神经科学与百年诺贝尔奖

神经科学是21世纪生物科学的基本研究内容之一。诺贝尔医学有生理学奖是对生物科学领域中所取得突出成就的最高评价。在诺贝尔奖设立一百年周年之际,神经科学已在神经元、神经活动、信号转导、感觉和知觉、脑的高级功能和神经发育等研究水平上取得了巨大成果,并获得近近二十项诺贝尔奖。预测了今后神经科学可能取得的突破性进展,并分析了我国神经科学发展的现状和研究的立足点。     

Cyclic nucleotide research -- still expanding after half a century

Since the discovery in 1957 that cyclic AMP acts as a second messenger for the hormone adrenaline, interest in this molecule and its companion, cyclic GMP, has grown. Over a period of nearly 50 years, research into second messengers has provided a framework for understanding transmembrane signal transduction, receptor-effector coupling, protein-kinase cascades and downregulation of drug responsiveness. The breadth and impact of this work is reflected by five different Nobel prizes.     

Celebrating the Millennium: Historical Highlights of Photosynthesis Research,Part 3

This paper introduces the third and final part of the 'millennium celebrations of historical highlights of photosynthesis research.' Part 1 (308 pages) was published in October 2002 as Vol. 73 of the journal Photosynthesis Research, and Part 2 (458 pages) was published in July 2003 as Vol. 76. Here, we recognize particularly the work of three major contributors to our understanding of photosynthesis: Roger Stanier (1916-1982); Germaine Cohen-Bazire (Stanier) (1920-2001); and William Arnold (1904-2001). We also introduce the historical papers contained in this volume; consider the legacy of Alfred Nobel (1833-1896); and identify Nobel prizes of special relevance to understanding the capture, conversion, and storage of light energy in both anoxygenic and oxygenic photosynthesis.     

From nerves and hormones to bacteria in the stomach; Nobel prize for achievements in gastrology during last century.

Rapid progress in gastroenterological research, during past century, was initiated by the discovery by W. Prout in early 18th century of the presence of inorganic, hydrochloric acid in the stomach and by I.P. Pavlov at the end of 19th century of neuro-reflex stimulation of secretion of this acid that was awarded by Nobel prize in 1904. Then, J. W. Black, who followed L. Popielski's concept of histamine involvement in the stimulation of this secretion, was awarded second Nobel prize in gastrology within the same century for the identification of histamine H2-receptor (H2-R) antagonists, potent gastric acid inhibitors, accelerating ulcer healing. The concept of H2-R interaction with other receptors such as muscarinic receptors (M3-R), mediating the action of acetylocholine released from local cholinergic nerves, and those mediating the action of gastrin (CCK2-R) on parietal cells, has been confirmed both in vivo studies and in vitro isolated parietal cells. The discovery of H2-R antagonists by Black and their usefulness in control of gastric secretion and ulcer healing, were considered as real breakthrough both in elucidation of gastric secretory mechanisms and in ulcer therapy. Discovery of even more powerful gastric acid inhibitors, proton pump inhibitors (PPI), also highly effective in acceleration of ulcer healing was, however, not awarded Nobel prize. Unexpectedly, two Australian clinical researchers, R.J. Warren and B.J. Marshall, who discovered in the stomach spiral bacteria, named Helicobacter pylori, received the third in past century Nobel prize in gastrology for the finding that this bacterium, is related to the pathogenesis of gastritis and peptic ulcer. They documented that eradication of H. pylori from the stomach, using antibiotics and potent gastric inhibitors, not only accelerates healing of ulcer but also prevents its recurrence, the finding considered as greatest discovery in practical gastrology during last century. Thus, the outstanding achievements in gastroenterology during last century have been awarded by three Nobel prizes and appreciated by millions of ulcer patients all over the world.     

Recent updates in cancer immunotherapy: a comprehensive review and perspective of the 2018 China Cancer Immunotherapy Workshop in Beijing

The immune system is the hard-wired host defense mechanism against pathogens as well as cancer. Five years ago, we pondered the question if the era of cancer immunotherapy was upon us (Li et al., Exp Hem Oncol 2013). Exciting progresses have been made at all fronts since then, including (1) sweeping approval of six agents by the US Food and Drug Administration (FDA) to block the PD-1/PD-L1 pathway for treatment of 13 cancer types; (2) a paradigm shifting indication of PD-1 and CTLA4 blockers for the management of a broad class of cancers with DNA mismatch repair defect, the first-ever tissue agnostic approval of cancer drugs; (3) real world practice of adoptive T cell therapy with two CD19-directed chimeric antigen receptor T cell products (CAR-T) for relapsed and/or refractory B cell malignancies including acute lymphoid leukemia and diffuse large B cell lymphoma, signaling the birth of a field now known as synthetic immunology; (4) the award of 2018 Nobel Prize in Physiology and Medicine from the Nobel Committee to Tasuku Honjo and James Allison “for their discovery of cancer medicine by inhibition of negative immune regulation” (www.nobelprize.org/prizes/medicine/2018); and (5) the emerging new concept of normalizing rather than amplifying anti-tumor immunity for guiding the next wave of revolution in the field of immuno-oncology (IO) (Sanmamed and Chen, Cell 2018).This article will highlight the significant developments of immune-oncology as of October 2018. The US FDA approved indications of all seven immune checkpoint blockers, and two CD19-directed CAR-T products are tabulated for easy references. We organized our discussion into the following sections: introduction, cell therapy, emerging immunotherapeutic strategies, expediting oncology drug development in an era of breakthrough therapies, new concepts in cancer immunology and immunotherapy, and concluding remarks. Many of these topics were covered by the 2018 China Cancer Immunotherapy Workshop in Beijing, the fourth annual conference co-organized by the Chinese American Hematologist and Oncologist Network (CAHON), China FDA (CFDA; now known as China National Medical Product Administration (NMPA)), and the Tsinghua University. We significantly expanded our discussion of important IO developments beyond what were covered in the conference, and proposed a new Three Rs conceptual framework for cancer immunotherapy, which is to reverse tolerance, rejuvenate the immune system, and restore immune homeostasis. We conclude that the future of immuno-oncology as a distinct discipline of cancer medicine has arrived.     

The choice of animal model and reduction

Careful choice of the animal model is essential, if research is to be conducted efficiently, by using the minimum number of animals in order to provide the maximum amount of information. Inbred strains of rodents provide an excellent way of controlling and investigating genetic variation in characters of interest and in response to experimental treatments. Outbred stocks, in which genetic and non-genetic factors are inextricably mixed, are much less suitable, because random and uncontrolled genetic variation tends to obscure any treatment responses. In some cases, the use of inbred strains has led to major advances in scientific understanding. The specific example given here is in the understanding of host-parasite relationships but, more generally, inbred strains have been of critical importance in research which has resulted in the award of at least 17 Nobel prizes. And yet, despite the extensive literature on the properties and scientific value of inbred strains, many scientists continue to use outbred stocks in the mistaken belief that the use of such animals will, in some mysterious way, make their research more applicable to humans. There is really no evidence that this is so, and there is much evidence that the use of inbred strains has been highly successful in many disciplines.     

A list of personal perspectives with selected quotations,along with lists of tributes,historical notes,Nobel and Kettering awards related to photosynthesis

The history of photosynthesis research can be found in original papers and books. However, a special history is available from the prefatory chapters and the personal perspectives of various researchers who published them in several journals over the last 40 years. We have compiled a list of such perspectives published since 1964. Selection is not easy, especially of authors who were not directly engaged in photosynthesis research; some are included for their special insights related to central issues in the study of photosynthesis. Our journal, Photosynthesis Research, contains other valuable historic data in the occasional tributes, obituaries and historical notes, that have been published. Lists of these items are included. This article ends by listing the Nobel prizes related to photosynthesis and the Kettering Awards for Excellence in Photosynthesis Research. Wherever possible, a web page address is provided. The web page addresses have been taken from the article `Photosynthesis and the Web: 2001' by Larry Orr and Govindjee, available at http://www.life.uiuc.edu/govindjee/photoweb and at http://photoscience.la.asu.edu/photosyn/ photoweb/default.html. ‘When I find a bit of leisure I trifle with my papers. This is one of the lesser frailities. – Horace, Satires I, IV. This revised version was published online in June 2006 with corrections to the Cover Date.     

The success of the RNase scaffold in the advance of biosciences and in evolution

In 1938 the new word "ribonuclease" was coined to name an enzyme capable of degrading RNA, before the name "ribonucleic acid" was accepted, as at that time RNA was still labeled YNA, for Yeast Nucleic Acid. Later, four Nobel prizes were awarded to investigators working with the "ribonuclease", RNase A from bovine pancreas. Their work greatly advanced our knowledge of protein chemistry and biology, by producing the first complete amino acid composition and the first covalent structure of a protein, the first complete synthesis of an enzyme, and the discovery that the three-dimensional structure of a protein is dictated by its amino acid sequence. Today, well over 100 homologs of RNase A have been identified in all tetrapods, and recently in fishes. Based on the latter findings, a vertebrate RNase superfamily has been appropriately defined, with RNase A as its prototype. Thus, the success of the RNase structure and function not only in promoting the advance of biosciences, but also in evolution, has become clear. Several RNases from the superfamily are endowed with non-catalytic "special" bioactions. Among these are angiogenins, characterized by their ability to stimulate the formation of blood vessels. Recently, four RNases have been identified in Danio rerio, or zebrafish, produced as recombinant proteins, and characterized. As two of them have angiogenic activity, the hypothesis is made that the whole superfamily of vertebrate RNases evolved from early angiogenic RNases. Given the microbicidal activity of some mammalian angiogenins, and of the reported fish angiogenins, the alternative hypothesis is also discussed, that the ancestral RNases were host-defense RNases.     

Ecology Institute prizes 1991 in the field of limnetic ecology

Ecology Institute prizes 1991 in the field of limnetic ecology     

Nuclear magnetic resonance Fourier transform spectroscopy

The development and current status of Fourier transform spectroscopy is described.Nobel Lecture given on December 9, 1991 by Professor R. Ernst and published in Les Prix Nobel 1991, printed in Sweden by Norstedts Tryckeri, Stockholm, Sweden, 1992, republished here with the permission of the Nobel Foundation, the copyright holder.     

Biotech industry highlights

New on the market German start-ups in the spotlight Biotech crops: Double-digit growth Industrial prizes and grants     

NVVC/NHJ Durrer Prizes 2012

At the annual Spring Congress of the NVVC the Durrer prizes were awarded to the authors of the best original/review articles published in the year 2012, one paper being more basically-oriented and one paper being more clinically-oriented. This annual tradition exists already since the year 2006.     

G proteins and regulation of adenylyl cyclase

The function and structures of G proteins and their role in the regulation of adenylyl cyclase is reviewed.The Nobel lecture given on December 8, 1994 by Dr Alfred Gilman and published inLes Prix Nobel 1994, printed by Norstedts Tryckeri, Stockholm, Sweden, republished here with the permission of the Nobel Foundation, the copyright holder.     

Transformation

The Nobel process for science are often somewhat controversial for who they omit. A posthumous Nobel honor could help recognize some neglected heroes.     

CpG methylation controls reactivation of HIV from latency

What are the purposes of prizes and recognitions? Are they lagging indicators of past achievements or leading indicators of things to come?     

Biotech news from industry

Three-year $28M drug discovery collaboration: Evotec-Novartis Regenerative medicine: Sigma-Aldrich/D-Finitive Cell Technologies Industrial prizes     

NVVC/NHJ Durrer prizes 2015

At the annual 2016 Spring Congress of the NVVC, the Durrer prizes were awarded to the authors of two of the best original articles published in the year 2015, one paper being more basically oriented and one paper being more clinically oriented. This annual tradition has existed since the year 2006.     

Elementary steps in synaptic transmission revealed by currents through single ion channels

An account is presented of how the molecular basis of synaptic transmission at peripheral and central synapses is elucidated by combining patch clamp and recombinant DNA techniques.Nobel lecture given on December 9, 1991, by Dr B. Sakmann and published inLes Prix Nobel 1991, Printed by Norstedts Tryckeri, Stockholm, Sweden, 1992, republished here with the permission of the Nobel Foundation, the copyright holder.     

The life and legacy of Marie Curie

Marie Curie was a remarkable woman whose discoveries broke new ground in physics and chemistry and also opened the door for advances in engineering, biology, and medicine. She broke new ground for women in science: she was, for example, the first woman to receive a doctor of science degree in France, the first woman to win Nobel Prize, the first woman to lecture at the Sorbonne, the first person to win two Nobel Prizes, and the first Nobel Laureate whose child also won a Nobel Prize. Her life offers insights into the changing role of women in science and academia over the past century. It also offers examples of many ways in which scientists can, and should, work to improve the educational programs and career opportunities available to those who follow in their footsteps.