Friend of the Good Earth: [Dr. ReneÌ Dubos]

Rockefeller University Research Profiles are a series of scientific profiles that were published quarterly, from 1980-1990, by the Rockefeller University. Each issue features the research and achievements of an individual Rockefeller University scientist.https://digitalcommons.rockefeller.edu/research_profiles/1032/thumbnail.jp

Zanvil Alexander Cohn 1926-1993

Zanvil Alexander Cohn, an editor of this Journal since 1973, died suddenly on June 28, 1993. Cohn is best known as the father of the current era of macrophage biology. Many of his scientific accomplishments are recounted here, beginning with seminal studies on the granules of phagocytes that were performed with his close colleague and former editor of thisJournaI, James Hirsch. Cohn and Hirsch identified the granules as lysosomes that discharged their contents of digestive enzymes into vacuoles containing phagocytosed microbes. These findings were part of the formative era of cell biology and initiated the modern study of endocytosis and cell-mediated resistance to infection. Cohn further explored the endocytic apparatus in pioneering studies of the mouse peritoneal macrophage in culture. He described vesicular inputs from the cell surface and Golgi apparatus and documented the thoroughness of substrate digestion within lysosomal vacuoles that would only permit the egress of monosaccharides and amino acids. These discoveries created a vigorous environment for graduate students, postdoctoral fellows, and junior and visiting faculty. Some of the major findings that emerged from Cohn’s collaborations included the radioiodination of the plasma membrane for studies of composition and turnover; membrane recycling during endocytosis; the origin of the mononuclear phagocyte system in situ; the discovery of the dendritic cell system of antigen-presenting cells; the macrophage as a secretory cell, including the release of proteases and large amounts of prostaglandins and leukotrienes; several defined parameters of macrophage activation, especially the ability of T cell-derived lymphokines to enhance killing of tumor cells and intracellular protozoa; the granule discharge mechanism whereby cytotoxic lymphocytes release the pore-forming protein perforin; the signaling of macrophages via myristoylated substrates of protein kinase C; and a tissue culture model in which monocytes emigrate across tight endothelial junctions. In 1983, Cohn turned to a long-standing goal of exploring host resistance directly in humans. He studied leprosy, focusing on the disease site, the parasitized macrophages of the skin. He injected recombinant lymphokines into the skin and found that these molecules elicited several cell-mediated responses. Seeing this potential to enhance host defense in patients, Cohn was extending his clinical studies to AIDS and tuberculosis. Zanvil Cohn was a consummate physician-scientist who nurtured the relationship between cell biology and infectious disease. He guided with a warm but incisive manner the careers of many individuals. He was deeply committed to several institutions of biomedical research; to medicine in the developing world; to The Rockefeller University, especially its programs for graduate study and patient-oriented research; and to the energy and spirit of this Journal

Ralph M. Steinman: Research and Career

General information about Dr. Ralph Steinman and his Nobel Prize winning research.https://digitalcommons.rockefeller.edu/steinman-nobel/1000/thumbnail.jp

An appreciation of Ralph Marvin Steinman (1943–2011)

Ralph Steinman, an editor at the Journal of Experimental Medicine since 1978, shared the 2011 Nobel Prize in Physiology or Medicine for his discovery of dendritic cells (DCs) and their role in immunity. Ralph never knew. He died of pancreatic cancer on September 30, 3 days before the Nobel announcement. Unaware of his death at the time of their announcement, the Nobel Committee made the unprecedented decision that his award would stand. Ralph was the consummate physician-scientist to the end. After his diagnosis, he actively participated in his 4.5 years of treatments, creating experimental therapies using his own DCs in conjunction with the therapies devised by his physicians, all the while traveling, lecturing, and most of all pursuing new investigations in his laboratory. For 38 years—from his discovery of DCs to his Nobel Prize—Ralph pioneered the criteria and methods used to identify, isolate, grow, and study DCs. He and his colleagues demonstrated that DCs are initiators of immunity and regulators of tolerance. In his most recent studies, Ralph was harnessing the specialized features of DCs to design improved vaccines. The following synopsis describes some of his seminal discoveries

The Way to a Man's Heart Is through His Stomach: What about Horses?

International audienceBACKGROUND: How do we bond to one another? While in some species, like humans, physical contact plays a role in the process of attachment, it has been suggested that tactile contact's value may greatly differ according to the species considered. Nevertheless, grooming is often considered as a pleasurable experience for domestic animals, even though scientific data is lacking. On another hand, food seems to be involved in the creation of most relationships in a variety of species. METHODOLOGY/PRINCIPAL FINDINGS: In this study, we used the horse training context to test the effects of food versus grooming during repeated human-horse interactions. The results reveal that food certainly holds a key role in the attachment process, while tactile contact was here clearly insufficient for bonding to occur. CONCLUSION/SIGNIFICANCE: This study raises important questions on the way tactile contact is perceived, and shows that large inter-species differences are to be expected

Global, regional, and national burden of disorders affecting the nervous system, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

BackgroundDisorders affecting the nervous system are diverse and include neurodevelopmental disorders, late-life neurodegeneration, and newly emergent conditions, such as cognitive impairment following COVID-19. Previous publications from the Global Burden of Disease, Injuries, and Risk Factor Study estimated the burden of 15 neurological conditions in 2015 and 2016, but these analyses did not include neurodevelopmental disorders, as defined by the International Classification of Diseases (ICD)-11, or a subset of cases of congenital, neonatal, and infectious conditions that cause neurological damage. Here, we estimate nervous system health loss caused by 37 unique conditions and their associated risk factors globally, regionally, and nationally from 1990 to 2021.MethodsWe estimated mortality, prevalence, years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs), with corresponding 95% uncertainty intervals (UIs), by age and sex in 204 countries and territories, from 1990 to 2021. We included morbidity and deaths due to neurological conditions, for which health loss is directly due to damage to the CNS or peripheral nervous system. We also isolated neurological health loss from conditions for which nervous system morbidity is a consequence, but not the primary feature, including a subset of congenital conditions (ie, chromosomal anomalies and congenital birth defects), neonatal conditions (ie, jaundice, preterm birth, and sepsis), infectious diseases (ie, COVID-19, cystic echinococcosis, malaria, syphilis, and Zika virus disease), and diabetic neuropathy. By conducting a sequela-level analysis of the health outcomes for these conditions, only cases where nervous system damage occurred were included, and YLDs were recalculated to isolate the non-fatal burden directly attributable to nervous system health loss. A comorbidity correction was used to calculate total prevalence of all conditions that affect the nervous system combined.FindingsGlobally, the 37 conditions affecting the nervous system were collectively ranked as the leading group cause of DALYs in 2021 (443 million, 95% UI 378–521), affecting 3·40 billion (3·20–3·62) individuals (43·1%, 40·5–45·9 of the global population); global DALY counts attributed to these conditions increased by 18·2% (8·7–26·7) between 1990 and 2021. Age-standardised rates of deaths per 100 000 people attributed to these conditions decreased from 1990 to 2021 by 33·6% (27·6–38·8), and age-standardised rates of DALYs attributed to these conditions decreased by 27·0% (21·5–32·4). Age-standardised prevalence was almost stable, with a change of 1·5% (0·7–2·4). The ten conditions with the highest age-standardised DALYs in 2021 were stroke, neonatal encephalopathy, migraine, Alzheimer's disease and other dementias, diabetic neuropathy, meningitis, epilepsy, neurological complications due to preterm birth, autism spectrum disorder, and nervous system cancer.InterpretationAs the leading cause of overall disease burden in the world, with increasing global DALY counts, effective prevention, treatment, and rehabilitation strategies for disorders affecting the nervous system are needed