Role of ACE2 in pregnancy and potential implications for COVID-19 susceptibility.

In times of coronavirus disease 2019 (COVID-19), the impact of severe acute respiratory syndrome (SARS)-coronavirus (CoV)-2 infection on pregnancy is still unclear. The presence of angiotensin-converting enzyme (ACE) 2 (ACE2), the main receptor for SARS-CoV-2, in human placentas indicates that this organ can be vulnerable for viral infection during pregnancy. However, for this to happen, additional molecular processes are critical to allow viral entry in cells, its replication and disease manifestation, particularly in the placenta and/or feto-maternal circulation. Beyond the risk of vertical transmission, COVID-19 is also proposed to deplete ACE2 protein and its biological actions in the placenta. It is postulated that such effects may impair essential processes during placentation and maternal hemodynamic adaptations in COVID-19 pregnancy, features also observed in several disorders of pregnancy. This review gathers information indicating risks and protective features related to ACE2 changes in COVID-19 pregnancies. First, we describe the mechanisms of SARS-CoV-2 infection having ACE2 as a main entry door and current evidence of viral infection in the placenta. Further, we discuss the central role of ACE2 in physiological systems such as the renin-angiotensin system (RAS) and the kallikrein-kinin system (KKS), both active during placentation and hemodynamic adaptations of pregnancy. Significant knowledge gaps are also identified and should be urgently filled to better understand the fate of ACE2 in COVID-19 pregnancies and the potential associated risks. Emerging knowledge will be able to improve the early stratification of high-risk pregnancies with COVID-19 exposure as well as to guide better management and follow-up of these mothers and their children.

Latitudinal species diversity gradient of marine zooplankton for the last three million years.

High tropical and low polar biodiversity is one of the most fundamental patterns characterising marine ecosystems, and the influence of temperature on such marine latitudinal diversity gradients is increasingly well documented. However, the temporal stability of quantitative relationships among diversity, latitude and temperature is largely unknown. Herein we document marine zooplankton species diversity patterns at four time slices [modern, Last Glacial Maximum (18,000 years ago), last interglacial (120,000 years ago), and Pliocene (~3.3-3.0 million years ago)] and show that, although the diversity-latitude relationship has been dynamic, diversity-temperature relationships are remarkably constant over the past three million years. These results suggest that species diversity is rapidly reorganised as species' ranges respond to temperature change on ecological time scales, and that the ecological impact of future human-induced temperature change may be partly predictable from fossil and paleoclimatological records.

Thirteen-lined ground squirrels (Ictidomys tridecemlineatus) show microstructural bone loss during hibernation but preserve bone macrostructural geometry and strength.

Lack of activity causes bone loss In most animals. Hibernating bears have physiological processes to prevent cortical and trabecular bone loss associated with reduced physical activity, but different mechanisms of torpor among hibernating species may lead to differences in skeletal responses to hibernation. There are conflicting reports regarding whether small mammals experience bone loss during hibernation. To investigate this phenomenon, we measured cortical and trabecular bone properties in physically active and hibernating juvenile and adult 13-lined ground squirrels (Ictidomys tridecemlineatus, previous genus name Spermophilus). Cortical bone geometry, strength and mineral content were similar in hibernating compared with active squirrels, suggesting that hibernation did not cause macrostructural cortical bone loss. Osteocyte lacunar size increased (linear regression, P=0.001) over the course of hibernation in juvenile squirrels, which may indicate an osteocytic role in mineral homeostasis during hibernation. Osteocyte lacunar density and porosity were greater (+44 and +59%, respectively; P<0.0001) in hibernating compared with active squirrels, which may reflect a decrease in osteoblastic activity (per cell) during hibernation. Trabecular bone volume fraction in the proximal tibia was decreased (-20%; P=0.028) in hibernating compared with physically active adult squirrels, but was not different between hibernating and active juvenile squirrels. Taken together, these data suggest that 13-lined ground squirrels may be unable to prevent microstructural losses of cortical and trabecular bone during hibernation, but importantly may possess a biological mechanism to preserve cortical bone macrostructure and strength during hibernation, thus preventing an increased risk of bone fracture during remobilization in the spring.

Both aldosterone and spironolactone can modulate the intracellular ACE/ANG II/AT1 and ACE2/ANG (1-7)/MAS receptor axes in human mesangial cells.

The kidney is an important target of the renin-ANG-aldosterone system (RAAS). To date, several studies have demonstrated the existence of a local RAAS in various tissues, including the renal tissue. The mineralocorticoid aldosterone is known to play a critical role in the classical RAAS; however, its effect on mesangial cells (MCs) remains to be elucidated. Based on this, our aim was to investigate whether aldosterone stimulation can modulate the intracellular RAAS of immortalized human MCs by evaluating ANG-converting enzyme (ACE)/ANG II/ANG II receptor type 1 (AT1) and ANG-converting enzyme 2 (ACE2)/ANG (1-7)/MAS receptor axes. To realise this, protein expression, enzyme activity, and immunofluorescence were performed under aldosterone stimulation and in the presence of the mineralocorticoid receptor (MR) antagonist spironolactone (SPI). We observed that high doses of aldosterone increase ACE activity. The effect of aldosterone on the catalytic activity of ACE was completely abolished with the pretreatment of SPI suggesting that the aldosterone-induced cell injuries through ANG II release were attenuated. Aldosterone treatment also decreased the expression of MAS receptor, but did not alter the expression or the catalytic activity of ACE 2 and ANG (1-7) levels. Spironolactone modulated the localization of ANG II and AT1 receptor and decreased ANG (1-7) and MAS receptor levels. Our data suggest that both aldosterone and the MR receptor antagonist can modulate both of these axes and that spironolactone can protect MCs from the damage induced by aldosterone.

The PRISM (Pliocene palaeoclimate) reconstruction: time for a paradigm shift.

Global palaeoclimate reconstructions have been invaluable to our understanding of the causes and effects of climate change, but single-temperature representations of the oceanic mixed layer for data-model comparisons are outdated, and the time for a paradigm shift in marine palaeoclimate reconstruction is overdue. The new paradigm in marine palaeoclimate reconstruction stems the loss of valuable climate information and instead presents a holistic and nuanced interpretation of multi-dimensional oceanographic processes and responses. A wealth of environmental information is hidden within the US Geological Survey's Pliocene Research, Interpretation and Synoptic Mapping (PRISM) marine palaeoclimate reconstruction, and we introduce here a plan to incorporate all valuable climate data into the next generation of PRISM products. Beyond the global approach and focus, we plan to incorporate regional climate dynamics with emphasis on processes, integrating multiple environmental proxies wherever available in order to better characterize the mixed layer, and developing a finer time slice within the Mid-Piacenzian Age of the Pliocene, complemented by underused proxies that offer snapshots into environmental conditions. The result will be a proxy-rich, temporally nested, process-oriented approach in a digital format-a relational database with geographic information system capabilities comprising a three-dimensional grid representing the surface layer, with a plethora of data in each cell.

Sea surface temperature of the mid-Piacenzian ocean: a data-model comparison.

The mid-Piacenzian climate represents the most geologically recent interval of long-term average warmth relative to the last million years, and shares similarities with the climate projected for the end of the 21(st) century. As such, it represents a natural experiment from which we can gain insight into potential climate change impacts, enabling more informed policy decisions for mitigation and adaptation. Here, we present the first systematic comparison of Pliocene sea surface temperature (SST) between an ensemble of eight climate model simulations produced as part of PlioMIP (Pliocene Model Intercomparison Project) with the PRISM (Pliocene Research, Interpretation and Synoptic Mapping) Project mean annual SST field. Our results highlight key regional and dynamic situations where there is discord between the palaeoenvironmental reconstruction and the climate model simulations. These differences have led to improved strategies for both experimental design and temporal refinement of the palaeoenvironmental reconstruction.