Smoking, and Stress with Transitions in Major Depression Diagnoses

Using data from the newly available U.S. National Epidemiologic Survey on Alcohol and Related Conditions (NESARC; Wave 3; n = 36,309), we evaluated relationships among gender, cigarette smoking status (current, former, non-smoker), life event stress (0-1 vs. 2+ events), and their impact on transitions in major depression diagnosis (MDD; new vs. absent cases; ongoing vs. remit cases). Women who were both current and former cigarette smokers with more than two stressful events had higher rates of new MDD diagnosis compared to men who were current or former smokers with two or more stressful events. Current smoking and experiencing two or more stressful events increased the odds of having an ongoing MDD diagnosis, while being a former smoker decreased these odds. Results suggest that smoking and stress are markers for depression risk in women and should help guide clinical assessment as well as gender-difference research on the biological underpinnings of these conditions.     

CAX‐ing a wide net: Cation/H+ transporters in metal remediation and abiotic stress signalling

Cation/proton exchangers (CAXs) are a class of secondary energised ion transporter that are being implicated in an increasing range of cellular and physiological functions. CAXs are primarily Ca²⁺ efflux transporters that mediate the sequestration of Ca²⁺ from the cytosol, usually into the vacuole. Some CAX isoforms have broad substrate specificity, providing the ability to transport trace metal ions such as Mn²⁺ and Cd²⁺, as well as Ca²⁺. In recent years, genomic analyses have begun to uncover the expansion of CAXs within the green lineage and their presence within non‐plant species. Although there appears to be significant conservation in tertiary structure of CAX proteins, there is diversity in function of CAXs between species and individual isoforms. For example, in halophytic plants, CAXs have been recruited to play a role in salt tolerance, while in metal hyperaccumulator plants CAXs are implicated in cadmium transport and tolerance. CAX proteins are involved in various abiotic stress response pathways, in some cases as a modulator of cytosolic Ca²⁺ signalling, but in some situations there is evidence of CAXs acting as a pH regulator. The metal transport and abiotic stress tolerance functions of CAXs make them attractive targets for biotechnology, whether to provide mineral nutrient biofortification or toxic metal bioremediation. The study of non‐plant CAXs may also provide insight into both conserved and novel transport mechanisms and functions.     

Predation on Moose Calves by European Brown Bears

Abstract: In North America, brown bears (Ursus arctos) can be a significant predator on moose (Alces alces) calves. Our study in Sweden is the first in which brown bears are the only predator on moose calves. Bears and moose occurred at densities of about 30/1,000 km² and 920/1,000 km², respectively, and bears killed about 26% of the calves. Ninety-two percent of the predation took place when calves were <1 month old. Bear predation was probably additive to other natural mortality, which was about 10% in areas both with and without bears. Females that lost their calves in spring produced more calves the following year (1.54 calves/F) than females that kept their calves (1.11 calves/F), which reduced the net loss of calves due to predation to about 22%.     

Does freshwater macroinvertebrate diversity along a pH‐gradient reflect adaptation to low pH?

1. The impacts of anthropogenic surface water acidification are much better known than those of natural acidity. Recent studies have indicated biodiversity is not degraded and species composition unaltered in naturally acidic compared to circumneutral watercourses.
2. Here, we use a geographically extensive dataset comprising sites in more than 200 Swedish streams to test whether the lack of effects on macroinvertebrate species diversity is due to exaptation and adaptation to natural acidity.
3. To this end, we modelled pH associated with spring flood episodes, which inflict the most challenging hydrochemical conditions to the biota. We compared taxonomic richness and species composition along the modelled pH gradient in northern Sweden, where acidity is largely natural, with southern Sweden, a region influenced by significant anthropogenic acidification.
4. We found Plecoptera richness did not respond to varying pH either in northern or southern Sweden. Ephemeroptera richness was sensitive to pH in both regions, while that of Trichoptera increased with increasing pH in southern Sweden, but decreased in the north. The taxonomic composition of Plecoptera changed along the pH gradient in both regions, whereas that of Ephemeroptera and Trichoptera changed more strongly with pH in southern Sweden.
5. Our results support the hypothesis that stream invertebrates are able to tolerate low pH through exaptation or adaptation, but that this capability varies among taxonomic groups.     

The effects of selection,drift and genetic variation on life‐history trait divergence among insular populations of natterjack toad,Bufo calamita

Although loss of genetic variation is frequently assumed to be associated with loss of adaptive potential, only few studies have examined adaptation in populations with little genetic variation. On the Swedish west coast, the northern fringe populations of the natterjack toad Bufo calamita inhabit an atypical habitat consisting of offshore rock islands. There are strong among‐population differences in the amount of neutral genetic variation, making this system suitable for studies on mechanisms of trait divergence along a gradient of within‐population genetic variation. In this study, we examined the mechanisms of population divergence using Q_ST–F_ST comparisons and correlations between quantitative and neutral genetic variation. Our results suggest drift or weak stabilizing selection across the six populations included in this study, as indicated by low Q_ST–F_ST values, lack of significant population × temperature interactions and lack of significant differences among the islands in breeding pond size. The six populations included in this study differed in both neutral and quantitative genetic variation. Also, the correlations between neutral and quantitative genetic variation tended to be positive, however, the relatively small number of populations prevents any strong conclusions based on these correlations. Contrary to the majority of Q_ST–F_ST comparisons, our results suggest drift or weak stabilizing selection across the examined populations. Furthermore, the low heritability of fitness‐related traits may limit evolutionary responses in some of the populations.     

A Simple Allele-Specific PCR Assay for Detecting <Emphasis Type="Italic">FAD2</Emphasis> Alleles in Both A and B Genomes of the Cultivated Peanut for High-Oleate Trait Selection

In cultivated tetraploid peanut (2n = 4x = 40, AABB), the conversion of oleic acid to linoleic acid is mainly catalyzed by the Δ¹² fatty acid desaturase (FAD). Two homoeologous genes (FAD2A and FAD2B) encoding for the desaturase are located on the A and B genomes, respectively. Abolishing or reducing the desaturase activity by gene mutation can significantly increase the oleic acid/linoleic acid ratio. F435-derived high-oleate peanut cultivars contain two key mutations within the Δ¹² fatty acid desaturase gene which include a 1-bp substitution of G:C→A:T in the A genome and a 1-bp insertion of A:T in the B genome. Both of these mutations contribute to abolishing or reducing the desaturase activity, leading to accumulation of oleate versus linoleate. Currently, detection of FAD2 alleles can be achieved by a cleaved amplified polymorphic sequence marker for the A genome and a real-time polymerase chain reaction (PCR) marker for the B genome; however, detection of these key mutations has to use different assay platforms. Therefore, a simple PCR assay for detection of FAD2 alleles on both genomes was developed by designing allele-specific primers and altering PCR annealing temperatures. This assay was successfully used for detecting FAD2 alleles in peanut. Gas chromatography (GC) was used to determine fatty acid composition of PCR-assayed genotypes. The results from the PCR assay and GC analysis were consistent. This PCR assay is quick, reliable, economical, and easy to use. Implementation of this PCR assay will greatly enhance the efficiency of germplasm characterization and marker-assisted selection of high oleate in peanut.     

Reproductive Physiology of Fishes

Atlantic cod Gadus morhua larvae reached four‐fold (at low larval density) to 11 fold higher body mass (high larval density) at 50 days post hatch (dph) when fed zooplankton rather than enriched rotifers. A short period (22–36 dph) of dietary change affected larval growth positively if changed from enriched rotifers to natural zooplankton and negatively if prey type changed vice versa. Overall survival did not differ between the two larval groups at low larval density, but at high density the rotifer group had a higher overall survival (10·8% v. 8·9%). Long‐term growth was affected significantly by larval diet in favour of the zooplankton diet; juveniles reached a 23% higher mass in a 12 week growth period. No difference in growth performance was found between juveniles fed natural zooplankton during the larval period for 36, 22 or 14 days, but all these juveniles performed significantly better compared with the rotifer‐fed group. These findings suggest that optimal diet during a short period in the larval period can result in improved growth in both the larval and juvenile period. Improved rotifer quality may, therefore, hold a large potential for growth improvement in this species.     

Rapid and unexpected effects of piscivore introduction on trophic position and diet of perch (Perca flavescens) in lakes recovering from acidification and metal contamination

1. Yellow perch (Perca flavescens) are often the only surviving fish species in acidified lakes. We studied four lakes along a gradient of recovery from acidification and that had different food web complexities. All had abundant yellow perch, two had low piscivore abundance, one had a well‐established piscivore population and one was manipulated by introducing piscivorous smallmouth bass (Micropterus dolomieu). We hypothesised that there would be strong effects on perch abundance, behaviour and diet induced by the presence of piscivores. 2. In the manipulated lake, the bass reduced yellow perch abundance by 75% over a 2‐year period. Concomitantly, perch use of the pelagic habitat fell from 48 to 40%. 3. In contrast to findings from less disturbed systems, yellow perch in the littoral zone of the manipulated lake did not strongly shift from zooplankton to benthic food sources after the arrival of piscivores. Diet analysis using stable carbon isotopes revealed a strong continued reliance on zooplankton in all lakes, independent of the degree of piscivory. The failure to switch to benthos in the refuge area of the littoral zone is most likely related to the depauperate benthos communities in these formerly acidified lakes. 4. Yellow perch in lakes recovering from acidification face a considerable ecological challenge as the necessary switch to benthic diet is hindered by a low abundance of benthos. The arrival of piscivores in these recovering lakes imposes further restrictions on perch access to food items. We infer that future recovery of perch populations (and higher trophic levels) will have to be preceded by the re‐establishment of diverse benthic macroinvertebrate communities in these lakes.