ACE2, the Receptor that Enables Infection by SARS-CoV-2: Biochemistry,Structure, Allostery and Evaluation of the Potential Development of ACE2 Modulators

Angiotensin converting enzyme 2 (ACE2) is the human receptor that interacts with the spike protein of coronaviruses, including the one that produced the 2020 coronavirus pandemic (COVID-19). Thus, ACE2 is a potential target for drugs that disrupt the interaction of human cells with SARS-CoV-2 to abolish infection. There is also interest in drugs that inhibit or activate ACE2, that is, for cardiovascular disorders or colitis. Compounds binding at alternative sites could allosterically affect the interaction with the spike protein. Herein, we review biochemical, chemical biology, and structural information on ACE2, including the recent cryoEM structures of full-length ACE2. We conclude that ACE2 is very dynamic and that allosteric drugs could be developed to target ACE2. At the time of the 2020 pandemic, we suggest that available ACE2 inhibitors or activators in advanced development should be tested for their ability to allosterically displace the interaction between ACE2 and the spike protein.     

Hydrogen adsorption studies in micro-size cobalt dots

Hydrogen desorption curves were obtained from a sample composed of a square arrangement of Co dots with average diameter of 4.4 μm, separated by a distance of 11.6 μm. A macroscopic sample of Co dots grown on a 2.5 × 2.5 cm Si substrate was made by standard lithographic techniques and used in these experiments. Thermal programmed desorption (TPD) was performed under ultra-high vacuum conditions. Hydrogen TPD curves were obtained from a 1 × 1 cm Co dots samples displaying a maximum of intensity at 425 K. Hydrogen TPD curve was also obtained from 1 cm× 1 cm samples of Co films and Co foils for comparison. The hydrogen TPD curves have decreasing intensity from the Co foils to the Co dots and finally to the Co films. This indicates that there are more sites for hydrogen adsorption on the Co dots than in the Co films. This is a surprising result because there is approximately 8.7 times less Co atoms exposed in the Co dots that in the Co film sample. A desorption energy of 27 kcal/mol was obtained for the Co dots suggesting that hydrogen is adsorbed on an hcp hollow site of the Co dot crystalline structure.     

Extracellular polysaccharides production by Arthrobacter viscosus

In this study the production of extracellular polysaccharides by the non-pathogenic soil bacteria Arthrobacter viscosus has been investigated. Different variables affecting extracellular polysaccharide production such as the carbon source (glucose or xylose), the agitation speed and the pH have been analysed.

In a first stage, experiments in shaken conical flasks (250 ml), containing 50 ml of culture medium, were carried out. Using xylose (25 g/l) as the carbon source at an initial pH 8 improved the extracellular polysaccharides levels obtained.

In a second stage, the experiments were scaling in bioreactors. Cultivation was carried out in discontinuous mode and with/without pH control. Polysaccharide production reached a maximum of 10 g of crude product per litre of growth medium after 14 days and the relationship between product formation and cell growth of A. viscosus is 2.7 g polysaccharide per gram biomass. This production was obtained at the optimal conditions determined with pH control at pH 7, xylose as carbon source (25 g/l) and an agitation rate of 800 rpm.     

The Possibilities of Community OR in a Third World Country

This paper shows a few possibilities for the application of Community OR in a Third World country based on experience in Venezuela. These possibilities are discussed in a framework of the relationship between the state and community organizations. Emphasis lies in showing that Community OR in Venezuela requires a deep critical commitment to emancipation in order to help community organizations develop in a rather hostile environment. Lastly, results in dealing with community organizations in Venezuela using the Interpretive Systemology approach are presented.     

Hepatic and splenic sarcoidosis: ultrasound and MR imaging

Two polypeptide antigens with molecular sizes of 34,000 daltons (34 kDa) and 38 kDa were separated from heated cells of a human clinical treponeme strain G7201 and Treponema denticola ATCC 35404, respectively. The rabbit polyclonal antisera against these antigens were produced and examined for their immunological reactions with the two heated antigens or intact spirochetal cells. Immunoblot analysis showed that the 34-kDa protein was also detected in T. denticola ATCC 35404 and ATCC 33520, and the 38-kDa protein was detected only in the two ATCC strains. Immunoelectron microscopy using the two rabbit antisera and protein A-gold complexes demonstrated that the 38-kDa protein antigen was present on the axial flagella of two T. denticola strains, and that the 34-kDa protein was located in the axial flagella of the G7201 cell, but neither in axial flagella nor on outer envelopes of the two ATCC strains cells, suggesting that the native 34-kDa axial flagellar protein of the G7201 strain may be different from that of T. denticola in terms of immunological reactivity.     

From abandonment to symbiosis: A developmental reversal in suicidal adolescents.

This article presents the abandonment-symbiosis hypothesis. This hypothesis pertains to the dynamics of suicide in youngsters who experience difficulties in separation from their symbiotic families. It is suggested that such youngsters have experienced various types of rejection and abandonment in early childhood and have developed insecure attachment styles and insufficient ego functions in order to cope with difficulties. It is also suggested that these youngsters have become scapegoats by their dysfunctional families and that they are held in a symbiotic grip in order to continue to bear the negative projections of their families. As such, they are prevented from developing a proper sense of individuation and autonomy. The sequence that begins with abandonment and continues with symbiosis is a reversal of normal development is critical for the emergence of suicidal behavior. The various aspects of the abandonment-symbiosis hypothesis are demonstrated by case studies and empirical data. A combination of individual and family treatment is recommended as the best approach for the treatment of such youngsters. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Using memory and fuzzy rules in a co-operative multi-thread strategy for optimization

In this article, we analyze a co-operative multi-thread search-based optimization strategy, where each solver thread represents a different optimization algorithm (or the same one with different settings), and they are all controlled by a centralized co-ordinator. We also propose the use of memory to keep track of both the state of the individual threads and the obtained solutions. Based on this memory, a very simple fuzzy rule base is used to control the system behavior.We also present the results of three computational experiments. The first of these checks the strategy by comparing it with an independent search strategy and a sequential algorithm, and the superiority of the co-operative scheme is confirmed. The second analyzes how definition of the threads affects the quality of the results, and the importance of there being a balanced set between intensification and diversification is corroborated. The third explores the use of memory with two different fuzzy rules, and the results indicate that the best combination is to use memory together with two rules (solver dependent and solver independent ones) (although this combination should not be activated at the beginning of the search in order to avoid premature convergence).