BACKGROUND: Treating memory and cognitive deficits requires knowledge about anatomical sites and neural activities to be targeted with particular therapies. Emerging technologies for local brain stimulation offer attractive therapeutic options but need to be applied to target specific neural activities, at distinct times, and in specific brain regions that are critical for memory formation. METHODS: The areas that are critical for successful encoding of verbal memory as well as the underlying neural activities were determined directly in the human brain with intracranial electrophysiological recordings in epilepsy patients. We recorded a broad range of spectral activities across the cortex of 135 patients as they memorised word lists for subsequent free recall. FINDINGS: The greatest differences in the spectral power between encoding subsequently recalled and forgotten words were found in low theta frequency (3-5 Hz) activities of the left anterior prefrontal cortex. This subsequent memory effect was proportionally greater in the lower frequency bands and in the more anterior cortical regions. We found the peak of this memory signal in a distinct part of the prefrontal cortex at the junction between the Broca's area and the frontal pole. The memory effect in this confined area was significantly higher (Tukey-Kramer test, p<0.05) than in other anatomically distinct areas. INTERPRETATION: Our results suggest a focal hotspot of human verbal memory encoding located in the higher-order processing region of the prefrontal cortex, which presents a prospective target for modulating cognitive functions in the human patients. The memory effect provides an electrophysiological biomarker of low frequency neural activities, at distinct times of memory encoding, and in one hotspot location in the human brain. FUNDING: Open-access datasets were originally collected as part of a BRAIN Initiative project called Restoring Active Memory (RAM) funded by the Defence Advanced Research Project Agency (DARPA). CT, ML, MTK and this research were supported from the First Team grant of the Foundation for Polish Science co-financed by the European Union under the European Regional Development Fund.

• Klíčová slova
• Anterior prefrontal cortex, Frontal pole, Human verbal memory, Intracranial recordings, Memory encoding,
• MeSH
• lidé MeSH
• magnetická rezonanční tomografie MeSH
• mapování mozku MeSH
• mozek fyziologie   MeSH
• paměť * fyziologie   MeSH
• prefrontální mozková kůra * fyziologie   MeSH
• rozpomínání fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Contactless digital tags are increasingly penetrating into many areas of human activities. Digitalization of our environment requires an ever growing number of objects to be identified and tracked with machine-readable labels. Molecules offer immense potential to serve for this purpose, but our ability to write, read, and communicate molecular code with current technology remains limited. Here we show that magnetic patterns can be synthetically encoded into stable molecular scaffolds with paramagnetic lanthanide ions to write digital code into molecules and their mixtures. Owing to the directional character of magnetic susceptibility tensors, each sequence of lanthanides built into one molecule produces a unique magnetic outcome. Multiplexing of the encoded molecules provides a high number of codes that grows double-exponentially with the number of available paramagnetic ions. The codes are readable by nuclear magnetic resonance in the radiofrequency (RF) spectrum, analogously to the macroscopic technology of RF identification. A prototype molecular system capable of 16-bit (65,535 codes) encoding is presented. Future optimized systems can conceivably provide 64-bit (~10^19 codes) or higher encoding to cover the labelling needs in drug discovery, anti-counterfeiting and other areas.

• MeSH
• lanthanoidy * MeSH
• lidé MeSH
• magnetická rezonanční spektroskopie MeSH
• magnetismus MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• lanthanoidy * MeSH

Space and time are fundamental attributes of the external world. Deciphering the brain mechanisms involved in processing the surrounding environment is one of the main challenges in neuroscience. This is particularly defiant when situations change rapidly over time because of the intertwining of spatial and temporal information. However, understanding the cognitive processes that allow coping with dynamic environments is critical, as the nervous system evolved in them due to the pressure for survival. Recent experiments have revealed a new cognitive mechanism called time compaction. According to it, a dynamic situation is represented internally by a static map of the future interactions between the perceived elements (including the subject itself). The salience of predicted interactions (e.g. collisions) over other spatiotemporal and dynamic attributes during the processing of time-changing situations has been shown in humans, rats, and bats. Motivated by this ubiquity, we study an artificial neural network to explore its minimal conditions necessary to represent a dynamic stimulus through the future interactions present in it. We show that, under general and simple conditions, the neural activity linked to the predicted interactions emerges to encode the perceived dynamic stimulus. Our results show that this encoding improves learning, memorization and decision making when dealing with stimuli with impending interactions compared to no-interaction stimuli. These findings are in agreement with theoretical and experimental results that have supported time compaction as a novel and ubiquitous cognitive process.

• Klíčová slova
• Neural networks, dynamic environments, interactions, learning, memory, spatiotemporal cognition,
• MeSH
• lidé MeSH
• modely neurologické * MeSH
• mozek * fyziologie   MeSH
• neuronové sítě * MeSH
• rozhodování fyziologie   MeSH
• učení fyziologie   MeSH
• vnímání času * fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

Enzymes offer a more environmentally friendly and low-impact solution to conventional chemistry, but they often require additional engineering for their application in industrial settings, an endeavour that is challenging and laborious. To address this issue, the power of machine learning can be harnessed to produce predictive models that enable the in silico study and engineering of improved enzymatic properties. Such machine learning models, however, require the conversion of the complex biological information to a numerical input, also called protein representations. These inputs demand special attention to ensure the training of accurate and precise models, and, in this review, we therefore examine the critical step of encoding protein information to numeric representations for use in machine learning. We selected the most important approaches for encoding the three distinct biological protein representations - primary sequence, 3D structure, and dynamics - to explore their requirements for employment and inductive biases. Combined representations of proteins and substrates are also introduced as emergent tools in biocatalysis. We propose the division of fixed representations, a collection of rule-based encoding strategies, and learned representations extracted from the latent spaces of large neural networks. To select the most suitable protein representation, we propose two main factors to consider. The first one is the model setup, which is influenced by the size of the training dataset and the choice of architecture. The second factor is the model objectives such as consideration about the assayed property, the difference between wild-type models and mutant predictors, and requirements for explainability. This review is aimed at serving as a source of information and guidance for properly representing enzymes in future machine learning models for biocatalysis.

• Klíčová slova
• Biocatalysis, Enzyme engineering, Machine learning, Predictive models, Protein dynamics, Protein representations, Representation learning,
• MeSH
• biokatalýza * MeSH
• enzymy metabolismus   chemie   genetika   MeSH
• neuronové sítě MeSH
• proteiny chemie   metabolismus   MeSH
• strojové učení * MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• enzymy MeSH
• proteiny MeSH

Pupil responses are known to indicate brain processes involved in perception, attention and decision-making. They can provide an accessible biomarker of human memory performance and cognitive states in general. Here we investigated changes in the pupil size during encoding and recall of word lists. Consistent patterns in the pupil response were found across and within distinct phases of the free recall task. The pupil was most constricted in the initial fixation phase and was gradually more dilated through the subsequent encoding, distractor and recall phases of the task, as the word items were maintained in memory. Within the final recall phase, retrieving memory for individual words was associated with pupil dilation in absence of visual stimulation. Words that were successfully recalled showed significant differences in pupil response during their encoding compared to those that were forgotten - the pupil was more constricted before and more dilated after the onset of word presentation. Our results suggest pupil size as a potential biomarker for probing and modulation of memory processing.

• MeSH
• dospělí MeSH
• kognice fyziologie   MeSH
• lidé MeSH
• mladý dospělý MeSH
• pupila fyziologie   MeSH
• rozpomínání fyziologie   MeSH
• světelná stimulace MeSH
• velikost orgánu fyziologie   MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Previously we have identified the rplA gene encoding ribosomal protein L1 in Streptomyces aureofaciens. Sequence comparison of ribosomal protein L1 among several bacterial genera revealed a high level of conservation. Based on this conservation, these proteins were used as a phylogenetic tool to compare evolutionary relationships among eubacteria and archaebacteria. This phylogenetic analysis of L1 ribosomal proteins including the S. aureofaciens rplA gene product revealed, except similar bacterial groupings, some new evolutionary relationships.

• MeSH
• Archaea klasifikace   genetika   MeSH
• Bacteria klasifikace   genetika   MeSH
• bakteriální geny MeSH
• bakteriální proteiny klasifikace   genetika   MeSH
• fylogeneze MeSH
• molekulární sekvence - údaje MeSH
• ribozomální proteiny klasifikace   genetika   MeSH
• sekvence aminokyselin MeSH
• sekvenční homologie aminokyselin MeSH
• sekvenční seřazení MeSH
• Streptomyces aureofaciens klasifikace   genetika   MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• bakteriální proteiny MeSH
• ribosomal protein L1 MeSH Prohlížeč
• ribozomální proteiny MeSH

The nucleotide sequence of a 3007-bp DNA fragment from Thermomonospora curvata CCM3352 containing the coding and regulatory region of the alpha-amylase-encoding gene (tam) was determined. Primer extension mapping was used to determine the 5' end of the transcript, and it was demonstrated that the gene is transcribed from a unique promoter which is also functional in Streptomyces lividans TK24. Transcription of tam in T. curvata was induced by maltose, even in the presence of glucose. In S. lividans, tam was expressed constitutively. The deduced amino acid sequence reveals a considerable similarity with alpha-amylases from streptomycetes.

• MeSH
• Actinomycetales enzymologie   genetika   MeSH
• alfa-amylasy chemie   genetika   MeSH
• glukosa farmakologie   MeSH
• klonování DNA MeSH
• maltosa farmakologie   MeSH
• molekulární sekvence - údaje MeSH
• promotorové oblasti (genetika) genetika   MeSH
• regulace genové exprese u bakterií účinky léků   MeSH
• sekvence aminokyselin MeSH
• sekvence nukleotidů MeSH
• Streptomyces enzymologie   genetika   MeSH
• teplota MeSH
• Publikační typ
• časopisecké články MeSH
• srovnávací studie MeSH
• Názvy látek
• alfa-amylasy MeSH
• glukosa MeSH
• maltosa MeSH

Pheromones convey rich ethological information and guide insects' search behavior. Insects navigating in turbulent environments are tasked with the challenge of coding the temporal structure of an odor plume, obliging recognition of the onset and offset of whiffs of odor. The coding mechanisms that shape odor offset recognition remain elusive. We designed a device to deliver sharp pheromone pulses and simultaneously measured the response dynamics from pheromone-tuned olfactory receptor neurons (ORNs) in male moths and Drosophila. We show that concentration-invariant stimulus duration encoding is implemented in moth ORNs by spike frequency adaptation at two time scales. A linear-nonlinear model fully captures the underlying neural computations and offers an insight into their biophysical mechanisms. Drosophila use pheromone cis-vaccenyl acetate (cVA) only for very short distance communication and are not faced with the need to encode the statistics of the cVA plume. Their cVA-sensitive ORNs are indeed unable to encode odor-off events. Expression of moth pheromone receptors in Drosophila cVA-sensitive ORNs indicates that stimulus-offset coding is receptor independent. In moth ORNs, stimulus-offset coding breaks down for short ( < 200 ms) whiffs. This physiological constraint matches the behavioral latency of switching from the upwind surge to crosswind cast flight upon losing contact with the pheromone.

• MeSH
• acetáty MeSH
• čich fyziologie   MeSH
• čichové buňky * fyziologie   MeSH
• čichové dráhy fyziologie   MeSH
• Drosophila melanogaster fyziologie   MeSH
• Drosophila fyziologie   MeSH
• feromony * MeSH
• kyseliny olejové MeSH
• můry * fyziologie   MeSH
• odoranty analýza   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• acetáty MeSH
• cis-vaccenyl acetate MeSH Prohlížeč
• feromony * MeSH
• kyseliny olejové MeSH

Processing of memory is supported by coordinated activity in a network of sensory, association, and motor brain regions. It remains a major challenge to determine where memory is encoded for later retrieval. Here, we used direct intracranial brain recordings from epilepsy patients performing free recall tasks to determine the temporal pattern and anatomical distribution of verbal memory encoding across the entire human cortex. High γ frequency activity (65-115 Hz) showed consistent power responses during encoding of subsequently recalled and forgotten words on a subset of electrodes localized in 16 distinct cortical areas activated in the tasks. More of the high γ power during word encoding, and less power before and after the word presentation, was characteristic of successful recall and observed across multiple brain regions. Latencies of the induced power changes and this subsequent memory effect (SME) between the recalled and forgotten words followed an anatomical sequence from visual to prefrontal cortical areas. Finally, the magnitude of the memory effect was unexpectedly found to be the largest in selected brain regions both at the top and at the bottom of the processing stream. These included the language processing areas of the prefrontal cortex and the early visual areas at the junction of the occipital and temporal lobes. Our results provide evidence for distributed encoding of verbal memory organized along a hierarchical posterior-to-anterior processing stream.

• Klíčová slova
• cognition, cortical mapping, electrocorticography, high-frequency oscillations, network oscillations,
• MeSH
• časové faktory MeSH
• elektrokortikografie MeSH
• gama rytmus EEG fyziologie   MeSH
• lidé MeSH
• mapování mozku MeSH
• mozková kůra fyziologie   patofyziologie   MeSH
• percepce řeči fyziologie   MeSH
• refrakterní epilepsie patofyziologie   psychologie   MeSH
• rozpomínání fyziologie   MeSH
• slovní zásoba MeSH
• zraková percepce fyziologie   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• multicentrická studie MeSH
• práce podpořená grantem MeSH
• Research Support, U.S. Gov't, Non-P.H.S. MeSH

The aim of the present study was to characterize sporadic cases and an outbreak of NDM-like-producing Enterobacteriaceae recovered from hospital settings, in Czechia. During 2016, 18 Entrobacteriaceae isolates including 10 Enterobacter cloacae complex (9 E. xiangfangensis and 1 E. asburiae), 4 Escherichia coli, 1 Kluyvera intermedia, 1 Klebsiella pneumoniae, 1 Klebsiella oxytoca, and 1 Raoultella ornithinolytica that produced NDM-like carbapenemases were isolated from 15 patients. Three of the patients were colonized or infected by two different NDM-like producers. Moreover, an NDM-4-producing isolate of E. cloacae complex, isolated in 2012, was studied for comparative purposes. All isolates of E. cloacae complex, except the E. asburiae, recovered from the same hospital, were assigned to ST182. Additionally, two E. coli belonged to ST167, while the remaining isolates were not clonally related. Thirteen isolates carried blaNDM-4, while six isolates carried blaNDM-1 (n = 3) or blaNDM-5 (n = 3). Almost all isolates carried blaNDM-like-carrying plasmids being positive for the IncX3 allele, except ST58 E. coli and ST14 K. pneumoniae isolates producing NDM-1. Analysis of plasmid sequences revealed that all IncX3 blaNDM-like-carrying plasmids exhibited a high similarity to each other and to previously described plasmids, like pNDM-QD28, reported from worldwide. However, NDM-4-encoding plasmids differed from other IncX3 plasmids by the insertion of a Tn3-like transposon. On the other hand, the ST58 E. coli and ST14 K. pneumoniae isolates carried two novel NDM-1-encoding plasmids, pKpn-35963cz, and pEsco-36073cz. Plasmid pKpn-35963cz that was an IncFIB(K) molecule contained an acquired sequence, encoding NDM-1 metallo-β-lactamase (MβL), which exhibited high similarity to the mosaic region of pS-3002cz from an ST11 K. pneumoniae from Czechia. Finally, pEsco-36073cz was a multireplicon A/C2+R NDM-1-encoding plasmid. Similar to other type 1 A/C2 plasmids, the blaNDM-1 gene was located within the ARI-A resistance island. These findings underlined that IncX3 plasmids have played a major role in the dissemination of blaNDM-like genes in Czech hospitals. In combination with further evolvement of NDM-like-encoding MDR plasmids through reshuffling, NDM-like producers pose an important public threat.

• Klíčová slova
• Enterobacter xiangfangensis, IncX3, NDM, ST182, metallo-β-lactamases,
• Publikační typ
• časopisecké články MeSH