An independent validation study of loci associated with nematode resistance in sheep

Gastrointestinal nematode infection is a constraint on sheep production worldwide. Selective breeding programmes to enhance resistance to nematode infection are currently being implemented in a number of countries. Identification of loci associated with resistance to infection or causative mutations for resistance would enable more effective selection. Loci associated with indicator traits for nematode resistance has been identified in previous studies. In this study, Scottish Blackface, Texel and Suffolk lambs were used to validate the effects at eight genomic regions previously associated with nematode resistance (OAR3, 4, 5, 7, 12, 13, 14, 21). No SNP was significantly associated with nematode resistance at the region‐wide level but seven SNPs in three of the regions (OAR4, 12, 14) were nominally associated with trichostrongyle egg count in this study and six of these were also significant when fitted as single SNP effects. Nematodirus egg count was nominally associated with SNPs on OAR3, 4, 7 and 12.     

Declining old‐forest species as a legacy of large trees lost

Aim

Global declines in large old trees from selective logging have degraded old‐forest ecosystems, which could lead to delayed declines or losses of old‐forest‐associated wildlife populations (i.e., extinction debt). We applied the declining population paradigm and explored potential evidence for extinction debt in an old‐forest dependent species across landscapes with different histories of large tree logging.

Location

Montane forests of the Sierra Nevada, California, USA.

Methods

We tested hypotheses about the influence of forest structure on territory extinction dynamics of the spotted owl (Strix occidentalis) using detection/non‐detection data from 1993 to 2011 across two land tenures: national forests, which experienced extensive large tree logging over the past century, and national parks, which did not.

Results

Large tree/high canopy cover forest was the best predictor of extinction rates and explained 26%–77% of model deviance. Owl territories with more large tree/high canopy cover forest had lower extinction rates, and this forest type was ~4 times more prevalent within owl territories in national parks ( = 19% of territory) than national forests ( = 4% of territory). As such, predicted extinction probability for an average owl territory was ~2.5 times greater in national forests than national parks, where occupancy was declining () and stable (), respectively. Large tree/high canopy cover forest remained consistently low, but did not decline, during the study period on national forests while owl declines were ongoing—an observation consistent with an extinction debt.

Main conclusions

In identifying a linkage between large trees and spotted owl dynamics at a regional scale, we provide evidence suggesting past logging of large old trees may have contributed to contemporary declines in an old‐forest species. Strengthening protections for remaining large old trees and promoting their recruitment in the future will be critical for biodiversity conservation in the world's forests.

     

THE CONTRIBUTION OF CEREBRAL ANGIOGRAPHY IN DIAGNOSIS

Angiography is important in the diagnosis of central nervous system disorders. In operable lesions it not only discloses the location of the lesion but also gives valuable information regarding its character and surrounding vascular architecture.The technique of both the pericutaneous and the open methods is described. The advantages of the controlled automatic arteriograph are described as well as pertinent information regarding cerebral circulation time.The choice of contrast media and the advantages and disadvantages of each are described.The three phases of angiography important in diagnosis—the arterial phase, the capillary phase and the venous phase—are discussed.The indications and contraindications are briefly outlined with respect to neoplasms, trauma, hemorrhage, aneurysms and other such operable lesions.The characteristic changes produced by aneurysms, vascular malformations, neoplasms and other space-occupying lesions as related to the circulatory apparatus show variations characterizing the type of lesion encountered.Angiography in traumatic conditions, while limited, is of exceptional value in the diagnosis of obscure lesions, particularly the subdural hematomas.     

The role of inhibitory dynamics in the loss and reemergence of macropodoid tooth traits

The reversibility of phenotypic evolution is likely to be strongly influenced by the ability of underlying developmental systems to generate ancestral traits. However, few studies have quantitatively linked these developmental dynamics to traits that reevolve. In this study, we assess how changes in the inhibitory cascade, a developmental system that regulates relative tooth size in mammals, influenced the loss and reversals of the posthypocristid, a molar tooth crest, in the kangaroo superfamily Macropodoidea. We find that posthypocristid loss is linked with reduced levels of posterior molar inhibition, potentially driven by selection for lophodont, higher‐crowned molar teeth. There is strong support for two posthypocristid reversals, each occurring after more than 15 million years of absence, in large‐bodied species of Macropus, and two giant extinct species of short‐faced sthenurine kangaroo (Procoptodon). We find that whereas primitive posthypocristid expression is linked to higher levels of posterior molar inhibition, reemergence is tied to a relative increase in third molar size associated with increasing body mass, producing molar phenotypes similar to those in mouse where the ectodysplasin pathway is upregulated. We argue that although shifts in the inhibitory cascade may enable reemergence, dietary ecology may limit the frequency of phylogenetic reversal.     

Molecular basis for DNA strand displacement by NHEJ repair polymerases

The non-homologous end-joining (NHEJ) pathway repairs DNA double-strand breaks (DSBs) in all domains of life. Archaea and bacteria utilize a conserved set of multifunctional proteins in a pathway termed Archaeo-Prokaryotic (AP) NHEJ that facilitates DSB repair. Archaeal NHEJ polymerases (Pol) are capable of strand displacement synthesis, whilst filling DNA gaps or partially annealed DNA ends, which can give rise to unligatable intermediates. However, an associated NHEJ phosphoesterase (PE) resects these products to ensure that efficient ligation occurs. Here, we describe the crystal structures of these archaeal (Methanocella paludicola) NHEJ nuclease and polymerase enzymes, demonstrating their strict structural conservation with their bacterial NHEJ counterparts. Structural analysis, in conjunction with biochemical studies, has uncovered the molecular basis for DNA strand displacement synthesis in AP-NHEJ, revealing the mechanisms that enable Pol and PE to displace annealed bases to facilitate their respective roles in DSB repair.     

Circulating peripheral blood fibrocytes in human fibrotic interstitial lung disease

Fibrotic interstitial lung diseases are illnesses of unknown cause characterized by progressive decline in lung function. Fibrocytes are bone marrow-derived, circulating progenitor cells capable of differentiating into diverse mesenchymal cell types. Prior work has shown fibrocytes to traffic to the lung via the CXCL12-CXCR4 chemokine axis in an animal model of pulmonary fibrosis. We therefore assessed the relevance of fibrocytes in patients with fibrotic interstitial lung disease. We found enhanced expression of CXCL12 in both the lungs and plasma of patients with lung fibrosis. CXCL12 levels were associated with an order of magnitude higher number of circulating fibrocytes in the peripheral blood of these patients. Most of the circulating fibrocytes in patients with interstitial lung diseases were negative for the myofibroblast marker alpha-smooth muscle actin, suggesting a relatively undifferentiated phenotype. Taken together, these data suggest that fibrocytes are involved in the pathogenesis of human lung fibrosis.     

Inferred expression regulator activities suggest genes mediating cardiometabolic genetic signals

Expression QTL (eQTL) analyses have suggested many genes mediating genome-wide association study (GWAS) signals but most GWAS signals still lack compelling explanatory genes. We have leveraged an adipose-specific gene regulatory network to infer expression regulator activities and phenotypic master regulators (MRs), which were used to detect activity QTLs (aQTLs) at cardiometabolic trait GWAS loci. Regulator activities were inferred with the VIPER algorithm that integrates enrichment of expected expression changes among a regulator’s target genes with confidence in their regulator-target network interactions and target overlap between different regulators (i.e., pleiotropy). Phenotypic MRs were identified as those regulators whose activities were most important in predicting their respective phenotypes using random forest modeling. While eQTLs were typically more significant than aQTLs in cis, the opposite was true among candidate MRs in trans. Several GWAS loci colocalized with MR trans-eQTLs/aQTLs in the absence of colocalized cis-QTLs. Intriguingly, at the 1p36.1 BMI GWAS locus the EPHB2 cis-aQTL was stronger than its cis-eQTL and colocalized with the GWAS signal and 35 BMI MR trans-aQTLs, suggesting the GWAS signal may be mediated by effects on EPHB2 activity and its downstream effects on a network of BMI MRs. These MR and aQTL analyses represent systems genetic methods that may be broadly applied to supplement standard eQTL analyses for suggesting molecular effects mediating GWAS signals.