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.     

Interleukin-1β Modulation of the Mechanobiology of Primary Human Pulmonary Fibroblasts: Potential Implications in Lung Repair

Pro-inflammatory cytokines like interleukin-1β (IL-1β) are upregulated during early responses to tissue damage and are expected to transiently compromise the mechanical microenvironment. Fibroblasts are key regulators of tissue mechanics in the lungs and other organs. However, the effects of IL-1β on fibroblast mechanics and functions remain unclear. Here we treated human pulmonary fibroblasts from control donors with IL-1β and used Atomic Force Microscopy to unveil that IL-1β significantly reduces the stiffness of fibroblasts concomitantly with a downregulation of filamentous actin (F-actin) and alpha-smooth muscle (α-SMA). Likewise, COL1A1 mRNA was reduced, whereas that of collagenases MMP1 and MMP2 were upregulated, favoring a reduction of type-I collagen. These mechanobiology changes were functionally associated with reduced proliferation and enhanced migration upon IL-1β stimulation, which could facilitate lung repair by drawing fibroblasts to sites of tissue damage. Our observations reveal that IL-1β may reduce local tissue rigidity by acting both intracellularly and extracellularly through the downregulation of fibroblast contractility and type I collagen deposition, respectively. These IL-1β-dependent mechanical effects may enhance lung repair further by locally increasing pulmonary tissue compliance to preserve normal lung distension and function. Moreover, our results support that IL-1β provides innate anti-fibrotic protection that may be relevant during the early stages of lung repair.     

Expectations about counseling in Yucatán, Mexico: Toward a "Mexican psychology."

Conducted a study of client expectations of psychological services in Yucatán, Mexico, under the sponsorship of a grant from the Organization of American States. The Expectations about Counseling–Brief form (EAC-B) questionnaire was translated and administered to 488 subjects across age, sex, and experience with psychological services. Subsequent analyses supported the reliability and robustness of the Spanish EAC-B, with factor structure similar to the EAC-B in English. Some relation was found among age, sex, prior counseling experience, and expectations about counseling. Implications of these data for future research and comparison with U.S. subjects are discussed. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

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.     

Relationships between urbanization and the oak resource of the Minneapolis/St. Paul Metropolitan area from 1991 to 1998

Urbanization was associated with loss and transformation of the oak forest in the Twin Cities (Minneapolis and St. Paul) metropolitan area (TCMA) over a recent 7-year interval. Between 1991 and 1998, urbanization increased based on several indicators: population density, area of developed land, and area of impervious surface—total impervious area and area within three classes of increasing degree of imperviousness (protected, affected, and degraded). We quantified relationships between changes in urbanization and changes in several parameters describing the oak forest at the scale of ecological subsection. Increased total and affected impervious area were strongly correlated with decreased area of oak forest when changes of the urbanization indicators and oak were expressed as percentages of the subsection area. Relationships were reversed when changes were expressed as percentages of the 1991 values. Increased population density was strongly correlated with increased loss in numbers and increased isolation of oak patches, but weakly correlated with loss of oak forest area. This is the first study to quantify relationships between changes in urbanization and changes in a specific forest cover type. Our results demonstrate complexities of urbanization impacts on a metropolitan forest resource, and highlight the importance of selected variables, spatial and temporal scales, and expressions of change when quantifying these relationships.     

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.     

Characterization of the chicken and quail homologues of the human gene responsible for the X-linked Kallmann syndrome

The human KAL gene, responsible for the X-linked Kallmann syndrome, was isolated previously. Southern blot analysis using human cDNA probes detected cross-hybridization with DNA from several organisms, including chicken and quail. The entire coding sequences of chicken and quail KAL cDNAs were determined. A comparison of these cDNAs with the human KAL cDNA reveals an overall identity of 73 and 72%, respectively. This results in 76 and 75% identity at the protein level. The highest conservation was found in the WAP four-disulfide core motif and in two of the four fibronectin type III repeats reported in the human protein. These results further support the hypothesis that the KAL protein is an extracellular matrix component with anti-protease and adhesion functions.     

Breast-feeding and the nutritional status of nursing children in Chile

4-Pentafluoroethylumbelliferyl-beta-D-glucoside is proposed as an efficient substrate for human leukocyte acid beta-glucosidase. Its synthesis is described. This substrate was compared directly with 4-trifluoromethylumbelliferyl-beta-D-glucoside synthesized by us earlier and with 4-methylumbelliferyl-beta-D-glucoside which is commonly used for acid beta-glucosidase activity assay. The specific activity of acid beta-glucosidase with 4-pentafluoroethylumbelliferyl-beta-D-glucoside was 3- and 8-fold higher than it was with the substrates mentioned above. The kinetic parameters KM and VMAX for human leukocyte acid beta-glucosidase with the three substrates was determined. One possible application of the newly synthesized substrate is its use in the diagnosis of acid beta-glucosidase hereditary deficiency (Gaucher's disease).