Long-term regulation of proximal tubule acid–base transporter abundance by angiotensin II

In the proximal tubule, angiotensin II (Ang-II) regulates HCO−3 reabsorption and H+ secretion by binding the type 1 Ang-II (AT1) receptor, stimulating Na+/HCO−3 cotransport and Na+/H+ exchange. Studies were carried out to determine if long-term changes in Ang-II receptor occupation alter the abundance of the basolateral Na+/HCO−3 cotransporter (NBC1) or the apical membrane type 3Na+/H+ exchanger (NHE3). In the first set of experiments, rats eating a low-sodium diet were infused with the AT1 blocker, candesartan, or vehicle. In the second, lisinopril-infused rats were infused with either Ang II or vehicle. Transporter abundances were determined in whole kidney homogenates (WKH) and in brush border membrane (BBM) preparations by semiquantitative immunoblotting. Tissue distribution of transporters was assessed by immunocytochemistry. Blockade of the AT1 receptor by candesartan caused decreased abundance of NBC1 in WKH (59±9% of control; P<0.05) and Ang-II infusion increased abundance (130±7% of control; P<0.05). Changes in NBC1 in response to candesartan were confirmed immunohistochemically. Neither candesartan nor Ang II infusion affected the abundance of NHE3 in WKH or cortical homogenates. Candesartan decreased type 2 sodium-phosphate cotransporter abundance in both WKH (52±7% of control; P<0.05) and BBM (32±7% of control; P<0.05). Serum bicarbonate was decreased by candesartan and increased by Ang-II. Candesartan also decreased urinary ammonium excretion (P<0.05). The long-term effects of Ang-II in the proximal tubule may be mediated in part by regulation of NBC1 abundance, modifying bicarbonate reabsorption

Benefits and risks of including the bromoform containing seaweed Asparagopsis in feed for the reduction of methane production from ruminants

The agricultural production of ruminants is responsible for 24% of global methane emissions, contributing 39% of emissions of this greenhouse gas from the agricultural sector. Strategies to mitigate ruminant methanogenesis include the use of methanogen inhibitors. For example, the seaweeds Asparagopsis taxiformis and Asparagopsis armata included at low levels in the feed of cattle and sheep inhibit methanogenesis by up to 98%, with evidence of improvements in feed utilisation efficiency. This has resulted in an increasing interest in and demand for these seaweeds globally. In response, research is progressing rapidly to facilitate Asparagopsis cultivation at large scale, and to develop aquaculture production systems to enable a high quality and consistent supply chain. In addition to developing robust strategies for sustainable production, it is important to consider and evaluate the benefits and risks associated with its production and subsequent use as an antimethanogenic feed ingredient for ruminant livestock. This review focuses on the relevant ruminal biochemical pathways, degradation, and toxicological risks associated with bromoform (CHBr3), the major active ingredient for inhibition of methanogenesis in Asparagopsis, and the effects that production of Asparagopsis and its use as a ruminant feed ingredient might have on atmospheric chemistry

Trends and transitions in the institutional environment for public and private science

The last quarter-century bore witness to a sea change in academic involvement with commerce. Widespread university-based efforts to identify, manage, and market intellectual property (IP) have accompanied broad shifts in the relationship between academic and proprietary approaches to the dissemination and use of science and engineering research. Such transformations are indicators of institutional changes at work in the environment faced by universities. This paper draws upon a fifteen-year panel (1981–1995) of university-level data for 87 research-intensive US campuses in order to document trends and transitions in relationships among multiple indicators of academic and commercial engagement. The institutional environment for public and private science is volatile, shifting in fits and starts from a situation conducive to organizational learning through high volume patenting to a more challenging arrangement that links indiscriminate pursuit of IP with declines in both the volume and impact of academic science. The pattern and timing of these transitions may support an enduring system of stratification that offers increasing returns to first-movers while limiting the opportunities available to universities that are later entrants to the commercial realm. Unpacking the systematic effects of university research commercialization requires focused attention on the sources and trajectories of profound institutional change.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/42839/1/10734_2004_Article_2916.pd

Whole-genome sequencing reveals host factors underlying critical COVID-19

Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care1 or hospitalization2,3,4 after infection with SARS-CoV-2. The GenOMICC (Genetics of Mortality in Critical Care) study enables the comparison of genomes from individuals who are critically ill with those of population controls to find underlying disease mechanisms. Here we use whole-genome sequencing in 7,491 critically ill individuals compared with 48,400 controls to discover and replicate 23 independent variants that significantly predispose to critical COVID-19. We identify 16 new independent associations, including variants within genes that are involved in interferon signalling (IL10RB and PLSCR1), leucocyte differentiation (BCL11A) and blood-type antigen secretor status (FUT2). Using transcriptome-wide association and colocalization to infer the effect of gene expression on disease severity, we find evidence that implicates multiple genes—including reduced expression of a membrane flippase (ATP11A), and increased expression of a mucin (MUC1)—in critical disease. Mendelian randomization provides evidence in support of causal roles for myeloid cell adhesion molecules (SELE, ICAM5 and CD209) and the coagulation factor F8, all of which are potentially druggable targets. Our results are broadly consistent with a multi-component model of COVID-19 pathophysiology, in which at least two distinct mechanisms can predispose to life-threatening disease: failure to control viral replication; or an enhanced tendency towards pulmonary inflammation and intravascular coagulation. We show that comparison between cases of critical illness and population controls is highly efficient for the detection of therapeutically relevant mechanisms of disease