Malaria transmission relies on concavin-mediated maintenance of Plasmodium sporozoite cell shape

During transmission of malaria-causing parasites from mosquitoes to mammals, Plasmodium sporozoites migrate rapidly in the skin to search for a blood vessel. The high migratory speed and narrow passages taken by the parasites suggest considerable strain on the sporozoites to maintain their shape. Here we report on a newly identified protein, concavin, that is important for maintenance of the sporozoite shape inside salivary glands of mosquitoes and during migration in the skin. Concavin-GFP localized at the cytoplasmic periphery of sporozoites and concavin(-) sporozoites progressively rounded up upon entry of salivary glands. These rounded concavin(-) sporozoites failed to pass through the narrow salivary ducts and were hence rarely ejected by mosquitoes. However, normally shaped concavin(-) sporozoites could be transmitted and migrated in the skin or skin like environments. Strikingly, motile concavin(-) sporozoites could disintegrate while migrating through narrow strictures in the skin leading to parasite arrest or death and decreased transmission efficiency. We suggest that concavin contributes to cell shape maintenance by riveting the plasma membrane to the subtending inner membrane complex.

The WAVE Regulatory Complex Is Required to Balance Protrusion and Adhesion in Migration

Cells migrating over 2D substrates are required to polymerise actin at the leading edge to form lamellipodia protrusions and nascent adhesions to anchor the protrusion to the substrate. The major actin nucleator in lamellipodia formation is the Arp2/3 complex, which is activated by the WAVE regulatory complex (WRC). Using inducible Nckap1 floxed mouse embryonic fibroblasts (MEFs), we confirm that the WRC is required for lamellipodia formation, and importantly, for generating the retrograde flow of actin from the leading cell edge. The loss of NCKAP1 also affects cell spreading and focal adhesion dynamics. In the absence of lamellipodium, cells can become elongated and move with a single thin pseudopod, which appears devoid of N-WASP. This phenotype was more prevalent on collagen than fibronectin, where we observed an increase in migratory speed. Thus, 2D cell migration on collagen is less dependent on branched actin.

Quantifying the correlation between spatially defined oxygen gradients and cell fate in an engineered three-dimensional culture model

A challenge in three-dimensional tissue culture remains the lack of quantitative information linking nutrient delivery and cellular distribution. Both in vivo and in vitro , oxygen is delivered by diffusion from its source (blood vessel or the construct margins). The oxygen level at a defined distance from its source depends critically on the balance of diffusion and cellular metabolism. Cells may respond to this oxygen environment through proliferation, death and chemotaxis, resulting in spatially resolved gradients in cellular density. This study extracts novel spatially resolved and simultaneous data on tissue oxygenation, cellular proliferation, viability and chemotaxis in three-dimensional spiralled, cellular collagen constructs. Oxygen concentration gradients drove preferential cellular proliferation rates and viability in the higher oxygen zones and induced chemotaxis along the spiral of the collagen construct; an oxygen gradient of 1.03 mmHg mm −1 in the spiral direction induced a mean migratory speed of 1015 μm day −1 . Although this movement was modest, it was effective in balancing the system to a stable cell density distribution, and provided insights into the natural cell mechanism for adapting cell number and activity to a prevailing oxygen regime.

Stochastic variations of migration speed between cells in clonal populations

We combined microfluidic tools and molecular probes to monitor the migration speed of successive generations of cancer cells. We found that the migratory speed of individual cells changes stochastically from parent cells to their descendants, while the average speed of successive generations of cells remains constant. Further studies of the interrelations between cell migration and division processes may help identify the molecular determinants of cell speed and lead to new therapies to slow the invasion of cancer cells and delay metastases.

Homing behaviour of Atlantic salmon (Salmo salar) during final phase of marine migration and river entry

Little is known about Atlantic salmon behaviour during the last phase of the marine homing migration and subsequent river entry. In this study, 56 adult Atlantic salmon in the Alta Fjord in northern Norway were equipped with acoustic transmitters. Salmon generally followed the coastline, but their horizontal distribution was also affected by wind-induced spreading of river water across the fjord. Mean swimming depth was shallow (2.5–0.5 m), but with dives down to 30 m depth. Timing of river entry was not affected by river flow, diel periodicity, or tidal cycles. Movements during the last part of the marine migration and river entry were unidirectional and relatively fast (mean 9.7 km·day−1). However, migratory speed slowed as salmon approached the estuary, with a significantly lower speed in the innermost part of the estuary than in the open fjord. Migration behaviour seemed not to be affected by handling and tagging, as there were no behavioural differences between newly tagged fish and those captured and tagged 1 year before their homing migration.

PAPIERELEKTROPHORETISCHE AUFSPALTUNG GONADOTROPER SUBSTANZEN

ABSTRACT The paperelectrophoresis of different charges of one chorion-gonadotrophin preparation and two charges of a serum-gonadotrophin preparation at different pH-levels showed in the course of systematic tests of electrophoresis-strips in the bio-test (weight-test of the ovary, uterus and the ventral lobe of the prostate-gland of intact infantile rats and the ovary weight-test of hypophysectomized infantile rats) with special consideration for the histology of the ovaries an exactly localised, biologically active complex. A suitable dose has been used for the different test-organs which resulted from the bioassays of the different charges. A weight-curve with multiple peaks at systematical tests is not caused by many or biologically different fractions but the result of a relative over-dosage. Through histological slides of the ovaries of hypophysectomized infantile rats a slight FSH-activity could be demonstrated in the center of the biological maximum for the chorion-gonadotrophin with higher dosage. The migratory speed of the biological activity at the same pH-level was almost the same for the different charges of the same chorion-gonadotrophin preparation, of which the mucopolysaccharide-spectrums in the electropherogram after staining with Ninhydrin, Amido-Black 10 B and Schiff's Stain differ partly to a higher degree. The biological activity therefore, migrated in differently constituted mucopolysaccharide-complexes.