Lumcorin: A leucine-rich repeat 9-derived peptide from human lumican inhibiting melanoma cell migration

We previously showed that lumican decreases melanoma progression. The aim of the present study was to determine the active sequence of the lumican core protein responsible for the inhibition of melanoma cell migration. Using different recombinant and synthetic peptides derived from lumican, we localized an active site in the leucine-rich repeat 9 domain of the lumican core protein. We propose the name lumcorin (fragment of lumican core protein) for the active peptide derived from this site. Lumcorin was able to inhibit melanoma cell migration in vitro.     

Porous gelatin hydrogels: 1. Cryogenic formation and structure analysis

In the present work, porous gelatin scaffolds were prepared by cryogenic treatment of a chemically cross-linked gelatin hydrogel, followed by removal of the ice crystals formed through lyophilization. This technique often leads to porous gels with a less porous skin. A simple method has been developed to solve this problem. The present study demonstrates that the hydrogel pore size decreased with an increasing gelatin concentration and with an increasing cooling rate of the gelatin hydrogel. Variation of the cryogenic parameters applied also enabled us to develop scaffolds with different pore morphologies (spherical versus transversal channel-like pores). In our opinion, this is the first paper in which temperature gradients during controlled cryogenic treatment were applied to induce a pore size gradient in gelatin hydrogels. With a newly designed cryo-unit, temperature gradients of 10 and 30 degrees C were implemented during the freezing step, resulting in scaffolds with average pore diameters of, respectively, +/-116 and +/-330 microm. In both cases, the porosity and pore size decreased gradually through the scaffolds. Pore size and structure analysis of the matrices was accomplished through a combination of microcomputed tomography using different software packages (microCTanalySIS and Octopus), scanning electron microscopy analysis, and helium pycnometry.     

Patchy recruitment patterns in marine invertebrates: a spatial test of the density-dependent hypothesis in the bivalve Spisula ovalis

Density-dependent and density-independent processes have been shown to influence the population dynamics of marine invertebrates, especially recruitment. However, their relative importance has not been evaluated in natural populations. High adult densities have been suggested to inhibit recruitment, especially in suspension-feeders which may ingest incoming larvae. Age structure and juvenile abundance were investigated in the bivalve Spisula ovalis in order to evaluate the importance of density dependence in generating spatial patterns. Age structure is readily established in this species owing to annual shell lines. An extensive sample (from about 100 sites a few hundred meters apart over 4 consecutive years) was analyzed in the statistical framework of spatial analyses, avoiding spurious correlations due to non-independence between neighboring sites. The area studied supports about ten annual cohorts, though only a few occur at each site. The overall picture is a mosaic of kilometer-scale patches of contrasted age structures, as revealed by highly significant spatial autocorrelations. To our knowledge, such large-scale spatial patterns in age structure have not previously been described in benthic invertebrates. Strong patterns are detected even for juveniles, and are independent of the adult biomass present before settlement. Therefore, patchy patterns of age structure mainly reflect density-independent effects, such as spatial variations in larval supply, passive transport of juveniles, or predation on recruits. In the absence of detailed spatial analyses, such patterns have been misinterpreted previously as negative effects of adult density on settlement success. Received: 21 November 1996 / Accepted: 20 February 1997     

Hepatic Mitogen-Activated Protein Kinase Phosphatase 1 Selectively Regulates Glucose Metabolism and Energy Homeostasis

The liver plays a critical role in glucose metabolism and communicates with peripheral tissues to maintain energy homeostasis. Obesity and insulin resistance are highly associated with nonalcoholic fatty liver disease (NAFLD). However, the precise molecular details of NAFLD remain incomplete. The p38 mitogen-activated protein kinase (MAPK) and c-Jun NH₂-terminal kinase (JNK) regulate liver metabolism. However, the physiological contribution of MAPK phosphatase 1 (MKP-1) as a nuclear antagonist of both p38 MAPK and JNK in the liver is unknown. Here we show that hepatic MKP-1 becomes overexpressed following high-fat feeding. Liver-specific deletion of MKP-1 enhances gluconeogenesis and causes hepatic insulin resistance in chow-fed mice while selectively conferring protection from hepatosteatosis upon high-fat feeding. Further, hepatic MKP-1 regulates both interleukin-6 (IL-6) and fibroblast growth factor 21 (FGF21). Mice lacking hepatic MKP-1 exhibit reduced circulating IL-6 and FGF21 levels that were associated with impaired skeletal muscle mitochondrial oxidation and susceptibility to diet-induced obesity. Hence, hepatic MKP-1 serves as a selective regulator of MAPK-dependent signals that contributes to the maintenance of glucose homeostasis and peripheral tissue energy balance. These results also demonstrate that hepatic MKP-1 overexpression in obesity is causally linked to the promotion of hepatosteatosis.     

Molecular composition and function of integrin-based collagen glues—Introducing COLINBRIs

Background

Despite detailed knowledge about the structure and signaling properties of individual collagen receptors, much remains to be learned about how these receptors participate in linking cells to fibrillar collagen matrices in tissues. In addition to collagen-binding integrins, a group of proteins with affinity both for fibrillar collagens and integrins link these two protein families together. We have introduced the name COLINBRI (COLlagen INtegrin BRIdging) for this set of molecules. Whereas collagens are the major building blocks in tissues and defects in these structural proteins have severe consequences for tissue integrity, the mild phenotypes of the integrin type of collagen receptors have raised questions about their importance in tissue biology and pathology.

Scope of review

We will discuss the two types of cell linkages to fibrillar collagen (direct- versus indirect COLINBRI-mediated) and discuss how the parallel existence of direct and indirect linkages to collagens may ensure tissue integrity.

Major conclusions

The observed mild phenotypes of mice deficient in collagen-binding integrins and the relatively restricted availability of integrin-binding sequences in mature fibrillar collagen matrices support the existence of indirect collagen-binding mechanisms in parallel with direct collagen binding in vivo.

General significance

A continued focus on understanding the molecular details of cell adhesion mechanisms to collagens will be important and will benefit our understanding of diseases like tissue- and tumor fibrosis where collagen dynamics are disturbed. This article is part of a Special Issue entitled Matrix-mediated cell behaviour and properties.     

Murine Spinal Cord Transcriptome Analysis Following Reduction of Prevalent Myelin cDNA Sequences

From 1,000 randomly selected colonies from cDNA libraries derived from murine spinal cord subtracted against white matter by means of suppression subtractive hybridization, 220 clones were identified as differentially expressed by dot blot analysis. Sequence analysis by the BLAST programming identified 140 unique genes. (1) The percentage of known sequences from myelin and other glial sources was reduced by approximately 75% over previous, similar subtractions employing visual cortex as the driver. (2) Differentially expressed genes tended to reflect existing expectations concerning structure and function of the spinal cord. (3) About 35% of all genes differentially expressed in the spinal cord in this study are also known to be differentially expressed for this structure as tabulated in the UniGene database. (4) About 33% of all genes differentially expressed in the present study are recorded as not present when measured in the spinal cord according to the UniGene database indicating that present techniques are not recording about a third of differentially expressed genes in this structure. (5) About 15% of all differentially expressed genes are for unknown, putative or hypothetical protein products. (6) About 4% of all differentially expressed genes are novel expressed sequence tags for the mouse. The current study demonstrates the importance of reducing the presence of glial associated sequences when comparing brain regions. It is concluded that the persistence of some myelin sequences in the spinal cord when white matter is used as the driver indicates that myelination is more active in this structure than for those areas represented by white matter and corpus callosum.     

Compensation for unfavorable characteristics of irregular individual shift rotas

Some employees of TV companies, such as those who produce remote TV programs, have to cope with very irregular rotas and many short-term schedule deviations. Many of these employees complain about the negative effects of such on their wellbeing and private life. Therefore, a working group of employers, council representatives, and researchers developed a so-called bonus system. Based on the criteria of the BESIAK system, the following list of criteria for the ergonomic assessment of irregular shift systems was developed: proportion of night hours worked between 22:00 and 01:00 h and between 06:00 and 07:00 h, proportion of night hours worked between 01:00 and 06:00 h, number of successive night shifts, number of successive working days, number of shifts longer than 9 h, proportion of phase advances, off hours on weekends, work hours between 17:00 and 23:00 h from Monday to Friday, number of working days with leisure time at remote places, and sudden deviations from the planned shift rota. Each individual rota was evaluated in retrospect. If pre-defined thresholds of criteria were surpassed, bonus points were added to the worker's account. In general, more bonus points add up to more free time. Only in particular cases was monetary compensation possible for some criteria. The bonus point system, which was implemented in the year 2002 for about 850 employees of the TV company, has the advantages of more transparency concerning the unfavorable characteristics of working-time arrangements, incentive for superiors to design “good” rosters that avoid the bonus point thresholds (to reduce costs), positive short-term effects on the employee social life, and expected positive long-term effects on the employee health. In general, the most promising approach to cope with the problems of shift workers in irregular and flexible shift systems seems to be to increase their influence on the arrangement of working times. If this is not possible, bonus point systems may help to achieve greater transparency and fairness in the distribution of unfavorable working-time arrangements within a team, and even reduce the unnecessary unfavorable aspects of shift systems.     

Mechanical stress,fracture risk and beak evolution in Darwin's ground finches (Geospiza)

Darwin''s finches have radiated from a common ancestor into 14 descendent species, each specializing on distinct food resources and evolving divergent beak forms. Beak morphology in the ground finches (Geospiza) has been shown to evolve via natural selection in response to variation in food type, food availability and interspecific competition for food. From a mechanical perspective, however, beak size and shape are only indirectly related to birds'' abilities to crack seeds, and beak form is hypothesized to evolve mainly under selection for fracture avoidance. Here, we test the fracture-avoidance hypothesis using finite-element modelling. We find that across species, mechanical loading is similar and approaches reported values of bone strength, thus suggesting pervasive selection on fracture avoidance. Additionally, deep and wide beaks are better suited for dissipating stress than are more elongate beaks when scaled to common sizes and loadings. Our results illustrate that deep and wide beaks in ground finches enable reduction of areas with high stress and peak stress magnitudes, allowing birds to crack hard seeds while limiting the risk of beak failure. These results may explain strong selection on beak depth and width in natural populations of Darwin''s finches.