The chronology and kinematics of late Palaeozoic deformation in the NW contact metamorphic aureole of the Land's End Granite

A structural investigation of coastal exposures between Cape Cornwall and Pendeen Watch, in the NW contact metamorphic aureole of the Land’s End Granite, has confirmed a similar deformation chronology as in a reference section around Porthleven. D1 deformation is represented by an ubiquitous bedding-parallel S1 cleavage although F1 folds have not been recognised. D2 deformation is more localised and characterised by open F2 folds that verge WSW to NW and are associated with an ENE to SE dipping S2 crenulation cleavage. These structures are commonly obscured by later deformation and contact metamorphism and have not been described previously. A set of steeply inclined NNW-SSE trending, and subordinate set of moderately SE dipping, post-D2 metamorphic quartz veins formed coevally during an episode of strike-slip deformation prior to, or during, the early stages of D3 deformation. D3 deformation is widespread and represented by F3 folds and a WNW to NW dipping S3 crenulation cleavage; it has been recorded previously as D2 deformation. Two orders of F3 folds are developed; first order folds have a wavelength of up to 50 m, verge ESE, and result in vertical or steeply inclined bedding and S1 cleavage on their short limbs. Second order folds usually have a wavelength of 1 m or less and usually verge ESE, unless on the short limb of first order folds, where they verge WNW. Previously published data, indicating a dominant NW to WNW vergence of F3 folds on the northern flank of the Land’s End Granite are incorrect. D3 structures are consistent with formation during the extensional reactivation of large-scale thrust faults. Granite emplacement post-dates all three episodes of ductile deformation but granites and their host rocks are deformed by a late brittle expression of D3 deformation. The Land’s End pluton has been accommodated, at the current exposure level, primarily by roof uplift that has resulted in the tilting of D3 and earlier structures to the NW by 40-50º; this may have been accompanied by differential vertical axis rotations of the host rock. The last significant Palaeozoic deformation episode formed F4 folds and S4 cleavage and was a consequence of Mid- to Late Permian ENE-WSW shortening

The importance of sedimenting organic matter, relative to oxygen and temperature, in structuring lake profundal macroinvertebrate assemblages

We quantified the role of a main food resource, sedimenting organic matter (SOM), relative to oxygen (DO) and temperature (TEMP) in structuring profundal macroinvertebrate assemblages in boreal lakes. SOM from 26 basins of 11 Finnish lakes was analysed for quantity (sedimentation rates), quality (C:N:P stoichiometry) and origin (carbon stable isotopes, d13C). Hypolimnetic oxygen and temperature were measured from each site during summer stratification. Partial canonical correspondence analysis (CCA) and partial regression analyses were used to quantify contributions of SOM, DO and TEMP to community composition and three macroinvertebrate metrics. The results suggested a major contribution of SOM in regulating the community composition and total biomass. Oxygen best explained the Shannon diversity, whereas TEMP had largest contribution to the variation of Benthic Quality Index. Community composition was most strongly related to d13C of SOM. Based on additional d13C and stoichiometric analyses of chironomid taxa, marked differences were apparent in their utilization of SOM and body stoichiometry; taxa characteristic of oligotrophic conditions exhibited higher C:N ratios and lower C:P and N:P ratios compared to the species typical of eutrophic lakes. The results highlight the role of SOM in regulating benthic communities and the distributions of individual species, particularly in oligotrophic systems

Turning around an ailing district hospital: a realist evaluation of strategic changes at Ho Municipal Hospital (Ghana)

<p>Abstract</p> <p>Background</p> <p>There is a growing consensus that linear approaches to improving the performance of health workers and health care organisations may only obtain short-term results. An alternative approach premised on the principle of human resource management described as a form of 'High commitment management', builds upon a bundles of balanced practices. This has been shown to contribute to better organisational performance. This paper illustrates an intervention and outcome of high commitment management (HiCom) at an urban hospital in Ghana. Few studies have shown how HiCom management might contribute to better performance of health services and in particular of hospitals in low and middle-income settings.</p> <p>Methods</p> <p>A realist case study design was used to analyse how specific management practices might contribute to improving the performance of an urban district hospital in Ho, Volta Region, in Ghana. Mixed methods were used to collect data, including document review, in-depth interviews, group discussions, observations and a review of routine health information.</p> <p>Results</p> <p>At Ho Municipal Hospital, the management team dealt with the crisis engulfing the ailing urban district hospital by building an alliance between hospital staff to generate a sense of ownership with a focus around participative problem analysis. The creation of an alliance led to improving staff morale and attitude, and contributed also to improvements in the infrastructure and equipment. This in turn had a positive impact on the revenue generating capacity of the hospital. The quick turn around in the state of this hospital showed that change was indeed possible, a factor that greatly motivated the staff.</p> <p>In a second step, the management team initiated the development of a strategic plan for the hospital to maintain the dynamics of change. This was undertaken through participative methods and sustained earlier staff involvement, empowerment and feelings of reciprocity. We found that these factors acted as the core mechanisms underlying the changes taking place at Ho Municipal Hospital.</p> <p>Conclusions</p> <p>This study shows how a hospital management team in Ghana succeeded in resuscitating an ailing hospital. Their high commitment management approach led to the active involvement and empowerment of staff. It also showed how a realist evaluation approach such as this, could be used in the research of the management of health care organisations to explain how management interventions may or may not work.</p

Inhibition of Histone Deacetylase Activity in Human Endometrial Stromal Cells Promotes Extracellular Matrix Remodelling and Limits Embryo Invasion

Invasion of the trophoblast into the maternal decidua is regulated by both the trophoectoderm and the endometrial stroma, and entails the action of tissue remodeling enzymes. Trophoblast invasion requires the action of metalloproteinases (MMPs) to degrade extracellular matrix (ECM) proteins and in turn, decidual cells express tissue inhibitors of MMPs (TIMPs). The balance between these promoting and restraining factors is a key event for the successful outcome of pregnancy. Gene expression is post-transcriptionally regulated by histone deacetylases (HDACs) that unpacks condensed chromatin activating gene expression. In this study we analyze the effect of histone acetylation on the expression of tissue remodeling enzymes and activity of human endometrial stromal cells (hESCs) related to trophoblast invasion control. Treatment of hESCs with the HDAC inhibitor trichostatin A (TSA) increased the expression of TIMP-1 and TIMP-3 while decreased MMP-2, MMP-9 and uPA and have an inhibitory effect on trophoblast invasion. Moreover, histone acetylation is detected at the promoters of TIMP-1 and TIMP-3 genes in TSA-treated. In addition, in an in vitro decidualized hESCs model, the increase of TIMP-1 and TIMP-3 expression is associated with histone acetylation at the promoters of these genes. Our results demonstrate that histone acetylation disrupt the balance of ECM modulators provoking a restrain of trophoblast invasion. These findings are important as an epigenetic mechanism that can be used to control trophoblast invasion

Low Level of Low-Density Lipoprotein Receptor-Related Protein 1 Predicts an Unfavorable Prognosis of Hepatocellular Carcinoma after Curative Resection

BACKGROUND: Low-density lipoprotein receptor-related protein 1 (LRP1) is a multifunctional receptor involved in receptor-mediated endocytosis and cell signaling. The aim of this study was to elucidate the expression and mechanism of LRP1 in hepatocellular carcinoma (HCC). METHODS: LRP1 expression in 4 HCC cell lines and 40 HCC samples was detected. After interruption of LRP1 expression in a HCC cell line either with specific lentiviral-mediated shRNA LRP1 or in the presence of the LRP1-specific chaperone, receptor-associated protein (RAP), the role of LRP1 in the migration and invasion of HCC cells was assessed in vivo and in vitro, and the expression of matrix metalloproteinase (MMP) 9 in cells and the bioactivity of MMP9 in the supernatant were assayed. The expression and prognostic value of LRP1 were investigated in 327 HCC specimens. RESULTS: Low LRP1 expression was associated with poor HCC prognosis, with low expression independently related to shortened overall survival and increased tumor recurrence rate. Expression of LRP1 in non-recurrent HCC samples was significantly higher than that in early recurrent samples. LRP1 expression in HCC cell lines was inversely correlated with their metastatic potential. After inhibition of LRP1, low-metastatic SMCC-7721 cells showed enhanced migration and invasion and increased expression and bioactivity of MMP9. Correlation analysis showed a negative correlation between LRP1 and MMP9 expression in HCC patients. The prognostic value of LRP1 expression was validated in the independent data set. CONCLUSIONS: LRP1 modulated the level of MMP9 and low level of LRP1 expression was associated with aggressiveness and invasiveness in HCCs. LRP1 offered a possible strategy for tumor molecular therapy

Light interception principally drives the understory response to boxelder invasion in riparian forests

Since several decades, American boxelder (Acer negundo) is replacing white willow (Salix alba) riparian forests along southern European rivers. This study aims to evaluate the consequences of boxelder invasion on understory community in riparian areas. We determined the understory species richness, composition and biomass in boxelder and white willow stands located in three riparian forests, representative of three rivers with distinct hydrological regimes. We investigated correlation of these variables to soil moisture and particle size, main soil nutrient stocks, potential nitrification and denitrification, tree canopy cover and photosynthetic active radiation (PAR) at the ground level. A greenhouse experiment was then conducted to identify the causal factors responsible for changes in the understory. The effect of soil type, PAR level and water level on the growth and the biomass production of Urtica dioica were examined. A lower plant species richness and biomass, and a modification of community composition were observed for boxelder understory in all sites, regardless of their environmental characteristics. The strongest modification that follows boxelder invasion was the decline in U. dioica, the dominant species of the white willow forest understory. These differences were mainly correlated with a lower incident PAR under boxelder canopy. The greenhouse experiment identified PAR level as the main factor responsible for the changes in U. dioica stem number and biomass. Our results indicate that adult boxelder acts as an ecosystem engineer that decreases light availability. The opportunistic invasion by boxelder leads to important understory changes, which could alter riparian ecosystem functioning

EB1 Is Required for Spindle Symmetry in Mammalian Mitosis

Most information about the roles of the adenomatous polyposis coli protein (APC) and its binding partner EB1 in mitotic cells has come from siRNA studies. These suggest functions in chromosomal segregation and spindle positioning whose loss might contribute to tumourigenesis in cancers initiated by APC mutation. However, siRNA-based approaches have drawbacks associated with the time taken to achieve significant expression knockdown and the pleiotropic effects of EB1 and APC gene knockdown. Here we describe the effects of microinjecting APC- or EB1- specific monoclonal antibodies and a dominant-negative EB1 protein fragment into mammalian mitotic cells. The phenotypes observed were consistent with the roles proposed for EB1 and APC in chromosomal segregation in previous work. However, EB1 antibody injection also revealed two novel mitotic phenotypes, anaphase-specific cortical blebbing and asymmetric spindle pole movement. The daughters of microinjected cells displayed inequalities in microtubule content, with the greatest differences seen in the products of mitoses that showed the severest asymmetry in spindle pole movement. Daughters that inherited the least mobile pole contained the fewest microtubules, consistent with a role for EB1 in processes that promote equality of astral microtubule function at both poles in a spindle. We propose that these novel phenotypes represent APC-independent roles for EB1 in spindle pole function and the regulation of cortical contractility in the later stages of mitosis. Our work confirms that EB1 and APC have important mitotic roles, the loss of which could contribute to CIN in colorectal tumour cells

LRP-1 Promotes Cancer Cell Invasion by Supporting ERK and Inhibiting JNK Signaling Pathways

Background: The low-density lipoprotein receptor-related protein-1 (LRP-1) is an endocytic receptor mediating the clearance of various extracellular molecules involved in the dissemination of cancer cells. LRP-1 thus appeared as an attractive receptor for targeting the invasive behavior of malignant cells. However, recent results suggest that LRP-1 may facilitate the development and growth of cancer metastases in vivo, but the precise contribution of the receptor during cancer progression remains to be elucidated. The lack of mechanistic insights into the intracellular signaling networks downstream of LRP-1 has prevented the understanding of its contribution towards cancer. Methodology/Principal Findings: Through a short-hairpin RNA-mediated silencing approach, we identified LRP-1 as a main regulator of ERK and JNK signaling in a tumor cell context. Co-immunoprecipitation experiments revealed that LRP-1 constitutes an intracellular docking site for MAPK containing complexes. By using pharmacological agents, constitutively active and dominant-negative kinases, we demonstrated that LRP-1 maintains malignant cells in an adhesive state that is favorable for invasion by activating ERK and inhibiting JNK. We further demonstrated that the LRP-1-dependent regulation of MAPK signaling organizes the cytoskeletal architecture and mediates adhesive complex turnover in cancer cells. Moreover, we found that LRP-1 is tethered to the actin network and to focal adhesion sites and controls ERK and JNK targeting to talin-rich structures. Conclusions: We identified ERK and JNK as the main molecular relays by which LRP-1 regulates focal adhesion disassembly of malignant cells to support invasion