Blocking of melatonin synthesis and MT1 receptor impairs the activation of Jurkat T cells

Melatonin has been proposed as regulating the immune system by affecting cytokine production in immunocompetent cells, enhancing the production of several T helper (Th)1 cytokines. To further investigate the melatonin’s role in IL-2/IL-2R system, we established an inducible T-REx expression system in Jurkat cells in which the protein levels of HIOMT enzyme or MT₁ receptor were significantly down-regulated upon tetracycline incubation. We found that T-REx Jurkat cells with lower levels of HIOMT activity, and consequently lower content of endogenous melatonin, showed IL-2 production decrease after activation with lectin. Likewise, tetracycline-inducible stable cell line expressing MT₁ antisense produced decreased amounts of IL-2 (mRNA and protein levels) after stimulation. Moreover, in T-Rex-MT₁ cells incubated with tetracycline, a sub-optimal PHA dose failed to induce the early activation marker CD25 on the cell surface. The results shown here support the relevance of endogenous melatonin and its signaling in T cell activation.     

Redescription of two species previously regarded as Marphysa de Quatrefages, 1865, with the description of new species of Treadwellphysa Molina-Acevedo and Carrera-Parra, 2017

Herein, two species described in Marphysa are transferred to the recently proposed genus Treadwellphysa. After a morphological analysis of the type and additional material, it was found that both species belong to Treadwellphysa, based on the shape of the ventral cirrus with a swollen base as a transverse welt and the shape of maxillae I and II of the maxillary apparatus. Also, two new species, T. rizzoae sp. nov. and T. villalobosi sp. nov., are formally described, with materials studied from Brazil and Costa Rica, respectively. A key to all species of Treadwellphysa is also given.

urn:lsid:zoobank.org:pub:693D9279-682F-44E1-B1D5-15A9A5029FB6     

An endogenous tumour-promoting ligand of the human aryl hydrocarbon receptor

Activation of the aryl hydrocarbon receptor (AHR) by environmental xenobiotic toxic chemicals, for instance 2,3,7,8-tetrachlorodibenzo-p-dioxin (dioxin), has been implicated in a variety of cellular processes such as embryogenesis, transformation, tumorigenesis and inflammation. But the identity of an endogenous ligand activating the AHR under physiological conditions in the absence of environmental toxic chemicals is still unknown. Here we identify the tryptophan (Trp) catabolite kynurenine (Kyn) as an endogenous ligand of the human AHR that is constitutively generated by human tumour cells via tryptophan-2,3-dioxygenase (TDO), a liver- and neuron-derived Trp-degrading enzyme not yet implicated in cancer biology. TDO-derived Kyn suppresses antitumour immune responses and promotes tumour-cell survival and motility through the AHR in an autocrine/paracrine fashion. The TDO-AHR pathway is active in human brain tumours and is associated with malignant progression and poor survival. Because Kyn is produced during cancer progression and inflammation in the local microenvironment in amounts sufficient for activating the human AHR, these results provide evidence for a previously unidentified pathophysiological function of the AHR with profound implications for cancer and immune biology.     

System Dynamics and Learning Scenarios for Process Improvement and Regional Resilience: A Study in The Footwear Industry of Southern Brazil

Systemic Practice and Action Research - By means of integrated and systemic resilience strategies, it is possible to reduce vulnerability and risk, and at the same time increase the capacity to...     

集成电路电磁适应性的时钟信号调制

电磁干扰(EMI)是瞬时功能故障的主要来源之一,原因是电源供电线上的噪声注入引起了VDD和GND的额定值的波动.介绍了一种新的方法来增强片上系统(SoC)关于电源和接地电压瞬变时的信号完整性,并且这种方法完全符合IEC 61000-4-29 标准.其基本思想是设计和IEC 61000-4-29兼容的集成电路,通过局部和动态地将时钟占空比去适应传播延迟的变化和扰动的逻辑路径.当无法满足时,该方法导致暂时把集成电路的工作频率减小到满足该标准的最小值.根据异常电网活动,时钟占空比调制(CDCM)是通过使用正和/或负边沿时钟展宽逻辑(CSL)块来实现的.基于这个概念,在尽可能保持时钟高速频率的同时,数字电路对于电源供电线上波动的耐受性将会更强.该方法可被视作一种在线提供动态自适应同步的监视技术.通过SPICE模拟,实验结果表明此方法的有效性.     

Antibiotics in early life alter the murine colonic microbiome and adiposity

Antibiotics administered in low doses have been widely used as growth promoters in the agricultural industry since the 1950s, yet the mechanisms for this effect are unclear. Because antimicrobial agents of different classes and varying activity are effective across several vertebrate species, we proposed that such subtherapeutic administration alters the population structure of the gut microbiome as well as its metabolic capabilities. We generated a model of adiposity by giving subtherapeutic antibiotic therapy to young mice and evaluated changes in the composition and capabilities of the gut microbiome. Administration of subtherapeutic antibiotic therapy increased adiposity in young mice and increased hormone levels related to metabolism. We observed substantial taxonomic changes in the microbiome, changes in copies of key genes involved in the metabolism of carbohydrates to short-chain fatty acids, increases in colonic short-chain fatty acid levels, and alterations in the regulation of hepatic metabolism of lipids and cholesterol. In this model, we demonstrate the alteration of early-life murine metabolic homeostasis through antibiotic manipulation.     

Late survival of Neanderthals at the southernmost extreme of Europe

The late survival of archaic hominin populations and their long contemporaneity with modern humans is now clear for southeast Asia. In Europe the extinction of the Neanderthals, firmly associated with Mousterian technology, has received much attention, and evidence of their survival after 35 kyr bp has recently been put in doubt. Here we present data, based on a high-resolution record of human occupation from Gorham's Cave, Gibraltar, that establish the survival of a population of Neanderthals to 28 kyr bp. These Neanderthals survived in the southernmost point of Europe, within a particular physiographic context, and are the last currently recorded anywhere. Our results show that the Neanderthals survived in isolated refuges well after the arrival of modern humans in Europe.     

Two different aggregation principles in reaggregation process of dissociated sponge cells (Geodia cydonium)

Zusammenfassung Chemisch dissoziierte Zellen des KieselschwammesGeodia cydonium reaggregieren aufgrund zweier verschiedenr Reaggregationsprinzipien. Der Aggnegationsfaktor, auf den die Primäraggregation zurückgeht, ist membrangebunden und wird durch Proteasen nicht inaktiviert. Der sekundäre Aggregationsfaktor wurde 500fach angereichert. Das Molekulargewicht dieses Aggregationsfaktors beträgt etwa 20000 Daltons; er ist mit einem ringförmigen Makromolekül (2×10⁹ Daltons) assoziiert.

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Acknowledgments. We wish to thank Mrs.V. Pondeljak, Mrs.U. Müller-Berger, Mr. R. Beyer andMr. M. Srecec for their excellent technical assistance. We gratefully acknowledge the advice of dipl. Chem.J. Obermeier for the carbodiimide coupling method. This work is supported by Fonds der Chemischen Industrie and by the Landesversicherungsantalt Rheinland-Pfalz, Speyer/Rh.