Hydrodynamics of Prey Capture and Transportation in Choanoflagellates

Choanoflagellates are unicellular microscopic organisms that are believed to be the closest living relatives of animals. They prey on bacteria through the act of the continuous beating of their flagellum, which generates a current through a crown-like filter. Subsequently, the filter retains bacterial particles from the suspension. The mechanism by which the prey is retained and transported along the filter remains unknown. We report here on the hydrodynamic effects on the transportability of bacterial prey of finite size using computational fluid dynamics. Here, the loricate choanoflagellate Diaphaoneca grandis serves as the model organism. The lorica is a basket-like structure found in only some of the species of choanoflagellates. We find that although transportation does not entirely rely on hydrodynamic forces, such forces positively contribute to the transportation of prey along the collar filter. The aiding effects are most possible in non-loricate choanoflagellate species, as compared to loricate species. As hydrodynamic effects are strongly linked to the beat and shape of the flagellum, our results indicate an alternative mechanism for prey transportation, especially in biological systems where having an active transport mechanism is costly or not feasible. This suggests an additional potential role for flagella in addition to providing propulsion and generating feeding currents.

Cefiderocol: A Novel Siderophore Cephalosporin Defeating Carbapenem-resistant Pathogens

Cefiderocol, a novel siderophore cephalosporin in late-stage clinical development, utilizes a “Trojan horse” active transport mechanism to enter bacteria and has proven in vitro activity against carbapenem-resistant gram-negative pathogens, including those with major carbapenem-resistance mechanisms, and stability against all carbapenemases.

Estimating Amoxicillin Influx/Efflux in Chinchilla Middle Ear Fluid and Simultaneous Measurement of Antibacterial Effect

ABSTRACT Understanding the transport process and the factors that control the influx/efflux of antibiotics between plasma and middle ear fluid is essential in optimizing the antimicrobial efficacy in the treatment of acute otitis media. In this study, an experimental chinchilla model with the application of a microdialysis technique was utilized to evaluate amoxicillin middle ear distribution kinetics. Amoxicillin solutions at various doses were instilled into the middle ear with a simultaneous intravenous bolus dose. Unbound amoxicillin levels were monitored by microdialysis in both ears. Serial phlebotomy provided samples for the measurement of unbound amoxicillin concentration in plasma ultrafiltrates. In infected chinchillas, discrete middle ear fluid samples were plated and cultured to characterize Streptococcus pneumoniae growth-kill kinetics. Noncompartmental analysis was used to estimate distributional and elimination clearances assuming linear pharmacokinetics. A nonlinear Michaelis-Menten equation was also used to determine the efflux clearance (from middle ear fluid to plasma) in a mammillary compartment model. No difference was observed in amoxicillin pharmacokinetics between control and infected chinchillas. Influx clearance was (4.6 ± 2.4) × 10−3 ml/min-kg and significantly lower than the efflux clearance estimated as (19.2 ± 9.7) × 10−3 ml/min-kg (P < 0.002). Nonlinear kinetics was observed in the locally dosed ear. The microdialysis procedure did not interfere with the bacterial growth-kill profile, thereby enabling pharmacokinetic and pharmacodynamic evaluation concurrently. In conclusion, the results suggested that the distribution equilibrium of amoxicillin in the middle ear favors efflux to plasma over influx. An active transport mechanism across middle ear mucosal epithelium may be involved in amoxicillin distribution.

Modeling of Coarsening Processes In Patterned Systems

ABSTRACTAlthough particle coarsening has been studied for over a century, it remains an active area of materials science research. The current work presents a theoretical analysis of the degradation of regular arrays of spherical particles through diffusional interaction. In order to understand the onset of coarsening, a linear stability analysis is performed on a simple square lattice of particles. It is predicted that particles will dissolve in a spatially ordered manner. The active transport mechanism plays a strong role in the selection of the coherent growth modes.

Nuclear Export of Map Kinase (ERK) Involves a Map Kinase Kinase (Mek-Dependent) Active Transport Mechanism

In response to extracellular stimuli, mitogen-activated protein kinase (MAPK, also known as ERK), which localizes to the cytoplasm in quiescent cells, translocates to the nucleus and then relocalizes to the cytoplasm again. The relocalization of nuclear MAPK to the cytoplasm was not inhibited by cycloheximide, confirming that the relocalization is achieved by nuclear export, but not synthesis, of MAPK. The nuclear export of MAPK was inhibited by leptomycin B (LMB), a specific inhibitor of the nuclear export signal (NES)-dependent transport. We have then shown that MAP kinase kinase (MAPKK, also known as MEK), which mostly localizes to the cytoplasm because of its having NES, is able to shuttle between the cytoplasm and the nucleus constantly. MAPK, when injected into the nucleus, was rapidly exported from the nucleus by coinjected wild-type MAPKK, but not by the NES-disrupted MAPKK. In addition, injection of the fragment corresponding to the MAPK-binding site of MAPKK into the nucleus, which would disrupt the binding of MAPK to MAPKK in the nucleus, significantly inhibited the nuclear export of endogenous MAPK. Taken together, these results suggest that the relocalization of nuclear MAPK to the cytoplasm involves a MAPKK-dependent, active transport mechanism.

Lactate and metabolic H+ transport and distribution after exercise in rainbow trout white muscle

An isolated-perfused tail-trunk preparation was employed to study the influence of transmembrane pH gradient and membrane potential on the transport and distribution of L(+)-lactate (Lac), metabolic H+ (delta Hm+), and related parameters in rainbow trout white muscle after exhaustive exercise. One resting [arterial pH (pHa) approximately 7.9] and four postexercise treatments (pHa approximately 7.4, 7.9, 8.4, and, high K+, pHa approximately 7.9, partially depolarized by 15 mM K+) were examined. Variations in HCO3- concentration (2-18 mM) at a constant PCO2 approximately 2 Torr were used to alter pHa. The elevated intracellular Lac (approximately 50 mM) remained unchanged after 60 min of perfusion because of very low rates of lactate efflux and oxidation. H+, HCO3-, and Lac- distributions were all well out of electrochemical equilibrium. Total CO2 efflux was reduced at high extracellular pH (pHe); alterations in the net driving force on HCO3- may have overshadowed the influence of PCO2 gradients in driving total CO2 efflux. Lac efflux and delta Hm+ flux were completely uncoupled. delta Hm+ flux reacted to both acid-base and electrochemical gradients as delta Hm+ efflux dropped and even reversed when pHe decreased, whereas partial depolarization in conjunction with depressed intracellular pH resulted in elevated delta Hm+ efflux. Lac efflux did not respond to changes in pHe. Changes in Lac efflux corresponded more closely to changes in the Lac- concentration gradient than in the lactic acid gradient. This study provides circumstantial evidence for the involvement of electroneutral mechanisms (i.e., Lac(-)-H+ cotransport and/or Lac-/anion exchange) in lactate efflux, but does not eliminate the possibility of an active transport mechanism contributing to the retention of Lac.