A Third Measure-Metastable State in the Dynamics of Spontaneous Shape Change in Healthy Human's White Cells

Human polymorphonuclear leucocytes, PMN, are highly motile cells with average 12-15 µm diameters and prominent, loboid nuclei. They are produced in the bone marrow, are essential for host defense, and are the most populous of white blood cell types. PMN also participate in acute and chronic inflammatory processes, in the regulation of the immune response, in angiogenesis, and interact with tumors. To accommodate these varied functions, their behavior is adaptive, but still definable in terms of a set of behavioral states. PMN morphodynamics have generally involved a non-equilibrium stationary, spheroid Idling state that transitions to an activated, ellipsoid translocating state in response to chemical signals. These two behavioral shape-states, spheroid and ellipsoid, are generally recognized as making up the vocabulary of a healthy PMN. A third, “random” state has occasionally been reported as associated with disease states. I have observed this third, Treadmilling state, in PMN from healthy subjects, the cells demonstrating metastable dynamical behaviors known to anticipate phase transitions in mathematical, physical, and biological systems. For this study, human PMN were microscopically imaged and analyzed as single living cells. I used a microscope with a novel high aperture, cardioid annular condenser with better than 100 nanometer resolution of simultaneous, mixed dark field and intrinsic fluorescent images to record shape changes in 189 living PMNs. Relative radial roundness, R(t), served as a computable order parameter. Comparison of R(t) series of 10 cells in the Idling and 10 in the Treadmilling state reveals the robustness of the “random” appearing Treadmilling state, and the emergence of behaviors observed in the neighborhood of global state transitions, including increased correlation length and variance (divergence), sudden jumps, mixed phases, bimodality, power spectral scaling and temporal slowing. Wavelet transformation of an R(t) series of an Idling to Treadmilling state change, demonstrated behaviors concomitant with the observed transition

Keeping an eye on noisy movements: On different approaches to perceptual-motor skill research and training

Contemporary theorising on the complementary nature of perception and action in expert performance has led to the emergence of different emphases in studying movement coordination and gaze behaviour. On the one hand, coordination research has examined the role that variability plays in movement control, evidencing that variability facilitates individualised adaptations during both learning and performance. On the other hand, and at odds with this principle, the majority of gaze behaviour studies have tended to average data over participants and trials, proposing the importance of universal 'optimal' gaze patterns in a given task, for all performers, irrespective of stage of learning. In this article, new lines of inquiry are considered with the aim of reconciling these two distinct approaches. The role that inter- and intra-individual variability may play in gaze behaviours is considered, before suggesting directions for future research

Interactions Between Laminin Receptor and the Cytoskeleton During Translation and Cell Motility

Human laminin receptor acts as both a component of the 40S ribosomal subunit to mediate cellular translation and as a cell surface receptor that interacts with components of the extracellular matrix. Due to its role as the cell surface receptor for several viruses and its overexpression in several types of cancer, laminin receptor is a pathologically significant protein. Previous studies have determined that ribosomes are associated with components of the cytoskeleton, however the specific ribosomal component(s) responsible has not been determined. Our studies show that laminin receptor binds directly to tubulin. Through the use of siRNA and cytoskeletal inhibitors we demonstrate that laminin receptor acts as a tethering protein, holding the ribosome to tubulin, which is integral to cellular translation. Our studies also show that laminin receptor is capable of binding directly to actin. Through the use of siRNA and cytoskeletal inhibitors we have shown that this laminin receptor-actin interaction is critical for cell migration. These data indicate that interactions between laminin receptor and the cytoskeleton are vital in mediating two processes that are intimately linked to cancer, cellular translation and migration

Enriched environment and physical activity reduce microglia and influence the fate of NG2 cells in the amygdala of adult mice

Proliferative cells expressing proteoglycan neuron-glia 2 (NG2) are considered to represent parenchymal precursor cells in the adult brain and are thought to differentiate primarily into oligodendrocytes. We have studied cell genesis in the adult amygdala and found that, up to 1 year after the labeling of proliferating cells with bromodeoxyuridine, most proliferating NG2 cells remain NG2 cells, and only a few slowly differentiate into mature oligodendrocytes, as assessed by the expression of 2',3'-cyclic nucleotide 3'-phosphodiesterase. We have detected no signs of neurogenesis but have confirmed the expression of “neuronal” markers such as Doublecortin in NG2 cells. Nestin-expressing NG2 cells in the amygdala show electrophysiological properties known for oligodendrocyte precursor cells in the corpus callosum. Application of the glutamate agonist kainate elicits a “complex” response consisting of a rapid and long-lasting blockade of the resting K+ conductance, a transient cationic current, and a transient increase of an outwardly directed K+ conductance, suggesting the responsiveness of NG2 cells to excitation. Proliferation of NG2 cells increases in response to behavioral stimuli of activity, voluntary wheel running, and environmental enrichment. In addition to reducing the number of newborn microglia, behavioral activity results in a decrease in S100β-expressing newborn NG2 cells in the amygdala. Because S100β expression in NG2 cells ceases with oligodendrocyte maturation, this finding suggests that NG2 cells in the amygdala undergo activity-dependent functional alterations, without resulting in a measurable increase in new mature oligodendrocytes over the time period covered by the present study. The adult amygdala thus shows signs of mixed activity-dependent plasticity: reduced numbers of microglia and, presumably, an altered fate of NG2 cells

Global variation in anastomosis and end colostomy formation following left-sided colorectal resection

Background End colostomy rates following colorectal resection vary across institutions in high-income settings, being influenced by patient, disease, surgeon and system factors. This study aimed to assess global variation in end colostomy rates after left-sided colorectal resection. Methods This study comprised an analysis of GlobalSurg-1 and -2 international, prospective, observational cohort studies (2014, 2016), including consecutive adult patients undergoing elective or emergency left-sided colorectal resection within discrete 2-week windows. Countries were grouped into high-, middle- and low-income tertiles according to the United Nations Human Development Index (HDI). Factors associated with colostomy formation versus primary anastomosis were explored using a multilevel, multivariable logistic regression model. Results In total, 1635 patients from 242 hospitals in 57 countries undergoing left-sided colorectal resection were included: 113 (6·9 per cent) from low-HDI, 254 (15·5 per cent) from middle-HDI and 1268 (77·6 per cent) from high-HDI countries. There was a higher proportion of patients with perforated disease (57·5, 40·9 and 35·4 per cent; P < 0·001) and subsequent use of end colostomy (52·2, 24·8 and 18·9 per cent; P < 0·001) in low- compared with middle- and high-HDI settings. The association with colostomy use in low-HDI settings persisted (odds ratio (OR) 3·20, 95 per cent c.i. 1·35 to 7·57; P = 0·008) after risk adjustment for malignant disease (OR 2·34, 1·65 to 3·32; P < 0·001), emergency surgery (OR 4·08, 2·73 to 6·10; P < 0·001), time to operation at least 48 h (OR 1·99, 1·28 to 3·09; P = 0·002) and disease perforation (OR 4·00, 2·81 to 5·69; P < 0·001). Conclusion Global differences existed in the proportion of patients receiving end stomas after left-sided colorectal resection based on income, which went beyond case mix alone