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Oligodendrogliomas are uncommon tumors in neurooncology that represent about 5% of primary brain malignancies. Their high sensitivity to radiotherapy and chemotherapy was observed a long time ago. Nonetheless, the evidence-based proof of the significantly longer survival in patients with oligodendrogliomas treated with combined chemotherapy and radiotherapy in comparison to radiotherapy-alone did not exist. The long-term follow-up of two landmark phase III clinical trials: RTOG 9402 and EORTC 26951, recently demonstrated favorable effects of combined radiotherapy and chemotherapy (procarbazine, lomustine and vincristine) in patients with anaplastic oligodendrogliomas and anaplastic oligoastrocytomas carrying the chromosomal mutation of co-deletion of 1p/19q. There is also an increasing role of other molecular biomarkers, such as mutations in the metabolic enzyme isocitrate dehydrogenase 1/2, O6-methylguanine DNA methyltransferase gene promoter methylation, or glioma genome cytosine-phosphate-guanine islands methylator phenotype. The analysis of molecular genetics in oligodendrogliomas is now recommended as an important part of the management of these tumors and together with the novel chemotherapeutic regimens means a paradigm shift in current clinical practice in neurooncology.
- Klíčová slova
- IDH1/2 mutations, MGMT promoter methylation, Oligodendroglioma, co-deletion 1p/19q, novel treatment, personalized medicine, review,
- MeSH
- chromozomální delece MeSH
- lidé MeSH
- lidské chromozomy, pár 1 MeSH
- nádory mozku diagnóza genetika terapie MeSH
- oligodendrogliom diagnóza genetika terapie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- přehledy MeSH
Motor learning and flexibility allow animals to perform routine actions efficiently while keeping them flexible. A number of paradigms are used to test cognitive flexibility, but not many of them focus specifically on the learning of complex motor sequences and their flexibility. While many tests use operant or touchscreen boxes that offer high throughput and reproducibility, the motor actions themselves are mostly simple presses of a designated lever. To focus more on motor actions during the operant task and to probe the flexibility of these well trained actions, we developed a new operant paradigm for mice, the "timed sequence task." The task requires mice to learn a sequence of lever presses that have to be emitted in precisely defined time limits. After training, the required pressing sequence and/or timing of individual presses is modified to test the ability of mice to alter their previously trained motor actions. We provide a code for the new protocol that can be used and adapted to common types of operant boxes. In addition, we provide a set of scripts that allow automatic extraction and analysis of numerous parameters recorded during each session. We demonstrate that the analysis of multiple performance parameters is necessary for detailed insight into the behavior of animals during the task. We validate our paradigm in an experiment using the valproate model of autism as a model of cognitive inflexibility. We show that the valproate mice show superior performance at specific stages of the task, paradoxically because of their propensity to more stereotypic behavior.
- Klíčová slova
- flexibility, mice, motor learning, operant learning,
- MeSH
- kyselina valproová * MeSH
- myši MeSH
- operantní podmiňování MeSH
- reprodukovatelnost výsledků MeSH
- učení * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Názvy látek
- kyselina valproová * MeSH
Ticks, as vectors of several notorious zoonotic pathogens, represent an important and increasing threat for human and animal health in Europe. Recent applications of new technology revealed the complexity of the tick microbiome, which may affect its vectorial capacity. Appreciation of these complex systems is expanding our understanding of tick-borne pathogens, leading us to evolve a more integrated view that embraces the 'pathobiome'; the pathogenic agent integrated within its abiotic and biotic environments. In this review, we will explore how this new vision will revolutionize our understanding of tick-borne diseases. We will discuss the implications in terms of future research approaches that will enable us to efficiently prevent and control the threat posed by ticks.
- Klíčová slova
- Ixodes ricinus, co-infections, emerging diseases, new paradigm, next-generation sequencing, pathobiome, unknown pathogens, vector competence, zoonoses,
- MeSH
- klíšťata mikrobiologie virologie MeSH
- lidé MeSH
- mikrobiota * MeSH
- nemoci přenášené klíšťaty epidemiologie mikrobiologie přenos virologie MeSH
- zoonózy epidemiologie mikrobiologie přenos virologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Geografické názvy
- Evropa epidemiologie MeSH
An historical survey is presented of mortality trials on angiotensin-aldosteron system inhibition in patients with chronic heart failure. From the CONSENSUS trial up to the PARADIGM-HF trial, ACE inhibitors/angiotensin II receptor antagonists (AT1-blockers, ARBs, sartans), along with mineralocorticoid receptor blockers, have been the gold standard of treatment. Both direct renin blocker aliskiren and dual blocker enalapril + neprilysin proved ineffective; on the other hand, the new dual inhibitor valsartan + neprilysin LCZ 696 is a new and promising therapeutic agent for future treatment of chronic heart failure.
- MeSH
- antagonisté receptorů pro angiotenzin terapeutické užití MeSH
- inhibitory ACE terapeutické užití MeSH
- konsensus * MeSH
- lidé MeSH
- renin-angiotensin systém účinky léků MeSH
- srdeční selhání farmakoterapie metabolismus MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
- Názvy látek
- antagonisté receptorů pro angiotenzin MeSH
- inhibitory ACE MeSH
In the past few years, aqueous zinc-metal batteries (ZMBs) have gained much attention and can be regarded as a potential alternative to lithium-metal batteries owing to their high safety, nature of abundance, and environmental sustainability. However, several challenges persist, including dendrite formation, corrosion, and unwanted side reactions, before ZMBs can be fully utilized in practical applications. To circumvent these issues, anode free zinc-metal batteries (AFZMBs) have emerged as a next-generation energy storage system. This review provides a comprehensive analysis of recent developments in AFZMBs, including their working mechanisms, advantages over conventional ZMBs, and the challenges for practical implementation. It also highlights the key strategies, including current collector modification, electrolyte engineering, and 3D printing techniques to enhance zinc deposition uniformity and cycling stability. The review also explores how 3D printing technology can revolutionize the design of advanced current collectors and zinc-rich cathodes, optimizing material utilization and enhancing battery performance. Finally, with a future perspective of AFZMBs is concluded, highlighting the need for further research to address existing bottlenecks and fully unlock their potential for next-generation energy storage.
- Klíčová slova
- 3D printing, advantages and challenges, anode free zinc‐metal batteries, current collector, electrolyte optimization, strategies,
- Publikační typ
- časopisecké články MeSH
- přehledy MeSH
The isolation of populations in the Iberian, Italian and Balkan peninsulas during the ice ages define four main paradigms that explain much of the known distribution of intraspecific genetic diversity in Europe. In this study we investigated the phylogeography of a wide-spread bat species, the bent-winged bat, Miniopterus schreibersii around the Mediterranean basin and in the Caucasus. Environmental Niche Modeling (ENM) analysis was applied to predict both the current distribution of the species and its distribution during the last glacial maximum (LGM). The combination of genetics and ENM results suggest that the populations of M. schreibersii in Europe, the Caucasus and Anatolia went extinct during the LGM, and the refugium for the species was a relatively small area to the east of the Levantine Sea, corresponding to the Mediterranean coasts of present-day Syria, Lebanon, Israel, and northeastern and northwestern Egypt. Subsequently the species first repopulated Anatolia, diversified there, and afterwards expanded into the Caucasus, continental Europe and North Africa after the end of the LGM. The fossil record in Iberia and the ENM results indicate continuous presence of Miniopterus in this peninsula that most probably was related to the Maghrebian lineage during the LGM, which did not persist afterwards. Using our results combined with similar findings in previous studies, we propose a new paradigm explaining the general distribution of genetic diversity in Europe involving the recolonization of the continent, with the main contribution from refugial populations in Anatolia and the Middle East. The study shows how genetics and ENM approaches can complement each other in providing a more detailed picture of intraspecific evolution.
- Klíčová slova
- Anatolia, Environmental niche modeling, Europe, Levant, Microsatellites, Miniopterus schreibersii, Mitochondrial DNA, North Africa, Phylogeography, Refugia,
- MeSH
- biologické modely MeSH
- Chiroptera klasifikace genetika MeSH
- fylogeneze MeSH
- fylogeografie MeSH
- genetická variace MeSH
- mitochondriální DNA izolace a purifikace metabolismus MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- Geografické názvy
- Balkánský poloostrov MeSH
- Evropa MeSH
- severní Afrika MeSH
- Střední východ MeSH
- Názvy látek
- mitochondriální DNA MeSH
Rabbits with chronically implanted Ag-AgCl electrodes over somatosensory and visual cortex were trained to a modified 'oddball' paradigm with visual stimulation. Event related potentials (ERP) and slow potential shifts (SPS) were recorded. By means of a computer controlled stimulator 'frequent' and 'rare' LED flashes were administered to the eyes of the rabbit. If 'rare' stimuli were reinforced by a weak electrical footshock, negative SPS rose steeper and reached significantly higher amplitudes than in 'frequent' conditions without reinforcement. Different kinds of the follow-up of 'frequent' and 'rare' series were tested. Best effects were obtained, if a session was divided into 3 blocks (3 srs. 'frequent'--5 srs. 'rare' reinforced--2 srs. 'frequent' and probability of 'rare' flashes was 20%. Our present data formed a basis for investigations on the neuronal and glial sources of SPS in rabbits.
- MeSH
- elektrická stimulace MeSH
- elektroencefalografie MeSH
- evokované potenciály fyziologie MeSH
- implantované elektrody MeSH
- králíci MeSH
- somatosenzorické korové centrum fyziologie MeSH
- světelná stimulace MeSH
- zrakové evokované potenciály fyziologie MeSH
- zrakové korové centrum fyziologie MeSH
- zvířata MeSH
- Check Tag
- králíci MeSH
- mužské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
Cancer cells can escape the effects of chemotherapy through mutations and upregulation of a tyrosine kinase protein called the epidermal growth factor receptor (EGFR). In the past two decades, four generations of tyrosine kinase inhibitors targeting EGFR have been developed. Using comparative structure analysis of 116 EGFR-drug complex crystal structures, cluster analysis produces two clans of 73 and 43 structures, respectively. The first clan of 73 structures is larger and is comprised mostly of the C-helix-IN conformation while the second clan of 43 structures correlates with the C-helix-OUT conformation. A deep rotamer analysis identifies 43 residues (18%) of the total of 237 residues spanning the kinase structures under investigation with significant rotamer variations between the C-helix-IN and C-helix-OUT clans. The locations of these rotamer variations take on the appearance of side chain conformational relays extending out from points of EGFR mutation to different regions of the EGFR kinase. Accordingly, we propose that key EGFR mutations act singly or together to induce drug resistant conformational changes in EGFR that are communicated via these side chain conformational relays. Accordingly, these side chain conformational relays appear to play a significant role in the development of tumour resistance. This phenomenon also suggests a new paradigm in protein conformational change that is mediated by supportive relays of rotamers on the protein surface, rather than through conventional backbone movements.
- Klíčová slova
- EGFR, NSCLC, Protein folding, Protein structure, Rotamer, Tumour resistance, Tyrosine kinase inhibitor,
- Publikační typ
- časopisecké články MeSH
First-principles electronic structure calculations are now accessible to a very large community of users across many disciplines, thanks to many successful software packages, some of which are described in this special issue. The traditional coding paradigm for such packages is monolithic, i.e., regardless of how modular its internal structure may be, the code is built independently from others, essentially from the compiler up, possibly with the exception of linear-algebra and message-passing libraries. This model has endured and been quite successful for decades. The successful evolution of the electronic structure methodology itself, however, has resulted in an increasing complexity and an ever longer list of features expected within all software packages, which implies a growing amount of replication between different packages, not only in the initial coding but, more importantly, every time a code needs to be re-engineered to adapt to the evolution of computer hardware architecture. The Electronic Structure Library (ESL) was initiated by CECAM (the European Centre for Atomic and Molecular Calculations) to catalyze a paradigm shift away from the monolithic model and promote modularization, with the ambition to extract common tasks from electronic structure codes and redesign them as open-source libraries available to everybody. Such libraries include "heavy-duty" ones that have the potential for a high degree of parallelization and adaptation to novel hardware within them, thereby separating the sophisticated computer science aspects of performance optimization and re-engineering from the computational science done by, e.g., physicists and chemists when implementing new ideas. We envisage that this modular paradigm will improve overall coding efficiency and enable specialists (whether they be computer scientists or computational scientists) to use their skills more effectively and will lead to a more dynamic evolution of software in the community as well as lower barriers to entry for new developers. The model comes with new challenges, though. The building and compilation of a code based on many interdependent libraries (and their versions) is a much more complex task than that of a code delivered in a single self-contained package. Here, we describe the state of the ESL, the different libraries it now contains, the short- and mid-term plans for further libraries, and the way the new challenges are faced. The ESL is a community initiative into which several pre-existing codes and their developers have contributed with their software and efforts, from which several codes are already benefiting, and which remains open to the community.
- Publikační typ
- časopisecké články MeSH
