空间天气对生物及其疾病的影响(英文)

生物圈与区域气象之间的各种联系纵横交错,十分复杂。近年来,不断有证据表明太阳和地球通过多种途径影响着我们。研究发现,在统计误差允许的范围内两个极为相似的生物体的生理学周期与地球的循环和/或太阳风有共振关系。于是我们估计,太阳和人类生理学的某些方面存在相关性,如对人类的感情、思想和行为有着或好或坏的影响。在此,这种相关性我们称为时间结构上的一致性。所谓一致性,在时间结构上的定义并非是相似、相同或等量,而是时间谱系分析中时段的重合或者说重叠或覆盖,且重合范围达95%。此外,与天和/或年的特质相比,虽然在人类身上非光节律的特征不够明显,但在生物圈中这种特征有时会更加显著。科学统计揭示,太阳磁力、地磁力和间接的太阳风对地球生物圈节律的变化有必然的影响。

Quantitative interactomic of CD40 in primary B cells

INTRODUCTION Over the past few decades,antibody-based therapies have emerged as an additional tool to treat patients developing cancer and auto-immune diseases.The natural properties of the developed antibodies may lead to agonist or blocking functions for the targeted molecule.Thus,antibodies developed for clinical trials are extensively analyzed in vitro and in vivo for safety and efficacy,yet they are not routinely evaluated for their potential signaling effectiveness.

Tumor cells educate mesenchymal stromal cells to release chemoprotective and immunomodulatory factors

Factors released by surrounding cells such as cancer-associated mesenchymal stromal cells(CA-MSCs)are involved in tumor progression and chemoresistance.In this study,we characterize the mechanisms by which naYve mesenchymal stromal cells(MSCs)can acquire a CA-MSCs phenotype.Ovarian tumor cells trigger the transformation of MSCs to CA-MSCs by expressing pro-tumoral genes implicated in the chemoresistance of cancer cells,resulting in the secretion of high levels of CXC chemokine receptors 1 and 2(CXCR1/2)ligands such as chemokine(C-X-C motif)ligand 1(CXCL1),CXCL2,and interleukin 8(IL-8).CXCR1/2 ligands can also inhibit the immune response against ovarian tumor cells.Indeed,through their released factors,CA-MSCs promote the differentiation of monocytes towards M2 macrophages,which favors tumor progression.When CXCR1/2 receptors are inhibited,these CA-MSC-activated macrophages lose their M2 properties and acquire an anti-tumoral phenotype.Both ex vivo and in vivo,we used a CXCR1/2 inhibitor to sensitize ovarian tumor cells to carboplatin and circumvent the pro-tumoral effects of CA-MSCs.Since high concentrations of CXCR1/2 ligands in patients*blood are associated with chemoresistance,CXCR1/2 inhibition could be a potential therapeutic strategy to revert carboplatin resistance.

Opposing regulatory functions of the TIM3 (HAVCR2) signalosome in primary effector T cells as revealed by quantitative interactomics

Deciphering how T-cell antigen receptor signals are modulated by coinhibitors is a fundamental goal in immunology and of considerable clinical interest because blocking coinhibitory signals via therapeutic antibodies have become a standard cancer immunotherapeutic strategy.Most of the attention devoted to T-cell immunoglobulin and mucin domain-3(TIM3;also known as HAVCR2 or CD366)molecules stems from their expression on exhausted T cells in settings of chronic viral infection and tumors.Moreover,T cells expressing high levels of both PD-1 and TIM3 coinhibitors appear more dysfunctional than those expressing PD-1 alone.Combination therapies intending to block both PD-1 and TIM3 are thus actively being explored in the cancer treatment setting.Upon interaction with Galectin-9(GAL-9)and carcinoembryonic antigen-related cell adhesion molecule 1(CEACAM-1),the tyrosines found in the TIM3 cytoplasmic tail are phosphorylated.1 Because these conserved tyrosines do not form a recognizable inhibitory signaling motif,the mechanism by which TIM3 transmits inhibitory signals has not been elucidated.Paradoxically,TIM3 also has costimulatory activity in T cells.2,3 Published biochemical studies attempting to unveil the mode of action of TIM3 have relied on approaches addressing one candidate effector at a time with limited quantitative insight,and most used transformed cells.Using mice expressing an affinity Twin-Strep-tag(OST)at the TIM3-protein C-terminus(TIM3OST mice)(Figs.1a and S1a)and affinity purification coupled with mass spectrometry(AP-MS),we herein defined the composition and dynamics of the signaling protein complex(signalosome)used by TIM3 in primary effector T cells.These results provide a more complete model of TIM3 signaling and explain its paradoxical coinhibitory and costimulatory functions.

RIP140 regulates POLK gene expression and the response to alkylating drugs in colon cancer cells

Aim:The transcription factor RIP140(receptor interacting protein of 140 kDa)is involved in intestinal tumorigenesis.It plays a role in the control of microsatellite instability(MSI),through the regulation of MSH2 and MSH6 gene expression.The aim of this study was to explore its effect on the expression of POLK,the gene encoding the specialized translesion synthesis(TLS)DNA polymeraseκknown to perform accurate DNA synthesis at microsatellites.Methods:Different mouse models and engineered human colorectal cancer(CRC)cell lines were used to analyze by RT-qPCR,while Western blotting and luciferase assays were used to elucidate the role of RIP140 on POLK gene expression.Published DNA microarray datasets were reanalyzed.The in vitro sensitivity of CRC cells to methyl methane sulfonate and cisplatin was determined.Results:RIP140 positively regulates,at the transcriptional level,the expression of the POLK gene,and this effect involves,at least partly,the p53 tumor suppressor.In different cohorts of CRC biopsies(with or without MSI),a strong positive correlation was observed between RIP140 and POLK gene expression.In connection with its effect on POLK levels and the TLS function of this polymerase,the cellular response to methyl methane sulfonate was increased in cells lacking the Rip140 gene.Finally,the association of RIP140 expression with better overall survival of CRC patients was observed only when the corresponding tumors exhibited low levels of POLK,thus strengthening the functional link between the two genes in human CRC.Conclusion:The regulation of POLK gene expression by RIP140 could thus contribute to the maintenance of microsatellite stability,and more generally to the control of genome integrity.

Characterization of cancer-associated adipocytes by Raman spectroscopy and trajectory inference

Cancer-associated adipocytes(CAAs)have emerged as pivotal players in various cancers,particularly in such as breast cancer,significantly influencing their progression and therapy resistance.Understanding the adipocytes/cancer cells crosstalk is crucial for effective treatment strategies.Raman spectroscopy,a label-free optical technique,offers potential for characterizing biological samples by providing chemical-specific information.In this study,we used Raman spectroscopy and Trajectory Inference methods,specifically the Partition-based graph abstraction algorithm,to investigate the interactions between 3T3-L1 differentiated adipocytes and MDA-MB-231 breast cancer cells in a 2D co-culture model.We demonstrate the existence of subpopulations of adipocytes and the molecular changes associated with CAAs phenotype.This work contributes to understanding the role of CAAs in breast cancer progression and may guide the development of targeted therapies disrupting this interaction.