Nobel Prize in Physiology or Medicine awarded to David Julius and Ardem Patapoutian

Location: Electronic Resource- 

Location: Electronic Resource- 

Location: Electronic Resource- 

Copyright 2019 NPR. To see more, visit ARI SHAPIRO, HOST: When William Kaelin was a pre-med student, one professor suggested he get a taste for laboratory research. It did not go well. WILLIAM KAELIN: It turns out in hindsight that virtually everything that could have been wrong in a laboratory was wrong in this laboratory. And I remember getting a C-minus, which for a pre-med is like having a wooden stake driven through your heart. SHAPIRO: Safe to say William Kaelin overcame that C-minus just fine. Not only did he make it through medical school and launch a career in research, today it was announced he will be awarded the 2019 Nobel Prize for Physiology or Medicine. NPR science correspondent Richard Harris picks up the story. RICHARD HARRIS, BYLINE: After his disastrous start in the lab, William Kaelin figured he would focus his attention on treating patients. And indeed, he started down that path, settling into a job at the Dana-Farber Cancer Institute in Boston. KAELIN: And it

CJ Fielding
Feb 1, 1995; 36:211-228
Reviews

Sphingolipids have emerged as bioactive lipids involved in the regulation of many physiological and pathological processes. In the retina, they have been established to participate in numerous processes, such as neuronal survival and death, proliferation and migration of neuronal and vascular cells, inflammation, and neovascularization. Dysregulation of sphingolipids is, therefore, crucial in the onset and progression of retinal diseases. This review examines the involvement of sphingolipids in retinal physiology and diseases. Ceramide (Cer) emerges as a common mediator of inflammation and death of neuronal and retinal pigment epithelium cells in animal models of retinopathies such as glaucoma, age-related macular degeneration (AMD), and retinitis pigmentosa. Sphingosine-1-phosphate (S1P) has opposite roles, preventing photoreceptor and ganglion cell degeneration but also promoting inflammation, fibrosis, and neovascularization in AMD, glaucoma, and pro-fibrotic disorders. Alterations in Cer, S1P, and ceramide-1-phosphate may also contribute to uveitis. Notably, use of inhibitors that either prevent Cer increase or modulate S1P signaling, such as Myriocin, desipramine, and Fingolimod (FTY720), preserves neuronal viability and retinal function. These findings underscore the relevance of alterations in the sphingolipid metabolic network in the etiology of multiple retinopathies and highlight the potential of modulating their metabolism for the design of novel therapeutic approaches.

In demanding listening situations, a listener's motivational state may affect their cognitive investment. Here, we aim to delineate how domain-specific sensory processing, domain-general neural alpha power, and pupil size as a proxy for cognitive investment encode influences of motivational state under demanding listening. Participants (male and female) performed an auditory gap-detection task while the pupil size and the magnetoencephalogram were simultaneously recorded. Task demand and a listener's motivational state were orthogonally manipulated through changes in gap duration and monetary-reward prospect, respectively. Whereas task difficulty impaired performance, reward prospect enhanced it. The pupil size reliably indicated the modulatory impact of an individual's motivational state. At the neural level, the motivational state did not affect auditory sensory processing directly but impacted attentional postprocessing of an auditory event as reflected in the late evoked-response field and alpha-power change. Both pregap pupil dilation and higher parietal alpha power predicted better performance at the single-trial level. The current data support a framework wherein the motivational state acts as an attentional top–down neural means of postprocessing the auditory input in challenging listening situations.

Sleep studies in Drosophila melanogaster rely mostly on behavioral read-outs to support molecular or circuit-level investigations in this model. Electrophysiology can provide an additional level of understanding in these studies to, for example, investigate changes in brain activity associated with sleep manipulations. In this protocol, we describe a procedure for performing multichannel local field potential (LFP) recordings in the fruit fly, with a flexible system that can be adapted to different experimental paradigms and situations. The approach uses electrodes containing multiple recording sites (16), allowing the acquisition of large amounts of neuronal activity data from a transect through the brain while flies are still able to sleep. The approach starts by tethering the fly, followed by positioning it on an air-supported ball. A multichannel silicon probe is then inserted laterally into the fly brain via one eye, allowing for recording of electrical signals from the retina through to the central brain. These recordings can be acquired under spontaneous conditions or in the presence of visual stimuli, and the minimal surgery promotes long-term recordings (e.g., overnight). Sleep and wake can be tracked using infrared cameras, which allow for the measurement of locomotive activity as well as microbehaviors such as proboscis extensions during sleep. The protocol has been optimized to promote subject survivability, which is an important factor when performing long-term (~16-h) recordings. The approach described here uses specific recording probes, data acquisition devices, and analysis tools. Although it is expected that some of these items might need to be adapted to the equipment available in different laboratories, the overall aim is to provide an overview on how to record electrical activity across the brain of behaving (and sleeping) flies using this kind of approach and technology.

Sleep is likely a whole-brain phenomenon, with most of the brain probably benefiting from this state of decreased arousal. Recent advances in our understanding of some potential sleep functions, such as metabolite clearance and synaptic homeostasis, make it evident why the whole brain is likely impacted by sleep: All neurons have synapses, and all neurons produce waste metabolites. Sleep experiments in the fly Drosophila melanogaster suggest that diverse sleep functions appear to be conserved across all animals. Studies of brain activity during sleep in humans typically involve multidimensional data sets, such as those acquired by electroencephalograms (EEGs) or functional magnetic resonance imaging (fMRI), and these whole-brain read-outs often reveal important qualities of different sleep stages, such as changes in frequency dynamics or connectivity. Recently, various techniques have been developed that allow for the recording of neural activity simultaneously across multiple regions of the fly brain. These whole-brain-recording approaches will be important for better understanding sleep physiology and function, as they provide a more comprehensive view of neural dynamics during sleep and wake in a relevant model system. Here, we present a brief summary of some of the findings derived from sleep activity recording studies in sleeping Drosophila flies and discuss the value of electrophysiological versus calcium imaging techniques. Although these involve very different preparations, they both highlight the value of multidimensional data for studying sleep in this model system, like the use of both EEG and fMRI in humans.

Gustavo Nader, professor of kinesiology and physiology in the Penn State College of Health and Human Development, has been named the Dorothy Foehr Huck and J. Loyd Huck Chair in Molecular, Cellular and Integrative Physiology by the Huck Institutes of the Life Sciences. 

Thermoregulation, responsible for maintaining a stable core temperature during wide fluctuations in external and internal thermal environments, is an iconic homeostatic process. However, we suggest that despite its fundamental physiological significance, the potential for required cool housing temperatures and thermoregulatory mechanisms to influence the interpretation of experimental data is not sufficiently appreciated. Moreover, although it is generally assumed that the major thermoregulatory pathways are well understood, here we discuss new research that suggests otherwise and reveals the emergence of a new wave of exciting ideas for this "old" field of research.

Karolinska Institutet is a medical university encompassing 21 departments distributed across three departmental or campus groups. Pharmacological research has a long and successful tradition at the institute with a multitude of seminal findings in the areas of neuronal control of vasodilatation, cardiovascular pharmacology, neuropsychopharmacology, receptor pharmacology, and pharmacogenomics that resulted in, among many other recognitions, two Nobel prizes in Physiology and Medicine, one in 1970 to Ulf von Euler for his discovery of the processes involved in storage, release, and inactivation of neurotransmitters and the other in 1982 to Sune Bergström and Bengt Samuelsson for their work on prostaglandins and the discovery of leukotrienes. Pharmacology at Karolinska Institutet has over the last decade been ranked globally among the top 10 according to the QS World University Ranking. With the Department of Physiology and Pharmacology now celebrating its 75-year anniversary, we wanted to take this as an opportunity to showcase recent research achievements and how they paved the way for current activities at the department. We emphasize examples from preclinical and clinical research where the dpartment's integrative environment and robust infrastructure have successfully facilitated the translation of findings into clinical applications and patient benefits. The close collaboration between preclinical scientists and clinical researchers across various disciplines, along with a strong network of partnerships within the department and beyond, positions us to continue leading world-class pharmacological research at the Department of Physiology and Pharmacology for decades to come.

Highlights: Kariko and Weissman's base modifications revolutionized mRNA, enabling rapid vaccine development mRN

The Nobel Assembly at Karolinska Institutet has today decided to award The Nobel Prize in Physiology or Medicine

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