Conservation of regional gene expression in mouse and human brain

Many neurodegenerative diseases have a hallmark regional and cellular pathology. Gene expression analysis of healthy tissues may provide clues to the differences that distinguish resistant and sensitive tissues and cell types. Comparative analysis of gene expression in healthy mouse and human brain provides a framework to explore the ability of mice to model diseases of the human brain. It may also aid in understanding brain evolution and the basis for higher order cognitive abilities. Here we compare gene expression profiles of human motor cortex, caudate nucleus, and cerebellum to one another and identify genes that are more highly expressed in one region relative to another. We separately perform identical analysis on corresponding brain regions from mice. Within each species, we find that the different brain regions have distinctly different expression profiles. Contrasting between the two species shows that regionally enriched genes in one species are generally regionally enriched genes in the other species. Thus, even when considering thousands of genes, the expression ratios in two regions from one species are significantly correlated with expression ratios in the other species. Finally, genes whose expression is higher in one area of the brain relative to the other areas, in other words genes with patterned expression, tend to have greater conservation of nucleotide sequence than more widely expressed genes. Together these observations suggest that region-specific genes have been conserved in the mammalian brain at both the sequence and gene expression levels. Given the general similarity between patterns of gene expression in healthy human and mouse brains, we believe it is reasonable to expect a high degree of concordance between microarray phenotypes of human neurodegenerative diseases and their mouse models. Finally, these data on very divergent species provide context for studies in more closely related species that address questions such as the origins of cognitive differences.     

The structure of a doripenem‐bound OXA‐51 class D β‐lactamase variant with enhanced carbapenemase activity

OXA‐51 is a class D β‐lactamase that is thought to be the native carbapenemase of Acinetobacter baumannii. Many variants of OXA‐51 containing active site substitutions have been identified from A. baumannii isolates, and some of these substitutions increase hydrolytic activity toward carbapenem antibiotics. We have determined the high‐resolution structures of apo OXA‐51 and OXA‐51 with one such substitution (I129L) with the carbapenem doripenem trapped in the active site as an acyl‐intermediate. The structure shows that acyl‐doripenem adopts an orientation very similar to carbapenem ligands observed in the active site of OXA‐24/40 (doripenem) and OXA‐23 (meropenem). In the OXA‐51 variant/doripenem complex, the indole ring of W222 is oriented away from the doripenem binding site, thereby eliminating a clash that is predicted to occur in wildtype OXA‐51. Similarly, in the OXA‐51 variant complex, L129 adopts a different rotamer compared to I129 in wildtype OXA‐51. This alternative position moves its side chain away from the hydroxyethyl moiety of doripenem and relieves another potential clash between the enzyme and carbapenem substrates. Molecular dynamics simulations of OXA‐51 and OXA‐51 I129L demonstrate that compared to isoleucine, a leucine at this position greatly favors a rotamer that accommodates the ligand. These results provide a molecular justification for how this substitution generates enhanced binding affinity for carbapenems, and therefore helps explain the prevalence of this substitution in clinical OXA‐51 variants.     

Expression in Escherichia coli, purification and kinetic characterization of human heparan sulfate 3-O-sulfotransferase-1.

Heparan sulfate (HS) glycosaminoglycans are a structurally diverse class of complex biomolecules that modulate many important events at the cell surface and within the extracellular matrix and whose structural heterogeneity derives largely from the sequence-specific N- and O-sulfations catalyzed by an extensive repertoire of sulfating enzymes. We have expressed the human heparan sulfate 3-OST-1 isoform in Escherichia coli and subsequently purified a soluble, active enzyme. To assess its functionality, we determined the kinetic parameters for the recombinant 3-O-sulfotransferase-1 using a radiochemical assay that directly measures the 3-O-sulfation of unlabeled bovine kidney heparan sulfate in vitro using [(35)S]PAPS as the sulfate donor. The apparent K(m) values measured were in the low micromolar range (K(HS)(m) = 4.3 microM; K(PAPS)(m) = 38.6 microM); V(max) values of 18 and 21 pmol sulfate/min/pmol of enzyme for HS and PAPS, respectively. These values were compared with kinetic parameters likewise measured for recombinant 3-OST-1 purified from baculovirus-infected sf9 cells. The two enzymes appear to modify heparan sulfate in vitro to roughly the same extent and with comparable specificities. The expression of 3-OST-1 in E. coli represents an important step in subsequent structure-function studies.     

Urbanization and biological invasion shape animal personalities

Novel selective pressures derived from human activities challenge the persistence of animal populations worldwide. Behavior is expected to be a major factor driving animals’ responses to global change because it largely determines how animals interact with the environment. However, the role of individual variation in behavior to facilitate the persistence of animals in changing environments remains poorly understood. Here, we adopted an animal personality approach to investigate whether different behavioral traits allow animals to deal with two major components of global change: urbanization and biological invasions. By studying six populations of Anolis sagrei lizards, we found for the first time that anoles vary consistently in their behavior across different times and contexts. Importantly, these animal personalities were consistent in the wild and in captivity. We investigated whether behavioral traits are pulled in different directions by different components of global change. On the one hand, we found that lizards from urban areas differ from nearby forest lizards in that they were more tolerant of humans, less aggressive, bolder after a simulated predator attack, and they spent more time exploring new environments. Several of these risk‐taking behaviors constituted a behavioral syndrome that significantly differed between urban and forest populations. On the other hand, the behavior of urban A. sagrei coexisting with the invasive predatory lizard Leiocephalus carinatus was associated with dramatic changes in their foraging niche. Overall, we provide evidence that differences in animal personalities facilitate the persistence of animals under novel selective regimes by producing adaptive behaviors relevant to their ecology such as predator avoidance. Our results suggest that natural selection can favor certain behaviors over others when animals are confronted with different ecological challenges posed by global change. Therefore, we underscore the need to incorporate behavioral ecology into the study of how animals adaptively respond to human‐induced environmental changes.     

Anthropogenic N deposition increases soil organic matter accumulation without altering its biochemical composition

Accumulating evidence indicates that future rates of atmospheric N deposition have the potential to increase soil C storage by reducing the decay of plant litter and soil organic matter (SOM). Although the microbial mechanism underlying this response is not well understood, a decline in decay could alter the amount, as well as biochemical composition of SOM. Here, we used size‐density fractionation and solid‐state ¹³C‐NMR spectroscopy to explore the extent to which declines in microbial decay in a long‐term (ca. 20 yrs.) N deposition experiment have altered the biochemical composition of forest floor, bulk mineral soil, as well as free and occluded particulate organic matter. Significant amounts of organic matter have accumulated in occluded particulate organic matter (~20%; oPOM); however, experimental N deposition had not altered the abundance of carboxyl, aryl, alkyl, or O/N‐alkyl C in forest floor, bulk mineral soil, or any soil fraction. These observations suggest that biochemically equivalent organic matter has accumulated in oPOM at a greater rate under experimental N deposition, relative to the ambient treatment. Although we do not understand the process by which experimental N deposition has fostered the occlusion of organic matter by mineral soil particles, our results highlight the importance of interactions among the products of microbial decay and the chemical and physical properties of silt and clay particles that occlude organic matter from microbial attack. Because oPOM can reside in soils for decades to centuries, organic matter accumulating under future rates of anthropogenic N deposition could remain in soil for long periods of time. If temperate forest soils in the Northern Hemisphere respond like those in our experiment, then unabated deposition of anthropogenic N from the atmosphere has the potential to foster greater soil C storage, especially in fine‐texture forest soils.     

Interpenetrating Triphase Cobalt‐Based Nanocomposites as Efficient Bifunctional Oxygen Electrocatalysts for Long‐Lasting Rechargeable Zn–Air Batteries

Rational construction of atomic‐scale interfaces in multiphase nanocomposites is an intriguing and challenging approach to developing advanced catalysts for both oxygen reduction (ORR) and evolution reactions (OER). Herein, a hybrid of interpenetrating metallic Co and spinel Co₃O₄ “Janus” nanoparticles stitched in porous graphitized shells (Co/Co₃O₄@PGS) is synthesized via ionic exchange and redox between Co²⁺ and 2D metal–organic‐framework nanosheets. This strategy is proven to effectively establish highways for the transfer of electrons and reactants within the hybrid through interfacial engineering. Specifically, the phase interpenetration of mixed Co species and encapsulating porous graphitized shells provides an optimal charge/mass transport environment. Furthermore, the defect‐rich interfaces act as atomic‐traps to achieve exceptional adsorption capability for oxygen reactants. Finally, robust coupling between Co and N through intimate covalent bonds prohibits the detachment of nanoparticles. As a result, Co/Co₃O₄@PGS outperforms state‐of‐the‐art noble‐metal catalysts with a positive half‐wave potential of 0.89 V for ORR and a low potential of 1.58 V at 10 mA cm^?2 for OER. In a practical demonstration, ultrastable cyclability with a record lifetime of over 800 h at 10 mA cm^?2 is achieved by Zn–air batteries with Co/Co₃O₄@PGS within the rechargeable air electrode.     

The early life of a leaf‐cutter ant colony constrains symbiont vertical transmission and favors horizontal transmission

Colonial organisms host a large diversity of symbionts (collectively, parasites, mutualists, and commensals) that use vertical transmission (from parent colony to offspring colony) and/or horizontal transmission to disperse between host colonies. The early life of some colonies, characterized by the dispersal and establishment of solitary individuals, may constrain vertical transmission and favor horizontal transmission between large established colonies. We explore this possibility with the miniature cockroach Attaphila fungicola, a symbiont of leaf‐cutter ants and the mutualist fungal gardens they cultivate. The early life of a leaf‐cutter colony is characterized by the dispersal of a female alate (winged “queen”) carrying a fungal pellet, and the subsequent establishment of a foundress (workerless “queen”) raising her incipient fungal garden and colony. Roaches hitchhike on female alates during leaf‐cutter nuptial flights, which strongly suggests that roaches are vertically transmitted to foundresses and their incipient colonies; however, weak compatibility between roaches and incipient gardens may constrain roach vertical transmission. Reciprocally, opportunities for horizontal transmission between large established colonies with abundant fungal gardens may weaken selection against roach‐induced harm (virulence) of incipient gardens. We use a laboratory experiment, behavioral observations, field surveys, and a transmission model to estimate the effect roaches have on the survivorship of incipient gardens and the frequency of roach vertical transmission. Contrary to traditional assumptions, our results indicate that roaches harm incipient gardens and predominantly use horizontal transmission between established leaf‐cutter colonies. Ultimately, “costs of generalism” associated with infecting disparate stages of a host''s lifecycle (e.g., incipient vs. established colonies) may constrain the vertical transmission of roaches and a broad range of symbionts.     

The sex determination gene shows no founder effect in the giant honey bee, Apis dorsata

Background

All honey bee species (Apis spp) share the same sex determination mechanism using the complementary sex determination (csd) gene. Only individuals heterogeneous at the csd allele develop into females, and the homozygous develop into diploid males, which do not survive. The honeybees are therefore under selection pressure to generate new csd alleles. Previous studies have shown that the csd gene is under balancing selection. We hypothesize that due to the long separation from the mainland of Hainan Island, China, that the giant honey bees (Apis dorsata) should show a founder effect for the csd gene, with many different alleles clustered together, and these would be absent on the mainland.

Methodology/Principal Findings

We sampled A. dorsata workers from both Hainan and Guangxi Provinces and then cloned and sequenced region 3 of the csd gene and constructed phylogenetic trees. We failed to find any clustering of the csd alleles according to their geographical origin, i.e. the Hainan and Guangxi samples did not form separate clades. Further analysis by including previously published csd sequences also failed to show any clade-forming in both the Philippines and Malaysia.

Conclusions/Significance

Results from this study and those from previous studies did not support the expectations of a founder effect. We conclude that because of the extremely high mating frequency of A. dorsata queens, a founder effect does not apply in this species.     

Extensive pyrosequencing reveals frequent intra-genomic variations of internal transcribed spacer regions of nuclear ribosomal DNA

Background

Internal transcribed spacer of nuclear ribosomal DNA (nrDNA) is already one of the most popular phylogenetic and DNA barcoding markers. However, the existence of its multiple copies has complicated such usage and a detailed characterization of intra-genomic variations is critical to address such concerns.

Methodology/Principal Findings

In this study, we used sequence-tagged pyrosequencing and genome-wide analyses to characterize intra-genomic variations of internal transcribed spacer 2 (ITS2) regions from 178 plant species. We discovered that mutation of ITS2 is frequent, with a mean of 35 variants per species. And on average, three of the most abundant variants make up 91% of all ITS2 copies. Moreover, we found different congeneric species share identical variants in 13 genera. Interestingly, different species across different genera also share identical variants. In particular, one minor variant of ITS2 in Eleutherococcus giraldii was found identical to the ITS2 major variant of Panax ginseng, both from Araliaceae family. In addition, DNA barcoding gap analysis showed that the intra-genomic distances were markedly smaller than those of the intra-specific or inter-specific variants. When each of 5543 variants were examined for its species discrimination efficiency, a 97% success rate was obtained at the species level.

Conclusions

Identification of identical ITS2 variants across intra-generic or inter-generic species revealed complex species evolutionary history, possibly, horizontal gene transfer and ancestral hybridization. Although intra-genomic multiple variants are frequently found within each genome, the usage of the major variants alone is sufficient for phylogeny construction and species determination in most cases. Furthermore, the inclusion of minor variants further improves the resolution of species identification.