Biomarkers in osteoarthritis

Biomarkers aid the study of osteoarthritis (OA) in a number of different ways. In this article we summarise briefly their multiple uses and reflect on how the study reported in a previous edition of Arthritis Research & Therapy should promote further investigation of cartilage oligomeric matrix protein (COMP). COMP is foremost among hitherto investigated biomarkers and is most consistently shown to predict knee OA progression. Precisely what role it plays in OA pathogenesis remains unclear and elucidating this may be key to defining, and then targeting, the cellular pathways involved in OA.     

Carbon Dioxide Exchange Between an Old-growth Forest and the Atmosphere

Eddy-covariance and biometeorological methods show significant net annual carbon uptake in an old-growth Douglas-fir forest in southwestern Washington, USA. These results contrast with previous assumptions that old-growth forest ecosystems are in carbon equilibrium. The basis for differences between conventional biomass-based carbon sequestration estimates and the biometeorologic estimates are discussed. Annual net ecosystem exchange was comparable to younger ecosystems at the same latitude, as quantified in the AmeriFlux program. Net ecosystem carbon uptake was significantly correlated with photosynthetically active radiation and air temperature, as well as soil moisture and precipitation. Optimum ecosystem photosynthesis occurred at relatively cool temperatures (5°–10°C). Understory and soil carbon exchange always represented a source of carbon to the atmosphere, with a strong seasonal cycle in source strength. Understory and soil carbon exchange showed a Q₁₀ temperature dependence and represented a substantial portion of the ecosystem carbon budget. The period of main carbon uptake and the period of soil and ecosystem respiration are out of phase, however, and driven by different climatic boundary conditions. The period of strongest ecosystem carbon uptake coincides with the lowest observed values of soil and ecosystem respiration. Despite the substantial contribution of soil, the overall strength of the photosynthetic sink resulted in the net annual uptake. The net uptake estimates here included two correction methods, one for advection and the other for low levels of turbulence.     

DETECTING DESERTIFICATION PROCESSES USING TM AND ETM+ DATA, NORTH OF ISFAHAN, IRAN

 Aims Desertification results in ecological and biological diminution of the earth, and can happen naturally or cause by anthropogenic activities. This process especially affects arid and semi-arid regions, such as the Isfahan region, where the spread of desertification is reaching critical proportions. The aim of this study is to use remotely sensed data to review the trend of desertification in the northern of Isfahan, Iran. Methods Multi-temporal images were employed to evaluate the trend of desertification, specifically the TM and ETM+ data of September, 1990 and September, 2001. Geometric and radiometric corrections were applied to each image prior to image processing and supervised classification, and vegetation indices were applied to produce a land use map of each image in nine classes. The land use classification s in the two map images were compared and changes between land use classes were detected over the 11 year period using a fuzzy and post-classification technique. Important findings The maps and their comparison with false color composite images showed the differences efficiently. With the fuzzy and post-classification method the land use changes were sited on the map. Fuzzy confirmed 53% changed area and 47% unchanged areas in the study region. The results verify the desertification expansion in the study areas. Because of poor land management, agricultural lands converted to desert and abandoned areas, and some marginal pasture lands had to be changed to agricultural land which are desertification spreading according to United Nations Conference on Desertification (UNCOD). Also farmland and pastures have been converted to urban and industrial areas, and the rangelands have been spoiled due to opencast mine excavations. With the mine margins eroding as well as their debris accumulating on the pasture lands, desertification has become worse. Three areas of less-elevated mountains have remained unchanged. This study confirmed that the anthropogenic activities accelerated the desertification process and severely endangered the remaining areas.     

Frequent occurrence of recognition Site-like sequences in the restriction endonucleases

Background  

There are two different theories about the development of the genetic code. Woese suggested that it was developed in connection with the amino acid repertoire, while Crick argued that any connection between codons and amino acids is only the result of an "accident". This question is fundamental to understand the nature of specific protein-nucleic acid interactions.     

Binding to serine 65‐phosphorylated ubiquitin primes Parkin for optimal PINK1‐dependent phosphorylation and activation

Mutations in the mitochondrial protein kinase PINK1 are associated with autosomal recessive Parkinson disease (PD). We and other groups have reported that PINK1 activates Parkin E3 ligase activity both directly via phosphorylation of Parkin serine 65 (Ser⁶⁵)—which lies within its ubiquitin‐like domain (Ubl)—and indirectly through phosphorylation of ubiquitin at Ser⁶⁵. How Ser⁶⁵‐phosphorylated ubiquitin (ubiquitin^{Phospho‐Ser65}) contributes to Parkin activation is currently unknown. Here, we demonstrate that ubiquitin^{Phospho‐Ser65} binding to Parkin dramatically increases the rate and stoichiometry of Parkin phosphorylation at Ser⁶⁵ by PINK1 in vitro. Analysis of the Parkin structure, corroborated by site‐directed mutagenesis, shows that the conserved His302 and Lys151 residues play a critical role in binding of ubiquitin^{Phospho‐Ser65}, thereby promoting Parkin Ser⁶⁵ phosphorylation and activation of its E3 ligase activity in vitro. Mutation of His302 markedly inhibits Parkin Ser⁶⁵ phosphorylation at the mitochondria, which is associated with a marked reduction in its E3 ligase activity following mitochondrial depolarisation. We show that the binding of ubiquitin^{Phospho‐Ser65} to Parkin disrupts the interaction between the Ubl domain and C‐terminal region, thereby increasing the accessibility of Parkin Ser⁶⁵. Finally, purified Parkin maximally phosphorylated at Ser⁶⁵ in vitro cannot be further activated by the addition of ubiquitin^{Phospho‐Ser65}. Our results thus suggest that a major role of ubiquitin^{Phospho‐Ser65} is to promote PINK1‐mediated phosphorylation of Parkin at Ser⁶⁵, leading to maximal activation of Parkin E3 ligase activity. His302 and Lys151 are likely to line a phospho‐Ser⁶⁵‐binding pocket on the surface of Parkin that is critical for the ubiquitin^{Phospho‐Ser65} interaction. This study provides new mechanistic insights into Parkin activation by ubiquitin^{Phospho‐Ser65}, which could aid in the development of Parkin activators that mimic the effect of ubiquitin^{Phospho‐Ser65}.     

The efficacy and cardiac evaluation of aminomethyl tetrahydronaphthalene ketopiperazines: a novel class of potent MCH-R1 antagonists

The design, synthesis, and biological studies of a novel class of MCH-R1 antagonists based on an aminotetrahydronaphthalene ketopiperazine scaffold is described. Compounds within this class promoted significant body weight reduction in mouse diet induced obesity studies. The potential for hERG blockage activity and QT interval studies in anesthetized dogs are discussed.     

在韩国境内Potentilla fragarioides var.sprengeliana的遗传多样 …

根据２２个等位酶位点遗传变异,探讨了韩国境内委陵菜（Ｐｏｔｅｎｔｉｌｌａ ｆｒａｇａｒｉｏｉｄｅｓ Ｌ．ｖａｒ．ｓｐｒｅｎｇｅｌｉａｎａ）的遗传多样性和种群结构。酶位点的多态位点百分比为５９．１％。种和种群水平上的遗传多样性比较高,分别为Ｈｅｓ＝０．２１０,Ｈｅｐ＝０．１９９;而种群的分化水平则相对较低（ＧＳＴ＝０．０７４）。１９个种群中随机交配的偏差为ＦＩＳ＝０．３３１。每代迁移数的间接估计     

Chemotaxis and cyclic-di-GMP signalling control surface attachment of Escherichia coli

Attachment to surfaces is an important early step during bacterial infection and during formation of submerged biofilms. Although flagella-mediated motility is known to be important for attachment of Escherichia coli and other bacteria, implications of motility regulation by cellular signalling remain to be understood. Here, we show that motility largely promotes attachment of E. coli, including that mediated by type 1 fimbriae, by allowing cells to reach, get hydrodynamically trapped at and explore the surface. Inactivation or inhibition of the chemotaxis signalling pathway improves attachment by suppressing cell reorientations and thereby increasing surface residence times. The attachment is further enhanced by deletion of genes encoding the cyclic diguanosine monophosphate (c-di-GMP)-dependent flagellar brake YcgR or the diguanylate cyclase DgcE. Such increased attachment in absence of c-di-GMP signalling is in contrast to its commonly accepted function as a positive regulator of the sessile state. It is apparently due to the increased swimming speed of E. coli in absence of YcgR-mediated motor control, which strengthens adhesion mediated by the type 1 fimbriae. Thus, both signalling networks that regulate motility of E. coli also control its engagement with both biotic and abiotic surfaces, which has likely implications for infection and biofilm formation.