Deciphering bioactive peptides and their action mechanisms through proteomics

Introduction: Bioactive peptides such as antimicrobial peptides (AMPs), ribosomally synthesized and post translationally modified peptides (RiPPs) and the non-ribosomal peptides (NRPs) have emerged with promising applications in medicine, agriculture and industry. However, their development has been limited by several difficulties making it necessary to search for novel discovery methods. In this context, proteomics has been considered a reliable tool.

Areas covered: This review highlights recent developments in proteomic tools that facilitate the discovery of AMPs, RiPPs and NRPs as well as the elucidation of action mechanisms of AMPs and resistance mechanisms of pathogens to them.

Expert commentary: Proteomic approaches have emerged as useful tools for the study of bioactive peptides, especially mass spectrometry-based peptidomics profiling, a promising strategy for AMP discovery. Furthermore, the rapidly expanding fields of genome mining and genome sequencing techniques, as well as mass spectrometry, have revolutionized the discovery of novel RiPPs and NRPs from complex biological samples.     

Comparative phylogeography of West African amphibians and reptiles

Comparative phylogeographic studies often support shared divergence times for co-distributed species with similar life histories and habitat specializations. During the late Holocene, West Africa experienced aridification and the turnover of rain forest habitats into savannas. These fragmented rain forests harbor impressive numbers of endemic and threatened species. In this setting, populations of co-distributed rain forest species are expected to have diverged simultaneously, whereas divergence events for species adapted to savanna and forest-edge habitats should be absent or idiosyncratic. We conducted a Bayesian analysis of shared evolutionary events to test models of population divergence for 20 species of anurans (frogs) and squamates (lizards and snakes) that are distributed across the Dahomey Gap, a climate change-induced savanna barrier responsible for fragmenting previously contiguous rain forests of Ghana into two regions: the Togo-Volta Hills and the Southwestern Forests. A model of asynchronous diversification is supported for anurans and squamates, suggesting that drivers of diversification are not specifically related to ecological and life history associations with habitat types. Instead, the wide variability of genetic divergence histories exhibited by these species suggests that biodiversity in this region has been shaped by diversification events that extend beyond the Holocene. Comparisons of the genealogical divergence index, a measure of the genetic divergence between populations due to the combined effects of genetic isolation and gene flow, illustrate that these populations represent a broad sampling of the speciation continuum.     

Determination of Moulting Events in Rock Lobsters from Pleopod Clipping

Rock lobster growth is routinely measured for research to optimise management measures such as size limits and quotas. The process of estimating growth is complicated in crustaceans as growth only occurs when the animal moults. As data are typically collected by tag-recapture methods, the timing of moulting events can bias results. For example, if annual moulting events take place within a very short time-at-large after tagging, or if time-at-large is long and no moulting occurs. Classifying data into cases where moulting has / has not occurred during time-at-large can be required and can generally be determined by change in size between release and recapture. However, in old or slow growth individuals the moult increment can be too small to provide surety that moulting has occurred. A method that has been used since the 1970’s to determine moulting in rock lobsters involves clipping the distal portion of a pleopod so that any regeneration observed at recapture can be used as evidence of a moult. We examined the use of this method in both tank and long-duration field trials within a marine protected area, which provided access to large animals with smaller growth increments. Our results emphasised that determination of moulting by change in size was unreliable with larger lobsters and that pleopod clipping can assist in identifying moulting events. However, regeneration was an unreliable measure of moulting if clipping occurred less than three months before the moult.     

Sub-lethal temperature thresholds indicate acclimation and physiological limits in brook trout Salvelinus fontinalis

The upper thermal tolerance of brook trout Salvelinus fontinalis was estimated using critical thermal maxima (CT_max) experiments on fish acclimated to temperatures that span the species' thermal range (5–25°C). The CT_max increased with acclimation temperature but plateaued in fish acclimated to 20, 23 and 25°C. Plasma lactate was highest, and the hepato-somatic index (I_H) was lowest at 23 and 25°C, which suggests additional metabolic costs at those acclimation temperatures. The results suggest that there is a sub-lethal threshold between 20 and 23°C, beyond which the fish experience reduced physiological performance.     

Cranial variation amongst independent lineages of the alligator snapping turtle (Macrochelys temminckii)

Recent interest in diagnoses and relationships between lineages of the alligator snapping turtle (Macrochelys temminckii) present conflicting patterns of molecular variation across the taxon's range. This study uses geometric morphometric techniques to test molecular hypotheses. We analyse alligator snapping turtle cranial variation amongst populations (i.e. drainages) with the hypothesis that populations of turtles recovered as monophyletic by previous molecular studies are more similar to each other in cranial shape. Dorsal, lateral and ventral cranial shape analyses corroborate the uniqueness of populations recovered by molecular genetic hypotheses. Additionally, analyses reveal near equal separation between drainages that were assigned to monophyletic clades by previous phylogenetic studies. These results reveal the potential for more independent lineages that have yet to be diagnosed, and unique cranial shapes are described for our three most heavily sampled drainages.     

The contribution of de novo and rare inherited copy number changes to congenital heart disease in an unselected sample of children with conotruncal defects or hypoplastic left heart disease

Congenital heart disease (CHD) is the most common congenital malformation, with evidence of a strong genetic component. We analyzed data from 223 consecutively ascertained families, each consisting of at least one child affected by a conotruncal defect (CNT) or hypoplastic left heart disease (HLHS) and both parents. The NimbleGen HD2-2.1 comparative genomic hybridization platform was used to identify de novo and rare inherited copy number variants (CNVs). Excluding 10 cases with 22q11.2 DiGeorge deletions, we validated de novo CNVs in 8 % of 148 probands with CNTs, 12.7 % of 71 probands with HLHS and none in 4 probands with both. Only 2 % of control families showed a de novo CNV. We also identified a group of ultra-rare inherited CNVs that occurred de novo in our sample, contained a candidate gene for CHD, recurred in our sample or were present in an affected sibling. We confirmed the contribution to CHD of copy number changes in genes such as GATA4 and NODAL and identified several genes in novel recurrent CNVs that may point to novel CHD candidate loci. We also found CNVs previously associated with highly variable phenotypes and reduced penetrance, such as dup 1q21.1, dup 16p13.11, dup 15q11.2-13, dup 22q11.2, and del 2q23.1. We found that the presence of extra-cardiac anomalies was not related to the frequency of CNVs, and that there was no significant difference in CNV frequency or specificity between the probands with CNT and HLHS. In agreement with other series, we identified likely causal CNVs in 5.6 % of our total sample, half of which were de novo.