Focus on nonlinear terahertz studies

Resulting from the availability of improved sources, research in the terahertz (THz) spectral range has increased dramatically over the last decade, leading essentially to the disappearance of the so-called 'THz gap'. While most work to date has been carried out with THz radiation of low field amplitude, a growing number of experiments are using THz radiation with large electric and magnetic fields that induce nonlinearities in the system under study. This 'focus on' collection contains a number of articles, both experimental and theoretical, in the new subfield of THz nonlinear optics and spectroscopy on various systems, among them molecular gases, superconductors, semiconductors, antiferromagnets and graphene

Biophysical evaluation of rhesus macaque Fc gamma receptors reveals similar IgG Fc glycoform preferences to human receptors

Rhesus macaques are a common non-human primate model used in the evaluation of human monoclonal antibodies, molecules whose effector functions depend on a conserved N-linked glycan in the Fc region. This carbohydrate is a target of glycoengineering efforts aimed at altering antibody effector function by modulating the affinity of Fc gamma receptors. For example, a reduction in the overall core fucose content is one such strategy that can increase antibody-mediated cellular cytotoxicity by increasing Fc-Fc gamma RIIIa affinity. While the position of the Fc glycan is conserved in macaques, differences in the frequency of glycoforms and the use of an alternate monosaccharide in sialylated glycan species add a degree of uncertainty to the testing of glycoengineered human antibodies in rhesus macaques. Using a panel of 16 human IgG1 glycovariants, we measured the affinities of macaque Fc gamma Rs for differing glycoforms via surface plasmon resonance. Our results suggest that macaques are a tractable species in which to test the effects of antibody glycoengineering.Proteomic

Evaluation of TruCount Absolute-Count Tubes for Determining CD4 and CD8 Cell Numbers in Human Immunodeficiency Virus-Positive Adults

A single-platform technology that uses an internal bead standard and three-color flow cytometry to determine CD4 and CD8 absolute counts was evaluated for reproducibility and agreement. Values obtained using TruCount absolute-count tubes were compared to those obtained using a two-color predicate methodology. Sixty specimens from human immunodeficiency virus type 1-infected donors were shipped to five laboratories. Each site also analyzed replicates of 14 human immunodeficiency virus type 1-infected local specimens at 6 h and again at 24 h. The interlaboratory variability was significantly less with TruCount (median difference in percent coefficient of variation [%CV] between the two methods was −8% and −3% for CD4 and CD8, respectively) than with the predicate method. Intralaboratory variability was smaller, with a median difference in %CV of −1% for both CD4 and CD8 with 6-h samples and −2% and −3% for CD4 and CD8, respectively, with 24-h samples. Use of TruCount for shipped samples resulted in a median CD4 count change of 7 cells (50th estimated percentile) when all laboratories and CD4 strata were combined. For on-site samples, the median CD4 count change was 10 CD4 cells for 6-h samples and 2 CD4 cells for 24-h samples. Individual site biases occurred in both directions and cancelled each other when the data were combined for all laboratories. Thus, the combined data showed a smaller change in median CD4 count than what may have occurred at an individual site. In summary, the use of TruCount decreased both the inter- and intralaboratory variability in determining absolute CD4 and CD8 counts

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease

Activity of HIV Entry And Fusion Inhibitors Expressed By The Human Vaginal Colonizing Probiotic Lactobacillus Reuteri RC-14

Novel therapeutic approaches are needed to combat the rapid increase in HIV sexual transmission in women. The probiotic organism Lactobacillus reuteri RC-14 which safely colonizes the human vagina and prevents microbial infections, has been genetically modified to produce anti-HIV proteins which were capable of blocking the three main steps of HIV entry into human peripheral blood mononuclear cells. The HIV entry or fusion inhibitors were fused to the native expression and secretion signals of BspA, Mlp or Sep in L. reuteri RC-14 and the expression cassettes were stably inserted into the chromosome. L. reuteri RC-14 expressed the HIV inhibitors in cell wall-associated and secreted forms. L. reuteri RC-14 expressing CD4D1D2-antibody-like fusion proteins were able to bind single or dual tropic coreceptor-using HIV-1 primary isolates. This is the first study to show that a well-documented and proven human vaginal probiotic strain can express potent functional viral inhibitors, which may potentially lower the sexual transmission of HIV. © 2006 The Authors; Journal compilation © 2006 Blackwell Publishing Ltd