A Potential Association between Helicobacter pylori CagA EPIYA and Multimerization Motifs with Cytokeratin 18 Cleavage Rate during Early Apoptosis

Background and Aims: Helicobacter pylori is a highly diverse pathogen, which encounters epithelial cells as the initial defense barrier during its lifelong infection. The structure of epithelial cells can be disrupted through cleavage of microfilaments. Cytokeratin 18 (CK18) is an intermediate filament, the cleavage of which is considered an early event during apoptosis following activation of effector caspases. Methods: Helicobacter pylori strains were isolated from 76 dyspeptic patients. cagA 3’ variable region and CagA protein status were analyzed by PCR and western blotting, respectively. Eight hours post‐co‐culture of AGS cells with different H. pylori strains, flow cytometric analysis was performed using M30 monoclonal antibody specific to CK18 cleavage‐induced neo‐epitope. Results: Higher rates of CK18 cleavage were detected during co‐culture of AGS cells with H. pylori strains bearing greater numbers of cagA EPIYA‐C and multimerization (CM) motifs. On the other hand, H. pylori strains with greater numbers of EPIYA‐B relative to EPIYA‐C demonstrated a decrease in CK18 cleavage rate. Thus, H. pylori‐mediated cleavage of CK18 appeared proportional to the number of CagA EPIYA‐C and CM motifs, which seemed to be downplayed in the presence of EPIYA‐B motifs. Conclusions: Our observation associating the heterogeneity of cagA variants with the potential of H. pylori strains in the induction of CK18 cleavage as an early indication of apoptosis in gastric epithelial cells supports the fact that apoptosis may be a type‐specific trait. However, additional cagA‐targeted experiments are required to clearly identify the role of EPIYA and CM motifs in apoptosis and/or the responsible effector molecules.     

The impact of the bystander effect on the low-dose hypersensitivity phenomenon

The aim of this study was to investigate the possible relationship between the bystander effect and the low-dose hypersensitivity/increased radio-resistance phenomenon in BJ fibroblast cells taking as response criteria different end points of radiation damage such as cell survival, chromosomal damage (as detected by using micronucleus assay) and double strand breaks (DSBs) of the DNA. Although γ-H2AX foci were observed in confluent bystander BJ cells, our data suggest that X-irradiation does not lead to a significant rate of DSBs in bystander cells. Thus, neither bystander effect induced unstable chromosomal aberrations nor bystander effect induced DSBs are sufficiently pronounced to explain the apparent relationship between bystander effect and low-dose hypersensitivity. The experiments described here suggest that the hyper-radiosensitivity phenomenon might be related to bystander factor induced cell inactivation in the low-dose region (lower than 1 Gy).     

Effect of mesenchymal stem cells-derived exosomes on tumor microenvironment: Tumor progression versus tumor suppression

Mesenchymal stem cells (MSCs) are multipotent cells with the potential to differentiate into different cell types. Owing to their immunosuppressive and anti-inflammatory properties, they are widely used in regenerative medicine, but they have a dual effect on cancer progression and exert both growth-stimulatory or -inhibitory effects on different cancer types. It has been proposed that these controversial effects of MSC in tumor microenvironment (TME) are mediated by their polarization to proinflammatory or anti-inflammatory phenotype. In addition, they can polarize the immune system cells that in turn influence tumor progression. One of the mechanisms involved in the TME communications is extracellular vesicles (EVs). MSCs, as one of cell populations in TME, produce a large amount of EVs that can influence tumor development. Similar to MSC, MSC-EVs can exert both anti- or protumorigenic effects. In the current study, we will investigate the current knowledge related to MSC role in cancer progression with a focus on the MSC-EV content in limiting tumor growth, angiogenesis, and metastasis. We suppose MSC-EVs can be used as safe vehicles for delivering antitumor agents to TME.     

Theoretical descriptions of novel triplet germylenes M<Subscript>1</Subscript>-Ge-M<Subscript>2</Subscript>-M<Subscript>3</Subscript> (M<Subscript>1</Subscript> = H,Li, Na,K; M<Subscript>2</Subscript> = Be,Mg, Ca; M<Subscript>3</Subscript> = H,F, Cl,Br)

In a quest to identify new ground-state triplet germylenes, the stabilities (singlet–triplet energy differences, ΔE_S–T) of 96 singlet (s) and triplet (t) M₁-Ge-M₂-M₃ species were compared and contrasted at the B3LYP/6–311++G**, QCISD(T)/6–311++G**, and CCSD(T)/6–311++G** levels of theory (M₁?=?H, Li, Na, K; M₂?=?Be, Mg, Ca; M₃?=?H, F, Cl, Br). Interestingly, F-substituent triplet germylenes (M₃?=?F) appear to be more stable and linear than the corresponding Cl- or Br-substituent triplet germylenes (M₃?=?Cl or Br). Triplets with M₁?=?K (i.e., the K-Ge-M₂-M₃ series) seem to be more stable than the corresponding triplets with M₁?=?H, Li, or Na. This can be attributed to the higher electropositivity of potassium. Triplet species with M₃?=?Cl behave similarly to those with M₃?=?Br. Conversely, triplets with M₃?=?H show similar stabilities and linearities to those with M₃?=?F. Singlet species of formulae K-Ge-Ca-Cl and K-Ge-Ca-Br form unexpected cyclic structures. Finally, the triplet germylenes M₁-Ge-M₂-M₃ become more stable as the electropositivities of the α-substituents (M₁ and M₂) and the electronegativity of the β-substituent (M₃) increase.     

Prey preference of predatory mite Amblyseius swirskii (Acari: Phytoseiidae) on Tetranychus urticae (Acari: Tetranychidae) and Bemisia tabaci (Hemiptera: Aleyrodidae)

Tetranychus urticae Koch (Acari: Tetranychidae) and Bemisia tabaci Gennadius (Hemiptera: Aleyrodidae) are major pests in greenhouse crops. Recently, Amblyseius swirskii Athias-Henriot (Acari: Phytoseiidae) was shown to be an effective biological control agent of both pests. Therefore, the prey preference of A. swirskii was determined using immature stages of T. urticae and B. tabaci in three various treatments based on Manly's β preference index (β). These treatments consisted of immature stages of two prey species (egg, first and second instar nymphs) with densities 12:12, 6:6 and 3:3, respectively, and with 13 replicates. After 24?h starvation, same-aged females of A. swirskii were added to the leaf discs. All experiments were done on bean leaf discs in Petri dishes (8?cm in diameter) in laboratory conditions with 25?±?2°C, 70?±?5% relative humidity and the photoperiod of 16L:8D hours. Comparing the preference indices using t-tests indicates a significant preference of the predator on eggs (t?=?10.80, df?=?24, P?t?=?8.17, df?=?24, P?T. urticae than B. tabaci. Our findings suggest that developmental stages of prey have effect on the prey selection by A. swirskii.     

Patterns of niche overlapping and richness among Geocoris species (Hemiptera: Geocoridae) in Iran

Several big-eyed bugs, Geocoris species, are abundant predators in many important agricultural cropping systems. Despite their apparent importance and high visibility little is known about their environmental relationships, niche overlap and species richness. To determine these ecological characteristics of 5 Geocoris species for use in conservation efforts, an extensive sampling was done in 152 localities of Iran. A richness model was developed using a maximum entropy modelling approach (Maxent) and ArcGIS software for the five species based on collection records in conjunction with eight environmental variables. Maps for habitat overlap were created for paired species using ArcGIS 10.2 and ENMTools. The species displayed different overlapping niche ranges from 1.97% to 37.25% in pair-wise comparisons. For species richness three categories (habitats dominated by 0–1, 2–3, and 4–5 species) represented 38.44%, 46.07%, and 15.49% of the modelled landscape, respectively. A direct relationship was found between humidity and the number of species present in different locations. Understanding the degree of ecological overlap between the Geocoris species, and their effective predation of aphids and mites, is critical in designing biological control methods in agroecosystems.     

Leukocyte Gene Expression and Plasma Concentration in Multiple Sclerosis: Alteration of Transforming Growth Factor-βs,Claudin-11, and Matrix Metalloproteinase-2

Multiple sclerosis is a neurodegenerative disease characterized by the present of leukocytes in the brain tissue and subsequently the formation of sclerotic plaques. Leukocytes penetration into the blood–brain barrier is related to several factors, such as, the conversion of leukocyte gene expression or plasma characteristics. In this frame, we explore alteration of matrix metalloproteinase-2 (MMP-2), transforming growth factor beta (TGF-β) family, and Claudin-11 (as a main myelin structural protein) in leukocytes and blood plasma of multiple sclerosis patients compared to the normal group. Blood samples were collected from thirteen men affected by MS and fifteen healthy men. Leukocyte gene expression was measured using real-time PCR and plasma parameters were examined by ELISA. The results of this study showed that the gene expression of Claudin-11 was significantly higher in MS group compared with normal. Interestingly, the MMP-2 pattern was similar to Claudin-11 and correlated positively with it. It was observed that, although the expressions of TGF-β1 and TGF-β2 are down-regulated in the leukocytes of subjects with MS, they showed higher levels of these cytokines in blood plasma. The plasma level of TGF-β3 in MS patients was higher than normal and correlated with Claudin-11 concentration. In conclusion, the aberrant pattern of Claudin-11, TGF-βs family, and MMP-2 expression in leukocytes of the MS patients was observed in this study. Moreover, the plasma levels of TGF-βs family increased in the MS group. The findings of this study provide clues for further investigations to assay MS pathogenesis.