Tanacetum joharchii sp. nov. (Asteraceae–Anthemideae) from Iran, and its taxonomic position based on molecular data

Tanacetum joharchii Sonboli & Kazempour Osaloo sp. nov. (Asteraceae–Anthemideae) is described and illustrated from the Khorasan province, northeast Iran. Tanacetum joharchii is a suffruticulose species from rocky limestone mountains in Hezarmasjed and Binalud (Khorasan province) at altitudes of 1900–2500 m a.s.l. The diagnostic morphological characteristics that distinguish it from the allied species T. kotschyi are presented. In addition, a distribution map of T. joharchii and the related species is given. In order to provide some hypothesis on its phylogenetic position, a molecular phylogenetic analysis based on nrDNA ITS sequence data of 14 representatives of the genus Tanacetum was performed.     

Only one independent genetic association with rheumatoid arthritis within the KIAA1109-TENR-IL2-IL21 locus in Caucasian sample sets: confirmation of association of rs6822844 with rheumatoid arthritis at a genome-wide level of significance

Introduction

To investigate whether accelerated hand bone mineral density (BMD) loss is associated with progressive joint damage in hands and feet in the first year of rheumatoid arthritis (RA) and whether it is an independent predictor of subsequent progressive total joint damage after 4 years.

Methods

In 256 recent-onset RA patients, baseline and 1-year hand BMD was measured in metacarpals 2-4 by digital X-ray radiogrammetry. Joint damage in hands and feet were scored in random order according to the Sharp-van der Heijde method at baseline and yearly up to 4 years.

Results

68% of the patients had accelerated hand BMD loss (>-0.003 g/cm²) in the first year of RA. Hand BMD loss was associated with progressive joint damage after 1 year both in hands and feet with odds ratios (OR) (95% confidence intervals [CI]) of 5.3 (1.3-20.9) and 3.1 (1.0-9.7). In univariate analysis, hand BMD loss in the first year was a predictor of subsequent progressive total joint damage after 4 years with an OR (95% CI) of 3.1 (1.3-7.6). Multivariate analysis showed that only progressive joint damage in the first year and anti-citrullinated protein antibody positivity were independent predictors of long-term progressive joint damage.

Conclusions

In the first year of RA, accelerated hand BMD loss is associated with progressive joint damage in both hands and feet. Hand BMD loss in the first year of recent-onset RA predicts subsequent progressive total joint damage, however not independent of progressive joint damage in the first year.     

Proteomic analysis of salt-responsive proteins in the leaves of two contrasting Tunisian barley landraces

Salinity is a brutal environmental factor that severely affects barley growth and development. In this context, local landraces, commonly cultivated under stressful conditions, could represent important reservoirs of valuable traits in barley breeding programs. Therefore, understanding salt-tolerance mechanisms in such genotypes is of great interest. Here, based on a 2D-PAGE comparative proteomic study, salt-induced proteome changes were explored in the seedling leaves of two contrasting Tunisian landraces, namely Boulifa (tolerant) and Testour (sensitive). The analysis showed that 11 salt-responsive proteins were differentially accumulated in both accessions under salt stress and 43 were genotype-specific (18 in Boulifa and 25 in Testour). Using mass spectrometry identification and annotation, 11 function categories revealed being involved in salt-stress response, specifically the defense/cell wall related metabolism. In fact, a chitinase, was up-regulated in the tolerant accession and down-regulated in the sensitive one in addition to a ricin B-like lectin R40G3 as well as a predicted BSP that were up-regulated in the tolerant one. Then, two other chitinases, PR10, glucan endo-1.3-β-glucosidase, were down-regulated in Testour, while still unchanged in the tolerant accession Boulifa. In the latter, signaling, redox/polyamine catabolism and the energy metabolism were found as part of the biochemical pathways underlying salt-tolerance. These results suggest that Boulifa may alleviate salt stress by activation of specific defense responses, and adjustment of both redox/polyamine catabolism and energy metabolism processes. Our findings represent a basis that would assist selection of candidates as markers in improving barley salt tolerance and elite genotypes creation.

     

LAMTOR5 expression level is a biomarker for colorectal cancer and lncRNA LAMTOR5-AS1 predicting miRNA sponging effect

Molecular Biology Reports - Strong evidence indicated that high expression of HBXIP (also known as LAMTOR5) promotes cancer cells proliferation and helps cancer progression. Long non-coding RNAs...     

Endogenous auxins in plant growth-promoting Cyanobacteria—Anabaena vaginicola and Nostoc calcicola

Three isolates of heterocystous cyanobacteria, belonging to the genera Anabaena and Nostoc, gathered from Iranian terrestrial and aquatic ecosystems exhibited considerable growth promotion effect on several vegetables and herbaceous plants. To study the ability of these three isolates to produce auxins, three endogenous auxins, including indole-3-acetic acid (IAA), and two of its main homologues, indole-3-propionic acid and indole-3-butyric acid, were extracted and analyzed with high-performance liquid chromatography equipped with diode array detector and fluorescence detector, and the results were further confirmed with liquid chromatography–tandem mass spectrometry (LC–MS/MS) in the negative-ion mode. The dominant auxin observed in all isolates was indole-3-butyric acid (IBA) in the range of 140.10–2146.96 ng g^?1 fresh weight (FW), and only small amounts of IAA (2.19–9.93 ng g^?1 FW) were detected. The predominance of IBA in these strains is reported for the first time which is different from the previously reported auxin profiles in microalgae and algae with the predominance of IAA.     

Molecular characterization and evolutionary pattern of the 9- cis -epoxycarotenoid dioxygenase NCED1 gene in grapevine

This study provides the first analysis of the level and patterns of nucleotide polymorphism of the NCED1 gene in grapevine (Vitis vinifera L.). A total of 123 sequences of the gene were analyzed to give a sample of 50 wild accessions and 73 cultivars. A high single nucleotide polymorphism and haplotype diversity was revealed in the cultivars studied, especially Tunisian germplasms which present an important and diverse reservoir of genetic diversity for grape breeding and conservation. The haplotype distribution highlights two origins of the cultivars studied: one may be related to primary grapevine gene pool domestication while the second seems to be more recent. Thus, besides domestication, gene introgression has also played a role in shaping the current varietal landscape of grape cultivars. Higher nucleotide and haplotype polymorphism was recorded for cultivars. This was accompanied by a higher recombination rate in cultivated grapevines for this gene, a recent selective sweep in wild samples and a balancing selection in cultivars. The conservation of genetic diversity of the endangered wild germplasm is important to ensure that the wild population can be used in future breeding programs of the domesticated cultivars. The high number of alleles discovered can be used as a valuable source for association studies between allele frequencies and phenotypic variations in this gene. In addition to natural selection, molecular evidence shows that genetic variation in this locus appears to be shaped by a combination of mutation and recombination events.     

3-Oxo-2-piperazinyl acetamides as potent bradykinin B1 receptor antagonists for the treatment of pain and inflammation

The discovery of novel and highly potent oxopiperazine based B1 receptor antagonists is described. Compared to the previously described arylsulfonylated (R)-3-amino-3-phenylpropionic acid series, the current compounds showed improved in vitro potency and metabolic stability. Compound 17, 2-((2R)-1-((4-methylphenyl)sulfonyl)-3-oxo-2-piperazinyl)-N-((1R)-6-(1-piperidinylmethyl)-1,2,3,4-tetrahydro-1-naphthalenyl)acetamide, showed EC₅₀ of 10.3 nM in a rabbit biochemical challenge model. The practical syntheses of chiral arylsulfonylated oxopiperazine acetic acids are also described.     

A novel Hv1 inhibitor reveals a new mechanism of inhibition of a voltage-sensing domain

Voltage-gated sodium, potassium, and calcium channels consist of four voltage-sensing domains (VSDs) that surround a central pore domain and transition from a down state to an up state in response to membrane depolarization. While many types of drugs bind pore domains, the number of organic molecules known to bind VSDs is limited. The Hv1 voltage-gated proton channel is made of two VSDs and does not contain a pore domain, providing a simplified model for studying how small ligands interact with VSDs. Here, we describe a ligand, named HIF, that interacts with the Hv1 VSD in the up and down states. We find that HIF rapidly inhibits proton conduction in the up state by blocking the open channel, as previously described for 2-guanidinobenzimidazole and its derivatives. HIF, however, interacts with a site slowly accessible in the down state. Functional studies and MD simulations suggest that this interaction traps the compound in a narrow pocket lined with charged residues within the VSD intracellular vestibule, which results in slow recovery from inhibition. Our findings point to a “wrench in gears” mechanism whereby side chains within the binding pocket trap the compound as the teeth of interlocking gears. We propose that the use of screening strategies designed to target binding sites with slow accessibility, similar to the one identified here, could lead to the discovery of new ligands capable of interacting with VSDs of other voltage-gated ion channels in the down state.     

HIFs: New arginine mimic inhibitors of the Hv1 channel with improved VSD–ligand interactions

The human voltage-gated proton channel Hv1 is a drug target for cancer, ischemic stroke, and neuroinflammation. It resides on the plasma membrane and endocytic compartments of a variety of cell types, where it mediates outward proton movement and regulates the activity of NOX enzymes. Its voltage-sensing domain (VSD) contains a gated and proton-selective conduction pathway, which can be blocked by aromatic guanidine derivatives such as 2-guanidinobenzimidazole (2GBI). Mutation of Hv1 residue F150 to alanine (F150A) was previously found to increase 2GBI apparent binding affinity more than two orders of magnitude. Here, we explore the contribution of aromatic interactions between the inhibitor and the channel in the presence and absence of the F150A mutation, using a combination of electrophysiological recordings, classic mutagenesis, and site-specific incorporation of fluorinated phenylalanines via nonsense suppression methodology. Our data suggest that the increase in apparent binding affinity is due to a rearrangement of the binding site allowed by the smaller residue at position 150. We used this information to design new arginine mimics with improved affinity for the nonrearranged binding site of the wild-type channel. The new compounds, named “Hv1 Inhibitor Flexibles” (HIFs), consist of two “prongs,” an aminoimidazole ring, and an aromatic group connected by extended flexible linkers. Some HIF compounds display inhibitory properties that are superior to those of 2GBI, thus providing a promising scaffold for further development of high-affinity Hv1 inhibitors.     

The <Emphasis Type="Italic">SLC2A9</Emphasis> nonsynonymous Arg265His variant and gout: evidence for a population-specific effect on severity

Introduction  

The C allele of the nonsynonymous Arg265His (rs3733591) variant of SLC2A9 confers risk for gout in Han Chinese, Solomon Island and Japanese samples, with a stronger role in tophaceous gout. There is no evidence for an association with gout in Caucasian populations. In the present study, we tested rs3733591 for association with gout in New Zealand (NZ) Māori, Pacific Island and Caucasian samples.