Nanoparticle delivery in infant lungs

The lung surface is an ideal pathway to the bloodstream for nanoparticle-based drug delivery. Thus far, research has focused on the lungs of adults, and little is known about nanoparticle behavior in the immature lungs of infants. Here, using nonlinear dynamical systems analysis and in vivo experimentation in developing animals, we show that nanoparticle deposition in postnatally developing lungs peaks at the end of bulk alveolation. This finding suggests a unique paradigm, consistent with the emerging theory that as alveoli form through secondary septation, alveolar flow becomes chaotic and chaotic mixing kicks in, significantly enhancing particle deposition. This finding has significant implications for the application of nanoparticle-based inhalation therapeutics in young children with immature lungs from birth to 2 y of age.     

Coordinated phenotype switching with large-scale chromosome flip-flop inversion observed in bacteria

Genome inversions are ubiquitous in organisms ranging from prokaryotes to eukaryotes. Typical examples can be identified by comparing the genomes of two or more closely related organisms, where genome inversion footprints are clearly visible. Although the evolutionary implications of this phenomenon are huge, little is known about the function and biological meaning of this process. Here, we report our findings on a bacterium that generates a reversible, large-scale inversion of its chromosome (about half of its total genome) at high frequencies of up to once every four generations. This inversion switches on or off bacterial phenotypes, including colony morphology, antibiotic susceptibility, hemolytic activity, and expression of dozens of genes. Quantitative measurements and mathematical analyses indicate that this reversible switching is stochastic but self-organized so as to maintain two forms of stable cell populations (i.e., small colony variant, normal colony variant) as a bet-hedging strategy. Thus, this heritable and reversible genome fluctuation seems to govern the bacterial life cycle; it has a profound impact on the course and outcomes of bacterial infections.     

Reconstitution of the central and peripheral nervous system during salamander tail regeneration

We show that after tail amputation in Ambystoma mexicanum (Axolotl) the correct number and spacing of dorsal root ganglia are regenerated. By transplantation of spinal cord tissue and nonclonal neurospheres, we show that the central spinal cord represents a source of peripheral nervous system cells. Interestingly, melanophores migrate from preexisting precursors in the skin. Finally, we demonstrate that implantation of a clonally derived spinal cord neurosphere can result in reconstitution of all examined cell types in the regenerating central spinal cord, suggesting derivation of a cell with spinal cord stem cell properties.     

Homology and homoplasy of swimming behaviors and neural circuits in the Nudipleura (Mollusca, Gastropoda, Opisthobranchia)

How neural circuit evolution relates to behavioral evolution is not well understood. Here the relationship between neural circuits and behavior is explored with respect to the swimming behaviors of the Nudipleura (Mollusca, Gastropoda, Opithobranchia). Nudipleura is a diverse monophyletic clade of sea slugs among which only a small percentage of species can swim. Swimming falls into a limited number of categories, the most prevalent of which are rhythmic left-right body flexions (LR) and rhythmic dorsal-ventral body flexions (DV). The phylogenetic distribution of these behaviors suggests a high degree of homoplasy. The central pattern generator (CPG) underlying DV swimming has been well characterized in Tritonia diomedea and in Pleurobranchaea californica. The CPG for LR swimming has been elucidated in Melibe leonina and Dendronotus iris, which are more closely related. The CPGs for the categorically distinct DV and LR swimming behaviors consist of nonoverlapping sets of homologous identified neurons, whereas the categorically similar behaviors share some homologous identified neurons, although the exact composition of neurons and synapses in the neural circuits differ. The roles played by homologous identified neurons in categorically distinct behaviors differ. However, homologous identified neurons also play different roles even in the swim CPGs of the two LR swimming species. Individual neurons can be multifunctional within a species. Some of those functions are shared across species, whereas others are not. The pattern of use and reuse of homologous neurons in various forms of swimming and other behaviors further demonstrates that the composition of neural circuits influences the evolution of behaviors.     

Continuous positive airway pressure therapy improves vascular dysfunction and decreases oxidative stress in patients with the metabolic syndrome and obstructive sleep apnea syndrome

Background:

Patients with obstructive sleep apnea syndrome (OSAS) are always exposed to intermittent hypoxia and reoxygenation. The metabolic syndrome (MetS) and OSAS are also known to accelerate atherosclerosis, diabetes, and dyslipidemia. Therefore, nasal continuous positive airway pressure (CPAP) therapy may have beneficial effects in patients with the MetS and OSAS.

Hypothesis:

This study in patients with the MetS and OSAS tested the validity of the hypothesis that chronic CPAP therapy improves factors involved in atherosclerosis, including impaired endothelial function.

Methods:

Thirty‐two patients (19 males and 13 females, mean age 54 ± 9 y) diagnosed with the MetS and OSAS were enrolled in the study and received CPAP therapy for 3 months. Vascular function was investigated by measuring forearm blood flow (FBF) responses to reactive hyperemia (RH) using venous occlusion strain‐gauge plethysmography. Biochemical markers were also measured before and after this procedure.

Results:

Basal apnea‐hypopnea index was statistically correlated with FBF response to RH. The FBF response to RH was increased significantly after 3 months of CPAP therapy. A significant increase in plasma nitric oxide levels and a decrease in the levels of asymmetrical dimethylarginine, thiobarbituric acid reactive substance, soluble Fas ligand, and soluble CD40 ligand were detected after CPAP therapy. The plasma concentrations of tumor necrosis factor‐α, interleukin (IL)‐6, and IL‐8 also decreased significantly with CPAP therapy, whereas IL‐1β levels remained unchanged.

Conclusions:

Continuous positive airway pressure therapy has beneficial effects on vascular function and inflammatory and oxidative stress in patients with the MetS and OSAS. The authors have no funding, financial relationships, or conflicts of interest to disclose.     

No evidence of association between 8q24 and susceptibility to nonsyndromic cleft lip with or without palate in Japanese population

Objective : Recent genome-wide association studies identified susceptibility loci for nonsyndromic cleft lip with or without cleft palate (NSCL±P) on 8q24.21, 10q25.3, 13q31.1, 15q13.3, 17q22, and 18q22 in populations of European origin. The purpose of this study was to determine, using DNA samples, whether 8q24.21 was a susceptibility locus for the development of NSCL±P in Japanese patients. Methods : We used DNA from 167 Japanese NSCL±P patients (45 cleft lip without cleft palate and 122 cleft lip with cleft palate patients) and 190 Japanese unaffected control individuals. We performed an association study using 13 single nucleotide polymorphisms (SNPs) selected on the 8q24.21 locus. Genotyping of each SNP was carried out by direct sequencing of genomic DNA. Additionally, a haplotype block was constructed using the selected SNPs. Results : The 13 selected SNPs were successfully genotyped in 357 individuals. The p values obtained were not low enough to indicate a significant association between the haplotypes and the development of NSCL±P in this population. Conclusions : Our results suggest that the 8q24.21 locus is not associated with susceptibility to NSCL±P in Japanese patients and provide further evidence that ethnicity is a strong factor in determining susceptibility loci, albeit using a limited number of samples. Further studies are needed to identify regions involved in the development of NSCL±P in the Japanese population.