skip to main content

Attention:

The NSF Public Access Repository (NSF-PAR) system and access will be unavailable from 11:00 PM ET on Thursday, October 10 until 2:00 AM ET on Friday, October 11 due to maintenance. We apologize for the inconvenience.


Title: Recent Advances in Stereocontrolled Mannosylation: Focus on Glycans Comprising Acidic and/or Amino Sugars
Abstract

The main focus of this review is to describe accomplishments made in the stereoselective synthesis ofβ‐linked mannosides functionalized with carboxyls or amines/amides. These ManNAc, ManA and ManNAcA residues found in many glycoconjugates, bacterial polysaccharides, and alginates have consistently captured interest of the glycoscience community both due to synthetic challenge and therapeutic potential.

 
more » « less
Award ID(s):
2147156 1800350
NSF-PAR ID:
10303425
Author(s) / Creator(s):
 ;  
Publisher / Repository:
Wiley Blackwell (John Wiley & Sons)
Date Published:
Journal Name:
The Chemical Record
Volume:
21
Issue:
11
ISSN:
1527-8999
Page Range / eLocation ID:
p. 3278-3294
Format(s):
Medium: X
Sponsoring Org:
National Science Foundation
More Like this
  1. Abstract Aim

    Identification of the processes that generate and maintain species diversity within the same region can provide insight into biogeographic patterns at broader spatiotemporal scales. Hawkfishes in the genusParacirrhitesare a unique taxon to explore with respect to niche differentiation, exhibiting diagnostic differences in coloration, and an apparent center of distribution outside of the Indo–Malay–Philippine (IMP) biodiversity hotspot for coral reef fishes. Our aim is to use next‐generation sequencing methods to leverage samples of a taxon at their center of maximum diversity to explore phylogenetic relationships and a possible mechanism of coexistence.

    Location

    Flint Island, Southern Line Islands, Republic of Kiribati.

    Methods

    A comprehensive review of museum records, the primary literature, and unpublished field survey records was undertaken to determine ranges for four “arc‐eye” hawkfish species in theParacirrhitesspecies complex and a potential hybrid. Fish from fourParacirrhitesspecies were collected from Flint Island in the Southern Line Islands, Republic of Kiribati. Hindgut contents were sequenced, and subsequent metagenomic analyses were used to assess the phylogenetic relatedness of the host fish, the microbiome community structure, and prey remains for each species.

    Results

    Phylogenetic analyses conducted with recovered mitochondrial genomes revealed clustering ofP. bicolorwithP. arcatusandP. xanthuswithP. nisus, which were unexpected on the basis of previous morphological work in this species complex. Differences in taxonomic composition of gut microbial communities and presumed prey remains indicate likely separation of foraging niches.

    Main Conclusions

    Our findings point toward previously unidentified relationships in this cryptic species complex at its proposed center of distribution. The three species endemic to the Polynesian province (P. nisus,P. xanthus, andP. bicolor) cluster separately from the more broadly distributedP. arcatuson the basis of relative abundance of metazoan sequences in the gut (presumed prey remains).Discordance between gut microbial communities and phylogeny of the host fish further reinforce the hypothesis of niche separation.

     
    more » « less
  2. Abstract Aim

    We investigate the evolutionary mechanisms that allow morphologically convergent lineages to share the same geographical space. We compared the evolutionary events that occurred along the diversification ofKarawataandAechmeasubgen.Chevalierain the Atlantic Forest by (a) verifying whether the climatic niches and habitats ofKarawataandChevalieraare similar; (b) testing whether the two groups had the same pattern of colonization in the Atlantic Forest; and (c) evaluating whether they had the same evolutionary dynamics of environmental space occupation.

    Location

    Brazilian Atlantic Forest

    Taxon

    KarawataandAechmeasubgen.Chevaliera(Bromeliaceae: Bromelioideae)

    Methods

    We explored differences in evolutionary dynamics betweenKarawataandChevalieraby (a) analyzing their divergence times using Bayesian inference with a relaxed molecular clock; (b) estimating ancestral ranges and habitats with Dispersion Extinction Cladogenesis Lagrange and Statistical Dispersal Vicariance analyses; (c) testing climatic niche similarity, equivalency and overlap using principal component analysis; and, (d) evaluating shifts in speciation dynamics using Bayesian Analysis of Macroevolutionary Mixtures.

    Results

    KarawataandChevalieramost likely originated in the Pliocene and diversified during the Pleistocene. The two clades originated in ombrophilous forests and shared a similar environmental space. However,KarawataandChevalierashow different dynamics in the occupation of geographical and environmental spaces.

    Main Conclusions

    Our results suggest that the São Francisco and Jequitinhonha Rivers acted as geographical barriers forKarawataandChevaliera. Differences in spatial and environmental evolutionary dynamics have allowed the two groups to occupy similar habitats as well as environmental and geographical spaces in the Brazilian Atlantic Forest.

     
    more » « less
  3. Abstract Aim

    A central aim of biogeography is to understand how biodiversity is generated and maintained across landscapes. Here, we establish phylogenetic and population genetic patterns in a widespread reptile to quantify the influence of historical biogeography and current environmental variation on patterns of genetic diversity.

    Location

    Western North America.

    Taxon

    Western terrestrial garter snake,Thamnophis elegans.

    Methods

    We used double‐digest RADseq to estimate phylogenetic relationships and characterize population genetic structure across the three widespread subspecies ofTelegans:T. e. vagrans(wandering garter snake),Teelegans(mountain garter snake) andTeterrestris(coast garter snake). We assessed patterns of dispersal and vicariance across biogeographic regions using ancestral area reconstruction (AAR) and deviations from isolation‐by‐distance across the landscape using estimated effective migration surfaces (EEMS). We identified environmental variables potentially shaping local adaptation in regional lineages using genetic‐environment association (GEA) analyses.

    Results

    We recovered three well‐differentiated genetic groups that correspond to the three subspecies. AAR analyses inferred the eastern Cascade Range as the ancestral area, with dispersal to both the east and west across western North America. Populations ofT. e. elegansdisplayed a latitudinal gradient in genetic variation across the Sierra Nevada and northern California, while populations ofTeterrestrisshow discrete genetic breaks consistent with well‐known biogeographic barriers. Lastly, GEA analyses identified allele frequency shifts at loci associated with a common set of environmental variables in bothTeelegansandTeterrestris.

    Main Conclusion

    T. elegansis composed of distinct evolutionary lineages, each with its own geographic range and history of diversification.TeelegansandTeterrestrisshow unique patterns of diversification as populations dispersed from east to west and while adapting to the new environments they colonized. Historical events, landscape features and environmental variation have all contributed to patterns of differentiation inTelegans.

     
    more » « less
  4. Abstract Aim

    Islands provide opportunities for isolation and speciation. Many landmasses in the Indo‐Australian Archipelago (IAA) are oceanic islands, and founder‐event speciation is expected to be the predominant form of speciation of volant taxa on these islands. We studied the biogeographic history of flying foxes, a group with many endemic species and a predilection for islands, to test this hypothesis and infer the biogeographic origin of the group.

    Location

    Australasia, Indo‐Australian Archipelago, Madagascar, Pacific Islands.

    Taxon

    Pteropus(Pteropodidae).

    Methods

    To infer the biogeographic history ofPteropus, we sequenced up to 6,169 bp of genetic data from 10 markers and reconstructed a multilocus species tree of 34 currently recognizedPteropusspecies and subspecies with threeAcerodonoutgroups usingBEASTand subsequently estimated ancestral areas using models implemented inBioGeoBEARS.

    Results

    Species‐level resolution was occasionally low because of slow rates of molecular evolution and/or recent divergences. Older divergences, however, were more strongly supported and allow the evolutionary history of the group to be inferred. The genus diverged in Wallacea from its common ancestor withAcerodon; founder‐event speciation out of Wallacea was a common inference.Pteropusspecies in Micronesia and the western Indian Ocean were also inferred to result from founder‐event speciation.

    Main conclusions

    Dispersal between regions of the IAA and the islands found therein fostered diversification ofPteropusthroughout the IAA and beyond. Dispersal inPteropusis far higher than in most other volant taxa studied to date, highlighting the importance of inter‐island movement in the biogeographic history of this large clade of large bats.

     
    more » « less
  5. Abstract Background

    Duchenne muscular dystrophy (DMD), caused by dystrophin deficiency, leads to progressive and fatal muscle weakness through yet‐to‐be‐fully deciphered molecular perturbations. Emerging evidence implicates RhoA/Rho‐associated protein kinase (ROCK) signalling in DMD pathology, yet its direct role in DMD muscle function, and related mechanisms, are unknown.

    Methods

    Three‐dimensionally engineered dystrophin‐deficientmdxskeletal muscles andmdxmice were used to test the role of ROCK in DMD muscle functionin vitroandin situ, respectively. The role of ARHGEF3, one of the RhoA guanine nucleotide exchange factors (GEFs), in RhoA/ROCK signalling and DMD pathology was examined by generatingArhgef3knockoutmdxmice. The role of RhoA/ROCK signalling in mediating the function of ARHGEF3 was determined by evaluating the effects of wild‐type or GEF‐inactive ARHGEF3 overexpression with ROCK inhibitor treatment. To gain more mechanistic insights, autophagy flux and the role of autophagy were assessed in various conditions with chloroquine.

    Results

    Inhibition of ROCK with Y‐27632 improved muscle force production in 3D‐engineeredmdxmuscles (+25% from three independent experiments,P < 0.05) and in mice (+25%,P < 0.001). Unlike suggested by previous studies, this improvement was independent of muscle differentiation or quantity and instead related to increased muscle quality. We found that ARHGEF3 was elevated and responsible for RhoA/ROCK activation inmdxmuscles, and that depleting ARHGEF3 inmdxmice restored muscle quality (up to +36%,P < 0.01) and morphology without affecting regeneration. Conversely, overexpressing ARHGEF3 further compromisedmdxmuscle quality (−13% vs. empty vector control,P < 0.01) in GEF activity‐ and ROCK‐dependent manner. Notably, ARHGEF3/ROCK inhibition exerted the effects by rescuing autophagy which is commonly impaired in dystrophic muscles.

    Conclusions

    Our findings uncover a new pathological mechanism of muscle weakness in DMD involving the ARHGEF3‐ROCK‐autophagy pathway and the therapeutic potential of targeting ARHGEF3 in DMD.

     
    more » « less