Identification of VIMP as a gene inhibiting cytokine production in human CD4+ effector T cells.

Many players regulating the CD4 T cell-mediated inflammatory response have already been identified. However, the critical nodes that constitute the regulatory and signaling networks underlying CD4 T cell responses are still missing. Using a correlation-network-guided approach, here we identified (VCP-interacting membrane protein), one of the 25 genes encoding selenoproteins in humans, as a gene regulating the effector functions of human CD4 T cells, especially production of several cytokines including IL2 and CSF2.

Induction of IL-10-producing type 2 innate lymphoid cells by allergen immunotherapy is associated with clinical response.

The role of innate immune cells in allergen immunotherapy that confers immune tolerance to the sensitizing allergen is unclear. Here, we report a role of interleukin-10-producing type 2 innate lymphoid cells (IL-10 ILC2s) in modulating grass-pollen allergy. We demonstrate that KLRG1 but not KLRG1 ILC2 produced IL-10 upon activation with IL-33 and retinoic acid.

Mitochondria interaction networks show altered topological patterns in Parkinson's disease.

Mitochondrial dysfunction is linked to pathogenesis of Parkinson's disease (PD). However, individual mitochondria-based analyses do not show a uniform feature in PD patients. Since mitochondria interact with each other, we hypothesize that PD-related features might exist in topological patterns of mitochondria interaction networks (MINs).

Applying next-generation sequencing to unravel the mutational landscape in viral quasispecies.

Next-generation sequencing (NGS) has revolutionized the scale and depth of biomedical sciences. Because of its unique ability for the detection of sub-clonal variants within genetically diverse populations, NGS has been successfully applied to analyze and quantify the exceptionally-high diversity within viral quasispecies, and many low-frequency drug- or vaccine-resistant mutations of therapeutic importance have been discovered. Although many works have intensively discussed the latest NGS approaches and applications in general, none of them has focused on applying NGS in viral quasispecies studies, mostly due to the limited ability of current NGS technologies to accurately detect and quantify rare viral variants.

Applying Unique Molecular Identifiers in Next Generation Sequencing Reveals a Constrained Viral Quasispecies Evolution under Cross-Reactive Antibody Pressure Targeting Long Alpha Helix of Hemagglutinin.

To overcome yearly efforts and costs for the production of seasonal influenza vaccines, new approaches for the induction of broadly protective and long-lasting immune responses have been developed in the past decade. To warrant safety and efficacy of the emerging crossreactive vaccine candidates, it is critical to understand the evolution of influenza viruses in response to these new immune pressures. Here we applied unique molecular identifiers in next generation sequencing to analyze the evolution of influenza quasispecies under in vivo antibody pressure targeting the hemagglutinin (HA) long alpha helix (LAH).

A roadmap towards personalized immunology.

Big data generation and computational processing will enable medicine to evolve from a "one-size-fits-all" approach to precise patient stratification and treatment. Significant achievements using "Omics" data have been made especially in personalized oncology. However, immune cells relative to tumor cells show a much higher degree of complexity in heterogeneity, dynamics, memory-capability, plasticity and "social" interactions.

Network-Guided Key Gene Discovery for a Given Cellular Process.

Identification of key genes for a given physiological or pathological process is an essential but still very challenging task for the entire biomedical research community. Statistics-based approaches, such as genome-wide association study (GWAS)- or quantitative trait locus (QTL)-related analysis have already made enormous contributions to identifying key genes associated with a given disease or phenotype, the success of which is however very much dependent on a huge number of samples. Recent advances in network biology, especially network inference directly from genome-scale data and the following-up network analysis, opens up new avenues to predict key genes driving a given biological process or cellular function.

Perinatal stress effects on later anxiety and hormone secretion in male mandarin voles.

The estradiol (E2), estrogen receptor-α (ERα), testosterone (T), and androgen receptor (AR) can contribute to anxiety, but whether they are associated with the reversion of prenatal adverse outcomes remains unclear. Here, we tested the interactive effects of prenatal maternal restraint stress and early postnatal short-term maternal separation on adult male mandarin vole (Microtus mandarinus) behavior and changes in E2, T, and their receptors. The results showed that PS adult males (PS/NH) exhibited an increase in anxiety-like behavior in open-field and elevated plus-maze tests than the other 3 groups, including adult male offspring controls (PC/NH), adult male offspring controls with short-term maternal separation (PC/H), and PS adult males with short-term maternal separation (PS/H).

Identification of molecular sub-networks associated with cell survival in a chronically SIVmac-infected human CD4+ T cell line.

Background: The deciphering of cellular networks to determine susceptibility to infection by HIV or the related simian immunodeficiency virus (SIV) is a major challenge in infection biology.

Results: Here, we have compared gene expression profiles of a human CD4+ T cell line at 24 h after infection with a cell line of the same origin permanently releasing SIVmac. A new knowledge-based-network approach (Inter-Chain-Finder, ICF) has been used to identify sub-networks associated with cell survival of a chronically SIV-infected T cell line.

Construction and verification of the transcriptional regulatory response network of Streptococcus mutans upon treatment with the biofilm inhibitor carolacton.

Background: Carolacton is a newly identified secondary metabolite causing altered cell morphology and death of Streptococcus mutans biofilm cells. To unravel key regulators mediating these effects, the transcriptional regulatory response network of S. mutans biofilms upon carolacton treatment was constructed and analyzed.

Essential O2-responsive genes of Pseudomonas aeruginosa and their network revealed by integrating dynamic data from inverted conditions.

Identification of the gene network through which Pseudomonas aeruginosa PAO1 (PA) adapts to altered oxygen-availability environments is essential for a better understanding of stress responses and pathogenicity of PA. We performed high-time-resolution (HTR) transcriptome analyses of PA in a continuous cultivation system during the transition from high oxygen tension to low oxygen tension (HLOT) and the reversed transition from low to high oxygen tension (LHOT). From those genes responsive to both transient conditions, we identified 85 essential oxygen-availability responsive genes (EORGs), including the expected ones (arcDABC) encoding enzymes for arginine fermentation.