Retinoic acid breakdown is required for proximodistal positional identity during amphibian limb regeneration.

Regenerating limbs retain their proximodistal (PD) positional identity following amputation. This positional identity is genetically encoded by PD patterning genes that instruct blastema cells to regenerate the appropriate PD limb segment. Retinoic acid (RA) is known to specify proximal limb identity, but how RA signaling levels are established in the blastema is unknown.

Biochemical and Structural Studies of the Carminomycin 4--Methyltransferase DnrK.

Structural and functional studies of the carminomycin 4--methyltransferase DnrK are described, with an emphasis on interrogating the acceptor substrate scope of DnrK. Specifically, the evaluation of 100 structurally and functionally diverse natural products and natural product mimetics revealed an array of pharmacophores as productive DnrK substrates. Representative newly identified DnrK substrates from this study included anthracyclines, angucyclines, anthraquinone-fused enediynes, flavonoids, pyranonaphthoquinones, and polyketides.

Do organisms need an impact factor? Citations of key biological resources including model organisms reveal usage patterns and impact.

Research resources like transgenic animals and antibodies are the workhorses of biomedicine, enabling investigators to relatively easily study specific disease conditions. As key biological resources, transgenic animals and antibodies are often validated, maintained, and distributed from university based stock centers. As these centers heavily rely largely on grant funding, it is critical that they are cited by investigators so that usage can be tracked.

Evolution of the nitric oxide synthase family in vertebrates and novel insights in gill development.

Nitric oxide (NO) is an ancestral key signalling molecule essential for life and has enormous versatility in biological systems, including cardiovascular homeostasis, neurotransmission and immunity. Although our knowledge of NO synthases (Nos), the enzymes that synthesize NO , is substantial, the origin of a large and diversified repertoire of gene orthologues in fishes with respect to tetrapods remains a puzzle. The recent identification of in the ray-finned fish spotted gar, which was considered lost in this lineage, changed this perspective.

HDAC Inhibitor Titration of Transcription and Axolotl Tail Regeneration.

New patterns of gene expression are enacted and regulated during tissue regeneration. Histone deacetylases (HDACs) regulate gene expression by removing acetylated lysine residues from histones and proteins that function directly or indirectly in transcriptional regulation. Previously we showed that romidepsin, an FDA-approved HDAC inhibitor, potently blocks axolotl embryo tail regeneration by altering initial transcriptional responses to injury.

Genetic basis for an evolutionary shift from ancestral preaxial to postaxial limb polarity in non-urodele vertebrates.

In most tetrapod vertebrates, limb skeletal progenitors condense with postaxial dominance. Posterior elements (such as ulna and fibula) appear prior to their anterior counterparts (radius and tibia), followed by digit-appearance order with continuing postaxial polarity. The only exceptions are urodele amphibians (salamanders), whose limb elements develop with preaxial polarity and who are also notable for their unique ability to regenerate complete limbs as adults.

Taxonomic and Metabolomics Profiling of Actinobacteria Strains from Himalayan Collection Sites in Pakistan.

Actinobacteria have proven themselves as the major producers of bioactive compounds with wide applications. In this study, 35 actinobacteria strains were isolated from soil samples collected from the Himalayan mountains region in Pakistan. The isolated strains were identified by polyphasic taxonomy and were prioritized based on biological and chemical screening to identify the strains with ability to produce inimitable metabolites.

Gene and transgenics nomenclature for the laboratory axolotl-Ambystoma mexicanum.

The laboratory axolotl (Ambystoma mexicanum) is widely used in biological research. Recent advancements in genetic and molecular toolkits are greatly accelerating the work using axolotl, especially in the area of tissue regeneration. At this juncture, there is a critical need to establish gene and transgenic nomenclature to ensure uniformity in axolotl research.

Chemical genetics of regeneration: Contrasting temporal effects of CoCl on axolotl tail regeneration.

Background: Histone deacetylases (HDACs) regulate transcriptional responses to injury stimuli that are critical for successful tissue regeneration. Previously we showed that HDAC inhibitor romidepsin potently inhibits axolotl tail regeneration when applied for only 1-minute postamputation (MPA).

Results: Here we tested CoCl a chemical that induces hypoxia and cellular stress, for potential to reverse romidepsin inhibition of tail regeneration.

Large-scale variation in single nucleotide polymorphism density within the laboratory axolotl (Ambystoma mexicanum).

Background: Recent efforts to assemble and analyze the Ambystoma mexicanum genome have dramatically improved the potential to develop molecular tools and pursue genome-wide analyses of genetic variation.

Results: To better resolve the distribution and origins of genetic variation with A mexicanum, we compared DNA sequence data for two laboratory A mexicanum and one A tigrinum to identify 702 million high confidence polymorphisms distributed across the 32 Gb genome. While the wild-caught A tigrinum was generally more polymorphic in a genome-wide sense, several multi-megabase regions were identified from A mexicanum genomes that were actually more polymorphic than A tigrinum.

The rax homeobox gene is mutated in the eyeless axolotl, Ambystoma mexicanum.

Background: Vertebrate eye formation requires coordinated inductive interactions between different embryonic tissue layers, first described in amphibians. A network of transcription factors and signaling molecules controls these steps, with mutations causing severe ocular, neuronal, and craniofacial defects. In eyeless mutant axolotls, eye morphogenesis arrests at the optic vesicle stage, before lens induction, and development of ventral forebrain structures is disrupted.

A reference transcriptome for , an Andean mountain salamander in Colombia.

The amphibian order Caudata, contains several important model species for biological research. However, there is need to generate transcriptome data from representative species of the primary salamander families. Here we describe a reference transcriptome for a terrestrial salamander, (Caudata: Plethodontidae).

Structure Determination, Functional Characterization, and Biosynthetic Implications of Nybomycin Metabolites from a Mining Reclamation Site-Associated .

We report the isolation and characterization of three new nybomycins (nybomycins B-D, -) and six known compounds (nybomycin, ; deoxynyboquinone, ; α-rubromycin, ; β-rubromycin, ; γ-rubromycin, ; and [2α(1,3),4β]-2-(1,3-pentadienyl)-4-piperidinol, ) from the Rock Creek (McCreary County, KY) underground coal mine acid reclamation site isolate sp. AD-3-6. Nybomycin D () and deoxynyboquinone () displayed moderate () to potent () cancer cell line cytotoxicity and displayed weak to moderate anti-Gram-(+) bacterial activity, whereas rubromycins - displayed little to no cancer cell line cytotoxicity but moderate to potent anti-Gram-(+) bacterial and antifungal activity.

OleD Loki as a Catalyst for Hydroxamate Glycosylation.

Herein we describe the ability of the permissive glycosyltransferase (GT) OleD Loki to convert a diverse set of >15 histone deacetylase (HDAC) inhibitors (HDACis) into their corresponding hydroxamate glycosyl esters. Representative glycosyl esters were subsequently evaluated in assays for cancer cell line cytotoxicity, chemical and enzymatic stability, and axolotl embryo tail regeneration. Computational substrate docking models were predictive of enzyme-catalyzed turnover and suggest certain HDACis may form unproductive, potentially inhibitory, complexes with GTs.

Towards comparative analyses of salamander limb regeneration.

Among tetrapods, only salamanders can regenerate their limbs and tails throughout life. This amazing regenerative ability has attracted the attention of scientists for hundreds of years. Now that large, salamander genomes are beginning to be sequenced for the first time, omics tools and approaches can be used to integrate new perspectives into the study of tissue regeneration.

Total synthesis of griseusins and elucidation of the griseusin mechanism of action.

A divergent modular strategy for the enantioselective total synthesis of 12 naturally-occurring griseusin type pyranonaphthoquinones and 8 structurally-similar analogues is described. Key synthetic highlights include Cu-catalyzed enantioselective boration-hydroxylation and hydroxyl-directed C-H olefination to afford the central pharmacophore followed by epoxidation-cyclization and maturation diastereoselective reduction and regioselective acetylation. Structural revision of griseusin D and absolute structural assignment of 2,8-epoxy--4'-deacetyl griseusin B are also reported.

Baraphenazines A-G, Divergent Fused Phenazine-Based Metabolites from a Himalayan Streptomyces.

The structures and bioactivities of three unprecedented fused 5-hydroxyquinoxaline/alpha-keto acid amino acid metabolites (baraphenazines A-C, 1-3), two unique diastaphenazine-type metabolites (baraphenazines D and E, 4 and 5) and two new phenazinolin-type (baraphenazines F and G, 6 and 7) metabolites from the Himalayan isolate Streptomyces sp. PU-10A are reported. This study highlights the first reported bacterial strain capable of producing diastaphenazine-type, phenazinolin-type, and izumiphenazine A-type metabolites and presents a unique opportunity for the future biosynthetic interrogation of late-stage phenazine-based metabolite maturation.

HDAC Regulates Transcription at the Outset of Axolotl Tail Regeneration.

Tissue regeneration is associated with complex changes in gene expression and post-translational modifications of proteins, including transcription factors and histones that comprise chromatin. We tested 172 compounds designed to target epigenetic mechanisms in an axolotl (Ambystoma mexicanum) embryo tail regeneration assay. A relatively large number of compounds (N = 55) inhibited tail regeneration, including 18 histone deacetylase inhibitors (HDACi).

Rediscovering the Axolotl as a Model for Thyroid Hormone Dependent Development.

The Mexican axolotl () is an important model organism in biomedical research. Much current attention is focused on the axolotl's amazing ability to regenerate tissues and whole organs after injury. However, not forgotten is the axolotl's equally amazing ability to thwart aspects of tissue maturation and retain juvenile morphology into the adult phase of life.

A chromosome-scale assembly of the axolotl genome.

The axolotl () provides critical models for studying regeneration, evolution, and development. However, its large genome (∼32 Gb) presents a formidable barrier to genetic analyses. Recent efforts have yielded genome assemblies consisting of thousands of unordered scaffolds that resolve gene structures, but do not yet permit large-scale analyses of genome structure and function.

Amputation-induced reactive oxygen species signaling is required for axolotl tail regeneration.

Background: Among vertebrates, salamanders are unparalleled in their ability to regenerate appendages throughput life. However, little is known about early signals that initiate regeneration in salamanders.

Results: Ambystoma mexicanum embryos were administered tail amputations to investigate the timing of reactive oxygen species (ROS) production and the requirement of ROS for regeneration.