Marked hemoglobin mass expansion and plasma volume contraction in Sherpas acclimatizing to 5,400 m altitude.

In lowlanders, high altitude (HA) acclimatization induces hemoconcentration by reducing plasma volume (PV) and increasing total hemoglobin mass (Hb). Conversely, Tibetan highlanders living at HA are reported to have a similar hemoglobin concentration ([Hb]) as lowlanders near sea level, and we investigated whether this reflects alterations in the PV or the Hb response to HA. Baseline assessment of PV and Hb was performed by carbon monoxide rebreathing at low altitudes (∼1,400 m) in Sherpas (an ethnic group of Tibetans living in Nepal) and native lowlanders.

The physiological basis for individualized oxygenation targets in critically ill patients with circulatory shock.

Background: Circulatory shock, defined as decreased tissue perfusion, leading to inadequate oxygen delivery to meet cellular metabolic demands, remains a common condition with high morbidity and mortality. Rapid restitution and restoration of adequate tissue perfusion are the main treatment goals. To achieve this, current hemodynamic strategies focus on adjusting global physiological variables such as cardiac output (CO), hemoglobin (Hb) concentration, and arterial hemoglobin oxygen saturation (SaO).

Substrate selectivity and catalytic activation of the type III CRISPR ancillary nuclease Can2.

Type III CRISPR-Cas systems provide adaptive immunity against foreign mobile genetic elements through RNA-guided interference. Sequence-specific recognition of RNA targets by the type III effector complex triggers the generation of cyclic oligoadenylate (cOA) second messengers that activate ancillary effector proteins, thus reinforcing the host immune response. The ancillary nuclease Can2 is activated by cyclic tetra-AMP (cA4); however, the mechanisms underlying cA4-mediated activation and substrate selectivity remain elusive.

Pushing the boundaries of phosphorylase cascade reaction for cellobiose production II: Model-based multiobjective optimization.

The inherent complexity of coupled biocatalytic reactions presents a major challenge for process development with one-pot multienzyme cascade transformations. Kinetic models are powerful engineering tools to guide the optimization of cascade reactions towards a performance suitable for scale up to an actual production. Here, we report kinetic model-based window of operation analysis for cellobiose production (≥100 g/L) from sucrose and glucose by indirect transglycosylation via glucose 1-phosphate as intermediate.

Pushing the boundaries of phosphorylase cascade reaction for cellobiose production I: Kinetic model development.

One-pot cascade reactions of coupled disaccharide phosphorylases enable an efficient transglycosylation via intermediary α-d-glucose 1-phosphate (G1P). Such transformations have promising applications in the production of carbohydrate commodities, including the disaccharide cellobiose for food and feed use. Several studies have shown sucrose and cellobiose phosphorylase for cellobiose synthesis from sucrose, but the boundaries on transformation efficiency that result from kinetic and thermodynamic characteristics of the individual enzyme reactions are not known.