The c-erbAα Protooncogene Induces Apoptosis in Glial Cells via a Protein Kinase C- and bcl-2-Suppressible Mechanism

Abstract: The c- erbA protooncogene encodes the thyroid hormone (3,5,3'-triiodothyronine; T₃) receptor α1 (TRα1). c- erbA /TRα1 is expressed in many cell types including glial cells, particularly in the immature state. We show here by morphological and biochemical criteria that c- erbA induces apoptosis of glial B3.1 cells in serum-deprived conditions. This effect is mostly T₃ independent. Growth factors such as platelet-derived growth factor, basic fibroblast growth factor, or transforming growth factor-α prevent B3.1 + TRα1 cell death. Protein kinase C(PKC) activators also prevent the apoptosis phenomenon, an effect that was blocked by the PKC-specific inhibitor GF109203X. Expression of an exogenous bcl-2 gene led also to B3.1 + TRα1 cell survival. Neither a series of inhibitors including GF109203X nor T₃ inhibits bcl-2 action, indicating that bcl-2 blocks a downstream step in the death-promoting process. B3.1 + TRα1 cell apoptosis is not blocked by caspase-1 or poly-ADP-ribosyltransferase inhibitors, suggesting that the activation of these classic pathways is not involved in the apoptotic mechanism. In addition, direct interaction with specific neuronal cells but not incubation with their conditioned medium inhibits also apoptosis of B3.1 + TRα1 cells. Our results show that c- erbA promotes an apoptotic process in glial B3.1 cells that is suppressible by PKC activation and bcl-2 , probably by distinct mechanisms.     

Effects of limonene and essential oil from Citrus aurantium on gastric mucosa: Role of prostaglandins and gastric mucus secretion

Essential oil from Citrus aurantium and the monoterpene limonene are widely used flavoring agents that are found in some common food items. This specie is also used medicinally throughout the world to treat gastritis and gastric disorders. Therefore, biological assays were performed in vivo on essential oil of C. aurantium (OEC) and its majority compound limonene (LIM) to evaluate their effect on gastric mucosa. The OEC (250 mg/kg, p.o.) and LIM (245 mg/kg, p.o.) provided effective (99%) gastroprotection against lesions induced by absolute ethanol and NSAID (non-steroidal anti-inflammatory drug) in rats. OEC and LIM do not interfere with gastric H⁺ secretion, serum gastrin or glutathione (GSH) level in gastric mucosa. But the gastroprotective action of OEC and LIM occurs due to an increase in the gastric mucus production induced by conserving the basal PGE₂ levels after challenge by agents harmful to the gastric mucosa. Given that LIM and OEC are excellent flavoring agents and also present gastroprotective actions, they can be regarded as a promising target for the development of a new drug for the prevention of gastric damage.     

Chlorophyll fluorescence parameters of three Mediterranean shrubs in a summer-autumn period in central Portugal

The photosynthetic performance of Cistus crispus, Centaurea africana and Thymus villosus, three shrubs of the Mediterranean-type maquis vegetation of Central Portugal, were studied between July and December 2003 by means of in vivo chlorophyll a fluorescence measurements. In C. africana total leaf decay occurred between August and October, in T. villosus no clear pattern of variation of the basal fluorescence (F_o) was observed, and in C. crispus an increase of this parameter was observed in late autumn. In all species, the limitation to photosynthesis by photoinhibition and the contribution of non-reversible processes to total photoinhibition were more pronounced in the summer than in the autumn. However, a pronounced decrease of the effective quantum yield of photosystem 2 (Φ_PS2) was found in late autumn, probably due to a decrease of the carboxylation efficiency of the Calvin-Benson cycle, which was also supported by a parallel decrease of the photochemical quenching coefficient (qP).     

Individuality matters for substrate-size preference in the Nile tilapia juveniles

Preference tests have usually been used to identify nonhuman animal preferences for welfare purposes (environmental enrichment), but they are mostly at the group level—that is, group preferences for resources or environmental conditions. However, a more robust method was developed to analyze animal preference, and this method detected clear individual variation in preferences of Nile tilapia fish (Oreochromis niloticus) selecting different background colors. Here, a clear individual variability of preference was found for another type of enrichment—the sizes of substrate. Despite this variability, a consistent response was detected at the group level: Small gravel was less frequently preferred than avoided, and the more decided fish (those who preferred only one substrate size) never preferred gravel over sand-size substrate. That is, Nile tilapia avoided gravel and preferred smaller substrate, and this finding was possibly associated with their mouth gap. Considering that small gravel is a substrate often used for fish rearing, these findings highlight fish keepers’ incorrect perception of fish needs, based mostly on arbitrary criteria instead of actual fish preferences and without considering individual needs.     

A SNP-based high-density linkage map of zoysiagrass (<Emphasis Type="Italic">Zoysia japonica</Emphasis> Steud.) and its use for the identification of QTL associated with winter hardiness

Zoysia japonica Steud. (2n?=?4×?=?40) is a C₄ turfgrass well-adapted for the warm-humid and transitional climatic zones of the USA. Its use is limited to warmer climates because of a relative lack of winter hardiness compared to C₃ grasses. Molecular markers associated with this trait would be useful for effective selection of winter hardy germplasm before field testing. A pseudo-F₂ mapping population of 175 individuals was developed from crosses between Z. japonica cultivars “Meyer” (freeze-tolerant) and “Victoria” (freeze-susceptible) and used to generate a high-density genetic map of 104 SSR markers and 2359 sequencing-derived SNP markers. The map covers 324 Mbp and 2520 cM as well as the 20 chromosomes for the zoysiagrass haploid genome. Phenotypic data on winter injury, establishment, and turf quality collected in North Carolina and Indiana in 2014–2016 were used in conjunction with this map to identify quantitative trait loci (QTL) associated with winter hardiness. Fifty-six QTL associated with winter injury, establishment, and turf quality were identified over six environments. Twelve of those were identified in two or more environments. Furthermore, seven regions of interest were identified on chromosomes 8, 11, and 13 where co-location of QTL for three or more traits occurred. Within these regions, analysis with NCBI basic local alignment search tool (BLAST) identified proteins related to cold and other abiotic stresses tolerance. These QTL and associated markers could be valuable in implementing marker-assisted selection for winter hardiness in zoysiagrass breeding programs.     

<Emphasis Type="Italic">BRCA1</Emphasis> and <Emphasis Type="Italic">BRCA2</Emphasis> mutations and clinical interpretation in 398 ovarian cancer patients: comparison with breast cancer variants in a similar population

Background

Ovarian cancer is the leading cause of death worldwide among gynecologic malignancies. The recent approval of inhibitors of poly (ADP-ribose) polymerase (iPARP) in the treatment of ovarian cancer in the presence of a BRCA1/2 mutation has sparked the analysis of women with such diagnosis, which can further benefit from the detection of carriers in the family. Germline sequence and large rearrangements for BRCA1/2 were tested in 398 consecutive epithelial ovarian cancer (EOC) patients.The aim of this study was to identify the frequency and spectrum of germline BRCA1/2 pathogenic alterations in a cohort of patients with ovarian serous carcinoma, with a view to adequately selecting patients for prevention through family counseling and correlating this frequency with platinum sensitivity as a guidance to identify patients eligible for iPARP in our population.

Results

A total of 96 patients carried a pathogenic germline mutation, accounting for an overall 24.1% mutation incidence. Among mutation carriers, BRCA1 showed 62.5% incidence, BRCA2 rendered 36.5%, and one patient exhibited a mutation in both genes. Three pathogenic mutations were recurrent mutations detected five, three, and four times and represented 12.5% of the mutated samples. Worth highlighting, a 50% mutation incidence was detected when breast and ovarian cancer coexisted in the same patient. Novel mutations amounted to 9.4% of the total mutations, as compared to 4.7% in breast cancer. Forty out of 60 BRCA1 mutations were beyond the ovarian cancer cluster region (OCCR), in stark contrast with 22 out of 36 BRCA2 mutations being inside the OCCR. Taken together, germline BRCA1/2 mutations in EOC patients showed a distinct mutational spectrum compared to our previously published data on breast cancer patients.

Conclusions

In sum, our study provides novel data on ovarian BRCA1/2 mutation prevalence worldwide, enhances adequate patient selection for family counseling and prevention, and sheds light on the benefits of iPARP treatment.

     

Response of epilithic diatom communities to environmental gradients along an Ecuadorian Andean River

Epilithic diatom communities are particularly suitable for the evaluation of freshwater quality. In Ecuador, however, no water quality index includes this biotic parameter. This work is the first attempt in the country to determine the composition of epilithic diatom communities associated with different degrees of eutrophication. This was accomplished by measuring physical, chemical and microbiological variables at five sampling sites along the Pita River, Ecuador, from August to December 2016. The results indicate a clear gradient of eutrophication from sampling sites P1 (good water) in the upper reaches to P5 (bad water) located in the lower reaches. Concerning diatom analyses, the results indicated a high diversity for tropical areas in terms of species richness, varying from S = 34 in headwaters to S = 42 downstream. Moreover, the results obtained suggest a lack of concordance with the trophic values given to some of the epilithic diatoms in the literature. There were also species that seem to be sensitive to downstream nutrient increases that were not considered as bioindicators in previous studies. We concluded that the trophic values of diatom species available in the scientific literature are not directly applicable to their sites in the Pita River. Hence, it is necessary to establish a trophic diatom index for the Andean region of Ecuador.     

Emergence of Resistance to Fluconazole in <Emphasis Type="Italic">Candida albicans</Emphasis> Isolated From Vaginal Discharge

Purpose of Review

To provide information about the emergence of fluconazole resistance in Candida albicans isolated from vaginal discharge, in a global context, and to update the in vitro susceptibility profile of this species from Argentina.

Recent Findings

Vulvovaginal candidiasis is the second most common vaginal infection after vaginal bacteriosis. C. albicans remains the prevalent etiological yeast species, and despite antifungal treatment, the rate of recurrence remains high, which may be associated to antifungal resistance.

Summary

Data here presented were obtained from the study of C. albicans strains isolated from patients with clinical signs of vulvovaginal candidiasis from 1996 to 2017. Data obtained could represent the susceptibility profile of C. albicans strains circulating in Argentina and could be of potential usefulness to monitor and guide therapy, and also suggests the need for greater surveillance programs to detect fluconazole resistance over time.