111 research outputs found
Bridging a Complete Transection Lesion of Adult Rat Spinal Cord with Growth Factor-Treated Nitrocellulose Implants
The ability of a substrate bound
neurotrophic factor to promote growth of
ascending sensory axons across a complete
transection lesion of the rat spinal cord was
examined in a transplantation model. Aspiration
lesions created a 3 mm long cavity in the upper
lumbar spinal cord of adult rats. Five weeks
after injury two strips of nerve growth factortreated
nitrocellulose, were implanted, each in a
medio-lateral position, and apposed to the
rostral and caudal surfaces of the cavity.
Control animals received untreated nitrocellulose
implants. Fetal spinal cord tissue was
transplanted alongsideand between these strips.
Six weeks post transplantation, animals were
sacrificed and vibratome sections through the
grafts were processed for immunocytochemical
demonstration of ingrowing axons expressing
calcitonin gene-related peptide (CGRP-IR),
Immunolabeled axons were abundant at the
caudal interface between host tissue and the
NGF-treated nitrocellulose implants, with dense
fascicles of fibers abutting the grafts. As the
distance from the caudal surface increased some
CGRP-IR fibers extended into the fetal tissue
although most appeared to remain oriented in a
longitudinal course adjacent to the nitrocellulose.
Labeled axons were evident along the
entire length of the nitrocellulose and appeared
to aggregate at the rostral tip of the implant,
with many fibers extending into the host spinal
cord rostral to the lesion/transplant site. When
untreated nitrocellulose was implanted, fewer
labeled axons appeared to extend beyond the
caudal host-graft interface. Most CGRP-IR
axons displayed limited association or contact
with the untreated nitrocellulose in this
condition. Computer-assisted quantitative
analysis indicated that NGF-treated nitrocellulose
supported regrowing host axons for
nearly three times the length exhibited by axons
associated with non-treated nitrocellulose
implants. These results indicate that substrate
bound nerve growth factor has the capacity to
enhance the regrowth of ascending sensory
axons across a traumatic spinal cord injury site.
The potential to reestablish functional contacts
across such a lesion may be heightened by the
ability of neurotrophic factors to promote more
extensive axonal regrowth
A damage model based on failure threshold weakening
A variety of studies have modeled the physics of material deformation and
damage as examples of generalized phase transitions, involving either critical
phenomena or spinodal nucleation. Here we study a model for frictional sliding
with long range interactions and recurrent damage that is parameterized by a
process of damage and partial healing during sliding. We introduce a failure
threshold weakening parameter into the cellular-automaton slider-block model
which allows blocks to fail at a reduced failure threshold for all subsequent
failures during an event. We show that a critical point is reached beyond which
the probability of a system-wide event scales with this weakening parameter. We
provide a mapping to the percolation transition, and show that the values of
the scaling exponents approach the values for mean-field percolation (spinodal
nucleation) as lattice size is increased for fixed . We also examine the
effect of the weakening parameter on the frequency-magnitude scaling
relationship and the ergodic behavior of the model
Deleterious Mutation Burden and Its Association with Complex Traits in Sorghum (Sorghum bicolor)
Sorghum (Sorghum bicolor L.) is a major food cereal for millions of people worldwide. The sorghum genome, like other species, accumulates deleterious mutations, likely impacting its fitness. The lack of recombination, drift, and the coupling with favorable loci impede the removal of deleterious mutations from the genome by selection. To study how deleterious variants impact phenotypes, we identified putative deleterious mutations among ∼5.5 M segregating variants of 229 diverse biomass sorghum lines. We provide the whole-genome estimate of the deleterious burden in sorghum, showing that ∼33% of nonsynonymous substitutions are putatively deleterious. The pattern of mutation burden varies appreciably among racial groups. Across racial groups, the mutation burden correlated negatively with biomass, plant height, specific leaf area (SLA), and tissue starch content (TSC), suggesting that deleterious burden decreases trait fitness. Putatively deleterious variants explain roughly one-half of the genetic variance. However, there is only moderate improvement in total heritable variance explained for biomass (7.6%) and plant height (average of 3.1% across all stages). There is no advantage in total heritable variance for SLA and TSC. The contribution of putatively deleterious variants to phenotypic diversity therefore appears to be dependent on the genetic architecture of traits. Overall, these results suggest that incorporating putatively deleterious variants into genomic models slightly improves prediction accuracy because of extensive linkage. Knowledge of deleterious variants could be leveraged for sorghum breeding through either genome editing and/or conventional breeding that focuses on the selection of progeny with fewer deleterious alleles
No Intra-Locus Sexual Conflict over Reproductive Fitness or Ageing in Field Crickets
Differences in the ways in which males and females maximize evolutionary fitness can lead to intra-locus sexual conflict in which genes delivering fitness benefits to one sex are costly when expressed in the other. Trade-offs between current reproductive effort and future reproduction and survival are fundamental to the evolutionary biology of ageing. This leads to the prediction that sex differences in the optimization of age-dependent reproductive effort may generate intra-locus sexual conflict over ageing rates. Here we test for intra-locus sexual conflict over age-dependent reproductive effort and longevity in the black field cricket, Teleogryllus commodus. Using a half-sib breeding design, we show that the most important components of male and female reproductive effort (male calling effort and the number of eggs laid by females) were positively genetically correlated, especially in early adulthood. However, the genetic relationships between longevity and reproductive effort were different for males and females, leading to low genetic covariation between male and female longevity. The apparent absence of intra-locus sexual conflict over ageing suggests that male and female longevity can evolve largely independently of one another
Early Developmental Responses to Seedling Environment Modulate Later Plasticity to Light Spectral Quality
Correlations between developmentally plastic traits may constrain the joint evolution of traits. In plants, both seedling de-etiolation and shade avoidance elongation responses to crowding and foliage shade are mediated by partially overlapping developmental pathways, suggesting the possibility of pleiotropic constraints. To test for such constraints, we exposed inbred lines of Impatiens capensis to factorial combinations of leaf litter (which affects de-etiolation) and simulated foliage shade (which affects phytochrome-mediated shade avoidance). Increased elongation of hypocotyls caused by leaf litter phenotypically enhanced subsequent elongation of the first internode in response to low red∶far red (R∶FR). Trait expression was correlated across litter and shade conditions, suggesting that phenotypic effects of early plasticity on later plasticity may affect variation in elongation traits available to selection in different light environments
A Gene-Phenotype Network for the Laboratory Mouse and Its Implications for Systematic Phenotyping
The laboratory mouse is the pre-eminent model organism for the dissection of human disease pathways. With the advent of a comprehensive panel of gene knockouts, projects to characterise the phenotypes of all knockout lines are being initiated. The range of genotype-phenotype associations can be represented using the Mammalian Phenotype ontology. Using publicly available data annotated with this ontology we have constructed gene and phenotype networks representing these associations. These networks show a scale-free, hierarchical and modular character and community structure. They also exhibit enrichment for gene coexpression, protein-protein interactions and Gene Ontology annotation similarity. Close association between gene communities and some high-level ontology terms suggests that systematic phenotyping can provide a direct insight into underlying pathways. However some phenotypes are distributed more diffusely across gene networks, likely reflecting the pleiotropic roles of many genes. Phenotype communities show a many-to-many relationship to human disease communities, but stronger overlap at more granular levels of description. This may suggest that systematic phenotyping projects should aim for high granularity annotations to maximise their relevance to human disease
Mate choice for genetic quality when environments vary: suggestions for empirical progress
Mate choice for good-genes remains one of the most controversial evolutionary processes ever proposed. This is partly because strong directional choice should theoretically deplete the genetic variation that explains the evolution of this type of female mating preferences (the so-called lek paradox). Moreover, good-genes benefits are generally assumed to be too small to outweigh opposing direct selection on females. Here, we review recent progress in the study of mate choice for genetic quality, focussing particularly on the potential for genotype by environment interactions (GEIs) to rescue additive genetic variation for quality, and thereby resolve the lek paradox. We raise five questions that we think will stimulate empirical progress in this field, and suggest directions for research in each area: 1) How is condition-dependence affected by environmental variation? 2) How important are GEIs for maintaining additive genetic variance in condition? 3) How much do GEIs reduce the signalling value of male condition? 4) How does GEI affect the multivariate version of the lek paradox? 5) Have mating biases for high-condition males evolved because of indirect benefits
Gut Microbial Gene Expression in Mother-Fed and Formula-Fed Piglets
Effects of diet on the structure and function of gut microbial communities in newborn infants are poorly understood. High-resolution molecular studies are needed to definitively ascertain whether gut microbial communities are distinct in milk-fed and formula-fed infants.Pyrosequencing-based whole transcriptome shotgun sequencing (RNA-seq) was used to evaluate community wide gut microbial gene expression in 21 day old neonatal piglets fed either with sow's milk (mother fed, MF; n = 4) or with artificial formula (formula fed, FF; n = 4). Microbial DNA and RNA were harvested from cecal contents for each animal. cDNA libraries and 16S rDNA amplicons were sequenced on the Roche 454 GS-FLX Titanium system. Communities were similar at the level of phylum but were dissimilar at the level of genus; Prevotella was the dominant genus within MF samples and Bacteroides was most abundant within FF samples. Screened cDNA sequences were assigned functional annotations by the MG-RAST annotation pipeline and based upon best-BLASTX-hits to the NCBI COG database. Patterns of gene expression were very similar in MF and FF animals. All samples were enriched with transcripts encoding enzymes for carbohydrate and protein metabolism, as well as proteins involved in stress response, binding to host epithelium, and lipopolysaccharide metabolism. Carbohydrate utilization transcripts were generally similar in both groups. The abundance of enzymes involved in several pathways related to amino acid metabolism (e.g., arginine metabolism) and oxidative stress response differed in MF and FF animals.Abundant transcripts identified in this study likely contribute to a core microbial metatranscriptome in the distal intestine. Although microbial community gene expression was generally similar in the cecal contents of MF and FF neonatal piglets, several differentially abundant gene clusters were identified. Further investigations of gut microbial gene expression will contribute to a better understanding of normal and abnormal enteric microbiology in animals and humans
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