Role of Angiotensin II Type 1A Receptors on Renal and Urinary Angiotensin Converting Enzyme 2 (ACE2) and Neprilysin (NEP) in the Two-Kidney One-Clip (2K1C) Model of Renovascular Hypertension

Activation of the renin angiotensin system (RAS) and increased formation of angiotensin (Ang) II contribute to the progression of chronic kidney disease (CKD). Ang II, the major biologically active peptide of RAS, acts mainly as a vasoconstrictor through binding to the Ang II type 1 receptor (AT1R), which leads to increased blood pressure, fluid retention, and aldosterone secretion. The actions of Ang II are antagonized by its conversion to the vasodilator Ang (1-7), partly generated by the action of angiotensin converting enzyme 2 (ACE2) and/or neprilysin (NEP). The metalloprotease ADAM17 has a crucial role in the shedding of renal ACE2 in diabetic mice model. The two-kidney, one clip (2K1C) Goldblatt model is an experimental approach designed to mimic renovascular hypertension. It consists of the unilateral clamping of the renal artery in one of the kidneys. The aim of this study is to test the hypotheses that: 1) renovascular hypertension and increased albuminuria in the 2K1C model is mediated by AT1AR and 2) up-regulation of renal ADAM17 increase the shedding of renal ACE2 and NEP into the urine. Wild type (WT) and AT1AR knockout (AT1 KO) mice were used to test our hypotheses. Mice were subjected to surgical procedures to implant radio-telemetry transmitters for measurement of blood pressure (BP), followed by induction of renovascular hypertension. BP at baseline was significantly lower in AT1 KO compared to WT mice, whereas in WT 2K1C, BP was significantly higher than controls (p\u3c0.05). However, 2K1C has no effect on BP in AT1 KO mice. Urinary albumin excretion significantly increased in WT 2K1C mice compared to sham -operated ones, while no change was observed in AT1 KO. In addition, a significant reduction of renal ADAM17 and NEP contents was observed in clipped kidney relative to the unclipped and sham kidneys. Western blot analysis showed a significant decrease in renal ACE2, NEP, and ADAM17 protein expression levels in the clipped kidney compared to the unclipped or sham-operated ones. Histological assessment of the kidneys in the 2K1C model revealed significant mesangial expansion and renal fibrosis. Data suggest that renovascular hypertension is mediated by AT1AR and deletion of this receptor attenuates albuminuria in the 2K1C model. In 2K1C, the downregulation of renal and urinary ACE2 and ADAM17 suggest a potential link between ADAM17 and ACE2 shedding in 2K1C mice. Decreased renal NEP in the clipped kidney of 2K1C model may thus worsen kidney injury via impairment of Ang (1-7) formation

Association or Causation? Exploring the Oral Microbiome and Cancer Links

Several epidemiological investigations have found associations between poor oral health and different types of cancer, including colorectal, lung, pancreatic, and oral malignancies. The oral health parameters underlying these relationships include deficient oral hygiene, gingival bleeding, and bone and tooth loss. These parameters are related to periodontal diseases, which are directly and indirectly mediated by oral bacteria. Given the increased accessibility of microbial sequencing platforms, many recent studies have investigated the link between the oral microbiome and these cancers. Overall, it seems that oral dysbiotic states can contribute to tumorigenesis in the oral cavity as well as in distant body sites. Further, it appears that certain oral bacterial species can contribute to carcinogenesis, in particular, Fusobacterium nucleatum and Porphyromonas gingivalis, based on results from epidemiological as well as mechanistic studies. Yet, the strength of the findings from these investigations is hampered by the heterogeneity of the methods used to measure oral diseases, the treatment of confounding factors, the study design, the platforms employed for microbial analysis, and types of samples analyzed. Despite these limitations, there is an overall indication that the presence of oral dysbiosis that leads to oral diseases may directly and/or indirectly contribute to carcinogenesis. Proper methodological standardized approaches should be implemented in future epidemiological studies as well as in the mechanistic investigations carried out to explore these results. © International & American Associations for Dental Research 202

Gonad Maturation of Angle Fish (Pterophyllum Scallare) Induced by Laser Puncture Exposure at Different TIME Duration

A research was conducted from January-February 2016 at the Fish Hatchery and Breeding Laboratory, Faculty of Fisheries and Marine Science, University of Riau Pekanbaru. The purpose of the research was to evaluate the duration of laser puncture exposure on gonad maturation of angle fish (Pterophyllum scallare). Completely randomized design was used to analyze the gonad maturation at the different duration of laser puncture exposure (0, 15, 20, and 25) seconds. The shooting was done twice a week for 4 weeks. The brood fish were reared in 54 L aquarium tank (60x30x35 cm) and fed on 38% protein pellet plus 57% protein tubifex worm.The results of research showed that there was an effect of laser puncture exposure duration, on gonad maturation of angle fish (Pterophyllum scallare). The best duration of laser puncture to stimulate gonad maturation was 20 second. At the duration the maturation was reached in 35 days with gonado somatic indeks 6,3 %, fecundity 908 eggs, and eggs diameter 1.5 mm. The temperature range from 26-27 oC, pH 5-6, and DO 5,7-6,8 ppm

Soliton-potential interaction in the nonlinear Klein-Gordon model

The interaction of solitons with external potentials in nonlinear Klein-Gordon field theory is investigated using an improved model. The presented model has been constructed with a better approximation for adding the potential to the Lagrangian through the metric of background space-time. The results of the model are compared with another model and the differences are discussed.Comment: 14 pages,8 figure

Differential Requirements for H/ACA Ribonucleoprotein Components in Cell Proliferation and Response to DNA Damage

H/ACA ribonucleoproteins (RNPs) are comprised of four conserved proteins, dyskerin, NHP2, NOP10, and GAR1, and a function-specifying, noncoding H/ACA RNA. H/ACA RNPs contribute to telomerase assembly and stabilization, and posttranscriptional processing of nascent ribosomal RNA and spliceosomal RNA. However, very little is known about the coordinated action of the four proteins in other biologic processes. As described herein, we observed a differential requirement for the proteins in cell proliferation and identified a possible reliance for these factors in regulation of specific DNA damage biomarkers. In particular, GAR1 expression was upregulated following exposure to all forms of genotoxic stress tested. In contrast, levels of the other proteins were either reduced or unaffected. Only GAR1 showed an altered subcellular localization with a shift from the nucleolus to the nucleoplasm after ultraviolet-C irradiation and doxorubicin treatments. Transient siRNA-mediated depletion of GAR1 and dyskerin arrested cell proliferation, whereas loss of either NHP2 or NOP10 had no effect. Finally, loss of dyskerin, GAR1, NHP2, and NOP10, respectively, limited the accumulation of DNA damage biomarkers. However, the individual responses were dependent upon the specific type of damage incurred. In general, loss of GAR1 had the most suppressive effect on the biomarkers tested. Since the specific responses to genotoxic stress, the contribution of each protein to cell proliferation, and the activation of DNA damage biomarkers were not equivalent, this suggests the possibility that at least some of the proteins, most notably GAR1, may potentially function independently of their respective roles within H/ACA RNP complexes

Diabetes Aggravates Periodontitis by Limiting Repair Through Enhanced Inflammation

Periodontitis is the most common lytic bone disease and one of the first clinical manifestations of diabetes. Diabetes increases the risk of periodontitis. The aim of the present study was to examine mechanisms by which diabetes aggravates periodontitis. Ligature-induced periodontitis was examined in Goto-Kakizaki rats with type 2 diabetes. A tumor necrosis factor (TNF)-specificinhibitor, pegsunercept, was applied to diabetic rats after the onset of periodontal disease. Interferon-γ (IFN-γ), TNF-α, interleukin-1 β (IL-1β), fibroblast growth factor-2 (FGF-2), transforming growth factor beta-1 (TGFβ-1), bone morphogenetic protein-2 (BMP-2), and BMP-6 were measured by real-time RT-PCR, and histological sections were examined for leukocyte infiltration and several parameters related to bone resorption and formation. Inflammation was prolonged in diabetic rats and was reversed by the TNF inhibitor, which reduced cytokine mRNA levels, leukocyte infiltration, and osteoclasts. In contrast, new bone and osteoid formation and osteoblast numbers were increased significantly vs. untreated diabetic animals. TNF inhibition in diabetic animals also reduced apoptosis, increased proliferation of bone-lining cells, and increased mRNA levels of FGF-2, TGFβ-1, BMP-2, and BMP-6. Thus, diabetes prolongs inflammation and osteoclastogenesis in periodontitis and through TNF limits the normal reparative process by negatively modulating factors that regulate bone. © FASEB

Multi-Center non-BPS Black Holes - the Solution

We construct multi-center, non-supersymmetric four-dimensional solutions describing a rotating anti-D6-D2 black hole and an arbitrary number of D4-D2-D0 black holes in a line. These solutions correspond to an arbitrary number of extremal non-BPS black rings in a Taub-NUT space with a rotating three-charge black hole in the middle. The positions of the centers are determined by solving a set of "bubble" or "integrability" equations that contain cubic polynomials of the inter-center distance, and that allow scaling solutions even when the total four-dimensional angular momentum of the scaling centers is non-zero.Comment: 16 pages, LaTe

NF-κB perturbation reveals unique immunomodulatory functions in Prx1 + Fibroblasts that Promote Development of Atopic Dermatitis

Skin is composed of diverse cell populations that cooperatively maintain homeostasis. Up-regulation of the nuclear factor кB (NF-кB) pathway may lead to the development of chronic inflammatory disorders of the skin, but its role during the early events remains unclear. Through analysis of single-cell RNA sequencing data via iterative random forest leave one out prediction, an explainable artificial intelligence method, we identified an immunoregulatory role for a unique paired related homeobox-1 (Prx1)+ fibroblast subpopulation. Disruption of Ikkb-NF-кB under homeostatic conditions in these fibroblasts paradoxically induced skin inflammation due to the overexpression of C-C motif chemokine ligand 11 (CCL11; or eotaxin-1) characterized by eosinophil infiltration and a subsequent TH2 immune response. Because the inflammatory phenotype resembled that seen in human atopic dermatitis (AD), we examined human AD skin samples and found that human AD fibroblasts also overexpressed CCL11 and that perturbation of Ikkb-NF-кB in primary human dermal fibroblasts up-regulated CCL11. Monoclonal antibody treatment against CCL11 was effective in reducing the eosinophilia and TH2 inflammation in a mouse model. Together, the murine model and human AD specimens point to dysregulated Prx1+ fibroblasts as a previously unrecognized etiologic factor that may contribute to the pathogenesis of AD and suggest that targeting CCL11 may be a way to treat AD-like skin lesions. © 2022 The Authors, some rights reserve

Sight and sound persistently out of synch: stable individual differences in audiovisual synchronisation revealed by implicit measures of lip-voice integration

Are sight and sound out of synch? Signs that they are have been dismissed for over two centuries as an artefact of attentional and response bias, to which traditional subjective methods are prone. To avoid such biases, we measured performance on objective tasks that depend implicitly on achieving good lip-synch. We measured the McGurk effect (in which incongruent lip-voice pairs evoke illusory phonemes), and also identification of degraded speech, while manipulating audiovisual asynchrony. Peak performance was found at an average auditory lag of ~100 ms, but this varied widely between individuals. Participants’ individual optimal asynchronies showed trait-like stability when the same task was re-tested one week later, but measures based on different tasks did not correlate. This discounts the possible influence of common biasing factors, suggesting instead that our different tasks probe different brain networks, each subject to their own intrinsic auditory and visual processing latencies. Our findings call for renewed interest in the biological causes and cognitive consequences of individual sensory asynchronies, leading potentially to fresh insights into the neural representation of sensory timing. A concrete implication is that speech comprehension might be enhanced, by first measuring each individual’s optimal asynchrony and then applying a compensatory auditory delay