scholarly journals On the impact of second generation mating and offspring in multi-generation reproductive toxicity studies on classification and labelling of substances in Europe

2011 ◽  
Vol 61 (2) ◽  
pp. 251-260 ◽  
Author(s):  
Emiel Rorije ◽  
André Muller ◽  
Manon E.W. Beekhuijzen ◽  
Ulla Hass ◽  
Barbara Heinrich-Hirsch ◽  
...  
2021 ◽  
Vol 22 (5) ◽  
pp. 2476
Author(s):  
Kento Fujiwara ◽  
Masaki Kitaura ◽  
Ayaka Tsunei ◽  
Hotaka Kusabuka ◽  
Erika Ogaki ◽  
...  

T cells that are genetically engineered to express chimeric antigen receptor (CAR) have a strong potential to eliminate tumor cells, yet the CAR-T cells may also induce severe side effects due to an excessive immune response. Although optimization of the CAR structure is expected to improve the efficacy and toxicity of CAR-T cells, the relationship between CAR structure and CAR-T cell functions remains unclear. Here, we constructed second-generation CARs incorporating a signal transduction domain (STD) derived from CD3ζ and a 2nd STD derived from CD28, CD278, CD27, CD134, or CD137, and investigated the impact of the STD structure and signaling on CAR-T cell functions. Cytokine secretion of CAR-T cells was enhanced by 2nd STD signaling. T cells expressing CAR with CD278-STD or CD137-STD proliferated in an antigen-independent manner by their STD tonic signaling. CAR-T cells incorporating CD28-STD or CD278-STD between TMD and CD3ζ-STD showed higher cytotoxicity than first-generation CAR or second-generation CARs with other 2nd STDs. The potent cytotoxicity of these CAR-T cells was not affected by inhibiting the 2nd STD signals, but was eliminated by placing the STDs after the CD3ζ-STD. Our data highlighted that CAR activity was affected by STD structure as well as by 2nd STD signaling.


Food Security ◽  
2021 ◽  
Author(s):  
Kathrine E. Wright ◽  
Julie E. Lucero ◽  
Jenanne K. Ferguson ◽  
Michelle L. Granner ◽  
Paul G. Devereux ◽  
...  

2004 ◽  
Vol 29 (3) ◽  
pp. 201-215 ◽  
Author(s):  
Hiroshi MINESHIMA ◽  
Yoshihiko ENDO ◽  
Hiroyuki OGASAWARA ◽  
Keiji NISHIGAKI ◽  
Toshiaki NUMA ◽  
...  

Author(s):  
Ninel Shepelska ◽  
Mykola Prodanchuk ◽  
Yana Kolianchuk

Currently, one of the main threats to human health is undoubtedly endocrine disruptors (ED), since they directly disrupt the processes of homeostasis maintenance, controlled by the endocrine system, the purpose of which is to maintain normal functions and development in a constantly changing environment. Pesticides can disrupt the physiological functioning of many endocrine axes, including the endocrine mechanisms that ensure reproductive health. It should be noted that research aimed at preventing chemically induced reproductive disorders in the human population is one of the central areas of preventive medicine, both in terms of their importance and the complexity of the tasks being solved. Analysis and generalization of the results of our own long-term studies have shown that the selective, and, therefore, the most dangerous toxicity of pesticides for the reproductive system is determined by endocrine-mediated mechanisms of etiopathogenesis. The low level of doses inducing pathological changes in reproductive function in our studies fully confirms one of the universal signs inherent in endocrine-distruptive compounds. The above examples demonstrate a wide range of possible endocrine-mediated mechanisms of reproductive toxicity of pesticides - endocrine disruptors. However, it is very important to note that low doses may be more effective in changing some endpoints compared to high (toxic) doses. Currently, several mechanisms have been identified and studied that demonstrate how hormones and ED induce non-monotonic reactions in animal cells, tissues and organs. The reproductive system, the functioning of which is ensured by a fine balancing of the action of androgens and estrogens, is one of the systems that presents a unique opportunity for modeling a non-monotonic dose dependence. All of the above indicates the extreme danger of the impact of hormonally active agents on the reproductive health of a person and his offspring. At the same time, the threat of endocrine-mediated disorders for subsequent generations can also be realized through the induction of mechanisms of development of epigenetic transgenerational effects. Taking into account the results of studies of the mechanisms of the ED destructive action, as well as their ability to induce non-monotonic dose dependence at an extremely low dose level, it should be admitted that, apparently, there is a need to revise the paradigm of methodological approaches to the regulation of pesticides with endocrine-disruptive properties. Key words: pesticides, endocrine disruptors, reproductive system


2015 ◽  
pp. 1695-1707 ◽  
Author(s):  
Anastasios Ntanos ◽  
Stamatios Ntanos

This chapter refers to small family businesses in Greece and examines the impact of their marketing strategy during an economic crisis period. The research took place in the broad area of Athens between December 2011 and March 2012. Data were collected to form a database of Greek independent private family companies (n=380) using personal interviews (structured questionnaire) with owners/managers of first- and second-generation family businesses. The chapter shows how small family businesses indicate marketing strategy using Carson's model. Limitations of expertise outline the marketing background, which can be described as “self-assisted.” The research offers a verification of a previous model so that problems that arise from companies not putting into practice any marketing concepts can be examined. The significance of the chapter is that there have not formerly been any reviews made about Carson's model in Greece during the economic crisis period emphasizing family businesses.


2019 ◽  
Vol 37 (5) ◽  
pp. 627-637 ◽  
Author(s):  
Dustin C. Read

Purpose In a controversial 2018 interview, commercial real estate mogul Sam Zell insinuated that companies should promote their employees based exclusively on merit and avoid purposefully taking steps to get “more pussy on the block” in the name of gender equality. The comment was criticized not only for its crassness, but also for its failure to recognize the challenges many women working in the commercial real estate industry face in their efforts to obtain the same opportunities, compensation and status as similarly-qualified men. In an effort to overcome these disparities, the purpose of this paper is to focus on the pervasiveness of second-generation gender bias and stereotyping in the field through a qualitative analysis. Design/methodology/approach Semi-structured interviews were conducted with 39 women serving as local chapter presidents of a prominent commercial real estate trade group to explore the impact of gender on their career advancement and their experiences with second-generation gender bias. Findings The findings suggest unintentional discrimination often influences women’s careers by drawing their communication skills, professional credibility and commitment to the organizations for whom they work into question. Originality/value The research contributes to the existing literature by offering additional evidence that unintentional discrimination is common in male-dominated industries, such as commercial real estate. It also provides clear examples of social cues women perceive to heighten tension along gender lines and impinge upon their ability to ascend to leadership positions.


2005 ◽  
Vol 27 (4) ◽  
pp. 421-425
Author(s):  
Ingrid H. Rima

My reflections are at least partly those of the child of an emigré who grew up to beome an economist. Since my father was an engineer from Germany's Barmen-Elberfeld textile city—also the city of Friedrich Engels—he clearly is not among the first generation of German scholars who were deprived of their professional positions as the Hitler regime came into power. Indeed, somewhat like Joseph Schumpeter, he came to America to grasp an opportunity rather than to avoid a threat. Like many of educated men of his generation, he was fluent in five languages and an ardent student of philosophy, history, and political economy. His move to America, after three or four trial visits, preceded my birth, because in those days before international air travel the seven day ocean voyage between Bremerhaven and New York was so daunting for a woman approaching childbirth that I was close to a year old before our arrival in America. My early childhood was uneventful except for the arrival of two siblings, and the only negative I recall from those early days was that I hated my first name, Ingrid (so carefully chosen by my parents), and longed to be called Jane, Anne or anything other than Ingrid.


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