Active Fragments from Pro- and Antiapoptotic BCL-2 Proteins Have Distinct Membrane Behavior Reflecting Their Functional Divergence

Background

The BCL-2 family of proteins includes pro- and antiapoptotic members acting by controlling the permeabilization of mitochondria. Although the association of these proteins with the outer mitochondrial membrane is crucial for their function, little is known about the characteristics of this interaction.

Methodology/Principal Findings

Here, we followed a reductionist approach to clarify to what extent membrane-active regions of homologous BCL-2 family proteins contribute to their functional divergence. Using isolated mitochondria as well as model lipid Langmuir monolayers coupled with Brewster Angle Microscopy, we explored systematically and comparatively the membrane activity and membrane-peptide interactions of fragments derived from the central helical hairpin of BAX, BCL-xL and BID. The results show a connection between the differing abilities of the assayed peptide fragments to contact, insert, destabilize and porate membranes and the activity of their cognate proteins in programmed cell death.

Conclusion/Significance

BCL-2 family-derived pore-forming helices thus represent structurally analogous, but functionally dissimilar membrane domains.     

Effects of combining <Emphasis Type="Italic">Beauveria bassiana</Emphasis> and <Emphasis Type="Italic">Nosema pyrausta</Emphasis> on the mortality of <Emphasis Type="Italic">Ostrinia nubilalis</Emphasis>

We tested the combined effect of the fungus Beauveria bassiana and the microsporidium Nosema pyrausta on the European corn borer larvae, Ostrinia nubilalis, in the laboratory. The first instar of O. nubilalis larvae was the most sensitive to the B. bassiana infection followed by the fifth, second, third, and fourth instar (LC₅₀s were 4.91, 6.67, 7.13, 9.15, and 6.51 × 10⁵ conidia/ml for the first to fifth instars, respectively). Mortality of each instar increases positively with concentration of conidia. When B. bassiana and N. pyrausta were used in combination, mortality increased significantly in all instars. Relative to the B. bassiana treatment alone, the B. bassiana + N. pyrausta treatment decreased the LC₅₀s by 42.16%, 37.63%, 21.60%, 27.11%, and 33.95% for the first to fifth instars, respectively. The combined effects of the two pathogens were mostly additive. However, at the two highest concentrations the pathogens interacted synergistically in the first and second instar. Individuals that survived the B. bassiana and B. bassiana + N. pyrausta treatments and developed into adults had significantly shorter lifespans and females oviposited fewer eggs than non-exposed insects. The effects on the longevity and the egg production were most pronounced at high concentration of B. bassiana conidia.     

Bone marrow‐derived mesenchymal stem cells mitigate caspase‐3 and 8‐hydroxy proline induced via β‐adrenergic agonist in pulmonary injured rats

Estimating the ability of bone marrow‐derived mesenchymal stem cells (BM‐MSCs) to alleviate pulmonary injury induced via isoproterenol (ISP). ISP was injected in a dose of (100 mg/kg, subcutaneously twice at an interval of 24 h). One month post BM‐MSCs transplantation by intravenous injection, pulmonary oxidative stress was assessed, and Western blot analyses and histopathological investigations were conducted. Compared with the normal control group, BM‐MSCs transplantation significantly decreased the expression of pulmonary anti‐oxidative stress marker. Western blot analysis revealed that ISP significantly reduced the protein expression of the anti‐oxidative stress marker nuclear related factor‐2 (Nrf2). However, the apoptotic marker (caspase‐3) and collagen content marker (8‐hydroxyproline) were markedly elevated. These biochemical markers were confirmed by histopathological investigations. Finally, it was demonstrated that BM‐MSCs transplantation showed a superior effect in improving pulmonary function through alleviating oxidative stress, apoptosis, and collagen content.     

Eimeria papillata: upregulation of specific miRNA-species in the mouse jejunum

Increasing evidence indicates miRNAs as critical regulators of gene expression, but little information is available for miRNAs in intestinal diseases. Here, we investigated intestinal infections of male Balb/c mice with the coccidian parasite Eimeria papillata. On day 4 after oral infection, mice were shedding 3150 ± 430 oocysts per gram feces. This was associated with a low inflammatory response of the jejunum of mice evidenced by histology, non-response of IL-1β mRNA, even slight downregulation of IL-6 mRNA, only slight increases in iNOS mRNA, nitrate/nitrate, malondialdehyde, and a small decrease in glutathione, respectively. Only IFNγ mRNA was strongly induced. Using miRNA microarray technology, there were significantly upregulated the four miRNA species miR-1959, MCMV-miR-M23-1-5P, miR-203, and miR-21 out of 634 miRNAs, which was also confirmed by quantitative RT-PCR. Our data provide evidence that E. papillata parasites are able to induce specific miRNA species in their host target organ.     

Effect of celecoxib on the antihypertensive effect of losartan in a rat model of renovascular hypertension

Certain nonsteroidal anti-inflammatory drugs have been reported to elevate blood pressure in some hypertensive patients, who are either untreated or treated with antihypertensive agents. This study was undertaken to determine the effect of a selective cyclooxygenase-2 (COX-2) inhibitor, celecoxib, on the antihypertensive effects of the angiotensin II type 1 receptor (AT1) antagonist, losartan potassium. We studied the effect of oral treatment with losartan (30?mg/kg), celecoxib (3?mg/kg), and their combination on the mean arterial blood pressure (MAP), plasma renin activity (PRA), and plasma prostaglandin E2 (PGE2) in male Sprague-Dawley rats with renovascular hypertension (RVH) induced by partial subdiaphragmatic aortic constriction. Treatment was continued for 7 days after aortic coarctation. Aortic coarctation led to significant increases in the MAP, PRA, and plasma PGE2. In RVH rats, losartan treatment caused a significant decrease of MAP with a significant increase in both plasma PGE2 and PRA. Celecoxib caused a nonsignificant change in MAP with a significant decrease in the raised levels of plasma PGE2 and PRA. Concomitant administration of celecoxib and losartan did not significantly affect the lowering effect of losartan on MAP with a subsequent significant decrease in the plasma PGE2 and PRA in RVH rats. Therefore, celecoxib could be used in renin-dependent hypertensive patients who receive losartan, without fear of a rise in their blood pressure.     

Growth stimulation and inhibition by salt in relation to Na<Superscript>+</Superscript> manipulating genes in xero-halophyte <Emphasis Type="Italic">Atriplex halimus</Emphasis> L.

In the present study, Na⁺ manipulating genes could contribute not only to ion homeostasis but also to growth stimulation with exposing the halophyte Atriplex halimus L. to moderate NaCl concentration. The stimulation of growth was attributed to Na⁺ accumulation inside the vacuole leading to increase leaf cell size as well as accelerate leaf cell division. Increasing the assimilatory surface could result in enhancing the photosynthetic rate. The reduction of A. halimus growth compared to optimum growth at 50 and 200 mM NaCl could be attributed to osmotic effect rather than the ionic one of salt stress. The inhibition of photosynthesis seemed to be resulted from limitation of CO₂ due to the osmotic effect on stomatal conductance rather than the activity loss of photosynthetic machinery. The depletion of starch content along with the increase in sucrose content could imply that photosynthesis may be a limiting for A. halimus growth. The fast coordinate induction of Na⁺ manipulating genes could reveal that the tolerance of A. halimus to high concentrations evolved from its ability to regulate and control Na⁺ influx and efflux. V-H ⁺-PPase may play a vital role in A. halimus tolerance to osmotic and/or ionic stress due to its kinetics of induction. It seemed that H⁺-ATPase plays a pivotal role in A. halimus tolerance to stress due to the increase in its protein level was detected with all NaCl concentrations as well as with PEG treatments. Both of these genes might be useful in improving stress tolerance in transgenic crops.     

Environmental relationships of aquatic vegetation in the fresh water ecosystem of the Nile Delta,Egypt

In generalized four sectors, 350 stands (water channels) in 50 selected and geo‐referenced sites with eighteen environmental factors were surveyed. The total number of recorded species varied from a sector to another: 21 in the northern, nineteen in the middle, seventeen in the western and sixteen in the eastern. New populations of Cyperus papyrus were explored. Vallisneria spiralis, Elodea canadensis and Najas armata were among seven extinct species that were not recorded few decades ago. The floristic composition alteration may be because of the addition of organic matter of plant and animal origin and the discharge of industrial and sewage effluents. Classification and ordination analyses (DCA) resulted in the segregation of seventeen vegetation groups (communities), three of them were repeatedly recorded; namely Phragmites australis‐Eichhornia crassipes, Phragmites australis‐Myriophyllum spicatum and Potamogeton pectinatus‐Myriophyllum spicatum. Phragmites australis‐Cyperus papyrus group was a new community spreading in the eastern sector of the Delta. Electric conductivity, Fe, Hg and chemical oxygen demand (COD) showed high significant variation (P < 0.001) among the vegetation groups. Other significant variables were Cl, Ca, NO₃, pH and SO₄ (P < 0.047). Redundancy analysis (RDA) was chosen as the appropriate ordination method to perform direct gradient analysis. Trace elements Cu, Fe, Hg and Pb participated in the floristic and chemical composition of each sector.     

Efficiency of diagnostic biomarkers among colonic schistosomiasis Egyptian patients

The schistosomal parasite plays a critical role in the development of malignant lesions in different organs. The pathogenesis of cancer is currently under intense investigation to identify reliable prognostic indices for disease detection. The objective of this paper is to evaluate certain biochemical parameters as diagnostic tools to efficiently differentiate between colonic carcinoma and colonic carcinoma associated with schistosomal infection among Egyptian patients. The parameters under investigation are interleukin 2 (IL-2), tumour necrosis factor alpha (TNF-α), carcinoembryonic antigen (CEA) levels, tissue telomerase, pyruvate kinase (PK), glucose-6-phosphate dehydrogenase (G-6-PD) and lactate dehydrogenase (LDH) enzyme activities. The results revealed a significant elevation in the level of the tumour markers IL-2, TNF-α and CEA as well as the activities of LDH, telomerase and G-6-PD among non-bilharzial and bilharzial colonic cancer groups, with a more potent effect in bilharzial infection-associated colonic cancer. A significant inhibition in PK activity was recorded in the same manner as compared to normal tissues. The efficacy of this biomarker was also evaluated through detecting sensitivity, specificity, negative and positive predictive values. In conclusion, schistosomal colonic carcinoma patients displayed more drastic changes in all parameters under investigation. The combination of the selected parameters succeeded in serving as biomarkers to differentiate between the two malignant types.     

Characterization of ISR region and development of a PCR assay for rapid detection of the fish pathogen Tenacibaculum soleae

The aims of this work were to characterize the 16S-23S internal spacer region of the fish pathogen Tenacibaculum soleae and to develop a PCR assay for its identification and detection. All T.?soleae strains tested displayed a single internal spacer region class, containing tRNA(I) (le) and tRNA(A) (la) genes; nevertheless, a considerable intraspecific heterogeneity was observed. However, this region proved to be useful for differentiation of T.?soleae from related and non-related species. Species-specific primers were designed targeting the 16S rRNA gene and the internal spacer region region, yielding a 1555-bp fragment. Detection limit was of 1?pg DNA per reaction (相似文献