Special delivery! Polyionic complex (PIC) micelles that contain the charge‐conversional moieties citaconic amide or cis‐aconitic amide were developed for cytoplasmic protein delivery. The increase of the charge density on the protein cargo helped the stability of the PIC micelles without cross‐linking, and the charge‐conversion in endosomes induced the dissociation of the PIC micelles to result in efficient endosomal release (see picture).

A highly efficient lambda phage recombination system previously utilized for studies of bacterial artificial chromosome (BAC)-maintained mouse chromosomal DNA was adapted for the study of the role of human cytomegalovirus (HCMV)-encoded pp28 (UL99) in virus replication. Incorporating a two-step mutagenesis strategy with blue/white selection in Escherichia coli containing a HCMV AD169 BAC, we have shown that we can rapidly introduce point mutations into the HCMV BAC using linear PCR fragments. All manipulations were carried out in bacteria, which greatly accelerated the introduction and analysis of mutations in the viral genome. Our results indicated that HCMV pp28 was essential for the production of infectious virus and that introduction of a single base change that resulted in loss of the myristylation site on pp28 was also associated with the lack of production of infectious virus. Although the block in the viral morphogenesis cannot be determined from these studies, the latter finding suggested that authentic intracellular localization of pp28, not only the expression of the protein, is required for virus assembly.The role of individual herpesvirus genes in virus replication and the pathogenesis of virus-induced disease have been best understood from studies using viral genetics. The propagation of infectious clones of herpesviruses as bacterial artificial chromosomes (BACs) has revolutionized the experimental manipulation of viral genomes. Importantly, this technology has allowed application of tools of prokaryotic molecular biology to the study of viral genetics, thereby facilitating the genetic analysis of many herpesviruses (4-6, 16, 23, 24, 27). Previously, mutagenic approaches based on homologous recombination in eukaryotic cells were limited to genetic manipulation of only the most rapidly replicating and promiscuous herpesviruses, such as herpes simplex virus (HSV) and pseudorabies virus (PRV) (19). In this study, we have adapted a recombination strategy originally developed for mutagenesis of BACs containing mouse chromosomes to mutagenize the human cytomegalovirus (HCMV) genome (8,10,25,26). This methodology takes advantage of a lambda phage recombination system (RED locus) expressed from a temperature-sensitive promoter that enables the use of linear single-stranded DNA to target genes of interest carried on BACs maintained in Escherichia coli (8,26). We have used this recombination system together with a blue/white lacZ-based selection approach to define the importance of HCMV tegument protein pp28 (UL99) for HCMV replication. The product of the HCMV UL99 open reading frame (ORF) is a 190-amino-acid (aa) phosphorylated tegument protein, which is modified by myristylation (17,18,21). Homologues of pp28 are found in all herpesviruses. Studies with the HSV homologue UL11 have indicated that this protein is also myristylated, traffics in the cytoplasm, and is essential for wild-type levels of virus replication in vitro (2, 3, 11-13). Furthermore, more recent studies of the PRV UL11 * Corresponding aut...

Viperin is an interferon (IFN)-inducible multifunctional protein. Recent evidence from high-throughput analyses indicates that most IFN-inducible proteins, including viperin, are intrinsically expressed in specific tissues; however, the respective intrinsic functions are unknown. Here we show that the intrinsic expression of viperin regulates adipose tissue thermogenesis, which is known to counter metabolic disease and contribute to the febrile response to pathogen invasion. Viperin knockout mice exhibit increased heat production, resulting in a reduction of fat mass, improvement of high-fat diet (HFD)-induced glucose tolerance, and enhancement of cold tolerance. These thermogenic phenotypes are attributed to an adipocyte-autonomous mechanism that regulates fatty acid β-oxidation. Under an HFD, viperin expression is increased, and its function is enhanced. Our findings reveal the intrinsic function of viperin as a novel mechanism regulating thermogenesis in adipose tissues, suggesting that viperin represents a molecular target for thermoregulation in clinical contexts.

The mobility of molecular shuttles inside a mechanically interlocked polymer (MIP) can improve the ionic conductivity and electron transport capacity of a solid polymer electrolyte (SPE) and maintain a mechanically tough structure. The polyrotaxane‐based MIP electrolyte with a necklace‐like molecular structure exhibits high ionic conductivity (σ = 5.93 × 10−3 S cm−1 at 25 °C and 1.44 × 10−2 S cm−1 at 60 °C), a high Li+ ion transference number (t+ = 0.71), and high electrochemical oxidation stability (≈4.7 V vs Li+/Li). When SPEs are used in Li‐based batteries, a high Coulombic efficiency (≥98.5%), an excellent rate capability, and fast charging (≥2C) can be achieved using a “built‐in molecular shuttle” design.

The global use of a capsular polysaccharide-based pneumococcal vaccine has been limited because of serotype-specific protection and poor effectiveness in individuals with low immunocompetency. The mucosal immune system develops earlier in infants and lasts longer in the elderly than does the systemic immune system. Furthermore, mucosal immunization is beneficial for AIDS patients, because human immunodeficiency virus-infected subjects can develop normal mucosal antibody responses even in late clinical phases. For these reasons, we evaluated recombinant pneumococcal surface adhesin A (rPsaA) of Streptococcus pneumoniae in terms of cross-protective immune responses after oral delivery. Encapsulated rPsaA provided higher immunogenicity than naked rPsaA. Coencapsulation or codelivery of the cholera toxin (CT) B subunit (CTB) and CT also increased the immunogenicity of rPsaA. Cross-protective immunities against five strains of S. pneumoniae (types 4, 6B, 14, 19F, and 23F) were induced after oral immunization with microencapsulated rPsaA. Lung colonization and septicemia caused by the five serotypes were significantly inhibited by oral immunization with microencapsulated rPsaA. These results suggest that rPsaA coencapsulated with CTB can be used as an oral vaccine to induce cross-protective immunity for the prevention of pneumococcal infection.