Holistic differential analysis of embryo-induced alterations in the proteome of bovine endometrium in the preattachment period

During the peri-implantation period, molecular signaling between embryo and endometrium (layer of tissue lining the uterus lumen) is supposed to be crucial for the maintenance of pregnancy. To investigate embryo-induced alterations in the proteome of bovine endometrium in the preattachment period (day 18), we used monozygotic cattle twins (generated by embryo splitting) as a model eliminating genetic variability as a source for proteome differences. One of the twins was pregnant after the transfer of two in vitro produced blastocysts, while the corresponding twin received a sham-transfer and served as a nonpregnant control. The two-dimensional fluorescence difference gel electrophoresis (2-D DIGE) analysis of the endometrium samples of three twin pairs (pregnant/nonpregnant) revealed four proteins with significantly higher abundance (p < 10(-9)) in each sample derived from the pregnant animals: Rho GDP dissociation inhibitor beta; 20 alpha-hydroxysteroid dehydrogenase (20 alpha-HSD); soluble NADP(+)-dependent isocitrate dehydrogenase 1; and acyl-CoA-binding protein. To verify the accuracy of the 2-D DIGE quantification, the abundances of 20 alpha-HSD were quantified by a targeted cleavable isotope-coded affinity tag (ICAT) approach. The mass spectrometry-based ICAT quantification matched perfectly the results obtained by 2-D DIGE quantification, demonstrating the accuracy of our data. These results demonstrate that our model (monozygotic twins) in combination with the appropriate analytical tools is particularly suitable for the detection of the proteins involved in the embryo-maternal interactions.     

Human mesenchymal stem cells in contact with their environment: surface characteristics and the integrin system

The identification of mesenchymal stem cells (MSCs) in adult human tissues and the disclosure of their self-renew-al and multi-lineage differentiation capabilities have provided exciting prospects for cell-based regeneration and tis-sue engineering. Although a considerable amount of data is available describing MSCs, there is still lack of information regarding the molecular mechanisms that govern their adhesion and migration. In this work, we will review the current state of knowledge on integrins and other adhesion molecules found to be expressed on MSCs. The discussed topics include the characteristics of MSCs and their clinical applications, integrins and their central role in cell-matrix attachment and migration, and comments on mobilization, differentiation and contribution to tumour development. Finally, by understanding the complex and fundamental pathways by which MSCs attach and migrate, it might be possible to fine-tune the strategies for effective and safe use of MSCs in regenerative therapies.     

Hydrological regulation drives regime shifts: evidence from paleolimnology and ecosystem modeling of a large shallow Chinese lake

Quantitative evidence of sudden shifts in ecological structure and function in large shallow lakes is rare, even though they provide essential benefits to society. Such ‘regime shifts’ can be driven by human activities which degrade ecological stability including water level control (WLC) and nutrient loading. Interactions between WLC and nutrient loading on the long‐term dynamics of shallow lake ecosystems are, however, often overlooked and largely underestimated, which has hampered the effectiveness of lake management. Here, we focus on a large shallow lake (Lake Chaohu) located in one of the most densely populated areas in China, the lower Yangtze River floodplain, which has undergone both WLC and increasing nutrient loading over the last several decades. We applied a novel methodology that combines consistent evidence from both paleolimnological records and ecosystem modeling to overcome the hurdle of data insufficiency and to unravel the drivers and underlying mechanisms in ecosystem dynamics. We identified the occurrence of two regime shifts: one in 1963, characterized by the abrupt disappearance of submerged vegetation, and another around 1980, with strong algal blooms being observed thereafter. Using model scenarios, we further disentangled the roles of WLC and nutrient loading, showing that the 1963 shift was predominantly triggered by WLC, whereas the shift ca. 1980 was attributed to aggravated nutrient loading. Our analysis also shows interactions between these two stressors. Compared to the dynamics driven by nutrient loading alone, WLC reduced the critical P loading and resulted in earlier disappearance of submerged vegetation and emergence of algal blooms by approximately 26 and 10 years, respectively. Overall, our study reveals the significant role of hydrological regulation in driving shallow lake ecosystem dynamics, and it highlights the urgency of using multi‐objective management criteria that includes ecological sustainability perspectives when implementing hydrological regulation for aquatic ecosystems around the globe.     

A new Mycena species with blue basidiomata and porioid hymenophore from Taiwan

A small blue stipitate-pileate mushroom with porioid hymenophore was found on dead Calamus sp. (Arecaceae) in Taiwan. Microscopic characteristics indicated a placement within the Mycenaceae. ITS as well as partial LSU ribosomal RNA gene sequences analyses showed a close relationship with Mycena illuminans within the Mycenaceae. A new species with completely blue basidiomata, Mycena indigotica, is proposed based on morphological and molecular evidence.     

Accuracy in the prediction of disease epidemics when ensembling simple but highly correlated models

Ensembling combines the predictions made by individual component base models with the goal of achieving a predictive accuracy that is better than that of any one of the constituent member models. Diversity among the base models in terms of predictions is a crucial criterion in ensembling. However, there are practical instances when the available base models produce highly correlated predictions, because they may have been developed within the same research group or may have been built from the same underlying algorithm. We investigated, via a case study on Fusarium head blight (FHB) on wheat in the U.S., whether ensembles of simple yet highly correlated models for predicting the risk of FHB epidemics, all generated from logistic regression, provided any benefit to predictive performance, despite relatively low levels of base model diversity. Three ensembling methods were explored: soft voting, weighted averaging of smaller subsets of the base models, and penalized regression as a stacking algorithm. Soft voting and weighted model averages were generally better at classification than the base models, though not universally so. The performances of stacked regressions were superior to those of the other two ensembling methods we analyzed in this study. Ensembling simple yet correlated models is computationally feasible and is therefore worth pursuing for models of epidemic risk.     

Identical mutations and phenotypic variation

The relationship between pathogenetic mutations and disease phenotype is becoming increasingly complex. Well-delineated clinical entities can be genetically heterogeneous, and mutations in a particular gene may result in fundamental clinical differences. Genetic heterogeneity includes mutations at different gene loci or allelic mutations within a single gene, resulting in a similar phenotype. However, one and the same mutation is expected to be associated with a uniform clinical picture. In the present article, evidence is presented that this is not necessarily the case, and examples of identical mutations resulting in highly variable combinations of clinical features are discussed. Although the number of examples of this puzzling phenomenon is rapidly increasing, the underlying mechanisms are as yet poorly understood. In some cases, interacting genetic alterations can be held responsible for the phenotypic heterogeneity; in others, epigenetic phenomena provide a plausible explanation. These and other mechanisms under discussion are considered here. The Mendelian concept of monofactorial disease causation appears to be increasingly untenable for a growing number of developmental errors. Received: 15 April 1997 / Accepted: 30 April 1997