Multiple-trait QTL mapping for body and organ weights in a cross between NMRI8 and DBA/2 mice

Multiple-trait analyses have been shown to improve the detection of quantitative trait loci (QTLs) with multiple effects. Here we applied a multiple-trait approach on obesity- and growth-related traits that were surveyed in 275 F2 mice generated from an intercross between the high body weight selected line NMRI8 and DBA/2 as lean control. The parental lines differed 2.5-fold in body weight at the age of 6 weeks. Within the F2 population, the correlations between body weight and weights of abdominal fat weight, muscle, liver and kidney at the age of 6 weeks were about 0.8. A least squares multiple-trait QTL analysis was performed on these data to understand more precisely the cause of the genetic correlation between body weight, body composition traits and weights of inner organs. Regions on Chr 1, 2, 7 and 14 for body weights at different early ages and regions on Chr 1, 2, 4, 7, 14, 17 and 19 for organ weights at 6 weeks were found to have significant multiple effects at the genome-wide level.     

The RNA-Binding Protein PUM2 Impairs Mitochondrial Dynamics and Mitophagy During Aging

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GAD67-mediated GABA synthesis and signaling regulate inhibitory synaptic innervation in the visual cortex

The development of GABAergic inhibitory circuits is shaped by neural activity, but the underlying mechanisms are unclear. Here, we demonstrate a novel function of GABA in regulating GABAergic innervation in the adolescent brain, when GABA is mainly known as an inhibitory transmitter. Conditional knockdown of the rate-limiting synthetic enzyme GAD67 in basket interneurons in adolescent visual cortex resulted in cell autonomous deficits in axon branching, perisomatic synapse formation around pyramidal neurons, and complexity of the innervation fields; the same manipulation had little influence on the subsequent maintenance of perisomatic synapses. These effects of GABA deficiency were rescued by suppressing GABA reuptake and by GABA receptor agonists. Germline knockdown of GAD67 but not GAD65 showed similar deficits, suggesting a specific role of GAD67 in the maturation of perisomatic innervation. Since intracellular GABA levels are modulated by neuronal activity, our results implicate GAD67-mediated GABA synthesis in activity-dependent regulation of inhibitory innervation patterns.     

Predominance of outcrossing in Lymnaea stagnalis despite low apparent fitness costs of self-fertilization

We have quantified the natural mating system in eight populations of the simultaneously hermaphroditic aquatic snail Lymnaea stagnalis, and studied the ecological and genetic forces that may be directing mating system evolution in this species. We investigated whether the natural mating system can be explained by the availability of mates, by the differential survival of self- and cross-fertilized snails in nature, and by the effects of mating system on parental fecundity and early survival. The natural mating system of L. stagnalis was found to be predominantly cross-fertilizing. Density of snails in the populations had no relationship with the mating system, suggesting that outcrossing rates are not limited by mate availability at the population densities observed. Contrary to expectations for outcrossing species, we detected no evidence for inbreeding depression in survival in nature with inferential population genetic methods. Further, experimental manipulations of mating system in the laboratory revealed that self-fertilization had no effect on parental fecundity, and only minor effects on offspring survival. Predominance of cross-fertilization despite low apparent fitness costs of self-fertilization is at odds with the paradigm that high self-fertilization depression is necessary for maintenance of cross-fertilization in self-compatible hermaphrodites.     

Domains in the 1alpha dynein heavy chain required for inner arm assembly and flagellar motility in Chlamydomonas.

Flagellar motility is generated by the activity of multiple dynein motors, but the specific role of each dynein heavy chain (Dhc) is largely unknown, and the mechanism by which the different Dhcs are targeted to their unique locations is also poorly understood. We report here the complete nucleotide sequence of the Chlamydomonas Dhc1 gene and the corresponding deduced amino acid sequence of the 1alpha Dhc of the I1 inner dynein arm. The 1alpha Dhc is similar to other axonemal Dhcs, but two additional phosphate binding motifs (P-loops) have been identified in the NH(2)- and COOH-terminal regions. Because mutations in Dhc1 result in motility defects and loss of the I1 inner arm, a series of Dhc1 transgenes were used to rescue the mutant phenotypes. Motile cotransformants that express either full-length or truncated 1alpha Dhcs were recovered. The truncated 1alpha Dhc fragments lacked the dynein motor domain, but still assembled with the 1beta Dhc and other I1 subunits into partially functional complexes at the correct axoneme location. Analysis of the transformants has identified the site of the 1alpha motor domain in the I1 structure and further revealed the role of the 1alpha Dhc in flagellar motility and phototactic behavior.     

The influence of age and breed on stallion semen

This study reports on the variation in semen quality and in spermatozoal and behavioral characteristics of 168 stallions representing 9 breeds and ranging in age from 2 to 26 yr. Semen samples were collected into an artificial vagina and the number of mounts and urethral pulsations per semen sample were recorded. Semen characteristics were examined for total volume, gel-free volume, gel volume, color score, mass activity, nonmotile spermatozoa, dead spermatozoa, semen density, spermatozoa concentration, total number of spermatozoa and semen pH. Morphological characteristics of the spermatozoa included abnormal heads, abnormal mid-pieces, abaxial mid-pieces, protoplasmic droplets and abnormal tails. Sources of variation were evaluated and the overall means calculated by least-squares analyses of variance for nonorthogonal data. The significance of breed effects and between stallion variability were estimated using mixed-model procedures. All semen characteristics with the exception of color and urethral pulsations had significant variation due to age. Semen quality (gel-free volume, sperm concentration, total sperm numbers and sperm abnormalities) was poorest in stallions under 3 yr of age and over 11 yr. Significant breed variation was apparent in most characteristics except for pH, semen color, abnormal midpieces and urethral pulsations. It is recommended that both the age and breed of stallion be taken into consideration when evaluating stallion semen.     

Neutron scattering shows a droplet of oleic acid at the center of the BAMLET complex

The anti‐cancer complex, Bovine Alpha‐lactalbumin Made LEthal to Tumors (BAMLET), has intriguing broad‐spectrum anti‐cancer activity. Although aspects of BAMLET's anti‐cancer mechanism are still not known, it is understood that it involves the oleic acid or oleate component of BAMLET being preferentially released into cancer cell membranes leading to increased membrane permeability and lysis. The structure of the protein component of BAMLET has previously been elucidated by small angle X‐ray scattering (SAXS) to be partially unfolded and dramatically enlarged. However, the structure of the oleic acid component of BAMLET and its disposition with respect to the protein component was not revealed as oleic acid has the same X‐ray scattering length density (SLD) as water. Employing the difference in the neutron SLDs of hydrogen and deuterium, we carried out solvent contrast variation small angle neutron scattering (SANS) experiments of hydrogenated BAMLET in deuterated water buffers, to reveal the size, shape, and disposition of the oleic acid component of BAMLET. Our resulting analysis and models generated from SANS and SAXS data indicate that oleic acid forms a spherical droplet of oil incompletely encapsulated by the partially unfolded protein component. This model provides insight into the anti‐cancer mechanism of this cache of lipid. The model also reveals a protein component “tail” not associated with the oleic acid component that is able to interact with the tail of other BAMLET molecules, providing a plausible explanation of how BAMLET readily forms aggregates. Proteins 2017; 85:1371–1378. © 2017 Wiley Periodicals, Inc.     

Wild Bornean orangutan (Pongo pygmaeus wurmbii) feeding rates and the Marginal Value Theorem

The Marginal Value Theorem (MVT) is an integral supplement to Optimal Foraging Theory (OFT) as it seeks to explain an animal's decision of when to leave a patch when food is still available. MVT predicts that a forager capable of depleting a patch, in a habitat where food is patchily distributed, will leave the patch when the intake rate within it decreases to the average intake rate for the habitat. MVT relies on the critical assumption that the feeding rate in the patch will decrease over time. We tested this assumption using feeding data from a population of wild Bornean orangutans (Pongo pygmaeus wurmbii) from Gunung Palung National Park. We hypothesized that the feeding rate within orangutan food patches would decrease over time. Data included feeding bouts from continuous focal follows between 2014 and 2016. We recorded the average feeding rate over each tertile of the bout, as well as the first, midpoint, and last feeding rates collected. We did not find evidence of a decrease between first and last feeding rates (Linear Mixed Effects Model, n = 63), between a mid-point and last rate (Linear Mixed Effects Model, n = 63), between the tertiles (Linear Mixed Effects Model, n = 63), nor a decrease in feeding rate overall (Linear Mixed Effects Model, n = 146). These findings, thus, do not support the MVT assumption of decreased patch feeding rates over time in this large generalist frugivore.