Characteristics of melanomacrophage centers in the liver and spleen of the roach Rutilus rutilus (Cypriniformes: Cyprinidae) in Lake Kotokel during the Haff disease outbreak

Characteristics of morphology and number of melanomacrophage centers (MMCs) in the liver and spleen of the roach Rutilus rutilus and the amount of pigments in MMCs during the Haff disease outbreak and the death of fish in Lake Kotokel in relation to these parameters in the roach from Lake Baikal are described. Pathological changes in the microvasculature and parenchyma in the liver of the roach from Lake Kotokel were found. The area of melanomacrophage centers in the liver of the roach from this lake was significantly smaller, whereas the number and size of these centers in the spleen was significantly larger than in the roaches from Lake Baikal. Among the pigments studied, the strongest response to the content of this toxin in the water body was shown by hemosiderin. An increase in its amount in the spleen MMCs testifies to an enhanced degradation of erythrocytes and iron release, which may be caused by the damage of cells of the erythrocyte lineage by the toxin.     

A bidirectional antagonism between aPKC and Yurt regulates epithelial cell polarity

During epithelial cell polarization, Yurt (Yrt) is initially confined to the lateral membrane and supports the stability of this membrane domain by repressing the Crumbs-containing apical machinery. At late stages of embryogenesis, the apical recruitment of Yrt restricts the size of the apical membrane. However, the molecular basis sustaining the spatiotemporal dynamics of Yrt remains undefined. In this paper, we report that atypical protein kinase C (aPKC) phosphorylates Yrt to prevent its premature apical localization. A nonphosphorylatable version of Yrt dominantly dismantles the apical domain, showing that its aPKC-mediated exclusion is crucial for epithelial cell polarity. In return, Yrt counteracts aPKC functions to prevent apicalization of the plasma membrane. The ability of Yrt to bind and restrain aPKC signaling is central for its role in polarity, as removal of the aPKC binding site neutralizes Yrt activity. Thus, Yrt and aPKC are involved in a reciprocal antagonistic regulatory loop that contributes to segregation of distinct and mutually exclusive membrane domains in epithelial cells.     

Lack of Significant Elevation of Myeloid-Derived Suppressor Cells in Peripheral Blood of Chronically Hepatitis C Virus-Infected Individuals

Myeloid-derived suppressor cells (MDSC) are immature myeloid cells with immunosuppressive function. Compared to the level in healthy controls (HC), no elevation of MDSC in chronic hepatitis C (cHEP-C) patients was found, and there was no difference in MDSC based on genotype or viral load (P > 0.25). Moreover, MDSC of cHEP-C patients inhibited CD8 T cell function as efficiently as MDSC of HC did. Since we detected neither quantitative nor qualitative differences in MDSC of cHEP-C patients relative to those of HC, we postulate that MDSC in peripheral blood are most likely not significant regarding immune dysfunction in cHEP-C.     

The problem of determination of cause of laboratory animal’s death: A critical review of definitions of “fatal” and “incidental” lesions

The determination of the cause of a laboratory animal’s death in gerontological experiments has become extraordinarily urgent in connection with the appearance of ideas on the programmed death of organisms. Unfortunately, the past approach to diagnosis of fatal and incidental changes based only on data of autopsy and histopathology (according to the human pathology model) is not correct for laboratory rodents. Nevertheless, the exact determination of death causes is principally possible in the future under conditions of adequate experimental design (including a large set of clinical, physiological, biochemical, and morphological examinations). However, it seems that even in this case causes of some experimental animal’s death will remain unclear.     

Flow and Diffusion in Channel-Guided Cell Migration

Collective migration of mechanically coupled cell layers is a notable feature of wound healing, embryonic development, and cancer progression. In confluent epithelial sheets, the dynamics have been found to be highly heterogeneous, exhibiting spontaneous formation of swirls, long-range correlations, and glass-like dynamic arrest as a function of cell density. In contrast, the flow-like properties of one-sided cell-sheet expansion in confining geometries are not well understood. Here, we studied the short- and long-term flow of Madin-Darby canine kidney (MDCK) cells as they moved through microchannels. Using single-cell tracking and particle image velocimetry (PIV), we found that a defined averaged stationary cell current emerged that exhibited a velocity gradient in the direction of migration and a plug-flow-like profile across the advancing sheet. The observed flow velocity can be decomposed into a constant term of directed cell migration and a diffusion-like contribution that increases with density gradient. The diffusive component is consistent with the cell-density profile and front propagation speed predicted by the Fisher-Kolmogorov equation. To connect diffusion-mediated transport to underlying cellular motility, we studied single-cell trajectories and occurrence of vorticity. We discovered that the directed large-scale cell flow altered fluctuations in cellular motion at short length scales: vorticity maps showed a reduced frequency of swirl formation in channel flow compared with resting sheets of equal cell density. Furthermore, under flow, single-cell trajectories showed persistent long-range, random-walk behavior superimposed on drift, whereas cells in resting tissue did not show significant displacements with respect to neighboring cells. Our work thus suggests that active cell migration manifests itself in an underlying, spatially uniform drift as well as in randomized bursts of short-range correlated motion that lead to a diffusion-mediated transport.