Budapest, Hungary

Hungarian Academy of Sciences

mta.hu/english/
Budapest, Hungary

The Hungarian Academy of science ) is the most important and prestigious learned society of Hungary. Its seat is at the bank of the Danube in Budapest. The main responsibilities are the cultivation of science, disseminate the results of science, the supporting of research and development and the representation of Hungarian science domestically and around the world. Wikipedia.


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News Article | April 17, 2017
Site: www.futurity.org

Whereas humans can look at a complex landscape like a mountain vista and almost immediately orient themselves to navigate its multiple regions over long distances, other mammals such as rodents orient relative to physical cues—like approaching and sniffing a wall—that build up over time. This ability to navigate our surroundings and understand our relative position includes an environment-dependent scaling mechanism, according to a new study. “Our research, based on human data, redefines the fundamental properties of the internal coordinate system,” says Zoltan Nadasdy, lead author of the study and an adjunct assistant professor in the University of Texas at Austin’s psychology department. Nadasdy is also a researcher at Eötvös Loránd University and the Sarah Cannon Research Institute at St. David’s Medical Center. “Dysfunction in this system causes memory problems and disorientation, such as we see in Alzheimer’s disease and age-related decline. So, it’s vital that we continue to further our understanding of this part of the brain,” he says. Through a partnership with Seton Healthcare Family, the researchers in the UT Austin Human Brain Stimulation and Electrophysiology Lab were able to measure relevant brain activity of epileptic patients whose diagnostic procedure requires that they have electrodes planted in the entorhinal cortex of the brain. Neurons there serve as the internal coordinate system for humans. (The brains of individuals with epilepsy function normally when not undergoing a seizure.) Patients performed a virtual navigation task on a tablet computer in four environments daily for seven to eight consecutive days. By measuring their brain activity, the researchers identified three previously unknown traits of the system: The findings illuminate the fabric of the human memory and spatial navigation, which are vulnerable to disease and deterioration. Deeper knowledge of these neuronal mechanisms can inform the development of techniques to prolong the health of this part of the brain and combat diseases such as Alzheimer’s. The study, published in the Proceedings of the National Academy of Sciences, builds on earlier Nobel Prize-winning research exploring the entorhinal cortex of rodents. Due to the differences discovered between the human and rodent systems of navigation, the researchers emphasize that generalizing results from studies on animal subjects may provide inaccurate conjectures. This study is one of the few on human subjects that report on the activity of individual neuron behavior, says György Buzsáki, an expert from New York University Medical Center who was not involved in the research. “They not only confirm a previous report but extend the findings by showing that the size of the neuronal representation by entorhinal grid cells scales with the environment,” Buzsáki says. “Our hypothesis is challenging the definition of a universal spatial scale of environment predominant in lower mammals, which may open up important avenues of discovery,” says Robert Buchanan, another lead author of the study and an associate professor at Dell Medical School. He is also an adjunct associate professor in the university’s psychology department and a chief of neurosurgery at Seton Brain and Spine Institute. “Now, we can continue to explore this key component of what it means to be human—how we think about our past and future, how we imagine and plan,” Buchanan says. By using virtual reality, the researchers also refined a new experimental technology for facilitating spatial experiences that can’t be reproduced in a laboratory. The data implies that humans can seamlessly switch between reality and virtual reality—a finding that can be applied in other studies of the brain. Additional coauthors are from Baylor College of Medicine; Eötvös Loránd University and Hungarian Academy of Sciences; and UT Austin’s Dell Medical School and Seton Brain and Spine Institute. The Brain and Behavior Research Foundation and the Seton Seed Grant for Research supported the work.


Grant
Agency: European Commission | Branch: H2020 | Program: SGA-RIA | Phase: FETFLAGSHIP | Award Amount: 89.00M | Year: 2016

Understanding the human brain is one of the greatest scientific challenges of our time. Such an understanding can provide profound insights into our humanity, leading to fundamentally new computing technologies, and transforming the diagnosis and treatment of brain disorders. Modern ICT brings this prospect within reach. The HBP Flagship Initiative (HBP) thus proposes a unique strategy that uses ICT to integrate neuroscience data from around the world, to develop a unified multi-level understanding of the brain and diseases, and ultimately to emulate its computational capabilities. The goal is to catalyze a global collaborative effort. During the HBPs first Specific Grant Agreement (SGA1), the HBP Core Project will outline the basis for building and operating a tightly integrated Research Infrastructure, providing HBP researchers and the scientific Community with unique resources and capabilities. Partnering Projects will enable independent research groups to expand the capabilities of the HBP Platforms, in order to use them to address otherwise intractable problems in neuroscience, computing and medicine in the future. In addition, collaborations with other national, European and international initiatives will create synergies, maximizing returns on research investment. SGA1 covers the detailed steps that will be taken to move the HBP closer to achieving its ambitious Flagship Objectives.


Grant
Agency: European Commission | Branch: H2020 | Program: RIA | Phase: PHC-03-2015 | Award Amount: 6.00M | Year: 2016

We hypothesize that inappropriate thyroid hormone action in target cells is a common mechanism underlying susceptibility to age-related degenerative diseases and co-morbidities. Although regulation of systemic thyroid status is well understood and underpins treatment of common thyroid disease, it is only in the last decade that the importance of local regulation of thyroid hormone action in tissue development, homeostasis and repair has been identified. During evolution, this complex temporal and cell-specific regulation has been optimized for development and reproductive fitness but NOT for ageing. Humans with their exceptional longevity are thus exposed to a prolonged period of suboptimal local thyroid hormone action. Consistent with this, thyroid status is a continuous variable within the population that is related to fracture risk, muscle mass and cognitive decline. Moreover, in healthy longevity thyroid status is characterized by thyroid stimulating hormone in the upper half of the reference range. In these studies, we will determine how local regulation of thyroid hormone action controls tissue homeostasis and repair, whilst its dysregulation is a common mechanism underlying chronic disease development during ageing. We focus on osteoporosis, osteoarthritis, neurodegeneration and sarcopenia as paradigm age-related, degenerative disorders. Using cutting-edge technology, we will (i) identify thyroid hormone dependent biomarkers for disease susceptibility in bone, cartilage, central nervous system and skeletal muscle, (ii) manipulate cell-specific thyroid hormone action in these tissues and (iii) develop cell-type specific modulators of thyroid hormone action. THYRAGE integrates cross-disciplinary expertise from clinical and basic scientists, endocrinologists, neuroscientists, gerontologists, and industry-based peptide scientists. These studies will identify and validate novel strategies for prevention and treatment of chronic age-related degenerative disease.


Kiss L.,University of Szeged | Fulop F.,University of Szeged | Fulop F.,Hungarian Academy of Sciences
Chemical Reviews | Year: 2014

Alicyclic and heterocyclic β-amino acids become an expanding area in organic and medicinal chemistry. The biological characteristics of the cyclic β-amino acids as independent molecular entities, together with their usage as precursors of different heterocycles, as chiral auxiliaries in asymmetric syntheses, and as precursors of β-lactams and in foldamer chemistry. Reductive amination of β-keto esters is a suitable method also for the synthesis of functionalized racemic carbocyclic β-amino acids. Carbocyclic β-amino acids can be prepared from acyclic β-amino acid derivatives by ring-closing metathesis. An important advantage of this methodology is that it gives cyclic β-amino acids whose olefinic bond may be functionalized to yield novel substituted derivatives. Stereoselective conjugate addition of an amine nucleophile derivative to an α,β-unsaturated carboxylate is an efficient strategy for access to five- or six-membered cyclic β-amino acids.


Tompa P.,Vrije Universiteit Brussel | Tompa P.,Hungarian Academy of Sciences
Chemical Reviews | Year: 2014

Allostery is a classical regulatory mechanism of proteins in which a signal at 'another site' modifies the activity/function of a protein. In fact, with the recognition of the generality of the structural disorder of proteins and the landscape theory of protein structure, a 'new view' of allostery started to emerge, in which emphasis is placed on ligand-induced shifts in the conformational ensemble of the protein. The ensuing changes in ligand binding/catalytic activity might stem from coupled folding transitions of distinct binding sites or remodeling of the conformational landscape to entropically favor a particular downstream binding/catalytic event. The ensuing sigmoidal binding isotherm cannot be described by a simple saturation; rather, it shows signs of cooperation between ligands. If binding of one ligand weakens that of the others, one can also speak about negative cooperativity. To elucidate the underlying mechanistic changes, two models have been suggested, which, even today, form the basis of our textbook wisdom of this phenomenon.


Tompa P.,Vrije Universiteit Brussel | Tompa P.,Hungarian Academy of Sciences
Trends in Biochemical Sciences | Year: 2012

The suggestion that the native state of many proteins is intrinsically disordered (or, as originally termed, unstructured) is now integral to our general view of protein structure and function. A little more than 10 years ago, however, such challenge to the almost dogmatic 'structure-function paradigm' was pure heresy due to the overwhelming evidence that structure determines function. A decade of steady progress turned skepticism around: this 10-year recap review outlines the situation a decade ago and the major directions of the breathtaking advance achieved by experimental and computational approaches. I show that the evidence for the generality and importance of this phenomenon is now so insurmountable that it demands the inclusion of 'unstructural' biology into mainstream biology and biochemistry textbooks. © 2012 Elsevier Ltd.


An insight into the homogeneous catalytic asymmetric reactions, the organocatalytic reactions, and the heterogeneous catalytic asymmetric reactions was studied. In asymmetric reactions/syntheses of this type, chiral induction is supplied by chiral molecules of natural origin and their synthetic derivatives, or other synthetic chiral compounds. Studies on the stereochemistry of homogeneous asymmetric reactions have taken their models from the hydrogenation and transfer hydrogenation of prochiral compounds with CdC bonds and prochiral ketones in the presence of Rh and Ru complexes. Supported IL catalysts (SILC) have been developed using surface-modified silica, which show good reactivity and reversal of enantioselectivity for the case of the magnesium-based BOX complexes. Studies using Pt catalysts modified with cinchona alkaloids gave unexpected results when derivatives of the parent alkaloids were used.


Sandi C.,Ecole Polytechnique Federale de Lausanne | Haller J.,Hungarian Academy of Sciences
Nature Reviews Neuroscience | Year: 2015

Stress often affects our social lives. When undergoing high-level or persistent stress, individuals frequently retract from social interactions and become irritable and hostile. Predisposition to antisocial behaviours-including social detachment and violence-is also modulated by early life adversity; however, the effects of early life stress depend on the timing of exposure and genetic factors. Research in animals and humans has revealed some of the structural, functional and molecular changes in the brain that underlie the effects of stress on social behaviour. Findings in this emerging field will have implications both for the clinic and for society. © 2015 Macmillan Publishers Limited. All rights reserved.


Grant
Agency: European Commission | Branch: H2020 | Program: ERC-STG | Phase: ERC-2016-STG | Award Amount: 1.50M | Year: 2017

Neuromodulators such as acetylcholine and dopamine are able to rapidly reprogram neuronal information processing and dynamically change brain states. Degeneration or dysfunction of cholinergic and dopaminergic neurons can lead to neuropsychiatric conditions like schizophrenia and addiction or cognitive diseases such as Alzheimers. Neuromodulatory systems control overlapping cognitive processes and often have similar modes of action; therefore it is important to reveal cooperation and competition between different systems to understand their unique contributions to cognitive functions like learning, memory and attention. This is only possible by direct comparison, which necessitates monitoring multiple neuromodulatory systems under identical experimental conditions. Moreover, simultaneous recording of different neuromodulatory cell types goes beyond phenomenological description of similarities and differences by revealing the underlying correlation structure at the level of action potential timing. However, such data allowing direct comparison of neuromodulatory actions are still sparse. As a first step to bridge this gap, I propose to elucidate the unique versus complementary roles of two classical neuromodulatory systems, the cholinergic and dopaminergic projection system implicated in various cognitive functions including associative learning and plasticity. First, we will record optogenetically identified cholinergic and dopaminergic neurons simultaneously using chronic extracellular recording in mice undergoing classical and operant conditioning. Second, we will determine the postsynaptic impact of cholinergic and dopaminergic neurons by manipulating them both separately and simultaneously while recording consequential changes in cortical neuronal activity and learning behaviour. These experiments will reveal how major neuromodulatory systems interact to mediate similar or different aspects of the same cognitive functions.

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