Maturation of the gastric microvasculature in Xenopus laevis (Lissamphibia, Anura) occurs at the transition from the herbivorous to the carnivorous lifestyle, predominantly by intussuceptive microvascular growth (IMG): a scanning electron microscope study of microvascular corrosion casts and correlative light microscopy

The microvascular bed of the stomach of Xenopus laevis and the changes it undergoes when the herbivorous tadpole becomes a carnivorous adult were studied by scanning electron microscopy of vascular corrosion casts and light microscopy of stained tissue sections. In tadpoles an upper and a lower gastric artery supplied, and upper, middle and lower medial and lateral gastric veins drained the vertically extending stomach. During metamorphosis, the stomach gained a horizontal cranio-caudal extension and vessels accordingly become dorsal and ventral gastric arteries, and anterior, middle and posterior gastric veins, respectively. Up to stage 64 (late climax) mucosal capillaries formed a polygonal network of wide immature-looking capillaries ensheathing gastric glands in a basket-like manner. From stage 64 onwards, blood vessels of the stomach appeared mature, revealed a clear hierarchy and were correlated closely with the histomorphology of the stomach, which had also gained the adult pattern. Within the gastric mucosa, ascending arterioles branched in a fountain-like pattern into wide subepithelial capillaries establishing a centripetal blood flow along the gastric glands, which makes an ultrashort control loop of glandular cells within the branched tubular gastric glands very unlikely. Formation of the stomach external muscular layer started at stage 57 when smooth muscle cells locally formed a single longitudinal and one-to-two single circular layers. Abundant signs of intussusceptive microvascular growth and rare vascular sprouts in vascular corrosion casts indicated that the larval-to-adult microvascular pattern formation of the stomach of Xenopus laevis Daudin occurs predominantly by non-sprouting angiogenesis

Population genomics of speciation and admixture

The application of population genomics to the understanding of speciation has led to the emerging field of speciation genomics. This has brought new insight into how divergence builds up within the genome during speciation and is also revealing the extent to which species can continue to exchange genetic material despite reproductive barriers. It is also providing powerful new approaches for linking genotype to phenotype in admixed populations. In this chapter, we give an overview of some of the methods that have been used and some of the novel insights gained. We also outline some of the pitfalls of the most commonly used methods and possible problems with interpretation of the results

Exploring the Trypanosoma brucei Hsp83 Potential as a Target for Structure Guided Drug Design

Human African trypanosomiasis is a neglected parasitic disease that is fatal if untreated. The current drugs available to eliminate the causative agent Trypanosoma brucei have multiple liabilities, including toxicity, increasing problems due to treatment failure and limited efficacy. There are two approaches to discover novel antimicrobial drugs--whole-cell screening and target-based discovery. In the latter case, there is a need to identify and validate novel drug targets in Trypanosoma parasites. The heat shock proteins (Hsp), while best known as cancer targets with a number of drug candidates in clinical development, are a family of emerging targets for infectious diseases. In this paper, we report the exploration of T. brucei Hsp83--a homolog of human Hsp90--as a drug target using multiple biophysical and biochemical techniques. Our approach included the characterization of the chemical sensitivity of the parasitic chaperone against a library of known Hsp90 inhibitors by means of differential scanning fluorimetry (DSF). Several compounds identified by this screening procedure were further studied using isothermal titration calorimetry (ITC) and X-ray crystallography, as well as tested in parasite growth inhibitions assays. These experiments led us to the identification of a benzamide derivative compound capable of interacting with TbHsp83 more strongly than with its human homologs and structural rationalization of this selectivity. The results highlight the opportunities created by subtle structural differences to develop new series of compounds to selectively target the Trypanosoma brucei chaperone and effectively kill the sleeping sickness parasite

Tipping points in the dynamics of speciation.

Speciation can be gradual or sudden and involve few or many genetic changes. Inferring the processes generating such patterns is difficult, and may require consideration of emergent and non-linear properties of speciation, such as when small changes at tipping points have large effects on differentiation. Tipping points involve positive feedback and indirect selection stemming from associations between genomic regions, bi-stability due to effects of initial conditions and evolutionary history, and dependence on modularity of system components. These features are associated with sudden 'regime shifts' in other cellular, ecological, and societal systems. Thus, tools used to understand other complex systems could be fruitfully applied in speciation research

A Bioinformatics Filtering Strategy for Identifying Radiation Response Biomarker Candidates

The number of biomarker candidates is often much larger than the number of clinical patient data points available, which motivates the use of a rational candidate variable filtering methodology. The goal of this paper is to apply such a bioinformatics filtering process to isolate a modest number (<10) of key interacting genes and their associated single nucleotide polymorphisms involved in radiation response, and to ultimately serve as a basis for using clinical datasets to identify new biomarkers. In step 1, we surveyed the literature on genetic and protein correlates to radiation response, in vivo or in vitro, across cellular, animal, and human studies. In step 2, we analyzed two publicly available microarray datasets and identified genes in which mRNA expression changed in response to radiation. Combining results from Step 1 and Step 2, we identified 20 genes that were common to all three sources. As a final step, a curated database of protein interactions was used to generate the most statistically reliable protein interaction network among any subset of the 20 genes resulting from Steps 1 and 2, resulting in identification of a small, tightly interacting network with 7 out of 20 input genes. We further ranked the genes in terms of likely importance, based on their location within the network using a graph-based scoring function. The resulting core interacting network provides an attractive set of genes likely to be important to radiation response

Consensus guidelines for the use and interpretation of angiogenesis assays

The formation of new blood vessels, or angiogenesis, is a complex process that plays important roles in growth and development, tissue and organ regeneration, as well as numerous pathological conditions. Angiogenesis undergoes multiple discrete steps that can be individually evaluated and quantified by a large number of bioassays. These independent assessments hold advantages but also have limitations. This article describes in vivo, ex vivo, and in vitro bioassays that are available for the evaluation of angiogenesis and highlights critical aspects that are relevant for their execution and proper interpretation. As such, this collaborative work is the first edition of consensus guidelines on angiogenesis bioassays to serve for current and future reference

Molecular mechanisms of cell death: recommendations of the Nomenclature Committee on Cell Death 2018.

Over the past decade, the Nomenclature Committee on Cell Death (NCCD) has formulated guidelines for the definition and interpretation of cell death from morphological, biochemical, and functional perspectives. Since the field continues to expand and novel mechanisms that orchestrate multiple cell death pathways are unveiled, we propose an updated classification of cell death subroutines focusing on mechanistic and essential (as opposed to correlative and dispensable) aspects of the process. As we provide molecularly oriented definitions of terms including intrinsic apoptosis, extrinsic apoptosis, mitochondrial permeability transition (MPT)-driven necrosis, necroptosis, ferroptosis, pyroptosis, parthanatos, entotic cell death, NETotic cell death, lysosome-dependent cell death, autophagy-dependent cell death, immunogenic cell death, cellular senescence, and mitotic catastrophe, we discuss the utility of neologisms that refer to highly specialized instances of these processes. The mission of the NCCD is to provide a widely accepted nomenclature on cell death in support of the continued development of the field