Thirty years of olfactory learning and memory research in Drosophila melanogaster

The last 30 years have witnessed tremendous progress in elucidating the basic mechanisms underlying a simple form of olfactory learning and memory in Drosophila. The application of the mutagenic approach to the study of olfactory learning and memory in Drosophila has yielded insights into the participation of a large number of genes in both the development of critical brain regions as well as in the physiology underlying the acquisition, storage, and retrieval of memory. Newer sophisticated molecular-genetic tools have further allowed for the specification and functional dissection of the neuronal circuitry involved in these processes at a systems level. With these advances in our understanding of the genes, neurons, and circuits involved in learning and memory, the field of Drosophila memory research is nearing a state of integration of the bottom up and top down approaches to understanding this form of behavioral plasticity.     

Thirty years of Batten disease research: present status and future goals

From a meager beginning in 1968, when Batten disease or neuronal ceroid lipofuscinosis was practically unheard of, tremendous advances have been made. It is now recognized worldwide as the most common neurodegenerative disease in children and young adults. It is recognized as a genetic disease. The infantile form has been localized to chromosome 1 p32 and the juvenile form, to 16p12.1; the gene for the late infantile is on chromosome 11p15 and for a variant form of the late infantile, the gene lies on chromosome 15q21-23. Finally, the molecular basis of the late infantile form is probably a pepstatin-insensitive lysomal peptidase. The future is to identify carriers, prevent the disease, and develop treatment by gene and enzyme replacement.     

Thirty years of computational autopoiesis: a review

Computational autopoiesis--the realization of autopoietic entities in computational media--holds an important and distinctive role within the field of artificial life. Its earliest formulation by Francisco Varela, Humberto Maturana, and Ricardo Uribe was seminal in demonstrating the use of an artificial, computational medium to explore the most basic question of the abstract nature of living systems--over a decade in advance of the first Santa Fe Workshop on Artificial Life. The research program it originated has generated substantive demonstrations of progressively richer, lifelike phenomena. It has also sharply illuminated both conceptual and methodological problems in the field. This article provides an integrative overview of the sometimes disparate work in this area, and argues that computational autopoiesis continues to provide an effective framework for addressing key open problems in artificial life.     

Thirty years of breast pathology in an anticancer center

Looking back to three decades of professional experience allows to evidence the dramatic changes of the role of the pathologist in breast cancer clinical management. Increasing means, fruitful exchanges within pathologists, and closer collaborations with other specialists have been key mediators of this evolution.     

Thirty years with Fc(sigma)R.

In his talk Henry Metzger [H. Metzger et al., Immunol. Lett. 68 (1999) 53-57] referred to a view recently expressed in an article by Koshland [D.E. Koshland Jr., Science 280 (1998) 852-853], that there are three stages in the study of biological systems: firstly, to describe what's happening; secondly, to define the molecules involved and what they are doing; thirdly, to quantitate these processes.     

Atrial natriuretic hormones — Thirty years after the discovery of atrial volume receptors

Summary Twenty-five years after the discoveries of the existence of atrial granules and of volume receptors in the heart atria the search for natriuretic hormones has led to the isolation and identification of the atrial natriuretic factors (ANF) now considered as a hormonal system. These peptides are probably synthesized and stored in the Golgi apparatus of cardiac myocytes and are released in response to atrial wall stretch following acute plasma volume expansion and increased central blood volume, e.g., during head-out water immersion, in arterial hypertension, or increased left and/or right atrial pressure in cardiac failure, but also possibly in response to increased frequency of myocardial contractions, e.g. in paroxysmal tachycardia. The mechanisms of the renal action of these potent natriuretic hormones are not yet precisely known. Increased GFR may contribute to the initial rise in urinary sodium excretion and increased renal medullary blood flow to the later phase of natriuresis. The proximal tubule, the thin descending and the ascending limb of Henle's loop and especially the medullary collecting tubule were so far incriminated as tubular sites of action of ANF. Finally, recycling of sodium in medullary tissue and secretion of sodium via back-flux from the interstitium into the medullary collecting tubule are postulated to result in the hypernatric urine observed after ANF administration. Direct suppression of the secretion of renin, aldosterone, vasopressin, and vasopressin-stimulated cAMP synthesis may also contribute to its diuretic, natriuretic, and antihypertensive effects. The renal hemodynamic and tubular as well as the adrenal and systemic vascular effects are related to enhanced cGMP synthesis in medium-sized arterial vessels, in glomeruli and specific tubular segments, and in adrenal tissue, and may be calcium dependent. Specific ANF-binding sites were detected in these target organs. Although increased ANF release was observed in response to atrial distension in various disease states, which may contribute to renal sodium elimination in human hypertension and congestive heart failure, further studies are needed to identify its precise physiological and pathophysiological significance.Abbreviations ACTH Adrenocorticotropic hormone - ANF Atrial natriuretic factor - AVP Arginine vasopressin - cAMP Cyclic adenosine monophosphate - cGMP Cyclic guanosine monophosphate - d-DAVP d-Desamino arginine vasopressin - DOCA Deoxycorticosterone acetate - ECFV Extracellular fluid volume - GFR Glomerular filtration rate - PAH Paraaminohippurate - PG Prostaglandin - PRA Plasma renin activity - RBF Renal blood flow - SNGFR Single nephron GFR Dedicated to Prof. Dr. F. Krück on the occasion of his 65th birthday     

Ten years of human metapneumovirus research

Described for the first time in 2001, human metapneumovirus (hMPV) has become one of the main viral pathogens responsible for acute respiratory tract infections in children but also in the elderly and immuno-compromised patients. The pathogen most closely related to hMPV is human respiratory syncytial virus (hRSV), the most common cause of bronchiolitis and pneumonia in young children. hMPV has been classified into two main viral groups A and B and has a seasonal distribution in temperate countries with most cases occurring in winter and spring. Given the difficulties encountered in culturing hMPV in vitro, diagnosis is generally achieved using real-time polymerase chain reaction.Like other Paramyxoviridae, hMPV has a negative-sense single-stranded RNA genome that includes 8 genes coding for 9 different proteins. The genomic organization and functions of surface attachment and fusion glycoproteins are relatively similar to those of hRSV. Although many groups have studied the viral life cycle of hMPV, many questions remain unanswered concerning the exact roles of the viral proteins in the attachment, fusion and replication of hMPV.To date, there remains no approved modality to combat hMPV infections. The majority of treatments that have been tested on hMPV have already demonstrated activity against hRSV infections. Some innovative approaches based on RNA interference and on fusion inhibitors have shown efficacy in vitro and in animal studies and could be beneficial in treating human hMPV disease. Difficulties faced inducing a durable immune response represent the biggest challenge in the development of an effective hMPV vaccine. Several strategies, such as the use of live-attenuated viruses generated by reverse genetics or recombinant proteins, have been tested in animals with encouraging results.     

Comparison of hippocampal synaptosome proteins in young-adult and aged rats

The hippocampus is important in learning and memory functions but its ability to aid in these functions declines during aging. In this study, we examined hippocampal proteins whose expressions changed in the aging process. A comparison of synaptosome proteins of hippocampus prepared from young-adult (9-week-old) rats with those from aged (30-month-old) rats by two-dimensional fluorescence difference gel electrophoresis revealed 24 spots that were expressed differently among about 1000 spots detected in both young-adult and aged rat samples. Nineteen of these 24 spots were identified by peptide mass fingerprinting. These proteins included chaperone proteins and proteins related to the cytoskeleton, neurotransmission, signal transduction and energy supply. The cytoskeleton-related proteins included actin and T-complex 1, which is thought to play a role in actin folding. Actin was up-regulated but T-complex 1 was down-regulated in aged rat synapses. These results suggest that age-dependent changes of actin filament formation are related to neuronal dysfunction associated with aging.     

抑郁小鼠模型脑突触体中突触蛋白表达的变化

目的:研究抑郁症发病过程中突触蛋白表达的变化。方法:小鼠随机分为对照组和造模组,使用社会失败模型对造模组小鼠造模,之后将其分为对抑郁症敏感组及对抑郁症不敏感组。将以上3组小鼠分别断头取前额叶皮层、海马、纹状体并提取突触小体,通过免疫印迹检测突触小体内突触后致密蛋白95(PSD-95)、桥尾蛋白(gephyrin)及突触蛋白1(synapsin-1)蛋白表达的变化。结果:与对照组相比,在前额叶皮层,对抑郁症敏感组及对抑郁症不敏感组小鼠的PSD-95水平下降,而对抑郁症敏感组小鼠的synapsin-1表达增多;在海马,对抑郁症敏感组及对抑郁症不敏感组小鼠的PSD-95水平下降;在纹状体,对抑郁症不敏感的小鼠gephyrin、synapsin-1蛋白表达显著增加。结论:在抑郁症发病中突触体内兴奋性及抑制性蛋白发生了变化,这些可能与突触功能的紊乱相关。