Specific protein changes contribute to the differential muscle mass loss during ageing

In the skeletal muscle, the ageing process is characterized by a loss of muscle mass and strength, coupled with a decline of mitochondrial function and a decrease of satellite cells. This profile is more pronounced in hindlimb than in forelimb muscles, both in humans and in rodents. Utilizing light and electron microscopy, myosin heavy chain isoform distribution, proteomic analysis by 2D‐DIGE, MALDI‐TOF MS and quantitative immunoblotting, this study analyzes the protein levels and the nuclear localization of specific molecules, which can contribute to a preferential muscle loss. Our results identify the molecular changes in the hindlimb (gastrocnemius) and forelimb (triceps) muscles during ageing in rats (3‐ and 22‐month‐old). Specifically, the oxidative metabolism contributes to tissue homeostasis in triceps, whereas respiratory chain disruption and oxidative‐stress‐induced damage imbalance the homeostasis in gastrocnemius muscle. High levels of dihydrolipoyllysine‐residue acetyltransferase (Dlat) and ATP synthase subunit alpha (Atp5a1) are detected in triceps and gastrocnemius, respectively. Interestingly, in triceps, both molecules are increased in the nucleus in aged rats and are associated to an increased protein acetylation and myoglobin availability. Furthermore, autophagy is retained in triceps whereas an enhanced fusion, decrement of mitophagy and of regenerative potential is observed in aged gastrocnemius muscle.     

Heliotherapy for Neonatal Hyperbilirubinemia in Southwest,Nigeria: A Baseline Pre-Intervention Study

Background

A novel filtered-sunlight phototherapy (FSPT) device has been demonstrated to be safe and efficacious for treating infants with neonatal jaundice in resource-constrained tropical settings. We set out to provide baseline data for evaluating the clinical impact of this device in a referral pediatric hospital.

Methods

We reviewed the medical records of infants admitted for neonatal hyperbilirubinemia in an inner-city Children’s Hospital in Lagos, between January 2012 and December 2014 to determine the pattern, treatment and outcomes during the pre-intervention period. Factors associated with adverse outcomes were identified through multivariable logistic regression.

Results

Of the 5,229 neonatal admissions over the period, a total of 1,153 (22.1%) were admitted for neonatal hyperbilirubinemia. Complete records for 1,118 infants were available for analysis. The incidence of acute bilirubin encephalopathy (ABE) and exchange transfusion (ET) were 17.0% (95% CI: 14.9%–19.3%) and 31.5% (95% CI: 28.8%–34.3%) respectively. A total of 61 (5.5%, 95% CI: 4.3%–6.9%) of the jaundiced infants died. Weight on admission, peak total serum bilirubin (TSB), sepsis and exposure to hemolytic products were predictive of ABE, while age on admission, peak TSB, ABO incompatibility and ABE were predictive of ET. Rhesus incompatibility, asphyxia, exposure to hemolytic substances and ABE were associated with elevated mortality risk, while ET was a protective factor. Lack of routine irradiance monitoring and steady energy supply were frequent challenges for conventional blue-light phototherapy.

Conclusions

Severe hyperbilirubinemia is associated with high rates of ABE and ET in this setting, and remains a significant contributor to neonatal admissions and mortality. To be impactful, FSPT, complemented with improved diagnostic facilities, should effectively curtail jaundice-related adverse outcomes in this and comparable settings.     

DNAH6 and Its Interactions with PCD Genes in Heterotaxy and Primary Ciliary Dyskinesia

Heterotaxy, a birth defect involving left-right patterning defects, and primary ciliary dyskinesia (PCD), a sinopulmonary disease with dyskinetic/immotile cilia in the airway are seemingly disparate diseases. However, they have an overlapping genetic etiology involving mutations in cilia genes, a reflection of the common requirement for motile cilia in left-right patterning and airway clearance. While PCD is a monogenic recessive disorder, heterotaxy has a more complex, largely non-monogenic etiology. In this study, we show mutations in the novel dynein gene DNAH6 can cause heterotaxy and ciliary dysfunction similar to PCD. We provide the first evidence that trans-heterozygous interactions between DNAH6 and other PCD genes potentially can cause heterotaxy. DNAH6 was initially identified as a candidate heterotaxy/PCD gene by filtering exome-sequencing data from 25 heterotaxy patients stratified by whether they have airway motile cilia defects. dnah6 morpholino knockdown in zebrafish disrupted motile cilia in Kupffer’s vesicle required for left-right patterning and caused heterotaxy with abnormal cardiac/gut looping. Similarly DNAH6 shRNA knockdown disrupted motile cilia in human and mouse respiratory epithelia. Notably a heterotaxy patient harboring heterozygous DNAH6 mutation was identified to also carry a rare heterozygous PCD-causing DNAI1 mutation, suggesting a DNAH6/DNAI1 trans-heterozygous interaction. Furthermore, sequencing of 149 additional heterotaxy patients showed 5 of 6 patients with heterozygous DNAH6 mutations also had heterozygous mutations in DNAH5 or other PCD genes. We functionally assayed for DNAH6/DNAH5 and DNAH6/DNAI1 trans-heterozygous interactions using subthreshold double-morpholino knockdown in zebrafish and showed this caused heterotaxy. Similarly, subthreshold siRNA knockdown of Dnah6 in heterozygous Dnah5 or Dnai1 mutant mouse respiratory epithelia disrupted motile cilia function. Together, these findings support an oligogenic disease model with broad relevance for further interrogating the genetic etiology of human ciliopathies.     

Causes and characteristics of reverse bird migration: an analysis based on radar,radio tracking and ringing at Falsterbo,Sweden

That birds migrate in the reverse direction of the expected is a phenomenon of regular occurrence which has been observed at many sites. Here we use three different methods; tracking radar, radiotelemetry and ringing, to characterize the flights of these reverse migrants and investigate possible causes of reverse migration of nocturnally migrating passerines during autumn migration at Falsterbo peninsula, Sweden. Using these different methods we investigated both internal factors, such as age and fuel load, and external factors such as weather variables, competition and predation risk. Birds flying in the reverse direction were more likely to be lean and to be juveniles. Reverse migration was also more common with overcast skies and winds with north and east components. We did not find any effect of temperature, visibility, number of migrating sparrowhawks, or the total number of ringed birds at the site on the day of departure. We found that reverse migration is characterized by slower flight speeds (airspeed) at high altitudes and that it takes place later in the night than forward migration.     

Comparative population genomics identified genomic regions and candidate genes associated with fruit domestication traits in peach

Crop evolution is a long‐term process involving selection by natural evolutionary forces and anthropogenic influences; however, the genetic mechanisms underlying the domestication and improvement of fruit crops have not been well studied to date. Here, we performed a population structure analysis in peach (Prunus persica) based on the genome‐wide resequencing of 418 accessions and confirmed the presence of an obvious domestication event during evolution. We identified 132 and 106 selective sweeps associated with domestication and improvement, respectively. Analysis of their tissue‐specific expression patterns indicated that the up‐regulation of selection genes during domestication occurred mostly in fruit and seeds as opposed to other organs. However, during the improvement stage, more up‐regulated selection genes were identified in leaves and seeds than in the other organs. Genome‐wide association studies (GWAS) using 4.24 million single nucleotide polymorphisms (SNPs) revealed 171 loci associated with 26 fruit domestication traits. Among these loci, three candidate genes were highly associated with fruit weight and the sorbitol and catechin content in fruit. We demonstrated that as the allele frequency of the SNPs associated with high polyphenol composition decreased during peach evolution, alleles associated with high sugar content increased significantly. This indicates that there is genetic potential for the breeding of more nutritious fruit with enhanced bioactive polyphenols without disturbing a harmonious sugar and acid balance by crossing with wild species. This study also describes the development of the genomic resources necessary for evolutionary research in peach and provides the large‐scale characterization of key agronomic traits in this crop species.