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.     

Influence of the Temperature on Coccolith-Containing Systems from Emiliania huxleyi Cultivations

Thermogravimetric analysis of a coccolith-containing biogenic broth showed a three-step degradation process. According to this system behavior, the biogenic broth was heated to specific temperatures and characterized in terms of its morphology, surface chemistry, and crystallinity. The elemental and organic composition of the treated samples was also evaluated and compared to the reference material. The presented results were acquired in an effort to exploit pretreatment scenarios for such a biogenic system that would improve and support a separation process.     

Health research in the developing world: a gastroenterological view from Bangladesh

OBJECTIVES: To identify knowledge levels of academic surgeons about Food and Drug Administration (FDA) and Institutional Review Board (IRB) regulations for clinical research and to determine whether being a member in an IRB, conducting or participating in clinical trials, or being a member in surgical societies affected knowledge levels. DESIGN: Survey of surgical department faculty members in 20 universities. RESULTS: Sixty-five responses were received from 14 sites. Overall mean (+/- SEM) correct score was 6.7 +/- 0.2 of a possible 20 points. The best predictor of overall score was being a primary investigator of a clinical trial (P < .001), followed by being or having been a member of an IRB (P < or = .02). The total mean score of members of the Surgical Infection Society (8.2 +/- 0.5) was significantly higher (P < .001) than that of nonmembers (6.1 +/- 0.2), a phenomenon not observed with other surgical societies. In certain hypothetical clinical scenarios, all respondents were mistakenly willing to conduct clinical trials without obtaining appropriate approval from the FDA. Four (22%) of 18 IRB member respondents and 16 (25%) of the 65 respondents were willing to conduct human research without appropriate approval from patients, the IRB, or both. CONCLUSIONS: Knowledge deficits exist in the academic surgical community about the role and requirements of the FDA and local IRBs for conducting clinical research. Further study is required to determine the reasons for this deficit and to identify appropriate interventions.     

Cloning and disruption of the antigenic catalase gene of Aspergillus fumigatus

Aspergillus fumigatus possesses two catalases (described as fast and slow on the basis of their electrophoretic mobility). The slow catalase has been recognized as a diagnostic antigen for aspergillosis in immunocompetent patients. The antigenic catalase has been purified. The enzyme is a tetrameric protein composed of 90-kDa subunits. The corresponding cat1 gene was cloned, and sequencing data show that the cat1 gene codes for a 728-amino-acid polypeptide. A recombinant protein expressed in Pichia pastoris is enzymatically active and has biochemical and antigenic properties that are similar to those of the wild-type catalase. Molecular experiments reveal that CAT1 contains a signal peptide and a propeptide of 15 and 12 amino acid residues, respectively. cat1-disrupted mutants that were unable to produce the slow catalase were as sensitive to H2O2 and polymorphonuclear cells as the wild-type strain. In addition, there was no difference in pathogenicity between the cat1 mutant and its parental cat1+ strain in a murine model of aspergillosis.     

Driver detection and recognition of lineside signals and signs at different approach speeds

A study was carried out using simulation to investigate driver responses to lineside signals and signs at various approach speeds. The objectives of the study were: (1) to find out whether train speed would significantly affect signal/sign reading; (2) to examine at which point certain types of signs or signals could be detected or recognised, and (3) to determine a speed cut-off level above which certain types of signs or signals are no longer recognisable or detectable. Fifty-seven train drivers from 12 Train Operating Companies in the UK participated in the trials. Twenty different types of lineside signs and ten types of signals were tested under six different approach speeds ranging from 100 to 350 km/h (62–218 mph). Driver performance measures were ‘time remaining to the signal/sign’ at the point of detection or recognition, and reading error rate. The results showed a significant influence of train speed on driver responses to lineside signals/signs and demonstrated a non-linear relationship between driver responses to signals/signs and approach speed. This has been used to estimate a maximum approach speed limit within which a specific signal or sign can be correctly detected or recognised. The findings and implications of the study are discussed in the paper.     

The social consequences of expressive suppression.

At times, people keep their emotions from showing during social interactions. The authors' analysis suggests that such expressive suppression should disrupt communication and increase stress levels. To test this hypothesis, the authors conducted 2 studies in which unacquainted pairs of women discussed an upsetting topic. In Study 1, one member of each pair was randomly assigned to (a) suppress her emotional behavior, (b) respond naturally, or (c) cognitively reappraise in a way that reduced emotional responding. Suppression alone disrupted communication and magnified blood pressure responses in the suppressors' partners. In Study 2, suppression had a negative impact on the regulators' emotional experience and increased blood pressure in both regulators and their partners. Suppression also reduced rapport and inhibited relationship formation. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Inorganic–organic hybrid materials with zirconium oxoclusters as protective coatings on aluminium alloys

Inorganic–organic hybrid materials are attracting a strong scientific interest mainly for their outstanding inherent mechanical and thermal properties, which can be traced back to the intimate coupling of both inorganic and organic components. By carefully choosing the experimental parameters used for their synthesis, chemically and thermally stable acrylate-based hybrid material embedding the zirconium oxocluster Zr₄O₄(OMc)₁₂, where OMcCH₂C(CH₃)C(O)O, can be deposited as UV-cured films on aluminium alloys.

In particular, the molar ratios between the oxocluster and the monomer, the polymerisation time, the amount of photo-initiator and the deposition conditions, by using an home-made spray-coating equipment, were optimised in order to obtain the best performing layers in terms of transparency and hardness to coat aluminium alloy (AA1050, AA6060 and AA2024) sheets. Furthermore, it was also evaluated whether the hybrid coatings behave as barrier to corrosion.

Several coated samples were prepared and characterised. Environmental scanning electronic microscopy (ESEM) and scratch test were used to investigate the morphology of the films and to evaluate their scratch resistance, respectively. Electrochemical impedance spectroscopy (EIS) was performed in order to evaluate if the coatings actually protect the metallic substrate from corrosion.

In order to measure shear storage modulus (G′) and loss modulus (G″) of the materials used for coatings, bulk samples were also obtained by UV-curing of the precursors solution. Dynamical mechanical thermal analysis (DMTA) was performed in shear mode on cured disks of both the hybrid materials and pristine polymer for comparison. The values of T_g were read off as the temperatures of peak of loss modulus. The length and mass of all the samples were measured before and after the DMTA analysis, so that the shrinkage of the materials in that temperature range was exactly evaluated.     

Prevalence of weight reducing and weight gaining in adolescent girls and boys.

Surveyed the prevalence of weight reducing and weight gaining in 1,373 high school students. 63% of the girls and 16.2% of the boys reported being on weight-reducing regimens; 9.1% of the girls and 28.4% of the boys were trying to gain weight. Most female reducers and male gainers were already normal weight. Whites and Hispanics were more likely to be reducing, whereas Blacks were more likely to be gaining. Exercise and moderate caloric reduction were most popular for weight reducing, and a small but significant number were regularly using fasting, vomiting, laxatives, and appetite suppressants. The rate of weight reducing in female high school adolescents has increased significantly since similar surveys of American youths 20 yrs ago. (PsycINFO Database Record (c) 2010 APA, all rights reserved)