Maternal high fat diet compromises survival and modulates lung development of offspring, and impairs lung function of dams (female mice)

© 2019 The Author(s). Published in Respiratory Research. Background: Epidemiological studies have identified strong relationships between maternal obesity and offspring respiratory dysfunction; however, the causal direction is not known. We tested whether maternal obesity alters respiratory function of offspring in early life. Methods: Female C57Bl/6 J mice were fed a high or low fat diet prior to and during two rounds of mating and resulting pregnancies with offspring lung function assessed at 2 weeks of age. The lung function of dams was measured at 33 weeks of age. Results: A high fat diet caused significant weight gain prior to conception with dams exhibiting elevated fasting glucose, and glucose intolerance. The number of surviving litters was significantly less for dams fed a high fat diet, and surviving offspring weighed more, were longer and had larger lung volumes than those born to dams fed a low fat diet. The larger lung volumes significantly correlated in a linear fashion with body length. Pups born from the second pregnancy had reduced tissue elastance compared to pups born from the first pregnancy, regardless of the dam's diet. As there was reduced offspring survival born to dams fed a high fat diet, the statistical power of lung function measures of offspring was limited. There were signs of increased inflammation in the bronchoalveolar lavage fluid of dams (but not offspring) fed a high fat diet, with more tumour necrosis factor-α, interleukin(IL)-5, IL-33 and leptin detected. Dams that were fed a high fat diet and became pregnant twice had reduced fasting glucose immediately prior to the second mating, and lower levels of IL-33 and leptin in bronchoalveolar lavage fluid. Conclusions: While maternal high fat diet compromised litter survival, it also promoted somatic and lung growth (increased lung volume) in the offspring. Further studies are required to examine downstream effects of this enhanced lung volume on respiratory function in disease settings

Activation and Deactivation of a Robust Immobilized Cp*Ir-Transfer Hydrogenation Catalyst: A Multielement in Situ X-ray Absorption Spectroscopy Study

A highly robust immobilized [Cp*IrCl2]2 precatalyst on Wang resin for transfer hydrogenation, which can be recycled up to 30 times, was studied using a novel combination of X-ray absorption spectroscopy (XAS) at Ir L3-edge, Cl K-edge, and K K-edge. These culminate in in situ XAS experiments that link structural changes of the Ir complex with its catalytic activity and its deactivation. Mercury poisoning and “hot filtration” experiments ruled out leached Ir as the active catalyst. Spectroscopic evidence indicates the exchange of one chloride ligand with an alkoxide to generate the active precatalyst. The exchange of the second chloride ligand, however, leads to a potassium alkoxide–iridate species as the deactivated form of this immobilized catalyst. These findings could be widely applicable to the many homogeneous transfer hydrogenation catalysts with Cp*IrCl substructure

Progress in Diamond Detector Development

Detectors based on Chemical Vapor Deposition (CVD) diamond have been used successfully in Luminosity and Beam Condition Monitors (BCM) in the highest radiation areas of the LHC. Future experiments at CERN will accumulate an order of magnitude larger fluence. As a result, an enormous effort is underway to identify detector materials that can operate under fluences of 1 · 1016 n cm−2 and 1 · 1017 n cm−2. Diamond is one candidate due to its large displacement energy that enhances its radiation tolerance. Over the last 30 years the RD42 collaboration has constructed diamond detectors in CVD diamond with a planar geometry and with a 3D geometry to extend the material's radiation tolerance. The 3D cells in these detectors have a size of 50 µm×50 µm with columns of 2.6 µm in diameter and 100 µm×150 µm with columns of 4.6 µm in diameter. Here we present the latest beam test results from planar and 3D diamond pixel detectors

A CD4(+) T-cell immune response to a conserved epitope in the circumsporozoite protein correlates with protection from natural Plasmodium falciparum infection and disease.

Many human T-cell responses specific for epitopes in Plasmodium falciparum have been described, but none has yet been shown to be predictive of protection against natural malaria infection. Here we report a peptide-specific T-cell assay that is strongly associated with protection of humans in The Gambia, West Africa, from both malaria infection and disease. The assay detects interferon-gamma-secreting CD4(+) T cells specific for a conserved sequence from the circumsporozoite protein, which binds to many human leukocyte antigen (HLA)-DR types. The correlation was observed using a cultured, rather than an ex vivo, ELISPOT assay that measures central memory-'type T cells rather than activated effector T cells. These findings provide direct evidence for a protective role for CD4(+) T cells in humans, and a precise target for the design of improved vaccines against P. falciparum

Enhanced T-cell immunogenicity of plasmid DNA vaccines boosted by recombinant modified vaccinia virus Ankara in humans.

In animals, effective immune responses against malignancies and against several infectious pathogens, including malaria, are mediated by T cells. Here we show that a heterologous prime-boost vaccination regime of DNA either intramuscularly or epidermally, followed by intradermal recombinant modified vaccinia virus Ankara (MVA), induces high frequencies of interferon (IFN)-gamma-secreting, antigen-specific T-cell responses in humans to a pre-erythrocytic malaria antigen, thrombospondin-related adhesion protein (TRAP). These responses are five- to tenfold higher than the T-cell responses induced by the DNA vaccine or recombinant MVA vaccine alone, and produce partial protection manifest as delayed parasitemia after sporozoite challenge with a different strain of Plasmodium falciparum. Such heterologous prime-boost immunization approaches may provide a basis for preventative and therapeutic vaccination in humans