Identification of a Novel Inhibitor of Coactivator-associated Arginine Methyltransferase 1 (CARM1)-mediated Methylation of Histone H3 Arg-17

Methylation of the arginine residues of histones by methyltransferases has important consequences for chromatin structure and gene regulation; however, the molecular mechanism(s) of methyltransferase regulation is still unclear, as is the biological significance of methylation at particular arginine residues. Here, we report a novel specific inhibitor of coactivator-associated arginine methyltransferase 1 (CARM1; also known as PRMT4) that selectively inhibits methylation at arginine 17 of histone H3 (H3R17). Remarkably, this plant-derived inhibitor, called TBBD (ellagic acid), binds to the substrate (histone) preferentially at the signature motif, “KAPRK,” where the proline residue (Pro-16) plays a critical role for interaction and subsequent enzyme inhibition. In a promoter-specific context, inhibition of H3R17 methylation represses expression of p21, a p53-responsive gene, thus implicating a possible role for H3 Arg-17 methylation in tumor suppressor function. These data establish TBBD as a novel specific inhibitor of arginine methylation and demonstrate substrate sequence-directed inhibition of enzyme activity by a small molecule and its physiological consequence.     

Latitudinal variation in seeds characteristics of Acer platanoides and A. pseudoplatanus

Climate change will likely affect population dynamics of numerous plant species by modifying several aspects of the life cycle. Because plant regeneration from seeds may be particularly vulnerable, here we assess the possible effects of climate change on seed characteristics and present an integrated analysis of seven seed traits (nutrient concentrations, samara mass, seed mass, wing length, seed viability, germination percentage, and seedling biomass) of Acer platanoides and A. pseudoplatanus seeds collected along a wide latitudinal gradient from Italy to Norway. Seed traits were analyzed in relation to the environmental conditions experienced by the mother trees along the latitudinal gradient. We found that seed traits of A. platanoides were more influenced by the climatic conditions than those of A. pseudoplatanus. Additionally, seed viability, germination percentage, and seedling biomass of A. platanoides were strongly related to the seed mass and nutrient concentration. While A. platanoides seeds were more influenced by the environmental conditions (generally negatively affected by rising temperatures), compared to A. pseudoplatanus, A. platanoides still showed higher germination percentage and seedling biomass than A. pseudoplatanus. Thus, further research on subsequent life-history stages of both species is needed. The variation in seed quality observed along the climatic gradient highlights the importance of studying the possible impact of climate change on seed production and species demography.     

Alkaptonuria is a novel human secondary amyloidogenic disease

Alkaptonuria (AKU) is an ultra-rare disease developed from the lack of homogentisic acid oxidase activity, causing homogentisic acid (HGA) accumulation that produces a HGA-melanin ochronotic pigment, of unknown composition. There is no therapy for AKU. Our aim was to verify if AKU implied a secondary amyloidosis. Congo Red, Thioflavin-T staining and TEM were performed to assess amyloid presence in AKU specimens (cartilage, synovia, periumbelical fat, salivary gland) and in HGA-treated human chondrocytes and cartilage. SAA and SAP deposition was examined using immunofluorescence and their levels were evaluated in the patients' plasma by ELISA. 2D electrophoresis was undertaken in AKU cells to evaluate the levels of proteins involved in amyloidogenesis. AKU osteoarticular tissues contained SAA-amyloid in 7/7 patients. Ochronotic pigment and amyloid co-localized in AKU osteoarticular tissues. SAA and SAP composition of the deposits assessed secondary type of amyloidosis. High levels of SAA and SAP were found in AKU patients' plasma. Systemic amyloidosis was assessed by Congo Red staining of patients' abdominal fat and salivary gland. AKU is the second pathology after Parkinson's disease where amyloid is associated with a form of melanin. Aberrant expression of proteins involved in amyloidogenesis has been found in AKU cells. Our findings on alkaptonuria as a novel type II AA amyloidosis open new important perspectives for its therapy, since methotrexate treatment proved to significantly reduce in vitro HGA-induced A-amyloid aggregates.     

Homogentisate 1,2 dioxygenase is expressed in human osteoarticular cells: implications in alkaptonuria

Alkaptonuria (AKU) results from defective homogentisate1,2-dioxygenase (HGD), causing degenerative arthropathy. The deposition of ochronotic pigment in joints is so far attributed to homogentisic acid produced by the liver, circulating in the blood and accumulating locally. Human normal and AKU osteoarticular cells were tested for HGD gene expression by RT-PCR, mono- and 2D-Western blotting. HGD gene expression was revealed in chondrocytes, synoviocytes, osteoblasts. Furthermore, HGD expression was confirmed by Western blotting, that also revealed the presence of five enzymatic molecular species. Our findings indicate that AKU osteoarticular cells produce the ochronotic pigment in loco and this may strongly contribute to induction of ochronotic arthropathy.     

Rapid evolution in sequence and length of the nuclear-located gene for mitochondrial L2 ribosomal protein in cereals.

The L2 ribosomal protein is typically one of the most conserved proteins in the ribosome and is universally present in bacterial, archaeal, and eukaryotic cytosolic and organellar ribosomes. It is usually 260-270 amino acids long and its binding to the large-subunit ribosomal RNA near the peptidyl transferase center is mediated by a beta-barrel RNA-binding domain with 10 beta strands. In the diverse land plants Marchantia polymorpha (liverwort) and Oryza sativa (rice), the mitochondrial-encoded L2 ribosomal protein is about 500 amino acids long owing to a centrally located expansion containing the beta3-beta4 strand region. We have determined that, in wheat, the functional rpl2 gene has been transferred to the nucleus and much of the plant-specific internal insert has been deleted. Its mRNA is only 1.2 kb, and two expressed copies in wheat encode proteins of 318 and 319 amino acids, so they are considerably shorter than the maize nuclear-located rpl2 gene of 448 codons. Comparative sequence analysis of cereal mitochondrial L2 ribosomal proteins indicates that the mid region has undergone unexpectedly rapid evolution during the last 60 million years.     

Nonea pisidica (Boraginaceae-Boragineae), a new species from southwest Anatolia and its relationships inferred from karyology and cpDNA sequences

The new species Nonea pisidica (Boraginaceae-Boragineae) is described based on two collections by the authors from the region of Lake Burdur in southwest Anatolia, Turkey. It shows a combination of morphological characteristics concerning habit, flower, and fruit that distinguishes it from N. caspica and N. pallens, the two more similar taxa in Nonea sect. Nonea. Karyological analyses corroborate the separation of the three species, which have different chromosome complements and even base numbers. N. pisidica is characterised by 2n = 30, a complement previously unknown for west Asiatic species of Nonea. The dibasic haploid number x = 15 may have originated through amphidiploid hybridisation between two annual, diploid taxa with x = 7 and x = 8, such as N. lutea and N. caspica. The relationships of the new species were further analysed using trnL_UAA sequences of the chloroplast genome, which were obtained for 16 selected species of Nonea. The resulting phylogeny confirms that it is related to N. caspica and N. lutea, but not to N. pallens, in spite of morphological resemblance. Lack of relationship with the south Mediterranean N. vesicaria, the only other species of Nonea known to have 2n = 30, suggests that amphidiploidy may have played an important role in speciation processes through recurrent and polytopical occurrence.     

Biodepolymerization studies of low rank Indian coals

Biodepolymerization of some of the lower rank Indian coals by Pleurotus djamor, Pleurotus citrinopileatus and Aspergillus species were studied in a batch system. The main disadvantage in burning low rank coals is the low calorific values. To get the maximum benefit from the low rank coals, the non fuel uses of coals needs to be explored. The liquefaction of coals is the preliminary processes for such approaches. The present study is undertaken specifically to investigate the optimization of bio depolymerization of neyveli lignite by P. djmor. The pH of the media reached a constant value of about 7.8 by microbial action. The effect of different carbon and nitrogen sources and influence of chelators and metal ions on depolymerization of lignite were also studied. Lignite was solubilized by P. djamor only to a limited extent without the addition of carbon and nitrogen sources. Sucrose was the best suitable carbon source for coal depolymerization by P. djamor and sodium nitrated followed by urea was the best nitrogen source. The Chelators like salicylic acid, TEA and metal ions Mg²⁺, Fe³⁺, Ca²⁺, Cu²⁺, Mn²⁺ has enhanced the lignite solubilization process. The finding of the study showed that, compared to sub-bituminous and bituminous coal, the lignite has higher rate of solubilization activity.