Heat Shock Protein Magic in Antigen Trafficking within Dendritic Cells:Implications in Antigen Cross-presentation in Immunity

Dendritic cells (DCs) take up soluble- or cell-associated antigens and digest them, delivering fragments to the MHC class I pathway to display antigenic peptides to CD8＋ T cells, a process known as cross-presentation. The pathway requires that, in order to be degraded by proteosomes, the extracellular antigens must have access to the cytosol across the endosomal membranes. Although the cross-presentation phenomena was first identified in the 1970s, the molecular mechanism responsible for the translocation is still not fully understood. In this context, we have recently found that cytosolic heat shock protein (HSP)90 translocates internalized antigen to the cytosol in DCs. Our results revealed the important role that cytosolic HSP90 plays in cross-presentation by pulling out endosomal antigen to the cytosol

Cancer immunotherapy with blocking of immune checkpoints

がんワクチンによる免疫治療では，如何にCD8T細胞を感作（プライミング）しその数を増やすか（免疫増強）という点に多大の努力が払われて来た．樹状細胞への抗原デリバリーと抗原プロセシング／提示，Toll様受容体などの刺激，即ち自然免疫系の活性化の併用などはそれに該当する．しかし十分に活性化されたＴ細胞をもってしても癌の拒絶は容易ではない．それには癌組織という特殊な環境が禍している．Ｔ細胞は癌塊内に入り込み莫大な数の癌細胞と遭遇する．癌組織内での繰り返す抗原認識の過程でＴ細胞は疲弊し，次第に本来あるべき機能を喪失していく．この疲弊（exhaustion）と呼ばれる現象は，Ｔ細胞に発現する複数の免疫抑制性分子―免疫チェックポイント分子―と腫瘍に発現するそのリガンドの結合によってもたらされる．代表的なチェックポイント分子の機能を抑制し，エフェクターＴ細胞が疲弊することなくその機能を長く維持できれば，これからのがん免疫治療に飛躍的な進展がみられるかもしれない

Indirect Optical Absorption of Single Crystalline beta-FeSi2

We investigated optical absorption spectra near the fundamental absorption edge of beta-FeSi2 single crystals by transmission measurements. The phonon structure corresponding to the emission and absorption component was clearly observed in the low-temperature absorption spectra. Assuming exciton state in the indirect allowed transition, we determined a phonon energy of 0.031 +- 0.004 eV. A value of 0.814 eV was obtained for the exciton transition energy at 4K.Comment: 10 pages with 3 figure

Rural Entrepreneurship in Nigeria: Lessons From Scientific Management

This article focussed on the lessons that can be garnered from the tenets of Scientific Management. We undertook an X-ray of the tenets of Scientific Management and how these tenets can be adopted to ensure the success of emerging entrepreneurs in the rural areas. Many rural entrepreneurs fail within a short period of start-up, yet these entrepreneurs are a sure springboard for the development of these rural areas and nation as a whole. It was observed that many causes of the failure of these entrepreneurs could have been taken care of through the adoption of the tenets of Scientific management such as a sound knowledge of the business proposed and capacity building. Key recommendations were that: Government should provide an enabling environment for innovation and entrepreneurship; provide sources of capital and build a repository of information on businesses.Key words: Rural entrepreneurship, scientific management

Heat Capacity study of β\beta-FeSi2_2 single crystals

Heat Capacity of needle-like [length=5mm, diameter=1 mm] $\beta$-FeSi$_{2}$ single crystal, grown by chemical vapor transport has been measured. Two anomalies are found, a broad deviation centered around 160 K and a clear deviation at a temperature of 255 K approximately. We have attempted to relate these to the anomalies previously reported in the case of the resistivity data. The Transient Thermoelectric Effect [TTE] results lead us to the inference that the system under goes from single carrier system to at least two carrier system at 220 K-our heat capacity results seem to provide further independent evidence for this transition in this system.Comment: 8 pages, 5 figure

Interaction of human heat shock protein 70 with tumor-associated peptides

Molecular chaperones of the heat shock protein 70 (Hsp70) family play a crucial role in the presentation of exogenous antigenic peptides by antigen-presenting cells (APCs). In a combined biochemical and immunological approach, we characterize the biochemical interaction of tumor-associated peptides with human Hsp70 and show that the strength of this interaction determines the efficacy of immunological cross-presentation of the antigenic sequences by APCs. A fluorescein-labeled cytosolic mammalian Hsc70 binding peptide is shown to interact with human Hsp70 molecules with high affinity (K(d)=0.58 mu M at 25 degrees C). Competition experiments demonstrate weaker binding by Hsp70 of antigenic peptides derived from the tumor-associated proteins tyrosinase (K(d)=32 mu M) and melanoma antigen recognized by T cells (MART-1) (K(d)=2.4 mu M). Adding a peptide sequence (pep70) with high Hsp70 binding affinity (K(d)=0.04 mu M) to the tumor-associated peptides enables them to strongly interact with Hsp70. Presentation of tumor-associated peptides by B cells resulting in T cell activation in vitro is enhanced by Hsp70 when the tumor-associated peptides contain the Hsp70 binding sequence. This observation has relevance for vaccine design, as augmented transfer of tumor-associated antigens to APCs is closely linked to the vaccine's efficacy of T cell stimulation

Hepatitis C virus infection reduces the lifespan of chimpanzees used in biomedical research

チンパンジーの肝炎感染実験の影響 --寿命が短くなり肝臓や腎臓に障害. 京都大学プレスリリース. 2022-08-10.Chimpanzees were used in hepatitis research for over three decades with the aim to identify and develop treatments for the virus, a leading cause of chronic liver disease in humans. We used a dataset of 120 chimpanzees housed at a single institution in Japan, 22 of whom became chronically infected with hepatitis C virus (HCV), to examine whether HCV infection results in a reduced lifespan as reported in humans. Survival analysis showed that HCV carriers experienced a higher mortality risk compared with non-carriers. Although no chimpanzee died from hepatic disease, carriers showed higher gamma-glutamyl transpeptidase (γGTP) levels compared with non-carriers suggesting that HCV infection negatively affected their liver condition. These results provide evidence that special attention is necessary to monitor the long-term condition of ex-biomedical primates