Epitope-Specific Regulation of Memory Programming by Differential Duration of Antigen Presentation to Influenza-Specific CD8+ T Cells

SummaryMemory CD8+ T cells are programmed during the primary response for robust secondary responsiveness. Here we show that CD8+ T cells responding to different epitopes of influenza virus received qualitatively different signals during the primary response that altered their secondary responsiveness. Nucleoprotein (NP)-specific CD8+ T cells encountered antigen on CD40-licensed, CD70-expressing, CD103−CD11bhi dendritic cells (DCs) at later times in the primary response. As a consequence, they maintained CD25 expression and responded to interleukin-2 (IL-2) and CD27, which together programmed their robust secondary proliferative capacity and interferon-γ (IFN-γ)-producing ability. In contrast, polymerase (PA)-specific CD8+ T cells did not encounter antigen-bearing, CD40-activated DCs at later times in the primary response, did not receive CD27 and CD25 signals, and were not programmed to become memory CD8+ T cells with strong proliferative and cytokine-producing ability. As a result, CD8+ T cells responding to abundant antigens, like NP, dominated the secondary response

The Biological Outcome of CD40 Signaling Is Dependent on the Duration of CD40 Ligand Expression: Reciprocal Regulation by Interleukin (IL)-4 and IL-12

CD40 ligand (CD154) expression on activated T cells can be separated into an early TCR-dependent phase, which occurs between 0 and 24 h after activation, and a later extended phase, which occurs after 24 h and is reciprocally regulated by the cytokines IL-4 and IL-12. IL-4 represses, whereas IL-12 sustains CD154 expression. Consistent with this, Th1, but not Th2, cells express CD154 for extended periods. Differences in the duration of CD154 expression have important biological consequences because sustained, but not transient, expression of CD154 on activated T cells can prevent B cell terminal differentiation. Thus, the differential ability of Th cells to sustain CD154 expression is an important part of their helper function and should influence the activities of other CD40-expressing cell types

Idiopathic retroperitoneal fibrosis associated with Hashimoto's thyroiditis in a patient with a single functioning kidney

AbstractRetroperitoneal fibrosis (RPF) is a rare disease characterized by the presence of fibroinflammatory tissue around the abdominal aorta and ureteral entrapment in most cases. Idiopathic RPF is frequently reported in association with autoimmune diseases; however, there have been few reports of idiopathic RPF associated with Hashimoto's thyroiditis. Here, we report a case of idiopathic RPF with Hashimoto's thyroiditis in a patient with a single functioning kidney, which was successfully treated by corticosteroid therapy and transient intraureteral stent insertion with a double-J catheter

Local government performance and democratic consolidation: Explaining ordinance proposal in Busan Metropolitan Council

This article assesses the role of local councils as a conduit for democratic consolidation through the examination of the legislative performance of the members of a South Korean metropolitan city council. We collected data on ordinance proposals in Busan Metropolitan Council from 2006 to 2018 (the 5th to 7th Councils) and analysed, first, the effects of individual attributes of local council members on legislative performance through negative binomial model analysis and, second, the effects of legislative networks on council members' performance. Three findings contribute to the literature: first, the number of proposed ordinances by council members increased over time, while those by the mayor decreased in the same period, suggesting an erosion of executive dominance of policymaking in local councils. Second, female and newly elected council members are most active in legislative proposals, which underlines that these members are more connected to the electorate than long-serving incumbents. Third, network analyses show increasingly diverse and multi-centred communities behind ordinance proposals; this suggests a move from personalistic politics to institutionalised politics.National Research Foundation of Korea, Grant/Award Number: NRF2018S1A5A2A03033767; Ministry of Education of the Republic of Kore

First results from the HAYSTAC axion search

The axion is a well-motivated cold dark matter (CDM) candidate first postulated to explain the absence of $CP$ violation in the strong interactions. CDM axions may be detected via their resonant conversion into photons in a "haloscope" detector: a tunable high-$Q$ microwave cavity maintained at cryogenic temperature, immersed a strong magnetic field, and coupled to a low-noise receiver. This dissertation reports on the design, commissioning, and first operation of the Haloscope at Yale Sensitive to Axion CDM (HAYSTAC), a new detector designed to search for CDM axions with masses above $20$ $\mu\mathrm{eV}$. I also describe the analysis procedure developed to derive limits on axion CDM from the first HAYSTAC data run, which excluded axion models with two-photon coupling $g_{a\gamma\gamma} \gtrsim 2\times10^{-14}$ $\mathrm{GeV}^{-1}$, a factor of 2.3 above the benchmark KSVZ model, over the mass range $23.55 < m_a < 24.0$ $\mu\mathrm{eV}$. This result represents two important achievements. First, it demonstrates cosmologically relevant sensitivity an order of magnitude higher in mass than any existing direct limits. Second, by incorporating a dilution refrigerator and Josephson parametric amplifier, HAYSTAC has demonstrated total noise approaching the standard quantum limit for the first time in a haloscope axion search.Comment: Ph.D. thesis. 346 pages, 58 figures. A few typos corrected relative to the version submitted to ProQues

Primary transcriptome and translatome analysis determines transcriptional and translational regulatory elements encoded in the Streptomyces clavuligerus genome

Determining transcriptional and translational regulatory elements in GC-rich Streptomyces genomes is essential to elucidating the complex regulatory networks that govern secondary metabolite biosynthetic gene cluster (BGC) expression. However, information about such regulatory elements has been limited for Streptomyces genomes. To address this limitation, a high-quality genome sequence of β-lactam antibiotic-producing Streptomyces clavuligerus ATCC 27 064 is completed, which contains 7163 newly annotated genes. This provides a fundamental reference genome sequence to integrate multiple genome-scale data types, including dRNA-Seq, RNA-Seq and ribosome profiling. Data integration results in the precise determination of 2659 transcription start sites which reveal transcriptional and translational regulatory elements, including -10 and -35 promoter components specific to sigma (σ) factors, and 5'-untranslated region as a determinant for translation efficiency regulation. Particularly, sequence analysis of a wide diversity of the -35 components enables us to predict potential σ-factor regulons, along with various spacer lengths between the -10 and -35 elements. At last, the primary transcriptome landscape of the β-lactam biosynthetic pathway is analyzed, suggesting temporal changes in metabolism for the synthesis of secondary metabolites driven by transcriptional regulation. This comprehensive genetic information provides a versatile genetic resource for rational engineering of secondary metabolite BGCs in Streptomyces

Energy levels of the soliton--heavy-meson bound states

We investigate the bound states of heavy mesons with finite masses to a classical soliton solution in the Skyrme model. For a given model Lagrangian we solve the equations of motion exactly so that the heavy vector mesons are treated on the same footing as the heavy pseudoscalar mesons. All the energy levels of higher grand spin states as well as the ground state are given over a wide range of the heavy meson masses. We also examine the validity of the approximations used in the literatures. The recoil effect of finite mass soliton is naively estimated.Comment: 24 pages, REVTeX v3.0, 6 figures are available upon request