Connexins mediate intercellular communication by assembling into hexameric channel complexes that act as hemichannels and gap junction channels. Most connexins are characterized by a very rapid turn-over in a variety of cell systems. The regulation of connexin turn-over by phosphorylation and ubiquitination events has been well documented. Moreover, different pathways have been implicated in connexin degradation, including proteasomal and lysosomal-based pathways. Only recently, autophagy emerged as an important connexin-degradation pathway for different connexin isoforms. As such, conditions well known to induce autophagy have an immediate impact on the connexin-expression levels. This is not only limited to experimental conditions but also several pathophysiological conditions associated with autophagy (dys)function affect connexin levels and their presence at the cell surface as gap junctions. Finally, connexins are not only substrates of autophagy but also emerge as regulators of the autophagy process. In particular, several connexin isoforms appear to recruit pre-autophagosomal autophagy-related proteins, including Atg16 and PI3K-complex components, to the plasma membrane, thereby limiting their availability and capacity for regulating autophagy.
Desbuquois dysplasia is a severe condition characterized by short stature, joint laxity, scoliosis, and advanced carpal ossification with a delta phalanx. Studying nine Desbuquois families, we identified seven distinct mutations in the Calcium-Activated Nucleotidase 1 gene (CANT1), which encodes a soluble UDP-preferring nucleotidase belonging to the apyrase family. Among the seven mutations, four were nonsense mutations (Del 5′ UTR and exon 1, p.P245RfsX3, p.S303AfsX20, and p.W125X), and three were missense mutations (p.R300C, p.R300H, and p.P299L) responsible for the change of conserved amino acids located in the seventh nucleotidase conserved region (NRC). The arginine substitution at position 300 was identified in five out of nine families. The specific function of CANT1 is as yet unknown, but its substrates are involved in several major signaling functions, including Ca2+ release, through activation of pyrimidinergic signaling. Importantly, using RT-PCR analysis, we observed a specific expression in chondrocytes. We also found electron-dense material within distended rough endoplasmic reticulum in the fibroblasts of Desbuquois patients. Our findings demonstrate the specific involvement of a nucleotidase in the endochondral ossification process. 相似文献
Being ectotherms, insects are predicted to suffer more severely from climate change than warm-blooded animals. We forecast
possible changes in diversity and composition of butterflies, grasshoppers and dragonflies in Belgium under increasingly severe
climate change scenarios for the year 2100. Two species distribution modelling techniques (Generalised Linear Models and Generalised
Additive Models), were combined via a conservative version of the ensemble forecasting strategy to predict present-day and
future species distributions, considering the species as potentially present only if both modelling techniques made such a
prediction. All models applied were fair to good, according to the AUC (area under the curve of the receiver operating characteristic
plot), sensitivity and specificity model performance measures based on model evaluation data. Butterfly and grasshopper diversity
were predicted to decrease significantly in all scenarios and species-rich locations were predicted to move towards higher
altitudes. Dragonfly diversity was predicted to decrease significantly in all scenarios, but dragonfly-rich locations were
predicted to move upwards only in the less severe scenarios. The largest turnover rates were predicted to occur at higher
altitudes for butterflies and grasshoppers, but at intermediate altitudes for dragonflies. Our results highlight the challenge
of building conservation strategies under climate change, because the changes in the sites important for different groups
will not overlap, increasing the area needed for protection. We advocate that possible conservation and policy measures to
mitigate the potentially strong impacts of climate change on insect diversity in Belgium should be much more pro-active and
flexible than is the case presently. 相似文献
Middle East respiratory syndrome coronavirus (MERS-CoV) replicates in cells of different species using dipeptidyl peptidase 4 (DPP4) as a functional receptor. Here we show the resistance of ferrets to MERS-CoV infection and inability of ferret DDP4 to bind MERS-CoV. Site-directed mutagenesis of amino acids variable in ferret DPP4 thus revealed the functional human DPP4 virus binding site. Adenosine deaminase (ADA), a DPP4 binding protein, competed for virus binding, acting as a natural antagonist for MERS-CoV infection. 相似文献
In the context of population genetic research, a faster and less invasive method of DNA sampling would allow large-scale assessments
of genetic diversity and genetic differentiation with the help of volunteer observers. The aim of this study was to investigate
the usefulness of eggshell membranes as a DNA source for population genetic research, by addressing eggshell membrane DNA
quality, degeneration and cross-contamination. To this end, a comparison was made with blood-derived DNA samples. We have
demonstrated 100% successful DNA extraction from post-hatched Black-tailed Godwit (Limosa limosa) eggshell membranes as well as from blood samples. Using 11 microsatellite loci, DNA amplification success was 99.1% for
eggshell membranes and 97.7% for blood samples. Genetic information within eggshell membrane DNA in comparison to blood DNA
was not affected (FST = −0.01735, P = 0.999) by degeneration or possible cross-contamination. Furthermore, neither degeneration nor cross-contamination was apparent
in total genotypic comparison of eggshell membrane DNA and blood sample DNA. Our research clearly illustrates that eggshell
membranes can be used for population genetic research. 相似文献
Summary The enzyme acetate kinase (EC 2.7.2.1) was purified fromDesulfovibrio vulgaris by a combination of ammonium sulfate precipitation, hydroxyl-apatite and dye-affinity chromatography. An overall-purification factor of 15 was obtained resulting in a specific activity of 24 U/mg protein. The purified enzyme was immobilized on differently derivatized controlled pore glass beads. 相似文献