Early increases in plasminogen activator activity following partial hepatectomy in humans

Background Increases in urokinase-like plasminogen activator (uPA) activity are reported to be amongst the earliest events occurring in remnant liver following partial hepatectomy in rats, and have been proposed as a key component of the regenerative response. Remodelling of the extracellular matrix, conversion of single chain hepatocyte growth factor to the active two-chain form and a possible activation of a mitogenic signalling pathway have all been ascribed to the increased uPA activity. The present study aimed to determine whether similar early increases in uPA activity could be detected in the remnant liver following resection of metastatic tumours in surgical patients. Results Eighteen patients undergoing partial hepatectomy for the removal of hepatic metastases secondary to primary colonic tumours were studied. Increased plasminogen activator activity was found in the final liver samples for the group of patients in whom the resection size was at least 50%. For smaller resections, the increased activity was not observed. The increased activity did not correlate with the age of the patient or with the time between the start of resection and the end of the operation. There was, however, a negative correlation between plasminogen activator activity and the time for which blood supply to the liver was clamped. Conclusions Our findings are in accordance with those from experimental animal models and show, for the first time, that rapid increases in plasminogen activator activity can occur following similarly large liver resection in humans. Thus, increases in plasminogen activator activity are an early event in the remnant liver following major liver resection in man. Our observations provide support for the contention that increases in plasminogen activators play a key role in the initiation of hepatic regeneration in man

The Mtoko quintuplets

A journal article on multiple pregnancies in the then Southern Rhodesia colony.The ratio of twin pregnancies to single pregnancies in England and the United. States of America is reported to be approximately one in eighty. By Hellins Law the incidence of quintuplets is therefore approximately one in 40 million. Quintuplets in these countries are obviously of extreme rarity. It is known, however, that in Rhodesia the incidence of twins is much higher among the African population and one would, therefore, expect the incidence of quintuplets to be higher. The incidence of twins is reported to be in the region of one in thirty-five, and by application of Hellins Law the incidence of quintuplets should be approximately one in 1.5 million births

The effects of man-marking on work intensity in small-sided soccer games

The aim of this study was to examine the effect of manipulating defensive rules: with and without man-marking (MM and NMM) on exercise intensity in 3 vs. 3 small-sided games (SSGs). Twelve adolescent soccer players (age: 16.2 ± 0.7 years; body mass: 55.7 ± 6.4 kg; body height: 1.70 ± 0.07 m) participated in this repeated measures study. Each participant performed in four different SSGs formats: 3 vs. 3 MM with and without goals and 3 vs. 3 NMM with and without goals. Each SSG lasted 3 x 4 minutes interspersed with 4 minutes passive recovery. The percentage heart rate reserve (%HRreserve) was recorded continuously during SSG and session-rating of perceived exertion (session-RPE) after the SSG. MANOVA showed that defensive rule had significant effects on intensity (F = 5.37, p < 0.01). Specifically, MM during SSG induced significantly higher %HRreserve compared to NMM (Goal: 80.5 vs. 75.7%; No goal: 80.5 vs. 76.1%; p < 0.05, effect size = 0.91-1.06), irrespective of the presence or absence of goals. However, only MM with the presence of goals induced significant higher session-RPE compared to NMM (7.1 vs. 6.0; p < 0.05, effect size = 1.36), whereas no difference in session-RPE was observed between MM and NMM (7.4 vs. 6.9; p > 0.05, effect size = 0.63) when no goals were used. Higher intra-class reliability and lower coefficient of variation values were also reported in MM as compared to NMM. This study in youth soccer players shows there is ~4.5% increase in heart rate response by using the man-marking in 3 vs. 3 SSG thus the intensity of SSG can be significantly increased when using man-marking tactics

Early warning signals in plant disease outbreaks

Infectious disease outbreaks in plants threaten ecosystems, agricultural crops and food trade. Currently, several fungal diseases are affecting forests worldwide, posing a major risk to tree species, habitats and consequently ecosystem decay. Prediction and control of disease spread are difficult, mainly due to the complexity of the interaction between individual components involved. In this work, we introduce a lattice-based epidemic model coupled with a stochastic process that mimics, in a very simplified way, the interaction between the hosts and pathogen. We studied the disease spread by measuring the propagation velocity of the pathogen on the susceptible hosts. Our quantitative results indicate the occurrence of a critical transition between two stable phases: local confinement and an extended epiphytotic outbreak that depends on the density of the susceptible individuals. Quantitative predictions of epiphytotics are performed using the framework early-warning indicators for impending regime shifts, widely applied on dynamical systems. These signals forecast successfully the outcome of the critical shift between the two stable phases before the system enters the epiphytotic regime. Our study demonstrates that early-warning indicators could be useful for the prediction of forest disease epidemics through mathematical and computational models suited to more specific pathogen–host-environmental interactions. Our results may also be useful to identify a suitable planting density to slow down disease spread and in the future, design highly resilient forests

Magnetic reconnection in Saturn's magnetotail: a comprehensive magnetic field survey

Reconnection within planetary magnetotails is responsible for locally energizing particles and changing the magnetic topology. Its role in terms of global magnetospheric dynamics can involve changing the mass and flux content of the magnetosphere. We have identified reconnection related events in spacecraft magnetometer data recorded during Cassini's exploration of Saturn's magnetotail. The events are identified from deflections in the north-south component of the magnetic field, significant above a background level. Data were selected to provide full tail coverage, encompassing the dawn and dusk flanks as well as the deepest midnight orbits. Overall 2094 reconnection related events were identified, with an average rate of 5.0 events per day. The majority of events occur in clusters (within 3 h of other events). We examine changes in this rate in terms of local time and latitude coverage, taking seasonal effects into account. The observed reconnection rate peaks postmidnight with more infrequent but steady loss seen on the dusk flank. We estimate the mass loss from the event catalog and find it to be insufficient to balance the input from the moon Enceladus. Several reasons for this discrepancy are discussed. The reconnection X line location appears to be highly variable, though a statistical separation between events tailward and planetward of the X line is observed at a radial distance of between 20 and 30RS downtail. The small sample size at dawn prevents comprehensive statistical comparison with the dusk flank observations in terms of flux closure

The relative involvement of Th1 and Th2 associated immune responses in the expulsion of a primary infection of Heligmosomoides polygyrus in mice of differing response phenotype

T helper cell (Th1 and Th2) associated responses were examined following a primary infection with the gastrointestinal nematode Heligmosomoides polygyrus in five inbred strains of mice with different resistance phenotypes. Levels of (i) mast cell protease, (ii) specific IgE, (iii) nitric oxide and (iv) specific IgG2a, as markers of Th2 and Th1 associated responses, respectively, were determined in sera and intestinal fluids and correlated with worm burdens. The ‘fast’ responder (resistant) strains SWR and SJL produced strong Th2 and Th1 associated responses respectively in a mutually exclusive fashion. The F1 hybrid(SWR £ SJL) F1, showed rapid expulsion of the parasite and expressed both intense Th1 and Th2 responses, suggesting synergism between Th1 and Th2 activity in these mice. The results indicate that both Th2 and Th1 responses operate in mice following a primary infection with H. polygyrus and that each Th response may be involved to a greater or lesser degree within certain strains. Resistance to H. polygyrus was found to correlate only to the intensity of either the gut-associated mastocytosis or nitric oxide production in these strains but not to either specific IgE or IgG2a titres. Chronic infections in the ‘slow’ response phenotype mouse strains CBA and C57BL/10, were associated with both poor Th2 and poor Th1-associated responses attributed to a general parasite-mediated immunosuppression of the host immune response to infection

Cell organisation in the colonic crypt: A theoretical comparison of the pedigree and niche concepts

The intestinal mucosa is a monolayer of rapidly self-renewing epithelial cells which is not only responsible for absorption of water and nutrients into the bloodstream but also acts as a protective barrier against harmful microbes entering the body. New functional epithelial cells are produced from stem cells, and their proliferating progeny. These stem cells are found within millions of crypts (tubular pits) spaced along the intestinal tract. The entire intestinal epithelium is replaced every 2–3 days in mice (3–5 days in humans) and hence cell production, differentiation, migration and turnover need to be tightly regulated. Malfunctions in this regulation are strongly linked to inflammatory bowel diseases and to the formation of adenomas and ultimately cancerous tumours. Despite a great deal of biological experimentation and observation, precisely how colonic crypts are regulated to produce mature colonocytes remains unclear. To assist in understanding how cell organisation in crypts is achieved, two very different conceptual models of cell behaviour are developed here, referred to as the ‘pedigree’ and the ‘niche’ models. The pedigree model proposes that crypt cells are largely preprogrammed and receive minimal prompting from the environment as they move through a routine of cell differentiation and proliferation to become mature colonocytes. The niche model proposes that crypt cells are primarily influenced by the local microenvironments along the crypt, and that predetermined cell behaviour plays a negligible role in their development. In this paper we present a computational model of colonic crypts in the mouse, which enables a comparison of the quality and controllability of mature coloncyte production by crypts operating under these two contrasting conceptual models of crypt regulation

Analysis of Wnt signaling β-catenin spatial dynamics in HEK293T cells

Background Wnt/β-catenin signaling is involved in different stages of mammalian development and implicated in various cancers (e.g. colorectal cancer). Recent experimental and computational studies have revealed characteristics of the pathway, however a cell-specific spatial perspective is lacking. In this study, a novel 3D confocal quantitation protocol is developed to acquire spatial (two cellular compartments: nucleus and cytosol-membrane) and temporal quantitative data on target protein (e.g. β-catenin) concentrations in Human Epithelial Kidney cells (HEK293T) during perturbation (with either cycloheximide or Wnt3A). Computational models of the Wnt pathway are constructed and interrogated based on this data. Results A single compartment Wnt pathway model is compared with a simple β-catenin two compartment model to investigate Wnt3A signaling in HEK293T cells. When protein synthesis is inhibited, β-catenin decreases at the same rate in both cellular compartments, suggesting diffusional transport is fast compared to β-catenin degradation in the cytosol. With Wnt3A stimulation, the total amount of β-catenin rises throughout the cell, however the increase is initially (~first hour) faster in the nuclear compartment. While both models were able to reproduce the whole cell changes in β-catenin, only the compartment model reproduced the Wnt3A induced changes in β-catenin distribution and it was also the best fit for the data obtained when active transport was included alongside passive diffusion transport. Conclusions This integrated 3D quantitation imaging protocol and computational modeling approach allowed cell-specific compartment models of the signaling pathways to be constructed and analyzed. The Wnt models constructed in this study are the first for HEK293T and have suggested potential roles of inter-compartment transport to the dynamics of signaling