Influence of altered gait patterns on the hip joint contact forces

Children who exhibit gait deviations often present a range of bone deformities, particularly at the proximal femur. Altered gait may affect bone growth and lead to deformities by exerting abnormal stresses on the developing bones. The objective of this study was to calculate variations in the hip joint contact forces with different gait patterns. Muscle and hip joint contact forces of four children with different walking characteristics were calculated using an inverse dynamic analysis and a static optimisation algorithm. Kinematic and kinetic analyses were based on a generic musculoskeletal model scaled down to accommodate the dimensions of each child. Results showed that for all the children with altered gaits both the orientation and magnitude of the hip joint contact force deviated from normal. The child with the most severe gait deviations had hip joint contact forces 30% greater than normal, most likely due to the increase in muscle forces required to sustain his crouched stance. Determining how altered gait affects joint loading may help in planning treatment strategies to preserve correct loading on the bone from a young age.     

Growth control of Golgi phosphoinositides by reciprocal localization of sac1 lipid phosphatase and pik1 4-kinase

Compartment-specific control of phosphoinositide lipids is essential for cell function. The Sac1 lipid phosphatase regulates endoplasmic reticulum (ER) and Golgi phosphatidylinositol-4-phosphate [PI(4)P] in response to nutrient levels and cell growth stages. During exponential growth, Sac1p interacts with Dpm1p at the ER but shuttles to the Golgi during starvation. Here, we report that a C-terminal region in Sac1p is required for retention in the perinuclear ER, whereas the N-terminal domain is responsible for Golgi localization. We also show that starvation-induced shuttling of Sac1p to the Golgi depends on the coat protein complex II and the Rer1 adaptor protein. Starvation-induced shuttling of Sac1p to the Golgi specifically eliminates a pool of PI(4)P generated by the lipid kinase Pik1p. In addition, absence of nutrients leads to a rapid dissociation of Pik1p, together with its non-catalytical subunit Frq1p, from Golgi membranes. Reciprocal rounds of association/dissociation of the Sac1p lipid phosphatase and the Pik1p/Frq1p lipid kinase complex are responsible for growth-dependent control of Golgi phosphoinositides. Sac1p and Pik1p/Frq1p are therefore elements of a unique machinery that synchronizes ER and Golgi function in response to different growth conditions.     

Plant and fertiliser effects on rhizodegradation of crude oil in two soils with different nutrient status

Soils and sediments polluted with crude oil are of major environmental concern on various contaminated sites. Outdoors pot experiments were conducted to test the phytodegradation potential of common reed (Phragmites australis) and poplar (Populus nigra × maximowiczii) in fertilised and non-fertilised control treatments. Two topsoils (E, G) of different texture were mixed with crude oil. Soil analysis included hydrocarbon (HC) measurements, detection of labile phosphorus and mineralised nitrogen as well as dehydrogenase activity. Increased HC degradation by native soil biota was clearly related to higher P availability in soil G and to fertilisation in soil E. Except of the non-fertilised common reed treatment, plants did not enhance crude oil degradation. We found even inhibited degradation of high molecular weight HC in the presence of plants together with declining labile phosphorous concentrations due to planting on soil E. Native soil biota were able to use the whole range of crude oil compounds (C₁₀ to C₆₀) as a carbon source in the presence of sufficient nutrient concentrations in soil. This study is the first to show that reduced HC degradation in the higher molecular weight crude oil fraction (C₂₀ to C₄₀) is likely to be a consequence of decreased phosphorus availability for microorganisms in the plant rhizosphere.     

Enhancement of late successional plants on ex-arable land by soil inoculations

Restoration of species-rich grasslands on ex-arable land can help the conservation of biodiversity but faces three big challenges: absence of target plant propagules, high residual soil fertility and restoration of soil communities. Seed additions and top soil removal can solve some of these constraints, but restoring beneficial biotic soil conditions remains a challenge. Here we test the hypotheses that inoculation of soil from late secondary succession grasslands in arable receptor soil enhances performance of late successional plants, especially after top soil removal but pending on the added dose. To test this we grew mixtures of late successional plants in arable top (organic) soil or in underlying mineral soil mixed with donor soil in small or large proportions. Donor soils were collected from different grasslands that had been under restoration for 5 to 41 years, or from semi-natural grassland that has not been used intensively. Donor soil addition, especially when collected from older restoration sites, increased plant community biomass without altering its evenness. In contrast, addition of soil from semi-natural grassland promoted plant community evenness, and hence its diversity, but reduced community biomass. Effects of donor soil additions were stronger in mineral than in organic soil and larger with bigger proportions added. The variation in plant community composition was explained best by the abundances of nematodes, ergosterol concentration and soil pH. We show that in controlled conditions inoculation of soil from secondary succession grassland into ex-arable land can strongly promote target plant species, and that the role of soil biota in promoting target plant species is greatest when added after top soil removal. Together our results point out that transplantation of later secondary succession soil can promote grassland restoration on ex-arable land.     

Identification and characterization of equine herpesvirus type 1 pUL56 and its role in virus-induced downregulation of major histocompatibility complex class I

Major histocompatibility complex class I (MHC-I) molecules play an important role in host immunity to infection by presenting antigenic peptides to cytotoxic T lymphocytes (CTLs), which recognize and destroy virus-infected cells. Members of the Herpesviridae have developed multiple mechanisms to avoid CTL recognition by virtue of downregulation of MHC-I on the cell surface. We report here on an immunomodulatory protein involved in this process, pUL56, which is encoded by ORF1 of equine herpesvirus type 1 (EHV-1), an alphaherpesvirus. We show that EHV-1 pUL56 is a phosphorylated early protein which is expressed as different forms and predominantly localizes to Golgi membranes. In addition, the transmembrane (TM) domain of the type II membrane protein was shown to be indispensable for correct subcellular localization and a proper function. pUL56 by itself is not functional with respect to interference with MHC-I and likely needs another unidentified viral protein(s) to perform this action. Surprisingly, pUL49.5, an inhibitor of the transporter associated with antigen processing (TAP) and encoded by EHV-1 and related viruses, appeared not to be required for pUL56-induced early MHC-I downmodulation in infected cells. In conclusion, our data identify a new immunomodulatory protein, pUL56, involved in MHC-I downregulation which is unable to perform its function outside the context of viral infection.     

Protection of Armadillo/β-Catenin by Armless,a Novel Positive Regulator of Wingless Signaling

The Wingless (Wg/Wnt) signaling pathway is essential for metazoan development, where it is central to tissue growth and cellular differentiation. Deregulated Wg pathway activation underlies severe developmental abnormalities, as well as carcinogenesis. Armadillo/β-Catenin plays a key role in the Wg transduction cascade; its cytoplasmic and nuclear levels directly determine the output activity of Wg signaling and are thus tightly controlled. In all current models, once Arm is targeted for degradation by the Arm/β-Catenin destruction complex, its fate is viewed as set. We identified a novel Wg/Wnt pathway component, Armless (Als), which is required for Wg target gene expression in a cell-autonomous manner. We found by genetic and biochemical analyses that Als functions downstream of the destruction complex, at the level of the SCF/Slimb/βTRCP E3 Ub ligase. In the absence of Als, Arm levels are severely reduced. We show by biochemical and in vivo studies that Als interacts directly with Ter94, an AAA ATPase known to associate with E3 ligases and to drive protein turnover. We suggest that Als antagonizes Ter94''s positive effect on E3 ligase function and propose that Als promotes Wg signaling by rescuing Arm from proteolytic degradation, spotlighting an unexpected step where the Wg pathway signal is modulated.     

Rapid Recovery from Eutrophication of a Stratified Lake by Disruption of Internal Nutrient Load

Restoration of anthropogenically eutrophied lake ecosystems is difficult due to feedback mechanisms that stabilize the trophically degraded state. Here, we show rapid recovery of a eutrophic stratified lake in response to multiple restoration that targeted the feedback mechanisms of high external and internal nutrient loads, lack of a trophic cascade, and lack of structured littoral habitats. Lake Tiefwarensee (Germany) was exposed to aluminium and calcium treatment and fisheries management over 5 years. Within this period, in-lake phosphorus concentrations declined by more than 80%, and transparency, zooplankton biomass and fish assemblage structure and biomass responded immediately and almost linearly to the reduction in phosphorus concentrations. Phytoplankton biomass and chlorophyll a (chl a) concentrations likewise decreased in response to restoration, but the declining trend was interrupted by one recovery year with unusually high phytoplankton biomasses. The zooplankton:phytoplankton biomass ratio and the chl a:phosphorus ratio approached values observed in other stratified lakes during natural recovery from eutrophication. The slow response of Tiefwarensee to the reduction of external load, and the quick response to the chemical treatment suggest that the disruption of internal P recycling and loading was the decisive restoration measure in Tiefwarensee. The external load reduction was a necessary but not sufficient measure, at least in the short-term, whereas the low-effort fisheries management was of minor importance. A comparison with other case studies confirms that measures aiming to inactivate phosphorus are the most efficient approaches to restore stratified lakes in the short-term, but a shift to a permanent near-pristine state is possible only by additional P input control. Author Contributions: T.M. designed the study, analyzed data, and wrote the paper. M.D. analyzed data. T.G. analyzed data. P.K. designed the study and analyzed data. R.K. conceived of and designed the study. L.K, M.R. and M.S. analyzed data. G.W. contributed new methods, analyzed data and wrote parts of the paper. All authors contributed to writing the final version.     

Perturbing mitosis for anti‐cancer therapy: is cell death the only answer?

Interfering with mitosis for cancer treatment is an old concept that has proven highly successful in the clinics. Microtubule poisons are used to treat patients with different types of blood or solid cancer since more than 20 years, but how these drugs achieve clinical response is still unclear. Arresting cells in mitosis can promote their demise, at least in a petri dish. Yet, at the molecular level, this type of cell death is poorly defined and cancer cells often find ways to escape. The signaling pathways activated can lead to mitotic slippage, cell death, or senescence. Therefore, any attempt to unravel the mechanistic action of microtubule poisons will have to investigate aspects of cell cycle control, cell death initiation in mitosis and after slippage, at single‐cell resolution. Here, we discuss possible mechanisms and signaling pathways controlling cell death in mitosis or after escape from mitotic arrest, as well as secondary consequences of mitotic errors, particularly sterile inflammation, and finally address the question how clinical efficacy of anti‐mitotic drugs may come about and could be improved.     

Plant presence reduces root and shoot litter decomposition rates of crops and wild relatives

Plant and Soil - Cerrado woody species are divided into a small group of aluminum (Al)-accumulating species and the rest of the woody species. Both groups grow well on acidic and Al-rich soils. We...