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An efficient stereoselective synthesis of a pivotal intermediate, a cyclic allyl alcohol derivative containing two methoxy groups [(±)-22], using for the preparation of (±)-trans-dihydronarciclasine analogues was elaborated starting from easily available and inexpensive methyl gallate. This new synthetic route consists of 17 reaction steps, and provides an opportunity to obtain the wanted alkaloid derivative containing an additional methoxy group at position 11, in the ring A of the phenanthridone scaffold.

New derivatives were synthesized by the acylation of α-amino-benzylphosphonates, and by reacting them in a second Kabachnik–Fields condensation.

Building a blastema from the stump is a key step of salamander limb regeneration. Stump-derived cells temporarily suspend their identity as they contribute to the blastema by a process generally referred to as dedifferentiation. Here, we provide evidence for a mechanism that involves an active inhibition of protein syn-thesis during blastema formation and growth. Relieving this inhibition results in a higher number of cycling cells and enhances the pace of limb regeneration. By small RNA profiling and fate mapping of skeletal muscle progeny as a cellular model for dedifferentiation, we find that the downregulation of miR-10b-5p is critical for rebooting the translation machinery. miR-10b-5p targets ribosomal mRNAs, and its artificial upregulation causes decreased blastema cell proliferation, reduction in transcripts that encode ribosomal subunits, dimin-ished nascent protein synthesis, and retardation of limb regeneration. Taken together, our data identify a link between miRNA regulation, ribosome biogenesis, and protein synthesis during newt limb regeneration.

Single cell sequencing technologies (scRNA-seq, scATAC-seq, etc.) have revolutionized the study of complex tissues and unique organisms, providing researchers with a much needed species agnostic tool to study biological processes at the cellular level. To date, scRNA-seq technologies are expensive, require sufficient cell quantities, and need biological replicates to avoid batch effects or artifactual results. Pooling cells from multiple individuals into a single scRNA-seq library can address these problems. However, sample labeling protocols for facilitating the computational separation of pooled scRNA-seq samples, termed demultiplexing, have undesirable limitations, particularly in resource-limited organisms. One promising solution developed for use in humans exploits the genetic diversity between individuals (i.e., single nucleotide polymorphisms (SNP)) to demultiplex pooled scRNA-seq samples. The use of SNP-based demultiplexing methods has not been validated for use in non-human species, but the widespread use of SNP-based demuxers would greatly facilitate research in commonly used, emerging, and more obscure species. In this study we applied SNP-based demultiplexing algorithms to pooled scRNA-seq datasets from numerous species and applied diverse ground truth confirmation assays to validate genetic demultiplexing results. SNP-based demultiplexers were found to accurately demultiplex pooled scRNA-seq data from species including zebrafish, African green monkey, Xenopus laevis, axolotl, Pleurodeles waltl, and Notophthalmus viridescens. Our results demonstrate that SNP-based demultiplexing of unlabeled, pooled scRNA-seq samples can be used with confidence in all of the species studied in this work. Further, we show that the only genomic resource required for this approach is the single-cell sequencing data and a de novo transcriptome. The incorporation of pooling and SNP-demultiplexing into scRNA-seq study designs will greatly increase the reproducibility and experimental options for studying species previously limited by technical uncertainties, computational hurdles, or limited cell quantities.

During this research, the catalogues of more than 200 libraries and museums of Hungary and its neighboring countries were examined. The authors calculated the amount and the size of the metadata and of the full content records in the databases of their collection management systems, as well as the size and the type of the full content data and the size of the databases. By analyzing the results, the goal was to answer the following three questions: (1) Can any significant difference be established between the results according to country, nationality, or type of institution?; (2) How large is a metadata record or a full content record?; (3) Is it possible to establish a methodology for selecting a representative sample of institutions to facilitate further research? For planning the costs of data management, the size of the databases, the number of metadata records, and the variability of metadata and media records shall all be considered. A distinction should be made between the indispensable “primary” data to be preserved for a long time, and the “secondary” data units which are derived from the primary data. It is investigated in this article how to establish the size of primary data in the databases of collection management systems.

The preparation of representatively selected 2-aryl-4,5-disubstituted-1,2,4-triazol-3-ones from cyclic β-nitroenamines in four steps is provided, with an overall yield of 8–70%. The nitrazone to am...

Application of nucleating agents is the most versatile and industrially applied way to manipulate the crystalline structure of isotactic polypropylene (iPP). Various materials possess a nucleating effect, but from the viewpoint of dispersibility, the partially soluble ones are the most advantageous. Our objective was to synthesize new N,N'-dicyclohexyldicarboxamide homologues and study their applicability as nucleating agents in iPP. Carbon-13 nuclear magnetic resonance (13C NMR) and infrared spectroscopy were used to prove that the synthesis reactions were successful. Thermal stability of the compounds was investigated with simultaneous thermal analysis. Nucleating efficiency and solubility were characterized by polarized light microscopy and differential scanning calorimetry. Polarized light microscopy was also applied to study the effect of novel additives on the morphology of iPP. The properties, important from the viewpoint of applicability, were also investigated. Tensile tests were performed to characterize the main mechanical properties, and standard haze measurements were performed to characterize optical properties. It can be concluded that the investigated compounds are partially soluble nucleating agents and influence the crystalline structure of iPP. Most of the studied compounds have a moderate nucleating efficiency, but a very interesting dendritic structure develops in their presence. Two of them proved to be non-selective β-nucleating agents, which result in a remarkable improvement of impact resistance and higher opacity.

PurposeDecline of the sensory and motor systems in older people negatively affects postural control. This increases the risk of falls, which is dangerous for older people in long-term care. Being aware of the quality of postural control and the factors affecting it among elderly people, is crucial in implementing an effective fall-prevention program. This study aimed to measure postural control and the demographic, health-related, and functional factors presumed to be correlated with it among nursing home residents. Another aim was to find valid screening tools based on these factors.Materials and methodsSeventy one nursing home residents were included. Postural control was measured using the Berg Balance Scale. Grip strength, the 30-s chair stand test, and the Timed Up and Go test were used to measure global muscle strength, and functional mobility, respectively. The results of these functional tests were dichotomized using age-specific reference values.ResultsPostural control was significantly worse in those who did not reach the age-specific reference values in any of the three functional tests. Effect sizes were large for functional mobility and medium for muscle strength. Multimorbidity and gender had no effect on postural control in our sample.ConclusionsAmong nursing home residents, postural control is related to functional mobility and muscle strength. Thus, routine testing of these skills among elderly people is an important task of the physiotherapist.

According to our experience the 12-lead electrocardiogram (ECG) may be used to estimate the pretest probability of acute pulmonary embolism (acPE). To this end, we devised a novel ECG score (nECGs) composed of 5 known ECG criteria, best characterizing the key pathogenetic steps of acPE. A retrospective derivation cohort including 136 patients with acPE and a prospective validation cohort including 149 consecutive patients were used to devise and validate the nECGs. The latter cohort consisted of 76 patients with acPE and 73 controls presenting with characteristic symptoms of acPE, in whom the work-up ruled out acPE. We compared the diagnostic value of our nECGs with those of another ECG score (Daniel-ECG-score) and of the best prediction rules (3 Wells score and 2 Geneva score variants). The sensitivity (98.7%), negative predictive value (98%), test accuracy (84.4%) and the negative likelihood ratio (LR) (0.019) of the nECGs were superior to those of all other investigated methods. There was no between-groups difference in the positive LR. The specificity (69%) of the nECGs was inferior to those of the Daniel-ECG-score and Wells scores and did not differ or was superior to those of the Geneva score variants. The positive predictive value (77.3%) of the nECGs was superior to those of the 2 Geneva scores and did not differ from those of the other methods. In conclusion, the nECGs due to its superior sensitivity, negative predictive value, test accuracy, and negative LR estimated the pretest probability of acPE better than the Daniel-ECG-score and the prediction rules.

Absztrakt: Bevezetés: Az ülő életmód nemcsak számos krónikus betegség, valamint a multimorbiditás kockázatát növeli, de az idős személyek hamarabb elveszítik funkcionális önállóságukat is. Az ülő életmód csökkentését célzó intézkedések megtervezéséhez fontos az ülő életmóddal kapcsolatos tényezők ismerete. Célkitűzés: Leírni az ülő tevékenységek formáit és időtartamát, továbbá az ülő életmóddal kapcsolatban álló szociodemográfiai, egészségi, valamint életmódbeli tényezőket a fővárosban és vonzáskörzetében lévő idősotthonokban élő, járásképes idős emberek körében. Módszer: A kutatásban részt vevő 248 személy körében kérdőívvel felvett adatainkat logisztikus regresszióval elemeztük. Eredmények: Az ülő életmód összesen 159 személyre, a minta 64,1%-ára volt jellemző. Mintánkban az ülő életmóddal a dohányzás, az időskorra jellemző krónikus betegségek száma, az intézményben élés időtartama és a járási segédeszköz használata mutatott összefüggést. Következtetés: Azokra az idősotthonban élő idős emberekre jellemző az ülő életmód, akik több krónikus betegségben szenvednek, régebben költöztek be az intézménybe, és dohányoznak. Ezért a vezető döntéshozó pozícióban dolgozó diplomás szakembereknek elsősorban az ő körükben kell erőfeszítéseket tenniük az ülő életmód megváltoztatására: tájékoztatással, felvilágosítással, érdeklődésüknek és állapotuknak megfelelő programok felkínálásával. Orv Hetil. 2020; 161(28): 1175–1180.

The evolution of advanced cognition in vertebrates is associated with two independent innovations in the forebrain: the six-layered neocortex in mammals and the dorsal ventricular ridge (DVR) in sauropsids (reptiles and birds). How these innovations arose in vertebrate ancestors remains unclear. To reconstruct forebrain evolution in tetrapods, we built a cell-type atlas of the telencephalon of the salamander Pleurodeles waltl . Our molecular, developmental, and connectivity data indicate that parts of the sauropsid DVR trace back to tetrapod ancestors. By contrast, the salamander dorsal pallium is devoid of cellular and molecular characteristics of the mammalian neocortex yet shares similarities with the entorhinal cortex and subiculum. Our findings chart the series of innovations that resulted in the emergence of the mammalian six-layered neocortex and the sauropsid DVR.

Mind a digitálisan született, mind az analóg módon keletkezett, és digitalizált tartalmak tömege állandóan növekszik. Tárolásuk, őrzésük és szolgáltatásuk tekintetében megkerülhetetlen a hosszútávú őrzés nagy költségekkel járó megoldása. Természetesen az analóg tartalmak állományvédelme is költséges, de ennek, illetve a megőrzendő objektumok válogatásának, selejtezésének bejáratott módszerei, megoldásai vannak. A digitális tartalmak esetében ráadásul a közgyűjtemények rendelkezésére álló tárolási kapacitás növelésének is jelentős korlátjai vannak. Az IT szektorban lassan állandósuló szakemberhiány mellett a gyártási kapacitások és a nyersanyag készletek is várhatóan nehezen fognak lépést tartani a jövőben a világban tapasztalható, az adathordozók iránt megnyilvánuló keresletnövekedéssel. A tartós őrzés költségeinek mérséklésének lehetséges módja, az őrzendő állomány mennyiségének csökkentése. A digitálisan keletkezett, illetve már digitalizált anyagok esetében célszerű elsősorban a primer és szekunder adatok elválasztása, a még analóg formában létező, digitalizálásra váró dokumentumok esetében pedig a digitalizálásra és tartós őrzésre érdemes tartalmak kiválogatása. A dokumentumszolgáltatás céljából történő digitalizálás során a válogatás szakszerű megalapozásához fontos lehet az integrált könyvtári rendszerekben őrzött tranzakciós rekordok vizsgálatával foglalkozni. A rendszerek kölcsönzési moduljai ugyanis évekre - évtizedekre visszamenőleg őrzik a tranzakciós rekordokat, egyebek mellett a kölcsönzési események tranzakcióinak rekordjait is. Ezeket elemezve megállapíthatjuk, milyen korú és milyen témájú könyvek kerülnek a legnagyobb tömegben kölcsönzésre. A szerző egyik kutatása könyvtárak százainak a kölcsönzési tranzakciós rekordjait vizsgálta a kölcsönzött könyvek átlagos korának tekintetében, ezen kutatás eredményéről számolna be tanulmányában.

This work presents the synthesis of six new phase-transfer organocatalysts in which the squaramide unit is directly linked to the nitrogen atom of an aza-crown ether. Four chiral skeletons, namely hydroquinine, quinine, cinchonine (cinchonas), and α-d-glucopyranoside were responsible for the asymmetric construction of an all-carbon quaternary stereogenic center in α-alkylation and Michael addition reactions of malonic esters. We investigated the effects of these different chiral units and that of crown ethers with different sizes on catalytic activity and enantioselectivity. During extensive parameter investigations, both conventional and emerging green solvents were screened, providing valuable α,α-disubstituted malonic ester derivatives with excellent yields (up to 98%).

The contribution of the epicardium, the outermost layer of the heart, to cardiac regeneration has remained controversial due to a lack of suitable analytical tools. By combining genetic marker-independent lineage-tracing strategies with transcriptional profiling and loss-of-function methods, we report here that the epicardium of the highly regenerative salamander species Pleurodeles waltl has an intrinsic capacity to differentiate into cardiomyocytes. Following cryoinjury, CLDN6+ epicardium-derived cells appear at the lesion site, organize into honeycomb-like structures connected via focal tight junctions and undergo transcriptional reprogramming that results in concomitant differentiation into de novo cardiomyocytes. Ablation of CLDN6+ differentiation intermediates as well as disruption of their tight junctions impairs cardiac regeneration. Salamanders constitute the evolutionarily closest species to mammals with an extensive ability to regenerate heart muscle and our results highlight the epicardium and tight junctions as key targets in efforts to promote cardiac regeneration.

Large-volume ultrastructural mapping approaches yield detailed circuit wiring diagrams but lack an integrated synaptic activity readout which is essential for functional interpretation of the connectome. Here we resolve this limitation by combining functional synaptic labelling in vivo with focused ion-beam scanning electron microscopy (FIBSEM) and machine learning-based segmentation. Our approach generates high-resolution near-isotropic three-dimensional readouts of activated vesicle pools across large populations of individual synapses in a volume of tissue, opening the way for detailed functional connectomics studies. We apply this method to measure presynaptic activity in an ultrastructural context in synapses activated by sensory input in primary visual cortex in awake head-fixed mice, showing that the numbers of recycling and non-recycling vesicles approximate to a lognormal distribution across a large number of synapses. We also demonstrate that neighbouring boutons of the same axon, which share the same spiking activity, can differ greatly in their presynaptic release probability.

Purpose Reduced functional mobility is a risk factor for falls. The Timed Up and Go test is a complex measurement tool for functional mobility. Our aims were to assess the functional mobility of: (a) community-living elderly who were participating in an exercise programme (n = 40; mean age = 73.7 years), (b) community-living elderly who were physically inactive (n = 40; mean age = 74.1 years), and (c) institutionalized elderly (n = 40; mean age = 73.5 years) and to compare the results with cut-off values for risk of fall. Materials and methods After measuring functional mobility, one-way independent ANOVAs and sample t-tests were used for analysis. Results The functional mobility of the active participants was better than that of the inactive (p p p = .990). The functional mobility of the active participants was better, whereas the functional mobility of the inactive participants was worse than the cut-off value of 13.5 s for risk of fall for community-living elderly. The functional mobility of the institutionalized participants did not differ from the 15-s reference value for predicting risk of fall. Conclusion The results indicate that regular physical activity has a positive effect on maintaining functional mobility among both community-living and institutionalized elderly individuals.

In this study, a novel approach for effective liquid-liquid microextraction based on deep eutectic solvent (DES) decomposition was suggested for the first time. It was established that DESs synthesized from tetrabutylammonium bromide and long-chain alcohols decomposed in aqueous phase resulting in in situ dispersion of organic phase and extraction of hydrophobic analyte(s). It this process long-chain alcohol acted as an extraction solvent and tetrabutylammonium bromide acted as a dispersive agent and promoted mass transfer between aqueous and organic phases as a salting out agent. Phenomenon of DES decomposition was studied in detail and applied for separation and preconcentration in chemical analysis for the first time. The developed approach was applied for 17β-estradiol microextraction from transdermal gel samples as a proof-of-concept example. The results showed that the in situ dispersed organic phase obtained can provide efficient extraction of 17β-estradiol with good extraction recovery (95 ± 5%) and excellent reproducibility (6%). The reported approach proves to be fast, simple, and inexpensive.

Abstract: Introduction: Due to fear of falling, older people may restrict their activities, causing muscle weakness and impaired balance and, consequently, admission to an institute. Accordingly, fear of falling is a common and serious health problem among older individuals. The prevalence of the fear of falling and its associated factors as well as possible preventive and therapeutic methods have been widely investigated in geriatrics. Aim: The aim of our study was to describe the prevalence of the fear of falling and its associations with demographic (age, gender) and health factors (age-related chronic diseases, functional mobility, falling in the previous year, medications) among community-living older adults. Method: Two-hundred individuals participated in the study. The fear of falling was diagnosed based on the cut-off value of the short Falls Efficacy Scale – International (FES-I). Logistic regression analysis was used to assess associations. In total, 61 participants were diagnosed with fear of falling. Results: In our sample, the fear of falling was associated with age, the number of diseases and functional mobility. Conclusion: The short FES-I is simple, easy to fill-out and has a validated Hungarian version as well. By its use, people of higher age affected by multiple chronic illnesses are primarily worth of screening in order to identify those who are in need for further more detailed examinations and, if needed, more targeted interventions. Orv Hetil. 2019; 160(5): 191–197.

This work presents the first successful applications of cinchona-thiosquaramides in asymmetric reactions. Binaphthyl-cinchona squaramides and thiosquaramides were synthesised, and then used as organocatalysts to promote the catalytic enantioselective Michael addition reaction of pentane-2,4-dione to trans-β-nitrostyrene with excellent yields (up to 99%) and enantioselectivities (up to 99% ee) at as low as 0.2 mol% catalyst loadings. Thiosquaramides gave higher enantioselectivities (up to 92% ee) in conjugate addition reaction of lawsone to β,γ-unsaturated α-keto ester than its oxo analogue, with high yields (up to 100%). Also, only thiosquaramide could catalyse the aza-Diels–Alder addition reaction of 2-siloxydiene to benzylideneacetone. Furthermore, quantum chemical computations showed that the geometrical structure of binaphthyl-cinchona thiosquaramide is similar to that of squaramide.

Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an awareness of their spatial location, a property termed positional identity. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/Rarres1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting Hoxa13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.

Salamander limb regeneration is an accurate process which gives rise exclusively to the missing structures, irrespective of the amputation level. This suggests that cells in the stump have an awareness of their spatial location, a property termed ‘positional identity’. Little is known about how positional identity is encoded, in salamanders or other biological systems. Through single-cell RNAseq analysis, we identified Tig1/Rarres1 as a potential determinant of proximal identity. Tig1 encodes a conserved cell surface molecule, is regulated by retinoic acid and exhibits a graded expression along the proximo-distal axis of the limb. Its overexpression leads to regeneration defects in the distal elements and elicits proximal displacement of blastema cells, while its neutralisation blocks proximo-distal cell surface interactions. Critically, Tig1 reprogrammes distal cells to a proximal identity, upregulating Prod1 and inhibiting Hoxa13 and distal transcriptional networks. Thus, Tig1 is a central cell surface determinant of proximal identity in the salamander limb.

Application of nucleating agents is the most versatile and industrially applied way to manipulate the crystalline structure of isotactic polypropylene (iPP). Various materials possess a nucleating effect, but from the viewpoint of dispersibility, the partially soluble ones are the most advantageous. Our objective was to synthesize new N,N′-dicyclohexyldicarboxamide homologues and study their applicability as nucleating agents in iPP. Carbon-13 nuclear magnetic resonance (13C NMR) and infrared spectroscopy were used to prove that the synthesis reactions were successful. Thermal stability of the compounds was investigated with simultaneous thermal analysis. Nucleating efficiency and solubility were characterized by polarized light microscopy and differential scanning calorimetry. Polarized light microscopy was also applied to study the effect of novel additives on the morphology of iPP. The properties, important from the viewpoint of applicability, were also investigated. Tensile tests were performed to characterize the main mechanical properties, and standard haze measurements were performed to characterize optical properties. It can be concluded that the investigated compounds are partially soluble nucleating agents and influence the crystalline structure of iPP. Most of the studied compounds have a moderate nucleating efficiency, but a very interesting dendritic structure develops in their presence. Two of them proved to be non-selective β-nucleating agents, which result in a remarkable improvement of impact resistance and higher opacity.

Physical exercise stimulates adult neurogenesis, yet the underlying mechanisms remain poorly understood. A fundamental component of the innate neuroregenerative capacity of zebrafish is the proliferative and neurogenic ability of the neural stem/progenitor cells. Here, we show that in the intact spinal cord, this plasticity response can be activated by physical exercise by demonstrating that the cholinergic neurotransmission from spinal locomotor neurons activates spinal neural stem/progenitor cells, leading to neurogenesis in the adult zebrafish. We also show that GABA acts in a non-synaptic fashion to maintain neural stem/progenitor cell quiescence in the spinal cord and that training-induced activation of neurogenesis requires a reduction of GABAA receptors. Furthermore, both pharmacological stimulation of cholinergic receptors, as well as interference with GABAergic signaling, promote functional recovery after spinal cord injury. Our findings provide a model for locomotor networks’ activity-dependent neurogenesis during homeostasis and regeneration in the adult zebrafish spinal cord., The mechanisms stimulating adult neurogenesis are unclear. Here, the authors show the contribution of cholinergic and GABAergic signalling within the locomotor network to spinal cord neurogenesis during homeostasis and regeneration, showing neurogenesis depends on circuit activity in the adult zebrafish.

How do four-legged animals adapt their locomotion to the environment? How do central and peripheral mechanisms interact within the spinal cord to produce adaptive locomotion and how is locomotion recovered when spinal circuits are perturbed? Salamanders are the only tetrapods that regenerate voluntary locomotion after full spinal transection. Given their evolutionary position, they provide a unique opportunity to bridge discoveries made in fish and mammalian models. Genetic dissection of salamander neural circuits is becoming feasible with new methods for precise manipulation, elimination, and visualisation of cells. These approaches can be combined with classical tools in neuroscience and with modelling and a robotic environment. We propose that salamanders provide a blueprint of the function, evolution, and regeneration of tetrapod locomotor circuits.

Due to sedentary lifestyle, not only the risk of many chronic diseases and multimorbidity increase, but older people also lose their functional independency earlier. The first step to design effective interventions aiming to decrease sedentary lifestyle is to explore the factors associated with sedentary lifestyle.Our aims were to describe the type and duration of sitting activities and to examine the factors associated with sedentary lifestyle, namely 1) sociodemographic factors (i.e., age, gender, education level, marital status); 2) medical factors (chronic diseases, use of walking aids); 3) lifestyle factors (i.e., duration of institutionalization, smoking status) among older people living in nursing homes providing long-term care.Data collected with questionnaire from 248 participants were analysed using logistic regression.There were 159 participants (64.1%) in total who were characterized by sedentary lifestyle. In our sample, the sedentary lifestyle was associated with the smoking status, the number of age-related chronic diseases, the duration of institutionalization, and the use of walking aids.The older people who have more chronic diseases, who are smokers and were institutionalized earlier are more likely to be characterised by sedentary lifestyle. Therefore, decision-making graduate health-care professionals should preferably focus their efforts on these older people in order to change the sedentary lifestyle by providing information about risk of this lifestyle, and offering programs relevant to older people's interests and functional status. Orv Hetil. 2020; 161(26): 1175-1180.