A 10.8-14.5-GHz eight-phase 12.5%-duty-cycle nonoverlapping LO generator is proposed for 60-GHz eight-path-filtering subsampling receivers. A four-stage ring oscillator (RO) is followed by ...reconfigurable injection-locked-oscillator NOR gates to generate eight-phase 12.5%-duty-cycle signals featuring automatic successive phase calibration and automatic frequency-domain duty-cycle calibration. The generator prototype measures minimum phase errors of ~0.1° and maximum fourth-harmonic output power of −5 dBm with >30-dB improvement while consuming 77.8 mW from a 1-V supply over the entire frequency tuning range from 10.8 to 14.5 GHz.
Human B cell antigen-receptor (BCR) repertoires reflect repeated exposures to evolving influenza viruses; new exposures update the previously generated B cell memory (Bmem) population. Despite ...structural similarity of hemagglutinins (HAs) from the two groups of influenza A viruses, cross-reacting antibodies (Abs) are uncommon. We analyzed Bmem compartments in three unrelated, adult donors and found frequent cross-group BCRs, both HA-head directed and non-head directed. Members of a clonal lineage from one donor had a BCR structure similar to that of a previously described Ab, encoded by different gene segments. Comparison showed that both Abs contacted the HA receptor-binding site through long heavy-chain third complementarity determining regions. Affinities of the clonal-lineage BCRs for historical influenza-virus HAs from both group 1 and group 2 viruses suggested that serial responses to seasonal influenza exposures had elicited the lineage and driven affinity maturation. We propose that appropriate immunization regimens might elicit a comparably broad response.
Display omitted
•Human Bmem cells were found with BCRs cross-reactive for influenza A groups 1 and 2•Cross-group Bmem cells were abundant, unlike cross-group serum antibodies•Structures of HA receptor-site directed, cross-group antibodies showed key contacts•Cross-group lineage antibodies were similar to a genetically unrelated antibody
Hemagglutinins (HAs) from the two influenza A subtype groups have similar structures, but cross-reacting serum antibodies are rare. McCarthy et al. nonetheless found, in three donors, abundant cross-group B cell receptors (BCRs), many with epitopes on the HA head. Members of one clonal lineage had a BCR structure similar to that of a previously described, genetically unrelated antibody. Serial responses to seasonal influenza appear to have elicited the lineage and driven affinity maturation. Appropriate immunization regimens might elicit comparable responses.
Influenza-virus antigenicity evolves to escape host immune protection. Antibody lineages within individuals evolve in turn to increase affinity and hence potency. Strategies for a “universal” ...influenza vaccine to elicit lineages that escape this evolutionary arms race and protect against seasonal variation and novel, pandemic viruses will require directing B cell ontogeny to focus the humoral response on conserved epitopes on the viral hemagglutinin (HA). The unmutated common ancestors (UCAs) of six distinct, broadly neutralizing antibody lineages from one individual bind the HA of a virus circulating at the time the participant was born. HAs of viruses circulating more than 5 years later no longer bind the UCAs, but mature antibodies in the lineages bind strains from the entire 18-year lifetime of the participant. The analysis shows how immunological memory shaped the response to subsequent influenza exposures and suggests that early imprinting by a suitable influenza antigen may enhance likelihood of later breadth.
Display omitted
•UCAs of RBS-directed lineages bind viruses circulating during a donor’s infancy•H1 viruses circulating after 1995 have escaped binding by lineage UCAs•Vaccination recalled lineages, with further maturation and increased breadth•Imprinting by H1 influenza early in life may direct later B cell responses
Schmidt et al. use an approach they call “immuno-viral archaeology” to probe the history of influenza exposure and antibody response in a single individual. They find that viruses, circulating during a donor’s infancy, bind tightly to the germline precursors of six distinct lineages of antibodies targeting the hemagglutinin receptor binding site.
Display omitted
•TBAB can promote or inhibit CO2 gas hydrate formation.•Water alignment underneath adsorption layer of TBA+ gives rise to the inhibition.•Water perturbation by TBA+ in the bulk gives ...rise to the promotion.•Interfacial water is of crucial importance to gas hydrate formation.
Gas hydrates formed under moderated conditions open up novel approaches to tackling issues related to energy supply, gas separation, and CO2 sequestration. Several additives such as tetra-n-butylammonium bromide (TBAB) have been empirically developed and used to promote gas hydrate formation. Here we report unexpected experimental results which show that TBAB inhibits CO2 gas hydrate formation when used at minuscule concentration. We also used spectroscopic techniques and molecular dynamics simulation to gain further insights and explain the experimental results. They have revealed the critical role of water alignment at the gas-water interface induced by surface adsorption of tetra-n-butylammonium cation (TBA+) which gives rise to the unexpected inhibition of dilute TBAB solution. The water perturbation by TBA+ in the bulk is attributed to the promotion effect of high TBAB concentration on gas hydrate formation. We explain our finding using the concept of activation energy of gas hydrate formation. Our results provide a step toward to mastering the control of gas hydrate formation.
Golgi-derived microtubules constitute an asymmetrical microtubule network that drives polarized transport of vesicles to support cell polarization and directional migration. Golgi-based microtubule ...nucleation requires the γ-tubulin ring complex (γTuRC), the principal microtubule nucleator in animal cells. In this chapter, we present methods for detecting γTuRC components and associated proteins on the Golgi, examining Golgi-based microtubule nucleation, and measuring the microtubule-nucleating activity of isolated γTuRCs. These approaches have been demonstrated to be effective for assessing the microtubule-organizing function of the Golgi complex.
Branched-chain α-keto acids (BCKAs) are catabolites of branched-chain amino acids (BCAAs). Intracellular BCKAs are cleared by branched-chain ketoacid dehydrogenase (BCKDH), which is sensitive to ...inhibitory phosphorylation by BCKD kinase (BCKDK). Accumulation of BCKAs is an indicator of defective BCAA catabolism and has been correlated with glucose intolerance and cardiac dysfunction. However, it is unclear whether BCKAs directly alter insulin signaling and function in the skeletal and cardiac muscle cell. Furthermore, the role of excess fatty acids (FAs) in perturbing BCAA catabolism and BCKA availability merits investigation. By using immunoblotting and ultra-performance liquid chromatography MS/MS to analyze the hearts of fasted mice, we observed decreased BCAA-catabolizing enzyme expression and increased circulating BCKAs, but not BCAAs. In mice subjected to diet-induced obesity (DIO), we observed similar increases in circulating BCKAs with concomitant changes in BCAA-catabolizing enzyme expression only in the skeletal muscle. Effects of DIO were recapitulated by simulating lipotoxicity in skeletal muscle cells treated with saturated FA, palmitate. Exposure of muscle cells to high concentrations of BCKAs resulted in inhibition of insulin-induced AKT phosphorylation, decreased glucose uptake, and mitochondrial oxygen consumption. Altering intracellular clearance of BCKAs by genetic modulation of BCKDK and BCKDHA expression showed similar effects on AKT phosphorylation. BCKAs increased protein translation and mTORC1 activation. Pretreating cells with mTORC1 inhibitor rapamycin restored BCKA's effect on insulin-induced AKT phosphorylation. This study provides evidence for FA-mediated regulation of BCAA-catabolizing enzymes and BCKA content and highlights the biological role of BCKAs in regulating muscle insulin signaling and function.
Adult neurogenesis is the process by which neural stem cells give rise to new functional neurons in specific regions of the adult brain, a process that occurs throughout life. Significantly, ...neurodegenerative and psychiatric disorders present suppressed neurogenesis, activated microglia, and neuroinflammation. Traffic-related air pollution has been shown to adversely affect the central nervous system. As the cardinal effects of air pollution exposure are microglial activation, and ensuing oxidative stress and neuroinflammation, we investigated whether acute exposures to diesel exhaust (DE) would inhibit adult neurogenesis in mice. Mice were exposed for 6 h to DE at a PM
2.5
concentration of 250–300 μg/m
3
, followed by assessment of adult neurogenesis in the hippocampal subgranular zone (SGZ), the subventricular zone (SVZ), and olfactory bulb (OB). DE impaired cellular proliferation in the SGZ and SVZ in males, but not females. DE reduced adult neurogenesis, with male mice showing fewer new neurons in the SGZ, SVZ, and OB, and females showing fewer new neurons only in the OB. To assess whether blocking microglial activation protected against DE-induced suppression of adult hippocampal neurogenesis, male mice were pre-treated with pioglitazone (PGZ) prior to DE exposure. The effects of DE exposure on microglia, as well as neuroinflammation and oxidative stress, were reduced by PGZ. PGZ also antagonized DE-induced suppression of neurogenesis in the SGZ. These results suggest that DE exposure impairs adult neurogenesis in a sex-dependent manner, by a mechanism likely to involve microglia activation and neuroinflammation.
This study is the first to investigate the chemical composition of essential oil and antioxidant activity of the essential oil and methanol extracts from the leaves of Knema globularia (Lam.) Warb. ...from Vietnam. According to gas chromatography and gas chromatography-mass spectrometry analysis, the major constituents of K. globularia essential oil were β-elemene (25.48%), α-copaene (17.05%), β-caryophyllene (9.37%), and α-humulene (8.42%). The antioxidant activity of the samples was determined using DPPH and ABTS methods. In both assays, the polar subfraction of the methanolic extract showed better antioxidative capacity than the nonpolar subfraction and the essential oil. In addition, the amounts of total phenol value in the polar subfraction and the nonpolar subfraction were determined to be 113.84 μg/mg and 47.52 μg/mg, respectively. The findings demonstrate that the essential oil and methanol extracts of K. globularia possess significant antioxidant activities and may be a new potential source of natural antioxidants.
Oocytes have a remarkable ability to reactivate silenced genes in somatic cells. However, it is not clear how the chromatin architecture of somatic cells affects this transcriptional reprogramming. ...Here, we investigated the relationship between the chromatin opening and transcriptional activation. We reveal changes in chromatin accessibility and their relevance to transcriptional reprogramming after transplantation of somatic nuclei into Xenopus oocytes. Genes that are silenced, but have pre-existing open transcription start sites in donor cells, are prone to be activated after nuclear transfer, suggesting that the chromatin signature of somatic nuclei influences transcriptional reprogramming. There are also activated genes associated with new open chromatin sites, and transcription factors in oocytes play an important role in transcriptional reprogramming from such genes. Finally, we show that genes resistant to reprogramming are associated with closed chromatin configurations. We conclude that chromatin accessibility is a central factor for successful transcriptional reprogramming in oocytes.
Display omitted
•ATAC-seq reveals chromatin accessibility changes during reprogramming in oocytes•Genes with open promoters are preferentially activated during reprogramming•Transcription factors play a role in transcriptional reprogramming in oocytes•Closed chromatin is associated with reprogramming-resistant genes
Miyamoto et al. show genome-wide changes in chromatin accessibility during transcriptional reprogramming in oocytes using the frog nuclear transfer system. They demonstrate that donor cell chromatin states affect transcriptional reprogramming and changes in open chromatin during reprogramming are associated with specific transcription factors.
Evolution of G-band modes of single metallic carbon nanotubes with the Fermi level shift is examined by simultaneous Raman and electron transport studies. Narrow Lorentzian line shape and upshifted ...frequencies are observed near the van Hove singularities. However, all G modes soften and broaden at the band crossing point. The concurrent appearance of an asymmetric Fano line shape at this point indicates that phonon-continuum coupling is intrinsic to single metallic tubes. The apparent Lorentzian line shapes of as-synthesized metallic tubes are induced by O2 adsorption causing the Fermi level shift.
PDF
