Matrix metalloproteinases 9 and 2 are necessary for the migration of Langerhans cells and dermal dendritic cells from human and murine skin

Dendritic cells migrate from the skin to the draining lymph nodes. They transport immunogenic MHC-peptide complexes, present them to Ag-specific T cells in the T areas, and thus generate immunity. Migrating dendritic cells encounter physical obstacles, such as basement membranes and collagen meshwork. Prior work has revealed that matrix metalloproteinase-9 (MMP-9) contributes to mouse Langerhans cell migration. In this study, we use mouse and human skin explant culture models to further study the role of MMPs in the migration and maturation of skin dendritic cells. We found that MMP-2 and MMP-9 are expressed on the surface of dendritic cells from the skin, but not from other sources. They are also expressed in migrating Langerhans cells in situ. The migration of both Langerhans cells and dermal dendritic cells is inhibited by a broad spectrum inhibitor of MMPs (BB-3103), by Abs to MMP-9 and -2, and by the natural tissue inhibitors of metalloproteinases (TIMP), TIMP-1 and TIMP-2. Inhibition by anti-MMP-2 and TIMP-2 define a functional role for MMP-2 in addition to the previously described function of MMP-9. The importance of MMP-9 was emphasized using MMP-9-deficient mice in which Langerhans cell migration from skin explants was strikingly reduced. However, MMP-9 was only required for Langerhans cell migration and not maturation, since nonmigrating Langerhans cells isolated from the epidermis matured normally with regard to morphology, phenotype, and T cell stimulatory function. These data underscore the importance of MMPs, and they may be of relevance for therapeutically regulating dendritic cell migration in clinical vaccination approaches.     

Using mouse models to dissect the genetics of obesity

Mice have proved to be powerful models for understanding obesity in humans and farm animals. Single-gene mutants and genetically modified mice have been used successfully to discover genes and pathways that can regulate body weight. For polygenic obesity, the most common pattern of inheritance, many quantitative trait loci (QTLs) have been mapped in crosses between selected and inbred mouse lines. Most QTL effects are additive, and diet, age and gender modify the genetic effects. Congenic, recombinant inbred, advanced intercross, and chromosome substitution strains are needed to map QTLs finely, to identify the genes underlying the traits, and to examine interactions between them.     

Ulaancricetodon badamae n. gen., n. sp. (Mammalia, Rodentia, Cricetidae) from the Valley of Lakes in Central Mongolia

The smallest and most primitive Oligocene cricetid,Ulaancricetodon badamae n. gen., n. sp. is described from the Hsanda Gol Formation in Mongolia. The fossils were recovered from stratified fossil horizons immediately below and above a basalt layer dated at 31.5 Ma (⁴⁰Ar/³⁹Ar-data), that is an Early Oligocene age. Although the dental formula is muroid (1-0-0-3/1-0-0-3), the tooth morphology and tooth size ofUlaancricetodon badamae n. gen., n. sp. point to a close relationship with the zapodidHeosminthus Wang 1985, which is known from the Asian Late Eocene to Early Oligocene.     

Abiotic stresses increase plant regeneration ability

In disturbed habitats, vegetative regeneration is partly ruled by plant reserves and intrinsic growth rates. Under nutrient-limiting conditions, perennial plants tend to exhibit an increased allocation to storage organs. Under mechanically stressful conditions, plants also tend to increase allocation to below-ground biomass and storage organs. We tested whether those stresses acting differently on plants (nutrient level versus mechanical forces) led to similar effect on storage organs and regeneration ability. We measured, for an aquatic plant species, (1) the size and allocation to storage organs (stems) and (2) the regeneration ability of the storage organs. Plant stems were collected in 4 habitats ranked along a nutrient stress gradient, and having encountered null versus significant mechanical stress (flowing water). All stems were placed in similar neutral conditions and left for a period of 6 weeks before measuring their survival and growth. Dry mass allocation to the storage organ (stem) was higher in stressful habitats. Moreover, stress encountered by plants before the experiment significantly affected regeneration: stems of previously stressed plants (i.e. plants that had grown in nutrient-poor or mechanically stressful habitats) survived better than unstressed ones. Stems of plants having encountered mechanical stress before the experiment had increased growth in nutrient-rich habitats but reduced growth in the poorest habitats. These results demonstrate that regeneration could rely on the level of stress previously encountered by plants. Stress could lead to greater regeneration ability following mechanical failure. The possible mechanisms involved in these results are discussed.     

The Involvement of Mitochondrial Amidoxime Reducing Components 1 and 2 and Mitochondrial Cytochrome b5 in N-Reductive Metabolism in Human Cells

The mitochondrial amidoxime reducing component mARC is a recently discovered molybdenum enzyme in mammals. mARC is not active as a standalone protein, but together with the electron transport proteins NADH-cytochrome b₅ reductase (CYB5R) and cytochrome b₅ (CYB5), it catalyzes the reduction of N-hydroxylated compounds such as amidoximes. The mARC-containing enzyme system is therefore considered to be responsible for the activation of amidoxime prodrugs. All hitherto analyzed mammalian genomes code for two mARC genes (also referred to as MOSC1 and MOSC2), which share high sequence similarities. By RNAi experiments in two different human cell lines, we demonstrate for the first time that both mARC proteins are capable of reducing N-hydroxylated substrates in cell metabolism. The extent of involvement is highly dependent on the expression level of the particular mARC protein. Furthermore, the mitochondrial isoform of CYB5 (CYB5B) is clearly identified as an essential component of the mARC-containing N-reductase system in human cells. The participation of the microsomal isoform (CYB5A) in N-reduction could be excluded by siRNA-mediated down-regulation in HEK-293 cells and knock-out in mice. Using heme-free apo-CYB5, the contribution of mitochondrial CYB5 to N-reductive catalysis was proven to strictly depend on heme. Finally, we created recombinant CYB5B variants corresponding to four nonsynonymous single nucleotide polymorphisms (SNPs). Investigated mutations of the heme protein seemed to have no significant impact on N-reductive activity of the reconstituted enzyme system.     

Adaptations to increasing hydraulic stress: morphology, hydrodynamics and fitness of two higher aquatic plant species

Sessile organisms often exhibit morphological changes in response to permanent exposure to mechanical stimulation (wind or water movements). The adaptive value of these morphological changes (hydrodynamic performance and consequences on fitness) has not been studied extensively, particularly for higher plants submitted to flow stress. The aim was to determine the adaptive value of morphological patterns observed within two higher aquatic plant species, Berula erecta and Mentha aquatica, growing along a natural flow stress gradient. The hydrodynamic ability of each ramet was investigated through quantitative variables (drag coefficient and E-value). Fitness-related traits based on vegetative growth and clonal multiplication were assessed for each individual. For both species, the drag coefficient and the E-value were explained only to a limited extent by the morphological traits used. B. erecta exhibited a reduction in size and low overall plant drag at higher flow velocities, despite high drag values relative to leaf area, due to a low flexibility. The plants maintained their fitness, at least in part, through biomass reallocation: one tall ramet at low velocity, but shorter individuals with many interconnected stolons when flow velocity increased. For M. aquatica, morphological differences along the velocity gradient did not lead to greater hydrodynamic performance. Plant size increased with increasing velocities, suggesting the indirect effects of current favouring growth in high velocities. The fitness-related traits did not demonstrate lower plant fitness for high velocities. Different developmental constraints linked to plant morphology and trade-offs between major plant functions probably lead to different plant responses to flow stress.     

The perceived temperature – a versatile index for the assessment of the human thermal environment. Part A: scientific basics

The Perceived Temperature (PT) is an equivalent temperature based on a complete heat budget model of the human body. It has proved its suitability for numerous applications across a wide variety of scales from micro to global and is successfully used both in daily forecasts and climatological studies. PT is designed for staying outdoors and is defined as the air temperature of a reference environment in which the thermal perception would be the same as in the actual environment. The calculation is performed for a reference subject with an internal heat production of 135 W m⁻² (who is walking at 4 km h⁻¹ on flat ground). In the reference environment, the mean radiant temperature equals the air temperature and wind velocity is reduced to a slight draught. The water vapour pressure remains unchanged. Under warm/humid conditions, however, it is implicitly related to a relative humidity of 50%. Clothing is adapted in order to achieve thermal comfort. If this is impossible, cold or heat stress will occur, respectively. The assessment of thermal perception by means of PT is based on Fanger’s Predicted Mean Vote (PMV) together with additional model extensions taking account of stronger deviations from thermal neutrality. This is performed using a parameterisation based on a two-node model. In the cold, it allows the mean skin temperature to drop below the comfort value. In the heat, it assesses additionally the enthalpy of sweat-moistened skin and of wet clothes. PT has the advantages of being self-explanatory due to its deviation from air temperature and being—via PMV—directly linked to a thermo-physiologically-based scale of thermal perception that is widely used and has stood the test of time. This paper explains in detail the basic equations of the human heat budget and the coefficients of the parameterisations.     

The removal of stickies with modified starch and chitosan-Highly cationic and hydrophobic types compared with unmodified ones

The removal of dissolved and colloidal substances (DCS) in paper cycling water, so called stickies, with tailored natural polymers, having cationic as well as hydrophobic groups, was investigated using model suspensions made by the recycling of paper. The sticky content, characterized by the turbidity, the anionic charge, and the total organic carbon content (TOC) was increased by the addition of latex. The dynamic surface tension was established as useful tool for the characterization of the sticky content. The sticky removal using the starch derivatives (with benzyl- as well as ethyl-substituents), from very low up to high cationic charge and N-(benzyl)chitosan was compared. Depending on the properties of the derivatives two possible mechanisms can be found: "charge dominated removal" or "removal dominated by hydrophobicity." It seems that turbidity and TOC are lowered especially due to charge interaction whereas the increase of the surface tension is mainly caused by the hydrophobic character of the modified natural polymers.