Adrenergic and cholinergic innervation of the atrioventricular valves in chinchilla (Chinchilla laniger)

The arrangement of autonomic fibres was studied in the cardiac atrioventricular valves of small chinchillas. The dissected valves were stained entirely using the modified histochemical acetylcholine esterase technique (AChE) and the SPG-De la Torre method. Double immunocytochemical staining was also used for the expression of vesicular acetylcholine transporter (VAChT) and dopamine beta hydroxylase (DBH). The study showed the presence of both cholinergic and adrenergic fibres, forming a kind of network on all cusps of both valves. The adrenergic network is always more strongly represented than the cholinergic network. The cholinergic nerve network of the “parietal” part formed mainly the parallel arrangement. As we move towards the free parts of the cusps, the arrangement becomes netted and radiant. The adrenergic fibres formed only the netted arrangement, which was the most dense in the peripheral (parietal) part of the cusps. Some of the fibres in the vicinity of tendinous cords extended as far as the papillary muscles. Double immunocytochemical tests confirmed the presence and distribution of DBH- and VAChT-positive fibres. Some fibres (especially within the tendinous cords) show VAChT and DBH colocalisation

Human mitochondrial ribosomes can switch structural tRNAs - but when and why?

High resolution cryoEM of mammalian mitoribosomes revealed the unexpected presence of mitochondrially encoded tRNA as a structural component of mitochondrial large ribosomal subunit (mt-LSU). Our previously published data identified that only mitochondrial (mt-) tRNA(Phe) and mt-tRNA(Val) can be incorporated into mammalian mt-LSU and within an organism there is no evidence of tissue specific variation. When mt-tRNA(Val) is limiting, human mitoribosomes can integrate mt-tRNA(Phe) instead to generate a translationally competent monosome. Here we discuss the possible reasons for and consequences of the observed plasticity of the structural mt-tRNA integration. We also indicate potential direction for further research that could help our understanding of the mechanistic and evolutionary aspects of this unprecedented system.This work was supported by the Wellcome Trust under Grant 096919/Z/11/Z and Medical Research Council UK under Grant MC_U105697135

Towards understanding the ordering behavior of hard needles: New analytical solutions in one dimension

We re-examine the ordering behavior of a one-dimensional fluid of freely rotating hard needles, where the centers of mass of the particles are restricted to a line. Analytical equations are obtained for the equation of state, order parameter and orientational correlation functions using the transfer-matrix method if some simplifying assumptions are applied for either the orientational freedom or the contact distance between two needles. The two-state Zwanzig model accounts for the orientational ordering, but it produces unphysical pressure at high densities and there is no orientational correlation. The four-state Zwanzig model gives reasonable results for orientational correlation function, but the pressure is still poorly represented at high densities. In the continuum limit, apart from the orientational correlation length it is managed to reproduce all relevant bulk properties of the hard needles using an approximate formula for the contact distance. The results show that the orientational correlation length diverges at zero and infinite pressures. The high density behavior of needles is not resolved.Comment: 21 pages, 3 figure

Small GTPase Rap1 Is Essential for Mouse Development and Formation of Functional Vasculature

BACKGROUND: Small GTPase Rap1 has been implicated in a number of basic cellular functions, including cell-cell and cell-matrix adhesion, proliferation and regulation of polarity. Evolutionarily conserved, Rap1 has been studied in model organisms: yeast, Drosophila and mice. Mouse in vivo studies implicate Rap1 in the control of multiple stem cell, leukocyte and vascular cell functions. In vitro, several Rap1 effectors and regulatory mechanisms have been proposed. In particular, Rap1 has been implicated in maintaining epithelial and endothelial cell junction integrity and linked with cerebral cavernous malformations. RATIONALE: How Rap1 signaling network controls mammalian development is not clear. As a first step in addressing this question, we present phenotypes of murine total and vascular-specific Rap1a, Rap1b and double Rap1a and Rap1b (Rap1) knockout (KO) mice. RESULTS AND CONCLUSIONS: The majority of total Rap1 KO mice die before E10.5, consistent with the critical role of Rap1 in epithelial morphogenesis. At that time point, about 50% of Tie2-double Rap1 KOs appear grossly normal and develop normal vasculature, while the remaining 50% suffer tissue degeneration and show vascular abnormalities, including hemorrhages and engorgement of perineural vessels, albeit with normal branchial arches. However, no Tie2-double Rap1 KO embryos are present at E15.5, with hemorrhages a likely cause of death. Therefore, at least one Rap1 allele is required for development prior to the formation of the vascular system; and in endothelium-for the life-supporting function of the vasculature

Tropological space : the imaginary space of figuration

The paper is devoted to the concept of tropological space, introduced by Michel Foucault in 1966 and alluded to in Hayden White’s tropics of discourse (1973, 1978, 2000), but never described in any detail in literary semantics or linguistic stylistics. The author presents her theory of a triple functional subdivision of stylistic figures and, consequently, of tropes (micro-, macro- and mega (meta)-level of description) and relates it to a gradually expanding tropological space of particular figures, their chains and groupings within a text. The author postulates that tropological space, the imaginary space created through figuration, is a sub-space of the Wittgensteinian logical space as well as a sub-space of textual / discursive space. Although the discussion refers mostly to literary texts, tropology – a branch of stylistics / poetics / rhetoric makes generalizations valid for the study of all kinds of texts / discourses. Figuration is assumed here to be an inherent feature of conceptual and linguistic expression. Finally, the author raises a methodological query as to the ontological status of tropological space, opting for the approach which treats it as a peculiar kind of semantic space rather than a mere metaphoric term. The discussion is based mostly on the Anglo-American studies on figuration (K. Burke, H. White, P. de Man, J. Hillis Miller, G. Hartman) that are rooted in the neo-classical rhetoric and writings of G. Vico. This line of thinking draws its philosophical inspiration from the European hermeneutics of P. Ricoeur, the Foucaultian theory of discourses and the Derridean deconstructionist ideas on the operation of language. The author brings additionally into consideration the conception of artistic space propagated by the Russian semiotic tradition and V. N. Toporov (1983/2003) in particular

Oncogenic Ras activation of Raf/mitogen-activated protein kinase-independent pathways is sufficient to cause tumorigenic transformation

Substantial evidence supports a critical role for the activation of the Raf-1/MEK/mitogen-activated protein kinase pathway in oncogenic Ras-mediated transformation. For example, dominant negative mutants of Raf-1, MEK, and mitogen-activated protein kinase all inhibit Ras transformation. Furthermore, the observation that plasma membrane-localized Raf-1 exhibits the same transforming potency as oncogenic Ras suggests that Raf-1 activation alone is sufficient to mediate full Ras transforming activity. However, the recent identification of other candidate Ras effectors (e.g., RalGDS and phosphatidylinositol-3 kinase) suggests that activation of other downstream effector-mediated signaling pathways may also mediate Ras transforming activity. In support of this, two H-Ras effector domain mutants, H-Ras(12V, 37G) and H-Ras(12V, 40C), which are defective for Raf binding and activation, induced potent tumorigenic transformation of some strains of NIH 3T3 fibroblasts. These Raf-binding defective mutants of H-Ras induced a transformed morphology that was indistinguishable from that induced by activated members of Rho family proteins. Furthermore, the transforming activities of both of these mutants were synergistically enhanced by activated Raf-1 and inhibited by the dominant negative RhoA(19N) mutant, indicating that Ras may cause transformation that occurs via coordinate activation of Raf-dependent and -independent pathways that involves Rho family proteins. Finally, cotransfection of H-Ras(12V, 37G) and H-Ras(12V, 40C) resulted in synergistic cooperation of their focus-forming activities, indicating that Ras activates at least two Raf-independent, Ras effector-mediated signaling events

CLINICAL COURSE OF SYSTEMIC SCLEROSIS PATIENTS

Background: Systemic sclerosis is a rare multisystem inflammatory connective tissue disorder of unclear etiology, characterized by progressive fibrosis of skin and internal organs as well as systemic vascular dysfunction. Disease severity is determined by the degree of internal organ involvement, especially pulmonary hypertension, interstitial lung disease, and peripheral vasculopathy. Objectives: Th e aim of this study was to analyze a group of patients diagnosed with systemic sclerosis. Methods: We retrospectively analyzed a group of 70 patients (42 women and 28 men) treated in the Department of Internal Medicine and Rheumatology, SUM, Katowice, Poland between 2013 and 2016. Patients were an average of 54.0 years old (+/–, range). Our study examined the incidence of cardiovascular and musculoskeletal symptoms as well as basic blood chemistry and imaging studies. We also assessed the degree of skin thickness by the Modified Rodnan Skin score (mRSS). Results: Among study group participants, 67 patients tested positive for ANA, 51- Scl-70, 6-ACA antibodies while 3 patients were not tested. Most patients had an abnormal nailfold capillaroscopy with a sclerodermal pattern, joint pain and features of interstitial lung disease on HRCT. 30% of patients demonstrated pulmonary hypertension and anemia, 7.1% chronic kidney disease, and 15.7% finger ulcers. Most patients were treated with immunosuppressants, and 9 subjects underwent autologous of stem cell transplantation from peripheral blood. Conclusions: Our results are comparable to other similar studies seen in the literature. A team based approach involving physicians of different specialties as well as immunosuppressive therapy (cyclophosphamide, mycophenolate mofetil) and autologous transplantation of stem cells from peripheral blood, can greatly increase quality of life and survival of patients with systemic sclerosis. It is clear that systemic sclerosis requires further extensive study. References: 1. Pope JE, Johnson SR. New Classifi cation Criteria for Systemic Sclerosis (Scleroderma), Rheum Dis Clin North Am. 2015 Aug;41(3): 383–98. doi: 10.1016/j.rdc.2015.04.003. Epub 2015 May 27. 2. Launay D, Sobanski V, Hachulla E, Humbert M. Pulmonary hypertension in systemic sclerosis: diff erent phenotypes, Eur Respir Rev. 2017 Sep 27;26(145). pii: 170056. doi: 10.1183/16000617.0056–2017. Print 2017 Sep 30. 3. Ingegnoli F, Ardoino I, Boracchi P, Cutolo M; EUSTAR co-authors. Nailfold capillaroscopy in systemic sclerosis: data from the EULAR scleroderma trials and research (EUSTAR) database. Microvasc Res. 2013 Sep;89:122–8. doi: 10.1016/j.mvr.2013.06.003. Epub 2013 Jun 17. 4. Cappelli S, Bellando Randone S, Camiciottoli G, De Paulis A, Guiducci S, Matucci-Cerinic M. Interstitial lung disease in systemic sclerosis: where do we stand?, European Respiratory Review 2015 24: 411–419; DOI: 10.1183/16000617.00002915 5. Kayser C and Fritzler M. J. Autoantibodies in Systemic Sclerosis: Unanswered Questions, Front Immunol. 2015; 6: 167. Published online 2015 Apr 15. doi: 10.3389/fi mmu.2015.0016

The novel gene Ny-1 on potato chromosome IX confers hypersensitive resistance to Potato virus Y and is an alternative to Ry genes in potato breeding for PVY resistance

Hypersensitive resistance (HR) is an efficient defense strategy in plants that restricts pathogen growth and can be activated during host as well as non-host interactions. HR involves programmed cell death and manifests itself in tissue collapse at the site of pathogen attack. A novel hypersensitivity gene, Ny-1, for resistance to Potato virus Y (PVY) was revealed in potato cultivar Rywal. This is the first gene that confers HR in potato plants both to common and necrotic strains of PVY. The locus Ny-1 mapped on the short arm of potato chromosome IX, where various resistance genes are clustered in Solanaceous genomes. Expression of HR was temperature-dependent in cv. Rywal. Strains PVYO and PVYN, including subgroups PVYNW and PVYNTN, were effectively localized when plants were grown at 20°C. At 28°C, plants were systemically infected but no symptoms were observed. In field trials, PVY was restricted to the inoculated leaves and PVY-free tubers were produced. Therefore, the gene Ny-1 can be useful for potato breeding as an alternative donor of PVY resistance, because it is efficacious in practice-like resistance conferred by Ry genes

Prevalence of overweight and obesity in children aged 6–13 years—alarming increase in obesity in Cracow, Poland

This study in children aged 6–13 years (n = 1,499) was performed between October 2008 and March 2009. Height and weight measurements were taken to calculate BMI. The prevalence of overweight and obesity was determined by means of IOTF cut-offs with respect to age. Alarming is the fact that the percentage of obese children in Cracow increased dramatically from 1.04% in boys and 0.20% in girls in 1971 to 7% in boys and 3.6% in girls in 2009. In this report, a higher percentage of overweight boys was observed in rural boys (28.14%) than in urban ones (27.31%). Obesity was identified in an almost twice as high percentage of urban boys (7.78%) as in rural ones (3.52%). A higher percentage of overweight girls was registered in rural areas (16.49%) than in urban ones (16.09%). Obesity was prevailing in rural girls (4.12%) relative to their urban counterparts (3.44%). The highest number of overweight urban boys was diagnosed in the group of 12-year-olds (n = 48) and rural boys in the group of 10-year-olds (n = 39), as well as in urban girls aged 11 (n = 17) and rural girls aged 9 (n = 9). The highest number of obesity was observed in rural boys aged 12 (n = 3) and in urban boys aged 9 and 10 (n = 9 in both groups). In the group of girls, obesity prevailed in urban 9-year-olds (n = 5) and in rural 7-year-olds (n = 5). Conclusions: Overweight and obesity affect boys almost twice as frequently as girls. Obesity is twice as frequent in urban boys as in their rural peers