scholarly journals A Perspective on Natural and Nature-Inspired Small Molecules Targeting Phosphodiesterase 9 (PDE9): Chances and Challenges against Neurodegeneration

2021 ◽  
Vol 14 (1) ◽  
pp. 58
Author(s):  
Giovanni Ribaudo ◽  
Maurizio Memo ◽  
Alessandra Gianoncelli
Keyword(s):  
Small Molecules ◽  
Microvascular Dysfunction ◽  
Structural Features ◽  
Point Of View ◽  
Protein Dimer ◽  
Suitable Target ◽  
Pde Inhibition ◽  
Chiral Species ◽  
The Brain ◽  
Structural Point

As life expectancy increases, dementia affects a growing number of people worldwide. Besides current treatments, phosphodiesterase 9 (PDE9) represents an alternative target for developing innovative small molecules to contrast neurodegeneration. PDE inhibition promotes neurotransmitter release, amelioration of microvascular dysfunction, and neuronal plasticity. This review will provide an update on natural and nature-inspired PDE9 inhibitors, with a focus on the structural features of PDE9 that encourage the development of isoform-selective ligands. The expression in the brain, the presence within its structure of a peculiar accessory pocket, the asymmetry between the two subunits composing the protein dimer, and the selectivity towards chiral species make PDE9 a suitable target to develop specific inhibitors. Additionally, the world of natural compounds is an ideal source for identifying novel, possibly asymmetric, scaffolds, and xanthines, flavonoids, neolignans, and their derivatives are currently being studied. In this review, the available literature data were interpreted and clarified, from a structural point of view, taking advantage of molecular modeling: 3D structures of ligand-target complexes were retrieved, or built, and discussed.

A crystallographic excursion in the extraordinary world of minerals: the case of Cu- and Ag-rich sulfosalts

2018 ◽  
Vol 74 (6) ◽  
pp. 527-538 ◽  
Author(s):  
Luca Bindi ◽  
Cristian Biagioni
Keyword(s):  
Materials Science ◽  
Three Dimensional ◽  
Structural Features ◽  
Point Of View ◽  
Tetrahedral Coordination ◽  
Solid State Physics ◽  
Incommensurate Modulation ◽  
Related Compounds ◽  
Variable Coordination ◽  
Structural Point

Copper and silver are common constituents in natural sulfosalts and can be present as minor or major components. Owing to the different kinds of coordination they can assume, these elements give rise to a number of sulfosalts that are usually quite complex to describe from a structural point of view because of the presence of twinning, disorder, polytypism and sometimes incommensurate modulation. Moreover, it is common to find them in different, partially occupied split sites, favoring the presence of strong ionic conductivity that can be related to a number of interesting technological properties. In this regard, a series of Cu- and Ag-rich sulfosalts showing an excess of these cations with respect to As, Sb and Bi is particularly interesting. Their crystal structures as well as their potential interest for materials science and solid-state physics are outlined. Copper- and mixed (Cu, Ag)-sulfosalts belonging to the wittichenite, tetrahedrite, galkhaite, routhierite and nowackiite series are discussed, together with some related compounds. Whereas in the wittichenite series Cu has either a trigonal planar or tetrahedral coordination, in members of the other series this element forms three-dimensional tetrahedral frameworks giving rise to cavities hosting other cations and anions. More difficult is the description of Ag-rich sulfosalts owing to the highly variable coordination environments shown by this element. Structural features of selected Ag sulfosalts together with members of the argyrodite series are discussed, highlighting the particular properties derived from the behavior of Ag.

Masonry: the brittle or plastic material?

2019 ◽  
pp. 22-28
Keyword(s):  
Plastic Material ◽  
Experimental Studies ◽  
Point Of View ◽  
Plastic Properties ◽  
Plastic Deformations ◽  
Base Materials ◽  
Stress States ◽  
Creep Deformations ◽  
Structural Point

The results of experimental studies of masonry on the action of dynamic and static (short-term and long-term) loads are presented. The possibility of plastic deformations in the masonry is analyzed for different types of force effects. The falsity of the proposed approach to the estimation of the coefficient of plasticity of masonry, taking into account the ratio of elastic and total deformations of the masonry is noted. The study of the works of Soviet scientists revealed that the masonry under the action of seismic loads refers to brittle materials in the complete absence of plastic properties in it in the process of instantaneous application of forces. For the cases of uniaxial and plane stress states of the masonry, data on the coefficient of plasticity obtained from the experiment are presented. On the basis of experimental studies the influence of the strength of the so-called base materials (brick, mortar) on the bearing capacity of the masonry, regardless of the nature of the application of forces and the type of its stress state, is noted. The analysis of works of prof. S. V. Polyakov makes it possible to draw a conclusion that at the long application of the load, characteristic for the masonry are not plastic deformations, but creep deformations. It is shown that the proposals of some authors on the need to reduce the level of adhesion of the mortar to the brick for the masonry erected in earthquake-prone regions in order to improve its plastic properties are erroneous both from the structural point of view and from the point of view of ensuring the seismic resistance of structures. It is noted that the proposal to assess the plasticity of the masonry of ceramic brick walls and large-format ceramic stone with a voidness of more than 20% is incorrect, and does not meet the work of the masonry of hollow material. On the basis of the analysis of a large number of research works it is concluded about the fragile work of masonry.

DIRECTIONS OF ASSOCIATIVE IDENTIFICATION OF PERSONAL NAMES

2019 ◽  
Vol 18 (28) ◽  
pp. 118-128
Author(s):  
Olena Karpenko ◽  
Tetiana Stoianova
Keyword(s):  
Proper Names ◽  
Mental Lexicon ◽  
Point Of View ◽  
Sound Symbolism ◽  
Personal Names ◽  
Communicative Process ◽  
Proper Name ◽  
Definition Of ◽  
Scientific Value ◽  
The Brain

The article is devoted to the study of personal names from a cognitive point of view. The study is based on the cognitive concept that speech actually exists not in the speech, not in linguistic writings and dictionaries, but in consciousness, in the mental lexicon, in the language of the brain. The conditions for identifying personal names can encompass not only the context, encyclopedias, and reference books, but also the sound form of the word. In the communicative process, during a free associative experiment, which included a name and a recipient’s mental lexicon. The recipient was assigned a task to quickly give some association to the name. The aggregate of a certain number of reactions of different recipients forms the associative field of a proper name. The associative experiment creates the best conditions for identifying the lexeme. The definition of a monosemantic personal name primarily includes the search of what it denotes, while during the process of identifying a polysemantic personal name recipients tend have different reactions. Scientific value is posed by the effect of the choice of letters for the name, sound symbolism, etc. The following belong to the generalized forms of identification: usage of a hyperonym; synonyms and periphrases or simple descriptions; associations denoting the whole (name stimulus) by reference to its part (associatives); cognitive structures such as “stimulus — association” and “whole (stimulus) — part (associative)”; lack of adjacency; mysterious associations. The topicality of the study is determined by its perspective to identify the directions of associative identification of proper names, which is one of the branches of cognitive onomastics. The purpose of the study is to identify, review, and highlight the directions of associative identification of proper names; the object of the research is the names in their entirety and variety; its subject is the existence of names in the mental lexicon, which determines the need for singling out the directions for the associative identification of the personal names.

Crimes against marriage and family before Criminal Code 1968

2020 ◽  
Vol 15 (1-3) ◽  
pp. 44-59
Author(s):  
Lidia Peneva
Keyword(s):  
Criminal Code ◽  
Point Of View ◽  
Marriage And Family ◽  
Historical Method ◽  
Legal Method ◽  
The Subject ◽  
The Republic ◽  
Criminal Groups ◽  
The Moment ◽  
Structural Point

Crimes against marriage and family are a particular group of social relation­ships that the law has defended properly in view of the high public significance and value they enjoy. At the moment they are regulated in Chapter VI, Section I, of the specific part of the Penal Code the Repub­lic of Bulgaria. The subject matter of this Statement will, however, be the legisla­tive provisions concerning these criminal­ized acts in retrospect. The purpose of the study is to show by historical method and through the comparatively legal method the development of these criminal groups during the periods of various criminal laws in Bulgaria. This will also provide a basis for reflection on possible de lege ferenda proposals. This report from a structural point of view will be divided into three distinct points, marking each of the penal laws in the Republic of Bulgaria, which were in force before 1968.

THE USE OF THE TRANSLATION METHOD IN MASTERING THE TERMS

2019 ◽  
pp. 87-95
Keyword(s):  
International Relations ◽  
English Language ◽  
Structural Features ◽  
Point Of View ◽  
General Classification ◽  
Optimal Methods ◽  
Foreign Companies ◽  
The Social ◽  
Problems Of Translation

The article is devoted to the role of Tourism terminology in linguistics and the issue of general classification, peculiarities in the expression and translation of terms related to tourism in English into Uzbek and Russian, as well as the choice of the most optimal methods for translating terms in accordance with the requirements of this professional sphere. The terminology of the English language tourism is distinguished by its brightness, versatility. Tourism terms are formed under the influence of a generalized lexical layer of language and perform a specific functional function.Tourism terms are formed through the affixation method (prefixation, suffixation, circumphixation) and get rich through the process.The terminology of English Tourism is distinguished by its content and structural features, forming a part of the language vocabulary from the linguistic point of view. Texts in the field of Tourism take into their composition concepts of Tourism and interpret them in their content. They will be mainly in the form of advertising, as well as enlighten information about a particular region or place, create informational precedents and ensure their manifestation in the social cultural presence. The relevance of the study of the problems of translation of terms in the field of tourism has been investigated, mainly due to the development of international relations, expansion of cooperation between local and foreign companies, as well as the increase in this area of communication.

Subjectivity as a sentient perspective and the role of interoception

2018 ◽  
Author(s):  
Helena De Preester
Keyword(s):  
Crucial Role ◽  
Point Of View ◽  
Basic Form ◽  
Bodily States ◽  
The Brain ◽  
Phenomenological Point

This chapter argues that the most basic form of subjectivity is different from and more fundamental than having a self, and forwards a hypothesis about the origin of subjectivity in terms of interoception. None of those topics are new, and a consensus concerning the homeostatic-interoceptive origin of subjectivity is rapidly growing in the domains of the neurosciences and psychology. This chapter critically explores that growing consensus, and it argues that the idea that the brain topographically represents bodily states is unfit for thinking about the coming about of subjectivity. In the first part, four inherent characteristics of subjectivity are discussed from a philosophical phenomenological point of view. The second part explores whether a model of subjectivity in which interoception maintains its crucial role is possible without relying on topographical representations of the in-depth body, and giving due to the inherent characteristics of subjectivity.

scholarly journals Recuperative Amino Acids Separation through Cellulose Derivative Membranes with Microporous Polypropylene Fiber Matrix

Membranes ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 429
Author(s):  
Aurelia Cristina Nechifor ◽  
Andreia Pîrțac ◽  
Paul Constantin Albu ◽  
Alexandra Raluca Grosu ◽  
Florina Dumitru ◽  
...  
Keyword(s):  
Amino Acids ◽  
Cellulose Acetate ◽  
Polypropylene Fiber ◽  
Point Of View ◽  
Hydroxyethyl Cellulose ◽  
Separation Performance ◽  
Thermal Gravimetric Analyzer ◽  
Microfiltration Membranes ◽  
Ft Ir ◽  
Structural Point

The separation, concentration and transport of the amino acids through membranes have been continuously developed due to the multitude of interest amino acids of interest and the sources from which they must be recovered. At the same time, the types of membranes used in the sepa-ration of the amino acids are the most diverse: liquids, ion exchangers, inorganic, polymeric or composites. This paper addresses the recuperative separation of three amino acids (alanine, phe-nylalanine, and methionine) using membranes from cellulosic derivatives in polypropylene ma-trix. The microfiltration membranes (polypropylene hollow fibers) were impregnated with solu-tions of some cellulosic derivatives: cellulose acetate, 2-hydroxyethyl-cellulose, methyl 2-hydroxyethyl-celluloseand sodium carboxymethyl-cellulose. The obtained membranes were characterized in terms of the separation performance of the amino acids considered (retention, flux, and selectivity) and from a morphological and structural point of view: scanning electron microscopy (SEM), high resolution SEM (HR-SEM), Fourier transform infrared spectroscopy (FT-IR), energy dispersive spectroscopy (EDS) and thermal gravimetric analyzer (TGA). The re-sults obtained show that phenylalanine has the highest fluxes through all four types of mem-branes, followed by methionine and alanine. Of the four kinds of membrane, the most suitable for recuperative separation of the considered amino acids are those based on cellulose acetate and methyl 2-hydroxyethyl-cellulose.

scholarly journals 4,7-Disubstituted 7H-Pyrrolo[2,3-d]pyrimidines and Their Analogs as Antiviral Agents against Zika Virus

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3779
Author(s):  
Ruben Soto-Acosta ◽  
Eunkyung Jung ◽  
Li Qiu ◽  
Daniel J. Wilson ◽  
Robert J. Geraghty ◽  
...  
Keyword(s):  
Antiviral Activity ◽  
Dengue Virus ◽  
Small Molecules ◽  
Zika Virus ◽  
Antiviral Agents ◽  
Structural Features ◽  
Molecular Target ◽  
Core Structure ◽  
Human Pathogens ◽  
Important Group

Discovery of compound 1 as a Zika virus (ZIKV) inhibitor has prompted us to investigate its 7H-pyrrolo[2,3-d]pyrimidine scaffold, revealing structural features that elicit antiviral activity. Furthermore, we have demonstrated that 9H-purine or 1H-pyrazolo[3,4-d]pyrimidine can serve as an alternative core structure. Overall, we have identified 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs including compounds 1, 8 and 11 as promising antiviral agents against flaviviruses ZIKV and dengue virus (DENV). While the molecular target of these compounds is yet to be elucidated, 4,7-disubstituted 7H-pyrrolo[2,3-d]pyrimidines and their analogs are new chemotypes in the design of small molecules against flaviviruses, an important group of human pathogens.

Information-based decoding of the coupling among human brain activity and movement paths

2021 ◽  
pp. 1-10
Author(s):  
Shahul Mujib Kamal ◽  
Norazryana Mat Dawi ◽  
Hamidreza Namazi
Keyword(s):  
Brain Activity ◽  
Point Of View ◽  
Physiological Signals ◽  
Human Walking ◽  
Eeg Signals ◽  
Rehabilitation Science ◽  
Information Contents ◽  
First Time ◽  
The Brain ◽  
Brain Reaction

BACKGROUND: Walking like many other actions of a human is controlled by the brain through the nervous system. In fact, if a problem occurs in our brain, we cannot walk correctly. Therefore, the analysis of the coupling of brain activity and walking is very important especially in rehabilitation science. The complexity of movement paths is one of the factors that affect human walking. For instance, if we walk on a path that is more complex, our brain activity increases to adjust our movements. OBJECTIVE: This study for the first time analyzed the coupling of walking paths and brain reaction from the information point of view. METHODS: We analyzed the Shannon entropy for electroencephalography (EEG) signals versus the walking paths in order to relate their information contents. RESULTS: According to the results, walking on a path that contains more information causes more information in EEG signals. A strong correlation (p= 0.9999) was observed between the information contents of EEG signals and walking paths. Our method of analysis can also be used to investigate the relation among other physiological signals of a human and walking paths, which has great benefits in rehabilitation science.

scholarly journals Crystallographic and structural characterization of heterometallic platinum compounds Part VII. Heterohepta- and heterooctanuclear clusters

2014 ◽  
Vol 13 (1) ◽  
Author(s):  
Milan Melnik ◽  
Peter Mikuš ◽  
Clive E. Holloway
Keyword(s):  
Structural Characterization ◽  
Structural Parameters ◽  
Bond Distance ◽  
Point Of View ◽  
Platinum Compounds ◽  
Metal Atoms ◽  
Platinum Clusters ◽  
Structural Point

AbstractThis review classifies and analyzes over fifty heterohepta- and heterooctanuclear platinum clusters. There are eight types of metal combinations in heteroheptanuclear: Pt6M, Pt5M2, Pt4M3, Pt3M4, Pt2M5, PtM6, Pt3Hg2Ru2 and Pt2Os3Fe2. The seven metal atoms are in a wide variety of arrangements, with the most common being one in which the central M atom (mostly M(I)) is sandwiched by two M3 triangles. Another arrangement often found is an octahedron of M6 atoms asymmetrically capped by an M atom. The shortest Pt-M bond distances (non-transition and transition) are 2.326(1) Å (M = Ga) and 2.537(6) Å (M = Fe). The shortest Pt-Pt bond distance is 2.576(2) Å.In heterooctanuclear platinum clusters there are eight types of metal combinations: Pt6M2, Pt4M4, Pt3Ru5, Pt2M6, PtM7, Pt2W4Ni2, PtAu6Hg and PtAu5Hg2. From a structural point of view, the clusters are complex with bicapped octahedrons of eight metal atoms prevailing. The shortest Pt-M bond distances (non-transition and transition) are 2.651(3) Å (M = Hg) and 2.624(1) Å (M = Os). The shortest Pt-Pt bond distance is 2.622(1) Å. These values are somewhat longer than those in the heteroheptanuclear clusters. Several relationships between the structural parameters were found, and are discussed and compared with the smaller heterometallic platinum clusters

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