Budapest, Hungary
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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Grant
Agency: Cordis | 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.


Szolnoki A.,Hungarian Academy of Sciences | Perc M.,University of Maribor
Physical Review X | Year: 2014

Economic experiments reveal that humans value cooperation and fairness. Punishing unfair behavior is therefore common, and according to the theory of strong reciprocity, it is also directly related to rewarding cooperative behavior. However, empirical data fail to confirm that positive and negative reciprocity are correlated. Inspired by this disagreement, we determine whether the combined application of reward and punishment is evolutionarily advantageous. We study a spatial public goods game, where in addition to the three elementary strategies of defection, rewarding, and punishment, a fourth strategy that combines the latter two competes for space. We find rich dynamical behavior that gives rise to intricate phase diagrams where continuous and discontinuous phase transitions occur in succession. Indirect territorial competition, spontaneous emergence of cyclic dominance, as well as divergent fluctuations of oscillations that terminate in an absorbing phase are observed. Yet, despite the high complexity of solutions, the combined strategy can survive only in very narrow and unrealistic parameter regions. Elementary strategies, either in pure or mixed phases, are much more common and likely to prevail. Our results highlight the importance of patterns and structure in human cooperation, which should be considered in future experiments.


Grant
Agency: Cordis | 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: Cordis | 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.


Grant
Agency: Cordis | Branch: H2020 | Program: ERC-COG | Phase: ERC-CoG-2015 | Award Amount: 2.00M | Year: 2016

The long-term aim of the investigation is to assess the feasibility of creating an artificial sense and, thereby, a possible sensory (visual) prosthetic. While working towards this goal, we will have to address the question of how neural assembly activity relates to subjective perceptions. Finding and understanding these functional assemblies will make it possible to reactivate them in a precise, biologically relevant manner to elicit similar cortical activation as visual stimulation. Recent publications suggest that cortical connectivity can be mapped by two-photon microscopy. Here we want, therefore, to develop a novel 3D Electro-Acousto-Optical microscope for high-throughput assembly mapping. The microscope will be capable of scanning neuronal activity with one order of magnitude higher speed (300-500 kHz/ROI) and simultaneously photoactivate neurons with three order of magnitude higher efficiency (2,500 25,000 neurons/ms) than existing 3D microscopes while preserving the subcellular resolution required to simultaneously measure the somatic, the dendritic and axonal computation units in the entire V1 region of the cortex. The microscope will be based on our current 3D AO technology; on novel ultra-fast scanning technologies; new, 10-fold faster AO deflectors; and novel (multi-ROI) scanning strategies. Using our microscope in combination with novel caged neurotransmitters and optogenetic tools, we want to map cell assemblies and to understand how they form larger clusters and how they are associated with visual features. Furthermore, as a proof-of-concept of this grant, we want to restore visual perception by recreating previously mapped assembly patterns with 3D artificial photositmulation in behaving mice and see if the animal responds to the artificial stimulus in the same way as to the visual stimulus. Moreover, we want to restore visual information based spatial navigation in head restrained animals orienting and moving in a virtual labyrinth for reward.

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