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.     

Consequences of dietary energy source and energy level on energy balance,lactogenic hormones,and lactation curve characteristics of cows after a short or omitted dry period

Omitting the dry period (DP) generally reduces milk production in the subsequent lactation. The aim of this study was to evaluate the effect of dietary energy source—glucogenic (G) or lipogenic (L)—and energy level—standard (std) or low—on milk production; energy balance (EB); lactogenic hormones insulin, insulin-like growth factor 1 (IGF-1), and growth hormone (GH); and lactation curve characteristics between wk 1 and 44 postpartum in cows after a 0-d or 30-d DP. Cows (n = 110) were assigned randomly to 3 transition treatments: a 30-d DP with a standard energy level required for expected milk yield [30-d DP(std)], a 0-d DP with the same energy level as cows with a 30-d DP [0-d DP(std)], and a 0-d DP with a low energy level [0-d DP(low)]. In wk 1 to 7, cows were fed the same basal ration but the level of concentrate increased to 6.7 kg/d for cows fed the low energy level and to 8.5 kg/d for cows fed the standard energy level in wk 4. From wk 8 postpartum onward, cows received a G ration (mainly consisting of corn silage and grass silage) or an L ration (mainly consisting of grass silage and sugar beet pulp) with the same energy level contrast (low or std) as in early lactation. Cows fed the G ration had greater milk, lactose, and protein yields, lower milk fat percentage, greater dry matter and energy intakes, and greater plasma IGF-1 concentration compared with cows fed the L ration. Dietary energy source did not affect EB or lactation curve characteristics. In cows with a 0-d DP, the reduced energy level decreased energy intake, EB, and weekly body weight gain, but did not affect milk production or lactation curve characteristics. A 30-d DP resulted in a greater total predicted lactation yield, initial milk yield after calving, peak milk yield, energy intake, energy output in milk, days to conception [only when compared with 0-d DP(low)], plasma GH concentration [only when compared with 0-d DP(std)], and decreased weekly body weight gain compared with a 0-d DP. A 30-d DP decreased both the increasing and the declining slope parameters of the lactation curve and the relative rate of decline in milk yield (indicating greater lactation persistency) compared with a 0-d DP, and decreased plasma insulin and IGF-1 concentration, and EB. In conclusion, feeding a G ration after wk 7 in milk improved energy intake and milk production, but did not affect EB compared with an L ration. For cows without a DP, a reduced dietary energy level did not affect milk production and lactation curve characteristics, but did decrease EB and weekly body weight gain. A 30-d DP increased milk yield and lactation persistency, but decreased milk fat and protein content, EB, and plasma insulin and IGF-1, compared with a 0-d DP.     

Transport of testosterone and estrogen from dairy-farm waste lagoons to groundwater

Although concentrated animal feeding operations constantly generate physiologically active steroidal hormones, little is known of their environmental fate. Estrogen and testosterone concentrations in groundwater and their distribution in sediments below a dairy-farm wastewater lagoon were therefore determined and compared to a reference site located upgradient of the farm. Forward simulations of flow as well as estrogen and testosterone transport were conducted based on data from the sediment profile obtained during drilling of a monitoring well belowthe dairy-farm waste lagoon. Testosterone and estrogen were detected in sediments to depths of 45 and 32 m, respectively. Groundwater samples were directly impacted by the dairy farm, as evidenced by elevated concentrations of nitrate, chloride, testosterone, and estrogen as compared to the reference site. Modeling potential transport of hormones in the vadose zone via advection, dispersion, and sorption could not explain the depths at which estrogen and testosterone were found, suggesting that other transport mechanisms influence hormone transport under field conditions. These mechanisms may involve interactions between hormones and manure as well as preferential flow paths, leading to enhanced transport rates. These types of interactions should be further investigated to understand the processes regulating hormone transport in the subsurface environment and parametrized to forecast long-term fate and transport of steroidal hormones.     

Protection and advocacy system standing--to vindicate the rights of persons with disabilities

A characteristic of perinatal encephalopathies are the distinct patterns of neuronal and glial cell loss. Cerebral hypoperfusion is thought to be a major cause of these lesions. Gestational age is likely to influence outcome. This study compares the cortical electrophysiologic and histopathologic responses to hypoperfusion injury between preterm and near term fetuses. Chronically instrumented 0.65 (93-99-d, n = 9) and 0.9 (119-133-d, n = 6) gestation fetal sheep underwent 30 min of cerebral hypoperfusion injury. The parasagittal cortical EEG and impedance (measure of cytotoxic edema) responses plus histologic outcome (3 d) were compared. The acute rise in impedance was similar in amplitude, but the onset was delayed (5.0 +/- 0.7 versus 9.1 +/- 1.1 min, p < 0.05) in the preterm fetuses relative to those near term. In contrast the extent of the secondary rise was reduced (p < 0.01) and peaked earlier in the preterm fetuses (19.8 +/- 1.0 versus 40.5 +/- 3.5 h, p < 0.01). Both groups had a similar fall in EEG spectral edge frequency. The preterm fetuses had a milder loss of EEG intensity at 72 h (-7.7 +/- 1.5 versus -12.8 +/- 0.9 dB, p < 0.05). At both ages there was a predominantly parasagittal cortical distribution of damage with a similar pattern of neuronal loss in the thalamus and striatum. There was extensive selective neuronal loss within the upper layers of the cortex in those near term. In contrast the preterm fetuses developed subcortical infarcts (p < 0.05). The cortical response to injury altered during the last trimester. The results suggest the severity of the delayed phase of cortical neuronal injury and selective neuronal loss increased near term. In contrast, the preterm fetuses had a more rapidly evolving injury leading to necrosis of the subcortical white matter.     

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)     

Lipopeptide phytotoxins produced by Pseudomonas syringae pv. syringae: comparison of the biosurfactant and ion channel-forming activities of syringopeptin and syringomycin

The maturational status of Adelta and C-fibers in the fetal rat spinal cord was examined using formalin-induced c-fos expression as a marker for neuronal activities. Awake 19-, 20-, and 21-day fetuses (FD) were injected ex utero with 5 microl of 10% formalin either into the ventral aspect of the forepaw or the hindpaw. FD 19 fetuses showed little response to the injection, but with increasing age, the fetuses exhibited more specific behaviors following injury of the paw. By FD 21, fetuses treated with formalin injection showed body curls and twitches, mouth opening, face wiping, and withdrawal of the injected paw. The anatomical data paralleled that of behavior; FD 19 animals expressed a small number of Fos labeled nuclei following the formalin injection that was not statistically different from control animals. The formalin-induced increase in Fos staining was first observed at FD 20 with a large increase in the number of Fos labeled cell occurring between FD 20 and 21. By FD 21, the pattern of Fos stained nuclei resembled that found in neonatal rats. There was constitutive bilateral staining in all untreated, saline and formalin injected fetuses that is unique to prenatal animals. Formalin treated fetuses showed constitutive level of staining in addition to the increase in the c-fos expression caused by formalin. We have thus demonstrated that, as indexed both by behavioral response and by Fos immunoreactivity, rat fetuses are capable of transmitting and responding to noxious input before birth.     

Atmospheric trace gas analysis with cavity ring-down spectroscopy

Cavity ring-down spectroscopy (CRDS) is a highly sensitive laser absorption method. It can be used for quantitative analysis of molecular species at the sub-ppb level. The absorption cell (cavity) is sealed by two high-reflective mirrors on each side, which results in an effective absorption path-length of some kilometers. Our experiments for atmospheric gas analysis have been carried out so far with an Excimer pumped dye laser in the UV-VIS and a CO overtone sideband laser in the wavelength region around 3 μm. Experiments with an all solid-state difference frequency laser system will follow. In the UV-VIS region, we measured trace gas molecules like SO₂, NO₂, and CH₂O. In the mid-infrared, around 3 μm, we measured hydrocarbons like CH₄, C₂H₆, and C₂H₄ with a detection limit of less than 1 ppb. The noise equivalent absorption coefficients in the MIR are in the order of 1.7·10⁻⁹ cm⁻¹. Due to the high data acquisition rate and the high sensitivity, CRDS enables real-time detection of trace gases in ambient air.