The Na
-activated Na
channel (Nax) and salt-inducible kinase (SIK) are stimulated by increases in local Na
concentration, affecting (Na
+ K
)-ATPase activity. To test the hypothesis that the triad ...Nax/SIK/(Na
+ K
)-ATPase contributes to kidney injury and salt-sensitive hypertension (HTN), uninephrectomized male Wistar rats (200 g;
= 20) were randomly divided into 4 groups based on a salt diet (normal salt diet; NSD-0.5% NaCl-or high-salt diet; HSD-4% NaCl) and subcutaneous administration of saline (0.9% NaCl) or deoxycorticosterone acetate (DOCA, 8 mg/kg), as follows: Control (CTRL), CTRL-Salt, DOCA, and DOCA-Salt, respectively. After 28 days, the following were measured: kidney function, blood pressure, (Na
+ K
)-ATPase and SIK1 kidney activities, and Nax and SIK1 renal expression levels. SIK isoforms in kidneys of CTRL rats were present in the glomerulus and tubular epithelia; they were not altered by HSD and/or HTN. CTRL-Salt rats remained normotensive but presented slight kidney function decay. HSD rats displayed augmentation of the Nax/SIK/(Na
+ K
)-ATPase pathway. HTN, kidney injury, and kidney function decay were present in all DOCA rats; these were aggravated by HSD. DOCA rats presented unaltered (Na
+ K
)-ATPase activity, diminished total SIK activity, and augmented SIK1 and Nax content in the kidney cortex. DOCA-Salt rats expressed SIK1 activity and downregulation in (Na
+ K
)-ATPase activity in the kidney cortex despite augmented Nax content. The data of this study indicate that the (Na
+ K
)-ATPase activity response to SIK is attenuated in rats under HSD, independent of HTN, as a mechanism contributing to kidney injury and salt-sensitive HTN.
Innovative approaches used to combat Chagas disease transmission tend to combine a set of comprehensive efforts to understand the ecology of local vectors. In this work we identified molecularly the ...blood meal of 181 Triatoma brasiliensis, distributed in 18 populations (8 sylvatic and 10 peridomestic), which were collected across a range of 240 km (East-West) and 95 km (North-South) in the semi-arid region of northeastern, Brazil. We used the vertebrate mitochondrial gene (cytochrome B) sequencing applied to DNA isolated from bug midgut to identify the insect blood meal sources via the BLAST procedure. The peridomestic populations were classified according to two main hypotheses of site-occupancy for T. brasiliensis: the first says that the infestation is mainly driven by structures that resemble its natural habitat (stony-like ecotopes) and the second assumes that it is associated with key-hosts (rodents and goats). Rodents of the Caviidae family (Galea spixii and Kerodon rupestris) were identified as the key-host of T. brasiliensis, but also the potential Trypanosoma cruzi reservoir-able to connect the sylvatic and domestic T. cruzi cycle. Cats also deserve to be studied better, as potential T. cruzi reservoirs. By modeling the food sources + site-occupancy + T. cruzi natural infection, we identified man-made ecotopes suitable for forming dense triatomine infestations with high rates of T. cruzi natural infection, which may be taken into account for vector control measures.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
The physiological roles of ANG-(3-4) (Val-Tyr), a potent ANG II-derived peptide, remain largely unknown. The present study 1)investigates whether ANG-(3-4) modulates ouabain-resistant Na(+)-ATPase ...resident in proximal tubule cells and 2) verifies whether its possible action on pumping activity, considered the fine tuner of Na(+) reabsorption in this nephron segment, depends on blood pressure. ANG-(3-4) inhibited Na(+)-ATPase activity in membranes of spontaneously hypertensive rats (SHR) at nanomolar concentrations, with no effect in Wistar-Kyoto (WKY) rats or on Na(+)-K(+)-ATPase. PD123319 (10(-7) M) and PKA(5-24) (10(-6) M), an AT2 receptor (AT2R) antagonist and a specific PKA inhibitor, respectively, abrogated this inhibition, indicating that AT2R and PKA are central in this pathway. Despite the lack of effect of ANG-(3-4) when assayed alone in WKY rats, the peptide (10(-8) M) completely blocked stimulation of Na(+)-ATPase induced by 10(-10) M ANG II in normotensive rats through a mechanism that also involves AT2R and PKA. Tubular membranes from WKY rats had higher levels of AT2R/AT1R heterodimers, which remain associated in 10(-10) M ANG II and dissociate to a very low dimerization state upon addition of 10(-8) M ANG-(3-4). This lower level of heterodimers was that found in SHR, and heterodimers did not dissociate when the same concentration of ANG-(3-4) was present. Oral administration of ANG-(3-4) (50 mg/kg body mass) increased urinary Na(+) concentration and urinary Na(+) excretion with a simultaneous decrease in systolic arterial pressure in SHR, but not in WKY rats. Thus the influence of ANG-(3-4) on Na(+) transport and its hypotensive action depend on receptor association and on blood pressure.
The PI3K/PTEN/Akt signaling pathway has emerged in recent years as a main player in human cancers, increasing proliferation and decreasing apoptosis of transformed cells, and thus becoming a ...potential target for therapeutic intervention. Our previous data have demonstrated that Akt-mediated signaling is of a key relevance in the mouse skin carcinogenesis system, one of the best-known models of experimental carcinogenesis. Here, we investigated the involvement of several pathways as mediators of Akt-induced increased proliferation and tumorigenesis in keratinocytes. Tumors produced by subcutaneous injection of Akt-transformed keratinocytes showed increased Foxo3a phosphorylation, but no major alterations in p21(Cip1/WAF1), p27(Kip1) or mdm2 expression and/or localization. In contrast, we found increased expression and nuclear localization of DeltaNp63, beta-catenin and Lef1. Concomitantly, we also found increased expression of c-myc and CycD1, targets of the beta-catenin/Tcf pathway. Such increase is associated with increased phosphorylation and stabilization of c-myc protein as well as increased translation of c-myc and CycD1 due to mTOR activation. Using immunohistochemistry approaches in samples of oral dysplasias and human head and neck squamous cell carcinomas, we confirmed that increased Akt activation significantly correlates with increased DeltaNp63 and CycD expression, c-myc phosphorylation and nuclear accumulation of beta-catenin. Collectively, these results demonstrate that Akt is able to transform keratinocytes by specific mechanisms involving transcriptional and post-transcriptional processes.
Aberrant activation of the phosphoinositide-3-kinase (PI3K)/PTEN/Akt pathway, leading to increased proliferation and decreased apoptosis, has been implicated in several human pathologies including ...cancer. Our previous data have shown that Akt-mediated signaling is an essential mediator in the mouse skin carcinogenesis system during both the tumor promotion and progression stages. In addition, overexpression of Akt is also able to transform keratinocytes through transcriptional and posttranscriptional processes. Here, we report the consequences of the increased expression of Akt1 (wtAkt) or constitutively active Akt1 (myrAkt) in the basal layer of stratified epithelia using the bovine keratin K5 promoter. These mice display alterations in epidermal proliferation and differentiation. In addition, transgenic mice with the highest levels of Akt expression developed spontaneous epithelial tumors in multiple organs with age. Furthermore, both wtAkt and myrAkt transgenic lines displayed heightened sensitivity to the epidermal proliferative effects of the tumor promoter 12-O-tetradecanoylphorbol-13-acetate (TPA) and heightened sensitivity to two-stage skin carcinogenesis. Finally, enhanced susceptibility to two-stage carcinogenesis correlated with a more sustained proliferative response following treatment with TPA as well as sustained alterations in Akt downstream signaling pathways and elevations in cell cycle regulatory proteins. Collectively, the data provide direct support for an important role for Akt signaling in epithelial carcinogenesis in vivo, especially during the tumor promotion stage.
Peroxidases (PODs) have many biological functions during the plant life cycle. In maize kernels, endosperm PODs have been identified as biochemical contributors to resistance against
Sitophilus ...zeamais
, but their identities have not been determined. In this study, we identified these PODs and determined whether their contributions are basal or inducible. Semi-purification and LC-MS/MS analyses showed that the protein ZmPrx35 is the predominant soluble endosperm POD from kernels of Pob84-C3R. Subsequent time-course analyses after mechanical damage showed that POD activity was regulated in a fluctuating kinetics pattern and that
zmprx35
mRNA expression levels reflected this pattern. After 48 h of infestation with
S. zeamais
or
Prostephanus truncatus
, soluble endosperm POD activities were 1.38- or 0.85-fold, respectively. Under the same conditions,
zmprx35
expression was induced 1.61-fold (
S. zeamais
infestation) and 1.17-fold (
P. truncatus
infestation). These findings suggest that ZmPrx35 contributes to the protective responses of aleurone cells against wounding and pest attacks, which could be enhanced/repressed by insect factors. Our data also provide evidence that the mechanisms of resistance of maize Pob84-C3R kernels toward the insect pests
S. zeamais
and
P. truncatus
are independent.
ANG II has many biological effects in renal physiology, particularly in Ca2+ handling in the regulation of fluid and solute reabsorption. It involves the systemic endocrine renin-angiotensin system ...(RAS), but tissue and intracrine ANG II are also known. We have shown that ANG II induces heterodimerization of its AT1 and AT2 receptors (AT1R and AT2R) to stimulate sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) activity. Thus, we investigated whether ANG II-AT1R/AT2R complex is formed and internalized, and also examined the intracellular localization of this complex to determine how its effect might be exerted on renal intracrine RAS. Living cell imaging of LLC-PK1 cells, quantification of extracellular ANG II, and use of the receptor antagonists, losartan and PD123319, showed that ANG II is internalized with AT1R/AT2R heterodimers as a complex in a microtubule-dependent and clathrin-independent manner, since colchicine-but not Pitstop2-blocked this process. This result was confirmed by an increase of β-arrestin phosphorylation after ANG II treatment, clathrin-mediated endocytosis being dependent on dephosphorylation of β-arrestin. Internalized ANG II colocalized with an endoplasmic reticulum (ER) marker and increased levels of AT1R, AT2R, and PKCα in ER-enriched membrane fractions. This novel evidence suggests the internalization of an ANG II-AT1/AT2 complex to target ER, where it might trigger intracellular Ca2+ responses.
Plants under herbivore attack often respond defensively by mounting chemical and physical defences. However, some herbivores can manipulate plant defences to their own benefit by suppressing the ...expression of induced defences. These herbivore‐induced changes specific to the attacking herbivore can either facilitate or impede the colonization and establishment of a second herbivore. Although recent studies have focused on the effect of multiple herbivory on plant induced response and the third trophic level, few have examined the ecological relevance of multiple herbivores sharing the host. Here, we investigated whether herbivory by the white mealybug Planococcus minor (Maskell) (Hemiptera: Pseudococcidae) or the red spider mite Olygonychus ilicis (McGregor) (Acari: Tetranychidae), two herbivores that peak in coffee plantations during the dry season, may facilitate the colonization and establishment of the other species in coffee plants. Dual‐choice arena tests showed that white mealybugs preferred mite‐infested over uninfested coffee plants as hosts. Fifteen days after the release of 50 first‐instar P. minor nymphs, greater numbers of nymphs and adults were found on mite‐infested than uninfested plants, indicating superior performance on mite‐infested plants. On the other hand, female red spider mites did not show clear preference between uninfested and mealybug‐infested plants and deposited similar numbers of eggs on both treatments. In a no‐choice test, red spider mites performed poorly on mealybug‐infested plants with a smaller number of eggs, nymphs, females and males found in mealybug‐infested plants relative to uninfested plants. Thus, our results indicate that coffee plants are more likely to be infested by the red spider mite before white mealybug, rather than the inverse sequence (i.e. mealybug infestation followed by red spider mites). Our findings are discussed in the context of plant manipulation reported for pseudococcid mealybugs and spider mites.
Electronic cigarettes (e-cigarettes) have emerged as a new paradigm in nicotine delivery systems. Although they are marketed as safer alternatives to tobacco, public perceptions of their safety and ...utility vary widely. This study aims to understand the percentage of use, factors associated, perceptions, and attitudes about e-cigarettes among Ecuadorian adults.
A cross-sectional survey was conducted among the Ecuadorian population aged 18-65 years through a convenience sample, using a structured online questionnaire designed to collect responses from voluntary participants over three months, from February to April 2023. The questionnaire assessed the respondents' attitudes and perceptions towards e-cigarettes. Data were analyzed using descriptive statistics, chi-squared tests, and adjusted logistic regression analyses to identify factors associated with e-cigarette use.
Out of a total of 3047 Ecuadorian adults, the percentage of e-cigarette ever use was 27.9% (n=850), with 19.4% being current users and 8.5% former users. A negative stance towards e-cigarettes was predominant, with 66.3% considering e-cigarette use a public health problem in Ecuador. A significant association was observed between e-cigarette use and perceived harmfulness (p<0.001). Among non-users, there was a predominant stance in favor of control measures and disapproval of e-cigarette use among minors (p<0.001). The factors associated with the use of electronic cigarettes included being health personnel (AOR=1.51; 95% CI: 1.26-1.80). Older age (aged >24 years) and a history of tobacco use were associated with lower e-cigarette use (current users, OR=0.31; 95% CI: 0.25-0.38; previous users, OR=0.23; 95% CI: 0.18-0.28).
The findings highlight a significant percentage of e-cigarette use among Ecuadorian adults, especially among younger groups. There is a need for comprehensive public health education about e-cigarettes in Ecuador. There is strong support from the public for control measures, suggesting the potential acceptability of regulations concerning e-cigarettes.
Squamous cell carcinomas (SCC) represent the most aggressive type of nonmelanoma skin cancer. Although little is known about the causal alterations of SCCs, in organ-transplanted patients the E7 and ...E6 oncogenes of human papillomavirus, targeting the p53- and pRb-dependent pathways, have been widely involved. Here, we report the functional consequences of the simultaneous elimination of Trp53 and retinoblastoma (Rb) genes in epidermis using Cre-loxP system. Loss of p53, but not pRb, produces spontaneous tumor development, indicating that p53 is the predominant tumor suppressor acting in mouse epidermis. Although the simultaneous inactivation of pRb and p53 does not aggravate the phenotype observed in Rb-deficient epidermis in terms of proliferation and/or differentiation, spontaneous SCC development is severely accelerated in doubly deficient mice. The tumors are aggressive and undifferentiated and display a hair follicle origin. Detailed analysis indicates that the acceleration is mediated by premature activation of the epidermal growth factor receptor/Akt pathway, resulting in increased proliferation in normal and dysplastic hair follicles and augmented tumor angiogenesis. The molecular characteristics of this model provide valuable tools to understand epidermal tumor formation and may ultimately contribute to the development of therapies for the treatment of aggressive squamous cancer.
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