Yalamanchili, K. | Search bioRxiv

bioRxiv2026

C4 photosynthetic pathway fluxes in transgenic rice plants

Most land plants photosynthesize using the C3 pathway, in which ribulose bisphosphate carboxylase/oxygenase (Rubisco) fixes CO2 into 3-carbon acids. The C4 pathway, a biochemical CO2-concentrating mechanism that operates in the context of specialized leaf anatomy to concentrate CO2 around Rubisco, is more efficient. Introduction of the C4 pathway into the C3 crop rice could increase yield by 50%. Expression of five C4 enzymes in transgenic rice previously led to flux through the first step. However, there was no evidence for flux later in the cycle. Here we developed new transgenic rice lines and novel protocols to detect C4 cycle activity: CO2 fixation into C4 acids by carboxylation of a C3 compound, decarboxylation, refixation of CO2 by Rubisco, and regeneration of the C3 donor. We demonstrate that these four core C4 reactions are operating in rice, establishing the in vivo flux framework needed to progress towards a functional carbon-concentrating mechanism

plant biology↗

bioRxiv2024

Semaglutide Improves Myocardial Perfusion and Performance in a Large Animal Model of Coronary Artery Disease

ObjectiveCoronary artery disease (CAD) is the leading cause of death worldwide. It imposes an enormous symptomatic burden on patients, leaving many with residual disease despite optimal procedural therapy, and up to 1/3 with debilitating angina amenable neither to procedures, nor to current pharmacologic options. Semaglutide, a glucagon-like peptide 1 agonist originally approved for management of diabetes, has garnered substantial attention for its capacity to attenuate cardiovascular risk. Although subgroup analyses in patients indicate promise, studies explicitly designed to isolate the impact of semaglutide on the sequelae of CAD, independently of comorbid diabetes or obesity, are lacking. Approach and ResultsYorkshire swine (n=17) underwent placement of an ameroid constrictor around the left circumflex coronary artery to induce CAD. Oral semaglutide was initiated postoperatively at 1.5 mg and scaled up in 2 weeks to 3 mg in treatment animals (SEM, n=8) for a total of 5 weeks, while control animals (CON, n=9) received no drug. All then underwent myocardial harvest with acquisition of perfusion and functional data using microsphere injection and pressure-volume loop catheterization. Immunoblotting, immunohistochemistry, and immunofluorescence were performed on the most ischemic myocardial segments for mechanistic elucidation. SEM animals exhibited improved left ventricular ejection fraction, both at rest and during rapid myocardial pacing (both p<0.03), accompanied by increased perfusion to the most ischemic myocardial region at rest and during rapid pacing (both p<0.03); reduced perivascular and interstitial fibrosis (both p <0.03); and apoptosis (p=0.008). These changes were associated with increased activation of the endothelial-protective AMPK pathway (p=0.005), coupled with downstream increases in endothelial nitric oxide synthase (p=0.014). ConclusionThis study is the first to reveal the capacity of oral semaglutide to augment cardiac function in the chronically ischemic heart in a highly translational large animal model, likely through AMPK-mediated improvement in endothelial function and perfusion to the ischemic myocardium.

molecular biology↗