From structure prediction to function: defining the domain on the African swine fever virus CD2v protein required for binding to erythrocytes.

Unlabelled: African swine fever virus (ASFV) is a high-consequence pathogen posing a substantial threat to global food security. This large DNA virus encodes more than 150 open reading frames, many of which are uncharacterized. The gene encodes CD2v, a glycoprotein expressed on the surface of infected cells and the only viral protein known to be present in the virus external envelope.

Structure of a fully assembled γδ T cell antigen receptor.

T cells in jawed vertebrates comprise two lineages, αβ T cells and γδ T cells, defined by the antigen receptors they express-that is, αβ and γδ T cell receptors (TCRs), respectively. The two lineages have different immunological roles, requiring that γδ TCRs recognize more structurally diverse ligands. Nevertheless, the receptors use shared CD3 subunits to initiate signalling.

Antibody agonists trigger immune receptor signaling through local exclusion of receptor-type protein tyrosine phosphatases.

Antibodies can block immune receptor engagement or trigger the receptor machinery to initiate signaling. We hypothesized that antibody agonists trigger signaling by sterically excluding large receptor-type protein tyrosine phosphatases (RPTPs) such as CD45 from sites of receptor engagement. An agonist targeting the costimulatory receptor CD28 produced signals that depended on antibody immobilization and were sensitive to the sizes of the receptor, the RPTPs, and the antibody itself.

Degradation and Erosion of Metal-Organic Frameworks: Comparative Study of a NanoMIL-100 Drug Delivery System.

To make a drug work better, the active substance can be incorporated into a vehicle for optimal protection and control of the drug delivery time and space. For making the drug carrier, the porous metal-organic framework (MOF) can offer high drug-loading capacity and various designs for effective drug delivery performance, biocompatibility, and biodegradability. Nevertheless, its degradation process is complex and not easily predictable, and the toxicity concern related to the MOF degradation products remains a challenge for their clinical translation.

A protective multiple gene-deleted African swine fever virus genotype II, Georgia 2007/1, expressing a modified non-haemadsorbing CD2v protein.

African swine fever virus is a complex DNA virus that causes high fatality in pigs and wild boar and has a great socio-economic impact. An attenuated genotype II strain was constructed by replacing the gene for wildtype CD2v protein with versions in which single or double amino acid substitutions were introduced to reduce or abrogate the binding to red blood cells and reduce virus persistence in blood. The mutant CD2v proteins were expressed at similar levels to the wildtype protein on the surface of infected cells.

Degradation of Polymer-Drug Conjugate Nanoparticles Based on Lactic and Itaconic Acid.

Tuberculosis (TB) is still a significant threat to human health. A promising solution is engineering nanoparticulate drug carriers to deliver anti-TB molecules. Itaconic acid (ITA) potentially has anti-TB activity; however, its incorporation in nanoparticles (NP) is challenging.

Structure of a fully assembled tumor-specific T cell receptor ligated by pMHC.

The T cell receptor (TCR) expressed by T lymphocytes initiates protective immune responses to pathogens and tumors. To explore the structural basis of how TCR signaling is initiated when the receptor binds to peptide-loaded major histocompatibility complex (pMHC) molecules, we used cryogenic electron microscopy to determine the structure of a tumor-reactive TCRαβ/CD3δγεζ complex bound to a melanoma-specific human class I pMHC at 3.08 Å resolution.

Mitigation of scintillation in FSO communication using a temporally and spatially incoherent spectrum-sliced light source.

We propose and demonstrate a temporally and spatially incoherent spectrum-sliced light source for scintillation mitigation in free-space optical (FSO) communications. For the temporal incoherence, we utilize the spectrum-sliced incoherent light (SSIL) modulated by gain-saturated reflective semiconductor optical amplifiers for data modulation and the suppression of excess intensity noise inherent in a narrowband incoherent light source. We then employ offset launching from a single-mode fiber to a multi-mode fiber to add the spatial incoherence to the SSIL source.

Malignant phyllodes tumor with synchronous metastases to axillary lymph nodes, lung at the presentation: a case report and literature review.

Phyllodes tumors are rare mesenchymal tumors of breast. Malignant phyllodes tumors can develop metastases to distal organs with spreading hematogenously to most frequent sites as lungs, bone and brain. Regional lymph node enlargement is common but metastasis to lymph node is a very rare phenomenon with prevalence about 1.

Aggregation and mobility of membrane proteins interplay with local lipid order in the plasma membrane of T cells.

To disentangle the elusive lipid-protein interactions in T-cell activation, we investigate how externally imposed variations in mobility of key membrane proteins (T-cell receptor [TCR], kinase Lck, and phosphatase CD45) affect the local lipid order and protein colocalisation. Using spectral imaging with polarity-sensitive membrane probes in model membranes and live Jurkat T cells, we find that partial immobilisation of proteins (including TCR) by aggregation or ligand binding changes their preference towards a more ordered lipid environment, which can recruit Lck. Our data suggest that the cellular membrane is poised to modulate the frequency of protein encounters upon alterations of their mobility, for example in ligand binding, which offers new mechanistic insight into the involvement of lipid-mediated interactions in membrane-hosted signalling events.

New insights on the supramolecular structure of highly porous core-shell drug nanocarriers using solid-state NMR spectroscopy.

Nano-sized metal-organic frameworks (nanoMOFs), with engineered surfaces to enhance the targeting of the drug delivery, have proven efficient as drug nanocarriers. To improve their performances a step further, it is essential to understand at the molecular level the interactions between the nanoMOF interfaces and both the surface covering groups and the drug loaded inside the micropores. Here we show how solid-state NMR spectroscopy allows us to address these issues in an aluminum-based nanoMOF coated and loaded with phosphorus-containing species.

Adaptive beam control techniques for airborne free-space optical communication systems.

In this paper, we study two adaptive beam control techniques, where the beam divergence angle is adjusted at the transmitter to (i) maximize link availability or (ii) minimize transmitter power while maintaining target link availability. For this purpose, we provide closed-form expressions about the link availability and optimum beam divergence angle under the effect of generalized two-dimensional Gaussian distribution of the alignment error between the transmitter and receiver. These simple and closed-form expressions reduce the computational complexity for performance optimization.

Focal electrical stimulation as an effective sham control for active rTMS and biofeedback treatments.

A valid sham control is important for determining the efficacy and effectiveness of repetitive transcranial magnetic stimulation (rTMS) as an experimental and clinical tool. Given the manner in which rTMS is applied, separately or in combination with self-regulatory approaches, and its intended impact on brain states, a valid sham control of this type may well serve as a meaningful control for biofeedback studies, where efforts to develop a credible control have often been less than ideal. This study examined the effectiveness of focal electrical stimulation of the frontalis muscle as a sham technique for blinding participants to high-frequency rTMS over the dorso-lateral prefrontal cortex (DLPFC) at durations, intensities, and schedules of stimulation similar to many clinical applications.

Protection from oxidative and electrophilic stress in the Gsta4-null mouse heart.

4-Hydroxynonenal (4-HNE) mediates many pathological effects of oxidative and electrophilic stress and signals to activate cytoprotective gene expression regulated by NF-E2-related factor 2 (Nrf2). By exhibiting very high levels of 4-HNE-conjugating activity, the murine glutathione transferase alpha 4 (GSTA4-4) helps regulate cellular 4-HNE levels. To examine the role of 4-HNE in vivo, we disrupted the murine Gsta4 gene.

T cell receptors are structures capable of initiating signaling in the absence of large conformational rearrangements.

Native and non-native ligands of the T cell receptor (TCR), including antibodies, have been proposed to induce signaling in T cells via intra- or intersubunit conformational rearrangements within the extracellular regions of TCR complexes. We have investigated whether any signatures can be found for such postulated structural changes during TCR triggering induced by antibodies, using crystallographic and mutagenesis-based approaches. The crystal structure of murine CD3ε complexed with the mitogenic anti-CD3ε antibody 2C11 enabled the first direct structural comparisons of antibody-liganded and unliganded forms of CD3ε from a single species, which revealed that antibody binding does not induce any substantial rearrangements within CD3ε.

Cost effectiveness of tobacco control policies in Vietnam: the case of population-level interventions.

Background: Tobacco smoking is one of the leading public health problems in the world. It is also possible to prevent and/or reduce the harm from tobacco use through the use of cost-effective tobacco control measures. However, most of this evidence comes from developed countries and little research has been conducted on this issue in developing countries.

Association of soluble CD89 levels with disease progression but not susceptibility in IgA nephropathy.

The Fc-α receptor (FcαR/CD89) is involved in IgA complex formation and may affect the development of IgA nephropathy (IgAN). In this study, we tested the genetic variations of the CD89 gene in relation to disease susceptibility in IgAN and the expression of soluble CD89 (sCD89) in sera of patients with IgAN and in controls. There was a significant difference between the levels of sCD89-IgA complexes, measured by sandwich enzyme-linked immunosorbent assay (ELISA), in 177 patients with IgAN with and without disease progression at the time of first diagnosis.

Genetic risk factors in lupus nephritis and IgA nephropathy--no support of an overlap.

Background: IgA nephropathy (IgAN) and nephritis in Systemic Lupus Erythematosus (SLE) are two common forms of glomerulonephritis in which genetic findings are of importance for disease development. We have recently reported an association of IgAN with variants of TGFB1. In several autoimmune diseases, particularly in SLE, IRF5, STAT4 genes and TRAF1-C5 locus have been shown to be important candidate genes.

Genetic variation in the transforming growth factor-beta1 gene is associated with susceptibility to IgA nephropathy.

Background: There is growing evidence of genetic risk for susceptibility to IgA nephropathy. Among several candidate genes related to immunological regulation in renal tissue, TGFB1 is known to be a contributor to proliferation and the development of fibrosis.

Methods: We analysed several SNPs in a region of this gene using 212 DNA samples from biopsy-proven IgA nephropathy patients, 146 men and 66 women and 477 healthy age-matched controls (321 men and 156 women) from the same population in Sweden.

Transcriptome-based identification of candidate membrane proteins.

A full understanding of leukocyte responses to external stimuli requires knowledge of the full complement of proteins found on their surfaces. Systematic examination of the mammalian cell surfaces at the protein level is hampered by technical difficulties associated with proteomic analysis of so many membrane proteins and the large amounts of starting material required. The use of transcriptomic analyses avoids challenges associated with protein stability and separation and enables the inclusion of an amplification step; thus allowing the use of cell numbers applicable to the study of sub populations of, for example, primary lymphocytes.

Impact and perspective on chronic kidney disease in an Asian developing country: a large-scale survey in North Vietnam.

Background: The prevalence of chronic kidney disease (CKD) in Asia is expected to increase along with increases of hypertension and diabetes. Most cases are not treated and progress to end-stage renal disease (ESRD) with an increased risk for cardiovascular complications. Renal replacement therapies are so expensive that most ESRD patients die without treatment.

Differential remodeling of a T-cell transcriptome following CD8- versus CD3-induced signaling.

CD8 engagement with class I major histocompatibility antigens greatly enhances T-cell activation, but it is not clear how this is achieved. We address the question of whether or not the antibody-mediated ligation of CD8 alone induces transcriptional remodeling in a T-cell clone, using serial analysis of gene expression. Even though it fails to induce overt phenotypic changes, we find that CD8 ligation profoundly alters transcription in the T-cell clone, at a scale comparable to that induced by antibody-mediated ligation of CD3.

Deep analysis of cellular transcriptomes - LongSAGE versus classic MPSS.

Background: Deep transcriptome analysis will underpin a large fraction of post-genomic biology. 'Closed' technologies, such as microarray analysis, only detect the set of transcripts chosen for analysis, whereas 'open' e.g.