Rebuild the Academy: Supporting academic mothers during COVID-19 and beyond

The issues facing academic mothers have been discussed for decades. Coronavirus Disease 2019 (COVID-19) is further exposing these inequalities as womxn scientists who are parenting while also engaging in a combination of academic related duties are falling behind. These inequities can be solved by investing strategically in solutions. Here we describe strategies that would ensure a more equitable academy for working mothers now and in the future. While the data are clear that mothers are being disproportionately impacted by COVID-19, many groups could benefit from these strategies. Rather than rebuilding what we once knew, let us be the architects of a new world.

The COVID-19 pandemic is highlighting the many long-standing inequalities that academic mothers face. This Essay describes solutions for a more equitable academia, now and in the future, maintaining that rather than rebuilding what we once knew, we should be the architects of a new world.     

Thermodynamics of carbonic anhydrase catalysis. A comparison between human isoenzymes B and C

The CO2 hydration and HCO3- dehydration activities of human red cell carbonic anhydrase isozymes B and C (HCAB and HCAC) have been studied as a function of temperature from 0 degrees to 37 degrees C. The Arrhenius plots of ln kcat versus 1/T are linear for both isozymes in both hydration and dehydration reactions, indicating that the rate-determining steps remain unchanged over this temperature range. The 37 degrees C hydration kcat, at pH 7.5, is 13 X 10(5) s-1 for isozyme C and 0.71 X 10(5) s-1 for isozyme B. Km, for hydration, is 10 mM for C and 5 mM for B, and invariant with temperature. The uncatalyzed reactions are significantly affected by temperature, 30- to 40-fold rate enhancements being observed from 0 degrees to 37 degrees C. The enzyme-catalyzed processes are much less sensitive to temperature, the rate enhancements being 2- to 3-fold for HCAB and 5- to 6-fold for HCAC in this temperature range. These observations are consistent with a significant lowering of the free energy of activation by both isozymes. This effect is greater for C accounting for its higher catalytic power. The enthalpy of activation, at pH 7.5 and 8.2, in the rate-limiting step is considerably less for the B enzyme compared to C. This is, however, more than offset by a large negative entropy of activation in the case of HCAB. This observation indicates either a mechanistic difference in the rate-limiting events or a difference in the structural organizations of the active sites of the two isozymes, or both.     

Bioavailability of apocynin through its conversion to glycoconjugate but not to diapocynin

Apocynin (4-hydroxy-3-methoxyacetophenone) is a major active ingredient from the rhizomes of Picrorhiza kurroa, a botanical plant used as an herbal medicine for treatment of a number of inflammatory diseases. Recently, apocynin is regarded as a specific inhibitor for NADPH oxidase in cell and animal models. In vitro studies indicated conversion of apocynin to diapocynin in the presence of peroxidases, e.g., myloperoxidase, posing the possibility that diapocynin also contributes to the anti-oxidative action of apocynin. The objectives of this study are to examine the bioavailability of apocynin to plasma, liver and brain tissue after intraperitoneal (i.p.) injection, and to examine whether apocynin is converted to diapocynin in vivo. Diapocynin was chemically synthetized and characterized by NMR and IR. Apocynin (5 mg/kg body wt) was injected i.p. to adult male Sprague-Dawley rats and plasma, liver and brain were collected at different times (30 min, 1 and 2 h) after injection. Samples were treated with β-glucuronidase to hydrolyze the glycosyl linkage and analyzed by HPLC/MS. At 30 min and 1 h after injection, approximately 50% of apocynin was converted to its glycosyl derivative and was distributed in plasma, liver and brain. No diapocynin was detected in any samples. These results indicate rapid glycosylation of apocynin and its transport to blood and other organs but no apparent conversion to diapocynin in vivo.     

Acetazolamide does not disrupt limb regenerate morphogenesis in the salamander, Plethodon cinereus

Acetazolamide, a potent and highly specific inhibitor of carbonic anhydrase, is teratogenic in mammalian embryos and when administered during early limb development causes unique limb defects in a time- and dose-dependent manner. The regenerating urodele limb is often considered to be a good experimental analog of limb development and, if it employs the same mechanisms of tissue interactions during pattern formation, should be susceptible to teratogens which selectively disrupt developmental limb patterning. This study demonstrates that while carbonic anhydrase inhibition is toxic to the red-backed salamander, Plethodon cinereus, it does not have the same teratogenic effect on limb regeneration as seen in mammalian limb development. Several points are considered as to why the regenerating limb, at least in this salamander species, may not be suitable for studying this class of teratogen.