Acetylcholine receptor pathway mutations explain various fetal akinesia deformation sequence disorders

Impaired fetal movement causes malformations, summarized as fetal akinesia deformation sequence (FADS), and is triggered by environmental and genetic factors. Acetylcholine receptor (AChR) components are suspects because mutations in the fetally expressed gamma subunit (CHRNG) of AChR were found in two FADS disorders, lethal multiple pterygium syndrome (LMPS) and Escobar syndrome. Other AChR subunits alpha1, beta1, and delta (CHRNA1, CHRNB1, CHRND) as well as receptor-associated protein of the synapse (RAPSN) previously revealed missense or compound nonsense-missense mutations in viable congenital myasthenic syndrome; lethality of homozygous null mutations was predicted but never shown. We provide the first report to our knowledge of homozygous nonsense mutations in CHRNA1 and CHRND and show that they were lethal, whereas novel recessive missense mutations in RAPSN caused a severe but not necessarily lethal phenotype. To elucidate disease-associated malformations such as frequent abortions, fetal edema, cystic hygroma, or cardiac defects, we studied Chrna1, Chrnb1, Chrnd, Chrng, and Rapsn in mouse embryos and found expression in skeletal muscles but also in early somite development. This indicates that early developmental defects might be due to somite expression in addition to solely muscle-specific effects. We conclude that complete or severe functional disruption of fetal AChR causes lethal multiple pterygium syndrome whereas milder alterations result in fetal hypokinesia with inborn contractures or a myasthenic syndrome later in life.     

The role of EMT in renal fibrosis

It is clear that the well-described phenomenon of epithelial–mesenchymal transition (EMT) plays a pivotal role in embryonic development, wound healing, tissue regeneration, organ fibrosis and cancer progression. EMTs have been classified into three subtypes based on the functional consequences and biomarker context in which they are encountered. This review will highlight findings on type II EMT as a direct contributor to the kidney myofibroblast population in the development of renal fibrosis, specifically in diabetic nephropathy, the signalling molecules and the pathways involved in type II EMT and changes in the expression of specific miRNA with the EMT process. These findings have provided new insights into the activation and development of EMT during disease processes and may lead to possible therapeutic interventions to suppress EMTs and potentially reverse organ fibrosis.     

Biochemical Characterisation and Localization in Brain of a Human Brain-Leucocyte Membrane Glycoprotein Recognised by a Monoclonal Antibody

Abstract: The F10-44-2 monoclonal antibody was originally shown to interact with a determinant found predominantly in human brain and leucocytes. In this study we demonstrate by quantitative absorption analysis with homogenates of the head of the caudate nucleus, putamen, thalamus, cerebral grey matter, cerebral white matter, corpus callosum and cerebellar folia that the determinant is restricted to the white matter of the CNS. Immunofluorescence studies on frozen sections of the above brain subregions confirm the absorption analyses, showing staining only of white matter. In addition, and unexpectedly, we found very bright staining around blood vessels, particularly in the cerebellum. Biochemical studies established that the molecule in white matter bearing the F10-44-2 determinants is a sialylated membrane glycoprotein with an apparent molecular weight of 90,000, which is similar to but slightly smaller than the T lymphocyte form of the antigen. Developmental studies comparing 16-week foetal and adult cerebrum showed a fivefold increase in F10-44-2 antigen content. Thus, in the human CNS, the F10-44-2 antigen is a medium-sized glycoprotein which is restricted to white matter and shows a marked increase in concentration during development. No such molecule has been described previously.     

Marking behaviour and census of Eurasian otters (Lutra lutra) in riverine habitats: what can scat abundances and non-invasive genetic sampling tell us about otter numbers?

Mammal Research - Growing human-wildlife conflicts and legal conservation obligations increased the need for precise information on Eurasian otter (Lutra lutra) population parameters for species...     

Synthesis of (2R,3S) 3-amino-4-mercapto-2-butanol, a threonine analogue for covalent inhibition of sortases

L-Threonine 2 was converted in seven steps into the protected aminomercaptoalcohol 8, a threonine mimic. This compound 8 was coupled to various oligopeptides to produce two different tetrapeptide analogues, for example, 11 and 17, which were shown to inhibit the Sortase enzymes (SrtA and SrtB) via covalent attachment of the thiol groups of 11 and 17 to the catalytically active cysteine residue of the Sortase enzymes.     

The distribution of seagrass (Zostera noltii) in the Ria Formosa lagoon system and the implications of clam farming on its conservation

Ria Formosa lagoon in southern Portugal has an important population of seagrasses that includes Zostera noltii in the intertidal area. The area is classified as a Natural Park and supports a major economic activity – clam farming. This activity has a direct influence on Z. noltii populations by removal of seagrass beds and altering habitat. Geographic Information Systems and spatial analysis were used to produce the first distribution map of Z. noltii in the Ria Formosa and to analyse interactions between clam farming and the level of seagrass protection according to the Natural Park of Ria Formosa. Stakeholder analyses, using interviews, questionnaires and participant observation, were conducted to gain a better understanding of clam farming's influence on seagrass populations. Seagrass covers 45% of the intertidal area while clam farming covers 14%. An additional 75% of the total area of Z. noltii can be potentially converted into clam cultures. The current management of clam farming is largely ineffective, representing a significant obstacle to seagrass conservation.     

A Cytohesin Homolog in Dictyostelium Amoebae

Background

Dictyostelium, an amoeboid motile cell, harbors several paralogous Sec7 genes that encode members of three distinct subfamilies of the Sec7 superfamily of Guanine nucleotide exchange factors. Among them are proteins of the GBF/BIG family present in all eukaryotes. The third subfamily represented with three members in D. discoideum is the cytohesin family that has been thought to be metazoan specific. Cytohesins are characterized by a Sec7 PH tandem domain and have roles in cell adhesion and migration.

Principal Findings

Dictyostelium SecG exhibits highest homologies to the cytohesins. It harbors at its amino terminus several ankyrin repeats that are followed by the Sec7 PH tandem domain. Mutants lacking SecG show reduced cell-substratum adhesion whereas cell-cell adhesion that is important for development is not affected. Accordingly, multicellular development proceeds normally in the mutant. During chemotaxis secG⁻ cells elongate and migrate in a directed fashion towards cAMP, however speed is moderately reduced.

Significance

The data indicate that SecG is a relevant factor for cell-substrate adhesion and reveal the basic function of a cytohesin in a lower eukaryote.     

Spatial patterns in age- and colony-specific survival in a long-lived seabird across 14 contrasting colonies

Demographic rates such as recruitment and survival probability can vary considerably among populations of the same species due to variation in underlying environmental processes. If environmental processes are spatially correlated, nearby populations are expected to have more similar demographic rates than those further apart. Breeding populations and foraging ranges are spatially segregated in colonial seabirds, making them ideal for studying spatial patterns in demographic rates and their effects on local population dynamics. Here we explored variation in age-dependent survival probabilities across 14 colonies of Herring Gulls Larus argentatus breeding along the Dutch North Sea coast. We used long-term mark–recapture data of marked fledglings to estimate survival, and estimated spatial autocorrelation of survival probabilities. We assessed whether survival until recruitment age or until 10 years old (close to their expected lifespan) explained variation in population trajectories of each colony. Juvenile and adult survival showed a strong, but different, north-to-south gradient in survival probability, with lower juvenile but higher adult survival in northern colonies than southern colonies, whereas the spatial pattern of immature survival was less distinct. Neither recruitment nor the proportion of 10-year-old adults alive predicted whether a colony collapsed, declined, remained stable or increased. The distinct spatial pattern in survival suggests variation in regional food availability, which do not seem to drive local population dynamics. The absence of a link between survival and colony trajectories implies that connectivity between populations plays an important role affecting population dynamics.