Natural variability of minimotifs in 1092 people indicates that minimotifs are targets of evolution

Since the function of a short contiguous peptide minimotif can be introduced or eliminated by a single point mutation, these functional elements may be a source of human variation and a target of selection. We analyzed the variability of ∼300 000 minimotifs in 1092 human genomes from the 1000 Genomes Project. Most minimotifs have been purified by selection, with a 94% invariance, which supports important functional roles for minimotifs. Minimotifs are generally under negative selection, possessing high genomic evolutionary rate profiling (GERP) and sitewise likelihood-ratio (SLR) scores. Some are subject to neutral drift or positive selection, similar to coding regions. Most SNPs in minimotif were common variants, but with minor allele frequencies generally <10%. This was supported by low substation rates and few newly derived minimotifs. Several minimotif alleles showed different intercontinental and regional geographic distributions, strongly suggesting a role for minimotifs in adaptive evolution. We also note that 4% of PTM minimotif sites in histone tails were common variants, which has the potential to differentially affect DNA packaging among individuals. In conclusion, minimotifs are a source of functional genetic variation in the human population; thus, they are likely to be an important target of selection and evolution.     

Enhancement of the anti‐inflammatory activity of temporin‐1Tl‐derived antimicrobial peptides by tryptophan,arginine and lysine substitutions

Temporin‐1Tl (TL) is a 13‐residue frog antimicrobial peptide (AMP) exhibiting potent antimicrobial and anti‐inflammatory activity. To develop novel AMP with improved anti‐inflammatory activity and antimicrobial selectivity, we designed and synthesized a series of TL analogs by substituting Trp, Arg and Lys at selected positions. Except for Escherichia coli and Staphylococcus epidermidis, all TL analogs exhibited retained or increased antimicrobial activity against seven bacterial strains including three methicillin‐resistant Staphylococcus aureus strains compared with TL. TL‐1 and TL‐4 showed a little increase in antimicrobial selectivity, while TL‐2 and TL‐3 displayed slightly decreased antimicrobial selectivity because of their about twofold increased hemolytic activity. All TL analogs demonstrated greatly increased anti‐inflammatory activity, evident by their higher inhibition of the production tumor necrosis factor‐α (TNF‐α) and nitric oxide and the mRNA expression of inducible nitric oxide synthase and TNF‐α in lipopolysaccharide (LPS)‐stimulated RAW264.7 macrophage cells, compared with TL. Taken together, the peptide anti‐inflammatory activity is as follows: TL‐2 ≈ TL‐3 ≈ TL‐4 > TL‐1 > TL. In addition, LPS binding ability of the peptides corresponded with their anti‐inflammatory activity. These results apparently suggest that the anti‐inflammatory activity of TL analogs is associated with the direct binding ability between these peptides and LPS. Collectively, our designed TL analogs possess improved anti‐inflammatory activity and retain antimicrobial activity without a significant increase in hemolysis. Therefore, it is evident that our TL analogs constitute promising candidates for the development of peptide therapeutics for gram‐negative bacterial infection. Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.     

Endogenous and exogenous ethylene induces needle abscission and cellulase activity in post-harvest balsam fir (Abies balsamea L.)

Post-harvest needle loss is a major problem for balsam fir and other Christmas tree species. Recent evidence has implicated ethylene as a signal responsible for post-harvest needle abscission, but enzymological changes remain unknown. The objective of this study was to identify and quantify cellulase activity associated with endogenous and exogenous ethylene-induced abscission. An experiment was designed with three treatments (control, endogenous ethylene, or exogenous ethylene) with five replicates. Key response variables include needle retention duration, xylem pressure potential, ethylene evolution rate, and cellulase activity. Two complimentary methods were used to assess cellulase activity: a cellulose plate digestion and zymography. The results confirm ethylene as a signal for post-harvest abscission and identify ethylene-induced cellulase. Ethylene evolution was typically between 15 and 16 μL g⁻¹ h⁻¹, but there was no difference among the three treatments. However, exogenous ethylene significantly decreased needle retention by 60% and resulted in a sixfold decrease in xylem pressure potential. In addition, cellulase activity increased by 8- and 12-fold in endogenous and exogenous ethylene-induced abscission, respectively, compared to the control. Identification of ethylene-induced cellulase activity has increased our understanding of the post-harvest needle abscission process and confirms ethylene’s role as a signal molecule.     

Renal clear-cell carcinoma: an ultrastructural study on the junctional complexes

Junctional complexes such as tight junctions, adherens junctions, and desmosomes play crucial roles in the structure and function of epithelial cells. These junctions are involved in increasing cell-cell contact and as well serve as signaling centers regulating multiple functions in epithelial cells. Carcinoma cell lines cultured in the laboratory generally lack junctional complexes. However, studies directed towards understanding the distribution of junctional complexes in human cancer tissues are lacking. In this study, we analyzed by electron microscopy the distribution of junctional complexes in patients diagnosed with renal clear-cell carcinoma. We found that both tight junctions and adherens junctions were drastically reduced in patients with cancer compared to normal tissues. Desmosomes were not detected in normal proximal tubules while distinctly present in cancer tissues. These results suggest that analysis of junctional complexes in human tumors should provide valuable information that might have prognostic and diagnostic value.     

Mineral contents of Aloe vera leaf gel and their role on streptozotocin-induced diabetic rats

The role of some inorganic elements like vanadium, zinc, sodium, potassium, calcium, copper, manganese, and traces of chromium in the improvement of impaired glucose tolerance and their indirect role in the management of diabetes mellitus are being increasingly recognized. In traditional methods, medicinal plants are being used, which contain both organic and inorganic constituents. In the present study, an attempt has been made to analyze the inorganic elements present in Aloe vera leat gel and their role on diabetes-related biochemical alterations in experimental rats. Special emphasis was given to the inorganic parts by carefully preparing ash of the leaf gel. The results clearly indicate the presence of several hypoglycemic-activity-possessing elements in the gel. The ash treatment also resulted in hypoglycemic action. In conclusion, the presence of various inorganic trace elements in the gel might account for the hypoglycemic nature of the plant.     

IQGAP1: a regulator of intracellular spacetime relativity

Activating and inhibiting receptors of lymphocytes collect valuable information about their mikròs kósmos. This information is essential to initiate or to turn off complex signaling pathways. Irrespective of these advances, our knowledge on how these intracellular activation cascades are coordinated in a spatiotemporal manner is far from complete. Among multiple explanations, the scaffolding proteins have emerged as a critical piece of this evolutionary tangram. Among many, IQGAP1 is one of the essential scaffolding proteins that coordinate multiple signaling pathways. IQGAP1 possesses multiple protein interaction motifs to achieve its scaffolding functions. Using these domains, IQGAP1 has been shown to regulate a number of essential cellular events. This includes actin polymerization, tubulin multimerization, microtubule organizing center formation, calcium/calmodulin signaling, Pak/Raf/Mek1/2-mediated Erk1/2 activation, formation of maestrosome, E-cadherin, and CD44-mediated signaling and glycogen synthase kinase-3/adenomatous polyposis coli-mediated β-catenin activation. In this review, we summarize the recent developments and exciting new findings of cellular functions of IQGAP1.     

Characterization of phytohormonal and postharvest senescence responses of balsam fir (Abies balsamea (L.) Mill.) exposed to short-term low temperature

To fulfill the US Thanksgiving and Christmas tree markets, balsam fir (Abies balsamea (L.) Mill.) is generally harvested before the cold season, anecdotally leading to premature needle senescence. Accordingly, we tested the hypothesis that LT exposure before harvest induces specific hormonal changes and delays postharvest senescence and/or abscission in balsam fir. Two hundred and six seedlings exposed to two temperature treatments for 48?h, LT at 5?°C and controls at 22?°C were severed off roots and monitored for their postharvest needle senescence. Root and shoot (needles and buds) tissues were examined for major endogenous hormone metabolites. LT increased shoot ABA (2,007?ng?g^?1 DW) by 2.5× and decreased GA₄₄ (9.84?ng?g^?1 DW) by 3.5× over those in roots. LT did not alter cytokinins, auxins or any root hormonal concentration. With auxins, only IAA, IAA-Asp, IAA-Leu and IAA-Glu were detected and the concentrations of IAA and IAA-Asp in shoots were lower than those found in roots. Among cytokinins, shoot c-ZR (58.95?ng?g^?1 DW) and t-ZR (4.17?ng?g^?1 DW) were 3× higher than those in roots. Apart from GA₄₄, GA₉ (136.76?ng?g^?1 DW) was abundant in shoots. The PBL and PNL were 46 and 1.2?%, irrespective of treatments. LT seedlings held needles 11?days longer than the controls (122?days). In balsam fir, short-term LT exposure augmented ABA and decreased GA₄₄ levels in shoots and delayed postharvest needle senescence.