Evolutionary divergence of a Hoxa2b hindbrain enhancer in syngnathids mimics results of functional assays

SLC6A19 (B0AT1) is a neutral amino acid transporter, the loss of function of which results in Hartnup disease. SLC6A19 is also believed to have an important role in amino acid homeostasis, diabetes, and weight control. A small-molecule inhibitor of human SLC6A19 (hSLC6A19) was identified using two functional cell-based assays: a fluorescence imaging plate reader (FLIPR) membrane potential (FMP) assay and a stable isotope-labeled neutral amino acid uptake assay. A diverse collection of 3440 pharmacologically active compounds from the Microsource Spectrum and Tocriscreen collections were tested at 10 µM in both assays using MDCK cells stably expressing hSLC6A19 and its obligatory subunit, TMEM27. Compounds that inhibited SLC6A19 activity in both assays were further confirmed for activity and selectivity and characterized for potency in functional assays against hSLC6A19 and related transporters. A single compound, cinromide, was found to robustly, selectively, and reproducibly inhibit SLC6A19 in all functional assays. Structurally related analogs of cinromide were tested to demonstrate structure–activity relationship (SAR). The assays described here are suitable for carrying out high-throughput screening campaigns to identify modulators of SLC6A19.

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Segregation and speciation in the Neogene planktonic foraminiferal clade Globoconella

Paleobiology ◽

10.1017/s0094837300021345 ◽

1999 ◽

Vol 25 (3) ◽

pp. 383-395 ◽

Cited By ~ 6

Author(s):

Cynthia E. Schneider ◽

James P. Kennett

Keyword(s):

Morphological Evolution ◽

Evolutionary Divergence ◽

Clinal Variation ◽

Near Surface ◽

Surface Warming ◽

Isotopic Analyses ◽

Oxygen Isotopic ◽

Morphological Differences ◽

Middle Pliocene ◽

Water Depths

The origin of the Neogene planktonic foraminifer Globorotalia (Globoconella) pliozea in the subtropical southwest Pacific has been attributed to its isolation resulting from intensification of the Subtropical Divergence (Tasman Front). Oxygen isotopic analyses suggest that, although the Subtropical Divergence may have played a role, the evolution of Gr. (G.) pliozea was facilitated by depth segregation of Gr. (G.) conomiozea morphotypes (low and high conical) during an interval of near-surface warming and increasing thermal gradient. Oxygen isotopic analyses suggest that low conical morphotypes of Gr. (G.) conomiozea inhabited greater depths than high conical morphotypes. Low conical forms of Gr. (G.) conomiozea are considered ancestral to the low conical species, Gr. (G.) pliozea. Oxygen isotopes indicate that Gr. (G.) pliozea inhabited greater depths than its ancestor, Gr. (G.) conomiozea.These data are consistent with depth-parapatric and depth-allopatric models, but not with a sympatric model of speciation. In the allopatric model, reproduction at different water depths acts as a barrier between morphotypes. In the parapatric model, clinal variation along a depth gradient acts as a barrier between morphotypes living at the limits of the gradient. Depth segregation in both models results in genetic isolation and evolutionary divergence. Our data support a correlation between morphological evolution and habitat changes in the Globoconella clade, implying separation of populations as a driving force for morphological evolution.Ecological segregation of morphotypes and species may be related to morphology (height of the conical angle), based on the data from Gr. (G.) conomiozea and Gr. (G.) pliozea. However, morphological differences alone do not necessarily produce depth differences. Large morphological differences between Gr. (G.) pliozea and closely related Gr. (G.) puncticulata did not result in isotopic and therefore depth differences between these species. These species coexisted at the same water depths for nearly 1 m.y. Thus, it is unlikely that the extinction of Gr. (G.) pliozea in the middle Pliocene resulted from competition with Gr. (G.) puncticulata, as previously suggested.

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Expansion and accelerated evolution of 9-exon odorant receptors in Polistes paper wasps

Molecular Biology and Evolution ◽

10.1093/molbev/msab023 ◽

2021 ◽

Author(s):

Andrew W Legan ◽

Christopher M Jernigan ◽

Sara E Miller ◽

Matthieu F Fuchs ◽

Michael J Sheehan

Keyword(s):

Gene Family ◽

Odorant Receptor ◽

Receptor Gene ◽

Gene Tree ◽

Gene Family Evolution ◽

Paper Wasp ◽

Gene Copy ◽

Evolutionary Divergence ◽

Wasp Species ◽

Or Gene

Abstract Independent origins of sociality in bees and ants are associated with independent expansions of particular odorant receptor (OR) gene subfamilies. In ants, one clade within the OR gene family, the 9-exon subfamily, has dramatically expanded. These receptors detect cuticular hydrocarbons (CHCs), key social signaling molecules in insects. It is unclear to what extent 9-exon OR subfamily expansion is associated with the independent evolution of sociality across Hymenoptera, warranting studies of taxa with independently derived social behavior. Here we describe odorant receptor gene family evolution in the northern paper wasp, Polistes fuscatus, and compare it to four additional paper wasp species spanning ∼40 million years of evolutionary divergence. We find 200 putatively functional OR genes in P. fuscatus, matching predictions from neuroanatomy, and more than half of these are in the 9-exon subfamily. Most OR gene expansions are tandemly arrayed at orthologous loci in Polistes genomes, and microsynteny analysis shows species-specific gain and loss of 9-exon ORs within tandem arrays. There is evidence of episodic positive diversifying selection shaping ORs in expanded subfamilies. Values of omega (d N/dS) are higher among 9-exon ORs compared to other OR subfamilies. Within the Polistes OR gene tree, branches in the 9-exon OR clade experience relaxed negative (purifying) selection relative to other branches in the tree. Patterns of OR evolution within Polistes are consistent with 9-exon OR function in CHC perception by combinatorial coding, with both natural selection and neutral drift contributing to interspecies differences in gene copy number and sequence.

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Evaluation of the Expression of CCR5 and CX3CR1 Receptors and Correlation with the Functionality of T Cells in Women infected with ZIKV during Pregnancy

Viruses ◽

10.3390/v13020191 ◽

2021 ◽

Vol 13 (2) ◽

pp. 191

Author(s):

Débora Familiar-Macedo ◽

Iury Amancio Paiva ◽

Jessica Badolato-Corrêa da Silva ◽

Fabiana Rabe de Carvalho ◽

Helver Gonçalves Dias ◽

...

Keyword(s):

Flow Cytometry ◽

T Cells ◽

Clinical Outcome ◽

Cell Responses ◽

Functional Assays ◽

Asymptomatic Children ◽

Cd107a Expression ◽

Congenital Zika Syndrome ◽

Ifn Γ

There have been reports of neurological abnormalities associated with the Zika virus (ZIKV), such as congenital Zika syndrome (CZS) in children born to mothers infected during pregnancy. We investigated how the immune response to ZIKV during pregnancy is primed and conduct a thorough evaluation of the inflammatory and cytotoxic profiles as well as the expression of CCR5 and CX3CR1. We compared the reactivity of T cells to ZIKV peptides in convalescent mothers infected during pregnancy. The child’s clinical outcome (i.e., born with or without CZS) was taken to be the variable. The cells were stimulated in vitro with ZIKV peptides and evaluated using the ELISPOT and flow cytometry assays. After in vitro stimulation with ZIKV peptides, we observed a tendency toward a higher Interferon gamma (IFN-γ)-producing T cell responses in mothers who had asymptomatic children and a higher CD107a expression in T cells in mothers who had children with CZS. We found a higher frequency of T cells expressing CD107a+ and co-expressing CX3CR1+CCR5+, which is much clearer in the T cells of mothers who had CZS children. We suggest that this differential profile influenced the clinical outcome of babies. These data need to be further investigated, including the evaluation of other ZIKV peptides and markers and functional assays.

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