Az MBL-hez kapcsolódó szerin proteázok szubsztrát specificitása és fiziológiai jelentősége = Substrate specificity and physiological relevance of MBL-associated serine proteases

A komplement rendszer aktiválódásának lektin útja az egyik első védelmi vonalnak tekinthető a szervezet fertőzések elleni védekezésében. A mannóz kötő lektin (MBL) baktérium felszínhez való kötődése után szerin proteáz zimogének (MASP= MBL-kötött szerin proteáz) aktiválódnak, melyek többféle mechanizmus révén járulnak hozzá az idegen mikroorganizmus megsemmisítéséhez ill. eltávolításához. Munkánk során felderítettük, a proteolitikus kaszkádrendszer beindításáért felelős MASP-2 enzim autoaktiválódásásnak mechanizmusát atomi szinten. Felfedeztük a MASP-2 egy eddig ismeretlen biológiai funkcióját, amely kapcsolatot teremt a véralvadási és a komplement kaszkád között. A MASP-2 hasítja és aktiválja a protrombint. Ugyancsak részletesen tanulmányoztuk a MASP-1 trombin-szerű aktivitását is. Ezek az eredmények arra utalnak, hogy a vérben lévő két proteolitikus kaszkádrendszer szoros evolúciós és funkcionális kapcsolatban van egymással, a komplement lektin útja által indukált limitált koaguláció az immunvédekezés egy ősi formájának tekinthető. | The lectin pathway of the complement system forms one of the first defence lines against the infections in our body. Upon MBL (mannose-binding lectin) binds to the bacterial surface serine protease zymogens (MASP=MBL-associated serine protease) become activated, and the active MASPs contribute to the inactivation and elimination of the foreign microorganism in several ways. In the course of our work we revealed the detailed atomic mechanism of the autoactivation of MASP-2 that is responsible for the initiation of the complement cascade. We discovered a new biological function of MASP-2 which makes contact between the complement and the coagulation cascades. MASP-2 cleaves and activates prothrombin. We also studied the thrombin-like activity of MASP-1 in detail. These results suggest that the two proteolytic cascade systems are in close evolutionary and functional relationship. The limited coagulation induced by the lectin pathway of the complement system can be regarded as an ancient form of immunity

Functional Properties of Dendritic Gap Junctions in Cerebellar Golgi Cells.

The strength and variability of electrical synaptic connections between GABAergic interneurons are key determinants of spike synchrony within neuronal networks. However, little is known about how electrical coupling strength is determined due to the inaccessibility of gap junctions on the dendritic tree. We investigated the properties of gap junctions in cerebellar interneurons by combining paired somato-somatic and somato-dendritic recordings, anatomical reconstructions, immunohistochemistry, electron microscopy, and modeling. By fitting detailed compartmental models of Golgi cells to their somato-dendritic voltage responses, we determined their passive electrical properties and the mean gap junction conductance (0.9 nS). Connexin36 immunofluorescence and freeze-fracture replica immunogold labeling revealed a large variability in gap junction size and that only 18% of the 340 channels are open in each plaque. Our results establish that the number of gap junctions per connection is the main determinant of both the strength and variability in electrical coupling between Golgi cells

Distinct axo-somato-dendritic distributions of three potassium channels in CA1 hippocampal pyramidal cells

Potassium channels comprise the most diverse family of ion channels and play critical roles in a large variety of physiological and pathological processes. In addition to their molecular diversity, variations in their distributions and densities on the axo-somato-dendritic surface of neurons are key parameters in determining their functional impact. Despite extensive electrophysiological and anatomical investigations, the exact location and densities of most K(+) channels in small subcellular compartments are still unknown. Here we aimed at providing a quantitative surface map of two delayed-rectifier (Kv1.1 and Kv2.1) and one G-protein-gated inwardly rectifying (Kir3.2) K(+) channel subunits on hippocampal CA1 pyramidal cells (PCs). Freeze-fracture replica immunogold labelling was employed to determine the relative densities of these K(+) channel subunits in 18 axo-somato-dendritic compartments. Significant densities of the Kv1.1 subunit were detected on axon initial segments (AISs) and axon terminals, with an approximately eight-fold lower density in the latter compartment. The Kv2.1 subunit was found in somatic, proximal dendritic and AIS plasma membranes at approximately the same densities. This subunit has a non-uniform plasma membrane distribution; Kv2.1 clusters are frequently adjacent to, but never overlap with, GABAergic synapses. A quasi-linear increase in the Kir3.2 subunit density along the dendrites of PCs was detected, showing no significant difference between apical dendritic shafts, oblique dendrites or dendritic spines at the same distance from the soma. Our results demonstrate that each subunit has a unique cell-surface distribution pattern, and predict their differential involvement in synaptic integration and output generation at distinct subcellular compartments

Unpacking the modeling process for energy policy making

This article explores how the modeling of energy systems may lead to an undue closure of alternatives by generating an excess of certainty around some of the possible policy options. We retrospectively exemplify the problem with the case of the International Institute for Applied Systems Analysis (IIASA) global modeling in the 1980s. We discuss different methodologies for quality assessment that may help mitigate this issue, which include Numeral Unit Spread Assessment Pedigree (NUSAP), diagnostic diagrams, and sensitivity auditing (SAUD). We illustrate the potential of these reflexive modeling practices in energy policy‐making with three additional cases: (i) the case of the energy system modeling environment (ESME) for the creation of UK energy policy; (ii) the negative emission technologies (NETs) uptake in integrated assessment models (IAMs); and (iii) the ecological footprint indicator. We encourage modelers to adopt these approaches to achieve more robust, defensible, and inclusive modeling activities in the field of energy research

Digital & Cognitive Corporate Reality

As part of the most recent developments in human co-evolution with information and communication technologies, the increasing complexity of our digital realities, as well as the expanding capabilities of omni-present artificial intelligence, are having profound implications. This transformative shift leads to a new era in many fields, including corporate management and business. Newly co-evolved cognitive capabilities, both natural and artificial, are emerging, necessitating a paradigm shift in our understanding and approaches to corporate management and business science. This paper introduces the concept of Digital and Cognitive Corporate Reality (DCR) to establish a new broader view for higher-level conceptual discussion, adopting a holistic perspective that encompasses related scientific fields. Following this definition, the paper briefly explores how different scientific disciplines can be expected to contribute to the development of DCR. Use case examples are also provided to demonstrate the benefits of the holistic perspective adopted in DCR