Architecture and function of metallopeptidase catalytic domains

The cleavage of peptide bonds by metallopeptidases (MPs) is essential for life. These ubiquitous enzymes participate in all major physiological processes, and so their deregulation leads to diseases ranging from cancer and metastasis, inflammation, and microbial infection to neurological insults and cardiovascular disorders. MPs cleave their substrates without a covalent intermediate in a single‐step reaction involving a solvent molecule, a general base/acid, and a mono‐ or dinuclear catalytic metal site. Most monometallic MPs comprise a short metal‐binding motif (HEXXH), which includes two metal‐binding histidines and a general base/acid glutamate, and they are grouped into the zincin tribe of MPs. The latter divides mainly into the gluzincin and metzincin clans. Metzincins consist of globular ～130–270‐residue catalytic domains, which are usually preceded by N‐terminal pro‐segments, typically required for folding and latency maintenance. The catalytic domains are often followed by C‐terminal domains for substrate recognition and other protein–protein interactions, anchoring to membranes, oligomerization, and compartmentalization. Metzincin catalytic domains consist of a structurally conserved N‐terminal subdomain spanning a five‐stranded β‐sheet, a backing helix, and an active‐site helix. The latter contains most of the metal‐binding motif, which is here characteristically extended to HEXXHXXGXX(H,D). Downstream C‐terminal subdomains are generally shorter, differ more among metzincins, and mainly share a conserved loop—the Met‐turn—and a C‐terminal helix. The accumulated structural data from more than 300 deposited structures of the 12 currently characterized metzincin families reviewed here provide detailed knowledge of the molecular features of their catalytic domains, help in our understanding of their working mechanisms, and form the basis for the design of novel drugs.     

Compartmentation and fluxes of carbon in leaf blades and leaf sheaths of Poa annua L. and Poa x jemtlandica (Almq.) Richt

Abstract The allocation of photosynthetically fixed carbon in the leaf blades and sheaths of Poa annua (a ruderal grass) and Poa x jemtlandica (a sub-arctic grass) was followed over a light-dark cycle. Labelling with ¹⁴Carbon and gas exchange measurements provide data for an eight-compartment model describing the partitioning of carbon between spatially and chemically separated pools and their rates of turnover. Soluble sugars and fructans were turned over rapidly in the leaf blades of both species. The flux of carbon through pools of storage carbohydrates was higher in the leaves of P. x jemtlandica than in P. annua. The exchange of carbon between pools was slower in the sheath than the blade. Carbohydrates stored in the sheath appeared to have no significant role in metabolism over the light-dark cycle studied here.     

Complex Genetic Effects on Early Vegetative Development Shape Resource Allocation Differences Between Arabidopsis lyrata Populations

Costs of reproduction due to resource allocation trade-offs have long been recognized as key forces in life history evolution, but little is known about their functional or genetic basis. Arabidopsis lyrata, a perennial relative of the annual model plant A. thaliana with a wide climatic distribution, has populations that are strongly diverged in resource allocation. In this study, we evaluated the genetic and functional basis for variation in resource allocation in a reciprocal transplant experiment, using four A. lyrata populations and F₂ progeny from a cross between North Carolina (NC) and Norway parents, which had the most divergent resource allocation patterns. Local alleles at quantitative trait loci (QTL) at a North Carolina field site increased reproductive output while reducing vegetative growth. These QTL had little overlap with flowering date QTL. Structural equation models incorporating QTL genotypes and traits indicated that resource allocation differences result primarily from QTL effects on early vegetative growth patterns, with cascading effects on later vegetative and reproductive development. At a Norway field site, North Carolina alleles at some of the same QTL regions reduced survival and reproductive output components, but these effects were not associated with resource allocation trade-offs in the Norway environment. Our results indicate that resource allocation in perennial plants may involve important adaptive mechanisms largely independent of flowering time. Moreover, the contributions of resource allocation QTL to local adaptation appear to result from their effects on developmental timing and its interaction with environmental constraints, and not from simple models of reproductive costs.     

PDB-wide identification of physiological hetero-oligomeric assemblies based on conserved quaternary structure geometry

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Recombination of repeat elements generates somatic complexity in human genomes

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Spontaneous gallbladder pathology in baboons

Background Gallbladder pathology (GBP) is a relatively uncommon, naturally occurring morbidity in both baboons and humans. Methods A retrospective analysis was performed on 7776 necropsy reports over a 20 year period to determine the prevalence of baboon GBP. Results Ninety‐seven cases of GBP were identified, yielding a 20 year population prevalence of 1.25%. GBP is more common in adult female baboons, occurring with a female to male ratio of nearly 2:1. Among gallbladder pathologies, cholecystitis (35.1%) and cholelithiasis (29.9%) were the most prevalent abnormalities, followed by hyperplasia (16.5%), edema (15.5%), amyloidosis (5.2%), fibrosis (4.1%), necrosis (4.1%), and hemorrhage (1.0%). Conclusion Many epidemiologic similarities exist between GBP in baboons and humans suggesting that the baboon may serve as a reliable animal model system for investigating GBP in humans.     

Coupling Neuropeptide Levels to Structural Plasticity in Drosophila Clock Neurons

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The Structural Basis for Specific Recognition of H3K14 Acetylation by Sth1 in the RSC Chromatin Remodeling Complex

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The infectivity and host range of Orgyia anartoides nucleopolyhedrovirus

The painted apple moth (PAM), Teia anartoides (Walker) (Lepidoptera: Lymantriidae) made a recent incursion into New Zealand. A nucleopolyhedrovirus (NPV), Orgyia anartoides NPV (OranNPV), originally isolated from PAM in Australia, was tested for its pathogenicity to PAM and a range of non‐target insect species found in New Zealand, to evaluate its suitability as a microbial control for this insect invader. Dosage‐mortality tests showed that OranNPV was highly pathogenic to PAM larvae; mean LT₅₀ values for third instars ranged from 17.9 to 8.1 days for doses from 10² to 10⁵ polyhedral inclusion bodies/larva, respectively. The cause of death in infected insects was confirmed as OranNPV. Molecular analysis established that OranNPV can be identified by PCR and restriction digestion, and this process complemented microscopic examination of infected larvae. No lymantriid species occur in New Zealand; however, the virus had no significant effects on species from five other lepidopteran families (Noctuidae, Tortricidae, Geometridae, Nymphalidae and Plutellidae) or on adult honeybees. Thus, all indications from this initial investigation are that OranNPV would be an important tool in the control of PAM in a future incursion of this species into New Zealand.