p63 heterozygous mutant mice are not prone to spontaneous or chemically induced tumors

Homology between p63 and p53 has suggested that these proteins might function similarly. However, the majority of data from human tumors have not supported a similar role for p63 in tumor suppression. To investigate this issue, we studied spontaneous tumorigenesis in p63+/- mice in both WT and p53-compromised backgrounds. We found that p63+/- mice were not tumor prone and mice heterozygous for both p63 and p53 had fewer tumors than p53+/- mice. The rare tumors that developed in mice with compromised p63 were also distinct from those of p53+/- mice. Furthermore, p63+/- mice were not prone to chemically induced tumorigenesis, and p63 expression was maintained in carcinomas. These findings demonstrate that, in agreement with data from human tumors, p63 plays a markedly different biological role in cancer than p53

Geogenic and atmospheric sources for volatile organic compounds in fumarolic emissions from Mt. Etna and Vulcano Island (Sicily, Italy)

In this paper, fluid source(s) and processes controlling the chemical composition of volatile organic compounds (VOCs) in gas discharges from Mt. Etna and Vulcano Island(Sicily, Italy) were investigated. The main composition of the Etnean and Volcano gas emissions is produced by mixing, to various degrees, of magmatic and hydrothermal components. VOCs are dominated by alkanes, alkenes and aromatics, with minor, though significant, concentrations of O-, S- and Cl(F)-substituted compounds. The main mechanism for the production of alkanes is likely related to pyrolysis of organic-matterbearing sediments that interact with the ascending magmatic fluids. Alkanes are then converted to alkene and aromatic compounds via catalytic reactions (dehydrogenation and dehydroaromatization, respectively). Nevertheless, an abiogenic origin for the light hydrocarbons cannot be ruled out. Oxidative processes of hydrocarbons at relatively high temperatures and oxidizing conditions, typical of these volcanic-hydrothermal fluids, may explain the production of alcohols, esters, aldehydes, as well as O- and S-bearing heterocycles. By comparing the concentrations of hydrochlorofluorocarbons (HCFCs) in the fumarolic discharges with respect to those of background air, it is possible to highlight that they have a geogenic origin likely due to halogenation of both methane and alkenes. Finally, chlorofluorocarbon (CFC) abundances appear to be consistent with background air, although the strong air contamination that affects the Mt. Etna fumaroles may mask a possible geogenic contribution for these compounds. On the other hand, no CFCs were detected in the Vulcano gases, which are characterized by low air contribution. Nevertheless, a geogenic source for these compounds cannot be excluded on the basis of the present data

Rare deleterious variants in genes involved in tissue structure and epithelial integrity are found in patients with group A streptococcal necrotising fasciitis by whole-exome sequencing

Necrotising fasciitis (NF) is a rare manifestation of invasive Streptococcus pyogenes (GAS) infection associated with a substantial risk of death or disability. Hypothesising that host genetic factors might contribute, we sought to identify rare deleterious variants contributing to NF susceptibility

“University of the People” – the third mission of Dagestan State University: an innovative approach to sustainability policy

Aim. To develop an effective and innovative policy approach to Dagestan State University’s third mandated mission to support sustainable community development by acknowledging and enhancing through specialist education the undervalued knowledge capital inherent in individuals and organizations throughout the community.Discussion. Dagestan State University has 90 years of experience in providing support for the people of Dagestan in scientific research and higher education and is cognizant of the deep reservoir of community knowledge and competencies in articulating aspirations for sustainable development. On this basis, the university’s Institute of Ecology and Sustainable Development is instituting an innovative community engagement program, the University of the People, to deliver effective scientific support for such development through co‐creative collaborations which draw on and enhance community knowledge in the diverse regions of the republic. In consultation with the administration and community stakeholders of the alpine Tsumadinskiy district of the Dagestan Caucasus, through the present policy document a launch phase of the University of the People program has been formulated for 2022 which will provide year‐long local vocational guidance to schools and an annual “Summer Field Faculty” which will undertake research, developmental needs analysis and offer in‐service specialist training opportunities and support for local experts and administrations in implementing their desired sustainability initiatives. Following literature research and fieldwork in 2020‐2021, the first outcome of the regional sustainability initiative, “Conserving the Koisu: Sustaining the Mountain Fastness of the Upper Andiiskoe River – A Uniquely Surviving Socio‐Ecological Continuum in the Dagestan Caucasus”, has been completedConclusion. Implementation of the University of the People concept has the potential to effectively harness the vast resources of traditional knowledge of individuals and local bodies in regional sustainable development by providing communities with concrete support and interaction of university specialists and educators in ecology and sustainable development. It is hoped that the program will stimulate and enable members of the community to themselves attain tertiary qualifications in these fields, who, in turn, will create a future knowledge resource for continuing local applications of sustainable development principles. The concept has potential for application to other societies in the Caspian region which share similar histories and challenges

The Solar Stag of the Chamalals and Tindals and other masonry petroglyphs in the upper Andiiskoe Koisu region of Dagestan and their relationships to similar phenomena in the mountain communities of the Caucasus: Socio-ecological and historical perspectives

Aim. Following the discovery of a number of iconographically unique masonry petroglyphs depicting a red deer solar stag (i.e. bearing the sun between its antlers) in settlements of the Chamalal ethno‐linguistic group in the upper Andiiskoe Koisu region of the Tsumadinskiy district of Dagestan, the aim of the research has been: (1) to survey the region to ascertain whether other images of this nature existed and to understand the relationship of the corpus to other petroglyphs produced within the Avar‐Ando‐Dido metacultural zone and of neighbouring ethnic groups in the Caucasus; (2) to study the evolution and meaning to the community of the petroglyphic imagery and (3) to understand the mechanisms by which peoples of the Caucasus shared and adapted polytheistic belief systems arising from the deep past following their conversion to Christianity and Islam.Materials and Methods. Research activities involved field surveys of traditional buildings within the ethno‐linguistic enclaves of the upper Andiiskoe Koisu which might contain masonry petroglyphs and their photographic documentation. A thorough survey of the scientific literature impacting on this field in the Caucasus was undertaken in the libraries and institutions of Dagestan, Moscow and Saint Petersburg. This data added to the documentation of masonry petroglyphs already undertaken in the Gidatli communities of the upper Avarskoe Koisu region.Results. Field surveys resulted in the discovery of more petroglyphs of the solar stag iconography both within Chamalal territory and that of the neighbouring Tindals as well as other petroglyphs of interest in neighbouring republics of the North Caucasus. A socioecological assessment of local habitats which might have sustained both red deer and bezoar goat (the principal game animals since human presence in the region) indicated that the bezoar goat inhabited the territories of both groups but were now rarely found in Chamalal lands. While red deer did inhabit the forests of the Tindals, it appears that they never frequented those of the Chamalals, who must have travelled to hunt them in forests further to the south.Conclusion. The research confirmed the presence of a unique corpus of petroglyphic imagery attesting to beliefs in a solar stag which may date back to period of man’s re‐inhabiting the upper Andiiskoe Koisu region in the early Holocene. Indigenous beliefs relating both to the red deer and the bezoar goat initially represented in rock face petroglyphs of the eastern Dagestan piedmonts and rock paintings of the mountainous regions were by the late Bronze Age represented on masonry blocks used in building in the Avar‐Ando‐Dido metacultural zone. As Christianity spread in Transcaucasia and the Great Caucasus Range, including north‐western Dagestan, indigenous images representing the solar stag were conflated with those of the popular Christian cult of the Miracle of Saint Eustace, resulting in the unique petroglyphs of the solar stag common t

A direct comparison of strategies for combinatorial RNA interference

<p>Abstract</p> <p>Background</p> <p>Combinatorial RNA interference (co-RNAi) is a valuable tool for highly effective gene suppression of single and multiple-genes targets, and can be used to prevent the escape of mutation-prone transcripts. There are currently three main approaches used to achieve co-RNAi in animal cells; multiple promoter/shRNA cassettes, long hairpin RNAs (lhRNA) and miRNA-embedded shRNAs, however, the relative effectiveness of each is not known. The current study directly compares the ability of each co-RNAi method to deliver pre-validated siRNA molecules to the same gene targets.</p> <p>Results</p> <p>Double-shRNA expression vectors were generated for each co-RNAi platform and their ability to suppress both single and double-gene reporter targets were compared. The most reliable and effective gene silencing was achieved from the multiple promoter/shRNA approach, as this method induced additive suppression of single-gene targets and equally effective knockdown of double-gene targets. Although both lhRNA and microRNA-embedded strategies provided efficient gene knockdown, suppression levels were inconsistent and activity varied greatly for different siRNAs tested. Furthermore, it appeared that not only the position of siRNAs within these multi-shRNA constructs impacted upon silencing activity, but also local properties of each individual molecule. In addition, it was also found that the insertion of up to five promoter/shRNA cassettes into a single construct did not negatively affect the efficacy of each individual shRNA.</p> <p>Conclusions</p> <p>By directly comparing the ability of shRNAs delivered from different co-RNA platforms to initiate knockdown of the same gene targets, we found that multiple U6/shRNA cassettes offered the most reliable and predictable suppression of both single and multiple-gene targets. These results highlight some important strengths and pitfalls of the currently used methods for multiple shRNA delivery, and provide valuable insights for the design and application of reliable co-RNAi.</p

Recognition and social freedom

In this paper I develop an account of social freedom grounded in intersubjective recognition, which I term the “normative authorisation” account. According to this model, a person enjoys social freedom if she is recognised as a discursive equal who can engage in justificatory dialogue with other social agents about the appropriateness of her reasons for action. I contrast this with Axel Honneth’s theory of social freedom, which I label the “self-realisation” account. Within this model, the affirmative recognition of others is required in order to achieve a positive relation-to-self and hence freedom. I highlight several issues with this account, which challenge the relationship Honneth draws between social recognition and freedom. I demonstrate that the normative authorisation account avoids these problems. I also show how it captures some basic features of our everyday, normative interactions. Finally, I suggest that the account fits well with recent work on epistemic injustice. Specifically, it shows that establishing the social conditions of freedom requires ensuring epistemically-just social relations. In sum, the normative authorisation account is an explanatorily powerful, inclusive theory of social freedom that fits well with wider accounts of justice and freedom. It represents the most promising way of construing social freedom in terms of interpersonal recognition

Nowhere Home: The Waiting of Vulnerable Child Refugees

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Herpesvirus Telomerase RNA(vTR)-Dependent Lymphoma Formation Does Not Require Interaction of vTR with Telomerase Reverse Transcriptase (TERT)

Telomerase is a ribonucleoprotein complex involved in the maintenance of telomeres, a protective structure at the distal ends of chromosomes. The enzyme complex contains two main components, telomerase reverse transcriptase (TERT), the catalytic subunit, and telomerase RNA (TR), which serves as a template for the addition of telomeric repeats (TTAGGG)n. Marek's disease virus (MDV), an oncogenic herpesvirus inducing fatal lymphoma in chickens, encodes a TR homologue, viral TR (vTR), which significantly contributes to MDV-induced lymphomagenesis. As recent studies have suggested that TRs possess functions independently of telomerase activity, we investigated if the tumor-promoting properties of MDV vTR are dependent on formation of a functional telomerase complex. The P6.1 stem-loop of TR is known to mediate TR-TERT complex formation and we show here that interaction of vTR with TERT and, consequently, telomerase activity was efficiently abrogated by the disruption of the vTR P6.1 stem-loop (P6.1mut). Recombinant MDV carrying the P6.1mut stem-loop mutation were generated and tested for their behavior in the natural host in vivo. In contrast to viruses lacking vTR, all animals infected with the P6.1mut viruses developed MDV-induced lymphomas, but onset of tumor formation was significantly delayed. P6.1mut viruses induced enhanced metastasis, indicating functionality of non-complexed vTR in tumor dissemination. We discovered that RPL22, a cellular factor involved in T-cell development and virus-induced transformation, directly interacts with wild-type and mutant vTR and is, consequently, relocalized to the nucleoplasm. Our study provides the first evidence that expression of TR, in this case encoded by a herpesvirus, is pro-oncogenic in the absence of telomerase activity

Different expressions of the same mode: a recent dialogue between archaeological and contemporary drawing practices

In this article we explore what we perceive as pertinent features of shared experience at the excavations of an Iron Age Hillfort at Bodfari, North Wales, referencing artist, archaeologist and examples of seminal art works and archaeological records resulting through inter-disciplinary collaboration. We explore ways along which archaeological and artistic practices of improvisation become entangled and productive through their different modes of mark-making. We contend that marks and memories of artist and archaeologist alike emerge interactively, through the mutually constituting effects of the object of study, the tools of exploration, and the practitioners themselves, when they are enmeshed in the cross-modally bound activities. These include, but are not limited to, remote sensing, surveying, mattocking, trowelling, drawing, photographing, videoing and sound recording. These marks represent the co-signatories: the gesture of the often anonymous practitioners, the voice of the deposits, as well as the imprint of the tools, and their interplay creates a multi-threaded narrative documenting their modes of intra-action, in short our practices. They occupy the conceptual space of paradata, and in the process of saturating the interstices of digital cognitive prosthetics they lend probity to their translations in both art form and archive